UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

______________________________________________________________________

FORM 10-K

~~☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934~~______________________________________________________________________

~~For~~x ~~the~~ANNUAL ~~fiscal~~REPORT ~~year~~PURSUANT ~~ended~~TO ~~December~~SECTION ~~31,~~13 ~~2024~~OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

☐For ~~TRANSITION~~the ~~REPORT~~fiscal ~~PURSUANT~~year TOended ~~SECTION~~December 1331, ~~OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934~~2025


o			TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the transition period from ____ to _____

Commission File No. 001-36913

______________________________________________________________________

Zevra Therapeutics, Inc.

(Exact Name of Registrant as Specified in Its Charter)

Delaware	20-5894398
(State or Other Jurisdiction of Incorporation or Organization)	(I.R.S. Employer Identification No.)
1180 Celebration Boulevard, Suite 103, Celebration, FL 34747	(321) 939-3416
(Address of Principal Executive Offices and Zip Code)	(Registrant’s Telephone Number, Including Area Code)

______________________________________________________________________


Delaware			20-5894398
(State or Other Jurisdiction of Incorporation or Organization)			(I.R.S. Employer Identification No.)

101 Federal Street, Boston, MA 02110			(888) 958-1253
(Address of Principal Executive Offices and Zip Code)			(Registrant’s Telephone Number, Including Area Code)

Securities registered pursuant to Section 12(b) of the Act:

Title of Each Class	~~Trading Symbol~~	~~Name of Each Exchange on Which Registered~~	Trading Symbol			Name of Each Exchange on Which Registered
Common Stock, $0.0001 par value	~~ZVRA~~	~~The Nasdaq Stock Market LLC (Nasdaq Global Select Market)~~	ZVRA			The Nasdaq Stock Market LLC(Nasdaq Global Select Market)

Securities registered pursuant to Section 12(g) of the Act: None

~~Indicate by check mark if the Registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act Yes ☐ No ☒~~______________________________________________________________________

Indicate by check mark if the Registrant is ~~not~~a ~~required~~well-known toseasoned ~~file~~issuer, ~~reports~~as ~~pursuant~~defined toin ~~Section~~Rule 13405 ~~or Section 15(d)~~ of the ~~Act~~Securities Act Yes ☐ o No ☒ x

~~Table~~Indicate by check mark if the Registrant is not required to file reports pursuant to Section 13 or Section 15(d) of ~~Contents~~ the Act Yes o No x

Indicate by check mark whether the Registrant: (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes ☒ x No ☐ o

Indicate by check mark whether the Registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes ☒ x No ☐ o

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.:

Large accelerated filer ☐o Accelerated filer ☐o Non-accelerated filer ☒ x Smaller reporting company ☒ x Emerging growth company ☐o

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐ o

Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☐ o

If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐ o

Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant's executive officers during the relevant recovery period pursuant to § 240.10D-1(b). ☐ o

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ o No ☒ x

The aggregate market value of the voting and non-voting common equity held by non-affiliates of the registrant as of June 28, 2024, the last business day of the registrant’s most recently completed second fiscal quarter, was approximately $204.8 million, based upon the closing sales price for the registrant’s common stock, as reported on the Nasdaq Global Select Market on June 28, 2024. The calculation of the aggregate market value of voting and non-voting common equity excludes shares of common stock the registrant held by executive officers, directors and stockholders that the registrant concluded were affiliates of the registrant on that date. Exclusion of such shares should not be construed to indicate that any such person possesses the power, direct or indirect, to direct or cause the direction of management or policies of the registrant or that such person is controlled by or under common control with the registrant.______________________________________________________________________

AsThe aggregate market value of ~~March~~ 7the voting and non-voting common equity held by non-affiliates of the registrant as of June 30, 2025, the last business day of the registrant’s ~~had~~most 54recently completed second fiscal quarter,~~115~~ was approximately $454.8 million,~~869~~ based upon the closing sales price for the registrant’s common stock, as reported on the Nasdaq Global Select Market on June 30, 2025. The calculation of the aggregate market value of voting and non-voting common equity excludes shares of common stock ~~outstanding~~the registrant held by executive officers, directors and stockholders that the registrant concluded were affiliates of the registrant on that date. Exclusion of such shares should not be construed to indicate that any such person possesses the power, direct or indirect, to direct or cause the direction of management or policies of the registrant or that such person is controlled by or under common control with the registrant.

As of March 6, 2026, the registrant had 58,711,584 shares of common stock outstanding.

______________________________________________________________________

Documents Incorporated by Reference

Portions of the registrant’s definitive proxy statement relating to its ~~2025~~ 2026 annual meeting of stockholders are incorporated by reference into Part III of this Annual Report on Form 10-K where indicated. Such proxy statement will be filed with the U.S. Securities and Exchange Commission within 120 days after the end of the fiscal year to which this report relates.

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ZEVRA THERAPEUTICS, INC.

FORM 10-K

		~~Page~~		Page
PART I	~~PART I~~
Item 1.	~~Business~~	7	Business	7
Item 1A.	~~Risk Factors~~	29	Risk Factors	29
Item 1B.	~~Unresolved Staff Comments~~	76	Unresolved Staff Comments	51
Item 1C.	~~Cybersecurity~~		Cybersecurity	51
Item 2.	~~Properties~~	77	Properties	52
Item 3.	~~Legal Proceedings~~	77	Legal Proceedings	53
Item 4.	~~Mine Safety Disclosures~~	77	Mine Safety Disclosures	53
PART II	~~PART II~~
Item 5.	~~Market for Registrant's Common Equity, Related Stockholder Matters, and Issuer Purchases of Equity Securities~~	81	Market for Registrant's Common Equity, Related Stockholder Matters, and Issuer Purchases of Equity Securities	54
Item 6.	~~[Reserved]~~	81	[Reserved]	54
Item 7.	~~Management's Discussion and Analysis of Financial Condition and Results of Operations~~	82	Management's Discussion and Analysis of Financial Condition and Results of Operations	55
Item 7A.	~~Quantitative and Qualitative Disclosures About Market Risk~~	94	Quantitative and Qualitative Disclosures About Market Risk	67
Item 8.	~~Financial Statements and Supplementary Data~~	94	Financial Statements and Supplementary Data	67
Item 9.	~~Changes in and Disagreements With Accountants on Accounting and Financial Disclosures~~	94	Changes in and Disagreements With Accountants on Accounting and Financial Disclosures	67
Item 9A.	~~Controls and Procedures~~	94	Controls and Procedures	68
Item 9B.	~~Other Information~~	95	Other Information	68
Item 9C.	~~Disclosure Regarding Foreign Jurisdictions that Prevent Inspections~~	95	Disclosure Regarding Foreign Jurisdictions that Prevent Inspections	68
PART III	~~PART III~~
Item 10.	~~Directors, Executive Officers and Corporate Governance~~	96	Directors, Executive Officers and Corporate Governance	69
Item 11.	~~Executive Compensation~~	96	Executive Compensation	69
Item 12.	~~Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters~~	96	Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters	69
Item 13.	~~Certain Relationships and Related Transactions, and Director Independence~~	96	Certain Relationships and Related Transactions, and Director Independence	69
Item 14.	~~Principal Accounting Fees and Services~~	96	Principal Accountant Fees and Services	69
PART IV	~~PART IV~~
Item 15.	~~Exhibits and Financial Statement Schedules~~	97	Exhibits and Financial Statement Schedules	70
Item 16.	~~Form 10-K Summary~~	~~134~~	Form 10-K Summary	108
	~~Signatures~~	~~135~~	Signatures	109

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SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

This Annual Report on Form 10-K, including the section entitled “Management’s Discussion and Analysis of Financial Condition and Results of Operations,” contains forward-looking statements regarding future events and our future results that are subject to the safe harbors created under the Securities Act of 1933, as amended, or (the “Securities Act”), and the Securities Exchange Act of 1934, as amended, or (the “Exchange Act”). Forward-looking statements relate to future events or our future financial performance. We generally identify forward-looking statements by terminology such as “may,” “will,” “would,” “should,” “expects,” “plans,” “anticipates,” “could,” “intends,” “target,” “projects,” “contemplates,” “believes,” “estimates,” “predicts,” “assume,” “~~intend,” “~~potential,” “continue” or other similar words or the negative of these terms. We have based these forward-looking statements largely on our current expectations about future events and financial trends that we believe may affect our business, financial condition and results of operations. The ~~outcome~~outcomes of the events described in these forward-looking statements isare subject to risks, uncertainties and other factors described in “Risk Factors” and elsewhere in this report. Accordingly, you should not place undue reliance upon these forward-looking statements. We cannot assure you that the events and circumstances reflected in the forward-looking statements will be achieved or occur, and the timing of events and circumstances and actual results could differ materially from those anticipated in the forward-looking statements. Forward-looking statements contained in this report include, but are not limited to, statements about:

● •our ability to commercialize and the timing of commercializing our products and product candidates, if approved; ● the potential therapeutic benefits and effectiveness of our products and product candidates; ● the progress of, timing of and expected amount of expenses associated with our research, development and commercialization activities; ● the size and characteristics of the markets that may be addressed by our products and product candidates; ● the consummation of the transaction contemplated by the PRV Transfer Agreement (as defined herein) and our anticipated net proceeds therefrom; ● the expected timing of our clinical trials for our product candidates and the availability of data and results of those trials; ● the progress of, outcome or and timing of any regulatory approval for any of our product candidates and the expected amount or timing of any payment related thereto under any of our collaboration agreements; ● our expectations regarding federal, state and foreign legal and regulatory requirements; ● our intention to seek to establish, and the potential benefits to us from, any strategic collaborations or partnerships for the development or sale of our products and product candidates, if approved; ● our expectations as to future financial performance, expense levels and liquidity sources; ● the sufficiency of our cash resources to fund our operating expenses and capital investment requirements for any period; ● our ability to raise additional funds on commercially reasonable terms, or at all, in order to support our continued operations; ● our ability to continue as a going concern; ● senior leadership and board member transitions and refreshments; and ● other factors discussed elsewhere in this report.

~~The forward-looking statements made in this report relate only to events as of~~ •the date on which the statements are made. We have included important factors in the cautionary statements included in this report, particularly in the section entitled “Risk Factors” that we believe could cause actual results or events to differ materially from the forward-looking statements that we make. Our forward-looking statements do not reflect the potential ~~impact~~therapeutic ofbenefits ~~any~~and ~~future~~effectiveness acquisitions, mergers, dispositions, joint ventures or investments we may make. Except as required by law, we do not assume any intent to update any forward-looking statements after the date on which the statement is made, whether as a result of ~~new~~our ~~information,~~products ~~future~~and ~~events~~product ~~or circumstances or otherwise.~~candidates;

•the progress of, timing of and expected amount of expenses associated with our commercialization, research, and development activities;

•the size and characteristics of the markets that may be addressed by our products and product candidates;

•the expected timing of clinical trials for our product candidates and the availability of data and results of those trials;

•the progress of, outcome of, and timing of any regulatory approval for any of our product candidates;

•our expectations regarding federal, state and foreign tax, legal and regulatory requirements;

•our intention to seek to establish, and the potential benefits to us from, any strategic collaborations or partnerships for the development or sale of our products and product candidates, if approved;

•our expectations as to future financial performance, expense levels and liquidity sources;

•the sufficiency of our cash resources to fund our operating expenses and capital investment requirements for any period;

•our ability to raise additional funds if needed on commercially reasonable terms, or at all, in order to support our continued operations;

•senior leadership and board member transitions and refreshments; and

•other factors discussed elsewhere in this report.

The forward-looking statements made in this report relate only to events as of the date on which the statements are made. We have included or made reference to important factors in the cautionary statements included in this report, particularly in the section entitled “Risk Factors” that we believe could cause actual results or events to differ materially from the forward-looking statements that we make. Our forward-looking statements do not reflect the potential impact of any future developments, including acquisitions, mergers, dispositions, joint ventures or investments we may make. Except as required by law, we do not assume any intent to update any forward-looking statements after the date on which the statement is made, whether as a result of new information, future events or circumstances or otherwise.

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RISK FACTORS SUMMARY

The risk factors summarized below could materially harm our business, operating results, and/or financial condition, impair our future prospects, and/or cause the price of our common stock to decline. These risks are discussed more fully in the section titled "“Risk Factors"”. Material risks that may affect our business, financial condition, results of operations, and trading price of our common stock include the following:

●Risks IfRelated commercialization of our approved products, or any of our product candidates, if approved, are not successful, or we experience significant delays in commercialization, our business will be harmed. ● If we are not able to ~~obtain required regulatory approvals for any of our product candidates, or~~ the ~~approved~~Commercialization labels are not sufficiently differentiated from other competing products, we will not be able to commercialize them and our ability to generate revenue or profits or to raise future capital could be limited. ● Arimoclomol is currently available to Niemann-Pick disease type C patients in France, Germany, and other EU member states through our various expanded access programs ("EAPs"). EAPs are expected to remain in place until arimoclomol becomes commercially available in each of the current EAP markets. If an EAP is terminated prior to commercialization of arimoclomol in varying jurisdictions, it will have a material adverse effect on our business, results of operations, cash flows, financial condition and/or prospects. ● If we fail to maintain effective internal control over financial reporting and disclosure controls and procedures, we may not be able to accurately report our financial results or report them in a timely manner, which may adversely affect investor confidence in us and, as a result, the value of our common stock. ● Clinical drug development involves a lengthy and expensive process, with an uncertain outcome. We may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of our product candidates. ● We may need additional funding to pursue our business objectives. If we are unable to raise capital when needed, we could be forced to delay, reduce or altogether cease our prodrug development programs or commercialization efforts or cease operations altogether. ● We have incurred significant recurring negative net operating cash flows. We cannot predict if we will incur positive or negative net operating cash flows over the next several years which may impact our ability to continue as a going concern, and we may never achieve or maintain profitability. ● If we are unable to obtain and maintain trade secret protection or patent protection for our technology, our approved products or our product candidates, or if the scope of the patent protection obtained is not sufficiently broad, our competitors could develop and commercialize technology and drugs similar or identical to ours, and our ability to successfully commercialize our technology, our approved products, or our product candidates, if approved, may be impaired. ● If the FDA does not conclude that our product candidates satisfy the requirements for the 505(b)(2) NDA pathway, the approval pathway for our product candidates will likely take significantly longer, cost significantly more and entail significantly greater complications and risks than anticipated, and the FDA may not ultimately approve our product candidates. ● We have entered into collaborations with Commave Therapeutics, S.A., or Commave, to develop, manufacture and commercialize AZSTARYS worldwide. In addition, we may seek collaborations with third parties for the development, or commercialization of our other product candidates, or in other territories. If those collaborations are not successful, we may not be able to capitalize on the market potential of AZSTARYS or any of our other product candidates, if approved. ● The trading price of the shares of our common stock is likely to be volatile, and purchasers of our common stock could incur substantial losses. ● Our ~~future~~Approved ~~success~~Products ~~depends on our ability to retain key executives~~ and toProduct attract, retain and motivate qualified personnel. ● We could be negatively affected as a result of the actions of activist stockholders, which could be disruptive and costly and may conflict with or disrupt the strategic direction of our business. ● Adverse developments affecting the financial services industry, including events or concerns involving liquidity, defaults, or non-performance by financial institutions, could adversely affect our business, financial condition or results of operations.Candidates

•If we are unable to establish effective sales, marketing and distribution capabilities for our products, or if our products fail to achieve expected market acceptance, we may not be successful in commercializing such products.

•The target patient population for our rare disease products is small, so we must achieve significant market share and obtain relatively high per-patient prices to be successful.

•We may be subject to enforcement action if we engage in improper marketing or promotion of our products.

•Product liability claims could cause us to incur substantial liabilities and adversely affect commercialization of our products.

•Significant political, trade or regulatory developments, such as increased tariffs or other measures that can restrict international trade can negatively effect development and commercialization of our products and product candidates.

•We are subject to a number of risks associated with commercializing our products internationally.

•Arimoclomol is currently available to Niemann-Pick disease type C patients in select foreign jurisdictions through a global expanded access program (“EAP”), and if the EAP is terminated prior to regulatory approval of arimoclomol and commercialization in any such foreign jurisdiction, our business would be harmed.

Risks Related to Our Business and Our Financial Position

•We are highly dependent on MIPLYFFA (arimoclomol) for substantially all of our revenues, and any loss of revenue from this product could materially harm our business.

•We have had recurring negative net operating cash flows throughout our operating history, and we cannot guarantee or predict when we may begin to consistently generate positive net cash flows from operations, or if at all.

Risks Related to Our Dependence on Third Parties

•We rely on a limited number of suppliers, in some cases sole-source suppliers, and the inability of such sole-source suppliers to meet our supply requirements would materially harm our business.

•The facilities used by our third-party contract manufacturers are subject to regulatory requirements and inspections, and any failure by such third-party contract manufacturers to comply with regulatory requirements could materially harm our business.

•We rely on and expect to continue to rely on third parties to conduct our clinical trials for our product candidates, and those third parties may not perform satisfactorily.

•We have entered into a collaboration with Commave, to develop, manufacture and commercialize AZSTARYS worldwide, a party with whom we are currently in dispute, and if this collaboration is not successful, we may not be able to capitalize on the market potential of AZSTARYS.

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Risks Related to Our Intellectual Property

•If we are unable to obtain and maintain adequate intellectual property protection for our technology and products, our competitors could develop and commercialize technology and products similar or identical to ours, and our ability to successfully commercialize our products would be impaired.

•We may become involved in lawsuits to protect or enforce our patents or other intellectual property against infringing third parties, which could be expensive, time consuming and unsuccessful.

•Third parties may initiate legal proceedings against us alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could significantly harm our business.

Risks Related to Regulatory Approval of Our Product Candidates and Other Legal Compliance Matters

•If we are not able to obtain required regulatory approvals for any of our product candidates, we will not be able to commercialize them and our ability to generate revenue or profits could be limited.

•If we experience delays or difficulties in the enrollment of subjects in clinical trials, our receipt of necessary regulatory approvals could be delayed or prevented.

•Our approved products are, and any of our product candidates for which we obtain marketing approval will be, subject to significant post-marketing regulatory requirements and oversight.

•Current and future healthcare reform legislation or regulation in the United States and foreign jurisdictions may increase the difficulty and cost for us to obtain marketing approval of our product candidates and increase the cost to commercialize our approved products.

•We may not be able to obtain or maintain the benefits associated with orphan drug designation, including the potential for market exclusivity.

•Our relationships with healthcare professionals, principal investigators, consultants, customers and third-party payors in the United States and elsewhere may be subject to applicable anti-kickback, fraud and abuse, false claims, physician payment transparency, and other healthcare laws and regulations, which could expose us to penalties.

•If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate Program or other governmental pricing programs in which we participate, we could be subject to additional reimbursement requirements, penalties, sanctions and fines.

Risks Related to Cybersecurity and Data Privacy

•Cybersecurity breaches, loss of data and other disruptions could compromise sensitive information related to our business or prevent us from accessing critical information and expose us to liability, which could adversely affect our business and our reputation.

•We are currently subject to, and may in the future become subject to additional, U.S. federal and state and international laws and regulations imposing obligations on how we collect, store and process personal information.

Risks Related to Ownership of Our Common Stock

•The trading price of the shares of our common stock is likely to be volatile, and purchasers of our common stock could incur substantial losses.

•Anti-takeover provisions in our certificate of incorporation and bylaws, as well as provisions of Delaware law and the terms of some or our contracts, might discourage, delay or prevent a change in control of the company or changes in our board of directors or management and, therefore, depress the price of our common stock.

•We could be negatively affected as a result of the actions of activist stockholders, which could be disruptive and costly and may conflict with or disrupt the strategic direction of our business.

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NOTE REGARDING COMPANY REFERENCE

Unless the context otherwise requires, we use the terms “Zevra,” “Company,” “we,” “us” and “our” in this Annual Report on Form 10-K to refer to Zevra Therapeutics, Inc. and its subsidiaries. We have proprietary rights to a number of trademarks and service marks used in this Annual Report on Form 10-K that are important to our business, including ~~LAT®,~~ ~~OLPRUVA~~MIPLYFFA® and its related logo, ~~MIPLYFFA™~~OLPRUVA® and its related logo, LAT®, and the Zevra ~~logo~~ companies' logos. In addition, Zevra Therapeutics® and Zevra® are both registered trademarks of the Company. All other trademarks, trade names and service marks appearing in this Annual Report on Form 10-K are the property of their respective owners. Solely for convenience, the trademarks and trade names in this Annual Report on Form 10-K are referred to without the ® and ™ symbols, but such references should not be construed as any indicator that their respective owners will not assert, to the fullest extent under applicable law, their rights thereto.

On August 30, 2023, the Company and Aspen Z Merger Sub, Inc., a wholly-owned subsidiary of Zevra ("Merger Sub") entered into an Agreement and Plan of Merger (the "Merger Agreement") with Acer Therapeutics, Inc. ("Acer"). On November 17, 2023 (the "Closing Date"), we completed the acquisition of Acer. Pursuant to the Merger Agreement, on the Closing Date, Merger Sub was merged with and into Acer (the "Merger"), with Acer continuing as the surviving entity and as a wholly-owned subsidiary of Zevra.

NOTE REGARDING MARKET AND INDUSTRY DATA

This Annual Report on Form 10-K contains statistical data, estimates and forecasts that are based on independent industry publications or other publicly available information, as well as other information based on our internal sources. While we believe the industry and market data included in this Annual Report on Form 10-K is reliable and is based on reasonable assumptions, this data involves many assumptions and limitations, and you are cautioned not to give undue weight to these estimates. We have not independently verified the accuracy or completeness of the data contained in these industry publications and other publicly available information. The industry in which we operate is subject to a high degree of uncertainty and risk due to a variety of factors, including those described in the section titled “Risk Factors” and “Special Note Regarding Forward-Looking Statements” included in this Annual Report on Form 10-K.

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PART I

ITEM 1. BUSINESS.

Overview

We are a commercial-stage company ~~focused~~with ona ~~addressing~~late-stage ~~unmet~~pipeline ~~needs~~committed ~~for~~to ~~the~~redefining ~~treatment~~what ~~of rare diseases. Our mission~~ is topossible ~~bring~~in bringing life-changing ~~therapeutics~~therapies to people living with rare diseases. ~~With~~We ~~data-driven~~are ~~development~~focused ~~and~~on ~~commercialization~~expanding ~~strategies~~patient access, weprogressing ~~are overcoming~~our ~~complex~~pipeline ~~drug~~toward ~~development~~key ~~challenges~~milestones, toand ~~make~~delivering ~~new~~meaningful ~~therapies~~therapeutics. ~~available~~Our tovision ~~the~~is ~~rare~~realized ~~disease~~through ~~community.~~disciplined Weexecution ~~have~~of aour ~~diverse~~strategic ~~portfolio~~plan ofand ~~products~~our ~~and~~core ~~product~~values ~~candidates,~~— ~~which~~patient ~~includes~~centricity, ~~pre-clinical~~integrity, ~~clinical~~accountability, innovation, and ~~commercial~~courage ~~stage~~— ~~assets.~~which ~~Our~~guide ~~team~~our ~~has~~efforts ~~specialized~~to ~~expertise~~deliver ~~and~~long-term avalue. ~~track~~The ~~record~~commercialization of ~~success~~our lead product, marketed in ~~advancing~~the ~~promising~~United ~~therapies~~States ~~that~~for ~~face~~Niemann-Pick ~~complex~~disease ~~clinical~~type C (NPC), ~~regulatory~~a rare, ~~and~~progressive ~~commercial~~neurodegenerative ~~challenges~~disease, ~~with~~provides ana ~~approach~~strong ~~that~~corporate ~~balances~~foundation ~~science~~and ~~with~~demonstrates ~~patient~~our ~~need~~ability to advance therapies from development to market.

~~Following~~In ~~the~~February ~~U.S. approval of AZSTARYS® (further described below) in March 2021~~2023, we ~~undertook~~changed ~~a strategic process to evaluate how to leverage and potentially augment the Company’s existing capabilities while also considering where to invest in~~ our ~~pipeline~~name to ~~generate~~Zevra ~~long-term~~Therapeutics, ~~shareholder value~~Inc. ~~With~~Zevra, ais ~~track~~the ~~record~~Greek ofword ~~drug development success leading to approvals~~ for ~~products~~zebra, which ~~had~~is ~~either difficult pathways to approval or where approvals were won following a complete response letter (“CRL”) from~~ the ~~U.S.~~internationally ~~Food~~recognized ~~and~~symbol ~~Drug~~for ~~Administration (“FDA”), we determined to focus our expertise on~~ rare disease. ~~indications,~~This asname ~~well~~reflects asour ~~seeking~~intense ~~value-creating~~focus ~~opportunities by building~~ and ~~directly~~dedication ~~commercializing~~to ~~product~~developing ~~candidates~~transformational, ~~in lieu of an out-licensing model. We are executing on this balanced approach by building a high-performing culture that is~~ patient-focused ~~and~~therapies ~~driven~~for byrare ~~our~~diseases ~~commitment~~with tolimited ~~developing~~or ~~and~~no ~~commercializing~~treatment ~~therapies~~options toavailable, ~~address~~or ~~the~~treatment ~~myriad~~areas ~~unmet~~with ~~needs~~significant ~~within~~unmet ~~the rare disease community~~needs.

AsOur ~~part~~strategic ofplan ~~our~~is ~~commitment~~focused toon ~~serving~~transforming ~~the~~Zevra ~~rare~~into ~~disease~~a ~~community,~~leading inrare-disease ~~February~~company. ~~2023,~~We weare ~~changed~~prioritizing ~~our~~the ~~name~~commercialization toand ~~Zevra~~global ~~Therapeutics,~~expansion ~~Inc.~~of ~~Our~~our ~~name~~lead product, ~~Zevra~~MIPLYFFA, iswhile ~~the~~OLPRUVA ~~Greek~~remains ~~word~~commercially ~~for~~available. ~~zebra,~~We ~~which~~are isalso advancing the ~~internationally~~development ~~recognized~~of ~~symbol~~our ~~for~~clinical ~~rare~~stage ~~disease.~~asset, ~~This~~celiprolol, ~~name~~and ~~reflects~~plan to further expand our ~~intense~~pipeline ~~focus~~through ~~and~~inorganic ~~dedication~~growth. We intend to ~~developing~~become ~~transformational,~~the ~~patient-focused~~preferred ~~therapies~~partner for ~~rare~~assets ~~diseases~~that ~~with~~we ~~limited~~believe orwill noallow ~~treatment~~us ~~options~~to ~~available,~~leverage orthe ~~treatment~~expertise ~~areas~~and ~~with~~infrastructure ~~significant~~that ~~unmet~~we ~~needs~~have built to help mitigate risk and enhance our probability of success.

In May 2022, we purchased all of the assets and operations of Orphazyme A/S (“Orphazyme”) related to arimoclomol. On September 20, ~~settled~~ ~~all~~2024, the U.S. Food and Drug Administration (“FDA”) approved the New Drug Application (“NDA”) for MIPLYFFA, for use in combination with miglustat for the treatment of ~~Orphazyme’s~~neurological ~~actual~~manifestations ~~outstanding~~of ~~liabilities~~NPC toin ~~its~~adult ~~creditors~~and pediatric patients 2 years of age and older, and MIPLYFFA became commercially available for dispense in the United States in November 2024. In connection with this approval, we received a ~~cash~~transferable ~~payment~~rare ofpediatric ~~$12~~disease priority review voucher (“PRV”).8 ~~million~~On April 1, ~~and agreed~~2025, towe ~~assume~~consummated anthe ~~estimated~~sale ~~reserve~~of ~~clawback~~the ~~liability~~PRV, resulting in net proceeds of $5148.23 million ~~related~~ to ~~revenue~~us. ~~generated~~MIPLYFFA ~~from~~has ~~Orphazyme’s~~also ~~EAP~~been granted orphan medicinal product designation for the treatment of NPC by the European Commission. We are pursuing regulatory approval in ~~France~~E.U. and filed a Marketing Authorization Application (“MAA”) with the European Medicines Agency (“EMA”) in July 2025; the application is currently under review.

On November 17, 2023, we completed the acquisition of Acer Therapeutics, Inc. ~~Pursuant~~ to(“Acer”), ~~the~~pursuant ~~Merger~~to ~~Agreement,~~which Acer ~~continues~~became as a wholly-owned subsidiary of Zevra. ~~The~~This ~~Merger~~ included the acquisition of OLPRUVA® (sodium phenylbutyrate) for oral suspension, which ~~was~~is ~~approved~~commercially byavailable in the ~~FDA on December 27~~U.S., ~~2022,~~ for the treatment of certain urea cycle disorders ("“UCDs"”). In addition, we acquired Acer's pipeline of investigational product candidates, including celiprolol for the treatment of Vascular Ehlers-Danlos syndrome ("VEDS") in, patients with a confirmed type III collagen (COL3A1) mutation. We are actively enrolling a Phase 3 clinical trial, known as DiSCOVER, to determine whether celiprolol reduces the risk of clinical events in patients with VEDS.

OnOur ~~September~~Product ~~20,~~Candidates ~~2024, the FDA approved the New Drug Application (“NDA") for MIPLYFFA™ (arimoclomol), an orally-delivered treatment for Niemann-Pick disease type C (“NPC"), which is an ultra-rare~~ and ~~progressive~~Approved neurodegenerative disease. In addition, we received a transferable rare pediatric disease priority review voucher (“PRV”) in conjunction with the approval. MIPLYFFA has also been granted orphan medical product designation for the treatment of NPC by the European Commission. In November 2024, MIPLYFFA became commercially available for dispense.Products

~~Our~~We ~~five-year~~have ~~strategic~~built ~~plan is focused on the continued transformation of Zevra into~~ a ~~leading~~diverse ~~rare-disease~~portfolio ~~company. In addition to the commercialization~~ of ~~OLPRUVA~~ products and ~~the~~product ~~approval~~candidates ~~and~~through ~~subsequent~~a ~~launch~~combination of ~~MIPLYFFA, we~~internal ~~discontinued our in-house drug discovery activities and closed our laboratory facilities in Iowa and Virginia to prioritize near-term resources for our late-stage clinical~~ development and ~~commercial~~strategic ~~opportunities~~investments inthrough ~~the third quarter of 2024~~acquisition. InFor ~~the~~example, ~~future~~ we ~~plan~~employed ~~to outsource~~ our ~~discovery and~~proprietary ~~early~~Ligand ~~development~~Activated ~~activities,~~Technology as(LAT) ~~well~~platform ~~as seek~~ to ~~further~~develop ~~expand~~approved ~~our~~product ~~pipeline~~AZSTARYS. ~~through~~Through ~~both internal development and through~~ our business development ~~activities to collaborate~~efforts, ~~partner, and potentially acquire additional assets. We intend to target assets that will allow us to leverage the expertise and infrastructure that~~ we have ~~built~~added tocommercial ~~help~~products ~~mitigate~~(MIPLYFFA ~~risk~~ and ~~enhance our probability of success. If we are successful~~OLPRUVA), ~~expanding our pipeline could be accretive to our value proposition~~ and ~~has~~a ~~the~~clinical ~~potential~~development tocandidate ~~create incremental long-term value for stockholders~~(celiprolol).

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~~Our~~Current ~~Product~~commercial ~~Candidates~~products and ~~Approved~~active ~~Products~~development assets are summarized in the table below:

WeActive ~~have~~Zevra ~~built~~Commercial ~~a diverse portfolio of products~~ and ~~product~~Active ~~candidates~~Development through a combination of internal development and strategic investments through acquisition. For example, we have employed our proprietary Ligand Activated Technology ("LAT") platform to develop approved products (e.g., AZSTARYS), and clinical development candidates (KP1077IH and KP1077N). Through our business development efforts, we have added commercial products (OLPRUVA and MIPLYFFA), and a clinical development candidate (celiprolol). We furthermore have a variety of product candidates and compounds that are clinical-stage and designed to address a variety of rare diseases and other indications.Assets

Currently active commercial products and development assets are summarized in the table below:

Parent Drug

Indication

Product / Candidate

Status and IP

Arimoclomol

Niemann-Pick disease type C (NPC)

MIPLYFFA

FDA Approval: Sep. 20, 2024; Orphan Drug Exclusivity (“ODE”) through 2031

Expanded Access Program (“EAP”)

Marketing Authorisation Application (“MAA”) under review by EMA, Submitted July 28, 2025

Sodium phenylbutyrate

Urea Cycle Disorders (UCD)

OLPRUVA

FDA Approval: Dec. 22, 2022; IP through 2036

Celiprolol

Vascular Ehlers Danlos Syndrome (VEDS)

Celiprolol

Clinical - Phase 3 trial ongoing; IP potential through 2038

Serdexmethylphenidate

Idiopathic Hypersomnia (IH)

KP1077IH

Clinical - Phase 3 trial ready; IP potential through 2038

Serdexmethylphenidate

Narcolepsy

KP1077N

Clinical - Phase 3 trial potential; IP potential through 2038

Serdexmethylphenidate and dexmethylphenidate

Attention Deficit and Hyperactivity Disorder (ADHD)

AZSTARYS

FDA Approved and Partnered - Receiving royalties and milestones on net sales; IP through 2037

Active Zevra Commercial and Development Assets

Parent Drug	Indication	Product / Candidate	Development Status	Next Milestone(s)
Arimoclomol	Niemann Pick disease type C (NPC)	MIPLYFFA	FDA Approved European EAP	Tracking Commercial Progress Target MAA Submission in H2 2025
Sodium phenylbutyrate	Urea Cycle Disorders (UCD)	OLPRUVA	FDA Approved	Tracking Commercial Progress
Celiprolol	Vascular Ehlers Danlos Syndrome (VEDS)	Celiprolol	Clinical - Phase 3	Phase 3 ongoing
Serdexmethylphenidate	Idiopathic Hypersomnia (IH)	KP1077IH	Clinical - Phase 2	Seeking Strategic Alternatives
Serdexmethylphenidate	Narcolepsy	KP1077N	Clinical - Phase 1/2	Seeking Strategic Alternatives
Serdexmethylphenidate and dexmethylphenidate	Attention Deficit and Hyperactivity Disorder (ADHD)	AZSTARYS	FDA Approved and Partnered	Collecting royalties and milestones

These anticipated milestones are based on information currently available to us. Our current plans and expectations are subject to a number of uncertainties, risks and other important factors that could materially impact our plans, including risks which are not solely within our control. See Part I, Item 1A. “Risk Factors” in this Annual Report on Form 10-K.

MIPLYFFA

OnNPC ~~September~~is ~~20,~~an ~~2024,~~ultra-rare ~~the~~and ~~FDA~~progressive ~~approved~~neurodegenerative ~~the~~disease ~~NDA~~characterized ~~for~~by ~~MIPLYFFA,~~ an ~~orally-delivered~~inability ~~treatment~~of ~~for~~the ~~NPC,~~body ~~which~~to istransport ancholesterol ~~ultra-rare~~ and ~~progressive~~lipids ~~neurodegenerative~~inside ~~disease~~of cells. ~~MIPLYFFA,~~Symptoms ~~the~~of ~~first~~NPC ~~FDA-approved~~include ~~treatment~~a ~~for~~progressive ~~NPC~~impairment of mobility, iscognition, ~~indicated~~speech, ~~for~~and ~~use~~swallowing, inoften ~~combination~~culminating ~~with~~in ~~miglustat~~premature ~~for~~death. ~~the~~The ~~treatment~~incidence of ~~neurological~~NPC ~~manifestations~~is ofestimated ~~NPC~~to be one in ~~adult~~100,000 ~~and~~to ~~pediatric~~130,000 ~~patients~~live ~~two~~births. ~~years~~We ofestimate ~~age~~that ~~and~~there ~~older.~~are Inapproximately ~~addition~~2,000 weindividuals ~~received~~with aNPC ~~transferable~~in ~~rare~~the ~~pediatric~~United ~~disease~~States ~~PRV in~~and ~~conjunction~~Europe ~~with~~combined, ~~the~~of ~~approval.~~which Onapproximately ~~February~~900 ~~27,~~are ~~2025,~~in wethe ~~announced~~United ~~entry~~States ~~into~~and an1,100 ~~asset~~are ~~purchase~~in ~~agreement~~Europe, ~~with~~where anthere ~~undisclosed~~is ~~party~~a ~~for~~mature ~~the~~market ~~sale~~with ofan ~~the PRV~~approved treatment available for ~~gross~~NPC. ~~proceeds~~Of ofthis ~~$150~~estimated ~~million~~population, ~~subject~~ approximately 300 to ~~customary~~350 ~~closing~~people ~~conditions.~~have ~~MIPLYFFA~~been ~~has~~diagnosed ~~also~~in ~~been~~the ~~granted~~United ~~orphan~~States. ~~medical~~NPC ~~product~~is ~~designation~~clinically ~~for~~heterogenous, ~~the~~with ~~treatment~~significant ofvariability ~~NPC~~in bysymptom ~~the~~presentation ~~European~~and ~~Commission. As~~rate of ~~December~~progression. Although ~~31,~~it ~~2025,~~has ~~there~~traditionally ~~was~~been considered a ~~total~~pediatric ofdisease ~~109~~due ~~enrollments~~ to ~~receive~~its ~~MIPLYFFA~~genetic origins, ~~which~~nearly ~~included~~half ~~conversion~~ of ~~all~~the ~~active~~people ~~participants~~treated inwith ~~our~~MIPLYFFA Uare adults.S. Low ~~EAP,~~diagnostic ~~which~~rates wemay ~~expect~~affect ~~to close by~~ the ~~end~~number of ~~the~~potential ~~second~~patients, ~~quarter~~and ofwe ~~2025. Our~~believe ~~commercial~~that ~~plans~~the ~~will~~availability ~~focus~~of ontreatment ~~continuing~~options toin ~~raise~~the ~~awareness~~United ~~among~~States ~~people~~could ~~who~~increase ~~are~~awareness ~~living~~of ~~with~~the ~~NPC~~disease ~~that~~and ~~are~~assist ~~diagnosed~~in ~~and~~more ~~untreated,~~accurately oridentifying ~~undiagnosed~~patients.

~~Soon~~On ~~after~~September ~~approval~~20, ~~of MIPLYFFA~~2024, the FDA approved athe ~~second~~NDA ~~therapy~~for MIPLYFFA, an orally-delivered treatment, for NPC,. ~~AQNEURSA~~MIPLYFFA, ~~which~~the isfirst FDA-approved treatment for ~~symptomatic~~NPC, is indicated for use in combination with miglustat for the treatment of ~~ataxia~~neurological inmanifestations of NPC in adult and pediatric patients, two years of age and isolder. ~~marketed~~In byaddition, ~~IntraBio~~we received a transferable rare pediatric disease PRV in conjunction with the approval. On April 1, ~~Inc~~2025, we completed the sale of the PRV and received net proceeds of $148.3 ~~("IntraBio")~~million.

ToEffective ~~commercialize~~therapies ~~both~~to oftreat ~~our~~NPC ~~commercial~~are ~~products~~desperately needed, ~~MIPLYFFA~~ and ~~OLPRUVA~~, infor ~~the~~this ~~U.S.~~reason, weMIPLYFFA ~~have~~is ~~built,~~currently orbeing ~~are~~made ~~making~~available ~~arrangements~~to ~~with~~NPC ~~third~~patients ~~parties~~in ~~to perform~~France, ~~marketing,~~ ~~sales~~Germany, ~~medical~~and ~~affairs,~~other ~~distribution~~EU member states, ~~managerial~~along ~~and~~with ~~other~~select ~~non-technical~~territories ~~capabilities. We~~outside ~~initiated~~of ~~the~~Europe ~~commercial~~under ~~launch~~our ofglobal EAP. MIPLYFFA inhas ~~the~~also ~~U.S.~~been ~~immediately~~granted ~~following~~orphan ~~receipt~~medicinal product designation for the treatment of ~~FDA~~NPC ~~approval~~by the European Commission. ~~Product~~ ~~became~~In ~~available~~July ~~for~~2025, ~~dispensing~~we atfiled ~~our~~an ~~specialty~~MAA, ~~pharmacy~~which onis ~~November~~under ~~21,~~review ~~2024~~by the EMA.

~~NPC~~As ~~is characterized by an inability~~ of ~~the body to transport cholesterol and lipids inside of cells. Symptoms of NPC include a progressive impairment of mobility~~December 31, ~~cognition~~2025, ~~speech,~~there ~~and~~were ~~swallowing,~~a ~~often~~total ~~culminating in premature death. The incidence~~ of ~~NPC~~161 isenrollments ~~estimated~~ to bereceive ~~one in 100,000 to 130,000 live births~~MIPLYFFA. WeFor ~~estimate that there are approximately 1~~MIPLYFFA,~~800~~ ~~individuals~~an ~~with~~enrollment ~~NPC in the U.S. and Europe combined, of which approximately 900 are in the U.S. and 1,100 are in the EU where there~~ is a ~~mature~~prescription ~~market~~submitted ~~with~~to anour ~~approved~~specialty ~~treatment available for NPC. Of these~~pharmacy, ~~approximately~~initiating ~~300 to 350 people have been diagnosed in~~ the ~~U.S.~~benefits ~~However,~~investigation ~~diagnostic~~process ~~challenges~~to ~~may~~determine ~~affect~~reimbursement ~~the~~and ~~number~~can oflead ~~potential~~to ~~patients,~~a ~~and~~30-day wepaid ~~believe~~dispense ~~that the availability~~ of ~~treatment~~MIPLYFFA. ~~options~~Our incommercial ~~the~~plans ~~U.S.~~focus ~~could~~on ~~increase~~raising awareness ofamong ~~the~~people ~~disease~~who ~~and~~are ~~assist~~living inwith ~~more accurately identifying patients. Effective therapies to treat~~ NPC that are ~~desperately~~diagnosed ~~needed,~~ and ~~for this reason~~untreated, ~~MIPLYFFA~~or ~~is currently being made available to NPC patients in France, Germany, and other EU member states under various EAPs~~undiagnosed.

~~Zevra~~To ~~holds global rights to develop and~~ commercialize MIPLYFFA. ~~We intend to seek regulatory approval for MIPLYFFA~~ in the ~~European~~United ~~Union ("EU")~~States, ~~and~~ we ~~are~~have ~~currently evaluating the potential to commercialize outside of the U.S.~~built, ~~and/~~or tohave ~~seek~~arrangements ~~additional~~with ~~regulatory~~third ~~approvals~~parties to ~~support~~perform, ~~future~~marketing, ~~global~~sales, ~~commercialization~~medical ~~opportunities.~~affairs, ~~Our~~distribution, ~~focus~~managerial isand ~~currently~~other onnon-technical ~~preparing~~capabilities. ~~for~~Zevra ~~submission~~holds ofglobal arights ~~Marketing~~to ~~Authorisation~~develop ~~Application,~~and orcommercialize ~~MAA, in Europe in the second half of 2025~~MIPLYFFA.

MIPLYFFA summary:

● Demonstrated halting of disease progression. MIPLYFFA in combination with miglustat is the only currently approved NPC therapy to demonstrate halting of disease progression through 12 months of treatment. ● Ease of flexible administration as an oral treatment. MIPLYFFA is administered as an oral capsule that can be swallowed whole, opened and contents mixed with foods or liquids, or delivered through a feeding tube. ● Extensive clinical experience with favorable safety data. No significant safety findings have been reported with more than 600 patients treated in various clinical trials conducted for multiple indications and through our EAPs. ● Regulatory designations. MIPLYFFA has been granted orphan drug designation for the treatment of NPC by the European Commission. We received a transferable PRV upon approval of MIPLYFFA. On February 26, 2025, we entered into the PRV Transfer Agreement, pursuant to which we agreed to sell the PRV to the buyer, subject to customary closing conditions

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MIPLYFFA summary:

•Demonstrated halting of disease progression. MIPLYFFA in combination with miglustat demonstrated a clinically significant improvement compared to placebo as early as 12 weeks and a halting of progression of the disease through 12 months of treatment. Data from the 48-month Open Label Extension study confirms the effectiveness of MIPLYFFA in halting disease progression over multiple years.

•Ease of flexible administration as an oral treatment. MIPLYFFA is administered as an oral capsule that can be swallowed whole, opened and contents mixed with foods or liquids, or delivered through a feeding tube.

•Extensive clinical experience with favorable safety data. Over 600 patients have been treated with arimoclomol across various clinical trials and indications as well as through our global EAP, with no safety findings of concern found. Further, in a pediatric sub-study of patients aged 6–24 months, arimoclomol was well tolerated following at least 12 months of treatment with no new safety concerns observed.

•Advantageous regulatory designations. MIPLYFFA has been granted orphan medicinal product designation for the treatment of NPC by the European Commission.

OLPRUVA

~~OLPRUVA (sodium~~UCDs ~~phenylbutyrate)~~are ~~for~~a ~~oral~~group ~~suspension~~of israre ~~approved~~genetic indisorders ~~the~~that ~~U.S.~~can ascause ~~adjunctive~~harmful ~~therapy~~ammonia to ~~standard~~build ~~of care~~up in the blood, ~~which~~potentially ~~includes~~resulting ~~dietary~~in ~~management~~brain damage and neurocognitive impairments, ~~for~~if ~~the~~ammonia ~~chronic~~levels ~~management~~are ofnot ~~UCDs involving~~controlled. ~~deficiencies~~Any ofincrease ~~carbamylphosphate~~in ~~synthetase~~ammonia ~~(CPS),~~over ~~ornithine~~time ~~transcarbamylase~~is ~~(OTC)~~serious. Therefore, orit ~~argininosuccinic~~is ~~acid~~important ~~synthetase~~to ~~(AS)~~adhere to any dietary protein restrictions and have alternative medication options to help control ammonia levels. ~~OLPRUVA~~Approximately ~~for~~1 ~~oral~~in ~~suspension is~~100,000 apeople ~~proprietary~~have UCD, and ~~novel~~there ~~formulation~~are ofan ~~sodium~~estimated ~~phenylbutyrate~~800 ~~powder,~~patients ~~packaged~~who are actively treated with nitrogen scavenging therapy in ~~pre-measured~~the ~~single-dose~~United ~~envelopes~~States While there are therapies currently approved for the treatment of UCDs, there remain unmet needs for this community of patients. We believe that ~~has~~OLPRUVA ~~shown~~offers ~~bioequivalence~~benefits toover ~~existing~~other ~~sodium~~UCD ~~phenylbutyrate~~treatments ~~powder~~by ~~but~~eliminating issues with apalatability, ~~pH-sensitive~~offering ~~polymer~~improved ~~coating~~portability ~~that~~with isits ~~designed~~single-dose toenvelopes, ~~minimize~~and ~~dissolution~~being ofprovided ~~the~~in ~~coating~~a ~~for~~dosage uppersonalized to ~~five~~the ~~(5)~~patient ~~minutes~~based ~~after~~on ~~preparation~~weight.

~~UCDs~~OLPRUVA ~~are~~(sodium aphenylbutyrate) ~~group~~for oforal ~~rare genetic~~suspension ~~disorders~~is ~~that~~approved ~~can cause harmful ammonia to build up~~ in the ~~blood,~~United ~~potentially~~States ~~resulting~~as inadjunctive ~~brain~~therapy ~~damage~~to ~~and~~standard ~~neurocognitive~~of ~~impairments~~care, ifwhich ~~ammonia~~includes ~~levels~~dietary ~~are not controlled. Any increase in ammonia over time is serious. Therefore~~management, itfor isthe ~~important~~chronic tomanagement ~~adhere~~of toUCDs ~~any~~involving ~~dietary~~deficiencies ~~protein~~of ~~restrictions~~carbamylphosphate ~~and~~synthetase ~~have~~(CPS), ~~alternative~~ornithine ~~medication~~transcarbamylase ~~options~~(OTC), toor ~~help~~argininosuccinic ~~control~~acid ~~ammonia~~synthetase ~~levels~~(AS). ~~Approximately~~OLPRUVA 1for inoral ~~100,000~~suspension ~~people~~is ~~have~~a ~~UCD,~~proprietary and ~~there~~novel ~~are~~formulation anof ~~estimated~~sodium ~~800~~phenylbutyrate ~~patients~~powder, ~~who~~packaged ~~are actively treated with nitrogen scavenging therapy~~ in ~~the~~pre-measured ~~U.S. While there are therapies currently approved for the treatment of UCDs~~ single-dose ~~specifically RAVICTI~~envelopes, ~~marketed~~that byhas ~~Amgen,~~shown ~~Inc.~~bioequivalence ~~(formerly~~to ~~Horizon~~existing ~~Therapeutics)~~sodium ~~and~~phenylbutyrate ~~PHEBURANE,~~powder ~~marketed~~but bywith ~~Medunik~~a ~~USA~~ pH-sensitive ~~there~~polymer ~~remain~~coating ~~unmet~~that ~~needs~~is ~~for~~designed ~~this~~to ~~community~~minimize dissolution of ~~patients.~~the ~~OLPRUVA~~coating ~~offers~~for ~~benefits~~up ~~over~~to ~~other~~five ~~UCD~~minutes ~~treatments~~after bypreparation ~~eliminating~~to ~~issues~~help ~~with~~minimize ~~palatability,~~the ~~offering~~unpleasant ~~improved~~taste ~~portability~~of ~~with its single-dose envelopes, and it comes in a dosage personalized to~~ the ~~patient~~sodium ~~based~~phenylbutyrate ~~on weight~~powder.

~~During~~In the fourth quarter ~~ended~~of ~~December 31,~~ 2023, we began generating revenue from the sale of OLPRUVA in the ~~U.S.~~United ~~For additional information regarding the Merger, see Note T of our consolidated financial statements included elsewhere in this Annual Report on Form 10-K~~States. Zevra has a partnership with Relief Therapeutics ~~who~~SA (“Relief”), which has rights to commercialize OLPRUVA in various EU European countries, if approved. InFor ~~addition~~the year ended December 31, ~~Zevra~~2025, iswe ~~obligated~~had to$0.8 ~~pay royalties~~million ofin ~~10%~~revenue from sales of UOLPRUVA.S. ~~net~~We ~~sales~~have upmade the decision to ascale ~~maximum~~back ofour ~~$45~~sales ~~million,~~and ~~plus~~marketing ~~specified~~efforts ~~regulatory~~for ~~milestones~~OLPRUVA toas ~~Relief~~we ~~Therapeutics~~evaluate the path forward and weigh strategic alternatives.

During the first half of 2024, we initiated the commercial launch of OLPRUVA in the U.S. We have focused our initial efforts on the approximately 40 metabolic treatment centers of excellence across the United States which treat the majority of UCD patients to build awareness with physicians regarding the benefits of OLPRUVA. In the months since launch, our team has been able to engage with more than 90% of our prescribers. We have seen meaningful growth in reimbursement coverage, which was approximately 55% of U.S. covered lives at the time of acquisition, to now approximately 76%. In the third quarter of 2024, Zevra made a data-driven shift in our OLPRUVA commercial strategy to target specific patient segments that will receive the greatest benefit from OLPRUVA and face fewer reimbursement hurdles. To support this refinement in strategy, we focused our resources and promotional efforts in the third quarter to drive patient identification and to improve pull-through with payors. Specifically, we are targeting patients seeking greater lifestyle independence who could benefit from the “ammonia control on the go” that OLPRUVA offers.

OLPRUVA summary:

● •OLPRUVA is available in the U.S for the treatment of ~~UCD~~certain types of UCDs. OLPRUVA is an adjunctive therapy for ~~long-term~~the chronic management of adults and children weighing 20kg or greater with UCD from deficiencies of CPS, OTC, or AS. ● OLPRUVA is differentiated from currently available forms of phenylbutyrate. OLPRUVA is formulated to improve palatability while providing patients with a portable and discrete pre-measured dose. ● Zevra has assembled a team to support OLPRUVA and additional future commercial products. We have established an efficient commercial team which is designed to fully service the patients and prescribers within the rare disease indications we are pursuing.

•OLPRUVA is differentiated from currently available forms of phenylbutyrate. OLPRUVA is formulated to improve palatability while providing patients with a portable and discrete pre-measured dose.

•Currently evaluating strategic alternatives. We have had limited success in commercializing OLPRUVA in the United States, and we are currently evaluating the path forward and weighing strategic alternatives.

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Celiprolol

~~The~~Ehlers-Danlos ~~Merger~~Syndrome ~~with~~(EDS) ~~Acer~~is ~~included~~a ~~the~~rare ~~acquisition~~inherited ofdisorder ~~celiprolol.~~caused Weby ~~are~~mutations ~~advancing~~in ~~celiprolol~~the asgenes anresponsible ~~investigational~~for ~~product~~the ~~candidate~~structure, ~~for~~production, ~~the~~or ~~treatment~~processing of ~~VEDS~~collagen, an important component of the connective tissues in ~~patients~~the ~~with~~human abody, ~~confirmed~~or ~~type~~proteins ~~III~~that ~~collagen~~interact ~~(COL3A1)~~with ~~mutation~~collagen. ~~Celiprolol~~VEDS is athe ~~selective~~most ~~adrenergic~~severe ~~modulator~~of ~~(“SAM“)~~the ~~and,~~13 iftypes weof ~~receive~~EDS ~~the~~and ~~first~~causes ~~approval~~abnormal fragility in large to medium sized arteries and hollow organs, such as the Uuterus and colon.S. ~~for~~This ~~celiprolol~~fragility can result in aneurysms, weabnormal ~~believe~~connections itbetween ~~would~~blood bevessels ~~deemed~~known aas ~~new~~arteriovenous ~~chemical~~fistulas, ~~entity~~arterial ~~(“NCE”)~~dissections, inand ~~the~~spontaneous Uvascular and organ ruptures, all of which can be potentially life-threatening.S. ~~Celiprolol~~The incidence of VEDS is ~~currently~~estimated ~~approved~~to be one in ~~certain~~50,000 EUto ~~states~~200,000 ~~for~~people. ~~the~~There ~~treatment~~are ofapproximately ~~hypertension~~7,500 ~~and~~patients ~~angina~~in the United States.

~~Ehlers-Danlos~~We ~~Syndrome~~are isadvancing anceliprolol ~~inherited~~as ~~disorder~~an ~~caused~~investigational byproduct ~~mutations~~candidate ~~in the genes responsible~~ for the ~~structure,~~treatment ~~production, or processing~~ of ~~collagen,~~VEDS ~~an important component of the connective tissues~~ in ~~the~~patients ~~human~~with ~~body,~~a orconfirmed ~~proteins~~type ~~that~~III ~~interact~~collagen ~~with~~(COL3A1) ~~collagen~~mutation. ~~VEDS~~Celiprolol ~~causes~~is ~~abnormal~~a ~~fragility~~selective inadrenoceptor ~~blood~~modulator ~~vessels,~~(“SAM”) ~~which~~that ~~can~~we ~~give~~believe ~~rise~~would toqualify ~~aneurysms, abnormal connections between blood vessels known~~ as ~~arteriovenous~~a ~~fistulas,~~new ~~arterial~~chemical ~~dissections,~~entity ~~and~~(“NCE”) ~~spontaneous~~if ~~vascular~~approved ~~ruptures,~~in ~~all~~the ofUnited ~~which can be potentially life-threatening~~States. ~~The~~Celiprolol ~~incidence of VEDS~~ is ~~estimated~~currently toapproved ~~be one~~ in ~~50,000~~certain toEU ~~200,000~~states ~~people.~~for ~~There~~the ~~are~~treatment ~~approximately~~of ~~7,500~~hypertension ~~patients~~and ~~in the U~~angina.S.

Currently, there are no approved therapies anywhere in the world for VEDS. However, celiprolol, prescribed off label, has become the standard of care therapy for VEDS in some European countries. Medical intervention for VEDS focuses on surgery, symptomatic treatment, genetic counseling, and prophylactic measures, such as avoiding intense physical activity, scuba diving, and violent sports. Therefore, patients must adopt a “watch and wait” approach following any confirmed diagnosis. Unfortunately, many of these arterial events have high mortality associated with them,; ~~and~~ thus, a pharmacologic intervention that reduces the rate of events would be clinically meaningful.

Celiprolol received orphan drug designation from the FDA for the treatment of VEDS in 2015. In October 2018, a new celiprolol NDA was submitted to the FDA by Acer based on data obtained from the BBEST trial and was subsequently accepted by the FDA in October 2018 with priority review status. Following FDA review, Acer received a complete response letter (“CRL”) from the FDA stating that it will be necessary to conduct an adequate and well-controlled trial to determine whether celiprolol reduces the risk of clinical events in patients with VEDS. Subsequently, Acer appealed the FDA decision,. ~~and~~While ~~while~~ the FDA denied the appeal, it described possible paths forward toward approval. In a May 2021 Type B meeting with the FDA, Acer discussed the conduct of ana U.S.-based prospective, randomized, double-blind, placebo-controlled, decentralized clinical trial in patients with COL3A1 positive VEDS, and sought the FDA’s opinion on various proposed design features of the study.

Based on the FDA's feedback during the Type B meeting, weAcer adopted a decentralized (virtual) event-based clinical trial design and use of an independent centralized adjudication committee with a primary endpoint based on clinical events associated with disease outcome. In April 2022, the FDA granted celiprolol Breakthrough Therapy designation ~~(“BTD”)~~ in the ~~U.S.~~United States for the treatment of patients with COL3A1-positive VEDS.

In July 2022, Acer initiated enrollment in a Phase 3 long-term event-driven clinical trial designed based on the discussions from the May 2021 Type B meeting with the FDA, also known as the DiSCOVER trial. The DiSCOVER trial intends to enroll 150 VEDS patients, with 100 patients receiving celiprolol and 50 patients receiving placebo. Recruitment in the Phase-3 trial was restarted mid-2024 ~~after~~ ~~a brief hiatus~~ and the trial ishas ~~actively~~52 ~~enrolling~~enrolled ~~patients~~participants as of December 31, 2025. We believe that celiprolol could address significant unmet needs, as there are currently no approved treatments for VEDS in the U.S. We have implemented a broad recruitment drive focusing on collaborating with medical clinics where most patients are being managed. In parallel, we are engaging with the FDA to discuss regulatory options to accelerate the development program.

Celiprolol summary:

● •Currently, no approved treatments for VEDS in the UUnited States.S. There are currently no approved treatments offor VEDS in the ~~U.S.~~United States, and we believe that celiprolol, if approved, could be a significant innovation in the treatment of VEDS ~~in the U.S.~~ where current treatment options are focused primarily on surgical intervention. ● Unique pharmacological profile. Mechanism of action in VEDS patients is thought to be through vascular dilatation and smooth muscle relaxation, the effect of which is to reduce the mechanical stress on collagen fibers in the arterial wall, and thereby potentially less incidence of vascular ruptures. ● Evidence of efficacy in the EU and extensive clinical experience from multiple trials. Celiprolol has become the primary treatment for VEDS patients in several European countries. BBEST Clinical Trial data showed 76% reduction in risk of arterial events observed in COLA3A1+ subpopulation, with additional data from a long-term observational study in France. ● Regulatory designations. Celiprolol for VEDS would be considered an NCE in the U.S. and has been granted Orphan Drug designation and Breakthrough Therapy designation. ● Solid patent protection through 2038. Celiprolol is generally protected by U.S. patents that will expire, after utilizing all appropriate patent term adjustments but excluding possible term extensions, in 2038.

•Unique pharmacological profile. Mechanism of action in VEDS patients is thought to be through vascular dilatation and smooth muscle relaxation, the effect of which is to reduce the mechanical stress on collagen fibers in the arterial wall, potentially resulting in less incidence of vascular and hollow organ ruptures.

•Evidence of efficacy in Europe and extensive clinical experience from multiple trials. Celiprolol has become the primary treatment for VEDS patients in several European countries. BBEST Clinical Trial data showed 76% reduction in risk of arterial events observed in COLA3A1+ subpopulation, with additional data from a long-term observational study in France.

•Regulatory designations. Celiprolol for VEDS has been granted Orphan Drug designation and Breakthrough Therapy designation and, we believe, would be deemed an NCE in the United States if approved before any other celiprolol product.

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•Solid patent protection through 2038. Celiprolol is generally protected by U.S. patents that will expire, after utilizing all appropriate patent term adjustments but excluding possible term extensions, in 2038.

KP1077

~~KP1077~~Idiopathic ishypersomnia ~~being developed and evaluated for the treatment of~~ (“IH”) ~~and narcolepsy. IH~~ is a rare neurological sleep disorder affecting approximately 37,000 patients in the United States. The cardinal feature of IH is excessive daytime sleepiness ("“EDS"”), characterized by daytime lapses into sleep, or an irrepressible need to sleep that persists even with adequate or prolonged nighttime sleep. Additionally, those with IH have extreme difficulty waking, otherwise known as “sleep inertia,” suffer from severe and debilitating brain fog, and may fall asleep unintentionally or at inappropriate times, also known as narcolepsy. These symptoms often further lead to reported memory problems, difficulty maintaining focus, and depression.

~~There~~Narcolepsy is ~~currently~~a ~~only~~rare, ~~one~~chronic, ~~approved~~debilitating ~~product~~neurologic ~~for~~disorder ~~the treatment~~ of ~~IH,~~sleep-wake ~~XYWAV,~~state ~~developed~~instability bythat ~~Jazz~~impacts ~~Pharmaceuticals.~~up Ato ~~second product~~200,000 ~~WAKIX,~~Americans ~~developed by Harmony Biosciences ("Harmony")~~ and ~~originally~~is ~~approved~~primarily ~~for~~characterized ~~the~~by ~~treatment of~~ EDS orand cataplexy in(sudden ~~adult~~loss ~~patients~~of ~~with~~muscle ~~narcolepsy,~~tone ~~but~~while ina ~~October~~person ~~2023,~~is ~~Harmony~~awake) ~~announced~~along ~~that~~with ~~the~~other ~~difference~~manifestations inof ~~outcome~~rapid ~~for~~eye ~~EDS~~movement ~~when comparing WAKIX~~ and ~~placebo~~sleep indysregulation, ~~its~~which ~~Phase~~intrude 3into ~~trial~~wakefulness. ~~with~~In IHmost patients, ~~did not reach statistical significance. Prescribers also utilize~~ narcolepsy ~~medications~~is ~~and~~caused ~~various~~by ~~stimulant~~the ~~products~~loss ~~“off-label”~~of ~~to treat IH symptoms~~hypocretin, ~~with methylphenidate,~~ a ~~stimulant~~neuropeptide ~~which~~in ~~has been classified by~~ the ~~DEA~~brain asthat asupports ~~Schedule~~sleep-wake IIstate ~~controlled~~stability. ~~substance,~~Typical ~~being~~symptom ~~one~~onset ofoccurs ~~the~~in ~~most~~adolescence ~~commonly~~or ~~used~~young ~~stimulants~~adulthood, ~~for~~but ~~treating~~it ~~IH.~~can ~~While~~take ~~each~~up ofto ~~these~~a ~~medications~~decade ~~can help~~ to ~~address~~be ~~certain~~properly IHdiagnosed. ~~symptoms,~~Although there are ~~also~~several ~~potential~~approved ~~shortcomings,~~medications ~~including~~for ~~dosing inconvenience~~narcolepsy, ~~serious~~we ~~adverse~~believe ~~events,~~a ~~such~~treatment asoption ~~elevated~~based ~~blood~~on ~~pressure~~serdexmethylphenidate ~~and~~(“SDX”), ~~heart~~our ~~rate,~~proprietary ~~and~~prodrug ~~significant~~of ~~drug~~d-~~to-drug~~methylphenidate ~~interactions~~ (~~"DDIs"~~“d-MPH”), ~~including~~which ~~with~~has ~~medications~~previously ~~used~~been toclassified ~~manage~~as ~~contraception~~a ~~and~~Schedule ~~depression.~~IV Incontrolled ~~addition~~substance, ~~patients~~may ~~have~~be ~~indicated that the effectiveness of their current medication was poor~~beneficial.

~~Narcolepsy is a rare~~KP1077, chronic, debilitating neurologic disorder of sleep-wake state instability that impacts up to 200,000 Americans and is primarily characterized by EDS and cataplexy (sudden loss of muscle tone while a person is awake) along with other manifestations of rapid eye movement ("REM"), sleep dysregulation, which ~~intrude~~utilizes into wakefulness. In most patients, narcolepsy is caused by the loss of hypocretin, a neuropeptide in the brain that supports sleep-wake state stability. Typical symptom onset occurs in adolescence or young adulthood, but it can take up to a decade to be properly diagnosed. Although there are several approved medications for narcolepsy, we believe a treatment option based on serdexmethylphenidate (“SDX”), our ~~proprietary~~ prodrug of d-~~methylphenidate (“d-~~MPH”), ~~which has previously been classified~~ as aits ~~Schedule~~active IVpharmaceutical ~~controlled substance~~ingredient, ~~with~~is ~~superior~~being ~~exposure/duration~~developed ~~characteristics~~ and ~~low~~evaluated ~~abuse~~for ~~potential~~the ~~may~~treatment beof ~~beneficial~~IH and narcolepsy.

WeIn ~~reported~~December ~~final~~2022, ~~data~~we ~~for~~announced the ~~Phase~~initiation ~~1 proof-~~of~~-concept~~ ~~study~~a ~~of SDX in the first quarter of 2022. Increased wakefulness~~double-blind, ~~alertness~~placebo-controlled, ~~hypervigilance~~randomized-withdrawal, ~~and insomnia effects were reported by study participants~~dose-optimizing, ~~which~~multicenter wePhase ~~believe~~2 ~~suggests~~clinical ~~that~~trial ~~SDX~~evaluating ~~produced~~the ~~targeted~~efficacy ~~pharmacodynamic~~and ~~effects~~safety ~~that~~of ~~have~~KP1077 for the ~~potential~~treatment toof ~~benefit patients with~~ IH. ~~and~~The ~~other~~trial ~~sleep~~concluded ~~disorders.~~in InMarch ~~November~~2024 ~~2022,~~and weprovided ~~announced~~meaningful ~~that~~information of the ~~FDA~~optimal ~~has~~dose ~~granted~~and ~~the~~dosing ~~orphan~~regimen ~~drug designation~~ to ~~SDX~~inform ~~for~~Phase ~~the~~3 ~~treatment~~trial ~~of IH~~design.

~~KP1077~~Clinically ~~utilizes~~meaningful ~~SDX,~~improvements ~~our~~were ~~prodrug~~observed ofacross ~~d-MPH,~~all asendpoints ~~its API~~studied. ~~During~~The ~~the~~exploratory ~~first~~endpoints ~~quarter~~ of ~~2022,~~sleep weinertia ~~initiated~~and abrain ~~Phase~~fog 1performed ~~clinical~~in-line ~~trial~~with ~~comparing~~expectations ~~the~~and ~~cardiovascular~~were ~~safety~~stable ofwhen ~~SDX~~compared toacross ~~immediate-release~~a ~~and~~variety ~~long-acting formulations~~ of ~~RITALIN,~~other ~~a commonly prescribed central nervous system ("CNS") stimulant~~endpoints. InSymptom ~~September~~improvements ~~2022,~~in wepatients ~~announced~~receiving ~~topline~~KP1077 ~~data~~were ~~from~~similar ~~our~~after ~~exploratory~~both Phase 1 clinical trial, which showed the potential for higher dose formulations of SDX to be safe and well tolerated while avoiding the potential for greater cardiovascular safety risk compared to immediateonce-~~release~~per-day and ~~long~~twice-~~acting~~per-day ~~formulations of RITALIN~~dosing.

Based on the data, in December 2022, we announced the initiation of a double-blind, placebo-controlled, randomized-withdrawal, dose-optimizing, multicenter Phase 2 clinical trial evaluating the efficacy and safety of KP1077 ~~for the treatment of IH. The trial concluded in March 2024 and provided meaningful information of the optimal dose and dosing regimen to inform Phase 3 trial design.~~summary:

~~Clinically~~•No ~~meaningful~~drug-to-drug ~~improvements~~interactions ~~were~~ observed ~~across~~to ~~all studied endpoints~~date. ~~The~~We ~~exploratory~~have ~~endpoints~~not ofobserved ~~sleep inertia and brain fog performed in~~drug-~~line~~to-drug ~~with~~interactions ~~expectations and were stable when compared across a variety of other endpoints. Symptom improvements~~ in ~~patients~~clinical ~~receiving KP1077 were similar after both once~~drug-~~per-day,~~drug ~~and~~interaction ~~twice-per-day dosing~~studies.

In•Possible ~~the~~reduction ~~Phase~~of 2abuse ~~trial,~~potential ~~KP1077~~as ~~was~~a ~~observed~~Schedule toIV becontrolled ~~well-tolerated at all dose levels and both dosing regimens, with adverse events that are typical for stimulants and mostly mild in severity~~substance. ~~These~~All ~~results~~other ~~are consistent with data from the Phase 1 trial with SDX that indicated no greater cardiovascular safety risk despite higher overall exposure levels when compared to both immediate and long~~methylphenidate-~~acting~~based ~~methylphenidate~~ products ~~currently~~have ~~used~~been ~~off-label~~designated for the treatment of IH. On June 3, 2024, we announced final results from the Phase 2 Clinical Trial of KP1077 for IH. The proof-of-concept study was designed to evaluate safety and tolerability and was not powered to demonstrate statistical significance. However, the trial included several important secondary and exploratory endpoints, such as ~~the~~Schedule ~~change~~II incontrolled ~~Epworth Sleepiness Scale ("ESS") total score~~substances, ~~the~~which IHindicates ~~Severity~~stricter ~~Scale~~control ~~("IHSS"),~~over the ~~Sleep~~prescribing ~~Inertia Visual Analog Scale ("SIVAS"),~~ and ause ~~new scale to assess the symptoms and severity~~ of ~~brain~~such ~~fog~~products. ~~These data gathered from the secondary endpoints will help inform the study design for a potential Phase 3 clinical trial of~~ KP1077.'s Wesole ~~held~~active ~~the~~pharmaceutical ~~end-of-Phase~~ingredient 2is ~~meeting with the FDA in September 2024~~SDX, towhich ~~discuss~~has ~~the~~been ~~design~~designated of a ~~Phase~~Schedule 3IV ~~trial~~controlled ~~to study KP1077 in IH~~substance. The FDA indicated that a single pivotal study with appropriate confirmatory evidence will be sufficient to submit a new NDA. We are evaluating strategic alternatives to advance clinical development toward NDA submission and later, commercialization. KP1077 is subject to the terms and conditions of the AZSTARYS License Agreement (as defined below) but is not currently licensed to Commave thereunder.

•No currently approved generic equivalent product. KP1077 contains SDX, our proprietary prodrug of d-methylphenidate, also known as the new chemical name, serdexmethylphenidate, by the U.S. Adopted Names Council of the American Medical Association, which means that there may be no generic equivalent product for KP1077 in most states, making drug-equivalent substitution potentially difficult at the pharmacy.

•Orphan drug designation. Because the size of the IH patient population is small, the FDA has granted KP1077 orphan drug designation for the treatment of IH. We believe KP1077 may potentially be eligible for fast-track and breakthrough therapy designation, which may provide various regulatory benefits for the development program.

AZSTARYS (partnered product)

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~~Key~~Commave ~~Takeaways~~has ~~from~~tasked ~~Phase~~its 2affiliate, ~~Clinical~~Corium, ~~Trial~~Inc. (“Corium”), to lead all commercialization activities for AZSTARYS in the United States. Corium commercially launched AZSTARYS in the United States during the third quarter of KP2021. ~~1077~~In December 2021, Commave entered into a sublicense of commercialization rights for ~~IH include:~~AZSTARYS in greater China to Shanghai Ark Biopharmaceutical Ltd.

●Pursuant ~~KP1077~~to ~~was~~the ~~well~~AZSTARYS ~~tolerated~~License atAgreement, ~~all~~Commave ~~dose~~agreed ~~levels~~to ~~evaluated~~pay up to $63.0 million in milestone payments upon the ~~trial~~occurrence of specified regulatory milestones related to AZSTARYS, including FDA approval and specified conditions with respect to the ~~highest~~final ~~dose~~approval label. In addition, Corium agreed to make additional payments upon the achievement of ~~320~~specified mgU.S. ~~daily,~~sales ~~regardless~~milestones of up to $420.0 million in the ~~dosing~~aggregate. ~~regimen:~~Further, ~~once~~Commave ~~daily~~will ~~(QD)~~pay us quarterly, tiered royalty payments based on a percentage of net sales on a product-by-product basis. Corium also agreed to be responsible for and reimburse us for all of development, commercialization and regulatory expenses for any products or ~~twice~~product ~~daily~~candidates ~~(BID)~~containing SDX, subject to certain limitations as set forth in the AZSTARYS License Agreement, including consultation fees to be paid to us for services provided to Corium in performing such activities.

○In ~~Adverse~~April ~~events~~2021, we entered into the AZSTARYS Amendment (~~AEs~~“AZSTARYS Amendment”), ~~were~~pursuant ~~similar~~to which we and Commave agreed to ~~other~~modify ~~methylphenidate~~the ~~products~~compensation terms of the AZSTARYS License Agreement. Commave paid us $10.0 million in connection with the execution of the AZSTARYS Amendment following the FDA approval of AZSTARYS in the United States. Corium also paid us $10.0 million following the SDX scheduling determination by the DEA, which occurred on May 7, 2021. In addition, the AZSTARYS Amendment increased the total remaining future regulatory and sales milestone payments related to AZSTARYS up to an aggregate of $590.0 million. The AZSTARYS License Agreement will continue on a product-by-product basis (i) until expiration of the royalty term for the applicable product candidate in the United States and (ii) perpetually for all other countries.

○In ~~Most~~May ~~common~~2021, ~~AEs~~we ~~included~~announced ~~insomnia,~~that ~~headache~~SDX, ~~anxiety~~our proprietary prodrug of d-MPH and the primary active pharmaceutical ingredient in AZSTARYS, ~~decreased~~was ~~appetite~~classified as a Schedule IV controlled substance by the DEA. AZSTARYS is classified as a Schedule II controlled substance, as its formulation includes a 70:30 mixture of SDX (Schedule IV) and ~~nausea~~d-MPH (Schedule II), respectively.

○ Most AEs occurred during the titration period, were mild, and did not lead to early discontinuation

● Although the study was not designed to be powered for statistical significance, KP1077 was associated with clinically meaningful improvements in EDS as assessed by change from baseline in the ESS during both the 5-week open-label (OL) titration period which was maintained during the 2-week double-blind withdrawal period for both dosing regimens.

○ Mean total ESS scores decreased by approximately 9 points after 5 weeks of OL treatment.

● Although the study was not designed to be powered for statistical significance, at the end of 7 weeks of treatment, patients administered KP1077 showed clinically meaningful benefits in change from baseline for the ESS, IHSS, SIVAS, and Brain Fog Scale (BFS):

○ Mean total ESS score decreased by 9.4 (QD) and 8.8 (BID)

○ Mean total IHSS score decreased by 16.1 (QD) and 12.3 (BID)

○ Mean SIVAS score decreased by 25.9 (QD) and 17.2 (BID)

○ Mean total BFS symptom score decreased by 23.8 (QD) and 22.3 (BID)

● The study fulfilled the objectives of providing key information for the design of a potentially pivotal efficacy trial, and the results of the secondary efficacy endpoints were supportive of initiating a Phase 3 trial of KP1077.

KP1077 Summary:

● No drug-to-drug interactions observed to date. We have not observed drug-to-drug interactions in clinical drug-drug interaction studies. ● Potential for reduced abuse potential as a Schedule IV controlled substance. All other methylphenidate-based products have been designated as Schedule II controlled substances, which indicates stricter control over the prescribing and use of such products. KP1077 is based on SDX, which has been designated a Schedule IV controlled substance. ● No currently approved generic equivalent product. KP1077 contains SDX, our proprietary prodrug of d-methylphenidate, also known as the new chemical name, serdexmethylphenidate, by the U.S. Adopted Names Council of the American Medical Association (“USAN”), which means that there may be no generic equivalent product for KP1077 in most states, making drug-equivalent substitution potentially difficult at the pharmacy. ● Orphan drug designation. Because the size of the IH patient population is small, the FDA has granted KP1077 orphan drug designation for the treatment of IH. We believe KP1077 may potentially be eligible for fast-track and breakthrough therapy designation, which may provide various regulatory benefits for the development program.

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AZSTARYS (Partnered product)

AZSTARYS contains d-MPH and our prodrug of d-MPH, SDX. On March 2, 2021, the FDA approved AZSTARYS as a once-daily treatment for attention deficit hyperactivity disorder (ADHD), in patients age six years and older. AZSTARYS is currently being marketed in the U.S. under our September 2019 collaboration and license agreement, or the AZSTARYS License Agreement, with Commave. Under the AZSTARYS License Agreement, we granted Commave an exclusive, worldwide license, to develop, manufacture, and commercialize AZSTARYS and any of our product candidates containing SDX and used to treat ADHD or any other CNS disease. In July 2020, we entered into the consulting agreement with Corium, Inc. ("Corium") (the “Corium Consulting Agreement”), under which Corium and Commave, respectively, engaged us to guide the product development and regulatory activities for certain current and potential future products in their portfolio, as well as continue supporting preparation for the potential commercial launch of AZSTARYS.

Commave has tasked Corium, another affiliate of Gurnet Point Capital, L.P., to lead all commercialization activities for AZSTARYS in the U.S. Corium commercially launched AZSTARYS in the U.S. during the third quarter of 2021. In December 2021, Commave entered into a sublicense of commercialization rights for AZSTARYS in greater China to Shanghai Ark Biopharmaceutical Ltd.

Pursuant to the AZSTARYS License Agreement, Commave agreed to pay up to $63.0 million in milestone payments upon the occurrence of specified regulatory milestones related to AZSTARYS, including FDA approval and specified conditions with respect to the final approval label. In addition, Corium agreed to make additional payments upon the achievement of specified U.S. sales milestones of up to $420 million in the aggregate. Further, Commave will pay us quarterly, tiered royalty payments based on a percentage of net sales on a product-by-product basis. Corium also agreed to be responsible for and reimburse us for all of development, commercialization and regulatory expenses for any products or product candidates containing SDX, subject to certain limitations as set forth in the AZSTARYS License Agreement, including consultation fees to be paid to us for services provided to Corium in performing such activities.

In April 2021, we entered into the AZSTARYS Amendment ("AZSTARYS Amendment"). Pursuant to the AZSTARYS Amendment, we and Commave agreed to modify the compensation terms of the AZSTARYS License Agreement. Commave paid us $10.0 million in connection with the execution of the AZSTARYS Amendment following the FDA approval of AZSTARYS in the United States. Corium also paid us $10.0 million following the SDX scheduling determination by the DEA, which occurred on May 7, 2021. In addition, the AZSTARYS Amendment increased the total remaining future regulatory and sales milestone payments related to AZSTARYS up to an aggregate of $590.0 million. The AZSTARYS License Agreement will continue on a product-by-product basis (i) until expiration of the royalty term for the applicable product candidate in the United States and (ii) perpetually for all other countries.

In May 2021, we announced that SDX, our proprietary prodrug of d-MPH and the primary active pharmaceutical ingredient ("API") in AZSTARYS, was classified as a Schedule IV controlled substance by the DEA. AZSTARYS is classified as a Schedule II controlled substance as its formulation includes a 70:30 mixture of SDX (Schedule IV) and d-MPH (Schedule II), respectively.

During the first half of 2023, annual net sales of AZSTARYS surpassed $25 million, triggering the first annual net sales milestone payment of $5.0 million under the AZSTARYS License Agreement, which was earned and recognized as revenue in the second quarter of 2023, and received after quarter-end. During the second half of 2023, annual net sales of AZSTARYS surpassed $50 million, triggering the second net sales milestone payment of $10.0 million under the AZSTARYS License Agreement, which was earned and recognized in the fourth quarter of 2023.

Other Third-Party Agreements

Aquestive Termination Agreement

Under our March 2012 termination agreement with Aquestive Therapeutics ("Aquestive"), Aquestive has the right to receive a royalty amount equal to 10% of any value generated by AZSTARYS and any product candidates containing SDX. In connection with the AZSTARYS License Agreement, we paid Aquestive a royalty equal to 10% of the quarterly royalty payments and of the regulatory and net sales milestones earned in 2020, 2021, and 2023.

Distributor Agreement

Our current single distributor for sales of our approved products, OLPRUVA and MIPLYFFA, is a specialty pharmacy provider. The Company, however, may establish additional specialty distributors or other retail pharmacies and certain medical centers or hospitals. In addition to distribution agreements, we may enter into arrangements with health care providers and payors that provide for government mandated and/or privately negotiated rebates with respect to the purchase of our products.

Relief Exclusive License Agreement

As a condition to entering into the Merger Agreement, Acer and Relief Therapeutics SA ("Relief") entered into an exclusive license agreement on August 30, 2023 (the "Relief License Agreement"). Pursuant to the Relief License Agreement, Relief will hold exclusive development and commercialization rights for OLPRUVA in the EU, Liechtenstein, San Marino, Vatican City, Norway, Iceland, Principality of Monaco, Andorra, Gibraltar, Switzerland, United Kingdom, Albania, Bosnia, Kosovo, Montenegro, Serbia and North Macedonia ("Geographical Europe"). We have the right to receive a royalty of up to 10% of the net sales of OLPRUVA in Geographical Europe.

License Agreements Related to MIPLYFFA (arimoclomol)

Prior to our acquisition of the assets of Orphazyme in May 2022, Orphazyme had entered into an asset purchase agreement with LadRx Corporation, which was assigned to XOMA (US) LLC, a wholly-owned subsidiary of XOMA Corporation ("XOMA"), in June 2023 ("XOMA License Agreement"), as well as a license agreement with Kansas University (“KU”) and UCLB Business, PLC (“UCLB”) (the “KU/UCLB License Agreement”). Under the XOMA License Agreement, XOMA is entitled to certain net sales and regulatory milestone payments in addition to a mid-single digit royalty with respect to worldwide net sales of MIPLYFFA. Under the KU/UCLB License Agreement, KU and UCLB, respectively, are entitled to a low-single digit royalty with respect to worldwide net sales of MIPLYFFA.

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Our Intellectual Property

Our intellectual property (“IP”) strategy includes seeking composition-of-matter patents, among other patents, for ~~our~~compounds ~~prodrugs,~~ and product candidates ~~and conjugates of our prodrugs~~ while also protecting, where appropriate as trade secrets, our proprietary ~~LAT~~technologies. ~~platform~~In ~~technology,~~utilizing ~~the~~these ~~process by which we identify~~technologies, ~~screen,~~the ~~evaluate~~resulting ~~and~~compounds select ligands to be conjugated with parent drugs to create our prodrugs. Our current prodrugs all consist of an approved parent drug and one or more ligands that we have selected using our proprietary LAT platform technology. The parent drug and ligand or ligands together may potentially constitute a new molecule and thus may be eligible for composition-of-matter patent protection, among other patent protections, in the ~~U.S.~~United States and abroad. Beyond our internally -generated IP, we have also acquired extensive IP portfolios through our business development efforts which support the products and product candidates that we are seeking to ~~commercialize~~develop and/or ~~develop~~commercialize.

In addition to the execution of our IP strategy, we also depend upon the skills, knowledge and experience of our scientific and technical personnel, as well as that of our advisors, consultants and other contractors. ToWe ~~help~~also ~~protect our LAT platform technology, as well as any proprietary know-how and show-how beyond that which is patentable, we~~ rely on trade secret protection, assignments and confidentiality agreements to protect our interests. To this end, we generally require our employees, consultants and advisors to enter into confidentiality agreements prohibiting the disclosure of confidential information and, in some cases, requiring disclosure and assignment to us of the ideas, developments, discoveries, inventions and improvements important to our business.

As of December 31, ~~2024~~2025, we have been granted and maintain 89 about 87 active patents within the United States, and about an additional ~~375~~ 497 active foreign patents covering our selected prodrugs and product candidates. The terms of the 89 issued U.S. patents extend to various dates ranging, for example, between at least 2029 and 2042. The term of our overall domestic and foreign patent portfolio related to our selected prodrugs and product candidates, including patent term adjustments but excluding possible patent term extensions, extend to various dates ranging, for example, between 2029 and ~~2042~~2044, if pending patent applications in each of our patent families are issued as patents. As of December 31, ~~2024~~2025, we had 25about 51 pending patent applications under active prosecution in the United States, and about an additional ~~109~~250 pending foreign patent applications potentially covering our selected prodrugs and product candidates. Our issued and granted patents provide protection in jurisdictions that include the United States, Australia, Canada, Chile, China, European ~~Countries~~countries, Hong Kong, India, Indonesia, Israel, Japan, Kazakhstan, Malaysia, Mexico, New Zealand, Philippines, Romania, Russia, Singapore, South Africa, South Korea, and Vietnam.

MIPLYFFA (arimoclomol)

Pursuant to our acquisition of the ~~assets of~~ Orphazyme assets, we have received method of use and method of treatment patents, and have filed related patent applications, related to the arimoclomol families in various jurisdictions, including the ~~U.S.~~United States, European countries, Israel, Japan, South Korea, Canada, China, Brazil, Russia and Turkey, with anticipated patent expiration dates of 2029, excluding any potential patent term adjustments or extensions. We ~~anticipate~~have ~~filing~~filed and continue to file additional patent applications related to the arimoclomol families, including next generation of arimoclomol prodrug conjugate compounds which would have, if granted, an anticipated patent expiration date of about 2044, excluding any potential patent term adjustments or extensions. As of December 31, 2025, the MIPLYFFA related family included 13 granted U.S. patents and 38 active foreign patents, with an additional 11 pending U.S. patent applications and 73 foreign patent applications.

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OLPRUVA (sodium phenylbutyrate)

We acquired the IP portfolio supporting OLPRUVA as part of the Merger with Acer. We have both U.S. and foreign patents with claims related to OLPRUVA. Our U.S. patents are directed to pharmaceutical compositions, including OLPRUVA's polymer coated, multi-particulate dosage formulation for oral administration and covers certain methods of use claims related to OLPRUVA. Additionally, we have patents in Europe, Israel, and Mexico related to pharmaceutical compositions, including OLPRUVA's polymer coated, multi-particulate dosage formulation for oral administration. These patents expire in 2036.

InFurthermore, ~~October~~we ~~2022,~~have ~~the~~exclusive ~~U.S.~~rights ~~Patent~~to certain patents and ~~Trademark~~other ~~Office~~intellectual property from Baylor College of Medicine (~~"USPTO"~~“BCM”) ~~issued~~for athe ~~Notice~~use of ~~Allowance~~sodium phenylbutyrate (NaPB) for ~~U.S.~~the ~~patent~~treatment ~~application~~of ~~No.~~inborn ~~16/624~~errors of BCAA metabolism,~~834~~ ~~for~~including ~~claims~~Maple ~~related~~Syrup toUrine aDiease ~~kit~~(“MSUD”), ~~comprising~~with the latest patent expiring in 2032. Additionally, we have a combination therapeutic product composed of sodium phenylbutyrate or glycerol phenylbutyrate and sodium benzoate., ~~That~~which ~~application~~was exclusively licensed to Acer from BCM, which has ~~now~~an ~~issued~~expiration asdate ~~U.S.~~in ~~Patent~~June No2038. ~~11,517,547~~We ~~and~~made ~~was~~filings ~~exclusively~~in ~~licensed~~the togeographic ~~Acer,~~regions ~~which~~that werepresent ~~acquired~~the inlargest ~~November~~incidence ~~2023~~and prevalence of MSUD, ~~from~~including ~~Baylor~~the ~~College~~United ofStates, ~~Medicine~~selected countries in Europe (~~"BCM"~~including Turkey), ~~with~~and anBrazil. ~~expiration~~BCM ~~date~~has received three patents in ~~June~~ ~~2038~~the United States and one in the EU with respect to OLPRUVA, each of which is exclusively licensed to us pursuant to our agreement with BCM.

In July 2022, the China National Intellectual Property Administration (“CNIPA”) issued Electronic Patent Certificate ZL202122004991.9 in May 2022, for Utility Model directed to OLPRUVA (sodium phenylbutyrate). Specifically, the patent covers dosage form claims related to OLPRUVA’s polymer coated formulation for oral administration as a potential treatment for UCDs and Maple Syrup Urine Disease ("MSUD"). The patent has an expiration date in August 2031.Celiprolol

We ~~have exclusive~~intend to protect our commercial rights tofor ~~certain~~celiprolol ~~patents~~in ~~and~~the ~~other~~United ~~intellectual~~States ~~property~~via ~~from~~multiple ~~BCM~~pathways. We believe celiprolol will be eligible for ~~the~~NCE ~~use~~exclusivity which provides upon approval as an NCE five years of ~~sodium~~marketing ~~phenylbutyrate~~exclusivity, ~~(NaPB)~~during ~~for~~which time the ~~treatment~~FDA ofwill ~~inborn~~not ~~errors~~approve another drug with the same active ingredient, regardless of ~~BCAA~~the ~~metabolism~~indication for use, ~~including~~in ~~MSUD. The~~the ~~licensed~~United ~~patents~~States. ~~cover~~In ~~methods~~January ~~and~~2015, ~~compositions~~the ~~for~~FDA ~~treating~~granted ~~humans~~celiprolol ~~(and~~Orphan ~~animals)~~Drug ~~with~~designation, ~~various~~which ~~formulations~~provides ~~and~~seven ~~prodrugs~~years of ~~NaPB~~marketing exclusivity for ~~inborn~~a ~~errors~~drug ofintended ~~BCAA~~to ~~metabolism~~treat a rare condition, ~~including~~if ~~MSUD~~approved. During the Orphan Drug exclusivity period, ~~with~~the FDA cannot approve the ~~latest~~same ~~expiring in~~drug ~~2032~~for the same indication, unless it demonstrates clinical superiority. WeOrphan ~~made~~Drug ~~filings~~exclusivity indoes ~~the~~not ~~geographic~~prevent ~~regions~~the ~~that~~FDA ~~represent~~from approving the ~~largest~~same ~~incidence~~drug ~~and~~for ~~prevalence~~a ofdifferent ~~MSUD~~indication, ~~including~~ or a different drug for the Usame indication.S NCE exclusivity and Orphan Drug exclusivity periods run concurrently. Furthermore, ~~selected~~celiprolol ~~countries~~may qualify for an additional six months of pediatric exclusivity in ~~Europe~~the ~~(including~~United ~~Turkey)~~States, ~~and~~which ~~Brazil.~~requires ~~BCM~~the ~~has~~submission ~~received three~~of ~~patents~~one or more studies in pediatric subjects that meet requirements to be specified by the UFDA in a written request for pediatric studies.S Pediatric exclusivity can be obtained either before or after NDA approval. Pediatric exclusivity is attached to the end of an existing exclusivity and ~~one~~runs consecutively. We may also consider making modifications to the formulation in order to improve the ~~EU with~~product ~~respect~~profile and to ~~OLPRUVA~~seek additional intellectual property. While unapproved drugs may be imported into the United States under specified circumstances, ~~each~~such ofas ~~which~~for ~~is exclusively~~use ~~licensed~~in toclinical usstudies ~~pursuant~~under a valid and effective investigational new drug (“IND”) or for further manufacture into an IND drug or an approved drug, we intend to aggressively assert our ~~agreement~~rights, ~~with~~via ~~BCM~~regulatory and legal means, to limit the importation of non-FDA approved versions of celiprolol.

We ~~also~~have ~~expect~~exclusively tolicensed ~~benefit~~ from ~~potential~~Assistance ~~commercial~~Publique—Hôpitaux ~~exclusivity~~de ~~afforded~~Paris (AP-HP) a now-issued U.S. patent (US 11,523,997) titled “Method of Providing Celiprolol Therapy to ~~the~~a ~~first~~Patient,” ~~drug~~with ~~approved~~an ~~after~~expiration ~~obtaining~~date ~~orphan~~in ~~drug~~November ~~designation~~2038, ~~for~~excluding ~~the~~any ~~treatment~~potential ofpatent ~~MSUD.~~term ~~Orphan~~extension, ~~drug~~which ~~designation~~covers ~~for~~certain ~~OLPRUVA~~ methods for ~~the~~treating ~~treatment~~VEDS ofwith ~~MSUD~~celiprolol. ~~was~~There is also one granted bypatent ~~the~~in ~~FDA~~Mexico, and further pending applications in ~~August~~various ~~2014~~jurisdictions, including the United States, Mexico, Canada, and Brazil.

Furthermore, we may qualify to receive an additional six months of pediatric exclusivity in the U.S., which runs consecutively to an existing exclusivity, if we conduct a successful pediatric study of OLPRUVA for the treatment of MSUD, approved by the FDA for this purpose.

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AZSTARYS and Serdexmethylphenidate (SDX)

We have received composition-of-matter patents and also additionally filed composition-of-matter and method of treatment patent applications related to the AZSTARYS and SDX families in the United States and in Argentina, Australia, Brazil, Canada, Chile, China, Egypt, Hong Kong, European Countries, India, Israel, Indonesia, Japan, South Korea, Kazakhstan, Mexico, Malaysia, New Zealand, Philippines, Russia, Singapore, South Africa, Thailand, Ukraine, and Vietnam. We anticipate filing additional patent applications for our prodrugs and product candidates covering SDX and KP1077.

~~Celiprolol~~License Agreements

~~The~~XOMA ~~Merger~~License ~~with~~Agreement Acer included the acquisition of celiprolol, for which we intend to protect our commercial rights in the U.S. via multiple pathways. We believe celiprolol will be eligible for NCE exclusivity which provides upon approval as an NCE five years of marketing exclusivity, during which time the FDA will not approve another drug with the same active ingredient, regardless of the indication for use, in the U.S. In January 2015, the FDA granted celiprolol Orphan Drug designation, which provides seven years of marketing exclusivity for a drug intended to treat a rare condition, if approved. During the Orphan Drug exclusivity period, the FDA cannot approve the same drug for the same indication, unless it demonstrates clinical superiority. Orphan Drug exclusivity does not prevent the FDA from approving the same drug for a different indication, or a different drug for the same indication. NCE exclusivity and Orphan Drug exclusivity periods run concurrently. Furthermore, celiprolol may qualify for an additional six months of pediatric exclusivity in the U.S., which requires the submission of one or more studies in pediatric subjects that meet requirements to be specified by the FDA in a written request for pediatric studies. Pediatric exclusivity can be obtained either before or after NDA approval. Pediatric exclusivity is attached to the end of an existing exclusivity and runs consecutively. We may also consider making modifications to the formulation in order to improve the product profile and to seek additional intellectual property. While unapproved drugs may be imported into the U.S. underspecified circumstances, such as for use in clinical studies under a valid and effective investigational new drug (~~"IND"~~MIPLYFFA) or for further manufacture into an IND drug or an approved drug, we intend to aggressively assert our rights, via regulatory and legal means, to limit the importation of non-FDA approved versions of celiprolol.

In May 2022, ~~the~~we ~~USPTO~~purchased ~~issued~~all athe ~~Notice~~assets and operations of ~~Allowance~~Orphazyme ~~for~~related ato ~~patent~~arimoclomol. ~~application~~Prior ~~exclusively~~to ~~licensed~~this ~~from~~acquisition, ~~Assistance~~Orphazyme ~~Publique—Hôpitaux~~had deentered ~~Paris~~into ~~(AP-HP)~~an asset purchase agreement with LadRx Corporation, ~~for~~which ~~claims~~was ~~related~~assigned to ~~certain~~XOMA ~~methods~~(US) ofLLC, ~~VEDS~~a ~~with~~wholly-owned ~~celiprolol.~~subsidiary ~~This~~of ~~application~~XOMA Corporation (“XOMA”), ~~titled~~in June 2023 (“~~Method~~XOMA ofLicense ~~Providing~~Agreement”). ~~Celiprolol~~Under ~~Therapy~~the toXOMA aLicense ~~Patient~~Agreement,” ~~has~~XOMA ~~now~~is ~~issued~~entitled asto a ~~U.S.~~mid-single ~~patent~~digit ~~(US~~percentage ~~11,523,997)~~ royalty with anrespect ~~expiration~~to ~~date~~net insales ~~November~~of ~~2038. There~~MIPLYFFA isas ~~one~~well ~~granted~~as ~~patent~~milestone inpayments ~~Mexico,~~based ~~and~~on ~~further~~future ~~pending~~potential ~~applications~~sales inand ~~various~~regulatory ~~jurisdictions~~milestones, including ~~the~~a U$4.S.0 asmillion ~~well~~regulatory asmilestone ~~Mexico,~~payment ~~Canada,~~upon ~~and~~approval ~~Brazil~~in the E.U.

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Relief License Agreement (OLPRUVA)

In connection with our acquisition of Acer, Acer and Relief entered into an exclusive license agreement on August 30, 2023 (the “Relief License Agreement”), which was assumed by Zevra. Pursuant to the Relief License Agreement, Zevra is obligated to pay royalties of 10% of U.S. net sales up to a maximum of $45.0 million, plus specified regulatory milestones, for total payments to Relief of up to $56.5 million. On April 10, 2025, the rights to this royalty were sold to Soleus Capital Management L.P.

Pursuant to the Relief License Agreement, Relief will hold exclusive development and commercialization rights for OLPRUVA in the EU, Liechtenstein, San Marino, Vatican City, Norway, Iceland, Principality of Monaco, Andorra, Gibraltar, Switzerland, United Kingdom, Albania, Bosnia, Kosovo, Montenegro, Serbia and North Macedonia (“Geographical Europe”). We have the right to receive a royalty of up to 10% of the net sales of OLPRUVA in Geographical Europe.

Aquestive Termination Agreement (AZSTARYS)

Under our March 2012 termination agreement with Aquestive Therapeutics (“Aquestive”), Aquestive has the right to receive a royalty amount equal to 10% of any value generated by AZSTARYS and any product candidates containing SDX. We pay Aquestive a royalty equal to 10% of the quarterly royalty payments and of the regulatory and net sales milestones we receive from Commave under the AZSTARYS License Agreement.

Commercialization

InTo ~~March~~support ~~2021~~the launch of MIPLYFFA and OLPRUVA, we ~~announced~~have ~~that~~built ~~the~~in-house ~~FDA~~capabilities ~~approved~~including ~~the~~rare ~~NDA~~disease ~~for~~sales ~~AZSTARYS,~~specialists awho ~~once-daily~~are ~~product~~working ~~for~~with ~~the~~prescribing ~~treatment~~clinicians ofand ~~ADHD~~healthcare inproviders, ~~patients~~as ~~ranging~~well ~~from~~as ~~six~~marketing, ~~years~~patient ~~and~~reimbursement ~~older.~~services, ~~Corium~~market isaccess ~~leading~~and ~~the~~contracting, ~~commercialization~~patient ofadvocacy, ~~AZSTARYS~~and inmedical ~~the~~affairs Uteams.S. ~~under~~We ~~the~~continue ~~AZSTARYS~~to ~~License~~engage ~~Agreement.~~with ~~Corium~~commercial ~~commercially~~payers ~~launched~~and ~~AZSTARYS~~governmental inorganizations ~~the~~to ~~U.S. in~~gain ~~July~~access ~~2021.~~for InMIPLYFFA ~~December~~and ~~2021,~~OLPRUVA. ~~Commave~~We ~~Therapeutics,~~have ~~S.A.~~established ~~sublicensed~~promotional programs to ~~Shanghai~~drive ~~Ark~~awareness ~~Biopharmaceutical~~and ~~Co.,~~patient ~~Ltd.~~experience ~~the~~with ~~commercialization~~MIPLYFFA ~~rights~~and ~~Greater~~OLPRUVA ~~China~~including Quick Start, ~~including~~a ~~mainland~~thirty-day ~~China~~free trial program designed to provide patient experience, ~~Hong~~and ~~Kong~~other patient co-pay programs, ~~Macau~~reflecting ~~and~~our ~~Taiwan~~commitment to ensure access to innovative treatments to those in need.

InWe ~~December~~currently ~~2022,~~have an arrangement with a specialty pharmacy provider as the ~~FDA~~distributor for sales of our approved ~~OLPRUVA (sodium~~products. ~~phenylbutyrate)~~We, however, may establish additional specialty distributors or other retail pharmacies and certain medical centers or hospitals. In addition to distribution agreements, we may enter into arrangements with health care providers and payors that provide for ~~oral~~government ~~suspension~~mandated inand/or privately negotiated rebates with respect to the Upurchase of our products.S.

InCommave’s ~~September~~affiliate, ~~2024~~Corium, is leading the ~~FDA~~commercialization ~~approved~~of AZSTARYS in the ~~NDA~~United ~~for~~States ~~MIPLYFFA™~~under ~~(arimoclomol),~~the anAZSTARYS ~~orally-delivered~~License ~~treatment~~Agreement. ~~for~~Corium ~~NPC~~commercially launched AZSTARYS in the United States in July 2021. ~~MIPLYFFA~~In ~~has~~December ~~also~~2021, ~~been~~Commave ~~granted~~sublicensed ~~orphan~~to ~~designation~~Shanghai ~~for~~Ark Biopharmaceutical Co., Ltd. the ~~treatment~~commercialization ofrights ~~NPC~~in byGreater ~~the~~China, ~~European~~including ~~Commission~~mainland China, Hong Kong, Macau and Taiwan.

To support the launch of OLPRUVA and MIPLYFFA, we have built in-house capabilities including rare disease sales specialists who are working with prescribing clinicians and healthcare providers, which include metabolic specialists and clinical geneticists, as well as marketing, patient reimbursement services, market access and contracting, patient advocacy, and medical affairs teams. We have successfully recruited, on-boarded and trained our full commercial team and full launch for OLPRUVA began on January 29, 2024. We also have arrangements with third parties to provide additional services such as distribution and specialty pharmacy offerings. To support the efforts of our team members which are in the field engaging with HCPs, we are actively engaged in negotiations with the major commercial payers and state Medicaid organizations to seek access for OLPRUVA and MIPLYFFA. We have established promotional programs to drive awareness and patient experience with OLPRUVA and MIPLYFFA including Quick Start, a thirty-day free trial program designed to provide patient experience, and other patient co-pay programs, reflecting our commitment to ensure access to innovative treatments to those in need.

We have established a targeted commercial team which is designed to fully service the patients and prescribers within the rare disease indications for which we are successful in gaining approval for our product candidates. However, if our product candidates have large potential market opportunities that would require significant marketing resources, we may conclude that the most appropriate approach to their commercialization, if they receive regulatory approval, will involve forming a commercial collaboration or strategic relationship similar to those we have entered into with Commave, or consummating some type of strategic transaction, with a larger pharmaceutical or other marketing organization. As we get closer to potential approval of our product candidates, we will work to identify and implement the most appropriate commercialization strategies that we conclude are the most desirable with regard to each specific product candidate.

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Competition

Our industry is characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary products. We will face competition and potential competition from any number of pharmaceutical and biotechnology companies, specialty pharmaceutical companies, generic drug companies, drug delivery companies and academic and research institutions. Our competitors may develop or market drugs that are more effective, more convenient, more widely used and less costly or have a better safety profile than our products or product candidates and these competitors may also have significantly more resources than us and be more successful than us in manufacturing and marketing their products. We anticipate facing intense and increasing competition as new products enter the market and advanced technologies become available.

~~OLPRUVA~~ 14

~~OLPRUVA~~Table ~~competes against several currently marketed, branded and generic forms~~ of phenylbutyrate. In particular, RAVICTI, which is marketed by Amgen Inc. (formerly Horizon Therapeutics), and PHEBURANE,, which is marketed by Medunik USA. We are also aware that there are drug candidates in clinical development for the potential treatment of UCDs. In addition, there is the potential entrance of authorized generics for RAVICTI which could enter the market as early as July 2025.Contents

MIPLYFFA

~~There~~Soon isafter ~~another~~approval ~~treatment~~of MIPLYFFA, the FDA approved a second therapy for NPC, AQNEURSA, ~~(IntraBio)~~which ~~that~~is ~~was~~approved ~~recently~~for ~~approved~~the treatment of neurological manifestations of NPC in ~~the~~adults Uand pediatric patients weighing ≥15 kg and is marketed by IntraBio, Inc.S. While AQNEURSA has a similar indication, data included on its label has a different clinical endpoint and safety profile from MIPLYFFA. We are also aware that there are several other drug candidates in clinical development for the treatment of NPC. These include adrabetadex (Mandos), and cyclodextrin (Cyclo Therapeutics). We believe MIPLYFFA’s clinical profile, mechanism of action, and development program differentiate it within the emerging NPC treatment landscape.

OLPRUVA

OLPRUVA competes against several currently marketed, branded and generic forms of phenylbutyrate. In particular, RAVICTI, which is marketed by Amgen Inc. (formerly Horizon Therapeutics), and PHEBURANE, which is marketed by Medunik USA. We are also aware that there are drug candidates in clinical development for the potential treatment of UCDs. In addition, authorized generics of RAVICTI, marketed by Par and Lupin, entered the market in the fourth quarter of 2025.

Celiprolol

We are not aware of any active ongoing clinical trials for the treatment of VEDS. ~~Aytu BioPharma, Inc. development program known as AR101/enzastaurin was indefinitely suspended in October 2022.~~

KP1077

If approved, we intend for KP1077 to compete against XYWAV, marketed by Jazz Pharmaceuticals, and potentially with other products that are currently in development for the treatment of IH. KP1077 could face potential competition from any products for the treatment of IH that are currently in or which may enter into clinical development.

AZSTARYS

AZSTARYS competes against currently marketed, branded and generic methylphenidate products for the treatment of ADHD. Some of these currently marketed products include CONCERTA, marketed by J&J Innovative Medicines (formerly Jannsen), QUELBREE, marketed by Supernus Pharmaceuticals, Inc., QUILLIVANT XR and QUILLICHEW ER, marketed by Tris Pharma, RITALIN, FOCALIN and FOCALIN XR, marketed by Novartis AG, METADATE CD, marketed by UCB SA, DAYTRANA, marketed by Noven Therapeutics, LLC, Neos Therapeutics’ CONTEMPLA XR-ODT, marketed Aytu BioScience, Inc., JORNAY PM, ~~Ironshore~~marketed ~~Pharmaceuticals,~~by Collegium Pharmaceutical Inc. (formerly Ironshore), and ADHANSIA XR, marketed by Adlon Therapeutics, in addition to multiple other branded and generic methylphenidate products. In addition, AZSTARYS will face potential competition from any other methylphenidate products for the treatment of ADHD that are currently in, or which may enter into clinical development.

Many of our competitors either alone or with strategic partners, have or will have substantially greater financial, technical, and human resources compared with us. Accordingly, our competitors may be more successful in developing or marketing products and technologies that are more effective, safer or less costly. Additionally, our competitors may obtain regulatory approval for their products more rapidly and may achieve more widespread market acceptance. These companies also compete with us in recruiting and retaining qualified scientific and management personnel, establishing clinical study sites and patient registration for clinical studies and acquiring technologies complementary to, or necessary for, our programs. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. There are other non-pharmaceutical therapeutic approaches that are used or may be used for our targeted indications. ~~For example, liver transplantation may be used in some cases to treat UCDs in pediatric patients who have developed acute liver failure.~~

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Manufacturing

Our manufacturing strategy is to rely on contract manufacturers to produce our approved products and product candidates for clinical trials and, if approved, drug product for commercial sale. We currently have no manufacturing facilities and limited personnel in our manufacturing department. We have contracted with third parties for the manufacture, testing, and storage of our approved products and product candidates and intend to continue to do so in the future. We expect to contract with third-party manufacturers for the manufacture of all API supply needs outside the United States if and when we receive approval from regulatory authorities outside the United States.

Our current and any future third-party manufacturers, their facilities and all lots of drug substance and drug products used in our clinical trials are required to be in compliance with current good manufacturing practices ("cGMPs") and comparable foreign regulations. The cGMP and comparable foreign regulations include requirements relating to organization of personnel, buildings and facilities, equipment, control of components and drug product containers and closures, production and process controls, packaging and labeling controls, holding and distribution, laboratory controls, records and reports, and returned or salvaged products. The manufacturing facilities for our products must meet cGMP and comparable foreign requirements and FDA and foreign regulatory authorities' satisfaction before any product is approved and we can manufacture commercial products. Our current and any future third-party manufacturers are also subject to periodic inspections of facilities by the FDA and other authorities, including procedures and operations used in the testing and manufacture of our products to assess our compliance with applicable regulations.15

~~Failure~~Table to comply with statutory and regulatory requirements subjects a manufacturer to possible legal or regulatory action, including refusal to approve pending applications, license suspension or revocation, withdrawal of an approval, imposition of a clinical hold or termination of clinical trials, warning letters, untitled letters, cyber letters, modification of promotional materials or labeling, product recalls, product seizures or detentions, refusal to allow imports or exports, total or partial suspension of production or distribution, debarment, injunctions, fines, consent decrees, additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreements to resolve allegations of non-compliance with these laws, refusals of government contracts and new orders under existing contracts, exclusion from participation in federal and state healthcare programs, restitution, disgorgement or civil or criminal penalties, including fines and individual imprisonments.Contents

Our current and any future third-party manufacturers, their facilities and all lots of drug substance and drug products used in our clinical trials are required to be in compliance with current good manufacturing practices (“cGMPs”) and comparable foreign regulations. The cGMP and comparable foreign regulations include requirements relating to organization of personnel, buildings and facilities, equipment, control of components and drug product containers and closures, production and process controls, packaging and labeling controls, holding and distribution, laboratory controls, records and reports, and returned or salvaged products. The manufacturing facilities for our products must meet cGMP and comparable foreign requirements and FDA and foreign regulatory authorities' satisfaction before any product is approved and we can manufacture commercial products. Our current and any future third-party manufacturers are also subject to periodic inspections of facilities by the FDA and other authorities, including procedures and operations used in the testing and manufacture of our products to assess our compliance with applicable regulations.

Failure of third-party manufacturers to comply with statutory and regulatory requirements may subject us to possible legal or regulatory action, including refusal to approve pending applications, license suspension or revocation, withdrawal of an approval, imposition of a clinical hold or termination of clinical trials, warning letters, untitled letters, cyber letters, modification of promotional materials or labeling, product recalls, product seizures or detentions, refusal to allow imports or exports, total or partial suspension of production or distribution, debarment, injunctions, fines, consent decrees, additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreements to resolve allegations of non-compliance with these laws, refusals of government contracts and new orders under existing contracts, exclusion from participation in federal and state healthcare programs, restitution, disgorgement or civil or criminal penalties, including fines and individual imprisonments.

Third-Party Payor Coverage and Reimbursement

Sales of pharmaceutical products depend in significant part on the availability of coverage and adequate reimbursement by third-party payors, such as state and federal governmental authorities, including those that administer the Medicare and Medicaid programs, and private managed care organizations and health insurers. Decisions regarding the extent of coverage and amount of reimbursement to be provided for each of our product and product candidates is and will be made on a plan-by-plan basis. One payor’s determination to provide coverage for a product does not assure that other payors will also provide coverage, and adequate reimbursement, for the product. Each third-party payor determines whether or not it will provide coverage for a drug, what amount it will pay providers for the drug, and on what tier of its formulary the drug will be placed. These decisions are influenced by the existence of multiple drug products within a therapeutic class and the net cost to the plan, including the amount of the prescription price, if any, rebated by the drug’s manufacturer. Typically, generic versions of drugs are placed in a preferred tier. The position of a drug on the formulary generally determines the co-payment that a patient will need to make to obtain the drug and can strongly influence the adoption of a drug by patients and physicians. Patients who are prescribed treatments for their conditions and providers performing the prescribed services generally rely on third-party payors to reimburse all or part of the associated healthcare costs. Patients are unlikely to use our products unless coverage is provided, and reimbursement is adequate to cover a significant portion of the cost of our products. Additionally, a third-party payor’s decision to provide coverage for a drug does not imply that an adequate reimbursement rate will be approved. Also, third-party payors are developing increasingly sophisticated methods of controlling healthcare costs. As a result, coverage, reimbursement and placement determinations are complex and are often the subject of extensive negotiations between the payer and the manufacturer of the drug.

17 Unless we enter into a strategic collaboration under which our collaborator assumes responsibility for seeking coverage and reimbursement for a given product, we will be responsible for negotiating coverage, reimbursement and placement decisions for our product candidates, if approved. Coverage, reimbursement and placement decisions for a new product are based on many factors including the coverage, reimbursement and placement of already marketed branded drugs for the same or similar indications, the safety and efficacy of the new product, availability of generics for similar indications, the clinical need for the new product and the cost-effectiveness of the product. Increasingly, both purchasers and payors are also conducting comparative clinical and cost effectiveness analyses involving application of metrics, including data on patient outcomes, provided by manufacturers.

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~~Unless~~In weorder ~~enter into a strategic collaboration under which our collaborator assumes responsibility~~ for ~~seeking~~reimbursement ~~coverage~~to ~~and~~be ~~reimbursement~~available for aour ~~given~~products ~~product~~under ~~(such~~Medicare asor ~~the AZSTARYS License Agreement)~~Medicaid, we ~~will~~participate bein ~~responsible for negotiating coverage, reimbursement~~ and ~~placement~~have ~~decisions~~rebate ~~for~~obligations ~~our~~under ~~product~~the ~~candidates,~~Medicaid ifDrug ~~approved.~~Rebate ~~Coverage,~~Program ~~reimbursement~~ and ~~placement~~are ~~decisions~~enrolled ~~for~~in athe ~~new~~340B ~~product~~drug ~~are~~pricing ~~based~~program, onas ~~many~~well ~~factors~~as ~~including~~ the ~~coverage,~~U.S. ~~reimbursement~~Department ~~and~~of ~~placement~~Veterans ofAffairs ~~already~~Federal ~~marketed~~Supply ~~branded~~Schedule ~~drugs~~pricing ~~for~~program. ~~the~~The ~~same~~programs orwe ~~similar~~participate ~~indications~~in, ~~the~~as ~~safety~~well ~~and~~as ~~efficacy~~our ofobligations ~~the~~under ~~new~~these ~~product~~programs, ~~availability~~are ofdescribed ~~generics~~under ~~for~~the ~~similar~~risk ~~indications,~~factor ~~the~~“If ~~clinical~~we ~~need~~fail ~~for~~to ~~the~~comply ~~new~~with ~~product~~our reporting and ~~the~~payment ~~cost-effectiveness~~obligations ofunder the ~~product.~~Medicaid ~~Increasingly,~~Drug ~~both~~Rebate ~~purchasers~~Program ~~and~~or ~~payors~~other ~~are~~governmental ~~also~~pricing ~~conducting~~programs ~~comparative~~in ~~clinical~~which ~~and~~we ~~cost~~participate, ~~effectiveness~~we ~~analyses~~could ~~involving~~be ~~application~~subject ofto ~~metrics,~~additional ~~including~~reimbursement ~~data~~requirements, ~~on patient outcomes~~penalties, ~~provided~~sanctions byand ~~manufacturers~~fines.”

Within the Medicare program, as self-administered drugs, our product and product candidates would be reimbursed under the expanded prescription drug benefit known as Medicare Part D. This program is a voluntary Medicare benefit administered by private plans that operate under contracts with the federal government. These plans develop formularies that determine which products are covered and what co-pay will apply to covered drugs. The plans have considerable discretion in establishing formularies and tiered co-pay structures, negotiating rebates with manufacturers and placing prior authorization and other restrictions on the utilization of specific products, subject to review by the Centers for Medicare & Medicaid Services ("CMS"), for discriminatory practices. These Part D plans negotiate discounts with drug manufacturers, which are passed on, in whole or in part, to each of the plan’s enrollees through reduced premiums. Historically, Part D beneficiaries have been exposed to significant out-of-pocket costs after they surpass an annual coverage limit and until they reach a catastrophic coverage threshold. However, changes made by recent legislation reduced this patient coverage gap, known as the “donut hole”, by transitioning patient responsibility in that coverage range from 100% in 2010 to only 25% currently. To help achieve this reduction, pharmaceutical manufacturers were required to provide quarterly discounts of 70%, which commenced January 1, 2019, and was replaced, beginning on January 1, 2025 (described below). In 2020, drug manufacturers became responsible for a larger share of total drug costs due to an increase to the catastrophic threshold. Such increase also resulted in a higher out-of-pocket threshold paid by Part D beneficiaries.

If a drug product is available for reimbursement by Medicare or Medicaid, its manufacturer must comply with various health regulatory requirements and price reporting metrics, which may include, as applicable, the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, the Medicaid rebate requirements of the Omnibus Budget Reconciliation Act of 1990 (the "OBRA"), and the Veterans Health Care Act of 1992 (the "VHCA"), each as amended. Among other things, the OBRA requires drug manufacturers with certain drugs covered by Medicaid to pay rebates on prescription drugs to state Medicaid programs. States may also negotiate “supplemental” Medicaid rebates on drug products dispensed under Medicaid. Manufacturers participating in Medicaid are also generally required to participate in the Public Health Service 340B Drug Discount Program, which imposes a mandatory discount on purchases by certain customers. Manufacturers of innovator drugs, including 505(b)(2) drugs, that participate in the Medicaid program are also required to offer the drugs on the Federal Supply Schedule purchasing program of the General Services Administration for purchase by the Department of Veterans Affairs, the Department of Defense and other authorized users at a mandatory discount. Additional laws and requirements apply to these contracts. Participation in such federal programs may result in prices for our future products that will likely be lower than the prices we might otherwise obtain.

Third-party payers, including the U.S. government, continue to apply downward pressure on the reimbursement of pharmaceutical products. Also, the trend towards managed health care in the United States and the concurrent growth of organizations such as health maintenance organizations may result in lower reimbursement for pharmaceutical products. We expect that these trends will continue as these payors implement various proposals or regulatory policies, including various provisions of the recent health reform legislation that affect reimbursement of these products. There are currently, and we expect that there will continue to be, a number of federal, state and foreign proposals to implement controls on reimbursement and pricing, directly and indirectly.

In international markets, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies. For example, in the EU, pricing and reimbursement schemes vary widely from country to country. Some countries may require the completion of additional studies that compare the cost-effectiveness of a particular medicinal product candidate to currently available therapies. This Health Technology Assessment (“HTA”) which is currently governed by the national laws of the individual EU member states, is the procedure according to which the assessment of the public health impact, therapeutic impact and the economic and societal impact of use of a given medicinal product in the national healthcare systems of the individual country is conducted. The outcome of HTA regarding specific medicinal products will often influence the pricing and reimbursement status granted to these medicinal products by the competent authorities of individual EU member states. The downward pressure on healthcare costs in general, particularly prescription medicines, has become very intense. Pharmaceutical products may face competition from lower-priced products in foreign countries that have placed price controls on pharmaceutical products and may also compete with imported foreign products. Furthermore, there is no assurance that a product will be considered medically reasonable and necessary for a specific indication, will be considered cost-effective by third-party payors, that an adequate level of reimbursement will be established even if coverage is available or that the third-party payors’ reimbursement policies will not adversely affect the ability for manufacturers to sell products profitably. Historically, products launched in the EU do not follow the price structures which prevail in the ~~U.S.~~United States, and generally, prices tend to be significantly lower.

U.S. Government Regulation and Product Approval

Government authorities in the United States, at the federal, state and local level extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing and export and import of products such as those we are developing. The pharmaceutical products that we develop must be approved by the U.S. Food and Drug Administration (“FDA”) before they may be legally marketed in the United States.

U.S. Pharmaceutical Product Development Process

In the United States, the FDA regulates pharmaceutical products under the Federal Food, Drug and Cosmetic Act (“FDCA”) and implementing regulations. Pharmaceutical products are also subject to other federal, state and local statutes and regulations. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources. Failure to comply with the applicable U.S. requirements at any time during the product development process, approval process or after approval, may subject an applicant to administrative or judicial enforcement. FDA noncompliance enforcement could include a refusal to review and or approve pending applications, withdrawal of an approval, a clinical study hold, warning letters, product recalls, product seizures, total or partial suspension of production or distribution injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal penalties. Any regulatory enforcement action could have a material adverse effect on us.

The process required by the FDA before a non-biological pharmaceutical product may be marketed in the United States generally involves the following:

•Completion of preclinical laboratory tests, animal studies and formulation studies according to Good Laboratory Practices (“GLP”), and other applicable regulations;

•Submission of an Investigational New Drug application (“IND”), which must become effective before human clinical studies may begin;

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•Conduct of adequate and well-controlled human clinical studies according to current Good Clinical Practices (“GCP”), to establish the safety and efficacy of the proposed pharmaceutical product for its intended use;

•Submission of a New Drug Application (“NDA”) for a new pharmaceutical product;

•Satisfactory completion of an FDA inspection of the manufacturing facility or facilities where the pharmaceutical product is produced to assess compliance with s current Good Manufacturing Practice standards (“cGMP”), to assure that the facilities, methods and controls are adequate to preserve the pharmaceutical product’s identity, strength, quality and purity;

•Potential FDA inspection of the preclinical and clinical study sites that generated the data in support of the NDA; and

•FDA review and approval of the NDA.

The lengthy process of seeking required approvals and the continuing need for compliance with applicable statutes and regulations require the expenditure of substantial resources and approvals are inherently uncertain.

Before testing any pharmaceutical product with potential therapeutic value in humans, the pharmaceutical product candidate enters the preclinical testing stage. Preclinical tests include laboratory evaluations of product chemistry, toxicity and formulation, as well as animal studies to assess the potential safety and activity of the pharmaceutical product candidate. These early studies are conducted using sound scientific procedures and require thorough documentation. The conduct of a single and repeat dose toxicology and toxicokinetic studies in animals must comply with federal regulations and requirements including GLP. The pharmaceutical product sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and a proposed clinical protocol, to the FDA as part of the IND. The IND becomes effective 30 days after receipt by the FDA, unless the FDA has concerns and notifies the sponsor. In such a case, the IND sponsor must resolve any outstanding concerns to the satisfaction of FDA before a clinical study can begin. If resolution cannot be reached within the 30-day review period, FDA can place the IND on clinical hold, or the sponsor may withdraw the application. The FDA may also impose clinical holds on a pharmaceutical product candidate at any time before or during clinical studies due to safety concerns or regulatory non-compliance. Accordingly, it is not certain that submission of an IND will result in the FDA allowing clinical studies to begin, or that, once begun, issues will not arise that can lead to the suspension or termination of such clinical studies.

During the development of a new drug, sponsors are given opportunities to meet with the FDA to discuss progress. These meeting may occur prior to submission of an IND, at the end of Phase 2 clinical development, and before an NDA is submitted. Meetings at other times may be requested. These meetings can provide an opportunity for the sponsor to share information about the data gathered to date, for the sponsor to ask specific questions of the FDA, for the FDA to provide advice, and for the sponsor and FDA to reach agreement on the next phase of development. Sponsors typically use the end of Phase 2 meeting to discuss their Phase 2 clinical results and present their plans for the pivotal Phase 3 clinical (registration) trial(s) that they believe will support approval of the new drug. A sponsor may be able to request a Special Protocol Assessment (“SPA”), the purpose of which is to reach agreement with the FDA on the Phase 3 clinical trial protocol design and analyses that will form the primary basis of an efficacy claim.

According to FDA guidance for industry on the SPA process, a sponsor which meets the prerequisites may make a specific request for a SPA and provide information regarding the design and size of the proposed clinical trial. The FDA’s goal is to evaluate the protocol within 45 days of the request to assess whether the proposed trial is adequate, and that evaluation may result in discussions and a request for additional information. A SPA request must be made before the proposed trial begins, and all open issues must be resolved before the trial begins. If a written agreement is reached, it will be documented and made part of the IND record. The agreement will be binding on the FDA and may not be changed by the sponsor or the FDA after the trial begins except with the written agreement of the sponsor and the FDA or if the FDA determines that a substantial scientific issue essential to determining the safety or efficacy of the drug was identified after the testing began.

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~~Government~~Conducting ~~Regulation~~Clinical Trials

~~The~~Clinical ~~FDA~~trials ~~and~~are ~~comparable~~voluntary ~~regulatory~~research ~~agencies~~studies ininvolving ~~state~~the ~~and~~administration ~~local~~of ~~jurisdictions~~the ~~and~~pharmaceutical inproduct ~~foreign~~candidate ~~countries~~to ~~impose~~healthy ~~substantial~~volunteers ~~requirements~~or ~~upon~~patients under the ~~clinical~~supervision ~~development~~of qualified investigators, ~~manufacture~~typically ~~and~~physicians ~~marketing~~independent of ~~pharmaceutical~~the ~~products~~clinical study sponsor’s control. ~~These~~Clinical ~~agencies~~studies ~~and~~are conducted according to protocols detailing, among other ~~federal~~things, ~~state~~the ~~and~~objectives ~~local~~of ~~entities~~the ~~regulate~~clinical ~~research~~study, dosing procedures, subject selection and ~~development~~exclusion ~~activities~~criteria, how the results will be analyzed and presented and the ~~testing,~~parameters ~~manufacture,~~to ~~quality~~be ~~control,~~used ~~safety,~~to ~~effectiveness,~~monitor ~~labeling,~~subject ~~storage,~~safety. ~~packaging,~~Each ~~recordkeeping,~~protocol ~~tracking,~~must ~~approval,~~be ~~import,~~submitted ~~export,~~to ~~distribution,~~the ~~advertising~~FDA ~~and~~as ~~promotion~~part of ~~our~~the ~~products~~IND. ~~and~~Clinical ~~product~~studies ~~candidates~~must be conducted in accordance with GCP requirements. AFurther, ~~new~~each ~~drug~~clinical study must be reviewed and approved by an independent institutional review board (“IRB”), at, or servicing, each institution at which the ~~FDA~~clinical ~~through~~study will be conducted. An IRB is charged with protecting the ~~NDA~~welfare ~~process~~and ~~before~~rights itof ~~may~~study beparticipants ~~legally~~and ~~marketed~~is tasked with considering such items as whether the safety risks to individuals participating in the ~~United~~clinical ~~States~~studies are minimized and are reasonable in relation to anticipated benefits. The ~~process~~IRB ofapproves ~~obtaining~~the ~~regulatory~~informed ~~approvals~~consent ~~and~~that ~~the~~must ~~subsequent~~be ~~compliance~~provided ~~with~~to ~~applicable~~each ~~federal,~~clinical ~~state,~~study ~~local~~subject ~~and~~or ~~foreign~~his ~~statutes~~or her legal representative and ~~regulations~~will ~~require~~also monitor the ~~expenditure~~clinical ofstudy ~~substantial~~to ~~time~~ensure ~~and~~patient ~~financial~~safety ~~resources~~until completed.

The process required by the FDA before product candidates may be marketed in the United States generally involves the following:

● certain non-clinical laboratory and animal tests that must be conducted in accordance with good laboratory practices ("GLP") requirements and other applicable regulations; ● submission of an IND, which must be received by the FDA and become effective before human clinical trials may begin; ● approval by an independent institutional review board ("IRB") or ethics committee at each clinical site or centrally before each trial may be initiated; ● performance of adequate and well-controlled human clinical trials to establish the safety and efficacy of the proposed product candidate for its intended use, performed in accordance with good clinical practice requirements ("GCPs"); ● preparation and submission of an NDA to the FDA; ● satisfactory completion of an FDA advisory committee review, if applicable; ● pre-approval inspection of manufacturing facilities at which the drug is produced to assess their compliance with cGMPs and of selected clinical investigation sites to assess compliance with GCPs; and ● FDA approval of an NDA to permit commercial marketing for particular indications for use.

Clinical Trials

The testing and regulatory approval process requires substantial time, effort and financial resources. Preclinical studies include laboratory evaluation of drug substance chemistry, pharmacology, toxicity and drug product formulation, as well as animal studies to assess potential safety and efficacy. Prior to commencing the first human clinical trial with a product candidate, we must submit the results of the preclinical tests and preclinical literature, together with manufacturing information, analytical data and any available clinical data or literature, among other things, to the FDA as part of an IND. An IND is a request for authorization from the FDA to administer an investigational new drug product to humans. The central focus of an IND submission is on the general investigational plan and the protocol(s) for clinical studies.

The IND becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises safety concerns or questions about the conduct of the clinical trial by imposing a clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. Submission of an IND may not result in FDA authorization to commence a clinical trial.

Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with GCPs, which include the requirement that all research subjects provide their informed consent for their participation in any clinical study. Clinical trials are conducted under protocols detailing, among other things, the objectives of the study, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. A separate submission to the existing IND must be made for each successive clinical trial conducted during product development, as well as amendments to previously submitted clinical trials. Further, an independent IRB for each study site proposing to conduct the clinical trial must review and approve the plan for any clinical trial, its informed consent form and other communications to study subjects before the clinical trial commences at that site. The IRB must continue to oversee the clinical trial while it is being conducted, including any changes to the study plans. Regulatory authorities, an IRB or the sponsor may suspend or discontinue a clinical trial at any time on various grounds, including a finding that the subjects are being exposed to an unacceptable health risk, the clinical trial is not being conducted in accordance with the FDA’s or the IRB’s requirements, if the drug has been associated with unexpected serious harm to subjects, or based on evolving business objectives or competitive climate. Some studies also include a data safety monitoring board, which receives special access to unblinded data during the clinical trial and may advise us to halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy. Depending on its charter, this group may determine whether a trial may move forward at designated check points based on access to certain data from the trial. The FDA, or the sponsor, may suspend a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients. There are also requirements governing the reporting of ongoing clinical studies and clinical study results to public registries.

In general, for purposes of NDA approval, human clinical trials are typically conducted in three sequential phases that may overlap.

● •Phase 1 - The pharmaceutical product ~~candidate~~ is initially ~~introduced~~administered ~~into~~to healthy ~~subjects~~volunteers orand ~~patients~~tested ~~with the target disease or condition. These studies are conducted to test the product candidate~~ for safety, dosage tolerance, ~~structure-activity relationships, mechanism of action,~~ absorption, metabolism, distribution and excretion. If possible, Phase 1 trials may also be used to gain early evidence of product effectiveness. ● Phase 2 - The product candidate is administered to a limited patient population with a specified disease or condition to evaluate the preliminary efficacy, optimal dosage and dosing schedule and to identify possible adverse side effects and safety risks. Multiple Phase 2 clinical trials may be conducted to obtain information prior to beginning larger and more expensive Phase 3 clinical trials. ● Phase 3 - The product candidate is administered to an expanded patient population to further evaluate dosage to provide statistically significant evidence of clinical efficacy and to further test for safety in an expanded subject population at multiple clinical trial sites. These clinical trials are intended to establish the overall risk/benefit ratio of the product and provide an adequate basis for product labeling.

•Phase 2 - The pharmaceutical product is studied in a limited patient population with the disease or condition to evaluate its effectiveness for a particular indication or indications and to determine the common short-term side effects and risks associated with the product.

•Phase 3 - Clinical trials are undertaken to further evaluate dosage, clinical efficacy and safety in an expanded patient population at geographically dispersed clinical study sites. These clinical studies are intended to establish the overall risk/benefit of the product and provide an adequate basis for product labeling. The studies must be well-controlled and usually include a control arm for comparison. One or two Phase 3 studies may be required by the FDA for an NDA, depending on the disease severity and other available treatment options.

•Post-approval studies, or Phase 4 clinical studies, may be conducted after initial marketing approval. These studies are used to gain additional experience from the treatment of patients in the intended therapeutic indication.

•Progress reports detailing the results of the clinical studies must be submitted at least annually to the FDA and written IND safety reports must be submitted to the FDA and the investigators for serious and unexpected adverse events or any finding from tests in laboratory animals that suggests a significant risk for human subjects. Phase 1, Phase 2 and Phase 3 clinical studies may not be completed successfully within any specified period, if at all. The FDA or the sponsor or its data safety monitoring board may suspend a clinical study at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical study at its institution if the clinical study is not being conducted in accordance with the IRB’s requirements or if the pharmaceutical product has been associated with unexpected serious harm to patients.

Concurrent with clinical studies, companies usually complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the pharmaceutical product as well as finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the pharmaceutical product candidate and, among other things, must include methods for testing the identity, strength, quality and purity of the final pharmaceutical product. Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the pharmaceutical product candidate does not undergo unacceptable deterioration over its shelf life.

U.S. Review and Approval Processes

The results of product development, preclinical studies and clinical trials, along with descriptions of the manufacturing process, analytical tests conducted on the chemistry of the pharmaceutical product, proposed labeling and other relevant information are submitted to the FDA as part of an NDA requesting approval to market the product. The submission of an NDA is subject to the payment of substantial user fees; a waiver of such fees may be obtained under certain limited circumstances.

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In addition, under the ~~case~~Pediatric ofResearch aEquity ~~505~~Act (b“PREA”)~~(2)~~, an NDA, ~~some~~or a supplement thereof must contain data to assess the safety and effectiveness of the ~~above-described~~pharmaceutical ~~studies~~product for the claimed indications in all relevant pediatric subpopulations and ~~preclinical~~to ~~studies~~support ~~may~~dosing ~~not~~and beadministration ~~required~~for oreach ~~may~~pediatric besubpopulation ~~abbreviated.~~for ~~Pharmacokinetic~~which the product is safe and ~~other~~effective. ~~bridging~~The ~~studies~~FDA may begrant ~~needed,~~deferrals ~~however~~for submission of data or full or partial waivers. Unless otherwise required by regulation, PREA does not apply to ~~demonstrate~~any pharmaceutical product for an indication for which orphan designation has been granted. The FDA reviews all NDAs submitted before it accepts them for filing and may request additional information rather than accepting an NDA for filing. Once the ~~relevance~~submission is accepted for filing, the FDA begins an in-depth review of the ~~studies~~NDA. ~~that~~Under ~~were~~the ~~previously~~goals ~~conducted~~and policies agreed to by ~~other~~the ~~sponsors~~FDA tounder the ~~drug~~Prescription ~~that~~Drug isUser Fee Act (“PDUFA”), the ~~subject~~FDA has 10 months in which to complete its initial review of a standard NDA and respond to the applicant, and six months for a priority NDA. The FDA does not always meet its PDUFA goal dates for standard and priority NDAs. The review process and the PDUFA goal date may be extended by three months if the FDA requests or if the NDA sponsor otherwise provides additional information or clarification regarding information already provided in the submission within the last three months before the PDUFA goal date.

~~The~~After ~~FDA~~the ~~may~~NDA ~~require~~submission is accepted for filing, orthe ~~companies~~FDA ~~may~~reviews ~~pursue~~the NDA to determine, ~~additional~~among ~~clinical~~other ~~trials~~things, ~~after~~whether athe proposed product is ~~approved.~~safe ~~These~~and ~~clinical~~effective ~~trials~~for its intended use, ~~sometimes~~and ~~referred~~whether the product is being manufactured in accordance with cGMP to asassure ~~Phase~~and 4preserve the product’s identity, strength, quality and purity. The FDA may refer applications for novel pharmaceutical products or ~~post-market~~pharmaceutical products which present difficult questions of safety or efficacy to an advisory committee, ~~studies~~typically ~~may~~a bepanel ~~used~~that includes clinicians and other experts, for review, evaluation and a recommendation as to ~~gain~~whether ~~additional~~the ~~experience~~application ~~from~~should be approved and under what conditions. The FDA is not bound by the ~~treatment~~recommendations of ~~patients~~an inadvisory ~~the~~committee, ~~intended~~but ~~therapeutic~~it ~~indication~~considers such recommendations carefully when making decisions. InDuring ~~certain~~the ~~instances~~pharmaceutical product approval process, the FDA ~~may~~also ~~mandate~~will determine whether a risk evaluation and mitigation strategy (“REMS”), is necessary to assure the ~~performance~~safe use of ~~Phase~~the 4pharmaceutical ~~clinical~~product. ~~trials~~If asthe FDA concludes that a ~~condition~~REMS ofis ~~approval~~needed, the sponsor of anthe NDA must submit a proposed REMS; the FDA will not approve the NDA without a REMS, if required.

~~The~~Before ~~manufacture~~approving ofan ~~investigational~~NDA, ~~drugs for~~ the ~~conduct of human clinical trials is subject to cGMP requirements. Investigational drugs and active pharmaceutical ingredients imported into the United States are also subject to regulation by the~~ FDA ~~relating~~will toinspect ~~their labeling and distribution. Further,~~ the ~~export~~facilities ofat ~~investigational~~which ~~drug products outside of~~ the ~~United~~product ~~States~~ is ~~subject to regulatory requirements of the receiving country as well as U~~manufactured.S. ~~export~~The ~~requirements~~FDA ~~under~~will ~~the~~not ~~FFDCA. In~~approve ~~addition, while~~ the ~~IND~~product isunless ~~active~~it ~~and~~determines ~~before~~that ~~approval, progress reports summarizing~~ the ~~results~~manufacturing ofprocesses ~~the clinical trials~~ and ~~nonclinical~~facilities ~~studies~~are ~~performed~~in ~~since~~compliance ~~the~~with ~~last~~cGMP ~~progress~~requirements ~~report must be submitted at least annually to the FDA,~~ and ~~written~~adequate ~~IND safety reports must be submitted~~ to ~~the~~assure ~~FDA~~consistent ~~and~~production investigators for serious and unexpected suspected adverse events, findings from other studies suggesting a significant risk to humans exposed to the same or similar drugs, findings from animal or in vitro testing suggesting a significant risk to humans, and any clinically important increased incidence of ~~a serious suspected adverse reaction compared to that listed in~~ the ~~protocol~~product orwithin ~~investigator’s~~required ~~brochure~~specifications.

~~Concurrent with clinical trials~~Additionally, ~~companies~~before ~~usually~~approving ~~complete~~an ~~additional~~NDA, ~~animal studies and must also develop additional information about~~ the ~~chemistry~~FDA ~~and~~will ~~physical~~typically ~~characteristics~~inspect ofone ~~the~~or ~~product~~more ~~candidate~~clinical astrial ~~well~~sites asto ~~finalize~~assure acompliance ~~process~~with ~~for~~GCPs. ~~manufacturing~~If the ~~product~~FDA indetermines ~~commercial~~the ~~quantities~~application, ~~in accordance with cGMP requirements. The~~ manufacturing process ~~must~~or bemanufacturing ~~capable~~facilities, ofor ~~consistently~~clinical ~~producing~~study ~~quality~~sites ~~batches~~are ofnot ~~the product candidate and~~acceptable, ~~among~~it ~~other~~will ~~things,~~outline ~~must~~the ~~develop~~deficiencies ~~methods~~in ~~for testing~~ the ~~identity,~~submission ~~strength,~~and ~~quality~~often ~~and~~will ~~purity~~request ofadditional ~~the~~testing ~~final~~or ~~product~~information. ~~Additionally~~In addition, ~~appropriate~~the ~~packaging~~FDA ~~must~~will berequire ~~selected~~the ~~and~~review ~~tested,~~ and ~~stability~~approval ~~studies~~of ~~must be conducted to demonstrate that the~~ product ~~candidate does not undergo unacceptable deterioration over its shelf life~~labeling.

The NDA ~~Submission~~review and ~~Review~~approval process is lengthy and involved and the FDA may refuse to approve an NDA if the applicable regulatory criteria are not satisfied or may require additional clinical data or other data and information. Even if such data and information are submitted, the FDA may ultimately decide that the NDA does not satisfy the criteria for approval. Data obtained from clinical trials are not always conclusive and the FDA may interpret data differently than the sponsor interprets the same data. The FDA will issue a complete response letter if the agency decides not to approve the NDA. The complete response letter usually describes all of the specific deficiencies in the NDA identified by the FDA. The deficiencies identified may be minor, for example, requiring labeling changes, or major, for example, requiring additional clinical studies.

~~Assuming successful completion of the required clinical and preclinical testing~~Additionally, ~~among other items,~~ the ~~results~~complete ofresponse ~~product~~letter ~~development,~~may ~~including~~include ~~chemistry,~~recommended ~~manufacture~~actions ~~and~~that ~~controls, non-clinical studies and clinical trials are submitted to~~ the ~~FDA,~~applicant ~~along~~might ~~with~~take ~~proposed labeling, as part of an NDA requesting approval~~ to ~~market~~place the ~~product.~~application ~~Data~~in ~~can come from company-sponsored clinical studies intended to test the safety and effectiveness of~~ a ~~use~~condition offor ~~the product, or from a number of alternative sources, including studies initiated by independent investigators~~approval. ~~The~~If ~~submission of an NDA requires payment of~~ a ~~substantial~~complete ~~application~~response ~~user~~letter ~~fee~~is toissued, the ~~FDA.~~applicant ~~These~~may ~~user~~either ~~fees~~resubmit ~~must~~the beNDA, ~~filed~~addressing atall ~~the time~~ of the ~~first~~deficiencies ~~submission~~identified ofin the ~~application~~letter, ~~even~~or ifwithdraw the application ~~is being submitted on a rolling basis~~. ~~Fee waivers or reductions are available in some circumstances.~~

InIf ~~addition,~~a ~~under~~product ~~the~~receives ~~Pediatric~~regulatory ~~Research~~approval, ~~Equity~~the ~~Act ("PREA"),~~approval anmay ~~NDA~~be orsignificantly ~~supplement~~limited to anspecific ~~NDA~~diseases ~~for~~and adosages ~~new active ingredient, indication, dosage form, dosage regimen~~ or ~~route~~the ofindications ~~administration~~for ~~must~~use ~~contain~~may ~~data~~otherwise ~~that~~be ~~are~~limited, ~~adequate~~which tocould ~~assess~~restrict the ~~safety~~commercial ~~and~~value ~~efficacy~~ of the ~~drug~~product. ~~for~~Further, the ~~claimed~~FDA ~~indications~~may inrequire ~~all~~that ~~relevant~~certain ~~pediatric subpopulations~~contraindications, ~~and~~warnings toor ~~support~~precautions ~~dosing~~be ~~and~~included ~~administration~~in ~~for each pediatric subpopulation for which~~ the product islabeling. ~~safe~~In ~~and~~addition, ~~effective.~~the ~~The~~ FDA may, onrequire ~~its~~Phase ~~own~~4 ~~initiative~~testing orwhich atinvolves ~~the~~clinical ~~request~~trials ofdesigned ~~the~~to ~~applicant,~~further ~~grant~~assess ~~deferrals~~pharmaceutical ~~for~~product ~~submission~~safety ofand ~~some~~effectiveness orand ~~all~~may ~~pediatric~~require ~~data~~testing ~~until~~and ~~after~~surveillance ~~approval~~programs ofto monitor the ~~product~~safety ~~for~~of ~~use~~approved inproducts ~~adults~~that orhave ~~full~~been ~~or partial waivers from the pediatric data requirements~~commercialized.

The FDA may refer drugs which present difficult questions of safety or efficacy to an advisory committee. An advisory committee is a panel that typically includes clinicians and other experts who review, evaluate and make a recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

Once the FDA receives an application, it has 60 days to review the NDA to determine if it is substantially complete to permit a substantive review, before it accepts the application for filing. Once the submission is accepted for filing, the FDA begins an in-depth review of the NDA. The timeline for the FDA to complete its review of an NDA may differ based on whether the application is a standard review or priority review application. The FDA may give a priority review to applications for drugs that are intended to treat serious conditions and if approved, would provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of such serious conditions. Under the goals and policies agreed to by the FDA under the Prescription Drug User Fee Act ("PDUFA"), the FDA has set the review goal of ten months from the 60-day filing date to complete its initial review of a standard NDA for a new molecular entity, or NME, and make a decision on the application. For non-NME standard applications, the FDA has set the review goal of ten months from the submission date to complete its initial review and to make a decision on the application. For priority review applications, the FDA has set the review goal of reviewing NME NDAs within six months of the 60-day filing date and non-NME applications within six months of the date of receipt. Such deadlines are referred to as the PDUFA date. The review process and the PDUFA date may also be extended if the FDA requests or the NDA sponsor otherwise provides additional information or clarification regarding the submission.

The FDA reviews applications to determine, among other things, whether a product is safe and effective for its intended use and whether the manufacturing controls are adequate to assure and preserve the product’s identity, strength, quality and purity. Before approving an NDA, the FDA will typically inspect the facility or facilities where the product is manufactured. The FDA will not approve an application unless it determines that the manufacturing processes and facilities, including contract manufacturers and subcontracts, are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. Additionally, before approving an NDA, the FDA will typically inspect one or more clinical trial sites to assure compliance with GCPs.

Once the FDA’s review of the application is complete, the FDA will issue either a CRL or approval letter. A CRL indicates that the review cycle of the application is complete, and the application cannot be approved in its current form. A CRL will usually describe all of the deficiencies that the FDA has identified in the NDA, except that where the FDA determines that the data supporting the application are inadequate to support approval, the FDA may issue the CRL without first conducting required inspections and/or reviewing proposed labeling. In issuing the CRL, the FDA may recommend actions that the applicant might take to place the NDA in condition for approval, including requests for additional information or clarification. Even with the submission of additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval. If and when those conditions have been met to the FDA’s satisfaction, the FDA may issue an approval letter. An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications.

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~~The~~Expedited ~~FDA~~Development ~~may delay or refuse approval of an NDA if applicable regulatory criteria are not satisfied, require additional testing or information~~ and~~/or~~ ~~require~~Review post-marketing testing and surveillance to monitor safety or efficacy of a product, or impose other conditions, including distribution restrictions or other risk management mechanisms. For example, the FDA may require a risk evaluation and mitigation strategy ("REMS"), as a condition of approval or following approval. A REMS is a safety strategy to manage a known or potential serious risk associated with a medicine and to enable patients to have continued access to such medicines by managing their safe use, and could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries, and other risk minimization tools. Programs

IfThe ~~regulatory~~FDA ~~approval~~has of a ~~product~~Fast isTrack ~~granted,~~program ~~such~~that ~~approval~~is ~~may~~intended ~~entail~~to ~~limitations~~expedite onor facilitate the ~~indicated~~process ~~uses~~ for ~~which~~reviewing ~~such~~new ~~product~~pharmaceutical ~~may~~products bethat ~~marketed~~meet orcertain ~~may~~criteria. ~~include contraindications~~Specifically, ~~warnings~~new orpharmaceutical ~~precautions~~products inare ~~the~~eligible ~~product~~for ~~labeling,~~Fast ~~including~~Track adesignation ~~boxed~~if ~~warning.~~they Ifare ~~the~~intended ~~FDA~~to ~~requires~~treat a ~~boxed~~serious ~~warning,~~or ~~the~~life-threatening ~~sponsor~~condition ~~may~~and ~~also~~demonstrate bethe ~~subject~~potential to ~~specified~~address ~~promotional~~unmet ~~restrictions,~~medical ~~such~~needs asfor the ~~prohibition~~condition. ofThe ~~reminder~~Fast ~~advertisements.~~Track ~~The~~designation ~~FDA~~must ~~also~~be ~~may~~requested ~~not~~by ~~approve~~the sponsor. Fast Track designation applies to the ~~inclusion~~combination of ~~labeling~~the ~~claims~~product ~~necessary~~and the specific indication for ~~successful~~which ~~marketing~~it is being studied. ~~Once~~With ~~approved~~a Fast Track designated product, the FDA may ~~withdraw~~consider ~~the~~for ~~product~~review ~~approval~~sections ifof ~~compliance~~the ~~with~~NDA ~~pre-~~on ~~and~~a ~~post-marketing~~rolling ~~regulatory~~basis ~~standards~~before isthe ~~not~~complete ~~maintained~~application oris submitted, if ~~problems~~the ~~occur~~sponsor ~~after~~provides a schedule for the ~~product~~submission ~~reaches~~of the ~~marketplace.~~sections Inof ~~addition~~the NDA, if the FDA ~~may~~agrees ~~require~~to ~~post-marketing~~accept ~~studies~~sections toof ~~monitor~~ the ~~effect~~NDA ofand ~~approved~~determines ~~products~~that ~~and~~the ~~may~~schedule ~~limit~~is ~~further~~acceptable, ~~marketing~~and ofif the ~~product~~sponsor ~~based~~pays onany ~~the~~required ~~results~~user fees upon submission of ~~these~~the ~~post-marketing~~first ~~studies~~section of the NDA.

~~Advertising~~Any product submitted to the FDA for marketing approval, including a Fast Track program, may also be eligible for other types of FDA programs intended to expedite development and ~~Promotion~~review, such as priority review and accelerated approval. Any product is eligible for priority review if it has the potential to provide safe and effective therapy where no satisfactory alternative therapy exists or a significant improvement in the treatment, diagnosis or prevention of a disease compared to marketed products. The FDA will attempt to direct additional resources to the evaluation of an application for a new pharmaceutical product designated for priority review in an effort to facilitate the review. Additionally, a product may be eligible for accelerated approval. Pharmaceutical products studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may receive accelerated approval, which means that the products may be approved on the basis of adequate and well-controlled clinical trials establishing that the product has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit, or on the basis of an effect on a clinical endpoint other than survival or irreversible morbidity. As a condition of approval, the FDA may require that a sponsor of a pharmaceutical product receiving accelerated approval perform adequate and well-controlled post-marketing clinical studies. In addition, the FDA currently requires as a condition for accelerated approval pre-approval of promotional materials, which could adversely impact the timing of the commercial launch of the product. Fast Track designation, priority review and accelerated approval do not change the standards for approval but may expedite the development or approval process.

~~The~~Breakthrough ~~FDA~~Therapy and other federal regulatory agencies closely regulate the marketing and promotion of drugs through, among other things, guidance and regulations for direct-to-consumer advertising, communications regarding unapproved uses, industry-sponsored scientific and educational activities, and promotional activities involving the internet. A product cannot be commercially promoted before it is approved. After approval, product promotion can include only those claims relating to safety and efficacy that are consistent with the labeling approved by the FDA. Healthcare providers are permitted to prescribe drugs for “off-label” uses — that is, uses not approved by the FDA and therefore not described in the drug’s labeling because the FDA does not regulate the practice of medicine. However, FDA regulations impose stringent restrictions on manufacturers’ communications regarding off-label uses. Failure to comply with applicable FDA requirements and restrictions in this area may subject a company to adverse publicity and enforcement action by the FDA, the U.S. Department of Justice, or the Office of the Inspector General of HHS, as well as state authorities. This could subject a company to a range of penalties that could have a significant commercial impact, including civil and criminal fines and agreements that materially restrict the manner in which a company promotes or distributes drug products.Designation

~~Post~~The FDA is also required to expedite the development and review of the application for approval of drugs that are intended to treat a serious or life-~~Approval~~threatening ~~Requirements~~disease or condition where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. Under the breakthrough therapy program, the sponsor of a new product candidate may request that the FDA designate the product candidate for a specific indication as a breakthrough therapy concurrent with, or after, the filing of the IND for the product candidate. The FDA must determine if the product candidate qualifies for breakthrough therapy designation within 60 days of receipt of the sponsor’s request.

~~Any~~Orphan ~~products~~Drug manufactured or distributed pursuant to FDA approvals are subject to continuing regulation by the FDA, including manufacturing, periodic reporting, product sampling and distribution, advertising, promotion, drug shortage reporting, compliance with any post-approval requirements imposed as a conditional of approval such as post-marketing clinical trials, REMS and surveillance, recordkeeping and reporting requirements, including adverse experiences.Designation

~~After~~Under ~~approval,~~the ~~most~~Orphan ~~changes~~Drug toAct, the ~~approved~~FDA ~~product,~~may ~~such~~grant asorphan ~~adding~~designation ~~new~~to ~~indications~~a ordrug ~~other~~intended ~~labeling claims are subject~~ to ~~prior~~treat ~~FDA~~a ~~review~~rare ~~and~~disease ~~approval.~~or ~~There~~condition ~~also~~affecting ~~are~~fewer ~~continuing~~than 200,000 ~~annual~~individuals ~~human~~in ~~prescription~~the ~~drug~~United ~~program~~States, ~~fee~~or ~~requirements~~in ~~for~~other ~~approved~~limited ~~products~~cases. ~~Drug~~Orphan ~~manufacturers~~drug ~~and~~designation ~~their~~(ODD) ~~subcontractors~~provides ~~are~~for ~~required~~seven toyears ~~register~~of ~~their~~market ~~establishments~~exclusivity, ~~with~~independent ~~the~~of ~~FDA~~patent ~~and~~protection, ~~certain state agencies and~~ to ~~list their drug products and are subject to periodic announced and unannounced inspections by~~ the ~~FDA~~company ~~and~~with ~~these~~ODD ~~state~~that ~~agencies~~brings ~~for~~a ~~compliance~~particular ~~with~~product ~~cGMPs~~to ~~and~~market. ~~other~~In ~~requirements~~addition, ~~which~~companies ~~impose~~developing ~~procedural~~orphan ~~and~~drugs ~~documentation~~are ~~requirements~~eligible ~~upon~~for ~~us and our third-party manufacturers. We cannot be~~ certain ~~that~~incentives, weincluding ortax ~~our~~credits ~~present~~for orqualified ~~future~~clinical ~~suppliers will be able to comply with the cGMP regulations and other FDA regulatory requirements~~testing.

~~Changes~~To togain ~~the~~exclusivity, ~~manufacturing~~if ~~process~~a ~~are~~product ~~strictly~~that ~~regulated~~has ~~and~~orphan ~~often~~drug ~~require~~designation ~~prior~~subsequently receives the first FDA approval ~~before~~for ~~being~~the ~~implemented,~~disease or ~~FDA~~condition ~~notification.~~for ~~FDA~~which ~~regulations~~it ~~also~~has ~~require~~such ~~investigation~~designation, ~~and~~the ~~correction~~product ofis ~~any~~entitled ~~deviations~~to ~~from~~the ~~cGMPs~~orphan ~~and~~drug ~~specifications~~exclusivity, ~~and~~which ~~impose~~means ~~reporting~~that ~~and~~the ~~documentation~~FDA ~~requirements~~may ~~upon~~not ~~the~~approve ~~sponsor and~~ any ~~third-party~~other ~~manufacturers~~applications ~~that~~to market the ~~sponsor~~same ~~may~~drug ~~decide~~or tobiologic for the same approved use. ~~Accordingly,~~or ~~manufacturers~~indication ~~must~~within ~~continue~~such torare ~~expend~~disease ~~time,~~or ~~money~~condition ~~and~~for ~~effort~~seven years, except in limited circumstances, such as another drug’s showing of clinical superiority over the ~~area~~drug with orphan exclusivity. Orphan drug exclusivity could block the approval of ~~production~~one ~~and~~of ~~quality~~our ~~control~~product candidates for seven years if a competitor obtains approval for a drug or biologic with the same active moiety for the same approved use or indication within the rare disease or condition before we do, unless we are able to ~~maintain~~demonstrate ~~cGMP~~that ~~compliance~~our product is clinically superior.

Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in withdrawal of marketing approval, mandatory revisions to the approved labeling to add new safety information or other limitations, imposition of post-market studies or clinical trials to assess new safety risks, or imposition of distribution or other restrictions under a REMS program, among other consequences.

The FDA closely regulates the marketing and promotion of drugs. A company can make only those claims relating to safety and efficacy, purity and potency that are approved by the FDA. Physicians, in their independent professional medical judgment, may prescribe legally available products for uses that are not described in the product’s labeling and that differ from those tested by us and approved by the FDA. Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances. The FDA does not regulate the behavior of physicians in their choice of treatments. The FDA does, however, restrict manufacturer’s communications on the subject of off-label use of their products. However, companies may share truthful and not misleading information that is otherwise consistent with a product’s FDA-approved labelling.

In addition, the distribution of prescription pharmaceutical products, including samples, is subject to the Prescription Drug Marketing Act ("PDMA"), which regulates the distribution of drugs and drug samples at the federal level, and sets minimum standards for the registration and regulation of drug distributors by the states. Both the PDMA and state laws limit the distribution of prescription pharmaceutical product samples and impose requirements to ensure accountability in distribution. The Drug Supply Chain Security Act also imposes obligations on manufacturers of pharmaceutical products related to product tracking and tracing.

Failure to comply with any of the FDA’s requirements could result in significant adverse enforcement actions. These include a variety of administrative or judicial sanctions, such as refusal to approve pending applications, withdrawal of an approval, imposition of a clinical hold or termination of clinical trials, warning letters, untitled letters, modification of promotional materials or labeling, product recalls, product seizures or detentions, refusal to allow imports or exports, total or partial suspension of production or distribution, debarment, injunctions, fines, consent decrees, additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, refusals of government contracts and new orders under existing contracts, exclusion from participation in federal and state healthcare programs, restitution, disgorgement or civil or criminal penalties, including fines and individual imprisonment. Any of these sanctions could result in adverse publicity, among other adverse consequences.

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~~Orphan~~A ~~Drug~~sponsor ~~Designation~~may request orphan drug designation of a previously unapproved product or new orphan indication for an already marketed product. In addition, a sponsor of a product that is otherwise the same product as an already approved orphan drug may seek and ~~Exclusivity~~obtain orphan drug designation for the subsequent product for the approved use or indication within the same rare disease or condition if it can present a plausible hypothesis that its product may be clinically superior to the first, approved product. More than one sponsor may receive orphan drug designation for the same product for the same rare disease or condition, but each sponsor seeking orphan drug designation must file a complete request for designation, and only the first sponsor that obtains approval for that drug for the orphan indication will obtain market exclusivity, effectively preventing the FDA from approving products under development by competitors for a drug or biologic for the same approved use or indication, unless the competitor is able to demonstrate that the product under development is clinically superior to the approved product or the approved product is not available in sufficient quantities. To permit the FDA to end another manufacturer’s orphan exclusivity period, the FDA must determine that the manufacturer has demonstrated clinical superiority by showing the later drug is safer, more effective, or otherwise makes a major contribution to patient care.

~~Under~~The ~~the~~period ~~Orphan~~of ~~Drug~~exclusivity ~~Act,~~begins on the ~~FDA~~date ~~may~~that ~~grant~~the ~~orphan~~marketing ~~designation~~application tois aapproved ~~drug~~by ~~intended~~the toFDA ~~treat~~and aapplies ~~rare~~only ~~disease~~to the approved use or ~~condition,~~indication ~~defined~~within asthe arare disease or condition ~~with~~for awhich ~~patient~~the ~~population~~product ofhas ~~fewer~~been ~~than~~designated. ~~200,000~~The ~~individuals~~FDA inmay ~~the~~approve ~~U.S., or~~ a ~~patient~~second ~~population~~application ~~greater~~for ~~than 200,000 individuals in~~ the ~~U.S. and~~same ~~when~~product ~~there~~for isa nodifferent ~~reasonable~~use ~~expectation~~or ~~that~~a ~~the~~subsequent ~~cost~~application offor ~~developing~~a ~~and~~different ~~making available the~~ drug infor the ~~U.S. will~~same ~~be recovered from sales in the United States for that drug~~indication. Orphan drug designation ~~must~~neither beshortens ~~requested~~the ~~before~~development ~~submitting~~time anor ~~NDA.~~regulatory ~~After~~review ~~the~~time ~~FDA~~of ~~grants~~a ~~orphan~~ drug ~~designation,~~nor ~~the~~gives ~~generic identity of~~ the ~~therapeutic~~drug ~~agent~~any ~~and~~advantage ~~its~~in ~~potential~~the ~~orphan~~regulatory ~~use~~review ~~are~~or ~~disclosed~~approval ~~publicly by the FDA~~process..

IfWe amay ~~product~~plan ~~that~~to ~~has~~pursue orphan drug designation ~~subsequently~~and ~~receives~~exclusivity ~~the first FDA approval~~ for asome ~~particular~~of ~~active~~our ~~ingredient~~product ~~for~~candidates in the ~~disease~~United ~~for which it has such designation~~States, ~~the~~European ~~product is entitled to orphan product exclusivity~~Union, ~~which~~and ~~means~~other ~~that~~geographies ~~the~~of ~~FDA~~interest ~~may~~for ~~not~~specific ~~approve~~products. ~~any~~We ~~other~~cannot ~~applications,~~guarantee ~~including~~that awe ~~full~~will ~~NDA,~~obtain toorphan ~~market the same~~ drug ~~for~~designation ~~the same indication~~ for ~~seven~~any ~~years,~~products ~~except~~ in ~~limited~~any ~~circumstances,~~jurisdiction. ~~such~~Even asif awe ~~showing~~are ofable ~~clinical superiority~~ to ~~the~~obtain ~~product with~~ orphan drug ~~exclusivity~~designation orfor ifa ~~the~~product, ~~FDA~~we ~~finds~~cannot ~~that~~be ~~the~~sure ~~holder~~that ofsuch ~~the~~product ~~orphan~~will ~~drug~~be ~~exclusivity~~approved, ~~has not shown~~ that itwe ~~can~~will ~~assure~~be ~~the~~able ~~availability~~to ofobtain ~~sufficient quantities of the~~ orphan drug ~~to meet the needs of patients with the disease or condition for which the drug was designated. Orphan drug~~ exclusivity ~~does~~upon ~~not~~approval, ~~prevent~~if ~~the FDA from approving a different drug for the same disease or condition~~ever, or ~~the~~that ~~same~~we ~~drug~~will ~~for~~be aable ~~different~~to ~~disease~~maintain orany ~~condition.~~exclusivity ~~Among~~that ~~the~~is ~~other benefits of orphan drug designation are tax credits for certain research and a waiver of the NDA application user fee~~granted.

APost-Approval ~~designated~~Requirements orphan drug may not receive orphan drug exclusivity if it is approved for a use that is broader than the indication for which it received orphan designation. In addition, orphan drug exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or, as noted above, if a second applicant demonstrates that its product is clinically superior to the approved product with orphan exclusivity or the manufacturer of the approved product is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.

~~Rare~~After ~~Pediatric~~approval, ~~Disease~~most ~~Priority~~changes ~~Review~~to ~~Voucher~~the ~~Program~~approved product, such as adding new indications or other labeling claims are subject to prior FDA review and approval. There also are continuing, annual human prescription drug program fee requirements for approved products. Drug manufacturers and their subcontractors are required to register their establishments with the FDA and certain state agencies and to list their drug products and are subject to periodic announced and unannounced inspections by the FDA and these state agencies for compliance with cGMPs and other requirements, which impose procedural and documentation requirements upon us and our third-party manufacturers. We cannot be certain that we or our present or future suppliers will be able to comply with the cGMP regulations and other FDA regulatory requirements.

InChanges ~~2012,~~to the ~~U.S.~~manufacturing ~~Congress~~process ~~authorized~~are ~~the~~strictly ~~FDA~~regulated toand ~~award~~often ~~priority~~require ~~review~~prior ~~vouchers~~FDA toapproval ~~sponsors~~before ofbeing ~~certain~~implemented, ~~rare~~or ~~pediatric~~FDA ~~disease product applications~~notification. ~~This~~FDA ~~program~~regulations isalso ~~designed~~require toinvestigation ~~encourage~~and ~~development~~correction of ~~new~~any ~~drug~~deviations ~~and~~from ~~biological~~cGMPs ~~products~~and ~~for~~specifications ~~prevention~~ and ~~treatment~~impose ofreporting ~~certain~~and ~~rare~~documentation ~~pediatric~~requirements ~~diseases.~~upon ~~Specifically,~~the ~~under this program, a~~ sponsor ~~who~~and ~~receives~~any anthird-party ~~approval~~manufacturers ~~for a drug or biologic for a “rare pediatric disease” may qualify for a voucher~~ that ~~can~~the ~~be redeemed to receive priority review of a subsequent marketing application for a different product. The~~ sponsor ~~of a rare pediatric disease drug product receiving a priority review voucher~~ may ~~transfer~~decide ~~(including by sale) the voucher~~ to ~~another sponsor~~use. ~~The~~Accordingly, ~~voucher~~manufacturers ~~may~~must becontinue ~~further~~to ~~transferred~~expend ~~any number of times before the voucher is used~~time, asmoney ~~long~~and aseffort ~~the~~on ~~sponsor~~production ~~making~~and ~~the~~quality ~~transfer~~control ~~has~~to ~~not~~maintain ~~yet~~cGMP ~~submitted the application~~compliance. ~~The FDA may also revoke any priority review voucher if the rare pediatric disease drug for which the voucher was awarded is not marketed in the U.S. within one year following the date of approval.~~

~~For~~Later ~~purposes~~discovery of ~~this~~previously ~~program,~~unknown aproblems ~~“rare~~with ~~pediatric disease” is~~ a ~~(a)~~product, ~~serious~~including oradverse ~~life-threatening~~events ~~disease~~of inunanticipated ~~which~~severity ~~the~~or ~~serious~~frequency, or ~~life-threatening~~with ~~manifestations~~manufacturing ~~primarily~~processes, ~~affect~~or ~~individuals~~failure ~~aged from birth~~ to 18comply ~~years,~~with ~~including~~regulatory ~~age groups often called neonates~~requirements, ~~infants,~~may ~~children,~~result ~~and~~in ~~adolescents;~~withdrawal ~~and (b) rare diseases or conditions within the meaning~~ of ~~the~~marketing ~~Orphan Drug Act. Under the current statutory sunset provisions~~approval, asmandatory ~~amended~~revisions byto the ~~Continuing~~approved ~~Appropriations and Extensions Act~~labeling, ~~2025,~~imposition ~~FDA~~of ~~may~~post-market ~~only~~studies ~~award~~or aclinical ~~voucher~~trials ~~for~~to anassess ~~approved~~new ~~rare~~safety ~~pediatric disease product application if the Sponsor has rare pediatric disease designation for the drug~~risks, ~~and~~or ~~that~~imposition ~~designation~~of ~~was~~distribution ~~granted~~or byother ~~December~~restrictions ~~20,~~under ~~2024.~~a ~~After~~REMS ~~September 30~~program, ~~2026,~~among ~~FDA~~other ~~may not award any Rare Pediatric Disease Priority Review Voucher~~consequences.

~~Hatch~~The FDA closely regulates the marketing and promotion of drugs. A company can make only those claims relating to safety and efficacy, purity and potency that are approved by the FDA. Physicians, in their independent professional medical judgment, may prescribe legally available products for uses that are not described in the product’s labeling and that differ from those tested by us and approved by the FDA. Physicians may believe that such off-~~Waxman~~label ~~Act~~uses are the best treatment for many patients in varied circumstances. The FDA does not regulate the behavior of physicians in their choice of treatments. The FDA does, however, restrict manufacturer’s communications on the subject of off-label use of their products.

~~Section 505~~In ofaddition, the ~~FFDCA~~distribution ~~describes three types~~ of ~~marketing~~prescription ~~applications~~pharmaceutical ~~that~~products, ~~may~~including besamples, ~~submitted~~is subject to the ~~FDA~~Prescription toDrug ~~request~~Marketing ~~marketing~~Act ~~authorization for a new drug. A Section 505~~(b“PDMA”)~~(1)~~, ~~NDA~~which isregulates anthe ~~application~~distribution ~~that contains full reports~~ of ~~investigations~~drugs ~~of safety~~ and ~~efficacy.~~drug Asamples ~~505(b)(2) NDA is an application that contains full reports of investigations of safety and efficacy but where~~ at ~~least some of~~ the ~~information~~federal ~~required~~level, ~~for~~and ~~approval~~sets ~~comes~~minimum ~~from~~standards ~~investigations that were not conducted by or~~ for the ~~applicant~~registration and ~~for~~regulation ~~which the applicant has not obtained a right~~ of ~~reference~~drug ordistributors ~~use from the person~~ by ~~or for whom~~ the ~~investigations were conducted~~states. ~~This~~Both ~~regulatory pathway enables~~ the ~~applicant~~PDMA toand ~~rely,~~state inlaws ~~part,~~limit on the ~~FDA’s~~distribution ~~prior findings~~ of ~~safety~~prescription ~~and~~pharmaceutical ~~efficacy for an existing~~ product, orsamples ~~published~~and ~~literature,~~impose inrequirements ~~support of its application. The FDA may also require 505(b)(2) applicants~~ to ~~perform~~ensure ~~additional~~accountability ~~studies~~in ~~or measurements to support any changes from the reference listed drug~~distribution. The ~~FDA~~Drug ~~may~~Supply ~~then~~Chain ~~approve~~Security ~~the~~Act ~~new~~also ~~product~~imposes ~~candidate~~obligations ~~for~~on ~~all~~manufacturers ~~or some~~ of ~~the~~pharmaceutical labeled indications for which the referenced product has been approved, as well as for any new indication sought by the 505(b)(2) applicant. Section 505(j) establishes an abbreviated approval process for a generic version of approved drug products ~~through~~related the submission of an abbreviated new drug application ("ANDA"). An ANDA provides for marketing of a generic drug product that has the same active ingredients, dosage form, strength, route of administration, labeling, performance characteristics and intended use, among other things, to ~~a previously approved~~ product. ~~ANDAs~~tracking ~~are termed “abbreviated” because they are generally not required to include preclinical~~ and ~~clinical data to establish safety and efficacy~~tracing. Instead, generic applicants must scientifically demonstrate that their product is bioequivalent to, or performs in the same manner as, the innovator drug through in vitro, in vivo, or other testing. The generic version must deliver the same amount of active ingredients into a subject’s bloodstream in the same amount of time as the innovator drug and can often be substituted by pharmacists under prescriptions written for the reference listed drug.

In seeking approval for a drug through an NDA, including a 505(b)(2) NDA, applicants are required to list with the FDA patents whose claims cover the applicant’s product. Upon approval of an NDA, each of the patents listed in the application for the drug is then published in the Orange Book. These products may be cited by potential competitors in support of approval of an ANDA or 505(b)(2) NDA.

Any applicant who files an ANDA seeking approval of a generic equivalent version of a drug listed in the Orange Book or a 505(b)(2) NDA referencing a drug listed in the Orange Book must certify to the FDA that (1) no patent information on the drug or method of use that is the subject of the application has been submitted to the FDA; (2) such patent has expired; (3) the date on which such patent expires; or (4) such patent is invalid or will not be infringed upon by the manufacture, use or sale of the drug product for which the application is submitted. This last certification is known as a Paragraph IV certification. Generally, the ANDA or 505(b)(2) NDA cannot be approved until all listed patents have expired, except where the ANDA or 505(b)(2) NDA applicant challenges a listed patent through a Paragraph IV certification. If the applicant does not challenge the listed patents or does not indicate that it is not seeking approval of a patented method of use, the ANDA or 505(b)(2) NDA application will not be approved until all of the listed patents claiming the referenced product have expired, or, if permissible, are carved out.

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IfFailure ~~the ANDA or 505(b)(2) NDA applicant has provided a Paragraph IV certification~~ to ~~the~~comply ~~FDA,~~with ~~the~~any ~~applicant must also send notice~~ of the ~~Paragraph IV certification to the holder of the NDA for the reference listed drug and the patent owner once the application has been accepted for filing by the~~ FDA.’s ~~The~~requirements ~~NDA~~could ~~holder~~result ~~or patent owner may then initiate a patent infringement lawsuit~~ in ~~response~~significant toadverse ~~the~~enforcement ~~notice of the Paragraph IV certification~~actions. ~~The~~These ~~filing~~include of a ~~patent~~variety ~~infringement lawsuit within 45 days~~ of ~~the~~administrative ~~receipt~~or ofjudicial asanctions, ~~Paragraph~~such IVas ~~certification~~refusal ~~prevents~~to ~~the~~approve ~~FDA~~pending ~~from~~applications, ~~approving~~withdrawal ~~the~~of ~~application~~an ~~until~~approval, ~~the~~imposition ~~earlier~~ of 30a ~~months~~clinical ~~from~~hold ~~the~~or ~~date~~termination of ~~the~~clinical ~~lawsuit~~trials, ~~expiration~~warning ofletters, ~~the~~untitled ~~patent~~letters, ~~settlement~~modification of ~~the~~promotional ~~lawsuit,~~materials aor ~~decision~~labeling, inproduct ~~the~~recalls, ~~infringement~~product ~~case~~seizures ~~that~~or isdetentions, ~~favorable~~refusal to ~~the~~allow ~~applicant~~imports or ~~such~~exports, ~~shorter~~total or ~~longer~~partial ~~period~~suspension asof ~~may~~production ~~be ordered by a court. This prohibition is generally referred to as the 30-month stay. In instances where an ANDA~~ or ~~505(b)(2)~~distribution, ~~NDA~~debarment, ~~applicant~~injunctions, ~~files~~fines, aconsent ~~Paragraph IV certification~~decrees, ~~the~~additional ~~NDA~~reporting ~~holder~~requirements orand ~~patent~~oversight ~~owner~~if ~~regularly~~we ~~take~~become ~~action~~subject to ~~trigger~~a ~~the 30-month stay,~~corporate ~~recognizing~~integrity ~~that~~agreement ~~the related patent litigation may take many months~~ or ~~years~~similar agreement to resolve. ~~Thus,~~allegations ~~approval~~ of annon-compliance ~~ANDA~~with orthese ~~505(b)(2)~~laws, ~~NDA~~refusals ~~could~~of begovernment ~~delayed~~contracts ~~for~~and anew ~~significant~~orders ~~period~~under ofexisting ~~time~~contracts, ~~depending~~exclusion onfrom ~~the~~participation ~~patent~~in ~~certification~~federal ~~the applicant makes~~ and ~~the~~state ~~reference~~healthcare ~~drug~~programs, ~~sponsor’s~~restitution, ~~decision~~disgorgement toor ~~initiate~~civil ~~patent~~or ~~litigation.~~criminal ~~The~~penalties, ~~applicant~~including ~~may~~fines ~~also~~and ~~elect~~individual toimprisonment. ~~submit~~Any aof ~~statement~~these ~~certifying~~sanctions ~~that~~could ~~its~~result ~~proposed~~in ~~label~~adverse ~~does not contain~~publicity, oramong ~~carves~~other ~~out,~~adverse ~~any language regarding the patented method-of-use rather than certify to a listed method-of-use patent~~consequences.

~~The~~Rare ~~FDA~~Pediatric ~~provides~~Disease ~~periods~~Priority ofReview ~~regulatory~~Voucher ~~exclusivity,~~Program which provides the holder of an approved NDA limited protection from new competition in the marketplace for the innovation represented by its approved drug for a period of three or five years following the FDA’s approval of the NDA. Five years of exclusivity are available to new chemical entities ("NCEs"). An NCE is a drug that contains no active moiety that has been approved by the FDA in any other NDA. An active moiety is the molecule or ion, excluding those appended portions of the molecule that cause the drug to be an ester, salt, including a salt with hydrogen or coordination bonds, or other noncovalent derivatives, such as a complex, chelate, or clathrate, of the molecule, responsible for the therapeutic activity of the drug substance. During the exclusivity period, the FDA may not accept for review or approve an ANDA or a 505(b)(2) NDA submitted by another company that contains the previously approved active moiety. An ANDA or 505(b)(2) application, however, may be submitted one year before NCE exclusivity expires if a Paragraph IV certification is filed. Applicants may also seek to carve out certain drug labeling that is protected by exclusivity.

IfIn a2012, ~~product~~the isU.S. ~~not~~Congress ~~eligible~~authorized ~~for~~ the ~~NCE~~FDA ~~exclusivity,~~to itaward ~~may~~priority bereview ~~eligible~~vouchers ~~for~~to ~~three~~sponsors ~~years~~ of ~~exclusivity~~certain rare pediatric disease product applications. ~~Three-year~~This ~~exclusivity~~program is ~~available~~designed to ~~the~~encourage ~~holder~~development of annew ~~NDA,~~drug ~~including~~and abiological ~~505(b)(2)~~products ~~NDA,~~ for aprevention ~~particular~~and ~~condition~~treatment of ~~approval,~~certain orrare ~~change~~pediatric todiseases. aSpecifically, ~~marketed~~under ~~product~~this program, ~~such~~a assponsor awho ~~new~~receives ~~formulation~~an approval for a ~~previously~~drug ~~approved~~or ~~product,~~biologic iffor ~~one~~a or“rare ~~more~~pediatric ~~new~~disease” ~~clinical~~may ~~trials,~~qualify ~~other~~for ~~than~~a ~~bioavailability~~voucher orthat ~~bioequivalence~~can ~~trials,~~be ~~was~~redeemed ~~essential~~ to ~~the~~receive ~~approval~~priority review of ~~the~~a subsequent marketing application ~~and~~for ~~was~~a ~~conducted~~different orproduct. ~~sponsored~~The bysponsor ~~the~~of ~~applicant.~~a ~~This~~rare ~~three-year~~pediatric ~~exclusivity~~disease ~~period~~drug ~~protects~~product ~~against~~receiving ~~FDA~~a ~~approval~~priority ofreview ~~ANDAs~~voucher ~~and~~may ~~505~~transfer (~~b)(2)~~including ~~NDAs~~by ~~for~~sale) the ~~condition~~voucher ofto ~~the~~another ~~new~~sponsor. ~~drug’s~~The ~~approval.~~voucher ~~Five-year~~may ~~and~~be ~~three-year~~further ~~exclusivity~~transferred ~~will~~any ~~not~~number ~~delay~~of times before the ~~submission~~voucher oris ~~approval~~used, ofas along ~~full~~as ~~NDA;~~the ~~however,~~sponsor anmaking ~~applicant~~the ~~submitting~~transfer ahas ~~full~~not ~~NDA~~yet ~~would~~submitted bethe ~~required~~application. toThe ~~conduct~~FDA ormay ~~obtain~~also arevoke ~~right~~any ofpriority ~~reference~~review tovoucher ~~all~~if ofthe rare pediatric disease drug for which the ~~preclinical~~voucher ~~studies~~was ~~and~~awarded ~~adequate~~is ~~and~~not ~~well-controlled~~marketed ~~clinical~~in ~~trials~~the ~~necessary~~United toStates ~~demonstrate~~within ~~safety~~one ~~and~~year ~~efficacy~~following the date of approval.

For purposes of this program, a “rare pediatric disease” is a (a) serious or life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years, including age groups often called neonates, infants, children, and adolescents; and (b) rare diseases or conditions within the meaning of the Orphan Drug Act. Congress has only authorized the Rare Pediatric Disease Priority Review Voucher program until September 30, 2029. Consequently, unless Congress reauthorizes the program, the sponsor of a marketing application for a drug that receives Rare Pediatric Disease Designation will only be eligible to receive a voucher if the FDA grants the designation on or before September 30, 2029.

DEA Regulation

Our products and certain of our product candidates are, or if approved, will be regulated as “controlled substances” as defined in the Controlled Substances Act of 1970 ("“CSA"”), and the DEA’s implementing regulations, which establish registration, security, recordkeeping, reporting, storage, distribution, importation, exportation, inventory, quota and other requirements administered by the DEA. These requirements are directly applicable to us and also applicable to our contract manufacturers and to distributors, prescribers and dispensers of our products and product candidates. The DEA regulates the handling of controlled substances through a closed chain of distribution. This control extends to the equipment and raw materials used in their manufacture and packaging in order to prevent loss and diversion into illicit channels of commerce.

The DEA regulates controlled substances as Schedule I, II, III, IV or V substances. Schedule I substances by definition have no established medicinal use and may not be marketed or sold in the United States. A pharmaceutical product may be listed as Schedule II, III, IV or V, with Schedule II substances considered to present the highest risk of abuse and Schedule V substances the lowest relative risk of abuse among such substances. Schedule II drugs are those that meet the following criteria:

● •the drug has a high potential for abuse; ● the drug has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions; and ● abuse of the drug may lead to severe psychological or physical dependence.

~~AZSTARYS is listed as Schedule II controlled substances under~~ •the ~~CSA.~~drug ~~For~~has ~~Schedule~~a IIcurrently ~~controlled~~accepted ~~substances,~~medical ~~the importation of APIs for our product candidates, as well as the manufacture, shipping, storage, sales and~~ use of the products, are subject to a high degree of regulation. In addition to maintaining an importer and/or exporter registration, importers and exporters of controlled substances must obtain a permit for every import of a Schedule I or II substance and a narcotic substance in ~~Schedule~~treatment ~~III, IV and V, as well as every export of a Schedule I or II substance and a narcotic substance~~ in ~~Schedule~~the ~~III~~United ~~and~~States ~~IV. For all other drugs in Schedule III, IV and V, importers and exporters must submit an import~~ or export declaration. Schedule II drugs are subject to the strictest requirements for registration, security, recordkeeping and reporting. Also, distribution and dispensing of these drugs are highly regulated. For example, all Schedule II drug prescriptions must be signed by a ~~physician,~~currently ~~physically~~accepted ~~presented~~medical touse ~~a pharmacist and may not be refilled without a new prescription. Electronic prescriptions may also be permissible depending on the state, so long as the prescription complies~~ with ~~the~~severe ~~DEA’s~~restrictions; ~~requirements~~and ~~for electronic prescriptions.~~

~~SDX,~~•abuse ~~which~~of is the sole API in KP1077, has been listed as a Schedule IV controlled substance under the CSA. Controlled substances classified in Schedule III, IV, and V are also subject to registration, recordkeeping, reporting, and security requirements. For example, Schedule III drug ~~prescriptions must be authorized by a physician and~~ may ~~not~~lead beto ~~refilled~~severe ~~more~~psychological ~~than six months after the date of the original prescription~~ or ~~more~~physical ~~than five times~~dependence. A prescription for controlled substances classified in Schedules III, IV, and V issued by a physician, may be communicated either orally, in writing or by facsimile to the pharmacies. Controlled substances that are also classified as narcotics, such as hydrocodone, oxycodone and hydromorphone, are also subject to additional DEA requirements, such as manufacturer reporting of the import of narcotic raw material.

Annual registration is required for any facility that manufactures, distributes, dispenses, imports or exports any controlled substance. The registration is specific to the particular location, activity and controlled substance schedule. For example, separate registrations are needed for import and manufacturing, and each registration will specify which schedules of controlled substances are authorized. Similarly, separate registrations are also required for separate facilities. Acquisition and distribution transactions must also be reported for Schedule I and II controlled substances, as well as Schedule III narcotic substances.

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The DEA typically inspects a facility to review its security measures prior to issuing a registration and on a periodic basis. Security requirements vary by controlled substance schedule, with the most stringent requirements applying to Schedule I and Schedule II substances. Required security measures include background checks on employees and physical control of inventory through measures such as cages, surveillance cameras and inventory reconciliations. Records must be maintained for the handling of all controlled substances, and periodic reports made to the DEA, for example distribution reports for Schedule I and II controlled substances, Schedule III substances that are narcotics, and other designated substances. Reports must also be made for thefts or losses of any controlled substance, and to obtain authorization to destroy any controlled substance. In addition, special permits and notification requirements apply to imports and exports of narcotic drugs. To enforce these requirements, the DEA conducts periodic inspections of registered establishments that handle controlled substances. Failure to maintain compliance with applicable requirements, particularly as manifested in loss or diversion, can result in administrative, civil or criminal enforcement action that could have a material adverse effect on our business, results of operations and financial condition. The DEA may seek civil penalties, refuse to renew necessary registrations, or initiate administrative proceedings to revoke those registrations. In some circumstances, violations could result in criminal proceedings.

In addition, a DEA quota system controls and limits the availability and production of controlled substances in Schedule I or II. Distributions of any Schedule I or II controlled substance or Schedule III narcotic must also be accompanied by special order forms, with copies provided to the DEA. Because AZSTARYS and our product candidates may be regulated as Schedule II controlled substances, they may be subject to the DEA’s production and procurement quota scheme. The DEA establishes annually an aggregate quota for how much of a controlled substance may be produced in total in the United States based on the DEA’s estimate of the quantity needed to meet legitimate scientific and medicinal needs. The limited aggregate amount of stimulants that the DEA allows to be produced in the U.S. each year is allocated among individual companies, which must submit applications annually to the DEA for individual production and procurement quotas. We and our contract manufacturers must receive an annual quota from the DEA in order to produce or procure any Schedule I or Schedule II substances for use in manufacturing of our product candidates. The DEA may adjust aggregate production quotas and individual production and procurement quotas from time to time during the year, although the DEA has substantial discretion in whether or not to make such adjustments. Our, or our contract manufacturers’, quota of an active ingredient may not be sufficient to meet commercial demand or complete clinical trials. Any delay, limitation or refusal by the DEA in establishing our, or our contract manufacturers’, quota for controlled substances could delay or stop our clinical trials or product launches, which could have a material adverse effect on our business, financial position and results of operations.

Individual states also independently regulate controlled substances. We and our contract manufacturers will be subject to state regulation on distribution of these products, including, for example, state requirements for licensures or registration.

Other Healthcare Regulatory Frameworks

Our business activities, including but not limited to, research, sales, promotion, distribution, medical education and other activities are subject to regulation by numerous regulatory and law enforcement authorities in the United States in addition to the FDA, including potentially the Department of Justice, the U.S. Department of Health and Human Services and its various divisions, including the CMS and the Health Resources and Services Administration, the Department of Veterans Affairs, the Department of Defense and state and local governments. Our business activities must comply with numerous healthcare laws, including those described below. Compliance with government regulations requires the expenditure of substantial time and financial resources.

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The federal Anti-Kickback Statute prohibits, among other things, any person or entity, from knowingly and willfully offering, paying, soliciting or receiving any remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward, or in return for, the referral of an individual for, or purchasing, leasing, ordering, or arranging for the purchase, lease or order of, any good, facility, item or service reimbursable under Medicare, Medicaid or other federal healthcare programs. The term remuneration has been interpreted broadly to include anything of value. There are a number of statutory exceptions and regulatory safe harbors protecting some common activities from prosecution. The exceptions and safe harbors are drawn narrowly and practices that involve remuneration that may be alleged to be intended to induce prescribing, purchasing or recommending may be subject to scrutiny if they do not qualify for an exception or safe harbor. Failure to meet all of the requirements of a particular applicable statutory exception or regulatory safe harbor does not make the conduct per se illegal under the federal Anti-Kickback Statute. Instead, the legality of the arrangement will be evaluated on a case-by-case basis based on a cumulative review of all of its facts and circumstances. Additionally, a person or entity does not need to have actual knowledge of the federal Anti-Kickback Statute, or the specific intent to violate it to have committed a violation.

The federal civil and criminal false claims laws, including the federal False Claims Act, which can be enforced by private citizens through civil whistleblower or qui tam actions, prohibit, among other things, any person or entity from knowingly presenting, or causing to be presented, a false claim for payment to, or approval by, the federal government, including the Medicare and Medicaid programs, or knowingly making, using, or causing to be made or used a false record or statement material to a false or fraudulent claim or to avoid, decrease or conceal an obligation to pay money to the federal government. In addition, a claim for payment of items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the False Claims Act.

The civil monetary penalties statute imposes penalties against any person or entity who, among other things, is determined to have presented or caused to be presented a claim to a federal health program that the person knows or should know is for an item or service that was not provided as claimed or is false or fraudulent.

The federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), created additional federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of whether the payor is public or private, knowingly and willfully embezzling or stealing from a health care benefit program, willfully obstructing a criminal investigation of a health care offense and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters. Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute, or the specific intent to violate it, to have committed a violation.

Additionally, the federal Physician Payments Sunshine Act and its implementing regulations, require certain manufacturers of drugs, devices, biologicals and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with specified exceptions) to report annually information related to specified payments or other transfers of value provided to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other healthcare providers (physician assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, anesthesiologist assistants, and certified nurse-midwives) and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, such providers and teaching hospitals and to report annually specified ownership and investment interests held by physicians and their immediate family members.

Depending on the circumstances, failure to comply with these laws can result in significant penalties, including criminal, civil and/or administrative penalties, damages, fines, disgorgement, debarment from government contracts, individual imprisonment, additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, exclusion from government programs, refusal to allow us to enter into supply contracts, including government contracts, reputational harm, diminished profits and future earnings and the curtailment or restructuring of our operations, any of which could adversely affect our business.

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Data Privacy and Security ~~Laws~~Law

We ~~may~~are be subject to data privacy and security laws, regulations, and standards by foreign, federal, state and local governments that govern the collection, use, access to, confidentiality and security of health-related and other personal information. In the United States, numerous federal and state laws and regulations, including data breach notification laws, health information privacy and security laws and consumer protection laws and regulations govern the collection, use, disclosure, and protection of health-related and other personal information. In addition, certain foreign laws govern the privacy and security of personal data, including health-related data. Privacy and security laws, regulations, and other obligations are constantly evolving, may conflict with each other to complicate compliance efforts, and can result in investigations, proceedings, or actions that lead to significant civil and/or criminal penalties and restrictions on data processing.

Healthcare Reform Measures

The United States and some foreign jurisdictions are considering or have enacted a number of legislative and regulatory proposals designed to change the healthcare system in ways that could affect our ability to sell our products profitably. Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and/or expanding access. In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives.

For example, in March 2010, the ACA was passed, which has substantially changed health care financing by both governmental and private insurers, and significantly affected the U.S. pharmaceutical industry. The ACA, among other things, subjected manufacturers to new annual fees and taxes for specified branded prescription drugs, increased the minimum Medicaid rebates owed by most manufacturers under the Medicaid Drug Rebate Program, expanded health care fraud and abuse laws, revised the methodology by which rebates owed by manufacturers to the state and federal government for covered outpatient drugs under the Medicaid Drug Rebate Program are calculated, imposed an inflation penalty on new formulations of drugs, extended the Medicaid Drug Rebate program to utilization of prescriptions of individuals enrolled in Medicaid managed care organizations, expanded the 340B program which caps the price at which manufacturers can sell covered outpatient pharmaceuticals to specified hospitals, clinics and community health centers, and provided incentives to programs that increase the federal government’s comparative effectiveness research.

Since its enactment there have been executive, judicial and congressional challenges to certain aspects of the ACA. On June 17, 2021, the U.S. Supreme Court dismissed the most recent judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA.

Other legislative changes have been proposed and adopted in the United States since the ACA was enacted. In August 2011, the Budget Control Act of 2011, among other things, included aggregate reductions of Medicare payments to providers, which went into effect in April 2013, and, due to subsequent legislative amendments, will remain in effect through 2032 with the exception of a temporary suspension from May 1, 2020, through March 31, 2022, unless additional Congressional action is taken. In addition, in January 2013, the American Taxpayer Relief Act of 2012 was signed into law, which, among other things, reduced Medicare payments to several categories of healthcare providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. On March 11, 2021, the American Rescue Plan Act of 2021 was signed into law, which eliminated the statutory Medicaid drug rebate cap, beginning January 1, 2024. The rebate was previously capped at 100% of a drug’s average manufacturer price.

Further, there has been increasing legislative and enforcement interest in the United States with respect to specialty drug pricing practices. Specifically, there have been several recent U.S. Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the cost of drugs under Medicare, and reform government program reimbursement methodologies for drugs. On August 16, 2022, the Inflation Reduction Act (“IRA”), of 2022, was signed into law. Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (beginning in 2026), imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023), and replaces the Part D coverage gap discount program with a new discounting program (which began in 2025). The IRA permits the Secretary of the Department of Health and Human Services, or HHS, to implement many of these provisions through guidance, as opposed to regulation, for the initial years. CMS has published the negotiated prices for the initial ten drugs, which will first be effective in 2026, and the list of the subsequent 15 drugs that will be subject to negotiation, although the drug price negotiation program is currently subject to legal challenges. For that and other reasons, it is currently unclear how the IRA will be effectuated. At the state level, legislatures are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure, drug price increase reporting and other transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. Some states have enacted legislation creating so-called prescription drug affordability boards, which ultimately may attempt to impose price limits on certain drugs in these states.

We expect that additional state, federal and foreign healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal, state and foreign governments will pay for healthcare product candidates and services, which could result in reduced demand for our products or additional pricing pressures.

On December 13, 2021, Regulation No 2021/2282 on HTA, amending Directive 2011/24/EU, was adopted. The Regulation entered into force in January 2022, and has been applicable since January 2025, with a phased implementation based on the type of product, i.e. oncology and advanced therapy medicinal products as of 2025, orphan medicinal products as of 2028, and all other medicinal products by 2030. The Regulation intends to boost cooperation among EU member states in assessing health technologies, including new medicinal products, and provide the basis for cooperation at the EU level for joint clinical assessments in these areas. It permits EU member states to use common HTA tools, methodologies, and procedures across the EU, working together in four main areas, including joint clinical assessment of the innovative health technologies with the highest potential impact for patients, joint scientific consultations whereby developers can seek advice from HTA authorities, identification of emerging health technologies to identify promising technologies early, and continuing voluntary cooperation in other areas. Individual EU member states will continue to be responsible for assessing non-clinical (e.g., economic, social, ethical) aspects of health technology, and making decisions on pricing and reimbursement.

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The Foreign Corrupt Practices Act

The Foreign Corrupt Practices Act (“FCPA”) prohibits any U.S. individual or business from paying, offering or authorizing payment or offering of anything of value, directly or indirectly, to any foreign official, political party or candidate for the purpose of influencing any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business. The FCPA also obligates companies whose securities are listed in the United States to comply with accounting provisions requiring the companies to maintain books and records that accurately and fairly reflect all transactions of the companies, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.

Foreign Regulation

In addition to regulations in the United States, we will be subject to a variety of foreign regulations governing clinical trials and commercial sales and distribution of our products to the extent we choose to develop or sell any products outside of the United States. The foreign regulatory approval process includes all of the risks associated with FDA approval set forth above, as well as additional country-specific regulation.

Whether or not we obtain FDA approval for a product, we must obtain approval of a product by the comparable regulatory authorities of foreign countries before we can commence clinical trials or marketing of the product in those countries. Approval by one regulatory authority does not ensure approval by regulatory authorities in other jurisdictions. The approval process varies from country to country and the time may be longer or shorter than that required to obtain FDA approval. The requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from country to country.

EU Non-clinical Studies and Clinical Trials

Similarly to the United States, the various phases of non-clinical and clinical research in the EU are subject to significant regulatory controls.

Non-clinical studies are performed to demonstrate the health or environmental safety of new chemical or biological substances. Non-clinical (pharmaco-toxicological) studies must be conducted in compliance with the principles of good laboratory practice (“GLP”) as set forth in EU Directive 2004/10/EC (unless otherwise justified for certain particular medicinal products, e.g., radio-pharmaceutical precursors for radio-labeling purposes). In particular, non-clinical studies, both in vitro and in vivo, must be planned, performed, monitored, recorded, reported and archived in accordance with the GLP principles, which define a set of rules and criteria for a quality system for the organizational process and the conditions for non-clinical studies. These GLP standards reflect the Organization for Economic Co-operation and Development requirements.

Clinical trials of medicinal products in the EU must be conducted in accordance with EU and national regulations and the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (“ICH”) guidelines on Good Clinical Practices as well as the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

If the sponsor of the clinical trial is not established within the EU, it must appoint an EU entity to act as its legal representative. The sponsor must take out a clinical trial insurance policy, and in most EU member states, the sponsor is liable to provide ‘no fault’ compensation to any study subject injured in the clinical trial.

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The regulatory landscape related to clinical trials in the EU has been subject to recent changes. The EU Clinical Trials Regulation (“CTR”) which was adopted in April 2014 and repeals the EU Clinical Trials Directive, became applicable on January 31, 2022. Unlike directives, the CTR is directly applicable in all EU member states without the need for member states to further implement it into national law. The CTR notably harmonizes the assessment and supervision processes for clinical trials throughout the EU via a Clinical Trials Information System, which contains a centralized EU portal and database.

While the EU Clinical Trials Directive required a separate clinical trial application (“CTA”) to be submitted in each member state in which the clinical trial takes place, to both the competent national health authority and an independent ethics committee, much like the FDA and IRB respectively, the CTR introduces a centralized process and only requires the submission of a single application for multi-center trials. The CTR allows sponsors to make a single submission to both the competent authority and an ethics committee in each member state, leading to a single decision per member state. The CTA must include, among other things, a copy of the trial protocol and an investigational medicinal product dossier containing information about the manufacture and quality of the medicinal product under investigation. The assessment procedure of the CTA has been harmonized as well, including a joint assessment by all member states concerned, and a separate assessment by each member state with respect to specific requirements related to its own territory, including ethics rules. Each member state’s decision is communicated to the sponsor via the centralized EU portal. Once the CTA is approved, clinical study development may proceed.

The CTR transition period ended on January 31, 2025, and all clinical trials (and related applications) are now fully subject to the provisions of the CTR. Medicines used in clinical trials must be manufactured in accordance with Good Manufacturing Practice (“GMP”). Other national and EU-wide regulatory requirements may also apply.

26 EU Marketing Authorization

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Marketing Authorization

In order to market our product candidates in the EU and many other foreign jurisdictions, we must obtain separate regulatory approvals. More concretely, in the EU, medicinal product candidates can only be commercialized after obtaining a marketing authorization (“MA”). To obtain regulatory approval of a product candidate under EU regulatory systems, we must submit a MA application (“MAA”). The process for this depends, among other things, on the nature of the medicinal product. There are two types of MAs:

• “Centralized MAs” are issued by the European Commission through the centralized procedure based on the opinion of the Committee for Medicinal Products for Human Use (“CHMP”) of the European Medicines Agency (“EMA”) and are valid throughout the EU. The centralized procedure is compulsory for certain types of medicinal products such as (i) medicinal products derived from biotechnological processes, (ii) designated orphan medicinal products, (iii) advanced therapy medicinal products (“ATMPs”) (such as gene therapy, somatic cell therapy and tissue engineered products) and (iv) medicinal products containing a new active substance indicated for the treatment of certain diseases, such as HIV/AIDS, cancer, diabetes, neurodegenerative diseases or autoimmune diseases and other immune dysfunctions, and viral diseases. The centralized procedure is optional for products containing a new active substance not yet authorized in the EU, or for products that constitute a significant therapeutic, scientific or technical innovation or which are in the interest of public health in the EU.

• “National MAs” are issued by the competent authorities of the EU member states, only cover their respective territory, and are available for product candidates not falling within the mandatory scope of the centralized procedure. Where a product has already been authorized for marketing in an EU member state, this national MA can be recognized in another member state through the mutual recognition procedure. If the product has not received a national MA in any member state at the time of application, it can be approved simultaneously in various member states through the decentralized procedure. Under the decentralized procedure an identical dossier is submitted to the competent authorities of each of the member states in which the MA is sought, one of which is selected by the applicant as the reference member state.

Under the above-described procedures, in order to grant the MA, the EMA or the competent authorities of the EU member states make an assessment of the risk benefit balance of the product on the basis of scientific criteria concerning its quality, safety and efficacy. MAs have an initial duration of five years. After these five years, the authorization may be renewed based on a reevaluation of the risk-benefit balance.

~~Data and Marketing Exclusivity~~27

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Failure to comply with EU and member state laws that apply to the conduct of clinical trials, manufacturing approval, MA of medicinal products and marketing of such products, both before and after grant of the MA, manufacturing of pharmaceutical products, statutory health insurance, bribery and anti-corruption or with other applicable regulatory requirements may result in administrative, civil or criminal penalties. These penalties could include delays or refusal to authorize the conduct of clinical trials, or to grant MA, product withdrawals and recalls, product seizures, suspension, withdrawal or variation of the MA, total or partial suspension of production, distribution, manufacturing or clinical trials, operating restrictions, injunctions, suspension of licenses, fines and criminal penalties.

EU Data and Marketing Exclusivity

In the EU, new products authorized for marketing (i.e., reference products) generally receive eight years of data exclusivity and an additional two years of market exclusivity upon MA. If granted, the data exclusivity period prevents generic and biosimilar applicants from relying on the preclinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar MA in the EU during a period of eight years from the date on which the reference product was first authorized in the EU. The market exclusivity period prevents a successful generic or biosimilar applicant from commercializing its product in the EU until ten years have elapsed from the initial MA of the reference product in the EU. The overall ten-year market exclusivity period can be extended to a maximum of eleven years if, during the first eight years of those ten years, the MA holder obtains an authorization for one or more new therapeutic indications, which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies. However, there is no guarantee that a product will be considered by the EU’s regulatory authorities to be a new chemical or biological entity, and products may not qualify for data exclusivity.

EU Orphan Medicinal Products

The criteria for designating an “orphan medicinal product” in the EU are similar in principle to those in the United States. A medicinal product can be designated as an orphan if its sponsor can establish that: (1) the product is intended for the diagnosis, prevention or treatment of a life threatening or chronically debilitating condition (2) either (a) such condition affects not more than five in 10,000 persons in the EU when the application is made, or (b) the product, without the benefits derived from the orphan status, would not generate sufficient return in the EU to justify the necessary investment; and (3) there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorized for marketing in the EU or, if such method exists, the product will be of significant benefit to those affected by that condition.

Orphan designation must be requested before submitting an MAA. An EU orphan designation entitles a party to incentives such as reduction of fees or fee waivers, protocol assistance, and access to the centralized procedure. Upon grant of a MA, orphan medicinal products are entitled to ten years of market exclusivity for the approved indication, which means that the competent authorities cannot accept another MAA, or grant a MA, or accept an application to extend a MA for a similar medicinal product for the same indication for a period of ten years. The period of market exclusivity is extended by two years for orphan medicinal products that have also complied with an agreed pediatric investigation plan (“PIP”). No extension to any supplementary protection certificate can be granted based on pediatric studies for orphan indications. Orphan designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.

The orphan exclusivity period may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for which it received orphan destination, including where it is shown that the product is sufficiently profitable not to justify maintenance of market exclusivity or where the prevalence of the condition has increased above the threshold. Additionally, MA may be granted to a similar product for the same indication at any time if (i) the second applicant can establish that its product, although similar, is safer, more effective or otherwise clinically superior; (ii) the applicant consents to a second orphan medicinal product application; or (iii) the applicant cannot supply enough orphan medicinal product.

27 EU Pediatric Development

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Pediatric Development

In the EU, MAAs for new medicinal products must include the results of studies conducted in the pediatric population, in compliance with a PIP agreed with the EMA’s Pediatric Committee (“PDCO”). The PIP sets out the timing and measures proposed to generate data to support a pediatric indication of the drug for which MA is being sought. The PDCO can grant a deferral of the obligation to implement some or all of the measures of the PIP until there are sufficient data to demonstrate the efficacy and safety of the product in adults. Further, the obligation to provide pediatric clinical trial data can be waived by the PDCO when these data is not needed or appropriate because the product is likely to be ineffective or unsafe in children, the disease or condition for which the product is intended occurs only in adult populations, or when the product does not represent a significant therapeutic benefit over existing treatments for pediatric patients. Once the MA is obtained in all the EU member states and study results are included in the product information, even when negative, the product is eligible for six months’ supplementary protection certificate extension (if any is in effect at the time of approval) or, in the case of orphan pharmaceutical products, a two-year extension of the orphan market exclusivity is granted.

Controlled substances

The aforementioned EU rules are generally applicable in the European Economic Area (“EEA”) which consists of the 27 EU member states plus Norway, Liechtenstein and Iceland.

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EU Controlled Substances

The EU legislation does not establish different classes of narcotic or psychotropic substances. However, the United Nations (“UN”) Single Convention on Narcotic Drugs of 1961 and the UN Convention on Psychotropic Substances of 1971 (“UN Conventions”) codify internationally applicable control measures to ensure the availability of narcotic drugs and psychotropic substances for medical and scientific purposes. The individual EU member states are all signatories to these UN Conventions. All signatories have a dual obligation to ensure that these substances are available for medical purposes and to protect populations against abuse and dependence. The UN Conventions regulate narcotic drugs and psychotropic substances as Schedule I, II, III, IV substances with Schedule II substances presenting the lowest relative risk of abuse among such substances and Schedule I and IV substances considered to present the highest risk of abuse. The UN Conventions require signatories to require all persons manufacturing, trading (including exporting and importing) or distributing controlled substances to obtain a license from the relevant authority. Each individual export or import of a controlled substance must also be subject to an authorization. The obligations provided in the UN Conventions and additional requirements are implemented at national level and requirements may vary from one member state to another.

Employees

As of December 31, ~~2024~~2025, we employed 59 61 full-time employees.

Corporate Information

We were incorporated under the laws of the State of Iowa in October 2006 and were reincorporated under the laws of the State of Delaware in May 2014. We changed our name from KemPharm, Inc. to Zevra Therapeutics, Inc. effective as of February 21, 2023. Our website address is www.zevra.com.

ITEM 1A. RISK FACTORS.

Risk Factors Summary

We are providing the following summary of the risk factors contained in our Form 10-K to enhance the readability and accessibility of our risk factor disclosures. We encourage our stockholders to carefully review the full risk factors contained in this Form 10-K in their entirety for additional information regarding the risks and uncertainties that could cause our actual results to vary materially from our recent results or from our anticipated future results.

Risks Related to the Commercialization of Our Approved Products and Product Candidates

● If we are unable to establish effective sales, marketing and distribution capabilities for our approved products ~~or product candidates~~, ifincluding ~~approved, we may not be successful in commercializing~~ any ~~approved product or product candidate in the United States or any other jurisdictions. ● Our approved products, or any~~ of our product candidates that may receive marketing approval, may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success. ● Because the target patient populations for OLPRUVA® and MIPLYFFATM are small, we ~~must achieve significant market share and obtain relatively high per-patient prices for our products to achieve meaningful gross margins. ● We face substantial competition, which~~ may ~~result in others developing or commercializing products before or more successfully than we do. ● We may~~ not be ~~able~~successful toin ~~obtain~~commercializing ~~either~~such ~~three-year FDA regulatory exclusivity or five-year FDA regulatory exclusivity as a new chemical entity. ● Even if we or our collaborators are able to commercialize our approved~~ products, or any of our product candidates, if approved, they may be subject to unfavorable pricing regulations, third-party coverage and reimbursement policies. ● We may be subject to enforcement action if we engage in ~~improper~~the ~~marketing~~United orStates ~~promotion of our products. ● If commercialization of our approved products,~~ or any ofother ~~our product candidates, if approved, are not successful, or we experience significant delays in commercialization, our business will be harmed~~jurisdictions.

~~Risks~~We ~~Related~~currently have limited marketing and sales experience. In order to commercialize our approved products, we have added marketing, sales, medical affairs, distribution, managerial and other non-technical capabilities, or have made arrangements with third parties to perform these services. For any of our other product candidates that receive marketing approval, we may have to augment our commercial capabilities or make arrangements with third parties to perform additional services. Building and maintaining a targeted specialty sales force is expensive and time consuming. Any failure or delay in the ~~Development~~development of ~~Our~~our ~~Product~~internal ~~Candidates~~sales, marketing and distribution capabilities would adversely impact our commercialization efforts. We may choose to collaborate with third parties that have their own sales forces and established distribution systems, in lieu of or to augment any sales force and distribution systems we may create. If we are unable to enter into collaborations with third parties for the commercialization of approved products on acceptable terms or at all, or if any such collaborator does not devote sufficient resources to the commercialization of our products or otherwise fails in commercialization efforts, we may not be able to successfully commercialize our approved products.

●Our ~~If we are not able to obtain required regulatory approvals for any of our product candidates, or the~~ approved ~~labels are not sufficiently differentiated from other competing~~ products, weas ~~will~~well not be able to commercialize them and our ability to generate revenue or profits or to raise future capital could be limited. ● Disruptions at the FDA, the EMA and other government agencies, including those caused by funding shortages or global health concerns could hinder their ability to hire, retain or deploy key leadership and other personnel, or otherwise prevent new or modified products from being developed, approved or commercialized in a timely manner or at all, which could negatively impact our business. ● If the FDA does not conclude that our product candidates satisfy the requirements for selected regulatory pathways, such as ~~the~~any ~~505(b)(2)~~of ~~NDA pathway, the approval process for~~ our product candidates ~~will~~that ~~likely take significantly longer, cost significantly more and entail significantly greater complications and risks than anticipated, and the FDA~~ may ~~not~~receive ~~ultimately~~marketing ~~approve our product candidates. ● Clinical drug development involves a lengthy and expensive process~~approval, ~~with an uncertain outcome. We~~ may ~~incur~~fail ~~additional costs or experience delays in completing, or ultimately be unable~~ to ~~complete,~~achieve the ~~development~~degree ~~and commercialization~~ of ~~our~~market ~~product~~acceptance ~~candidates.~~by ~~● If we experience delays or difficulties in the enrollment of subjects in clinical trials~~physicians, ~~our receipt of necessary regulatory approvals could be delayed or prevented. ● Interim~~patients, ~~topline,~~third-party orpayors ~~preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available~~ and ~~are~~others ~~subject to audit and verification procedures that could result~~ in ~~materials changes in~~ the ~~final~~medical ~~data.~~community ●necessary ~~We may not be able to obtain or maintain orphan drug designations which we pursue~~ for any of our product candidates, and we may be unable to maintain the benefits associated with orphan drug designation, including the potential for market exclusivity. ● Certain of our approved products and product candidates contain controlled substances, the manufacture, use, sale, importation, exportation, prescribing and distribution of which are subject to regulation by the DEA and other regulatory agencies. ● Our products and product candidates may be associated with serious adverse events, undesirable side effects or have other properties that could halt their clinical development, prevent their regulatory approval, limit their commercial potential or result in significant negative consequences. ● We may expend our limited resources to pursue a particular product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success. ● If the EAP is terminated prior to commercialization of arimoclomol in the EU, if approved, it will have a material adverse effect on our business, results of operations, cash flows, financial condition and/or prospects.

~~Risks~~Our ~~Related~~approved products, as well as any of our product candidates that may receive marketing approval, may fail to ~~Our~~gain ~~Business~~sufficient market acceptance by physicians, ~~Our~~patients, ~~Financial~~third-party ~~Position~~payors and ~~Our~~others ~~Capital~~in ~~Needs~~the medical community. The degree of market acceptance of our approved products will depend on a number of factors, including:

● Our future results will suffer if we do not effectively manage our operations. ● A variety of risks associated with international operations could materially adversely affect our business. ● We may not be able to retain suppliers or distributors, or suppliers or distributors may seek to modify contractual relationships with us, which could have an adverse effect on our business and operations. Third parties may terminate or alter existing contracts or relationships with us. ● If we fail to maintain effective internal controls over financial reporting and disclosure controls and procedures, we may not be able to accurately report our financial results or report them in a timely manner, which may adversely affect investor confidence in us and, as a result, •the ~~value~~efficacy ~~of our common stock. ● We have incurred significant recurring negative~~ and ~~operating~~potential ~~cash~~advantages ~~flows.~~compared ~~We cannot predict if we will incur positive or negative net operating cash flows over the next several years, and we may never achieve or maintain profitability. ● We may need additional funding~~ to ~~pursue~~alternative ~~our business objectives. If we are unable to raise capital when needed~~treatments, weincluding ~~could~~less beexpensive ~~forced~~generic ~~to delay, reduce or altogether cease our development programs or commercialization efforts or cease operations altogether.~~treatments;

~~Risks~~•the ~~Related~~ability to ~~Our~~obtain ~~Dependence~~differentiating onclaims ~~Third~~in ~~Parties~~the labels for approved products;

●•the ~~We rely on and expect to continue to rely on third parties to conduct our~~ clinical ~~trials~~indications for ~~our~~which ~~product candidates, and those third parties may not perform satisfactorily, including failing to meet deadlines for the completion of such trials. ● The facilities used by~~ our ~~contract manufacturers to manufacture our approved~~ products, ~~and any of our product candidates~~ are subject to review by the FDA or comparable foreign regulatory authorities pursuant to inspections that will be conducted after we submit our marketing application to the FDA or the EMA, and such inspections could result in findings that lead to failure to obtain FDA or comparable foreign approval of such marketing applications. ● Our approved products that we are commercializing, and product candidates that we are currently developing, or may develop in the future, may compete with other product candidates and drugs for access to manufacturing facilities, and we may be unable to obtain access to these facilities on favorable terms. ● We have entered into collaborations with Commave, to develop, manufacture and commercialize AZSTARYS worldwide. In addition, we may seek collaborations with third parties for the development or commercialization of our other product candidates, or in other territories. If those collaborations are not successful, we may not be able to capitalize on the market potential of AZSTARYS or any of our other product candidates, if approved. ● If we are not able to establish collaborations for our product candidates, we may have to alter our development and commercialization plans.;

~~Risks~~•the ~~Related~~convenience toand ~~Our~~ease ~~Intellectual~~of ~~Property~~administration compared to alternative treatments;

● If we are unable to obtain and maintain trade secret protection or patent prosecution for our technology, our approved products or our product candidates, or if the scope of the patent protection obtained is not sufficiently broad, our competitors could develop and commercialize technology and drugs similar or identical to ours, and our ability to successfully commercialize our technology, our approved products, or our product candidates, if approved, may be impaired. ● Changes in patent law in the United States and other jurisdictions could alter or diminish the value of patents in general, thereby impairing our ability to protect our products and technologies. ● We may become involved in lawsuits to protect or enforce our patents or other intellectual property, which could be expensive, time consuming and unsuccessful. ● Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could significantly harm our business. ● Intellectual property litigation could cause us to spread substantial resources and distract our personnel from their normal responsibilities. ● We may need to license intellectual property from third parties, and such licenses may not be available or may not be available on commercially reasonable terms. ● If we or our third-party licensors fail to comply with our obligations in our intellectual property licenses and funding arrangements with third parties, we could lose rights that are important to our business. ● The scope of our intellectual property may be reduced or may need to be reduced due to third-party intellectual property claims. ● We may be subject to claims by third parties asserting that we or our employees have misappropriated their intellectual property or claiming ownership of what we regard as our own intellectual property. ● Any trademarks we may obtain may be infringed or successfully challenged, resulting in harm to our business. ● If we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be harmed. ● We may not be able to protect our intellectual property rights throughout the world. ● Our decision to seek approval of our product candidates under certain regulatory pathways, such as the 505(b)(2) NDA pathway for the FDA, may increase the risk that patent infringement suits are filed against us, which would delay FDA or comparable foreign regulatory authorities' approval of such product candidates.

Risks Related to Regulatory Approval of Our Product Candidates and Other Legal Compliance Matters

● Failure to obtain marketing approval in international jurisdictions would prevent our approved products, and any of our other product candidates from being marketed abroad. ● A variety of risks associated with marketing our approved products, and any of our other product candidates, if approved, internationally, could affect our business. ● Our approved products are, and any of our product candidates for which we obtain marketing approval will remain subject to significant post-marketing regulatory requirements and oversights. ● Our employees, independent contractors, principal investigators, CROs, consultants, commercial collaborators, contract manufacturers, service providers and other vendors may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements. ● Our current and future relationships with healthcare professionals, principal investigators, consultants, customers and third-party payors in the United States and elsewhere may be subject, directly or indirectly, to applicable anti-kickback, fraud and abuse, false claims, physician payment transparency, and other healthcare laws and regulations, which could expose us to penalties. ● Recently enacted and future legislation may increase the difficulty and cost for us to obtain marketing approval of our product candidates and increase the cost to commercialize our approved products, and any of our product candidates that may be approved in the future and affect the prices thereof. ● If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate Program or other governmental pricing programs in which we participate, we could be subject to additional reimbursement requirements, penalties, sanctions and fines, which could have a material adverse effect on our business, financial condition, results of operations and growth prospects. ● Governments outside the United States tend to impose strict price controls, which may affect our revenue, if any. ● If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could harm our business. ● If our security measures are compromised now, or in the future, or the security, confidentiality, integrity or availability of, our information technology systems, software, services, communications or data is compromised, limited or fails, this could result in a material adverse impact, including without limitation, a material interruption to our operations, harm to our reputation, significant fines, penalties and liability, breach or a triggering of data protection laws, privacy policies and data protection obligations, loss of customers or sales, or material disruption of our clinical trials, commercialization or other business activities. ● Failure or perceived failure to comply with existing or future laws, regulations, contracts, self-regulatory schemes, policies, standards and other obligations related to data privacy or security could lead to government enforcement actions (which could include civil or criminal fines or penalties), a disruption of our clinical trials or commercialization of our products, private litigation, other liabilities and/or adverse publicity. Compliance, or the failure to comply with such obligations, could increase the costs of our products, could limit their use, and could otherwise negatively affect our operating results and business. ● We are subject to complex and changing laws and regulations, which exposes us to potential liabilities, increased costs and other adverse effects on our business.

Risks Related to Employee Matters and Managing Our Growth

● Our future success depends on our ability to retain key executives and to attract, retain and motivate qualified personnel.

Risks Related to Ownership of Our Common Stock and Our Status as a Public Company

● The trading price of the shares of our common stock is likely to be volatile, and purchasers of our common stock could incur substantial losses. ● Future sales and issuances of equity and debt could result in additional dilution to our stockholders. ● Sales of a substantial number of shares of our common stock in the public market could cause the market price of our common stock to drop significantly, even if our business is doing well. ● Anti-takeover provisions in our amended and restated certificate of incorporation and amended and restated bylaws, as well as provisions of Delaware law and the terms of some of our contracts, might discourage, delay or prevent a change in control of our company or changes in our board of directors or management and, therefore, depress the price of our common stock. ● If we engage in acquisitions to grow our business, we will incur a variety of costs and may potentially face numerous risks that could adversely affect our business and operations and cause our stock price to decline. ● We could be negatively affected as a result of the actions of activist stockholders, which could be disruptive and costly and may conflict with or disrupt the strategic direction of our business. ● We may be subject to securities litigation, class action and derivative lawsuits, which could result in substantial costs and could divert management attention away from other business concerns. ● Our amended and restated certificate of incorporation provides that the Court of Chancery of the State of Delaware is the exclusive forum for substantially all disputes between us and our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or other employees. ● We might not be able to utilize a significant portion of our net operating loss carryforwards, which could adversely affect our profitability. ● Changes in tax laws or regulations that are applied adversely to us may have a material adverse effect on our business, cash flow, financial condition or results of operations.

General Risk Factors

● An active trading market for our common stock may not be sustained and you may not be able to resell your shares of our common stock for a profit, if at all. ● If equity research analysts do not publish research or reports, or publish unfavorable research or reports, about us, our business or our market, our stock price and trading volume could decline. ● Because we do not anticipate paying any cash dividends on our common stock in the foreseeable future, capital appreciation, if any, will be your sole source of gains and you may never receive a return on your investment. ● We incur increased costs and demands upon management as a result of being a public company. ● Adverse developments affecting the financial services industry, including events or concerns involving liquidity, defaults, or non-performance by financial institutions, could adversely affect our business, financial conditions or results of operations.

You should carefully consider all the risk factors and uncertainties described below, in addition to other information contained in this Annual Report on Form 10-K, including the section of this report titled “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and our financial statements and related notes, before investing in our common stock. If any of the following risks materialize, our business, financial condition and results of operations could be seriously harmed. This Annual Report on Form 10-K also contains forward-looking statements that involve risks and uncertainties. Our actual results could differ materially from those anticipated in the forward-looking statements because of factors that are described below and elsewhere in this Annual Report on Form 10-K.

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~~Risks~~•the ~~Related~~willingness toof the ~~Commercialization~~target ofpatient ~~Our~~population ~~Approved~~to ~~Products~~try new therapies and ~~Product~~of ~~Candidates~~physicians to prescribe these therapies;

If•the wecost ~~are~~of ~~unable~~treatment ~~to establish effective sales, marketing and distribution capabilities for our approved products or product candidates, if approved, we may not be successful~~ in ~~commercializing~~relation ~~any~~to ~~approved~~alternative ~~product candidate in the United States or any other jurisdictions.~~treatments;

~~We currently have limited marketing and sales experience. In order to commercialize OLPRUVA for oral suspension in~~ •the ~~U.S.~~strength ~~for the treatment~~ of ~~certain patients with UCDs and MIPLYFFA, an orally-delivered treatment for NPC, we have added~~ marketing, ~~sales, medical affairs, distribution, managerial~~ and other non-technical capabilities, or have made arrangements with third parties to perform these services. For any of our other product candidates that receive marketing approval we may have to augment our commercial capabilities or make arrangements with third parties to perform additional services, and we may not be successful in doing any of the foregoing. Building and maintaining a targeted specialty sales force is expensive and time consuming. Any failure or delay in the development of our internal sales, marketing and distribution capabilities would adversely impact our commercialization efforts. We may choose to collaborate with third parties that have their own sales forces and established distribution systems, in lieu of or to augment any sales force and distribution systems we may create. If we are unable to enter into collaborations with third parties for the commercialization of approved product candidates, if any, on acceptable terms or at all, or if any such collaborator does not devote sufficient resources to the commercialization of our product or otherwise fails in commercialization efforts, we may not be able to successfully commercialize our product candidates that receive marketing approval. If we are not successful in commercializing our product candidates that receive marketing approval, either on our own or through collaborations with one or more third parties, our potential future revenue will be materially and adversely impacted.support;

~~Establishing~~•the ~~our~~availability ~~own~~of ~~sales,~~third-party ~~marketing~~coverage and ~~distribution~~adequate ~~capabilities,~~reimbursement ~~involves a~~or ~~number~~willingness of ~~risks.~~patients ~~For~~to ~~example,~~pay ~~recruiting~~out ~~and~~of ~~training~~pocket ain ~~sales force is expensive and time consuming and could delay any product launch. If~~ the ~~commercial~~absence ~~launch~~ of athird-party ~~product~~coverage; ~~candidate for which we recruit a sales force~~ and establish marketing capabilities is delayed or does not occur for any reason, we would have prematurely or unnecessarily incurred these commercialization expenses. This may be costly, and our investment would be lost if we cannot retain or reposition our sales and marketing personnel.

~~Factors~~•the ~~that~~prevalence ~~may inhibit our efforts to commercialize our approved products~~ and ~~product~~severity ~~candidates~~of onany ~~our~~side ~~own include:~~effects.

●If our ~~inability~~approved toproducts ~~recruit,~~do ~~train~~not ~~and~~achieve ~~retain~~an adequate ~~numbers~~level of ~~effective~~market sales and marketing personnel; ● our inability to access government and commercial health plan formularies or secure preferred coverage and adequate reimbursement levels; ● the inability of sales personnel to obtain access to physicians or achieve adequate numbers of physicians to prescribe any future prodrug products; ● the lack of complementary drugs to be offered by sales personnelacceptance, ~~which~~they may ~~put~~not usgenerate atsignificant ~~a competitive disadvantage relative to companies with more extensive~~ product ~~lines;~~revenue ~~● liability for personnel, including sales personnel, failing to comply with applicable legal requirements;~~ and ●we ~~costs~~may ~~associated~~not ~~with~~become maintaining compliance with the FDA’s marketing and promotional requirements, including ongoing training and monitoring, as well as unforeseen costs and expenses associated with creating an independent sales and marketing organizationprofitable.

IfFailure ~~we decide~~ to ~~enter~~obtain ~~into~~or ~~arrangements~~maintain ~~with~~coverage ~~third~~and ~~parties~~adequate toreimbursement ~~perform these services~~ for ~~certain of~~ our ~~product~~products ~~candidates,~~could ~~our~~limit ~~product revenue and~~ our ~~profitability,~~ability ~~if any, are likely~~ to ~~be lower than if we were to sell,~~ market ~~and~~those ~~distribute~~products ~~any product candidates that we develop ourselves. In addition, we may not be successful in entering into arrangements with third parties to sell, market~~ and ~~distribute our~~decrease product candidates in the future, or may be unable to do so on terms that are favorable to us. We likely will have little control over such third parties, including Corium, and any of them may fail to devote the necessary resources and attention to sell and market our ~~approved~~ability ~~products, or any of our product candidates, if approved, effectively. Further, we may be liable for conduct of third parties, including Corium, acting on our behalf, including failure~~ to ~~comply~~generate ~~with legal requirements applicable to sales and marketing of our product or product candidates, if approved~~revenue. If we do not establish sales, marketing and distribution capabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing our approved products, or any of our product candidates, if approved.

Sales of pharmaceutical products depend in significant part on the availability of coverage and adequate reimbursement by third-party payors, such as state and federal governmental authorities, including those that administer the Medicare and Medicaid programs, and private managed care organizations and health insurers. Decisions regarding the extent of coverage and amount of reimbursement to be provided for each of our products and product candidates is and will be made on a plan-by-plan basis. One payor’s determination to provide coverage for a product does not assure that other payors will also provide coverage, and adequate reimbursement, for the product. Each third-party payor determines whether or not it will provide coverage for a drug, what amount it will pay providers for the drug, and on what tier of its formulary the drug will be placed. These decisions are influenced by the existence of multiple drug products within a therapeutic class and the net cost to the plan, including the amount of the prescription price, if any, rebated by the drug’s manufacturer. Typically, generic versions of drugs are placed in a preferred tier. The position of a drug on the formulary generally determines the co-payment that a patient will need to make to obtain the drug and can strongly influence the adoption of a drug by patients and physicians. Patients who are prescribed treatments for their conditions and providers performing the prescribed services generally rely on third-party payors to reimburse all or part of the associated healthcare costs. Patients are unlikely to use our products unless coverage is provided, and reimbursement is adequate to cover a significant portion of the cost of our products. Additionally, a third-party payor’s decision to provide coverage for a drug does not imply that an adequate reimbursement rate will be approved. Also, third-party payors are developing increasingly sophisticated methods of controlling healthcare costs. As a result, coverage, reimbursement and placement determinations are complex and are often the subject of extensive negotiations between the payer and the manufacturer of the drug. Increasingly, both purchasers and payors are also conducting comparative clinical and cost effectiveness analyses involving application of metrics, including data on patient outcomes, provided by manufacturers.

In order for reimbursement to be available for our products under Medicare or Medicaid, we participate in and have rebate obligations under the Medicaid Drug Rebate Program and are enrolled in the 340B drug pricing program, as well as the U.S. Department of Veterans Affairs Federal Supply Schedule pricing program. The programs we participate in, as well as our obligations under these programs, are described under the risk factor “If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate Program or other governmental pricing programs in which we participate, we could be subject to additional reimbursement requirements, penalties, sanctions and fines.”

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~~Our~~In ~~approved~~international markets, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies. For example, orin ~~any~~the EU, pricing and reimbursement schemes vary widely from country to country. Some countries may require the completion of ~~our~~additional ~~product~~studies ~~candidates~~ that ~~may~~compare ~~receive~~the ~~marketing~~cost-effectiveness ~~approval~~of a particular medicinal product candidate to currently available therapies. This Health Technology Assessment (“HTA”) which is currently governed by the national laws of the individual EU member states, ~~may~~is ~~fail~~the procedure according to ~~achieve~~which the ~~degree~~assessment of ~~market~~the ~~acceptance~~public health impact, therapeutic impact and the economic and societal impact of use of a given medicinal product in the national healthcare systems of the individual country is conducted. The outcome of HTA regarding specific medicinal products will often influence the pricing and reimbursement status granted to these medicinal products by ~~physicians~~the competent authorities of individual EU member states. The downward pressure on healthcare costs in general, ~~patients~~particularly prescription medicines, has become very intense. Pharmaceutical products may face competition from lower-priced products in foreign countries that have placed price controls on pharmaceutical products and may also compete with imported foreign products. Furthermore, there is no assurance that a product will be considered medically reasonable and necessary for a specific indication, will be considered cost-effective by third-party payors, ~~and~~that ~~others~~an inadequate level of reimbursement will be established even if coverage is available or that the ~~medical~~third-party ~~community~~payors’ ~~necessary~~reimbursement policies will not adversely affect the ability for ~~commercial~~manufacturers ~~success~~to sell products profitably. Historically, products launched in the EU do not follow the price structures which prevail in the United States, and generally, prices tend to be significantly lower.

~~Our~~Because ~~approved~~the ~~products,~~target orpatient ~~any~~population offor our ~~product~~products ~~candidates that may receive marketing approval, may fail to gain sufficient market acceptance by physicians, patients, third-party payors~~ and ~~others in the medical community. If our approved products, or any of our~~ product candidates, ifis ~~approved for commercial sale~~small, dowe ~~not~~must achieve ansignificant ~~adequate level of~~ market ~~acceptance, they~~share ~~may not generate significant product revenue~~ and weobtain ~~may~~relatively ~~not~~high ~~become~~per-patient ~~profitable.~~prices ~~The~~for ~~degree of market acceptance of~~ our ~~approved~~ products, orto ~~any~~achieve ofmeaningful ~~our product~~gross ~~candidates~~margins. ~~if approved for commercial sale, will depend on a number of factors, including:~~

●We ~~the~~are ~~efficacy~~focused ~~and~~on ~~potential~~diseases ~~advantages~~with ~~compared~~a tosmall ~~alternative~~patient ~~treatments,~~population. ~~including~~A ~~less~~key ~~expensive~~component ~~generic~~of ~~treatments; ●~~ the ~~ability~~successful tocommercialization ~~obtain~~of ~~differentiating~~an ~~claims~~approved inproduct ~~the labels~~ for ~~most~~these ofindications ~~our~~includes ~~product~~identification ~~candidates;~~of ●patients ~~our~~and ~~ability~~a totargeted ~~offer~~prescriber ~~our~~base ~~prodrug products~~ for ~~sale~~such atproduct. ~~competitive~~Due ~~prices;~~to ●small ~~the~~patient ~~clinical~~populations ~~indications~~ for ~~which~~ our products and product candidates, ~~are~~we ~~approved;~~believe ●that ~~the~~we ~~convenience~~would ~~and~~need ~~ease~~to ofhave ~~administration~~significant ~~compared~~market penetration to ~~alternative~~achieve ~~treatments;~~meaningful ●revenues ~~the~~and ~~willingness~~identifying ofpatients and targeting the ~~target~~prescriber ~~patient~~base ~~population~~are key to ~~try~~achieving ~~new~~significant ~~therapies~~market ~~and~~penetration. ofTypically, ~~physicians~~drugs tofor ~~prescribe~~conditions ~~these~~with ~~therapies;~~small ●prevalence ~~the~~have ~~cost~~higher ofprices ~~treatment~~ in ~~relation~~order to ~~alternative~~generate ~~treatments;~~a ●return ~~the~~on ~~steps~~investment, ~~that prescribers~~ and ~~dispensers~~as ~~must~~a ~~take~~result, ~~for~~the ~~approved~~per-patient ~~products~~prices ~~are~~at orwhich ~~any~~we ofsell our ~~product~~products ~~candidates~~are ~~that~~relatively ~~may~~high bein ~~considered~~order ~~controlled~~for ~~substances~~us into ~~the~~generate ~~future,~~an asappropriate ~~well~~return asfor the ~~perceived~~investment ~~risks~~in ~~based~~these ~~upon~~product ~~their~~development ~~controlled~~programs ~~substance~~and ~~status;~~achieve ●meaningful ~~the~~gross ~~ability~~margins. toThere ~~manufacture~~can ~~our~~be ~~product~~no inassurance ~~sufficient~~that ~~quantities~~we ~~and~~will ~~yields;~~be ●successful ~~the~~in ~~strength~~achieving ofa ~~marketing~~sufficient ~~and~~degree ~~distribution support; ● the availability~~ of ~~third-party~~market ~~coverage~~penetration and/or ~~adequate~~obtaining ~~reimbursement~~ or ~~willingness~~maintaining ofhigh ~~patients~~per-patient toprices ~~pay~~for ~~out~~products offor ~~pocket~~diseases inwith ~~the~~small ~~absence~~patient ofpopulations. ~~third-party~~Further, ~~coverage;~~even ●if ~~the~~we ~~prevalence~~obtain ~~and~~significant ~~severity~~market ofshare ~~any~~for ~~side~~our ~~effects;~~products, ●because ~~any~~the potential ~~unfavorable~~target ~~publicity;~~populations ●are ~~any~~very ~~restrictions~~small, onwe ~~the~~may ~~use,~~not ~~sale~~be orable ~~distribution~~to ofmaintain ~~our~~profitability ~~approved~~despite ~~products~~obtaining orsuch ~~any~~significant ofmarket ~~our~~share. ~~product candidates~~Additionally, ~~including~~patients ~~through~~who ~~REMS;~~discontinue ~~and~~therapy ●or ~~any~~do ~~restrictions~~not onfill ~~the~~prescriptions ~~use~~are ofnot ~~our~~easily ~~prodrug~~replaced ~~products~~by ~~together~~new ~~with~~patients, ~~other~~given ~~medications~~the limited patient population.

~~Because~~We ~~the~~face ~~target~~substantial ~~patient population for certain of our products is small~~competition, wewhich ~~must~~may ~~achieve~~result ~~significant~~in ~~market~~others ~~share~~developing ~~and~~or ~~obtain~~commercializing ~~relatively~~products ~~high~~before ~~per-patient~~or ~~prices~~more ~~for~~successfully ~~our~~than ~~products~~we ~~to achieve meaningful gross margins~~do.

Our ~~products~~industry ~~target~~is ~~diseases~~characterized ~~with~~by arapidly ~~small~~advancing ~~patient~~technologies, ~~population.~~intense Acompetition ~~key~~and ~~component~~a ofstrong ~~the~~emphasis ~~successful~~on ~~commercialization~~proprietary ofproducts. anWe ~~approved~~will ~~product~~face ~~for~~competition ~~these~~and ~~indications~~potential ~~includes~~competition ~~identification~~from ~~of patients and~~ a ~~targeted~~number ~~prescriber base for such product. Due to small patient populations for certain~~ of ~~our products~~sources, weincluding ~~believe~~pharmaceutical ~~that~~and webiotechnology ~~would~~companies, ~~need~~specialty topharmaceutical ~~have~~companies, ~~significant~~generic ~~market~~drug ~~penetration~~companies, todrug ~~achieve~~delivery ~~meaningful~~companies ~~revenues~~ and ~~identifying~~academic ~~patients~~ and ~~targeting~~research ~~the~~institutions. ~~prescriber~~Our ~~base~~competitors ~~are~~may ~~key~~develop toor ~~achieving significant~~ market ~~penetration.~~drugs ~~Typically,~~that ~~drugs~~are ~~for~~more ~~conditions~~effective, ~~with~~more ~~small~~convenient, ~~prevalence~~more ~~have~~widely ~~higher~~used ~~prices~~and inless ~~order~~costly toor ~~generate~~have a ~~return~~better onsafety ~~investment,~~profile ~~and~~than asour aproducts ~~result,~~or ~~the~~product ~~per-patient~~candidates, ~~prices~~and atthese ~~which~~competitors wemay ~~sell~~also ~~our~~have ~~products~~significantly ~~are~~more ~~relatively~~resources ~~high~~than ~~in order for~~ us toand ~~generate~~be anmore ~~appropriate~~successful ~~return~~than ~~for~~us ~~the investment~~ in ~~these~~manufacturing ~~product development programs~~ and ~~achieve~~marketing ~~meaningful~~their ~~gross margins~~products.

~~There~~See ~~can~~Part beI. noItem ~~assurance~~1. ~~that~~“Business—Competitors” ~~we will be successful in achieving a sufficient degree~~ of ~~market~~this ~~penetration~~Annual ~~and/or~~Report ~~obtaining~~on orForm ~~maintaining high per~~10-~~patient~~K ~~prices~~ for ~~OLPRUVA~~additional ~~and~~information ~~MIPLYFFA~~regarding ~~for~~our ~~diseases with small patient populations~~competitors. Further, even if we obtain significant market share for OLPRUVA and MIPLYFFA, because the potential target populations are very small, we may not be able to maintain profitability despite obtaining such significant market share. Additionally, patients who discontinue therapy or do not fill prescriptions are not easily replaced by new patients, given the limited patient population.

We may be subject to enforcement action if we engage in improper marketing or promotion of our products.

The FDA and foreign regulatory bodies closely regulate promotional materials and other promotional activities. Even if the FDA initially approves product labeling, the FDA may object to our marketing claims and product advertising campaigns. Failure to comply with the FDA’s promotional, marketing and advertising laws and regulations could lead to the issuance of warning letters, cyber letters, or untitled letters, adverse publicity, the requirement for dear-health-care-provider letters or other corrective information, fines and other monetary penalties, civil or criminal prosecution, including False Claims Act liability, restrictions on our operations and other operating requirements through consent decrees or corporate integrity agreements, debarment, exclusion from participation in federal health care programs and refusal of government contracts or future orders under existing contracts, among other consequences. Similar risks exist in foreign jurisdictions. Any of these consequences would harm the commercial success of our products.

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WeFurther, ~~face~~our ~~substantial~~promotional ~~competition~~materials, statements and training methods must comply with regulatory prohibitions of the promotion of unapproved, or off-label, use. Any regulatory approval that the FDA grants is limited to those specific diseases and indications for which a product is deemed to be safe and effective by FDA. Physicians may ~~result~~use inour ~~others~~products ~~developing~~off-label, as the FDA does not restrict or ~~commercializing~~regulate ~~products~~a ~~before~~physician’s independent choice of treatment within the practice of medicine. However, if the FDA or ~~more~~any ~~successfully~~other ~~than~~federal, state or foreign enforcement authority determines that our promotional materials, statements or training constitutes promotion of an off-label use, it could request that we domodify our promotional materials, statements or training methods or subject us to regulatory or enforcement actions, such as the issuance of an untitled letter, a warning letter, injunction, seizure, civil fine, disgorgement of money, operating restrictions or criminal penalties. We may also be subject to actions by other governmental entities or private parties, such as the False Claims Act, civil whistleblower or “qui tam” actions. In that event, our reputation could be damaged and adoption of the products could be impaired. In addition, the off-label use of our products may increase the risk of product liability claims.

~~Our~~Product ~~industry~~liability islawsuits ~~characterized~~against byus ~~rapidly~~could ~~advancing~~cause ~~technologies,~~us ~~intense~~to ~~competition~~incur ~~and~~substantial aliabilities ~~strong emphasis on proprietary products. We will face competition~~ and ~~potential~~to ~~competition~~limit ~~from~~commercialization ~~a number~~ of ~~sources,~~our ~~including~~approved ~~pharmaceutical and biotechnology companies~~products, ~~specialty pharmaceutical companies, generic drug companies, drug delivery companies and academic and research institutions. Our competitors may develop~~ or ~~market~~any ~~drugs~~of ~~that are more effective, more convenient, more widely used and less costly or have a better safety profile than~~ our ~~products or~~ product candidates ~~and~~that ~~these~~we ~~competitors~~ may ~~also have significantly more resources than us and be more successful than us in manufacturing and marketing their products~~develop.

~~See~~We ~~Part~~face ~~I. Item~~an ~~1. "Business—Competitors”~~inherent risk of ~~this~~product ~~Annual~~liability ~~Report~~exposure onrelated ~~Form~~to ~~10-K~~commercializing ~~for~~drug ~~information~~products ~~regarding~~and testing our ~~competitors~~product candidates in human clinical trials. If we cannot successfully defend ourselves against claims that our product candidates or products caused injuries, we will incur substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:

~~Many~~•decreased ofdemand our potential competitors have substantially greater financial, technical and human resources than we do, as well as more experience in the development of product candidates, obtaining FDA and other regulatory approvals of products and the commercialization of those products. Consequently, our competitors may develop products for ~~indications we are pursuing or may pursue in the future, and such competitors’ products may be more effective, better tolerated and less costly than~~ our ~~product candidates. Our competitors may also be more successful in manufacturing and marketing their~~ products ~~than we are. We will also face competition in recruiting and retaining qualified personnel and establishing clinical trial sites and patient enrollment in clinical trials.~~;

~~Our~~•injury competitors also may obtain FDA or other regulatory approval for their product candidates more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to ~~enter the market. If the competitor’s product were similar to~~ our ~~product~~reputation ~~candidates,~~and wesignificant ~~may~~negative bemedia required to seek approval via alternative pathways, such as the ANDA, which is used for the development of generic drug products. We may also be blocked from product marketing by periods of patent protection or regulatory exclusivity.attention;

In•termination ~~addition, our ability to compete may be affected in many cases by insurers or other third-party payors seeking to encourage the use~~ of ~~generic drugs or giving drugs with improved attributes sufficient weight in a comparative~~ clinical ~~cost~~trial ~~effectiveness~~sites ~~analysis.~~or ~~For~~entire ~~some~~trial of the indications that we are pursuing, drugs used off-label serve as cheaper alternatives to our product candidates. Their lower prices could result in significant pricing pressure, even if our product candidates are otherwise viewed as a preferable therapy. Additional drugs may become available on a generic basis over the coming years.programs;

~~Mergers~~•withdrawal ~~and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number~~ of ~~our~~clinical ~~competitors.~~trial ~~Smaller and other early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.~~participants;

~~Consequently,~~•initiation ~~our competitors may develop products for the treatment~~ of ~~ADHD,~~investigations ~~pain,~~by UCDs, or for other indications pursue or we may pursue in the future, and such competitors’ products may be more effective, better tolerated and less costly than our product candidates. Our competitors may also be more successful in manufacturing and marketing their products than we are. We will also face competition in recruiting and retaining qualified personnel and establishing clinical trial sites and subject enrollment in clinical trials.regulators;

•significant costs to defend the related litigation;

•a diversion of management’s time and our resources;

•substantial monetary awards paid to trial participants or patients;

•product recalls, withdrawals or labeling revisions and marketing or promotional restrictions; and

•loss of revenue.

Although we maintain product liability insurance coverage, we cannot be sure that our insurance coverage will be adequate or otherwise protect us from or adequately mitigate liabilities or damages with respect to product liability claims, or that such coverage will continue to be available on acceptable terms at all. The successful assertion of one or more large claims against us that exceeds our available insurance coverage, or results in changes to our insurance policies (including premium increases or the imposition of a large deductible or co-insurance requirements), could have an adverse effect on our business. We may need to increase our insurance coverage as products become commercially successful. Insurance coverage is increasingly expensive, and we may not be able to maintain insurance coverage at a reasonable cost or in an amount adequate to satisfy any liability that may arise.

Significant political, trade, regulatory developments, and other circumstances beyond our control could delay, prevent or impair our development or commercialization efforts.

Trade policies, geopolitical disputes and other international conflicts can result in tariffs, sanctions and other measures that restrict international trade, and can materially adversely affect our business, particularly if these measures affect regions where manufacturing and product development activities take place or raw materials are sourced. The extent and duration of any tariffs and the resulting impact on general economic conditions and on our business are uncertain and depend on various factors, such as negotiations between the United States and other countries, the response of such countries, and exemptions or exclusions that may be granted. Countries may also adopt other measures, such as controls on imports or exports of goods, technology or data, that could adversely impact supply chains. As these tensions continue to rise, more targeted approaches on certain products, industries or companies could significantly impact our development and commercialization efforts. Further, such actions by the United States could result in other retaliatory actions by those countries which could impact our ability to profitably commercialize our products in those jurisdictions. As a result, our business, operations, and financial condition could be materially harmed.

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WeOur ~~may~~product ~~not~~candidates may be ~~able~~associated towith ~~obtain~~serious ~~either~~adverse ~~three-year~~events, ~~FDA~~undesirable ~~regulatory~~side ~~exclusivity~~effects or ~~five-year~~have ~~FDA~~other properties that could halt their clinical development, prevent their regulatory ~~exclusivity~~approval, aslimit atheir ~~new~~commercial ~~chemical~~potential ~~entity~~or result in significant negative consequences.

~~The~~Adverse ~~FDA~~events ~~provides~~or ~~periods~~other ofundesirable ~~regulatory~~side ~~exclusivity~~effects ~~following~~caused ~~their~~by ~~approval~~our ofproduct ancandidates ~~NDA,~~could ~~which~~cause ~~provide~~us ~~the~~or ~~holder~~regulatory ofauthorities anto ~~approved~~interrupt, ~~NDA~~delay ~~limited~~or ~~protection~~halt ~~from~~clinical ~~new~~trials ~~competition~~and incould ~~the~~result ~~marketplace~~in ~~for~~a ~~the~~more ~~innovation~~restrictive ~~represented~~label byor ~~its~~the ~~approved~~delay ~~drug.~~or ~~Five-year~~denial ~~exclusivity precludes approval~~ of ~~505(b)(2)~~regulatory ~~applications~~approvals ~~or ANDAs~~ by ~~delaying~~ the ~~submission~~FDA or ~~approval~~other ofcomparable ~~the~~foreign ~~application,~~regulatory ~~while~~authorities. ~~three-year~~If ~~exclusivity~~any ~~precludes~~serious ~~the~~adverse ~~approval~~events ofoccur, ~~the~~clinical ~~application.~~trials Wecould ~~intend~~be tosuspended ~~seek new chemical entity,~~ or ~~NCE~~terminated, ~~status~~and ~~for any of~~ our ~~prodrug~~ ~~product~~business ~~candidates~~could asbe ~~appropriate~~seriously harmed. ~~Five~~Regulatory ~~years~~authorities ofcould ~~exclusivity~~order ~~are~~us ~~available~~ to ~~NCEs~~cease ~~following~~further ~~the~~development ~~approval~~ of anor ~~NDA~~deny byapproval ~~the~~of ~~FDA.~~product ~~An NCE is a drug that contains no active moiety that has been approved by the FDA in any other NDA~~candidates. If awe ~~product~~are isrequired ~~not eligible for NCE exclusivity, it may be eligible for three years of exclusivity. Three-year exclusivity is available~~ to ~~the~~ ~~holder of an NDA~~delay, ~~including~~suspend ~~a 505(b)(2) NDA, for a particular condition of approval,~~ or ~~change~~terminate toany aclinical ~~marketed product~~trial, ~~such~~the ascommercial aprospects ~~new~~of ~~formulation~~our ~~for~~products aor ~~previously approved~~ product, ifcandidates ~~one~~may orbe ~~more new clinical trials~~harmed, ~~other~~and ~~than~~our ~~bioavailability~~ability ~~or bioequivalence trials, were essential~~ to ~~the~~generate ~~approval~~product ofrevenues ~~the~~may ~~application~~be ~~and~~delayed ~~were conducted~~ or ~~sponsored by the applicant~~eliminated.

~~There~~Any isside aeffects ~~risk~~or ~~that~~adverse ~~the~~events ~~FDA~~caused ~~may~~by ~~disagree~~approved ~~with~~products ~~any~~following ~~claim~~regulatory that we may make that any of our prodrug product candidates are NCEs and therefore entitled to five-year exclusivity. The FDA may also take the view that the studies that we are conducting are not clinical trials, other than bioavailability and bioequivalence studies, that are essential to approval ~~and therefore do not support three-year exclusivity. Further~~, tocould ~~the~~result ~~extent~~in ~~that the basis for exclusivity is not clear, the FDA may determine to defer~~ a ~~decision~~number ~~until~~of itpotentially ~~receives~~significant annegative ~~application which necessitates a decision~~consequences.

IfFor weapproved doproducts, ~~obtain~~if ~~either~~we ~~five~~ or ~~three~~others ~~years~~later ofidentify ~~exclusivity,~~undesirable ~~such~~side ~~exclusivity~~effects ~~will~~or ~~not~~adverse ~~block~~events ~~all~~caused ~~potential~~by ~~competitors~~such ~~from the market. Competitors may be able to obtain approval for similar~~ products, ~~with~~a ~~different~~number ~~forms~~ of ~~competitive~~potentially ~~differentiating mechanisms~~significant ornegative ~~may~~consequences becould ~~able~~result, toincluding ~~obtain~~but ~~approval~~not ~~for~~limited ~~similar products without a competitive differentiating mechanism.~~to:

~~Even~~•regulatory ifauthorities wemay orsuspend, ~~our~~limit ~~collaborators~~or ~~are~~withdraw ~~able~~approvals ~~to commercialize our approved products, or any~~ of ~~our~~such product ~~candidates~~, ifor ~~approved,~~seek ~~they~~an ~~may~~injunction beagainst ~~subject~~its tomanufacture ~~unfavorable~~or ~~pricing regulations, third-party coverage and reimbursement policies.~~distribution;

~~The~~•regulatory ~~successful~~authorities ~~commercialization~~may ofrequire ~~our~~additional ~~approved~~warnings ~~products, and any of our product candidates for which marketing approval is obtained will depend, in part,~~ on the ~~extent to which coverage and adequate reimbursement for AZSTARYS~~label, ~~OLPRUVA, MIPLYFFA or any of our product candidates for which marketing approval is obtained, will be available from government payor programs at the federal and state levels,~~ including ~~Medicare~~“boxed” ~~and Medicaid~~warnings, ~~private~~or ~~health~~issue ~~insurers~~safety ~~and managed care plans and other third-party payors. Government authorities and other third-party payors decide which medical products they will pay for and establish reimbursement levels~~alerts, ~~including co-payments. A~~Dear ~~trend~~Healthcare inProvider the U.S. healthcare industry and elsewhere is cost containment. Government authorities and other third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medical products. Increasinglyletters, ~~third-party~~press ~~payors~~releases are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for drugs and products. Coverage and reimbursement may not be available for any product that we commercialize and, even if these are available, the level of reimbursement may not be satisfactory. Inadequate reimbursement levels may adversely affect the demand for, or ~~the~~other ~~price~~communications ~~of,~~containing ~~our~~warnings ~~approved products,~~ or ~~any~~other ofsafety ~~our~~information ~~product~~about ~~candidates for which we obtain marketing approval. We may be required to conduct expensive pharmacoeconomic studies to justify coverage and reimbursement or~~ the level of reimbursement relative to other therapies. Moreover, the trend has been for government and commercial health plans and their pharmacy benefit managers to commoditize drug products through therapeutic equivalence determinations, making formulary decisions based on cost. If coverage and adequate reimbursement are not available or reimbursement is available only at limited levels, we may not be able to successfully commercialize our approved products or commercialize any of our product ~~candidates for which marketing approval is obtained.~~;

~~There~~•we may be ~~significant~~required delays in obtaining coverage and reimbursement for newly approved prodrug products, and coverage may be more limited than the indications for which the product is approved by the FDA or similar regulatory authorities outside the United States. Moreover, eligibility for coverage and reimbursement does not imply that a product will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution expenses. Interim reimbursement levels for new prodrug products, if applicable, may also not be sufficient to ~~cover~~change ~~our costs and may not be made permanent. Reimbursement rates may vary according to~~ the ~~use~~way of the product ~~and the clinical setting in which it~~ is ~~used,~~administered may be based on reimbursement levels already set for lower cost drugs and may be incorporated into existing payments for other services. Net prices for prodrug products may be reduced by mandatory discounts or ~~rebates~~conduct ~~required~~additional by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the United States. Private third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement policies. Except for certain government health care programs, such as the Department of Defense’s TRICARE Uniform Formulary, no uniform policy requirement for coverage and reimbursement for drug products exists among third-party payors in the United States. Even state Medicaid programs have their own preferred drug lists that may disadvantage non-preferred brand drugs. Therefore, coverage and reimbursement can differ significantly from payor to payor. As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical ~~support~~trials ~~for the use of our products to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently~~ or ~~obtained at all. Our inability to promptly obtain coverage and adequate reimbursement rates from both government~~post-~~funded~~approval and private payors for any approved products or product candidates that that we develop could significantly harm our operating results, our ability to raise capital needed to commercialize our products and our overall financial condition.studies;

~~The~~•we ~~regulations~~may ~~that~~be ~~govern~~required ~~marketing approvals, pricing, coverage and reimbursement for new drugs vary widely from country~~ to ~~country.~~create ~~Current~~a ~~and~~risk ~~future~~evaluation ~~legislation may significantly change the approval requirements in ways that could involve additional costs~~ and ~~cause~~mitigation ~~delays in obtaining approvals. Some countries require approval of the sale price of a product before it can be marketed. In many countries~~strategy, ~~the pricing review period begins after marketing~~ or ~~product licensing approval is granted. In some foreign markets~~REMS, ~~prescription~~which ~~pharmaceutical~~could ~~pricing~~include ~~remains subject to continuing governmental control even after initial approval is granted. As~~ a ~~result,~~ wemedication ~~might~~guide ~~obtain~~outlining ~~marketing~~the ~~approval~~risks ~~for a product in a particular country, but then be subject to price regulations that delay commercial launch~~ of ~~the~~such ~~product,~~side ~~possibly~~effects for ~~lengthy~~distribution ~~time periods, and negatively impact the revenue able~~ to be generated from the sale of the product in that country. Adverse pricing limitations may hinder our ability to recoup our investment in one or more product candidates, even if our product candidates obtain marketing approval.patients;

~~There~~•we ~~can~~may be nosubject ~~assurance~~to ~~that our approved products~~fines, orinjunctions ~~any of our product candidates, if they are approved for sale in the United States~~ or in other countries, will be considered medically reasonable and necessary for a specific indication, that they will be considered cost-effective by third-party payors, that coverage or an adequate level of reimbursement will be available, or that third-party payors’ reimbursement policies will not adversely affect the ~~ability~~imposition ~~to sell our approved products, or our ability to sell any~~ of ~~any~~criminal ~~of our product candidates profitably if they are approved for sale.~~penalties;

~~Table~~•we ofcould ~~Contents~~ be sued and held liable for harm caused to patients; and

We•our reputation may ~~be subject to enforcement action if we engage in improper marketing or promotion of our products~~suffer.

~~The~~Any ~~FDA closely regulates promotional materials and other promotional activities. Even if the FDA initially approves product labeling that includes a description~~ of ~~our~~ ~~improved~~these ~~attribute claims,~~events ~~the FDA may object to our marketing claims and product advertising campaigns. Failure to comply with the FDA’s promotional, marketing and advertising laws and regulations~~ could ~~lead~~prevent tous ~~the~~from ~~issuance~~achieving ~~of warning letters, cyber letters,~~ or ~~untitled~~maintaining ~~letters,~~market ~~adverse~~acceptance ~~publicity,~~of ~~the~~approved ~~requirement~~products ~~for dear-health-care-provider letters or other corrective information, fines~~ and ~~other~~could ~~monetary~~seriously penalties, civil or criminal prosecution, including False Claims Act liability, restrictions on our operations and other operating requirements through consent decrees or corporate integrity agreements, debarment, exclusion from participation in federal health care programs and refusal of government contracts or future orders under existing contracts, among other consequences. Any of these consequences would harm ~~the commercial success of~~ our ~~products~~business.

~~Further,~~A ~~our~~variety ~~promotional~~of ~~materials,~~risks ~~statements~~associated ~~and training methods must comply~~ with ~~the~~marketing ~~FDA’s~~our prohibition of the promotion of unapproved, or off-label, use. Any regulatory approval that the FDA grants is limited to those specific diseases and indications for which a product is deemed to be safe and effective by FDA. For example, the FDA-approved ~~label~~products ~~for AZSTARYS is limited to the acute treatment of ADHD in patients 6 years of age~~ and ~~older~~any ~~and the FDA approved label for OLPRUVA is limited to oral suspension in the U.S. for the treatment~~ of ~~certain patients with UCDs involving deficiencies of CPS, OTC, or AS. Physicians may use~~ our ~~products off-label, as~~product ~~the FDA does not restrict or regulate a physician’s independent choice of treatment within the practice of medicine. However~~candidates, if ~~the FDA determines that our promotional materials~~approved, ~~statements or training constitutes promotion of an off-label use~~internationally, it could ~~request~~affect ~~that we modify~~ our promotional materials, statements or training methods or subject us to regulatory or enforcement actions, such as the issuance of an untitled letter, a warning letter, injunction, seizure, civil fine, disgorgement of money, operating restrictions or criminal penaltiesbusiness. We may also be subject to actions by other governmental entities or private parties, such as the False Claims Act, civil whistleblower or “qui tam” actions. It is also possible that other federal, state or foreign enforcement authorities might take action if they consider our promotional or training materials to constitute promotion of an off-label use, which could result in significant fines or penalties under other statutory authorities, such as laws prohibiting false claims for reimbursement. In that event, our reputation could be damaged and adoption of the products could be impaired. In addition, the off-label use of our products may increase the risk of product liability claims. Product liability claims are expensive to defend and could divert our management’s attention, result in substantial damage awards against us and harm our reputation.

~~Product~~We ~~liability~~may ~~lawsuits~~seek ~~against~~regulatory usapproval ~~could~~for ~~cause~~our usapproved toproducts ~~incur~~and ~~substantial~~any ~~liabilities~~of ~~and~~our toproduct ~~limit~~candidates, ~~commercialization~~if approved, outside of ~~our~~the ~~approved~~United ~~products~~States. For example, orwe ~~any~~have submitted an MAA to the EMA for the evaluation of ~~our~~arimoclomol ~~product~~for ~~candidates~~ the treatment of NPC. Accordingly, we expect that we ~~may~~will ~~develop.~~be subject to additional risks related to operating in foreign countries including:

We•different ~~face~~regulatory anrequirements ~~inherent~~for ~~risk~~maintaining ofapproval ~~product liability exposure related to the testing~~ of ~~our~~drugs ~~product candidates~~ in ~~human~~foreign clinical trials and will face an even greater risk as our approved products, and any of our product candidates that may be approved in the future, are commercialized. This includes the risk that our products may be misused. For example, certain of our approved products do, and we anticipate that any of our product candidates we may choose to develop in the future, if approved, may carry, a boxed warning regarding lethality. If we cannot successfully defend ourselves against claims that our product candidates or products caused injuries, we will incur substantial liabilities on behalf of ourselves. Regardless of merit or eventual outcome, liability claims may result in:countries;

●•differing ~~decreased~~payor ~~demand~~reimbursement ~~for our approved products~~regimes, ~~and~~governmental ~~any~~payors ~~of our product candidates that we may develop; ● injury to our reputation and significant negative media attention; ● termination of clinical trial sites~~ or ~~entire~~patient ~~trial~~self-pay ~~programs;~~systems ~~● withdrawal of clinical trial participants; ● initiation of investigations by regulators; ● significant costs to defend the related litigation; ● a diversion of management’s time~~ and ~~our~~price ~~resources~~controls; ● substantial monetary awards paid to trial participants or patients; ● product recalls, withdrawals or labeling revisions and marketing or promotional restrictions; ● loss of revenue; ● reduced resources of our management to pursue our business strategy; and ● the inability to successfully commercialize any of our approved products, or any of our product candidates that might be approved in the future.

~~We currently hold $10.0 million in product liability insurance coverage in~~ •the ~~aggregate,~~potential ~~with~~for aso-called ~~per~~parallel ~~incident limit of $10.0 million~~importing, which ~~may~~is ~~not~~what behappens ~~adequate~~when toa ~~cover~~local ~~all~~seller, ~~liabilities~~faced ~~that~~with wehigh ~~may incur. We may need to increase our insurance coverage as we expand our clinical trials~~ or ~~upon~~ ~~commencement~~higher ~~of commercialization~~local ofprices, ~~any~~opts ~~product approved in the future. Insurance coverage is increasingly expensive. We may not be able~~ to ~~maintain~~import ~~insurance~~goods ~~coverage~~from at a ~~reasonable~~foreign ~~cost~~market orwith inlow anor ~~amount~~lower ~~adequate~~prices torather ~~satisfy~~than ~~any~~buying ~~liability~~them ~~that may arise.~~locally;

~~If commercialization~~•unexpected ~~of our~~changes ~~approved~~in ~~products~~tariffs, or ~~any~~trade ~~of our product candidates~~barriers, ifprice ~~approved,~~and ~~are not~~exchange ~~successful, or~~controls weand ~~experience~~other ~~significant~~regulatory ~~delays in commercialization, our business will be harmed.~~requirements;

We•economic ~~currently~~weakness, ~~generate~~including ~~minimal~~inflation, ~~commercial~~labor ~~revenue from the sale of our approved products~~shortages, ~~OLPRUVA~~supply ~~and~~chain ~~MIPLYFFA~~shortages, ~~and~~ ~~we may never be able to successfully commercialize a product candidate. We cannot guarantee that we~~ or ~~any~~ other ~~collaborators will~~economic ~~be able to successfully develop, manufacture~~ or ~~commercialize~~ ~~our~~political ~~approved~~uncertainties ~~products,~~ or ~~product~~instability ~~candidates, if approved, or that we will ever receive any future payments under the AZSTARYS License Agreement. Despite the FDA’s approval of OLPRUVA for oral suspension~~ in ~~the~~particular ~~U.S.~~foreign ~~for~~economies ~~the treatment of certain patients with UCDs,~~ and ~~MIPLYFFA, an orally-delivered treatment for NPC, the products may not gain market acceptance among physicians, key opinion leaders, healthcare payors, patients and the medical community.~~markets;

We•compliance ~~have~~with made significant investments in our internal discovery and development efforts and much of our financial resources in the identification of potential product candidates via our LAT® platform technology and the development of our product candidates. Our ability to generate revenue from our approved products and any of our product candidatestax, ~~if approved~~employment, ~~will~~immigration ~~depend heavily on their successful development~~ and ~~commercialization.~~labor ~~The~~laws ~~success~~for ofemployees ~~our~~living ~~approved~~or ~~products and~~traveling ~~any of our product candidates will depend on several factors, including:~~abroad;

● successful completion of preclinical studies and requisite clinical trials; ● successful completion and achievement of endpoints in our clinical trials; ● demonstration that the risks involved with our approved products and any of our product candidates are outweighed by the benefits; ● successful development of our manufacturing processes for our approved products and for any of our product candidates, including entering into and maintaining arrangements with third-party manufacturers; ● successful completion of an FDA or European pre-approval inspection of the facilities used to manufacture any of our product candidates for which we may submit an NDA or an MAA; ● receipt of timely marketing approvals from applicable regulatory authorities, including, if applicable, the determination by the DEA of the controlled substance schedule for a product candidate, taking into account the recommendation of the FDA; ● obtaining differentiating claims in the labels for our product candidates; ● obtaining and maintaining patent, trademark and trade secret protection and regulatory exclusivity for our approved products and any of our product candidates and otherwise protecting our rights in our intellectual property portfolio; ● maintaining compliance with regulatory requirements, including cGMPs; ● launching commercial sales of our approved products, and any of our product candidates, if and when approved, whether alone or in collaboration with others; ● acceptance of our approved products and any of our product candidates, if approved, by patients, the medical community and third-party payors; ● competing effectively with other therapies; ● obtaining and maintaining healthcare coverage and adequate reimbursement; and ● maintaining a continued acceptable safety and efficacy profile of any of our products following approval.

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Whether regulatory approval will be granted is unpredictable and depends upon numerous factors, including the substantial discretion of the regulatory authorities. If, following submission, our NDA or marketing authorization application for a product candidate is not accepted for substantive review or approval, the FDA or other comparable •foreign ~~regulatory~~currency ~~authorities may require that we conduct additional studies or clinical trials~~fluctuations, ~~provide~~which ~~additional~~could ~~data,~~result ~~take~~in additional manufacturing steps or require other conditions before they will reconsider our application. If the FDA or other comparable foreign regulatory authorities require additional studies, clinical trials or data, we would incur increased ~~costs~~operating ~~and~~expenses delays in the marketing approval process, which may require us to expend more resources than we have available. In addition, the FDA or other comparable foreign regulatory authorities may not consider sufficient any additional required studies, clinical trials, data or information that we perform and ~~complete~~reduced ~~or generate, or we may decide to abandon the program.~~revenue;

It•difficulties isstaffing ~~possible that none of our product candidates in clinical development or any of our future product candidates will ever obtain regulatory approval, even if we expend substantial time~~ and ~~resources~~managing ~~seeking~~foreign ~~such approval.~~operations;

If•workforce weuncertainty ~~do not achieve one or more of these factors~~ in acountries ~~timely~~where ~~manner~~labor orunrest atis ~~all,~~more wecommon ~~could~~than experience significant delays, we could experience an inability to successfully commercialize any of our approved products or product candidates, if approved, or we could experience an inability to successfully commercialize any of our product candidates approved for marketing in the ~~future,~~United ~~if any, which would harm our business.~~States;

~~Risks~~•potential ~~Related~~liability tounder the ~~Development~~Foreign Corrupt Practices Act of ~~Our~~1977 ~~Product~~or ~~Candidates~~comparable foreign regulations;

If•challenges weenforcing ~~are~~our ~~not~~contractual ~~able~~and tointellectual ~~obtain~~property ~~required regulatory approvals for any of our product candidates~~rights, orespecially ~~the~~in ~~approved~~those ~~labels~~foreign ~~are~~countries ~~not~~that ~~sufficiently~~do ~~differentiated from other competing products, we will~~ not berespect ~~able~~and toprotect ~~commercialize~~intellectual ~~them~~property ~~and~~rights ~~our ability~~ to ~~generate~~the ~~revenue~~same orextent ~~profits~~as orthe toUnited ~~raise~~States; ~~future capital could be limited.~~and

~~The~~•business ~~research,~~interruptions ~~testing,~~resulting ~~manufacturing,~~from ~~labeling,~~geo-political ~~packaging~~actions, ~~storage,~~including ~~approval,~~war ~~sale, marketing, advertising~~ and ~~promotion~~terrorism, pricing, export, import and distribution of drug products are subject to extensive regulation by the FDA and other regulatory authorities in the United States and other countries, which regulations differ from country to country and change over time. We are not permitted to market any of our product candidates in the United States until we receive approval of an NDA from the FDA, or in any foreign countries until we receive the requisite approvals in such ~~countries.~~as In the ~~United~~current ~~States,~~conflict ~~the~~with ~~FDA~~Ukraine ~~generally requires the completion of non-clinical testing~~ and ~~clinical trials of each drug to establish its safety and efficacy and extensive pharmaceutical development to ensure its quality and other factors before an NDA is approved~~Russia. Regulatory authorities in other jurisdictions impose similar requirements. Of the large number of drugs in development, only a small percentage result in the submission of an NDA to the FDA and even fewer are approved for commercialization.

~~Even~~These ifand ~~regulatory approval is obtained, subsequent safety, efficacy, quality or~~ other ~~issues~~risks ~~can~~associated result in a product approval being suspended or withdrawn, or the approved label for any approved product may not be sufficiently differentiated from other competing products to support market adoption thereof. In March 2021, the FDA approved the NDA for AZSTARYS, in December 2022, the FDA approved OLPRUVA, and in September 2024, the FDA approved MIPLYFFA. Even with ~~the regulatory approval of AZSTARYS, OLPRUVA, and MIPLYFFA by the FDA, we cannot guarantee that the FDA will approve any of~~ our ~~product~~international ~~candidates~~operations ~~for commercial sale or approve any proposed label we~~ may ~~have~~compromise ~~for any such product candidate. If~~ our ~~development~~ability ~~efforts for our product candidates, including our efforts~~ to ~~obtain regulatory~~achieve ~~approval, are not successful for their planned indications~~ or ~~are~~maintain ~~delayed, or if adequate demand for our product candidates that are approved for marketing, if any, is not generated, our business will be harmed~~profitability.

If our Global EAP program is terminated prior to regulatory approval and commercialization of arimoclomol in applicable foreign jurisdictions, it will have a material adverse effect on our business, results of operations, cash flows, financial condition and/or prospects.

Arimoclomol is currently available to NPC patients in France, Germany, and other EU member states, as well as select territories outside of Europe through an EAP. We have submitted an MAA to the EMA for the evaluation of arimoclomol for the treatment of NPC, and the EAP is expected to remain in place until arimoclomol becomes commercially available in each of these EAP markets. If the EAP is terminated prior to commercialization of arimoclomol in an applicable foreign jurisdiction, it will have a material adverse effect on our business, results of operations, cash flows, financial condition and/or prospects.

Risks Related to Our Business and Our Financial Position

We are highly dependent on one product for substantially all of our revenues, and any loss of revenue from this product could materially harm our business.

For the year ended December 31, 2025 we derived approximately 82% of our revenues from commercial sales of MIPLYFFA® (arimoclomol), which is indicated for a rare disease with a limited patient population. We expect that MIPLYFFA® (arimoclomol) will continue to be our main source of revenue for the foreseeable future. As a result, our business, financial condition, and results of operations are highly dependent on the continued commercial success of MIPLYFFA® (arimoclomol).

Sales of MIPLYFFA® (arimoclomol) may be negatively impacted by a number of factors, including competition from third parties, changes in clinical practice or treatment guidelines, pricing and reimbursement pressures from government and private payors, heightened scrutiny of high-cost rare disease therapies, adverse safety signals, manufacturing or supply disruptions, regulatory actions or labeling changes, and challenges to or expiration of our intellectual property rights. Because the target patient population is small, even modest changes in prescribing patterns, patient identification rates, or reimbursement decisions could have a disproportionate effect on our revenues.

If MIPLYFFA® (arimoclomol) fails to increase or maintain its current level of commercial success for any reason, we may be unable to replace the lost revenues, which could materially adversely affect our business, financial condition, and results of operations.

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~~The~~We ~~success~~have ofhad ~~our~~recurring ~~product candidates~~negative ~~will~~net ~~depend~~operating oncash ~~the~~flows ~~receipt~~throughout ~~and~~our ~~maintenance~~operating ofhistory, ~~regulatory~~and ~~approval~~we ~~and~~cannot ~~the~~guarantee ~~issuance~~or ~~and~~predict ~~maintenance~~when ofwe ~~such~~may ~~approval~~begin isto ~~uncertain~~consistently ~~and~~generate ~~subject~~positive tonet acash ~~number~~flows offrom ~~risks~~operations, ~~including~~or ~~the~~if ~~following:~~at all.

●We incurred a net loss of $105.5 million for the ~~FDA~~year ended December 31, 2024. Our net income of $83.2 million for the ~~EMA~~year ended December 31, or2025 ~~comparable~~was ~~foreign~~primarily ~~regulatory~~due ~~authorities~~to the sale of the PRV in the second quarter of 2025, ~~institutional~~which ~~review~~resulted ~~boards~~in net proceeds of $148.3 million. As of December 31, or2025, ~~IRBs~~we had an accumulated deficit of $422.1 million. We have had recurring negative net operating cash flows throughout our operating history, and we cannot guarantee or ~~ethics~~predict ~~committees~~when we may ~~disagree~~begin to consistently generate positive net cash flows from operations, or if at all. Because of the numerous risks and uncertainties associated with drug development, we are unable to accurately predict the ~~design~~timing or ~~conduct~~amount of expenses or when, or if, we will be able to achieve or maintain profitability. If we are required by regulatory authorities to perform studies in addition to those currently expected, or if there are any delays in the initiation and completion of our clinical trials; or the development of any of our product candidates, our expenses could increase. Even though we generated positive net income for the year ended December 31, 2025, we may not be able to sustain or increase profitability on a quarterly or annual basis. Our failure to become and remain profitable would depress our value and could impair our ability to raise capital, expand our business, maintain our research and development efforts, obtain product approvals, diversify our product offerings or continue our operations. A decline in our value could also cause you to lose all or part of your investment. We may incur significant losses in the future for a number of reasons, many of which are beyond our control, including the market acceptance of our products, competitive products, future product development, our market penetration and margins, as well as the other risks described in this Annual Report on Form 10-K.

●We ~~the~~might ~~results~~not ofbe ~~our~~able ~~clinical~~to ~~trials~~utilize ~~may~~a ~~not~~significant ~~meet~~portion ~~the level~~ of ~~statistical~~our ornet ~~clinical~~operating ~~significance~~loss ~~required by the FDA~~carryforwards, ~~the~~which ~~EMA,~~could oradversely ~~other~~affect ~~regulatory~~our ~~agencies for marketing approval or for us to receive approval for claims that are necessary for commercialization;~~profitability.

●As ~~the~~of ~~dosing~~December 31, 2025, we had federal net operating loss carryforwards of approximately $230.4 million, due to prior period losses, $11.1 million of which, if not utilized, will begin to expire in 2029 and $219.4 million of which have no expiration date. These net operating loss carryforwards could expire unused and be unavailable to offset future income tax liabilities, which could adversely affect our profitability. These federal net operating loss carryforwards are fully reserved under a ~~particular~~valuation ~~clinical~~allowance ~~trial~~in the consolidated balance sheet as of December 31, 2025. On December 22, 2017, the U.S. government enacted H.R. 1, “An Act to provide for reconciliation pursuant to titles II and V of the concurrent resolution on the budget for fiscal year 2018” (informally titled the Tax Cuts and Jobs Act). Under the Tax Cuts and Jobs Act, U.S. federal net operating losses incurred in 2018 and in future years may ~~not~~be carried forward indefinitely, but the deductibility of such federal net operating losses is limited. It is uncertain if and to what extent various states will conform or continue to conform to the Tax Cuts and Jobs Act or any subsequent or newly enacted federal tax legislation. To the extent that we continue to generate taxable losses in the United States, unused losses will carry forward to offset future taxable income (subject to any applicable limitations), if any. In addition, under Section 382 and Section 383 of the Code, if a corporation undergoes an “ownership change,” which is generally defined as a greater than 50% change, by value, in its equity ownership over a three-year period, the corporation’s ability to use its pre-change net operating loss carryforwards and other pre-change tax attributes to offset its post-change income may be atlimited. We performed a Section 382 ownership change analysis through the period ending November 26, 2025 and determined that we experienced ownership changes in 2016, 2020, and 2021, which resulted in a portion of our net operating loss carryforwards being subject to an ~~optimal~~annual ~~level;~~limitation under Section 382 for those respective tax years. No other ownership changes or limitations on our historical net operating loss carryforwards were noted through the period ending November 26, 2025. As of December 31, 2025, we maintain a full valuation allowance over our deferred tax assets for financial reporting purposes.

●We ~~patients~~recognized inan impairment charge related to intangible assets. If our ~~clinical~~remaining ~~trials~~assets ~~may~~become ~~suffer~~impaired ~~adverse~~in ~~effects~~the ~~for~~future, ~~reasons~~we ~~that~~would ~~may~~incur oradditional ~~may~~impairment ~~not~~charges, bewhich ~~related~~would tonegatively affect our ~~product~~operating ~~candidates;~~results.

●We recognized impairment charges of $58.7 million related to definite-lived intangible assets during the ~~data~~quarter ~~collected~~ended ~~from~~June ~~clinical~~30, ~~trials~~2025. ~~may~~If ~~not~~our beremaining ~~sufficient~~assets tobecome ~~support~~impaired ~~submissions~~in tothe ~~regulatory~~future, ~~authorities~~we orwould toincur ~~obtain~~additional ~~regulatory~~impairment ~~approval~~charges, which would negatively affect our results of operations. There is significant judgment required in the ~~United~~analysis ~~States~~of a potential impairment of identified intangible assets and other long-lived assets. Impairment may result from, among other things, significant changes in the manner of use of the acquired assets, negative industry or economic trends and/or significant underperformance relative to historic or projected operating results. For additional information, see Note S of our consolidated financial statements included elsewhere; in this Annual Report on Form 10-K.

● the FDA or comparable foreign regulatory authorities may fail to approve the manufacturing processes or facilities of third-party manufacturers with which we contract for clinical and commercial supplies or may later suspend or withdraw such approval;

● the approval policies or regulations of the FDA, the EMA and other EU institutions, or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval; and

● even if we obtain marketing approval in one or more countries, future safety or other issues could result in the suspension or withdrawal of regulatory approval in such countries.

We have only limited experience in submitting the applications necessary to gain regulatory approvals and have relied, and expect to continue to rely, on consultants and third-party contract research organizations, or CROs, with expertise in this area to assist us in this process. Securing FDA or comparable foreign approval requires the submission of extensive non-clinical and clinical data, information about product manufacturing processes and inspection of facilities and supporting information to the FDA and comparable foreign regulatory authorities for each therapeutic indication to establish a product candidate’s safety and efficacy for each indication and manufacturing quality. Additionally, we cannot guarantee that regulators will agree with our assessment of the results of the clinical trials we have conducted or that any future trials will be successful.

Any product candidates we develop may prove to have undesirable or unintended side effects, toxicities or other characteristics that may preclude our obtaining regulatory approval or prevent or limit commercial use with respect to one or all intended indications.

The process of obtaining regulatory approvals is expensive, often takes many years, if approval is obtained at all, and can vary substantially based upon, among other things, the type, complexity and novelty of the product candidates involved, the jurisdiction in which regulatory approval is sought and the substantial discretion of the regulatory authorities. Changes in the regulatory approval policy during the development period, changes in or the enactment of additional statutes or regulations, or changes in regulatory review for a submitted product application may cause delays in the approval or rejection of an application or may result in future withdrawal of approval. Regulatory approval obtained in one jurisdiction does not necessarily mean that a product candidate will receive regulatory approval in all jurisdictions in which we may seek approval, but the failure to obtain approval in one jurisdiction may negatively impact our ability to seek approval in a different jurisdiction. Failure to obtain regulatory marketing approval of our product candidates in any indication will prevent us from commercializing those product candidates for that indication, and our ability to generate revenue will be impaired.

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~~Disruptions~~Risks atRelated ~~the FDA, the EMA and other government agencies, including those caused by funding shortages or global health concerns could hinder their ability~~ to ~~hire,~~Our ~~retain~~Dependence oron ~~deploy~~Third key leadership and other personnel, or otherwise prevent new or modified products from being developed, approved or commercialized in a timely manner or at all, which could negatively impact our business.Parties

~~The~~We ~~ability~~rely ofon ~~the FDA and foreign regulatory authorities to review and or approve new products can be affected by~~ a ~~variety~~limited ofnumber factors, including government priorities, budget and funding levels, statutory, regulatory, and policy changes, the FDA’s and foreign regulatory authorities' ability to hire and retain key personnel and accept the payment of ~~user fees~~suppliers, ~~and other events that may otherwise affect the FDA’s ability to perform routine functions. Average review times at the FDA and foreign regulatory authorities have fluctuated~~ in ~~recent~~some ~~years~~cases assole-source ~~a result~~suppliers. In addition, government funding of government agencies that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable. Disruptions at the FDA and other agencies may also slow the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business. For example, in recent years, the U.S. government has shut down several times and certain regulatory agencies, such as the FDA, have had to furlough critical FDA employees and stop critical activities.

IfWe ado ~~prolonged~~not ~~government~~have ~~shutdown~~any ormanufacturing ~~similar~~facilities. ~~constraints~~We onprocure ~~funding~~approved orproducts ~~staffing~~and ~~occur~~bulk drug substances from sole-source, orthird-party ifsuppliers. ~~renewed~~We ~~global~~anticipate ~~health~~we ~~concerns~~will ~~prevent~~continue to do so for the ~~FDA~~foreseeable future. We do not currently have arrangements in place for redundant supply or ~~other~~a ~~regulatory~~second ~~authorities~~source for these approved products or ~~notified~~bulk ~~bodies~~drug ~~from~~substances. ~~conducting~~This ~~their~~reliance ~~regular~~on ~~inspections,~~third ~~reviews~~parties increases the risk that we will not have sufficient quantities of our approved products or product candidates, or ~~other~~such ~~regulatory~~quantities ~~activities~~at an acceptable cost or quality, itwhich could ~~significantly~~delay, ~~impact~~prevent ~~the~~or impair our ability ofto ~~the~~generate ~~FDA~~revenue or ~~other~~timely ~~regulatory~~conduct ~~authorities~~our clinical trials or ~~notified~~our ~~bodies~~other development or commercialization efforts. If a current contract manufacturer cannot perform as agreed, we may be required to ~~timely~~replace ~~review~~such manufacturer and ~~process~~we may incur added costs and delays in identifying and qualifying any such replacement. Even if we are able to maintain our ~~regulatory~~existing ~~submissions,~~third-party ~~which~~relationships ~~could~~or ~~have~~establish aany ~~material~~such ~~adverse~~agreements ~~effect~~with other third-party manufacturers, reliance on ~~our~~third-party ~~business.~~manufacturers entails additional risks, including:

If•failure ~~the~~by ~~FDA~~any ~~does~~of ~~not conclude that~~ our ~~product~~suppliers ~~candidates~~to ~~satisfy~~comply ~~the~~with ~~requirements~~applicable ~~for~~regulations; the 505(b)(2) NDA pathway as anticipated, the approval pathway for our product candidates will likely take significantly longer, cost significantly more and entail significantly greater complications and risks than anticipated, and the FDA may not ultimately approve our product candidates.

~~A key element of our strategy is to seek FDA approval for most of our product candidates under Section 505(b)(2) of~~ •the ~~FFDCA, otherwise known as the 505(b)(2) NDA pathway with any NDA submitted thereunder a 505(b)(2) NDA, where~~ possible. ~~The~~misappropriation ~~505(b)(2) NDA pathway permits the filing~~ of anour ~~NDA~~proprietary ~~where at least some of the~~ information ~~required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference. Section 505(b)(2)~~, ifincluding applicable to us under the FFDCA, would allow an NDA we submit to the FDA to rely in part on data in the public domain or the FDA’s prior conclusions regarding the safety and effectiveness of approved compounds, which could expedite the development program for our ~~future~~trade ~~product~~secrets ~~candidates by potentially decreasing the amount of nonclinical~~ and~~/or~~ clinical data that we would need to generate in order to obtain FDA approval. Such reliance is typically predicated on a showing of bioequivalence or comparable bioavailability to an approved drug. AZSTARYS was approved via the 505(b)(2) NDA pathway on March 2, 2021.know-how;

~~If the FDA does not allow us to pursue the 505(b)(2) NDA pathway as anticipated~~•disruption, ordelays ~~if we cannot demonstrate bioequivalence or comparable bioavailability of our product candidates to approved products, we may need to conduct additional clinical trials, provide additional data~~ and ~~information,~~costs and meet additional standards for regulatory approval. Moreover, even if the FDA does allow us to pursue the 505(b)(2) NDA pathway, depending on the product candidate, we may still need to conduct additional clinical trials, including clinical trials to assess product safety or efficacy. If this were to occur, the time and financial resources required to obtain FDA approval for our product candidates, and complications and risks associated with ~~our~~changing ~~product candidates~~suppliers, ~~would~~including ~~likely~~additional ~~substantially~~regulatory ~~increase.~~filings;

~~Moreover, our inability to pursue~~ •the ~~505(b)(2)~~possible ~~NDA pathway could result in new competitive products reaching the market more quickly than our product candidates~~breach, ~~which~~termination ~~could~~or ~~hurt~~nonrenewal ~~our~~of ~~competitive position and our business prospects. Even if we are allowed to pursue~~ the ~~505(b)(2)~~agreement ~~NDA~~by ~~pathway, we cannot assure you that our product candidates will receive~~ the ~~requisite~~third approvals for commercialization on a timely basis, if at all. Other companies may achieve product approval of similar products before we do, which would delay our ability to obtain product approval, expose us to greater competition, and would require that we seek approval via alternative pathways.party;

In•a addition, notwithstanding the approval of several products by the FDA under Section 505(b)(2) over the last few years, pharmaceutical companies and others have objected to the FDA’s interpretation of Section 505(b)(2). If the FDA’s interpretation of Section 505(b)(2) is successfully challenged, the FDA may change its policies and practices with respect to Section 505(b)(2) regulatory approvals, which could delay or ~~even~~inability ~~prevent the FDA from approving any NDA that we submit under Section 505(b)(2). In addition, the pharmaceutical industry is highly competitive, and Section 505(b)(2) NDAs are subject~~ to ~~certain~~procure requirements designed to protect the patent rights of sponsors of previously approved drugs that are referenced in a Section 505(b)(2) NDA. These requirements may give rise to patent litigation and mandatory delays in approval of our NDAs for up to 30 months or ~~longer~~expand ~~depending~~sufficient onmanufacturing ~~the~~capacity; outcome of any litigation. It is not uncommon for a manufacturer of an approved product to file a citizen petition with the FDA seeking to delay approval of, or impose additional approval requirements for, pending competing products. If successful, such petitions can significantly delay, or even prevent, the approval of a new product. Even if the FDA ultimately denies such a petition, the FDA may substantially delay approval while it considers and responds to the petition. In addition, even if we are able to utilize the Section 505(b)(2) regulatory pathway, there is no guarantee this would ultimately lead to streamlined product development or earlier approval.

32•the inability to negotiate manufacturing agreements with third parties under commercially reasonable terms; and

~~Table~~•carrier ofdisruptions ~~Contents~~ or increased costs that are beyond our control.

~~Clinical~~Any ~~drug~~of ~~development~~these ~~involves~~events acould ~~lengthy~~impact ~~and~~our ~~expensive~~ability ~~process,~~to ~~with~~successfully ancommercialize ~~uncertain~~our ~~outcome.~~products, Welead ~~may~~to ~~incur~~clinical ~~additional~~trial ~~costs or experience~~ delays ~~in completing~~, or ~~ultimately~~failure beto ~~unable~~obtain toregulatory ~~complete~~approval, ~~the~~and ~~development~~have ~~and~~a ~~commercialization~~material ofimpact on our ~~product candidates~~business.

The ~~risk~~facilities ofused ~~failure~~by ~~for~~ our ~~product~~third-party ~~candidates~~contract ismanufacturers ~~high. It is impossible~~ to ~~predict~~manufacture ~~when or if any of~~ our ~~current~~approved ~~product~~products ~~candidates will prove effective or safe in humans~~ and ~~will receive regulatory approval. Before obtaining marketing approval from regulatory authorities for the sale of~~ any ~~product candidate, we must complete preclinical development and then conduct clinical trials to demonstrate the safety and efficacy~~ of our product candidates inare ~~humans.~~subject ~~Clinical testing is expensive, difficult~~ to ~~design~~review ~~and~~by implement, can take many years to complete and is uncertain as to outcome. A failure of one or more clinical trials can occur at any stage of testing. The outcome of preclinical studies and early clinical trials may not be predictive of the ~~success~~FDA ofpursuant later clinical trials, and interim results of a clinical trial do not necessarily predict final results. Interpretation of results from early, usually smaller, studies that suggest positive trends in some subjects, requires caution. Results from later stages of clinical trials enrolling more subjects may fail to show the desired safety and efficacy results or otherwise fail to be consistent with the results of earlier trials of the same product candidates. Later clinical trial results may not replicate earlier clinical trials for a variety of reasonsinspections, including differences in trial design, different trial endpoints, or lack of trial endpoints in exploratory studies, subject population, number of subjects, subject selection criteria, trial duration, drug dosage and ~~formulation~~such ~~and~~inspections ~~lack~~could ofresult ~~statistical power~~ in ~~the~~findings ~~earlier~~that ~~studies.~~lead ~~Moreover, preclinical and clinical data are often susceptible~~ to ~~varying~~failure ~~interpretations and analyses, and many companies that have believed their product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed~~ to obtain ~~marketing~~FDA approval of ~~their~~such ~~products~~marketing applications.

We ~~may~~are ~~experience~~completely ~~numerous~~dependent ~~unforeseen~~on, ~~events~~our ~~during,~~contract ormanufacturing aspartners afor ~~result~~compliance with cGMP and similar regulatory requirements outside the United States and for manufacture of, ~~clinical~~both ~~trials~~active ~~that~~drug ~~could~~substances ~~delay~~and orfinished ~~prevent~~drug products. If our ~~ability~~contract manufacturers cannot successfully manufacture material that conforms to ~~receive~~our ~~marketing~~specifications ~~approval~~and the strict regulatory requirements of the FDA or ~~commercialize~~other regulatory authorities, we will not be able to secure and maintain regulatory approval of our ~~product~~marketing ~~candidates,~~applications ~~including:~~for the use of their manufacturing facilities for our products.

●The ~~regulators~~failure of our third-party manufacturers, ~~IRBs~~to comply with applicable regulations could result in sanctions being imposed on us, including warning letters, clinical holds or termination of clinical trials, fines, injunctions, restitution, disgorgement, civil penalties, delays, suspension or withdrawal of approvals or other ~~ethics~~permits, ~~committees~~FDA ~~may~~or ~~not~~foreign ~~authorize~~regulatory usauthorities refusal to approve pending applications, product detentions, FDA or ~~our~~DEA ~~investigators~~consent decrees placing significant restrictions on or suspending manufacturing and distribution operations, debarment, refusal to ~~commence~~allow aimport ~~clinical~~or ~~trial~~export, ~~conduct~~product adetentions, ~~clinical~~adverse ~~trial~~publicity, atdear-health-care-provider aletters ~~prospective~~or ~~trial~~other ~~site~~warnings, license revocation, seizures or ~~amend~~recalls ~~clinical~~of ~~trial~~product ~~protocols~~candidates, asoperating ~~needed;~~restrictions, refusal of government contracts or future orders under existing contracts and civil and criminal liability, including False Claims Act liability, exclusion from participation in federal healthcare programs, and corporate integrity agreements, among other consequences, any of which could significantly and adversely affect supplies of our products.

●Failure weby any of our suppliers to comply with applicable regulations may ~~experience~~result in long delays inand ~~reaching,~~interruptions orto ~~fail~~our manufacturing capacity while we seek to ~~reach,~~secure ~~agreement~~another onsupplier ~~acceptable~~that ~~clinical~~meets ~~trial~~all ~~contracts~~regulatory orrequirements, ~~clinical~~as ~~trial~~well ~~protocols~~as ~~with~~market ~~prospective~~disruption ~~trial~~related ~~sites~~to ~~and~~any ~~CROs;~~necessary recalls or other corrective actions.

● clinical trials of our product candidates may produce negative or inconclusive results, including failure to demonstrate statistical significance in cases where that is required, and we may decide, or regulators may require us, to conduct additional clinical trials or abandon prodrug development programs;

● we may be unable to obtain sufficient or adequate supply or quality of product candidates or other materials necessary for use in clinical trials, or experience delays in sufficiently developing, characterizing or controlling a manufacturing process suitable for clinical trials; ● we may experience delays in manufacturing, testing, releasing, validating or importing/exporting sufficient stable quantities of our product candidates for use in clinical trials or the inability to do any of the foregoing;

● the number of subjects required for clinical trials of our product candidates may be larger than we anticipate enrollment in these clinical trials may be slower than we anticipate, or participants may drop out of these clinical trials at a higher rate than we anticipate;

● our third-party contractors may fail to comply with regulatory requirements or trial protocols, or meet their contractual obligations to us in a timely manner, or at all;

● regulators, IRBs, or other ethics committees may require that we or our investigators suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks;

● the cost of clinical trials of our product candidates may be greater than we anticipate, including if we are not able to pursue the 505(b)(2) NDA pathway for approval of our product candidates;

● we will need to pay substantial application user fees, which we may not be able to afford;

● we may be required to transfer manufacturing processes to larger-scale facilities operated by a contract manufacturing organization, and we may experience delays or failures by our contract manufacturers to make any necessary changes to such manufacturing process;

● we may abandon our development program or programs based on the changing regulatory or commercial environment;

● regulatory authorities may not agree with our trial design or implementation; and

● our product candidates may have undesirable side effects or other unexpected characteristics, causing us or our investigators, regulators or IRBs to suspend or terminate the trials.

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IfWe werely ~~are~~on ~~required~~a tolimited ~~conduct~~number ~~additional clinical trials or other testing~~ of ~~our~~third‑party ~~product~~distribution ~~candidates~~partners ~~beyond~~to ~~those~~commercialize ~~that we currently contemplate~~MIPLYFFA, ifand wethe ~~are~~loss ~~unable~~or toinadequate ~~successfully~~performance ~~complete clinical trials~~ of ~~our~~any ~~product candidates or other testing, if the results~~ of these ~~trials~~partners orcould ~~tests~~materially ~~are~~and ~~not~~adversely ~~positive~~affect orour ~~are~~ability ~~only~~to ~~modestly~~supply ~~positive~~MIPLYFFA orin ifkey ~~there are safety concerns, we may:~~territories.

●We berely ~~delayed~~on a single specialty pharmacy to distribute MIPLYFFA in ~~obtaining~~the ~~marketing~~United ~~approval~~States. We also rely on a single distributor in the EU and another single distributor for select territories outside of Europe to distribute MIPLYFFA under our Global EAP. Because each of these geographic markets is served by only one distribution partner, our ability to commercialize our product ~~candidates;~~depends heavily on the continued satisfactory performance of these third parties.

●Any ~~not~~disruption ~~obtain~~in ~~marketing~~the ~~approval~~services atprovided ~~all;~~by these distributors—including failure to comply with regulatory requirements, breach of contractual obligations, operational failures, financial instability, changes in ownership, natural disasters or other business interruptions—could negatively impact product availability in the relevant markets. If any of these third parties were to cease providing services to us or were unable or unwilling to perform their obligations, we would be required to secure an alternative distributor. Identifying, qualifying, and contracting with a replacement distributor is often a time‑consuming process that may require regulatory notifications, new logistics arrangements, and additional compliance reviews. As a result, the transition to a new distribution partner could cause significant delays in our ability to supply our approved drug in affected territories, potentially resulting in reduced revenues, customer dissatisfaction, damage to our commercial reputation, and a material adverse effect on our business.

●We ~~obtain~~rely ~~approval~~on ~~for~~and ~~indications~~expect orto ~~patient~~continue ~~populations~~to ~~that~~rely ~~are~~on ~~not~~third asparties ~~broad~~to asconduct ~~intended~~our orclinical ~~desired;~~trials for our product candidates, and those third parties may not perform satisfactorily.

●We ~~obtain~~rely ~~approval~~on and expect to continue to rely on contract research organizations (“CROs”), as well as other third parties, such as clinical data management organizations, medical institutions and clinical investigators, to conduct clinical trials. Our reliance on these third parties for research and development activities reduces our control over these activities but ~~without~~does not relieve us of our responsibilities. We remain responsible for ensuring that each of our clinical trials is conducted in accordance with the ~~claims~~general ~~necessary~~investigational plan and protocols for the trial and comply with regulatory standards commonly referred to as good clinical practices, or GCPs. Regulatory authorities enforce these GCPs through periodic inspections of trial sponsors, investigators and trial sites. Similar requirements apply in foreign jurisdictions. Failure to comply with these regulations may require us to ~~successfully~~repeat ~~commercialize~~preclinical studies and clinical trials, which would delay the regulatory approval process. Failure to comply with the applicable requirements related to clinical investigations by us, our CROs or clinical trial sites can also result in clinical holds and termination of clinical trials, debarment, FDA or foreign regulatory authorities refusal to approve applications based on the clinical data, warning letters, withdrawal of marketing approval if the product ~~candidates;~~has already been approved, fines and other monetary penalties, delays, adverse publicity and civil and criminal sanctions, among other consequences.

●If ~~obtain~~the ~~approval~~third parties with ~~labeling~~whom ~~that~~we ~~includes~~contract ~~significant~~do ~~use~~not successfully carry out their contractual duties or ~~distribution~~obligations ~~restrictions~~or meet expected deadlines or ~~safety~~if ~~warnings;~~the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols or regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated, we may need to conduct additional trials, and we may not be able to obtain regulatory approval for or successfully commercialize our product candidates. As a result, the commercial prospects for our product candidates would be harmed, our costs could increase and our ability to generate revenue could be delayed, and our business may be adversely affected.

●We behave ~~subject~~entered tointo ~~additional~~a ~~post-marketing~~collaboration ~~testing~~with Commave, ~~surveillance~~to develop, ormanufacture ~~other~~and ~~requirements~~commercialize AZSTARYS worldwide. If this collaboration is not successful, ~~such~~we asmay ~~REMS;~~not orbe able to capitalize on the market potential of AZSTARYS.

●We ~~have~~entered into the AZSTARYS License Agreement with Commave pursuant to which we granted an exclusive, worldwide license to Commave to develop, manufacture and commercialize AZSTARYS. On behalf of Commave, Corium leads all commercialization activities in the United States for AZSTARYS under the AZSTARYS License Agreement. We cannot guarantee that the AZSTARYS License Agreement will be successful or that we will receive any future payments under the AZSTARYS License Agreement. Commave has the option to terminate the AZSTARYS License Agreement, in its entirety or on a product-by-product ~~removed~~and ~~from~~country-by-country basis, at their convenience. In addition, under the ~~market~~AZSTARYS ~~after~~License ~~obtaining~~Agreement, ~~marketing~~we ~~approval~~have limited control over the amount and timing of resources dedicated to the development, manufacturing or commercialization of AZSTARYS, so we cannot guarantee that we will receive any additional milestone or royalty payments. Our ability to generate revenue under the AZSTARYS License Agreement will depend on Corium’s ability to successfully perform the functions assigned to it under the AZSTARYS License Agreement.

Any inability to successfully initiate or complete clinical trials could result in additional costs to us or impair our ability to generate revenue from product sales. In addition, if we make manufacturing or formulation changes to our product candidates, we may be required to or we may elect to conduct additional studies to bridge our modified product candidates to earlier versions. Clinical trial delays could also shorten any periods during which our products have patent protection and may allow our competitors to bring products to market before we do, which could impair our ability to successfully commercialize our product candidates and may seriously harm our business.

Clinical trials must be conducted in accordance with the FDA, the EMA and other applicable regulatory authorities’ legal requirements, regulations or guidelines, and are subject to oversight by these governmental agencies and ethics committees or IRBs at the medical institutions where the clinical trials are conducted. We could encounter delays if a clinical trial is suspended or terminated by us, by the data safety monitoring board for such trial or by the FDA or any other regulatory authority, or if the IRBs of the institutions in which such trials are being conducted suspend or terminate the participation of their clinical investigators and sites subject to their review. Such authorities may suspend or terminate a clinical trial due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or other regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a product candidate, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial.

Further, conducting clinical trials in foreign countries, as we may do for our product candidates, presents additional risks that may delay completion of our clinical trials. These risks include the failure of enrolled patients in foreign countries to adhere to clinical protocol because of differences in healthcare services or cultural customs, managing additional administrative burdens associated with foreign regulatory schemes, as well as political and economic risks relevant to such foreign countries.

Moreover, principal investigators for our clinical trials may serve as scientific advisors or consultants to us from time to time and receive compensation in connection with such services. Under certain circumstances, we may be required to report some of these relationships to the FDA or comparable foreign regulatory authority. The FDA, the EMA, or comparable foreign regulatory authority may conclude that a financial relationship between us and a principal investigator has created a conflict of interest or otherwise affected interpretation of the study. The FDA, the EMA, or comparable foreign regulatory authority may therefore question the integrity of the data generated at the applicable clinical trial site and the utility of the clinical trial itself may be jeopardized. This could result in a delay in approval, or rejection, of our marketing applications by the FDA, the EMA, or comparable foreign regulatory authority, as the case may be, and may ultimately lead to the denial of marketing approval of one or more of our product candidates.

Delays in the completion of any clinical trial of our product candidates will increase our costs, slow down our product development and the regulatory approval processes and delay or potentially jeopardize our ability to commence product sales and generate product revenue. Any of these occurrences may harm our business, financial condition and prospects significantly.

In addition, the policies of the FDA and other regulatory authorities with respect to clinical trials, may change and additional government regulations may be enacted. For instance, the regulatory landscape related to clinical trials in the EU recently evolved. The CTR which was adopted in April 2014 and repeals the EU Clinical Trials Directive, became applicable on January 31, 2022. While the EU Clinical Trials Directive required a separate clinical trial application (“CTA”) to be submitted in each member state in which the clinical trial takes place, to both the competent national health authority and an independent ethics committee, the CTR introduces a centralized process and only requires the submission of a single application for multi-center trials. The CTR allows sponsors to make a single submission to both the competent authority and an ethics committee in each member state, leading to a single decision per member state. The assessment procedure of the CTA has been harmonized as well, including a joint assessment by all member states concerned, and a separate assessment by each member state with respect to specific requirements related to its own territory, including ethics rules. Each member state’s decision is communicated to the sponsor via the centralized EU portal. Once the CTA is approved, clinical study development may proceed. The CTR transition period ended on January 31, 2025, and all clinical trials (and related applications) are now fully subject to the provisions of the CTR. Compliance with the CTR requirements by us and our third-party service providers, such as CROs, may impact our developments plans.

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IfIn weaddition, ~~experience~~a ~~delays~~dispute orhas ~~difficulties~~arisen with Commave concerning the interpretation of certain provisions under the AZSTARYS License Agreement, and in September 2024, Commave filed a complaint against us in the ~~enrollment~~Court of ~~subjects~~Chancery of the State of Delaware alleging breach of contract and seeking injunctive relief, specific performance, declaratory relief, and damages regarding the parties' respective rights and obligations under the AZSTARYS License Agreement. The litigation is in ~~clinical~~its ~~trials~~early stages, and we strongly disagree with Commave's allegations and believe this lawsuit is without merit. While we intend to vigorously defend against Commave's claims, the outcome of this matter is inherently uncertain. We cannot predict with certainty the timing or ultimate outcome of this litigation or its potential impact on our ~~receipt~~business, financial condition, or results of ~~necessary~~operations. ~~regulatory~~The ~~approvals~~AZSTARYS ~~could~~License Agreement remains in effect during this litigation, and both parties continue to perform their respective obligations thereunder. However, there can be ~~delayed~~no assurance that this dispute will not have an adverse impact on our relationship with Commave or ~~prevented~~on our business.

We may ~~not~~seek ~~be able~~ to ~~initiate~~establish orcollaborations ~~continue clinical trials~~ for ~~our~~certain product candidates, ifwhich ~~we are unable to locate and enroll a sufficient number of eligible subjects to participate in these trials as~~ may not be ~~required~~available byon ~~the~~acceptable ~~FDA~~terms, or ~~similar regulatory authorities outside the United States. We cannot predict how successful we will be~~ at ~~enrolling subjects in future clinical trials~~all. If we are not successful at enrolling subjects in one clinical trial, it may affect when we are able to initiate our next clinical trial, which could result in significant delays in our efforts to pursue regulatory approval of and commercialize our product candidates. In addition, some of our competitors have ongoing clinical trials to treat the same indications as our product candidates, and subjects who would otherwise be eligible for our clinical trials may instead enroll in clinical trials of our competitors. Subject enrollment is affected by other factors including:

●We ~~the~~may ~~size~~seek ~~and~~to ~~nature~~collaborate ofwith ~~the~~pharmaceutical ~~subject~~and ~~population~~biotechnology ~~specified~~companies ~~in the trial protocol; ● the eligibility criteria~~ for the ~~study~~development ~~in question; ● the perceived risks~~ and ~~benefits~~potential commercialization of ~~the~~certain product ~~candidate~~candidates. ~~under~~We ~~study;~~face ●significant ~~the~~competition ~~fact~~in ~~that~~seeking ~~the~~appropriate ~~product~~collaborators. ~~candidate~~Whether iswe reach a ~~controlled~~definitive ~~substance;~~agreement ●for ~~severe~~a orcollaboration ~~unexpected~~will ~~drug-related~~depend, ~~adverse~~among ~~events~~other ~~experienced~~things, byupon ~~subjects~~our inassessment aof ~~clinical trial; ●~~ the ~~availability~~collaborator’s ofresources ~~drugs~~and ~~approved~~expertise, ~~to treat~~ the ~~diseases~~terms orand conditions ~~under~~of ~~study; ●~~ the ~~efforts~~proposed tocollaboration ~~facilitate~~and ~~timely enrollment in clinical trials; ●~~ the ~~patient~~proposed ~~referral~~collaborator’s ~~practices~~evaluation of ~~physicians;~~several ●factors. ~~the~~The ~~severity~~collaborator ofmay ~~the~~also ~~disease~~consider oralternative ~~condition~~product ~~under~~candidates ~~investigation;~~or ●technologies ~~the ability to obtain and maintain subject informed consent; ● the ability to retain subjects in the clinical trial and their return~~ for ~~follow-up;~~similar ●indications ~~the~~that ~~clinical~~may ~~trial~~be ~~design,~~available ~~including required tests, procedures and follow-up; ● the ability~~ to ~~monitor~~collaborate ~~subjects~~on ~~adequately during~~ and ~~after~~whether ~~treatment;~~such ●a ~~delays~~collaboration incould ~~adding~~be ~~new~~more ~~investigators~~attractive ~~and~~than ~~clinical sites; ● withdrawal of clinical trial sites from clinical trials; and ●~~ the ~~proximity~~one ~~and~~with ~~availability~~us ~~of clinical trial sites~~ for ~~prospective~~our ~~subjects~~product candidate.

~~Our~~Collaborations ~~inability~~are complex and time-consuming to ~~enroll~~negotiate and document. We may not be able to negotiate collaborations on a ~~sufficient~~timely ~~number~~basis, ofon ~~subjects~~acceptable ~~for~~terms, ~~clinical~~or ~~trials~~at ~~would~~all. ~~result~~If inwe ~~significant~~are ~~delays~~unable ~~and~~to ~~could~~do ~~require~~so, uswe may have to ~~abandon~~curtail the development of product candidates, reduce or delay one or more ~~clinical~~of ~~trials~~our ~~altogether.~~development ~~Enrollment~~programs, ~~delays~~delay inpotential ~~these~~commercialization ~~clinical~~of ~~trials~~our ~~may~~product ~~result~~candidates inor ~~increased~~reduce ~~development~~the ~~costs~~scope ~~for~~of any sales or marketing activities of our product candidates, ~~which~~or ~~could~~increase ~~cause~~our expenditures and undertake development or commercialization activities of our ~~value~~product candidates at our own expense. If we elect to ~~decline~~increase ~~and~~our ~~limit~~expenditures to fund development or commercialization activities on our ~~ability~~own, we may need to obtain additional ~~financing~~capital, which may not be available to us on acceptable terms or at all. If we do not have sufficient funds, we may not be able to further develop our product candidates or bring our product candidates to market and generate product revenue.

Risks Related to Our Intellectual Property

If we are unable to obtain and maintain intellectual property protection for our technology, our approved products or our product candidates, or if the scope of the intellectual property protection obtained is not sufficiently broad, our competitors could develop and commercialize technology and products similar or identical to ours, and our ability to successfully commercialize our technology, our approved products, or our product candidates if approved, may be impaired.

Our success depends in large part on our ability to obtain and maintain trade secret protection of our proprietary technology as well as patent protection in the United States and other countries with respect to our approved products and any of our product candidates. The patent prosecution process is expensive and time-consuming, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. Further, we may also not have the right to control the preparation, filing and prosecution of patent applications, or to maintain the rights to patents, licensed from third parties to us. Therefore, any such patents and applications may not be prosecuted and enforced in a manner consistent with the best interests of our business.

•our pending patent applications may not result in issued patents or patents that will provide us with any meaningful protection;

•we cannot be certain that we are the first to invent the inventions covered by pending patent applications or that we are the first to file such applications and, if we are not, we may be subject to priority disputes or lose rights;

•because of the extensive time required for development, testing and regulatory review of a product candidate, it is possible that before a potential product can be commercialized, any related patent may expire, or remain in existence for only a short period following commercialization thereby reducing, or eliminating any advantage of the patent;

•we may not be able to acquire patent term extensions or supplemental certificates of certain patents, domestic or foreign, due to regulatory delays, among others, which may affect the term of enforceability of such patents over time;

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~~Interim,~~•there ~~topline,~~could oralso ~~preliminary~~be ~~data~~delays ~~from~~at ~~our~~the ~~clinical~~USPTO ~~trials~~caused ~~that~~by westaffing ~~announce~~cuts orand ~~publish~~other ~~from~~U.S. ~~time~~government toactions ~~time may change~~ as ~~more~~a ~~patient~~result ~~data~~of ~~become~~the ~~available~~U.S. ~~and~~Department ~~are~~of ~~subject~~Government toEfficiency ~~audit~~or ~~and~~other ~~verification~~executive ~~procedures~~actions ~~that~~to ~~could~~reduce ~~result~~the insize ~~material~~of ~~changes in~~ the ~~final data~~U.S. government;

~~From~~•our ~~time~~competitors ~~to time, we~~ may ~~publicly~~be ~~disclose~~able topline or preliminary data from our preclinical studies and clinical trials, which is based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to ~~change~~design ~~following~~around ~~a more comprehensive review of the data related to the particular study or trial. We also make assumptions, estimations, calculations, and conclusions as part of~~ our ~~analyses~~owned ~~of data, and we may not have received~~ or ~~had~~licensed ~~the~~patents ~~opportunity~~by todeveloping ~~fully~~similar ~~and carefully evaluate all data. As a result, the preliminary~~ or ~~topline~~alternative ~~results~~technologies ~~that we report may differ from future results of the same studies,~~ or ~~different~~drugs ~~conclusions~~without orinfringing ~~considerations~~on ~~may~~our ~~qualify~~intellectual ~~such~~property results, once additional data has been received and fully evaluated. Topline data also remains subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. As a result, preliminary or topline data should be viewed with caution until the final data are available.rights;

~~From~~•third ~~time~~parties ~~to time, we~~ may ~~also~~develop ~~disclose~~products ~~interim data from our preclinical studies and clinical trials. Interim data from clinical trials~~ that wehave ~~may complete are subject to~~ the ~~risk~~same ~~that one~~ or ~~more~~similar ofeffect ~~the clinical outcomes may materially change~~ as ~~patient enrollment continues and more patient data become available or as patients from~~ our ~~clinical~~products ~~trials~~without ~~continue~~infringing ~~other treatments for their disease. Adverse differences between preliminary or interim data and final data could significantly harm~~ our ~~business~~patents; ~~prospects.~~and

~~Further,~~•there ~~disclosure of interim data by us or by our competitors could result in volatility in the price of our common stock. Further, others, including regulatory agencies,~~ may ~~not~~be ~~accept~~dominating or ~~agree~~intervening ~~with~~patents ~~our~~relevant assumptions, estimates, calculations, conclusions, or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular product candidate, and our company in general. If the interim, topline, or preliminary data that we report differs from actual results, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to ~~obtain approval for, and commercialize, any of~~ our ~~potential~~ product candidates ~~may~~of ~~be harmed,~~ which ~~could~~we ~~harm~~are ~~our~~not ~~business, operating results, prospects, or financial condition~~aware.

WeAny ~~may~~of ~~not~~these befactors ~~able~~could tohurt ~~obtain~~our orability ~~maintain~~to ~~orphan~~gain ~~drug~~full ~~designations~~patent ~~which~~protection ~~we pursue~~ for ~~any of~~ our ~~product~~products. ~~candidates,~~Registered trademarks and wetrademark ~~may~~applications bein ~~unable to maintain~~ the ~~benefits~~United ~~associated~~States ~~with~~and ~~orphan~~other ~~drug~~countries ~~designation,~~are ~~including~~subject ~~the~~to ~~potential~~similar ~~for market exclusivity~~risks.

~~Regulatory~~We ~~authorities in some jurisdictions, including the United States,~~ may ~~designate~~become ~~drugs~~involved ~~for~~in ~~relatively~~lawsuits ~~small patient populations as orphan drugs. Under the Orphan Drug Act of 1983, the FDA may designate a drug as an orphan product if it is intended~~ to ~~treat~~protect ~~a rare disease~~ or ~~condition,~~enforce ~~which~~our ispatents ~~generally defined as a patient population of fewer than 200,000 individuals in the United States,~~ or aother ~~patient~~intellectual ~~population of greater than 200~~property,~~000~~ ~~individuals in the United States, but for~~ which ~~there~~could ~~is no reasonable expectation that the cost of developing the drug will~~ be ~~recovered~~expensive, ~~from~~time ~~sales~~consuming ~~in the United States. While the FDA has granted KP1077 orphan drug designation for the treatment of IH,~~ and ~~celiprolol received orphan drug designation from the FDA for the treatment of VEDS, we have not received orphan drug designation for any other product candidate~~unsuccessful. We may seek to obtain orphan drug designation for product but there can be no assurance that the FDA will grant orphan designation for any indication for which we apply, or that we will be able to maintain such designation.

InCompetitors ~~the~~or ~~United~~other ~~States~~third parties may infringe our patents, ~~orphan~~trademarks, ~~designation~~copyrights ~~entitles~~or aother ~~party~~intellectual toproperty. ~~financial~~To ~~incentives~~counter ~~such~~infringement asor ~~opportunities~~unauthorized ~~for~~use, ~~grant~~we ~~funding~~may ~~toward~~be ~~clinical~~required ~~trial~~to ~~costs~~file infringement claims, ~~tax~~which ~~advantages~~can be expensive and ~~user-fee~~time ~~waivers~~consuming and divert the time and attention of our management and scientific personnel. InAny ~~addition,~~claims ifwe aassert ~~product~~against ~~candidate~~perceived ~~that~~infringers ~~has~~could ~~orphan~~provoke ~~designation~~these ~~subsequently~~parties ~~receives~~to ~~the~~assert ~~first~~counterclaims ~~FDA~~against ~~approval~~us ~~for~~alleging ~~the~~that ~~disease~~we ~~for~~infringe ~~which~~their itpatents, ~~has~~in ~~such~~addition ~~designation~~to counterclaims asserting that our patents are invalid or unenforceable, ~~the~~or ~~product~~both. The outcome following legal assertions of invalidity and unenforceability is ~~entitled~~unpredictable. toAn ~~orphan~~adverse ~~drug~~outcome ~~exclusivity,~~in ~~which~~a ~~means~~litigation ~~that~~or ~~the~~proceeding ~~FDA~~involving ~~may~~our ~~not~~patents ~~approve~~could ~~any~~limit our ability to assert our patents against those parties or other ~~applications,~~competitors ~~including~~and anmay ~~NDA,~~curtail or preclude our ability to ~~market~~exclude ~~the~~third ~~same~~parties ~~product~~from ~~for~~making ~~the~~and ~~same~~selling ~~indication~~similar ~~for~~or ~~seven~~competitive ~~years~~products and technologies. In addition, ~~except~~third inparties ~~limited~~may ~~circumstances~~use technology covered by patent applications, ~~such~~but aspending apatent ~~showing~~applications ofcannot ~~clinical~~be ~~superiority~~enforced toagainst third parties practicing the ~~product~~technology ~~with~~claimed ~~orphan~~in ~~drug~~such ~~exclusivity~~applications orunless ~~where~~and ~~the~~until ~~manufacturer~~a ispatent ~~unable~~issues tofrom ~~assure~~such ~~sufficient~~applications. ~~product~~Any ~~quantity~~of these occurrences could adversely affect our competitive business position, business prospects and financial condition.

InThird ~~the~~parties ~~EU, orphan designation is granted by the EC based on a scientific opinion of the EMA’s Committee for Orphan Medicinal Products. A medicinal product~~ may beinitiate ~~designated~~legal asproceedings ~~orphan~~against ifus ~~its~~alleging ~~sponsor can establish~~ that ~~(i)~~we ~~the~~are ~~product~~infringing istheir ~~intended~~intellectual ~~for~~property ~~the diagnosis~~rights, ~~prevention~~the oroutcome ~~treatment~~ of awhich life-threatening or chronically debilitating condition; (ii) either (a) such condition affects no more than 5 in 10,000 persons in the EU when the application is made, or (b) the product, without the benefits derived from orphan status, would not generate sufficient return in the EU to justify investment; and (iii) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the EU, or if such a method exists, the medicinal product will be ofuncertain significant benefit to those affected by the condition. The application for orphan designation must be submitted before the application for marketing authorization. Orphan designation entitles a party to financial incentives such as reduction of fees, fee waivers, protocol assistance, and ~~access~~could tosignificantly ~~the~~harm ~~centralized~~our ~~marketing authorization procedure~~business. Moreover, upon grant of a marketing authorization and assuming the requirement for orphan designation are also met at the time the marketing authorization is granted, orphan medicinal products are entitled to a ten-year period of market exclusivity for the approved therapeutic indication. The period of market exclusivity is extended by two years for orphan medicinal products that have also complied with an agreed Pediatric Investigation Plan.

~~Even~~Our ifcommercial wesuccess ~~obtain~~depends ~~orphan~~upon ~~drug~~our ~~exclusivity~~ability, ~~for~~and athe ~~product~~ability of any collaborators, ~~that~~to ~~exclusivity~~develop, ~~may~~manufacture, ~~not~~market ~~effectively~~and ~~protect~~sell ~~the~~our products, product ~~from~~candidates ~~competition~~and ~~because~~use ~~different~~our ~~drugs~~proprietary ~~can~~technologies bewithout ~~approved~~infringing ~~for~~the proprietary rights of third parties. There is considerable intellectual property litigation in the ~~same~~biotechnology ~~condition~~and pharmaceutical industries. ~~Even~~Although ~~after~~we anseek ~~orphan~~to ~~drug~~develop isproprietary ~~approved,~~formulations that do not infringe the ~~FDA~~intellectual property rights of others, we may become party to, or ~~comparable~~threatened with, future adversarial proceedings or litigation, domestic or foreign, ~~regulatory~~regarding ~~authority~~intellectual ~~can~~property ~~subsequently~~rights ~~approve~~with ~~the~~respect ~~same~~to ~~drug~~our ~~for~~products ~~the~~or ~~same~~other ~~condition~~aspects ifof ~~such~~our ~~regulatory~~technology. ~~authority~~We ~~concludes~~cannot be certain that ~~the~~we ~~later~~have ~~drug~~identified isor ~~clinically~~will ~~superior~~identify ~~because~~each itand every third party patent and pending patent application in the United States and abroad that is ~~shown~~relevant to beor ~~safer,~~necessary ~~more~~for ~~effective~~the orcommercialization ~~makes~~of aour ~~major~~current ~~contribution~~and tofuture ~~patient~~products ~~care~~and product candidates in any jurisdiction.

~~Orphan~~Litigation ~~drug~~regarding ~~exclusivity~~intellectual ~~may~~property ~~also~~rights beis ~~lost~~inherently ifuncertain ~~the~~due ~~FDA~~to ~~later determines that~~ the ~~initial~~complex ~~request~~issues ~~for designation was materially defective. In addition~~involved, ~~orphan~~and ~~drug~~we ~~exclusivity~~may ~~does~~ not ~~prevent~~be ~~the~~successful ~~FDA~~in ~~from~~defending ~~approving~~ourselves ~~competing~~in ~~drugs~~such ~~for~~matters. ~~the~~If ~~same~~we orare ~~similar~~found ~~indication~~to ~~containing~~infringe a ~~different~~third ~~active~~party’s ~~ingredient.~~intellectual Inproperty ~~addition~~rights, ifwe acould ~~subsequent~~be ~~drug~~required isto ~~approved~~obtain ~~for~~a ~~marketing~~license ~~for~~from ~~the~~such ~~same~~third orparty ato ~~similar~~continue ~~indication~~developing asand ~~any~~marketing of our ~~product~~technology ~~candidates~~and ~~that~~drugs. ~~receive marketing approval~~However, we may ~~face~~not ~~increased~~be ~~competition~~able ~~and~~to ~~lose~~obtain ~~market~~any ~~share~~required ~~regardless~~license ofon ~~orphan~~commercially ~~drug~~reasonable ~~exclusivity. In the EU~~terms, ~~during~~or ~~the~~at ~~market~~all. ~~exclusivity~~Even ~~period,~~if ~~marketing~~we ~~authorizations~~were ~~may~~able ~~be granted~~ to obtain a ~~similar~~license, ~~medicinal~~it ~~product~~could ~~with~~be ~~the~~non-exclusive, ~~same~~thereby ~~orphan~~giving ~~indication~~our ~~if:~~competitors ~~(i)~~access ~~the~~to ~~applicant can establish that~~ the ~~second~~same ~~medicinal~~technologies ~~product,~~licensed ~~although similar~~ to ~~the~~us. ~~orphan~~We ~~medicinal~~could ~~product~~be ~~already authorized is safer~~forced, ~~more~~including ~~effective~~by orcourt ~~otherwise~~order, ~~clinically superior~~ to ~~the~~cease ~~orphan~~commercializing ~~medicinal product already authorized; (ii)~~ the ~~marketing~~infringing ~~authorization~~technology ~~holder for the orphan medicinal product grants its consent;~~ or ~~(iii) if the marketing authorization holder of the orphan medicinal~~ product ~~is unable to supply sufficient quantities of product~~. ~~The~~In ~~European~~addition, ~~exclusivity~~we ~~period~~could ~~can~~ be ~~reduced~~found toliable ~~six~~for ~~years,~~monetary ifdamages, atincluding ~~the~~treble ~~end~~damages ofand ~~the~~attorneys’ ~~fifth~~fees ~~year~~if awe ~~medicine~~are nofound ~~longer~~to ~~meets~~have ~~the~~willfully ~~criteria~~infringed ~~for~~a ~~orphan designation (i~~patent.e. ~~the~~A ~~prevalence~~finding of ~~the~~infringement ~~condition~~could ~~has~~prevent ~~increased~~us ~~above~~from ~~the~~commercializing ~~orphan~~our ~~designation~~product ~~threshold,~~candidates or itforce isus ~~judged~~to ~~that~~cease ~~the~~some ~~product~~or isall ~~sufficiently profitable so as not to justify maintenance~~ of ~~market~~our ~~exclusivity)~~business operations.

~~Orphan~~Intellectual ~~drug~~property ~~designation~~litigation ~~neither~~could ~~shortens~~cause ~~the~~us ~~development~~to ~~time~~spend orsubstantial ~~regulatory~~resources ~~review~~and ~~time~~distract ofour apersonnel ~~drug~~from ~~nor~~their ~~gives~~normal ~~the drug any advantage in the regulatory review or approval process~~responsibilities.

Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses and could distract our technical and management personnel from their normal responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments. If securities analysts or investors perceive these results to be negative, it could hurt the price of our common stock. Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales, marketing or distribution activities. We may not have sufficient financial or other resources to conduct such litigation or proceedings adequately. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial resources.

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~~Certain~~If ofwe ~~our~~are ~~approved~~unable ~~products~~to ~~and product~~protect ~~candidates contain controlled substances,~~ the ~~manufacture,~~confidentiality ~~use,~~of ~~sale,~~our ~~importation,~~trade ~~exportation~~secrets, ~~prescribing~~our business and ~~distribution~~competitive ofposition ~~which~~would ~~are~~be ~~subject to regulation by the DEA and other regulatory agencies~~harmed.

~~Certain~~In ofaddition ~~our~~to ~~approved~~seeking ~~products~~patent and ~~certain~~trademark ofprotection for our product candidates, ~~are~~we ~~regulated~~also asrely ~~controlled~~on ~~substances~~trade secrets, ~~which~~including ~~are~~unpatented ~~subject~~show-how, know-how, technology and other proprietary information, to ~~state~~maintain our competitive position. We seek to protect our trade secrets, ~~federal~~in part, ~~and~~by ~~foreign~~entering ~~laws~~into non-disclosure and ~~regulations~~confidentiality ~~regarding~~agreements ~~their~~with ~~manufacture~~parties who have access to them, ~~use~~such as our employees, ~~sale~~corporate collaborators, ~~importation~~outside scientific collaborators, ~~exportation~~contract manufacturers, ~~and~~consultants, ~~distribution. Among~~advisors and other ~~things,~~third ~~controlled~~parties. ~~substances~~We ~~are~~also ~~regulated~~enter ~~under~~into ~~the~~confidentiality ~~Controlled~~and ~~Substances~~invention ~~Act~~or ofpatent ~~1970 and~~assignment ~~regulations~~agreements ofwith ~~the~~our ~~DEA~~employees and consultants. ~~Before~~Despite wethese ~~can~~efforts, ~~commercialize~~ any of ~~our~~ ~~products~~these ~~or product~~parties ~~candidates,~~may ifbreach ~~approved~~the agreements and disclose our proprietary information, ~~the~~including ~~DEA~~our ~~will~~trade secrets. Further, we may need to ~~determine~~share ~~the~~our ~~controlled~~trade ~~substance~~secrets ~~schedule,~~and ~~taking~~confidential ~~into~~know-how ~~account~~with ~~the~~future ~~recommendation~~business ofpartners, ~~the~~collaborators, ~~FDA.~~contractors ~~This~~and ~~may~~others belocated ain ~~lengthy~~countries ~~process~~at ~~that~~heightened ~~could~~risk ~~delay~~of ~~our~~theft ~~marketing~~ of atrade ~~product~~secrets. ~~candidate~~If ~~and~~any ~~could~~of ~~potentially~~our ~~diminish~~trade ~~any~~secrets ~~regulatory~~were ~~exclusivity~~to ~~periods~~be ~~for~~disclosed ~~which~~to wea ~~may~~competitor, our competitive position would be ~~eligible~~harmed.

~~The~~Any ~~DEA~~trademarks ~~regulates~~we ~~controlled substances as Schedule I, II, III, IV or V substances. Schedule I substances by definition have no established medicinal use and~~ may ~~not~~obtain ~~be marketed or sold in the United States. A pharmaceutical product~~ may be ~~listed~~infringed ~~as Schedule II, III, IV~~ or V,successfully with Schedule II substances considered to present the highest risk of abuse and Schedule V substances the lowest relative risk of abuse among such substances. The DEA determined AZSTARYS to be a Schedule II controlled substance. In additionchallenged, ~~the~~resulting ~~DEA~~in ~~scheduled~~harm SDX as a Schedule IV substance. We expect that most of our product candidates, including KP1077, if approved, will also be regulated as “controlled substances” by the DEA, which subjects AZSTARYS and this product candidate to ~~additional restrictions regarding their manufacture, shipment, storage, sale and use, depending on the scheduling of the active ingredients, and may limit the commercial potential of~~ our ~~products and any of our product candidates, if approved~~business.

~~Various~~We ~~states~~expect ~~also~~to ~~independently~~rely ~~regulate~~on ~~controlled~~trademarks ~~substances.~~as ~~Though~~one ~~state-controlled~~means ~~substances~~to ~~laws~~distinguish ~~often~~our ~~mirror~~product ~~federal~~candidates ~~law,~~that ~~because~~are approved for marketing from the ~~states~~products ~~are~~of ~~separate~~our ~~jurisdictions~~competitors. We have registered trademarks, ~~they~~including ~~may~~those ~~separately~~for ~~schedule~~LAT, ~~drugs~~Zevra, asMIPLYFFA ~~well~~and OLPRUVA. ~~While~~In ~~some~~addition, ~~states~~we ~~automatically~~have ~~schedule~~solicited aand ~~drug~~applied ~~when~~for ~~the~~trademarks ~~DEA~~for ~~does~~the ~~so,~~Zevra inlogo ~~other~~and ~~states~~several ~~there~~potential ~~must~~trade benames ~~rulemaking~~and orlogos afor ~~legislative~~future ~~action~~product candidates. ~~State~~Third ~~scheduling~~parties may ~~delay~~oppose ~~commercial~~or ~~sale~~attempt to cancel our trademark applications or trademarks, or otherwise challenge our use of ~~any~~the ~~controlled~~trademarks. ~~substance~~If ~~drug~~our ~~product~~trademarks ~~for~~are ~~which~~successfully challenged, we ~~obtain~~could ~~federal~~be ~~regulatory~~forced ~~approval~~to ~~and~~rebrand ~~adverse~~our ~~scheduling~~products, which could ~~impair~~result ~~the~~in ~~commercial~~loss ~~attractiveness~~ of ~~such~~brand ~~product~~recognition and could require us to devote resources to advertising and marketing new brands. WeOur orcompetitors ~~our~~may ~~collaborators~~infringe ~~must~~our ~~also~~trademarks ~~obtain~~and ~~separate~~we ~~state~~may ~~registrations~~not inhave ~~order~~adequate resources to beenforce ~~able~~our trademarks. We may license our trademarks and trade names to ~~obtain~~third parties, ~~handle~~such ~~and~~as ~~distribute~~distributors. ~~controlled~~Although ~~substances~~these ~~for~~license ~~clinical~~agreements ~~trials~~may orprovide ~~commercial~~guidelines ~~sale,~~for how our trademarks and ~~failure~~trade tonames ~~meet~~may ~~applicable~~be ~~regulatory~~used, ~~requirements~~a ~~could~~breach ~~lead~~of tothese ~~enforcement~~agreements or misuse of our trademarks and ~~sanctions~~tradenames ~~from~~by ~~the~~our ~~states~~licensees inmay ~~addition~~jeopardize toour ~~those~~rights ~~from~~in or diminish the ~~DEA~~goodwill orassociated ~~otherwise~~with ~~arising~~our ~~under~~trademarks ~~federal~~and ~~law~~trade names.

~~For~~We any of our products or product candidates classified as controlled substances, we and our suppliers, manufacturers, contractors, customers and distributors are required to obtain and maintain applicable registrations from state, federal and foreign law enforcement and regulatory agencies and comply with state, federal and foreign laws and regulations regarding the manufacture, use, sale, importation, exportation and distribution of controlled substances. There is a risk that DEA regulations may limit the supply of the compounds used in clinical trials for our product candidates, and, in the future, the ability to produce and distribute our products in the volume needed to meet commercial demand. For example, a DEA quota system controls and limits the availability and production of controlled substances in Schedule I or II. Because our products and most of our product candidates are or may be regulated as Schedule II controlled substances, they may be subject to the DEA’s production and procurement quota scheme. The DEA establishes annually an aggregate quota for how much of a controlled substance may be produced in total in the United States based on the DEA’s estimate of the quantity needed to meet legitimate scientific and medicinal needs. Manufacturers of Schedule I and II controlled substances are required to apply for quotas on an annual basis. If we or our contract manufacturers or suppliers do not ~~obtain a sufficient quota from the DEA, we may not~~ be able to ~~obtain~~protect ~~sufficient quantities of these controlled substances in order to complete~~ our ~~clinical~~intellectual ~~trials~~property orrights ~~meet~~throughout ~~commercial~~the ~~demand for any of our products or product candidates classified under Schedule II~~world.

~~Regulations~~Patents ~~associated~~are ~~with~~of ~~controlled~~national ~~substances~~or ~~govern~~regional ~~manufacturing~~effect, ~~labeling,~~and ~~packaging~~filing, ~~testing,~~prosecuting ~~dispensing,~~and ~~production~~defending patents on all of our products and ~~procurement~~technologies ~~quotas,~~throughout ~~recordkeeping,~~the ~~reporting,~~world ~~handling,~~would ~~shipment~~be ~~and~~prohibitively ~~disposal~~expensive. ~~These~~As ~~regulations~~such, ~~increase~~our intellectual property rights in some countries outside the ~~personnel~~United ~~needs~~States can be less extensive than those in the United States and we may not be able to prevent third parties from practicing our inventions in all countries outside the ~~expense~~United ~~associated~~States, ~~with~~or ~~development~~from selling or importing products made using our inventions in and ~~commercialization~~into ofthe ~~product~~United ~~candidates~~States ~~including~~or ~~controlled~~other ~~substances~~jurisdictions. ~~The~~Competitors ~~DEA,~~may use our technologies in jurisdictions where we have not obtained patent protection to develop their own products or technology and ~~some~~may ~~states~~export otherwise infringing products or technology to territories where we have patent protection, ~~conduct~~but ~~periodic~~enforcement ~~inspections~~rights ofare ~~registered~~not ~~establishments~~as ~~that~~strong ~~handle~~as ~~controlled~~those ~~substances~~in the United States. ~~Failure~~Further, tothe ~~obtain~~legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents and ~~maintain~~other ~~required~~intellectual ~~registrations~~property orprotection, ~~comply~~particularly ~~with~~those ~~any~~relating ~~applicable~~to ~~regulations~~pharmaceuticals or biologics, which could ~~delay~~make orit ~~preclude~~difficult for us ~~from~~to ~~developing~~stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally. Moreover, our ability to protect and ~~commercializing~~enforce our ~~product~~intellectual ~~candidates~~property ~~containing~~rights ~~controlled~~may ~~substances~~be adversely affected by unforeseen changes in intellectual property laws of other countries. In addition, certain countries, including China and ~~subject~~India, ushave compulsory licensing laws under which a patent owner may be compelled to ~~enforcement~~grant ~~action~~licenses to third parties. ~~The~~In ~~DEA~~those countries, we and our licensors may ~~seek~~have ~~civil~~limited ~~penalties,~~remedies ~~refuse~~if topatents ~~renew~~are ~~necessary~~infringed ~~registrations~~or if we or ~~initiate~~our ~~proceedings~~licensors are compelled to ~~revoke~~grant ~~those~~a ~~registrations.~~license Into ~~some~~a ~~circumstances~~third party, ~~violations~~which could ~~lead~~materially todiminish ~~criminal~~the ~~proceedings~~value of those patents. ~~Because~~In addition, many countries limit the enforceability of ~~their~~patents ~~restrictive~~against ~~nature,~~government ~~these~~agencies ~~regulations~~or government contractors. This could limit ~~commercialization~~our ofpotential ~~any~~revenue ofopportunities. Accordingly, our ~~products~~efforts orto ~~product~~enforce ~~candidates~~our ~~that~~intellectual ~~are~~property ~~classified~~rights asaround ~~controlled~~the ~~substances~~world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.

~~The~~In addition, in 2012, the European Patent Package, or EU ~~legislation~~Patent ~~does~~Package, ~~not~~regulations ~~establish~~were ~~different~~passed ~~classes~~with the goal of ~~narcotic~~providing ora ~~psychotropic~~single ~~substances.~~pan-European ~~However~~Unitary Patent and a new European Unified Patent Court, ~~the~~or ~~United~~UPC, ~~Nations~~for ~~(“UN”)~~litigation ~~Single~~involving ~~Convention~~European onpatents. ~~Narcotic~~The ~~Drugs~~EU ofPatent ~~1961~~Package ~~and~~went ~~the~~into UNeffect ~~Convention~~June on1, ~~Psychotropic~~2023. ~~Substances~~Under ofthe ~~1971~~UPC, ~~(“UN~~all ~~Conventions”)~~European ~~codify~~patents, ~~internationally~~including ~~applicable~~those ~~control~~issued ~~measures~~prior to ~~ensure~~ratification of the ~~availability~~European ofPatent ~~narcotic~~Package, ~~drugs~~will ~~and~~by ~~psychotropic~~default ~~substances~~automatically ~~for~~fall ~~medical~~under ~~and~~the ~~scientific~~jurisdiction ~~purposes~~of the UPC. The ~~individual~~UPC EUwill ~~member~~provide ~~states~~our ~~are~~competitors ~~all~~with ~~signatories~~a new forum to ~~these~~centrally UNrevoke ~~Conventions.~~our ~~All~~European ~~signatories~~patents, ~~have~~and aallow ~~dual~~for ~~obligation~~the possibility of a competitor to ~~ensure~~obtain ~~that~~pan-European ~~these~~injunctions. ~~substances~~It ~~are~~will ~~available~~be ~~for~~several ~~medical~~years ~~purposes~~before ~~and~~we towill ~~protect~~understand ~~populations~~the ~~against~~scope ~~abuse~~of patent rights that will be recognized and ~~dependence.~~the ~~The~~strength UNof ~~Conventions~~patent ~~regulate~~remedies ~~narcotic~~that ~~drugs~~will ~~and~~be ~~psychotropic~~provided ~~substances~~by asthe ~~Schedule~~UPC. I,Under ~~II,~~the ~~III~~EU Patent Package, IVwe ~~substances~~will ~~with~~have ~~Schedule~~the IIright ~~substances~~to ~~presenting~~opt our patents out of the ~~lowest~~UPC ~~relative~~over ~~risk~~the offirst ~~abuse~~seven ~~among~~years ~~such~~of ~~substances~~the ~~and~~court’s ~~Schedule~~existence, Ibut ~~and~~doing IVso ~~substances~~may ~~considered~~preclude tous ~~present~~from realizing the ~~highest~~benefits ~~risk~~ of ~~abuse~~the new unified court.

The UN Conventions require signatories to require all persons manufacturing, trading (including exporting and importing) or distributing controlled substances to obtain a license from the relevant authority. Each individual export or import of a controlled substance must also be subject to an authorization. The obligations provided in the UN Conventions and additional requirements are implemented at national level and requirements may vary from one member state to another. In order to develop and commercialize our products in the EU, we would need to comply with the national requirements related to controlled substances which is costly and may affect our development plans in the EU.

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~~Our~~Risks ~~products~~Related ~~and~~to ~~product~~Regulatory ~~candidates~~Approval ~~may~~of beOur ~~associated~~Product ~~with~~Candidates ~~serious~~and ~~adverse~~Other ~~events,~~Legal ~~undesirable~~Compliance ~~side effects or have other properties that could halt their clinical development, prevent their regulatory approval, limit their commercial potential or result in significant negative consequences.~~ Matters

~~Adverse~~If ~~events~~we orare ~~other~~not ~~undesirable~~able ~~side~~to ~~effects~~obtain ~~caused~~required byregulatory ~~our~~approvals ~~products~~for orany of our product candidates, ~~could~~we ~~cause~~will usnot orbe ~~regulatory~~able ~~authorities~~ to ~~interrupt,~~commercialize ~~delay~~them ~~or halt clinical trials~~ and ~~could~~our ~~result~~ability into agenerate ~~more~~revenue ~~restrictive label~~ or ~~the~~profits ~~delay~~could orbe ~~denial of regulatory approvals by the FDA or other comparable foreign regulatory authorities~~limited.

~~During~~The ~~the~~research, ~~conduct~~testing, ofmanufacturing, ~~clinical~~labeling, ~~trials~~packaging, ~~patients~~storage, ~~report~~approval, ~~changes~~sale, inmarketing, ~~their~~advertising ~~health~~and promotion, ~~including illnesses~~pricing, ~~injuries~~export, import and ~~discomforts,~~distribution toof ~~their~~drug ~~study~~products ~~doctor.~~are ~~Often,~~subject itto isextensive ~~not~~regulation ~~possible~~by tothe ~~determine~~FDA ~~whether~~and orother ~~not~~regulatory authorities in the ~~product~~United ~~candidate~~States ~~being~~and ~~studied~~other ~~caused~~countries, ~~these~~which ~~conditions~~regulations differ from country to country and change over time. ItWe isare ~~possible~~not ~~that~~permitted asto wemarket ~~test~~any of our product candidates in ~~larger,~~the ~~longer~~United ~~and~~States ~~more~~until ~~extensive~~we ~~clinical~~receive ~~trials~~approval of an NDA from the FDA, or asin ~~use~~any offoreign ~~these~~countries ~~product~~until ~~candidates~~we ~~becomes~~receive ~~more~~the ~~widespread~~requisite ifapprovals ~~they~~in ~~receive~~such ~~regulatory~~countries. ~~approval,~~In ~~illnesses,~~the ~~injuries~~United States, ~~discomforts~~the ~~and~~FDA ~~other~~generally ~~adverse~~requires ~~events~~the ~~that~~completion ~~were~~of ~~observed~~non-clinical intesting ~~previous~~and clinical trials, asof ~~well~~each asdrug ~~conditions~~to ~~that~~establish ~~did~~its ~~not~~safety ~~occur~~and orefficacy ~~went~~and ~~undetected~~extensive inpharmaceutical ~~previous~~development ~~trials,~~to ~~will~~ensure beits ~~reported~~quality byand ~~patients~~other factors before an NDA is approved. ~~Many~~Of ~~times,~~the ~~side~~large ~~effects~~number ~~are~~of drugs in development, only ~~detectable~~a ~~after~~small ~~investigational~~percentage ~~products~~result in the submission of an NDA to the FDA and even fewer are ~~tested~~approved infor ~~large-scale~~commercialization. ~~clinical~~Even ~~trials~~if ~~or,~~regulatory inapproval ~~some~~is ~~cases~~obtained, ~~after~~subsequent ~~they~~safety, ~~are~~efficacy, ~~made~~quality ~~available~~or toother ~~patients~~issues oncan aresult ~~commercial~~in ~~scale~~a ~~following~~product approval being suspended or withdrawn.

IfIn ~~any~~order ~~serious~~to ~~adverse~~market ~~events~~and ~~occur,~~sell ~~clinical~~our ~~trials~~products orin ~~commercial~~the ~~distribution~~EU ofand any ~~product~~other ~~candidates~~jurisdictions, ~~or products~~ we ~~develop~~must ~~could~~obtain beseparate ~~suspended~~marketing orapprovals ~~terminated,~~ and ~~our~~comply ~~business~~with ~~could~~numerous beand ~~seriously~~varying ~~harmed~~regulatory requirements. ~~Treatment-related~~The ~~side~~approval ~~effects~~procedure ~~could~~varies ~~also~~among ~~affect~~countries ~~patient~~and ~~recruitment~~can ~~and~~involve ~~the~~additional ~~ability~~testing. ofThe ~~enrolled~~time ~~patients~~required to ~~complete~~obtain ~~the~~approval ~~trial~~may ordiffer ~~result~~substantially infrom ~~potential~~that ~~liability~~required ~~claims~~to obtain FDA approval. ~~Regulatory~~The ~~authorities~~regulatory ~~could~~approval ~~order~~process usoutside tothe ~~cease~~United ~~further~~States ~~development~~generally includes all of, ~~deny~~the ~~approval~~risks ~~of,~~associated ~~and/or~~with ~~require~~obtaining usFDA toapproval. ~~cease~~In ~~selling~~addition, ~~our~~in ~~products~~many orcountries ~~product~~outside ~~candidates,~~the ifUnited ~~approved~~States, ~~for~~it ~~any~~is orrequired ~~all~~that ~~targeted~~the ~~indications.~~product Ifbe weapproved ~~are~~for ~~required~~reimbursement tobefore ~~delay,~~the ~~suspend~~product orcan ~~terminate~~be ~~any~~marketed ~~clinical~~in ~~trial~~that orcountry. ~~commercialization~~We ~~efforts,~~may ~~the~~not ~~commercial~~obtain ~~prospects~~approvals offrom ~~our~~regulatory ~~products~~authorities oroutside ~~product~~the ~~candidates~~United ~~may~~States beon ~~harmed,~~a ~~and~~timely ~~our~~basis, ~~ability~~if toat ~~generate~~all. ~~product~~Approval ~~revenues~~by ~~from~~the ~~them~~FDA ordoes ~~other~~not ~~product~~ensure ~~candidates~~approval ~~that~~by weregulatory ~~develop~~authorities ~~may~~in beother ~~delayed~~countries or ~~eliminated. Additionally~~jurisdictions, ifand ~~one~~approval orby ~~more~~one ofregulatory ~~our~~authority ~~product~~outside ~~candidates~~the ~~receives~~United ~~marketing~~States ~~approval~~does ~~and~~not weensure orapproval ~~others~~by ~~later~~regulatory ~~identify~~authorities ~~undesirable~~in ~~side~~other ~~effects~~countries or ~~adverse~~jurisdictions ~~events~~or ~~caused~~ by ~~such~~the ~~products~~FDA. However, afailure ~~number~~to ofobtain ~~potentially~~approval ~~significant~~in ~~negative~~one ~~consequences~~jurisdiction ~~could~~may ~~result,~~impact ~~including~~our ~~but~~ability ~~not~~to ~~limited~~obtain ~~to:~~approval elsewhere.

●The ~~regulatory~~process ~~authorities~~of ~~may~~obtaining ~~suspend,~~regulatory ~~limit or withdraw~~ approvals ofis ~~such product~~expensive, oroften ~~seek~~takes anmany ~~injunction~~years, ~~against~~if ~~its~~approval ~~manufacture~~is orobtained ~~distribution;~~at ●all, ~~regulatory~~and ~~authorities~~can ~~may~~vary ~~require~~substantially ~~additional~~based ~~warnings~~upon, onamong ~~the~~other ~~label~~things, ~~including~~the ~~“boxed” warnings~~type, orcomplexity ~~issue~~and ~~safety~~novelty ~~alerts,~~of ~~Dear~~the ~~Healthcare~~product ~~Provider~~candidates ~~letters~~involved, ~~press~~the ~~releases~~jurisdiction orin ~~other~~which ~~communications~~regulatory ~~containing~~approval ~~warnings~~is orsought ~~other~~and ~~safety information about~~ the ~~product;~~substantial ●discretion weof ~~may~~the beregulatory ~~required~~authorities. toChanges ~~change~~in the ~~way~~regulatory ~~the~~approval ~~product~~policy isduring ~~administered~~the ordevelopment ~~conduct~~period, ~~additional~~changes ~~clinical~~in ~~trials~~ or ~~post-approval~~the ~~studies;~~enactment ●of weadditional ~~may~~statutes beor ~~required~~regulations, toor ~~create~~changes ain ~~risk~~regulatory ~~evaluation~~review ~~and~~for ~~mitigation~~a ~~strategy,~~submitted orproduct ~~REMS,~~application ~~which~~may ~~could~~cause ~~include~~delays ain ~~medication~~the ~~guide~~approval ~~outlining~~or ~~the~~rejection ~~risks~~ of ~~such~~an ~~side~~application ~~effects~~or ~~for~~may ~~distribution~~result toin ~~patients;~~future ●withdrawal weof ~~may~~approval. beFailure ~~subject~~ to ~~fines,~~obtain ~~injunctions~~regulatory ormarketing ~~the~~approval ~~imposition~~ of ~~criminal~~our ~~penalties;~~product ●candidates wewill ~~could~~prevent beus ~~sued~~from ~~and~~commercializing ~~held~~those ~~liable~~product ~~for~~candidates, ~~harm~~and ~~caused~~our ability to ~~patients;~~generate ~~and~~revenue ●will ~~our~~be ~~reputation may suffer~~impaired.

~~Any~~For ofmore ~~these~~detailed ~~events~~information ~~could~~regarding ~~prevent~~the usregulatory ~~from~~requirements ~~achieving~~for orapproval ~~maintaining~~of ~~market~~product ~~acceptance~~candidates ofin ~~our~~the ~~products~~United orStates ~~any~~and ofEU, ~~our~~see ~~product~~"Item ~~candidates,~~1. ifBusiness ~~approved,~~- U.S. Government Regulation and ~~could~~Product ~~seriously~~Approval" ~~harm~~and ~~our~~"Item ~~business~~1. Business - Foreign Regulation" above in this Annual Report on Form 10-K.

If we experience delays or difficulties in the enrollment of subjects in clinical trials, our receipt of necessary regulatory approvals could be delayed or prevented.

We may not be able to initiate or continue clinical trials for our product candidates if we are unable to locate and enroll a sufficient number of eligible subjects to participate in these trials as may be required by the FDA or similar regulatory authorities outside the United States. Subject enrollment is affected by other factors including:

•the size and nature of the subject population specified in the trial protocol, especially in indications for rare diseases;

•the eligibility criteria for the study in question;

•the perceived risks and benefits of the product candidate under study;

•ongoing trials by competitors for similar indications as our product candidates;

•severe or unexpected drug-related adverse events experienced by subjects in a clinical trial;

•the availability of drugs approved to treat the diseases or conditions under study;

•the patient referral practices of physicians;

•the severity of the disease or condition under investigation;

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We•the ~~may~~ability ~~expend our limited resources~~ to ~~pursue~~obtain ~~a particular product candidate or indication~~ and ~~fail~~maintain tosubject ~~capitalize~~informed ~~on product candidates or indications that may be more profitable or for which there is a greater likelihood of success.~~consent;

Because we have limited financial and management resources, we focus on research programs and product candidates that we identify for specific indications. As a result, we may forego or delay pursuit of opportunities with other product candidates or for other indications that later prove to have greater commercial potential. Our resource allocation decisions may cause us to fail to capitalize on viable commercial drugs or profitable market opportunities. Our spending on current and future research and development programs and product candidates for specific indications may not yield any commercially viable products. If we do not accurately evaluate •the ~~commercial~~clinical ~~potential~~trial ~~or target market for a particular product candidate~~design, weincluding ~~may~~required ~~relinquish valuable rights to that product candidate through collaboration~~tests, ~~licensing~~procedures ~~or other royalty arrangements in cases in which it would have been more advantageous for us to retain sole development~~ and ~~commercialization rights to such product candidate.~~follow-up;

If •the ~~EAP~~ isability ~~terminated prior~~ to ~~commercialization~~monitor ofsubjects ~~arimoclomol~~adequately induring ~~the EU, if approved, it will have a material adverse effect on our business, results of operations, cash flows, financial condition~~ and~~/or~~ ~~prospects.~~after treatment;

~~Arimoclomol~~•delays ~~is currently available to NPC patients~~ in ~~France,~~adding ~~Germany~~new, ~~and~~ ~~other~~or ~~EU member~~withdrawals ~~states through the EAP. The EAP is expected to remain in place until arimoclomol becomes commercially available in each~~ of ~~the current EAP markets. If the EAP is terminated prior to commercialization of arimoclomol~~existing, itinvestigators ~~will~~and ~~have~~clinical asites; ~~material adverse effect on our business, results of operations, cash flows, financial condition~~ and~~/or prospects.~~

•the proximity and availability of clinical trial sites for prospective subjects.

Our inability to enroll a sufficient number of subjects for clinical trials would result in significant delays, increased costs and could require us to abandon one or more clinical trials altogether.

Interim, topline, or preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data.

From time to time, we may publicly disclose topline or preliminary data from our preclinical studies and clinical trials, which is based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change following a more comprehensive review of the data related to the particular study or trial. As a result, the preliminary or topline results that we report may differ from future results of the same studies, or different conclusions or considerations may qualify such results, once additional data has been received and fully evaluated. Topline data also remains subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. As a result, preliminary or topline data should be viewed with caution until the final data are available.

From time to time, we may also disclose interim data from our preclinical studies and clinical trials. Interim data from clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available or as patients from our clinical trials continue other treatments for their disease. Adverse differences between preliminary or interim data and final data could significantly harm our business prospects.

Our approved products are, and any of our product candidates for which we obtain marketing approval will be, subject to significant post-marketing regulatory requirements and oversight.

Our approved products are, and any of our product candidates for which we obtain marketing approval will be, subject to significant post-marketing regulatory requirements and oversight, including the submission of reports to regulatory authorities and surveillance to monitor the safety and efficacy of the product, significant limitations related to use restrictions for specified age groups, warnings, precautions or contraindications, and burdensome post-approval study or risk management requirements. For example, we are required to conduct pediatric studies related to AZSTARYS to evaluate its safety and effectiveness for the claimed indication in pediatric patients. Under the AZSTARYS License Agreement, Corium is responsible for these regulatory activities going forward, and we cannot guarantee they will be complied with.

For MIPLYFFA and any other approved products, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion and recordkeeping for the product will be subject to extensive and ongoing regulatory requirements. These requirements include submissions of safety and other post-marketing information and reports, registration, as well as continued compliance with cGMP and comparable foreign regulations and GCP for any clinical trials that we conduct post-approval. Non-compliance with EU requirements regarding safety monitoring or pharmacovigilance, and with requirements related to the development of drugs for the pediatric population, can also result in significant financial penalties.

Our inability to maintain compliance with post-marketing regulatory requirements may inhibit our ability to commercialize our products and generate revenue, and could require us to expend significant time and resources in response and could generate negative publicity. In addition, the policies of the FDA, the EMA and other regulatory authorities may change, and additional government regulations may be enacted that could impair our business. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may be subject to enforcement action.

For more detailed information regarding post-approval regulatory requirements, see "Item 1. Business - U.S. Government Regulation and Product Approval - Post-Approval Requirements" above in this Annual Report on Form 10-K.

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~~Risks~~Our ~~Related~~approved toproducts ~~Our~~are, ~~Business~~and if marketing approval of any of our product candidates is granted, ~~Our~~such ~~Financial~~product ~~Position~~candidates ~~and~~may ~~Our~~be, ~~Capital~~subject ~~Needs~~ to limitations on the indicated uses for which the product may be marketed.

~~Our~~Products ~~future~~may ~~results~~be ~~will~~approved ~~suffer~~with ifa label that limits their approved uses, including more limited subject populations, than we do request, and regulatory authorities may require that contraindications, warnings or precautions be included in the product labeling, including a boxed warning, or may approve a product candidate with a label that does not ~~effectively~~include ~~manage~~the ~~our~~labeling ~~expanded~~claims ~~operations~~necessary or desirable for the successful commercialization of that product candidate, which could limit sales of the product. For instance, the label for AZSTARYS contains black box warnings regarding the risks of abuse and dependence. Violations of the FFDCA relating to the promotion of prescription drugs may lead to a number of actions and penalties, including warning letters, cyber letters, or untitled letters, adverse publicity, the requirement for dear-health-care-provider letters or other corrective information, fines and other monetary penalties, civil or criminal prosecution, including False Claims Act liability, restrictions on our operations and other operating requirements through consent decrees or corporate integrity agreements, debarment, exclusion from participation in federal health care programs and refusal of government contracts or future orders under existing contracts, among other consequences.

~~Due~~Current ~~to the additional of our commercialization capabilities~~ and ~~through~~future ~~our~~healthcare ~~strategic~~reform ~~transactions,~~legislation ~~the~~or ~~size~~regulation ~~and scope of our operations increased. We~~ may ~~continue~~increase tothe ~~expand~~difficulty ~~our size~~ and ~~operations~~cost through further expansion of capabilities, additional acquisitions or other strategic transactions. Our future success depends, in part, upon our ability to manage our expanded business, which may pose substantial challenges for ~~our management,~~us ~~including challenges related~~ to ~~the~~obtain ~~management~~marketing ~~and~~approval ~~monitoring~~ of ~~new operations and locations and associated increased costs and complexity. There can be no assurances that we will be successful in managing~~ our ~~expanded~~product ~~business~~candidates ~~or that we will realize the expected economies of scale, synergies~~ and ~~other~~increase ~~benefits currently anticipated from~~ the ~~Merger~~cost orto ~~anticipated~~commercialize ~~from~~our ~~any~~approved ~~additional acquisitions or strategic transactions~~products.

AIn ~~variety~~the United States and many foreign jurisdictions, there have been a number of ~~risks~~legislative ~~associated~~and ~~with~~regulatory ~~international~~changes ~~operations~~and proposed changes regarding the healthcare system that could, ~~materially~~among ~~adversely~~other ~~affect~~things, prevent or delay marketing approval of our ~~business~~product candidates, restrict or regulate post-approval activities and affect the ability to profitably sell approved products. Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and/or expanding access. In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives. For example, in 2010, the ACA was signed into law. The ACA substantially changed the way healthcare is financed by both governmental and private insurers, and significantly affects the U.S. pharmaceutical industry.

WeIn ~~expect~~addition, toother ~~engage~~legislative inchanges that have a significant ~~cross-border~~impact ~~activities~~on the pharmaceutical industry have been proposed and adopted since the ACA was enacted. The Budget Control Act of 2011, among other things, included aggregate reductions to Medicare payments to providers, which went into effect in April 2013, and, wedue to subsequent legislative amendments, will bestay ~~subject~~in effect through 2032. The American Taxpayer Relief Act of 2012, among other things, further reduced Medicare payments to ~~risks~~several ~~related~~providers and increased the statute of limitations period for the government to ~~international~~recover ~~operations~~overpayments to providers from three to five years. The American Rescue Plan Act of 2021 eliminated the statutory Medicaid drug rebate cap, ~~including:~~beginning January 1, 2024. The rebate was previously capped at 100% of a drug's average manufacturer price.

●On ~~different~~August ~~regulatory~~16, ~~requirements~~2022, ~~for~~the ~~maintaining~~Inflation ~~approval~~Reduction Act of ~~drugs~~2022 in(the ~~foreign~~“IRA”) ~~countries;~~was ●signed ~~differing~~into ~~payor~~law. ~~reimbursement~~Among ~~regimes~~other things, ~~governmental~~the ~~payors~~IRA orrequires ~~patient~~manufacturers ~~self-pay~~of ~~systems~~certain ~~and~~drugs ~~price~~to ~~controls;~~engage ~~● reduced protection for contractual and intellectual property rights~~ in ~~some~~price ~~countries;~~negotiations ●with ~~unexpected changes in tariffs~~Medicare, ~~trade~~with ~~barriers~~prices ~~and~~that ~~regulatory~~can ~~requirements;~~be ●subject ~~economic~~to ~~weakness,~~a ~~including inflation~~cap, ~~labor~~imposes ~~shortages,~~rebates ~~supply~~under ~~chain~~Medicare ~~shortages,~~Part orB ~~other~~and ~~economic~~Medicare orPart ~~political~~D ~~uncertainties~~to orpenalize ~~instability~~price inincreases ~~particular~~that ~~foreign~~outpace ~~economies~~inflation ~~and~~(first ~~markets;~~due ●in ~~compliance with tax~~2023), ~~employment,~~and ~~immigration~~replaces ~~and~~the ~~labor~~Part ~~laws~~D ~~for~~coverage ~~employees~~gap ~~living~~discount orprogram ~~traveling~~with ~~abroad;~~a ●new ~~foreign~~manufacturer ~~currency~~discounting ~~fluctuations,~~program (which ~~could~~began ~~result~~ in ~~increased~~2025). ~~operating~~The ~~expenses~~drug ~~and~~price ~~reduced~~negotiation ~~revenue,~~program ~~and~~is ~~other~~currently ~~obligations~~subject ~~incident~~ to ~~doing~~legal ~~business~~challenges, ~~in another country; ● workforce uncertainty in countries where labor unrest is more common than in North America; ● tighter restrictions on privacy~~ and the ~~collection~~impact ~~and use~~ of ~~patient~~the ~~and~~IRA ~~clinical~~on ~~trial~~us ~~participant data;~~ and ●the ~~business~~pharmaceutical ~~interruptions~~industry ~~resulting~~cannot ~~from~~yet ~~geopolitical~~be ~~actions,~~fully ~~including war and terrorism~~determined, orbut ~~natural~~is ~~disasters~~likely ~~including~~to ~~earthquakes,~~be ~~typhoons, floods and fires~~significant.

WeThe ~~may~~One ~~not~~Big beBeautiful ~~able~~Bill toAct, ~~retain~~which ~~suppliers~~was orenacted ~~distributors~~in July 2025, orimposes ~~suppliers~~significant orreductions ~~distributors~~in ~~may~~the ~~seek~~funding toof ~~modify~~the ~~contractual~~Medicaid ~~relationships~~program. ~~with~~Such ~~us,~~reductions ~~which~~are ~~could~~expected ~~have~~to andecrease ~~adverse~~the ~~effect~~number onof ~~our business~~persons enrolled in Medicaid and ~~operations.~~reduce ~~Third~~the ~~parties~~services ~~may~~covered ~~terminate~~by orMedicaid, ~~alter~~which ~~existing~~could ~~contracts~~adversely affect sales of approved products or ~~relationships~~of ~~with~~any usproduct candidate that we commercialize.

WeThe ~~may~~current ~~experience~~U.S. ~~impacts~~administration onis ~~relationships~~pursuing ~~with~~a ~~customers,~~two-fold ~~suppliers~~strategy ~~and~~to ~~distributors~~reduce ~~that~~drug ~~may~~costs ~~harm~~in ~~our~~the ~~business~~United States. While it is unclear whether and ~~results~~how ofproposals ~~operations.~~will ~~Certain~~be ~~suppliers~~implemented, orthese ~~distributors~~policies ~~may~~are ~~seek~~likely to ~~terminate~~have ora ~~modify~~negative ~~contractual~~impact ~~obligations~~on ~~following~~the pharmaceutical industry and on our ability to receive adequate revenues for our products. On the ~~Merger~~one ~~whether~~hand, orthe current U.S. administration has threatened to impose significant tariffs on pharmaceutical manufacturers that do not ~~contractual~~adopt ~~rights~~pricing ~~are~~policies ~~triggered~~such as most favored nation pricing, which would tie the price for drugs in the United States to the lowest price in a ~~result~~group of other countries. In response, multiple manufacturers have entered into confidential pricing agreements with the ~~Merger~~federal government. ~~There~~On ~~can~~the beother nohand, ~~guarantee~~the ~~that~~current ~~our~~U.S. oradministration ~~Acer's~~is ~~prior~~pursuing ~~customers~~traditional regulatory pathways to impose drug pricing policies and published two proposed regulations in December 2025, ~~suppliers~~referred to as Globe and ~~distributors~~Guard. ~~will~~If ~~remain~~finalized, ~~with~~these orregulations ~~continue~~would implement mandatory payment models under which manufacturers of eligible drugs would be required to ~~have~~pay rebates to the federal government on a ~~relationship~~portion of the units of their drugs that are reimbursed by Medicare, with usthe orrebate doamount sobased on ~~contractual~~most ~~terms~~favored ~~amenable~~nation topricing. usImposing a rebate in the United States that is based on drug prices outside the United States would mark a drastic and unprecedented shift in the U.S. Ifpharmaceutical ~~any~~market, ~~suppliers~~and orwhile ~~distributors~~the ~~seek~~impact of the Globe and Guard proposed regulations, if finalized, cannot yet be determined, it is likely to ~~terminate~~be significant. Even proposals or ~~modify~~executive ~~contractual~~actions ~~obligations~~that orare ~~discontinue~~ultimately ~~their~~deemed ~~relationship~~unlawful ~~with~~could ~~us,~~negatively ~~then~~impact the U.S. pharmaceutical sector and our business, ~~and~~for ~~results~~example ofby ~~operations~~causing ~~may~~uncertainty beand ~~harmed~~delaying development and commercialization efforts.

If we fail to maintain effective internal control over financial reporting and disclosure controls and procedures, we may not be able to accurately report our financial results or report them in a timely manner, which may adversely affect investor confidence in us and, as a result, the value of our common stock.

Our management is required to report annually on the effectiveness of our internal control over financial reporting pursuant to Section 404 of the Sarbanes-Oxley Act, or Section 404. The rules governing the standards that must be met for our management to assess our internal control over financial reporting are complex and require significant documentation, testing and possible remediation.

Our failure to certify the effectiveness of our internal control over financial reporting or our disclosure controls and procedures, or the identification of the material weakness, could subject us to regulatory scrutiny and a loss of public confidence, which could have a material adverse effect on our business and our stock price. If we identify material weaknesses or significant deficiencies, we may not be able to remediate them in time to meet the deadline imposed by the Sarbanes-Oxley Act for compliance with the requirements of Section 404. In addition, we may encounter problems or delays in completing the implementation of any requested improvements and, if and when such a report is required, receiving a favorable attestation report from our independent registered public accounting firm. If we do not maintain adequate financial and management personnel, processes and controls, we may not be able to manage our business effectively or accurately report our financial performance on a timely basis, which could cause a decline in our common stock price and adversely affect our results of operations and financial condition.

We have incurred significant recurring negative net operating cash flows. We cannot predict if we will incur positive or negative net operating cash flows over the next several years, which may impact our ability to continue as a going concern, and we may never achieve or maintain profitability.

We have historically had significant negative net operating cash flows since inception. For the years ended December 31, 2024, and 2023, net cash used in operations was $69.7 million and $33.5 million, respectively. We have financed our operations through December 31, 2024, with funds raised in private placements of redeemable convertible preferred stock, the issuance of convertible promissory notes and term debt, our initial public offering and other public and private offerings of our common stock, as well as through royalties and milestone payments received under the AZSTARYS License Agreement, reimbursements related to arimoclomol under the EAP, and product sales of OLPRUVA and MIPLYFFA.

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WeAt ~~have~~the ~~devoted~~state ~~substantially~~level, ~~all~~legislatures ofare ~~our~~increasingly ~~financial~~passing ~~resources~~legislation and ~~efforts~~implementing regulations designed to ~~research~~control ~~and~~pharmaceutical ~~development~~product pricing, including ~~preclinical~~price ~~studies~~or ~~and~~patient ~~clinical~~reimbursement ~~trials~~constraints, ~~and~~discounts, ~~commercialization.~~restrictions Weon ~~are~~certain ~~still~~product inaccess ~~the~~and ~~early~~marketing ~~stages~~cost ofdisclosure, ~~commercializing~~drug ~~our~~price ~~approved~~reporting ~~products~~and other transparency measures. WeSome states have ~~devoted~~enacted ~~substantial~~legislation ~~financial~~creating ~~resources~~so-called ~~and~~prescription ~~efforts~~drug affordability boards, which ultimately may attempt to ~~research~~impose ~~and~~price ~~development,~~limits ~~including~~on ~~preclinical~~certain ~~studies~~drugs ~~and~~in ~~clinical~~these ~~trials~~states, and ~~our~~ ~~product~~at ~~candidates~~least ~~are in~~one ~~various~~state ~~stages~~board ofis ~~development~~imposing an upper payment limit. WeStates ~~have only~~are ~~completed~~also ~~development~~seeking ofto implement general, ~~and~~across ~~received~~the ~~regulatory~~board ~~approval~~price caps for pharmaceuticals, ~~AZSTARYS~~or ~~and~~are ~~MIPLYFFA.~~seeking ~~We expect~~ to ~~continue~~regulate todrug ~~incur~~distribution. ~~significant~~These ~~expenses~~new ~~and~~laws ~~operating~~may ~~losses~~result ~~over~~in ~~the~~additional ~~next~~reductions ~~several~~in ~~years~~Medicare and ~~our~~ ~~net~~other ~~losses~~healthcare ~~may~~funding, ~~fluctuate~~which ~~significantly~~could ~~from~~negatively ~~quarter~~impact tocommercialization ~~quarter~~of approved products, and, ~~year~~accordingly, toour ~~year as~~financial ~~we:~~operations.

●In ~~continue~~the ~~our~~EU, ~~ongoing~~pharmaceutical ~~preclinical~~legislation ~~studies,~~has ~~clinical~~been ~~trials~~undergoing ~~and~~a ~~our~~complete ~~product~~review ~~development~~process ~~activities~~in the context of the Pharmaceutical Strategy for ~~our~~Europe ~~pipeline~~initiative, oflaunched ~~product~~by ~~candidates;~~the ●European ~~seek~~Commission ~~regulatory~~in ~~approvals~~November ~~for~~2020. ~~product~~The ~~candidates~~European ~~that~~Commission’s ~~successfully~~proposal ~~complete~~for ~~clinical~~revision ~~trials;~~of ●several ~~continue~~legislative ~~research~~instruments ~~and~~related ~~preclinical~~to ~~development~~medicinal ~~and~~products ~~initiate~~(potentially ~~clinical~~reducing ~~trials~~the duration of ~~our~~regulatory ~~product~~data ~~candidates;~~protection, ●revising ~~seek~~the toeligibility ~~discover~~for ~~and~~expedited ~~develop~~pathways, ~~additional~~etc.) ~~product~~was ~~candidates~~published ~~either~~on ~~internally~~April or26, in2023. ~~partnership~~The ~~with~~proposed ~~other~~revisions ~~pharmaceutical~~(affecting ~~companies;~~the ●duration ~~adapt~~of ~~our~~ regulatory ~~compliance~~data ~~efforts~~protection toand ~~incorporate~~market ~~requirements~~protection, ~~applicable~~including tofor ~~marketed~~orphan medicinal products;, ●revising ~~maintain~~the eligibility for expedited pathways, ~~expand~~etc.) ~~and~~remain ~~protect~~to ~~our~~be ~~intellectual~~formally ~~property~~adopted ~~portfolio;~~by ●the ~~incur~~European ~~additional~~Parliament ~~legal~~and Council of the EU , ~~accounting~~which ~~and~~is ~~other~~not ~~expenses~~anticipated inbefore ~~operating~~early as2026. aThe ~~public~~proposed ~~company;~~changes ~~and~~are ●not ~~add~~expected ~~operational~~to ~~systems~~enter into application before 2028 and ~~personnel,~~may ifhave ~~needed,~~a tosignificant ~~support~~impact ~~any~~on ~~future~~the ~~commercialization~~biopharmaceutical ~~efforts~~industry in the long term.

ToWe ~~become~~cannot ~~and~~be ~~remain~~sure ~~profitable,~~whether weadditional ~~must~~legislative ~~succeed~~changes inwill ~~developing~~be ~~and~~enacted, ~~eventually~~or ~~commercializing~~whether ~~prodrugs~~the ~~that~~FDA's ~~generate~~or ~~significant~~foreign ~~revenue.~~regulations, ~~This~~guidance ~~will~~or ~~require~~interpretations uswill to be ~~successful~~changed. inWe aexpect ~~range~~that ofthe ~~challenging~~healthcare ~~activities,~~reform ~~including~~measures ~~completing~~that ~~preclinical~~have ~~studies~~been ~~and~~adopted ~~clinical trials~~ and ~~obtaining~~may ~~regulatory~~be ~~approval~~adopted ofin ~~our~~the ~~product~~future ~~candidates~~may, ~~and~~among ~~manufacturing,~~other ~~marketing and selling~~things, ~~whether~~result ~~ourselves~~in ormore ~~through~~rigorous acoverage ~~license~~criteria ~~with~~as awell ~~third~~as ~~party, any~~additional ofdownward ~~our product~~pressure ~~candidates~~on ~~for~~the ~~which~~price that we ~~may~~receive ~~obtain~~for ~~regulatory~~any ~~approval,~~approved ~~as well as discovering and developing additional~~ product ~~candidates~~. WeAny ~~are~~reduction in ~~various~~reimbursement ~~stages~~from ofMedicare ~~these~~or ~~activities~~other ~~for~~government ~~our~~programs ~~product~~may ~~candidates~~result ~~and~~in wea ~~cannot~~similar ~~guarantee~~reduction ~~that~~in ~~any~~payments ~~strategy~~from weprivate ~~adopt~~payors. ~~will~~The beimplementation ~~successful. We~~of ~~may~~cost ~~never~~containment ~~succeed~~measures inor ~~commercialization~~other ~~activities~~healthcare ~~and,~~reforms ~~even~~may ifprevent weus ~~do,~~from ~~may~~being ~~never~~able to generate revenue, ~~that~~attain isor ~~significant~~maintain ~~enough~~profitability, toor ~~achieve~~commercialize ~~profitability~~our product candidates.

~~Because~~We ofmay ~~the~~not ~~numerous risks and uncertainties associated with prodrug development, we are unable to accurately predict the timing or amount of expenses or when, or if, we will~~ be able to ~~achieve~~obtain ~~profitability. If we are required by regulatory authorities to perform studies in addition to those currently expected,~~ or ifmaintain ~~there are any delays in~~ the ~~initiation~~benefits ~~and~~associated ~~completion~~with oforphan ~~our~~drug ~~clinical~~designation, ~~trials~~including or the ~~development~~potential offor ~~any~~market ~~of our product candidates, our expenses could increase~~exclusivity.

~~Even~~Regulatory ifauthorities wein ~~achieve~~some ~~profitability~~jurisdictions, weincluding the United States, may ~~not~~designate bedrugs ~~able~~for torelatively ~~sustain~~small orpatient ~~increase~~populations ~~profitability~~as onorphan drugs. Under the Orphan Drug Act of 1983, the FDA may designate a ~~quarterly~~drug oras ~~annual~~an ~~basis.~~orphan ~~Our~~product ~~failure~~if it is intended to ~~become~~treat ~~and~~a ~~remain~~rare ~~profitable~~disease ~~would~~or ~~depress~~condition. ~~our~~In ~~value~~the ~~and~~United ~~could~~States, ~~impair~~orphan ~~our~~designation ~~ability~~entitles a party to ~~raise~~financial ~~capital~~incentives such as opportunities for grant funding toward clinical trial costs, ~~expand~~tax ~~our~~advantages ~~business~~and user-fee waivers. In addition, ~~maintain~~if ~~our~~a ~~research~~product ~~and~~candidate ~~development~~that ~~efforts~~has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, ~~obtain~~the product ~~approvals~~is entitled to orphan drug exclusivity, ~~diversify~~which ~~our~~means that the FDA may not approve any other applications, including an NDA, to market the same product ~~offerings~~for the same approved use or ~~continue~~indication ~~our~~within ~~operations.~~such Arare ~~decline~~disease or condition for seven years, except in ~~our~~limited ~~value~~circumstances, ~~could~~such ~~also~~as ~~cause~~a ~~you~~showing of clinical superiority to ~~lose~~the ~~all~~product orwith ~~part~~orphan ofdrug ~~your~~exclusivity ~~investment~~within the relevant approved use or indication.

Identifying potential product candidates and conducting preclinical studies and clinical trials is a time-consuming, expensive and uncertain process that takes years to complete, and we may not generate the necessary data or results required to obtain regulatory approval for our product candidates or claims necessary to make such candidates profitable and achieve product sales. In addition, our approved products or any of our product candidates, if approved, may not achieve commercial success. Our commercial revenue will be derived from sales of prodrug products. We cannot guarantee that we or Corium will be able to successfully commercialize OLPRUVA, MIPLYFFA, or AZSTARYS to any certain level, or any of the ~~product~~ ~~candidates subject to the AZSTARYS License Agreement~~EU, ~~even~~orphan ifdesignation ~~approved,~~is orgranted ~~that~~by ~~we will ever receive any additional payments under~~ the ~~AZSTARYS~~EC ~~License~~based ~~Agreement~~on ~~from~~a ~~the~~scientific ~~commercial~~opinion ~~sales~~ of ~~AZSTARYS or any future payments under~~ the ~~AZSTARYS~~EMA’s ~~License~~Committee ~~Agreement. Accordingly,~~for weOrphan ~~will~~Medicinal ~~need~~Products tobased ~~continue to rely~~ on ~~additional~~certain ~~financing to achieve our business objectives~~criteria. ~~Adequate~~Orphan ~~additional~~designation ~~financing~~entitles ~~may~~a ~~not~~party ~~be available~~ to usfinancial onincentives ~~acceptable~~such ~~terms,~~as orreduction ~~at all. To the extent that we raise additional capital through the sale~~ of ~~equity or debt securities~~fees, ~~the~~fee ~~terms of those securities or debt may restrict our ability to operate. Any future debt financing and equity financing~~waivers, ifprotocol ~~available~~assistance, ~~may involve agreements that include, covenants limiting~~ and ~~restricting~~access ~~our ability~~ to ~~take~~the ~~specific~~centralized ~~actions,~~marketing ~~such~~authorization asprocedure. ~~incurring additional debt~~Moreover, ~~making~~upon ~~capital~~grant ~~expenditures,~~of ~~entering~~a ~~into~~marketing ~~profit-sharing~~authorization orand ~~other~~assuming ~~arrangements~~the orrequirement ~~declaring~~for ~~dividends.~~orphan Ifdesignation weare ~~raise~~also ~~additional~~met ~~funds~~at ~~through~~the ~~collaborations,~~time ~~strategic~~the ~~alliances or~~ marketing, ~~distribution~~authorization oris ~~licensing arrangements with third parties~~granted, weorphan ~~may~~medicinal beproducts ~~required~~are toentitled ~~relinquish valuable rights~~ to ~~our~~a ~~technologies,~~ten-year ~~future~~period ~~revenue~~of ~~streams,~~market ~~research~~exclusivity ~~programs~~for orthe ~~product~~approved ~~candidates~~therapeutic ~~or to grant licenses on terms that may not be favorable to us~~indication. InThe ~~addition,~~period weof ~~may seek additional capital due to favorable~~ market ~~conditions~~exclusivity oris ~~strategic~~extended ~~considerations~~by ~~even~~two ifyears ~~we believe we have sufficient funds~~ for ~~our~~orphan ~~current~~medicinal orproducts ~~future~~that ~~operating~~have ~~plans.~~also Ifcomplied wewith ~~are~~an ~~unable~~agreed toPediatric ~~raise~~Investigation ~~capital when needed or on attractive terms, we could be forced to delay, reduce or altogether cease our research and development programs or future commercialization efforts~~Plan.

However, orphan drug exclusivity for a product may not effectively protect the product from competition because different drugs with different active ingredients can be approved for the same approved use or indication within the applicable rare disease or condition. Even after an orphan drug is approved, the FDA or comparable foreign regulatory authority can subsequently approve the same drug for the same approved use or indication within the relevant rare disease or condition if such regulatory authority concludes that the later drug is clinically superior because it is shown to be safer, more effective or makes a major contribution to patient care. Orphan drug exclusivity may also be lost if the FDA later determines that the initial request for designation was materially defective.

In the EU, during the market exclusivity period, marketing authorizations may be granted to a similar medicinal product with the same orphan indication if: (i) the applicant can establish that the second medicinal product, although similar to the orphan medicinal product already authorized is safer, more effective or otherwise clinically superior to the orphan medicinal product already authorized; (ii) the marketing authorization holder for the orphan medicinal product grants its consent; or (iii) if the marketing authorization holder of the orphan medicinal product is unable to supply sufficient quantities of product.

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WeOur ~~may need additional~~current ~~funding~~and tofuture ~~pursue~~relationships ~~our~~with ~~business~~healthcare ~~objectives.~~professionals, Ifprincipal weinvestigators, ~~are~~consultants, ~~unable~~customers toand ~~raise~~third-party ~~capital~~payors ~~when~~in ~~needed,~~the weUnited ~~could~~States and elsewhere may be ~~forced~~subject to ~~delay~~applicable anti-kickback, ~~reduce~~fraud orand ~~altogether~~abuse, ~~cease~~false ~~our development~~claims, ~~programs~~physician orpayment ~~commercialization~~transparency, ~~efforts~~and orother ~~cease~~healthcare ~~operations~~laws ~~altogether~~and regulations, which could expose us to penalties.

~~Based~~Healthcare onproviders ~~our~~and ~~current~~third-party ~~operating~~payors ~~plan,~~in ~~excluding~~ the ~~expected~~ ~~net~~United ~~proceeds~~States ~~from~~and ~~our~~elsewhere ~~sale~~play ofa ~~the~~primary ~~MIPLYFFA~~role ~~PRV~~in ~~(subject~~the torecommendation ~~customary closing conditions), our existing resources are expected to be sufficient to fund operating expense~~ and ~~capital~~prescription ~~investment~~of ~~requirements~~drug ~~into 2029~~products. Our ~~liquidity~~and ~~needs~~our ~~will~~commercial bepartners' ~~largely~~current ~~determined~~and byfuture ~~the~~arrangements ~~success~~with ofhealthcare ~~operations~~professionals, ~~through~~principal ~~the~~investigators, ~~progression~~consultants, ofcustomers ~~our products~~ and ~~product~~third-party ~~candidates~~payors ~~in the future. We also~~ may ~~consider~~expose ~~other~~us ~~sources~~ to ~~fund~~broadly ~~operations~~applicable ~~including:~~fraud ~~(1)~~and ~~out-licensing~~abuse ~~rights~~and toother ~~certain~~healthcare oflaws, ~~our~~including, ~~technologies~~without ~~and product candidates~~limitation, ~~pursuant~~the toAnti-Kickback ~~which~~Statute ~~we would receive cash royalties~~ and ~~milestones;~~the ~~(2)~~False ~~raising~~Claims ~~additional~~Act, ~~capital~~that ~~through~~may ~~equity~~constrain orthe ~~debt~~business ~~financings~~ or ~~from~~financial ~~other~~arrangements ~~sources;~~and ~~(3)~~relationships ~~obtaining~~through ~~product candidate regulatory approvals,~~ which ~~would~~we ~~generate revenue, milestones~~ and ~~cash~~our ~~flow;~~commercial ~~(4)~~partners ~~reducing spending on one or more research and development programs~~sell, ~~including~~market ~~by discontinuing development;~~ and~~/or~~ ~~(5)~~distribute ~~restructuring~~approved ~~operations to change our overhead structure~~products. WeIn ~~are~~addition, inwe ~~the~~may ~~early~~be ~~stages~~subject ofto ~~our~~transparency ~~commercialization~~laws ~~effort~~with ~~for~~respect ~~OLPRUVA~~to ~~and~~drug ~~MIPLYFFA~~pricing and dotransfers ~~not~~of ~~yet~~value ~~have~~made ~~a substantial basis~~ to ~~project~~physicians ~~future earnings,~~ and ~~our~~ other ~~sources~~healthcare ofprofessionals. ~~revenue~~The ~~are~~applicable ~~not~~federal, ~~sufficient~~state toand ~~sustain~~foreign ~~our~~healthcare ~~present~~laws ~~activities~~that onmay ~~their~~affect ~~own. Accordingly,~~ our ability to ~~continue~~operate asinclude athe ~~going concern may require us to obtain additional financing to fund our operations.~~following:

We expect that our only sources of revenues will be through payments arising from sales of our approved products and any other future arrangements related to one of our product candidates. We cannot guarantee that we will be able to generate sufficient proceeds from •the ~~sale~~federal ofAnti-Kickback our approved products or product candidates, if approved, or be successful in completing other transactions that will fully fund our operating expenses. Further, the recent economic uncertainty, may dramatically reduce our ability to secure debt or equity financing necessary to support our operations. If we are delayed in obtaining additional funding or are unable to complete a strategic transaction, we may discontinue our development activities on our product candidates or discontinue our operations. Our future capital requirements will depend on many factors, including:Statute;

●•federal ~~the~~civil ~~success in commercializing our approved products; ● the commercial revenue received from commercial sales of our approved products, MIPLYFFA~~ and ~~OLPRUVA,~~criminal orfalse any of our product candidates subject to the terms of the AZSTARYS License Agreement, or sales of our product candidates for which we receive marketing approval in the future, which may be affected by market conditions, including obtaining coverage and adequate reimbursement of our approved products, or any of our product candidates, from third-party payors, including government programs and managed care organizations, and competition within the therapeutic class to which our approved products, or any our product candidates are assigned; ● the progress and results of our preclinical studies, clinical trials, chemistry, manufacturing and controls, and other product development and commercialization activities; ● the scope, progress, results and costs of preclinical development, laboratory testing and clinical trials for our product candidates; ● the ability to obtain differentiating claims ~~in the labels for our product candidates; ● the number and development requirements of other product candidates that we may pursue; ● the costs~~laws, timing and outcome of regulatory review of our product candidates; ● the efforts necessary to institute post-approval regulatory compliance requirements; ● the costs and timing of future commercialization activities, including ~~product manufacturing, marketing, sales and distribution, for any of our product candidates for which we receive marketing approval; ●~~ the ~~costs~~False ~~and~~Claims ~~timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims~~Act; ~~and ● the extent to which we acquire or in-license other product candidates and technologies.~~

•the civil monetary penalties statute;

•the Health Insurance Portability and Accountability Act, or HIPAA;

•the federal Physician Payments Sunshine Act and its implementing regulations; and

•analogous state and foreign laws and regulations.

These laws may affect our and our commercial partners' sales, marketing, and other promotional activities by imposing administrative and compliance burdens. Efforts to ensure that our current and future business arrangements with third parties will comply with applicable healthcare laws and regulations may involve substantial costs. If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, including, without limitation, damages, fines, imprisonment, exclusion from participation in government healthcare programs, such as Medicare and Medicaid, corporate integrity agreements or similar agreements to resolve allegations of non-compliance with these laws, and the curtailment or restructuring of our operations, which could significantly harm our business. If any of the physicians or other healthcare providers or entities with whom we currently, or expect to, do business, including future collaborators, is found not to be in compliance with applicable laws, they and we may be subject to significant penalties and potential exclusion from participation in healthcare programs as a result of their non-compliance.

For more detailed information regarding applicable federal, state and foreign healthcare laws that may affect our ability to operate, see “Item 1. Business - U.S. Government Regulation and Product Approval - Other Healthcare Regulatory Frameworks” above in this Annual Report on Form 10-K.

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~~Risks~~If ~~Related~~we fail to ~~Our~~comply ~~Dependence~~with onour ~~Third~~reporting ~~Parties~~and payment obligations under the Medicaid Drug Rebate Program or other governmental pricing programs in which we participate, we could be subject to additional reimbursement requirements, penalties, sanctions and fines.

Medicaid is a joint federal and state program administered by the states for low income and disabled beneficiaries. We ~~rely~~participate onin and ~~expect~~have certain price reporting obligations under the Medicaid Drug Rebate Program (the “MDRP”) as a condition of having covered outpatient drugs payable under Medicaid and, if applicable, under Medicare Part B. The MDRP requires us to ~~continue~~pay a rebate to ~~rely~~state Medicaid programs every quarter for each unit of our covered outpatient drugs dispensed to Medicaid beneficiaries and paid for by a state Medicaid program. The rebate is based on ~~third~~pricing ~~parties~~data that we must report on a monthly and quarterly basis to ~~conduct~~the ~~our~~Centers ~~clinical~~for ~~trials~~Medicare & Medicaid Services (“CMS”), the federal agency that administers the MDRP and other governmental healthcare programs. These data include the average manufacturer price (AMP) for ~~our~~each ~~product~~drug ~~candidates~~and, in the case of innovator products, the best price, which in general represents the lowest price available from the manufacturer to certain entities in the United States in any pricing structure, calculated to include all sales and associated rebates, discounts and other price concessions. The Medicaid rebate consists of two components, the basic rebate and the additional rebate, which is triggered if the AMP for a drug increases faster than inflation. If we become aware that our MDRP government price reporting submission for a prior quarter was incorrect or has changed as a result of recalculation of the pricing data, we must resubmit the corrected data for up to three years after those ~~third~~data ~~parties~~originally were due. If we fail to provide information timely or are found to have knowingly submitted false information to the government, we may ~~not~~be ~~perform~~subject ~~satisfactorily~~to civil monetary penalties and other sanctions, including ~~failing~~termination from the MDRP. In the event that CMS terminates our rebate agreement pursuant to ~~meet~~which ~~deadlines~~we ~~for~~participate in the ~~completion~~MDRP, ofno ~~such~~federal ~~trials~~payments would be available under Medicaid or Medicare Part B for our covered outpatient drugs. Our failure to comply with our MDRP price reporting and rebate payment obligations could negatively impact our financial results.

WeThe ~~have~~IRA ~~engaged~~imposes ~~and~~rebates ~~expect~~under toMedicare ~~continue~~Part toB ~~engage~~and ~~CROs~~Medicare ~~for~~Part ~~our~~D ~~planned~~that ~~clinical~~are ~~trials~~triggered ofby ~~our~~price ~~product~~increases ~~candidates.~~that Weoutpace ~~rely~~inflation on(first ~~and~~due ~~expect~~in to2023), ~~continue~~as todescribed ~~rely~~under onthe ~~CROs,~~risk asfactor ~~well~~“Current asand ~~other~~future ~~third~~healthcare ~~parties,~~reform ~~such~~legislation asor ~~clinical~~regulation ~~data~~may ~~management~~increase ~~organizations,~~the ~~medical~~difficulty ~~institutions~~ and ~~clinical~~cost ~~investigators,~~for us to ~~conduct~~obtain ~~those~~marketing ~~clinical~~approval ~~trials.~~of ~~Agreements~~our ~~with~~product ~~such~~candidates ~~third~~and ~~parties~~increase ~~might~~the ~~terminate~~cost ~~for~~to acommercialize ~~variety~~our ofapproved ~~reasons~~products,” ~~including~~above. aThe ~~failure~~Medicare toPart ~~perform~~D byrebate, ~~the~~if ~~third~~applicable, ~~parties.~~will Ifbe wecalculated ~~need~~on tothe ~~enter~~basis ~~into~~of ~~alternative~~the ~~arrangements,~~AMP ~~our~~figures ~~drug~~we ~~development~~report ~~activities~~pursuant ~~would~~to bethe ~~delayed~~MDRP.

~~Our~~Federal ~~reliance~~law onrequires ~~these~~that ~~third~~any ~~parties~~company ~~for~~that ~~research~~participates ~~and~~in ~~development~~the ~~activities~~MDRP ~~reduces~~also ~~our~~participate ~~control~~in ~~over~~the ~~these~~Public ~~activities~~Health ~~but~~Service’s ~~does~~340B ~~not~~drug ~~relieve~~pricing usprogram ofin ~~our~~order ~~responsibilities.~~for ~~For~~federal ~~example,~~funds weto ~~remain~~be ~~responsible~~available for ~~ensuring~~the ~~that~~manufacturer’s ~~each~~drugs ofunder ~~our~~Medicaid ~~clinical~~and, ~~trials~~if isapplicable, ~~conducted~~Medicare inPart ~~accordance~~B. ~~with~~We participate in the ~~general~~340B ~~investigational~~program, ~~plan~~which ~~and~~is ~~protocols~~administered ~~for~~by the ~~trial.~~Health ~~Moreover,~~Resources ~~the~~and ~~FDA~~Services Administration (“HRSA”), and requires us to ~~comply~~charge ~~with~~statutorily ~~regulatory~~defined ~~standards,~~covered ~~commonly~~entities ~~referred~~no tomore asthan ~~good~~the ~~clinical~~340B ~~practices,~~“ceiling orprice” ~~GCPs,~~ for ~~conducting,~~our ~~recording~~covered ~~and~~outpatient ~~reporting~~drugs. ~~the~~These ~~results~~340B ofcovered ~~clinical~~entities ~~trials~~include toa ~~assure~~variety ~~that~~of ~~data~~community health clinics and ~~reported~~other ~~results~~entities ~~are~~that ~~credible~~receive ~~and~~health ~~accurate~~services ~~and~~grants ~~that~~from the ~~rights~~Public Health Service, ~~integrity~~as ~~and~~well ~~confidentiality~~as ofhospitals ~~trial~~that ~~participants~~serve ~~are~~a ~~protected.~~disproportionate ~~Regulatory~~share ~~authorities~~of ~~enforce~~low‑income ~~these~~patients. ~~GCPs~~The ~~through~~ACA ~~periodic~~expanded ~~inspections~~the list of ~~trial~~covered ~~sponsors~~entities to include certain free‑standing cancer hospitals, ~~investigators~~critical access hospitals, rural referral centers and ~~trial~~sole ~~sites~~community hospitals, but exempts “orphan drugs,” from the ceiling price requirements for these covered entities. WeThe ~~also~~340B ~~are~~ceiling ~~required~~price tois ~~register~~calculated ~~specified~~using ~~ongoing~~a ~~clinical~~statutory ~~trials~~formula based on AMP and ~~post~~rebate amount for the ~~results~~covered ofoutpatient ~~completed~~drug ~~clinical~~as ~~trials~~calculated under the MDRP. We must report 340B ceiling prices to HRSA on a ~~government-sponsored~~quarterly ~~database~~basis, ~~ClinicalTrials.gov,~~and ~~within~~HRSA ~~specified~~publishes ~~timeframes~~those prices to 340B covered entities. In addition, weHRSA ~~must~~has ~~conduct~~finalized ~~our~~regulations ~~clinical~~regarding ~~trials~~the ~~with~~calculation ~~product~~of ~~produced~~the ~~under~~340B ~~cGMP~~ceiling ~~requirements.~~price ~~Similar~~and ~~requirements~~the ~~apply~~imposition inof ~~foreign~~civil ~~jurisdictions.~~monetary ~~Failure to~~penalties ~~comply~~on ~~with~~manufacturers ~~these~~that ~~regulations~~knowingly ~~may~~and ~~require~~intentionally usovercharge tocovered ~~repeat~~entities ~~preclinical~~for ~~studies~~340B-eligible ~~and~~drugs. ~~clinical~~HRSA ~~trials,~~has ~~which~~also ~~would~~finalized ~~delay~~a ~~the~~revised ~~regulatory~~regulation ~~approval~~implementing an administrative dispute resolution process. ~~Failure~~through towhich ~~comply~~340B ~~with~~covered ~~the~~entities ~~applicable~~may ~~requirements~~pursue ~~related~~claims toagainst ~~clinical~~participating ~~investigations~~manufacturers byfor usovercharges, ~~our~~and ~~CROs~~through orwhich ~~clinical~~manufacturers ~~trial~~may ~~sites~~pursue ~~can~~claims ~~also~~against ~~result~~340B covered entities for engaging in ~~clinical~~unlawful ~~holds~~diversion ~~and~~or ~~termination~~duplicate discounting of ~~clinical~~340B ~~trials,~~drugs. ~~debarment,~~Our ~~FDA or~~failure ~~foreign~~to ~~regulatory~~comply ~~authorities~~with ~~refusal~~340B toprogram ~~approve~~requirements ~~applications~~could ~~based~~negatively onimpact ~~the~~our ~~clinical~~financial ~~data,~~results. ~~warning~~Any ~~letters,~~additional ~~withdrawal~~future changes to the definition of ~~marketing~~average ~~approval~~manufacturer ifor the ~~product~~Medicaid ~~has~~rebate ~~already~~amount ~~been~~under ~~approved,~~legislation ~~fines~~or ~~and~~regulation ~~other~~could ~~monetary~~affect ~~penalties,~~our ~~delays,~~340B ~~adverse~~ceiling ~~publicity~~price ~~and~~calculations ~~civil~~ and ~~criminal~~also ~~sanctions,~~negatively ~~among~~impact ~~other~~our ~~consequences~~financial results.

~~Furthermore,~~In ~~these~~order ~~third~~for ~~parties~~approved ~~may~~products ~~also~~to ~~have~~be ~~relationships~~paid for with ~~other~~federal ~~entities,~~funds ~~some~~under ofthe ~~which~~Medicaid ~~may~~and beMedicare ~~our~~Part ~~competitors~~B programs and purchased by certain federal agencies and grantees, we also participate in the U.S. IfDepartment ~~these~~of ~~third~~Veterans ~~parties~~Affairs do(“VA”) ~~not~~Federal ~~successfully~~Supply ~~carry~~Schedule ~~out~~(“FSS”) ~~their~~pricing ~~contractual~~program. ~~duties~~As part of this program, ~~meet~~we ~~expected~~are ~~deadlines~~required orto ~~conduct~~make our ~~clinical~~products ~~trials~~available infor ~~accordance~~procurement on an FSS contract under which we must comply with ~~regulatory~~standard ~~requirements~~government orterms ~~our~~and ~~stated~~conditions ~~protocols,~~and wecharge ~~will~~a ~~not~~price bethat ~~able~~is no higher than the statutory Federal Ceiling Price (“FCP”), to ~~obtain~~four federal agencies (VA, orU.S. ~~may~~Department beof ~~delayed~~Defense in(“DOD”), ~~obtaining~~Public Health Service, ~~marketing~~and ~~approvals~~U.S. ~~for~~Coast ~~our~~Guard). ~~product~~The ~~candidates~~FCP is based on the Non-Federal Average Manufacturer Price (“Non-FAMP”), which we must calculate and ~~will~~report ~~not~~to bethe ~~able~~VA on a quarterly and annual basis. Pursuant to applicable law, orknowing ~~may~~provision beof ~~delayed~~false information in ~~our~~connection ~~efforts~~with a Non-FAMP filing can subject a manufacturer to, ~~successfully~~significant ~~commercialize~~civil ~~our~~monetary ~~product~~penalties ~~candidates~~for each item of false information. The FSS pricing and contracting obligations also contain extensive disclosure and certification requirements.

In addition, investigators for our clinical trials may serve as scientific advisors or consultants to us from time to time and may receive cash or equity compensation in connection with such services. If these relationships and any related compensation result in perceived or actual conflicts of interest, or the FDA or foreign regulatory authorities conclude that the financial relationship may have affected the interpretation of the study, the integrity of the data generated at the applicable clinical trial site may be questioned and the utility of the clinical trial itself may be jeopardized, which could result in the delay or rejection of any NDA or foreign marketing authorization application we submit by the FDA or foreign regulatory authorities. Any such delay or rejection could prevent us from commercializing our product candidates. Further, our arrangements with investigators are also subject to scrutiny under other health care regulatory laws, such as the Anti-Kickback Statute and comparable foreign laws.

We also rely on and expect to continue to rely on other third parties to store and distribute product supplies for our clinical trials. Any performance failure on the part of our distributors could delay clinical development or marketing approval of our product candidates or commercialization of our products, producing additional losses and depriving us of potential product revenue.

If the third parties with whom we contract do not successfully carry out their contractual duties or obligations or meet expected deadlines or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols or regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated, we may need to conduct additional trials, and we may not be able to obtain regulatory approval for or successfully commercialize our product candidates. As a result, the commercial prospects for our product candidates would be harmed, our costs could increase and our ability to generate revenue could be delayed. To the extent we are unable to successfully identify and manage the performance of third-party service providers in the future, our business may be adversely affected.

We contract with third parties for the manufacture of our approved products, partnered products and product candidates that utilize SDX, sodium phenylbutyrate, and arimoclomol, and we expect to continue to do so. This reliance on third-party manufacturers increases the risk that we will not have sufficient quantities of SDX, sodium phenylbutyrate and arimoclomol, or such quantities at an acceptable cost, which could delay, prevent or impair commercialization or development efforts.

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We doalso ~~not~~participate ~~have~~in ~~any~~the ~~manufacturing~~Tricare ~~facilities.~~Retail WePharmacy ~~procure~~program, ~~the bulk~~under ~~drug~~which ~~substances~~we ~~for~~are ~~our~~required ~~approved~~to ~~products~~pay ~~and~~quarterly ~~product~~rebates ~~candidates~~on ~~from~~utilization ~~sole-source,~~of ~~third-party~~innovator ~~manufacturers and~~products that are dispensed through the ~~partnered~~ ~~products~~Tricare ~~and~~Retail ~~product~~Pharmacy ~~candidates that~~network ~~utilize~~to ~~these~~Tricare ~~moieties~~ beneficiaries. The rebates are calculated as the ~~API used~~difference inbetween ~~our~~the ~~clinical~~annual ~~trials from~~Non-FAMP ~~other~~and ~~third parties~~FCP. We ~~anticipate~~are werequired ~~will~~to ~~continue~~list toour doproducts soon ~~for~~a ~~the~~Tricare ~~foreseeable~~Agreement ~~future.~~in Weorder ~~also~~for ~~expect~~them to ~~continue~~be toeligible ~~rely~~for onDOD ~~third~~formulary ~~parties~~inclusion. asIf we ~~proceed~~overcharge ~~with~~the ~~preclinical~~government ~~and~~in ~~clinical~~connection ~~testing~~with of our ~~product~~FSS ~~candidates,~~contract asor ~~well~~Tricare asAgreement, ~~for~~whether ~~commercial~~due ~~manufacture~~to ofa ~~our~~misstated ~~approved~~FCP ~~products,~~ or ~~any~~otherwise, ofwe ~~our product~~are ~~candidates~~required ~~should~~to ~~such~~refund ~~candidates~~the ~~receive~~difference ~~marketing~~to ~~approval~~the government. ~~This~~Failure ~~reliance~~to onmake ~~third~~necessary ~~parties~~disclosures ~~increases~~and/or ~~the~~to ~~risk~~identify ~~that~~contract weovercharges ~~will~~could ~~not~~result ~~have~~in ~~sufficient~~allegations ~~quantities~~against ~~of SDX,~~us ~~sodium~~under ~~phenylbutyrate,~~the ~~arimoclomol,~~False orClaims ~~other bulk~~Act ~~drug~~and ~~substances~~other orlaws ~~our~~and ~~approved~~regulations. ~~products,~~Unexpected ~~partnered~~refunds ~~product~~to ~~or product~~the ~~candidates~~government, orand ~~such~~responding ~~quantities~~to ata angovernment ~~acceptable~~investigation ~~cost~~ or ~~quality~~enforcement action, ~~which~~would ~~could~~be ~~delay~~expensive and time-consuming, ~~prevent~~and orcould ~~impair~~have ~~our~~a ~~ability~~material toadverse ~~timely~~effect ~~conduct~~on our ~~clinical~~business, ~~trials~~financial orcondition, ~~our~~results ~~other~~of ~~development~~operations orand ~~commercialization~~growth ~~efforts~~prospects.

WePricing ~~may~~and berebate ~~unable~~calculations vary among products and programs. The calculations are complex and are often subject to ~~establish~~interpretation ~~any~~by ~~future~~us, ~~agreements~~governmental ~~with~~or ~~third-party~~regulatory agencies, and the courts. CMS, the Department of Health & Human Services Office of Inspector General, and other governmental agencies have pursued manufacturers orthat were alleged to dohave sofailed onto ~~acceptable~~report ~~terms~~these data to the government in a timely or accurate manner. ~~Even~~Governmental ifagencies wemay ~~are~~also ~~able~~make tochanges ~~maintain~~in ~~our~~program ~~existing~~interpretations, ~~third-party~~requirements ~~relationships~~or conditions of participation, some of which may have implications for amounts previously estimated or ~~establish~~paid. We cannot assure you that any ~~such~~submissions ~~agreements~~we ~~with~~are ~~other~~required ~~third-party~~to ~~manufacturers~~make under the MDRP, ~~reliance~~the on340B ~~third-party~~program, ~~manufacturers~~the ~~entails~~VA/FSS ~~additional~~program, ~~risks~~the Tricare Retail Pharmacy Program, ~~including:~~and other governmental drug pricing programs will not be found to be incomplete or incorrect.

●Risks ~~reliance~~Related onto ~~the~~Cybersecurity ~~third party for FDA, DEA, EMA~~ and ~~comparable~~Data ~~foreign authorities, regulatory compliance and quality assurance;~~Privacy

●Cybersecurity ~~the~~breaches, ~~possible~~loss ~~misappropriation~~ of data and other disruptions could compromise sensitive information related to our ~~proprietary~~business or prevent us from accessing critical information and expose us to liability, ~~including~~which ~~our~~could ~~trade~~adversely ~~secrets~~affect our business and ~~know-how;~~our reputation.

●In ~~disruption~~the ordinary course of our business, we may collect, process, transmit and ~~costs~~store ~~associated~~proprietary, ~~with~~confidential ~~changing~~and ~~suppliers~~sensitive information, including ~~additional~~personal ~~regulatory~~information ~~filings;~~(such as key-coded data and health information), intellectual property, trade secrets and proprietary business information owned or controlled by ourselves or other parties. It is critical that we do so in a secure manner to maintain the confidentiality and integrity of such information.

●There can be no assurance that our cybersecurity risk management program and processes, including our policies, controls or procedures, will be complied with or effective in protecting our systems and information. Despite the ~~possible~~implementation ~~breach~~of security measures, ~~termination~~our information technology systems and data, and those of our CROs and other third parties on which we rely, are vulnerable to system failure, interruption, compromise, attack or ~~nonrenewal~~damage from several sources, such as data corruption; breakdown; malicious human acts; malware (such as ransomware); misconfigurations, “bugs” or other vulnerabilities; malicious code (such as computer viruses or worms); fraudulent activity; employee misconduct, theft or error; denial-of-service ~~the~~attacks; ~~agreement~~public health epidemics; cyber-attacks by ~~the~~sophisticated ~~third~~nation-state ~~party~~and atnation-state supported actors; natural disasters; terrorism; war; and telecommunication and electrical failures. We have also outsourced elements of our information technology infrastructure, and as a ~~time~~result ~~that~~a isnumber ~~costly~~of third-party vendors may or ~~inconvenient~~could ~~for~~have ~~us;~~access to our confidential information. Our recovery systems (and those of third parties upon whom we rely) are similarly vulnerable. Any of these events could lead to the unauthorized access, disclosure and use of proprietary, confidential, or otherwise non-public information.

●The techniques used by criminal actors to attack computer systems are sophisticated, change frequently and may originate from less regulated and remote areas of the world. As a ~~delay~~result, we may not be able to address these techniques proactively or ~~inability~~implement adequate preventative measures. Attacks upon information technology systems are also increasing in their levels of persistence and intensity and are being conducted by sophisticated and organized groups and individuals with a wide range of motives and expertise. We may also experience security breaches that may remain undetected for an extended period. Even if identified, we may be unable to ~~procure~~adequately investigate or ~~expand~~remediate ~~sufficient~~incidents ~~manufacturing~~or ~~capacity;~~breaches due to attackers increasingly using tools and techniques – including artificial intelligence (“AI”) – that are designed to circumvent controls, to avoid detection, and to remove or obfuscate forensic evidence. As a result of the continued hybrid working environment, we may also face increased cybersecurity risks due to our reliance on internet technology and the number of our employees who are working remotely, which may create additional opportunities for cybercriminals to exploit vulnerabilities.

● manufacturing and product quality issues related to scale-up of manufacturing;

● costs and validation of new equipment and facilities required for scale-up;

● the inability to negotiate manufacturing agreements with third parties under commercially reasonable terms;

● termination or nonrenewal of manufacturing agreements with third parties in a manner or at a time that is costly or damaging to us;

● the reliance on a limited number of sources, and in some cases, single sources for product components, such that if we are unable to secure a sufficient supply of these product components, we will be unable to manufacture and sell our product candidates in a timely fashion, in sufficient quantities or under acceptable terms; and

● carrier disruptions or increased costs that are beyond our control.

Additionally, trade policies and geopolitical disputes and other international conflicts can result in tariffs, sanctions and other measures that restrict international trade, and can materially adversely affect our business, particularly if these measures affect regions where manufacturing and product development activities take place or raw materials are sourced. For example, tensions between the United States and China have led to a series of tariffs being imposed by the United States on imports from China, as well as other business restrictions. Countries may also adopt other measures, such as controls on imports or exports of goods, technology or data, that could adversely impact supply chains. As these tensions continue to rise, more targeted approaches on certain products, industries or companies could significantly impact our development and commercialization efforts. The U.S. government has recently imposed tariffs on certain foreign goods, and some foreign governments have threatened or instituted retaliatory tariffs on certain U.S. goods and have indicated a willingness to impose additional tariffs on U.S. products, which could increase the cost of goods needed to commercialize our products and continue development of our product candidates. Further, such actions by the U.S. could result in other retaliatory actions by those countries which could impact our ability to profitably commercialize our products in those jurisdictions. As a result, our business, operations, and financial condition could be materially harmed.

Any of these events could lead to clinical trial delays, failure to obtain regulatory approval or impact our ability to successfully commercialize our products, if approved. Some of these events could be the basis for FDA or foreign regulatory authorities action, including injunction, recall, seizure or total or partial suspension of production.

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~~The~~If ~~facilities~~we ~~used~~or by our ~~contract~~third-party ~~manufacturers~~vendors were to ~~manufacture~~experience a significant cybersecurity breach of our ~~approved~~or ~~products~~their information systems or data, ~~and~~it ~~any~~may result in a material adverse impact, including without limitation, fines, damages, litigation, enforcement actions, loss of trade secrets, personal information or other proprietary or sensitive information, a material disruption of our ~~product~~drug ~~candidates~~development ~~are~~programs, ~~subject~~regulatory scrutiny or other harm to ~~review~~our bybusiness. For example, the ~~FDA~~loss orof ~~comparable~~clinical ~~foreign~~trial ~~regulatory~~data ~~authorities~~from ~~pursuant~~completed toor ~~inspections~~ongoing ~~that~~or ~~will~~planned beclinical ~~conducted~~trials ~~after~~could weresult ~~submit~~in delays in our ~~marketing~~regulatory ~~application~~approval efforts and significantly increase our costs to ~~the~~recover ~~FDA~~ or reproduce the ~~EMA~~data. In addition, the costs associated with the investigation, remediation and ~~such~~potential ~~inspections~~notification of the breach to counter-parties and data subjects could ~~result~~be inmaterial. ~~findings~~We ~~that~~may ~~lead~~be required to ~~failure~~ expend significant resources, fundamentally change our business activities and practices, or modify our operations, including our clinical trial activities, or information technology in an effort to ~~obtain~~protect ~~FDA~~against security breaches and to mitigate, detect and remediate actual and potential vulnerabilities. The costs of maintaining or ~~comparable~~upgrading ~~foreign approval~~our cyber-security systems at the level commercially reasonable to keep up with our expanding operations and prevent against potential attacks are increasing, and despite our best efforts, our network security and data recovery measures and those of our vendors may still not be adequate to protect against such ~~marketing~~security ~~applications~~breaches and disruptions.

WeFurthermore, ~~do not~~federal, ~~other~~state ~~than~~and ~~through~~international ~~our~~laws ~~contractual~~and ~~arrangements,~~regulations ~~control~~can ~~the~~expose ~~manufacturing~~us ~~process of~~to ~~our~~enforcement ~~approved~~actions ~~products,~~and orinvestigations ~~any of~~by ~~our~~regulatory ~~other product candidates~~authorities, and ~~we are~~potentially ~~completely~~result ~~dependent~~in onregulatory penalties, ~~our~~fines ~~contract~~and ~~manufacturing~~significant ~~partners~~legal ~~for~~liability, ~~compliance~~if ~~with~~our ~~cGMP~~information ~~requirements~~technology ~~and~~security ~~for~~efforts ~~manufacture~~fail. ofAny ~~both~~adverse ~~active~~impact ~~drug~~to ~~substances~~the ~~and~~availability, ~~finished~~integrity ~~drug~~or ~~products.~~confidentiality Ifof our ~~contract~~or ~~manufacturers~~third-party ~~cannot~~systems ~~successfully~~or ~~manufacture~~confidential ~~material~~information ~~that~~can ~~conforms~~result toin ~~our~~legal ~~specifications~~claims ~~and~~or ~~the~~proceedings ~~strict~~(such ~~regulatory~~as ~~requirements~~class ofactions), ~~the~~regulatory ~~FDA~~investigations orand ~~other~~enforcement ~~regulatory~~actions, ~~authorities~~fines and penalties, wenegative ~~will~~reputational ~~not~~impacts bethat ~~able~~cause us to ~~secure~~lose ~~and~~existing ~~maintain~~or ~~regulatory~~future ~~approval~~customers, ofand/or ~~our~~significant ~~marketing~~incident ~~applications for~~response, ~~the~~system ~~use~~restoration ~~of their~~or ~~manufacturing~~remediation ~~facilities~~and ~~for~~future ~~our~~compliance ~~products~~costs. InWe ~~addition,~~may ~~other~~also ~~than~~be ~~through~~exposed ~~our~~to ~~contractual~~a ~~agreements,~~risk weof ~~have~~loss noor ~~control~~litigation ~~over~~and ~~the~~potential ~~ability~~liability, ofwhich ~~our~~could ~~contract~~materially ~~manufacturers~~and toadversely ~~maintain~~affect ~~adequate~~our ~~quality control~~business, ~~quality~~results ~~assurance~~of ~~and~~operations ~~qualified~~or ~~personnel~~financial condition. IfIn ~~the FDA~~addition, orour aremediation ~~comparable~~efforts ~~foreign~~may ~~regulatory authority, does~~ not ~~approve~~be ~~these~~successful. ~~facilities~~If ~~for~~we ~~the~~do ~~manufacturing~~not ofallocate ~~our~~and ~~approved~~effectively ~~products, or~~manage ~~any~~the ofresources ~~our~~necessary ~~other~~to ~~product~~build ~~candidates,~~and orsustain ifthe itproper ~~withdraws~~technology ~~any~~and ~~such~~cybersecurity ~~approval in the future~~infrastructure, we ~~may~~could ~~need~~suffer tosignificant ~~find~~business ~~alternative manufacturing facilities~~disruption, ~~which~~including ~~would~~transaction ~~significantly~~errors, ~~impact~~supply ~~our~~chain ~~ability~~or tomanufacturing ~~develop~~interruptions, ~~obtain~~processing ~~marketing~~inefficiencies, ~~approval~~data ~~for~~loss or ~~market~~the ~~our~~loss ~~approved~~of ~~products,~~ or ~~any~~damage ofto ~~our~~intellectual ~~other~~property ~~product~~or ~~candidates,~~other ifproprietary ~~approved~~information.

~~Further,~~We ~~for~~cannot be sure that our ~~approved~~insurance ~~products and~~coverage ~~any~~will ofbe ~~our product~~adequate ~~candidates,~~or ~~if approved,~~otherwise ~~our~~protect ~~suppliers will~~us befrom ~~subject~~or adequately mitigate liabilities or damages with respect to ~~regulatory~~claims, ~~requirements~~costs, ~~covering~~expenses, ~~manufacturing~~litigation, ~~testing~~fines, ~~quality~~penalties, ~~control~~business ~~and~~loss, ~~record~~data ~~keeping~~loss, ~~relating~~regulatory toactions ~~our~~or ~~approved~~materially ~~products or~~adverse ~~any~~impacts arising out of our ~~product~~ ~~candidates,~~privacy ifand ~~approved~~cybersecurity practices, ~~and~~processing ~~subject~~or tosecurity ~~ongoing~~breaches ~~inspections~~that bywe ~~the~~may ~~regulatory~~experience, ~~agencies.~~or ~~Failure~~that bysuch ~~any~~coverage ofwill ~~our~~continue ~~suppliers~~ to ~~comply~~be ~~with~~available ~~applicable~~on ~~regulations~~acceptable ~~may~~terms ~~result~~at inall. ~~long~~The ~~delays~~successful ~~and~~assertion ~~interruptions~~of toone or more large claims against us that exceeds our ~~manufacturing~~available ~~capacity~~insurance ~~while~~coverage, weor ~~seek~~results in changes to ~~secure~~our ~~another~~insurance ~~supplier~~policies ~~that~~(including ~~meets~~premium ~~all~~increases ~~regulatory~~or ~~requirements,~~the asimposition ~~well~~of asa ~~market~~large ~~disruption~~deductible ~~related~~or toco-insurance ~~any~~requirements), ~~necessary~~could ~~recalls~~have oran ~~other~~adverse ~~corrective~~effect ~~actions~~on our business.

~~Third-party~~We ~~manufacturers~~are ~~may~~currently ~~not~~subject ~~be able~~ to ~~comply with cGMP regulations or similar regulatory requirements outside the United States. Our failure~~, orand ~~the~~may ~~failure of our third-party manufacturers, to comply with applicable regulations could result~~ in ~~sanctions~~the ~~being~~future ~~imposed~~become onsubject us, including warning letters, clinical holds or termination of clinical trials, fines, injunctions, restitution, disgorgement, civil penalties, delays, suspension or withdrawal of approvals or other permits, FDA refusal to ~~approve pending applications~~additional, ~~product~~U.S. ~~detentions,~~federal ~~FDA~~and orstate ~~DEA consent decrees placing significant restrictions on or suspending manufacturing~~ and ~~distribution~~international ~~operations,~~laws debarment, refusal to allow import or export, product detentions, adverse publicity, dear-health-care-provider letters or other warnings, license revocation, seizures or recalls of product candidates, operating restrictions, refusal of government contracts or future orders under existing contracts and ~~civil~~regulations ~~and~~imposing ~~criminal~~obligations ~~liability,~~on ~~including~~how ~~False~~we ~~Claims Act liability~~collect, ~~exclusion~~store ~~from participation in federal health care programs,~~ and ~~corporate~~process ~~integrity~~personal ~~agreements among other consequences, any of which could significantly and adversely affect supplies of our prodrugs~~information.

~~Our~~The ~~approved~~secure ~~products~~processing, ~~that~~storage, wemaintenance, and transmission of sensitive personal information is vital to our operations and business. We are, ~~commercializing~~and may increasingly become, subject to various laws and ~~product~~ ~~candidates~~regulations, ~~that~~as wewell ~~are~~as ~~currently~~contractual ~~developing~~obligations, orgoverning ~~may~~the ~~develop~~collection, use, disclosure, retention, and security of personal information in the ~~future, may~~jurisdictions ~~compete~~in ~~with~~which ~~other~~we ~~product~~operate. ~~candidates~~The regulatory environment related to data privacy and ~~drugs~~security ~~for~~is ~~access~~increasingly rigorous, with new and constantly changing requirements applicable to ~~manufacturing~~our ~~facilities~~business, and weenforcement practices are likely to remain uncertain for the foreseeable future. These laws and regulations may be ~~unable~~interpreted toand ~~obtain~~applied ~~access~~differently over time and from jurisdiction to ~~these~~jurisdiction, ~~facilities~~and it is possible that they will be interpreted and applied in ways that may have a material adverse effect on ~~favorable~~our ~~terms~~business, financial condition, results of operations and prospects.

~~There~~In ~~are~~the aUnited ~~limited~~States, ~~number~~various offederal ~~manufacturers~~and ~~that~~state ~~operate~~regulators, ~~under~~including ~~cGMP~~governmental agencies like the Federal Trade Commission, have adopted, or ~~comparable~~are ~~foreign~~considering adopting, laws and regulations concerning personal information and ~~that~~data ~~might~~security. Certain state laws may be ~~capable~~more stringent or broader in scope, or offer greater individual rights, with respect to personal information than federal, international, or other state laws, and such laws may differ from each other, all of ~~manufacturing~~which ~~for~~may uscomplicate compliance efforts. ~~Any~~For ~~performance~~example, ~~failure~~the onCalifornia Consumer Privacy Act, as amended by the ~~part~~California Privacy Rights Act (collectively, the “CCPA”), requires covered businesses that process the personal information of ~~our~~California ~~existing~~residents orto, ~~future~~among ~~manufacturers~~other ~~could~~things: ~~delay~~(i) ~~clinical~~provide ~~development~~certain ordisclosures ~~marketing~~to ~~approval.~~California Weresidents doregarding ~~not~~the ~~currently~~business’s ~~have~~collection, ~~arrangements~~use, inand ~~place~~disclosure ~~for~~of ~~redundant~~their ~~supply~~personal orinformation; a(ii) ~~second~~receive ~~source~~and ~~for~~respond ~~our~~to ~~approved~~requests ~~products~~from California residents to access, delete, and correct their personal information, or ~~product~~to ~~candidates~~opt ~~bulk~~out ~~drug~~of ~~substance.~~certain ~~If our~~disclosures ~~current~~of ~~contract~~their ~~manufacturer~~personal ~~for~~information; ~~our~~and ~~approved~~(iii) ~~products~~enter orinto ~~product~~specific ~~candidates~~contractual ~~bulk~~provisions ~~drug~~with ~~substance~~service ~~cannot~~providers ~~perform~~that asprocess ~~agreed,~~California weresident personal information on the business’s behalf. Additional compliance investment and potential business process changes may also be required. toSimilar ~~replace~~laws ~~such~~have ~~manufacturer~~been passed in other states, and weare ~~may~~continuing ~~incur~~to ~~added~~be ~~costs~~proposed at the state and ~~delays~~federal inlevel, ~~identifying~~reflecting ~~and~~a ~~qualifying~~trend ~~any~~toward ~~such~~more ~~replacement.~~stringent ~~Any~~privacy ~~performance~~legislation ~~failure~~in orthe ~~significant~~United ~~delay~~States. ~~could~~These ~~negatively~~and ~~affect~~future ~~our~~laws ~~business,~~and ~~results~~regulations ofmay ~~operations~~increase our compliance costs and ~~financial~~potential ~~condition~~liability.

We have entered into collaborations with Commave, to develop, manufacture and commercialize AZSTARYS worldwide. In addition, we may seek collaborations with third parties for the development or commercialization of our other product candidates, or in other territories. If those collaborations are not successful, we may not be able to capitalize on the market potential of AZSTARYS or any of our other product candidates, if approved.

We entered into the AZSTARYS License Agreement with Commave pursuant to which we granted an exclusive, worldwide license to Commave to develop, manufacture and commercialize AZSTARYS. On behalf of Commave, Corium leads all commercialization activities in the United States for AZSTARYS under the AZSTARYS License Agreement. We cannot guarantee that the AZSTARYS License Agreement will be successful or that we will receive any future payments under the AZSTARYS License Agreement. For instance, Commave has the option to terminate the AZSTARYS License Agreement, in its entirety or on a product-by-product and country-by-country basis, at their convenience either (i) prior to the first regulatory approval of a product upon sixty days prior written notice or (ii) subsequent to the first regulatory approval of a product upon one hundred twenty days prior written notice. Further, even if Commave does not terminate the AZSTARYS License Agreement, we cannot guarantee that we will receive any additional milestone or royalty payments under the AZSTARYS License Agreement. In addition, under the AZSTARYS License Agreement, we have limited control over the amount and timing of resources that Corium will dedicate to the development, manufacturing or commercialization of AZSTARYS. Our ability to generate revenue under the AZSTARYS License Agreement will depend, in part, on Corium’s ability to successfully perform the functions assigned to it under the AZSTARYS License Agreement.

We may also seek additional third-party collaborators for the development or commercialization of any of our other product candidates, which are not subject to the AZSTARYS License Agreement, or those that are subject to the AZSTARYS License Agreement, but the option is not exercised by Commave. In such cases, our likely collaborators would include large and mid-size pharmaceutical companies, regional, national and international pharmaceutical companies and biotechnology companies. If we do enter into any such collaboration arrangements with any third parties, we will likely have limited control over the amount and timing of resources that our collaborators dedicate to the development or commercialization of our approved products or any of our other product candidates. Our ability to generate revenue from these arrangements will depend on our collaborators’ abilities to successfully perform the functions assigned to them in these arrangements.

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~~Our~~The ~~collaboration with~~Health ~~Commave~~Insurance Portability and Accountability Act of 1996, and regulations promulgated thereunder (“HIPAA”) imposes privacy, security and breach notification obligations on certain healthcare providers, health plans and healthcare clearinghouses, known as covered entities, as well as their business associates that perform certain services that involve creating, receiving, maintaining or ~~Collaborator~~transmitting individually identifiable health information for or on behalf of such covered entities, ~~poses~~ and their covered subcontractors. Among other requirements, HIPAA requires business associates to develop and maintain policies with respect to the ~~following~~protection ~~risks~~of, use and disclosure of protected health information (“PHI”), including the adoption of administrative, physical and technical safeguards to ~~us:~~protect such information, certain notification requirements in the event of a breach of unsecured PHI, and requirements to report breaches of unsecured PHI to covered entities within 60 days of discovery of the breach by the business associate or its agents. Depending on the facts and circumstances, we could be subject to significant civil, criminal and administrative fines and penalties and/or additional reporting and oversight obligations if found to be in violation of HIPAA.

●Foreign data protection laws may also apply to health-related and other personal data that we process, including personal data relating to clinical trial participants. European data protection laws impose strict obligations on the ~~Collaborator~~ability ~~has~~to ~~significant~~process ~~discretion~~health-related and other personal data of data subjects in ~~determining~~Europe, including standards relating to the ~~efforts~~privacy and ~~resources~~security of personal data. For example, in Europe, the European Union General Data Protection Regulation, or the “EU GDPR”, and in the United Kingdom, the United Kingdom General Data Protection Regulation and Data Protection Act 2018, or the “UK GDPR” (together with the EU GDPR, referred to as the “GDPR”) imposes strict requirements for processing the personal data of individuals within the European Economic Area, or the EEA, or in the context of our activities within the EEA. Companies that ~~they~~must ~~will~~comply ~~apply~~with the GDPR face increased compliance obligations and risk, including more robust regulatory enforcement of data protection requirements and potential fines for noncompliance under both the EU GDPR and UK GDPR of up to ~~these~~€20 ~~collaborations;~~million/GBP 17.5 million or 4% of the annual global revenues of the noncompliant company, whichever is greater. In addition to fines, a breach of the GDPR may result in regulatory investigations, reputational damage, orders to cease/ change our data processing activities, enforcement notices, assessment notices (for a compulsory audit) and/ or civil claims (including class actions). Among other requirements, the GDPR regulates transfers of personal data subject to the GDPR to third countries that have not been found to provide adequate protection to such personal data, including the United States, and the efficacy and longevity of current transfer mechanisms between the EEA and the United States remains uncertain. Case law from the Court of Justice of the European Union (“CJEU”) states that reliance on the standard contractual clauses – a standard form of contract approved by the European Commission as an adequate personal data transfer mechanism – alone may not necessarily be sufficient in all circumstances and that transfers must be assessed on a case-by-case basis.

●On July 10, 2023, the ~~Collaborator~~European ~~may~~Commission ~~not~~adopted ~~perform~~its ~~their~~Adequacy ~~obligations~~Decision in relation to the new EU-US Data Privacy Framework (“DPF”), rendering the DPF effective as ~~expected~~a GDPR transfer mechanism to U.S. entities self-certified under the DPF. In relation to such cross border transfers of personal data, we expect the existing legal complexity and uncertainty regarding international personal data transfers to continue, and international transfers to the United States, China, and to other jurisdictions more generally to continue to be subject to enhanced scrutiny by regulators. As the regulatory guidance and enforcement landscape in relation to data transfers continue to develop, we could suffer additional costs, complaints and/or regulatory investigations or fines; we may have to stop using certain tools and vendors and make other operational changes; we may have to implement alternative data transfer mechanisms under the GDPR and/ or take additional compliance and operational measures; and/or it could otherwise affect the manner in which we operate our business, and could adversely affect our business, operations and financial condition. Failure, or perceived failure, to comply with foreign data protection laws and regulations, privacy policies, contracts and other data protection obligations could result in government investigations and enforcement actions (which could include civil or criminal penalties, fines, or sanctions), private litigation, a diversion of management’s attention, adverse publicity and other negative effects on our operating results and business.

● the Collaborator may not pursue commercialization of AZSTARYS, any of our product candidates covered under the AZSTARYS License Agreement, if approved, or may elect not to continue or renew commercialization programs based on post-approval clinical trial results, changes in a Collaborator's strategic focus or available funding, or external factors, such as an acquisition, that divert resources or create competing priorities;

● the Collaborator could independently develop, or develop with third parties, products that compete directly or indirectly with AZSTARYS, or any of our other products covered under the AZSTARYS License Agreement, as applicable, if the Collaborator believes that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours;

● AZSTARYS, any of our other products covered under the AZSTARYS License Agreement, if approved, may be viewed by the Collaborator as competitive with their own product candidates or products, which may cause the Collaborator to cease to devote resources to the commercialization of AZSTARYS, or any of our other products covered under the AZSTARYS License Agreement, if approved;

● the Collaborator may not commit sufficient resources to the development, marketing and distribution of AZSTARYS and any of our other products covered under the AZSTARYS License Agreement, as applicable;

● disagreements with the Collaborator, including disagreements over proprietary rights, contract interpretation or the preferred course of development or commercialization, might cause delays or termination of the development or commercialization of AZSTARYS, or any of our other products covered under the AZSTARYS License Agreement, as applicable, might lead to additional responsibilities for us with respect to AZSTARYS or any of our other products covered under the AZSTARYS License Agreement, or might result in litigation or arbitration, any of which would be time-consuming and expensive;

● the Collaborator may not properly maintain or defend our or their intellectual property rights or may use our or their proprietary information in such a way as to invite litigation that could jeopardize or invalidate such intellectual property or proprietary information or expose us to potential litigation;

● the Collaborator may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability; and

● the license agreements may be terminated by the Collaborator under specified circumstances and, if terminated, we could be required to raise additional capital to pursue further development or commercialization of AZSTARYS or any of our other products covered under the AZSTARYS License Agreement.

If we enter into any future collaborations we will face similar risks with any future collaborators as well.

The AZSTARYS License Agreement and any other licensing or collaboration agreements we may enter into may not lead to commercialization of AZSTARYS, or development of KP1077, or any of our other product candidates in the most efficient manner or at all. If Commave or a future collaborator of ours were to be involved in a business combination, the continued pursuit and emphasis on our drug development or commercialization program could be delayed, diminished or terminated.

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If we are not able to establish collaborations for our product candidates, we may have to alter our development and commercialization plans.

Our prodrug development programs and the potential commercialization of our product candidates, if approved, will require substantial additional capital. For our product candidates, which are not subject to the terms of the AZSTARYS License Agreement, we may need to collaborate with pharmaceutical and biotechnology companies for the development and potential commercialization of those product candidates.

We face significant competition in seeking appropriate collaborators. Whether we reach a definitive agreement for a collaboration will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of several factors. Those factors may include the design or results of clinical trials, the likelihood of approval by the FDA or similar regulatory authorities outside the United States, the potential market for the subject product candidate, the costs and complexities of manufacturing and delivering such product candidate to patients, the potential of competing products, the existence of uncertainty with respect to our ownership of technology, which can exist if there is a challenge to such ownership without regard to the merits of the challenge, and industry and market conditions generally.

The collaborator may also consider alternative product candidates or technologies for similar indications that may be available to collaborate on and whether such a collaboration could be more attractive than the one with us for our product candidate.

Collaborations are complex and time-consuming to negotiate and document. In addition, there have been a significant number of recent business combinations among large pharmaceutical companies that have resulted in a reduced number of potential future collaborators.

We may not be able to negotiate collaborations on a timely basis, on acceptable terms, or at all. If we are unable to do so, we may have to curtail the development of product candidates, reduce or delay one or more of our development programs, delay potential commercialization of our product candidates or reduce the scope of any sales or marketing activities of our product candidates, or increase our expenditures and undertake development or commercialization activities at our own expense of our product candidate. If we elect to increase our expenditures to fund development or commercialization activities on our own, we may need to obtain additional capital, which may not be available to us on acceptable terms or at all. If we do not have sufficient funds, we may not be able to further develop our product candidates or bring our product candidates to market and generate product revenue.

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Risks Related to Our Intellectual Property

If we are unable to obtain and maintain trade secret protection or patent protection for our technology, our approved products or our product candidates, or if the scope of the patent protection obtained is not sufficiently broad, our competitors could develop and commercialize technology and drugs similar or identical to ours, and our ability to successfully commercialize our technology, our approved products, or our product candidates, if approved, may be impaired.

Our success depends in large part on our ability to obtain and maintain trade secret protection of our proprietary LAT platform technology as well as patent protection in the United States and other countries with respect to our approved products, and any of our product candidates. We seek to protect our proprietary position by filing patent applications in the United States and abroad related to our product technology and product candidates. As part of the AZSTARYS License Agreement, Commave obtained from us an exclusive, worldwide license to certain patents that cover AZSTARYS.

The patent prosecution process is expensive and time-consuming, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. It is also possible that we will fail to identify patentable aspects of our research and development output before it is too late to obtain patent protection. We may not have the right to control the preparation, filing and prosecution of patent applications, or to maintain the rights to patents, licensed to third parties by us.

Further, we may also not have the right to control the preparation, filing and prosecution of patent applications, or to maintain the rights to patents, licensed from third parties to us. Therefore, any such patents and applications may not be prosecuted and enforced in a manner consistent with the best interests of our business. If such licensors or licensees fail to maintain such patents, or lose rights to those patents, the rights we have in- or out-licensed may be reduced or eliminated.

The patent position of biotechnology and pharmaceutical companies, generally, is highly uncertain, involves complex legal and factual questions and has in recent years been the subject of much litigation. In addition, the laws of foreign countries may not protect our rights to the same extent as the laws of the United States or visa-versa. For example, European patent law restricts the patentability of methods of treatment of the human body more than United States law. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and utility, or equivalent, patent applications in the United States and other jurisdictions are typically, for example, not published until 18 months after the filing date of such patent applications, or in some cases not at all. Therefore, we cannot know with certainty whether we were the first to make and/or use the inventions claimed in our owned or licensed patents or pending patent applications, or that we were the first to file for patent protection of such inventions. As a result, the issuance, scope, priority, validity, enforceability and commercial value of our patent rights are highly uncertain. Our pending and future patent applications may not result in patents being issued that protect our product candidates, in whole or in part, or which effectively prevent others from commercializing competitive technologies and drugs. Changes in either the patent laws or interpretation of the patent laws in the United States and other countries may diminish the value of our patents or narrow the scope of our patent protection.

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Our patent position is subject to numerous additional risks, including the following:

● we may fail to seek patent protection for inventions that are important to our success; ● our pending patent applications may not result in issued patents; ● we cannot be certain that we are the first to invent the inventions covered by pending patent applications or that we are the first to file such applications and, if we are not, we may be subject to priority disputes or lose rights; ● we may be required to disclaim part or all of the term of certain patents or all of the term of certain patent applications; ● we may not be able to acquire patent term extensions or supplemental certificates of certain patents, domestic or foreign, due to regulatory delays, among others, which may affect the term of enforceability of such patents over time; ● we may file patent applications but have claims restricted or we may not be able to supply sufficient data to support our claims and, as a result, may not obtain the original claims desired or we may receive restricted claims; alternatively, it is possible that we may not receive any patent protection from an application; ● even if our owned and licensed patent applications issue as patents, they may not issue in a form that will provide us with any meaningful protection, and may not be of sufficient scope or strength to provide us with any commercial advantage; ● our competitors may be able to design around our owned or licensed patents by developing similar or alternative technologies or drugs without infringing on our intellectual property rights; ● we could inadvertently abandon a patent or patent application, resulting in the loss of protection of intellectual property rights in a particular country, and we, our collaborators or our patent counsel may take action resulting in a patent or patent application becoming abandoned which may not be able to be reinstated or if reinstated, may suffer patent term adjustments or loss; ● the claims of our issued patents or patent applications when issued may not cover our product candidates; ● no assurance can be given that our patents would be declared by a court or tribunal, domestic or foreign, to be valid or enforceable or that a competitor’s technology or product would be found by a court or tribunal, domestic or foreign, to infringe our patents and our patents or patent applications may be challenged by third parties in patent litigation, domestic or foreign, or in proceedings before the United States Patent and Trademark Office, or the USPTO, or its foreign counterparts, and may ultimately be declared invalid or unenforceable or narrowed in scope; ● there may be prior art of which we are not aware that may affect the validity or enforceability of a patent claim and there may be prior art of which we are aware, but which we do not believe affects the validity or enforceability of a claim, which may, nonetheless, ultimately be found to affect the validity or enforceability of a claim; ● third parties may develop products that have the same or similar effect as our products without infringing our patents; ● third parties may intentionally circumvent our patents by means of alternate designs or processes or file applications or be granted patents that would block or hurt our efforts; ● there may be dominating or intervening patents relevant to our product candidates of which we are not aware; ● obtaining regulatory approval for pharmaceutical products is a lengthy and complex process, and as a result, any patents covering our product candidates may expire before or shortly after such product candidates are approved and commercialized; ● the patent and patent enforcement laws of some foreign jurisdictions do not protect intellectual property rights to the same extent as laws in the United States, and many companies have encountered significant difficulties in protecting and defending such rights in foreign jurisdictions; and ● we may not develop additional proprietary technologies that are patentable.

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Any of these factors could hurt our ability to gain full patent protection for our products. Registered trademarks and trademark applications in the United States and other countries are subject to similar risks as described above for patents and patent applications, in addition to the risks described below.

Further, a third party may misappropriate or reverse engineer our proprietary LAT platform technology, which could limit our ability to stop others from using or commercializing similar or identical technology and resultant product candidates, product technology or prodrugs, or limit the duration of the trade secret protection of our proprietary LAT platform technology.

Moreover, we may be subject to a third-party pre-issuance submission of prior art to the USPTO, or become involved in opposition, litigation, nullity, derivation, reexamination, inter partes review, post-grant review or interference proceedings challenging our patent rights or the patent rights of others. An adverse determination in any such submission, proceeding or litigation could reduce the scope of, or invalidate, our patent rights, allow third parties to commercialize our technology or drugs and compete directly with us, without payment to us or result in our inability to manufacture or commercialize drugs without infringing third-party patent rights. In addition, if the breadth or strength of protection provided by our patents and patent applications is threatened, it could dissuade companies from collaborating with us to seek patent protection or to license, develop or commercialize current or future product candidates.

In addition, the issuance of a patent is not conclusive as to its inventorship, ownership, scope, priority, validity or enforceability, and our owned and licensed patents may be challenged in the courts, patent offices and tribunals in the United States and abroad. Such challenges may result in loss of exclusivity or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, which could limit our ability to stop others from using or commercializing similar or identical technology and drugs, or limit the duration of the patent protection of our product technology, product candidates and prodrugs.

Changes in patent law in the United States and other jurisdictions could alter or diminish the value of patents in general, thereby impairing our ability to protect our products and technologies.

The standards that the USPTO and patent offices in other countries use to grant patents are not always applied predictably or uniformly and can change. Changes in either the patent laws or interpretation of the patent laws in the United States and other countries could increase the uncertainties and costs, and may diminish our ability to protect our inventions, obtain, maintain, and enforce our intellectual property rights and, more generally, could affect the value of our intellectual property or narrow the scope of our owned and licensed patents.

In addition, the patent positions of companies in the development and commercialization of pharmaceuticals are particularly uncertain. The United States Supreme Court has ruled on several patent cases in recent years, either narrowing the scope of patent protection available in certain circumstances or weakening the rights of patent owners in certain situations. Depending on future actions by the United States Congress, the United States courts, the USPTO and the relevant law-making bodies in other countries, the laws and regulations governing patents could change in unpredictable ways that would weaken our ability to obtain new patents or to enforce our existing patents and patents that we might obtain in the future. For example, in the 2013 case Assoc. for Molecular Pathology v. Myriad Genetics, Inc., the United States Supreme Court held that certain claims to DNA molecules are not patentable. While we do not believe that any of the patents owned or licensed by us will be found invalid based on this decision, future decisions by the courts, the United States Congress or the USPTO may impact the value of our patents.

For another example, on September 16, 2011, the Leahy-Smith America Invents Act, or the Leahy-Smith Act, was signed into law. The Leahy-Smith Act includes a number of significant changes to U.S. patent law. These include provisions that affect the way patent applications are prosecuted in the United States, redefine prior art and may also affect patent litigation. The USPTO recently developed new regulations and procedures to govern administration of the Leahy-Smith Act, and many of the substantive changes to patent law associated with the Leahy-Smith Act, and in particular, the first-to-file provisions, only became effective on March 16, 2013.

The Leahy-Smith Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents. For instance, the Leahy-Smith Act established the inter partes review and post grant review procedures that has lowered the burden of proof for invalidity challenges to issued patents and limited the ability to amend patent claims in response to such challenges. In addition, patent reform legislation may pass in the future that could lead to additional uncertainties and increased costs surrounding the prosecution, enforcement and defense of our owned and licensed patents and/or patent applications.

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We may become involved in lawsuits to protect or enforce our patents or other intellectual property, which could be expensive, time consuming and unsuccessful.

Competitors or other third parties may infringe our patents, trademarks, copyrights or other intellectual property. To counter infringement or unauthorized use, we may be required to file infringement claims, which can be expensive and time consuming and divert the time and attention of our management and scientific personnel. Our pending patent applications cannot be enforced against third parties practicing the technology claimed in such applications unless and until a patent issues from such applications. Any claims we assert against perceived infringers could provoke these parties to assert counterclaims against us alleging that we infringe their patents, in addition to counterclaims asserting that our patents are invalid or unenforceable, or both. In patent litigation in the United States, defendant counterclaims alleging invalidity and/or unenforceability are commonplace. Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, including lack of novelty, obviousness, non-enablement or insufficient written description. Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld relevant information from the USPTO or made a misleading statement during prosecution. The outcome following legal assertions of invalidity and unenforceability is unpredictable. In any patent infringement proceeding, there is a risk that a court will decide that a patent of ours is invalid or unenforceable, in whole or in part, and that we do not have the right to stop the other party from using the invention at issue. There is also a risk that, even if the validity of such patents is upheld, the court will construe the patent’s claims narrowly or decide that we do not have the right to stop the other party from using the invention at issue on the grounds that our patent claims do not cover the invention, or decide that the other party’s use of our patented technology falls under the safe harbor to patent infringement under 35 U.S.C. §271(e)(1). An adverse outcome in a litigation or proceeding involving our patents could limit our ability to assert our patents against those parties or other competitors and may curtail or preclude our ability to exclude third parties from making and selling similar or competitive products and technologies. Any of these occurrences could adversely affect our competitive business position, business prospects and financial condition. Similarly, if we assert trademark infringement claims, a court may determine that the marks we have asserted are invalid or unenforceable, or that the party against whom we have asserted trademark infringement has superior rights to the marks in question. In this case, we could ultimately be forced to cease use of such trademarks.

Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could significantly harm our business.

Our commercial success depends upon our ability, and the ability of any collaborators, to develop, manufacture, market and sell our product candidates and use our proprietary technologies without infringing the proprietary rights of third parties. There is considerable intellectual property litigation in the biotechnology and pharmaceutical industries. In particular, we are focused on developing product candidates based on widely used therapeutic agents or drugs, many of which may be protected by proprietary rights of third parties.

Although we seek to develop proprietary prodrug formulations that do not infringe the intellectual property rights of others, we may become party to, or threatened with, future adversarial proceedings or litigation, domestic or foreign, regarding intellectual property rights with respect to our prodrugs or other aspects of our technology, including, for example, interference or derivation proceedings before the USPTO. Third parties may assert infringement claims against us based on existing patents or patents that may be granted in the future.

If we are found to infringe a third party’s intellectual property rights, we could be required to obtain a license from such third party to continue developing and marketing our technology and drugs. However, we may not be able to obtain any required license on commercially reasonable terms, or at all. Even if we were able to obtain a license, it could be non-exclusive, thereby giving our competitors access to the same technologies licensed to us. We could be forced, including by court order, to cease commercializing the infringing technology or product. In addition, we could be found liable for monetary damages, including treble damages and attorneys’ fees if we are found to have willfully infringed a patent. A finding of infringement could prevent us from commercializing our product candidates or force us to cease some or all of our business operations.

Competing products may also be sold in other countries in which our patent coverage might not exist or be as strong. If we lose a foreign patent lawsuit alleging our infringement of a competitor’s patent, we could be prevented from marketing our products in one or more foreign countries. As a result, our ability to grow our business and compete in the market may be harmed.

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Intellectual property litigation could cause us to spend substantial resources and distract our personnel from their normal responsibilities.

In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments. If securities analysts or investors perceive these results to be negative, it could hurt the price of our common stock. Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales, marketing or distribution activities. We may not have sufficient financial or other resources to conduct such litigation or proceedings adequately. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial resources. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could compromise our ability to compete in the marketplace.

We may need to license intellectual property from third parties, and such licenses may not be available or may not be available on commercially reasonable terms.

A third party may hold intellectual property rights, including patent rights, which are important or necessary to the development of our product candidates. It may be necessary for us to use the patented or proprietary technology of third parties to commercialize our product candidates, in which case we would be required to obtain a license from these third parties. Such a license may not be available on commercially reasonable terms, or at all, and we could be forced to accept unfavorable contractual terms. If we are unable to obtain such licenses on commercially reasonable terms, our business could be harmed.

If we or our third-party licensors fail to comply with our obligations in our intellectual property licenses and funding arrangements with third parties, we could lose rights that are important to our business.

We are currently party to license agreements for technologies that we anticipate using in our product development activities. In the future, we may become party to licenses that are important for product development and commercialization. If we or our third-party licensors fail to comply with the obligations under current or future license and funding agreements, our counterparties may have the right to terminate these agreements, we may be forced to terminate these agreement or we may no longer effectively rely on any licenses to us under these agreements, in which event we might not be able to develop, manufacture or market any product or utilize any technology that is covered by these agreements or may face other penalties under the agreements. Such an occurrence could materially and adversely affect the value of a product candidate being developed under any such agreement or could restrict our drug discovery activities. Termination of these agreements or reduction or elimination of our rights under these agreements may result in our having to negotiate new or reinstated agreements with less favorable terms or cause us to lose our rights under these agreements, including our rights to important intellectual property or technology.

The scope of our intellectual property may be reduced or may need to be reduced due to third-party intellectual property claims.

Our competitors may have filed, and may in the future file, patent applications covering technology similar to ours. Any such patent application may have priority over our patent applications, which could further require us to obtain rights to issued patents covering such technologies. If another party has filed a U.S. patent application on inventions similar to ours that claims priority to an application filed prior to March 16, 2013, we may have to participate in an interference proceeding declared by the USPTO to determine priority of invention in the United States. The costs of these proceedings could be substantial, and it is possible that such efforts would be unsuccessful if, unbeknownst to us, the other party had independently arrived at the same or similar invention prior to our own invention, resulting in a loss of our U.S. patent position with respect to such inventions. In addition, changes enacted on March 16, 2013, to the U.S. patent laws under the Leahy-Smith Act resulted in the United States changing from a “first to invent” country to a “first to file” country. As a result, we may lose the ability to obtain a patent if another party files with the USPTO first and could become involved in proceedings before the USPTO to resolve disputes related to inventorship. We may also become involved in similar proceedings in other jurisdictions.

Furthermore, recent changes in U.S. patent law under the Leahy-Smith Act allow for post-issuance challenges to U.S. patents, including ex parte re-examinations, inter partes reviews and post-grant reviews. There is significant uncertainty as to how the new laws will be applied. If our U.S. patents are challenged using such procedures, we may not prevail, possibly resulting in altered or diminished claim scope or loss of patent rights altogether. Similarly, some countries, notably in Europe, also have post-grant opposition proceedings or nullity proceedings that can result in changes in scope or cancellation of patent claims.

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We may be subject to claims by third parties asserting that we or our employees have misappropriated their intellectual property or claiming ownership of what we regard as our own intellectual property.

The FDA and foreign regulatory authorities closely regulate promotional materials and other promotional activities. Even if the FDA or foreign regulatory authorities initially approve product labeling that includes a description of our improved attribute claims, the FDA and foreign regulatory authorities may object to our marketing claims and product advertising campaigns. Failure to comply with the FDA’s and comparable foreign regulatory authorities’ promotional, marketing and advertising laws and regulations could lead to the issuance of warning letters, cyber letters, or untitled letters, adverse publicity, the requirement for dear-health-care-provider letters or other corrective information, fines and other monetary penalties, civil or criminal prosecution, including False Claims Act liability, restrictions on our operations and other operating requirements through consent decrees or corporate integrity agreements, debarment, exclusion from participation in federal health care programs and refusal of government contracts or future orders under existing contracts, among other consequences. Any of these consequences would harm the commercial success of our products.

Further, our promotional materials, statements and training methods must comply with the FDA’s and comparable foreign regulatory authorities’ prohibition of the promotion of unapproved, or off-label, use. Any regulatory approval that the FDA grants is limited to those specific diseases and indications for which a product is deemed to be safe and effective by FDA. Similar requirements apply in foreign jurisdictions. For example, the FDA-approved label for AZSTARYS is limited to the acute treatment of ADHD in patients 6 years of age and older, and the FDA-approved label for APADAZ is limited to the short-term (no more than 14 days) management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Physicians may use our products off-label, as the FDA does not restrict or regulate a physician’s independent choice of treatment within the practice of medicine. However, if the FDA or foreign regulatory authorities determine that our promotional materials, statements or training constitutes promotion of an off-label use, it could request that we modify our promotional materials, statements or training methods or subject us to regulatory or enforcement actions, such as the issuance of an untitled letter, a warning letter, injunction, seizure, civil fine, disgorgement of money, operating restrictions or criminal penalties. We may also be subject to actions by other governmental entities or private parties, such as the False Claims Act, civil whistleblower or “qui tam” actions. It is also possible that other federal, state or foreign enforcement authorities might take action if they consider our promotional or training materials to constitute promotion of an off-label use, which could result in significant fines or penalties under other statutory authorities, such as laws prohibiting false claims for reimbursement. In that event, our reputation could be damaged and adoption of the products could be impaired. In addition, the off-label use of our products may increase the risk of product liability claims. Product liability claims are expensive to defend and could divert our management’s attention, result in substantial damage awards against us and harm our reputation.

Any trademarks we may obtain may be infringed or successfully challenged, resulting in harm to our business.

We expect to rely on trademarks as one means to distinguish our product candidates that are approved for marketing from the products of our competitors. We have registered trademarks, including those for LAT, Zevra, and OLPRUVA. In addition, we have solicited and applied for trademarks for the Zevra logo and several potential trade names and logos for future product candidates. Third parties may oppose or attempt to cancel our trademark applications or trademarks, or otherwise challenge our use of the trademarks. If our trademarks are successfully challenged, we could be forced to rebrand our products, which could result in loss of brand recognition and could require us to devote resources to advertising and marketing new brands. Our competitors may infringe our trademarks and we may not have adequate resources to enforce our trademarks.

If we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be harmed.

In addition to seeking patent and trademark protection for our product candidates, we also rely on trade secrets, including unpatented show-how, know-how, technology and other proprietary information, to maintain our competitive position. We seek to protect our trade secrets, in part, by entering into non-disclosure and confidentiality agreements with parties who have access to them, such as our employees, corporate collaborators, outside scientific collaborators, contract manufacturers, consultants, advisors and other third parties. We also enter into confidentiality and invention or patent assignment agreements with our employees and consultants. Despite these efforts, any of these parties may breach the agreements and disclose our proprietary information, including our trade secrets. Further, we may need to share our trade secrets and confidential know-how with future business partners, collaborators, contractors and others located in countries at heightened risk of theft of trade secrets, including through direct intrusion by private parties or actors in other countries, and those affiliated with or controlled by state actors.

Monitoring unauthorized uses and disclosures of our intellectual property, including our trade secrets, is difficult, and we do not know whether the steps we have taken to protect our intellectual property will be effective. In addition, we may not be able to obtain adequate remedies for any such breaches. Enforcing a claim that a party illegally disclosed or misappropriated a trade secret is difficult, expensive and time-consuming, and the outcome is unpredictable. In addition, some courts inside and outside the United States are less willing or unwilling to protect trade secrets.

Moreover, our competitors may independently develop or reverse engineer knowledge, methods, show-how and know-how equivalent to our trade secrets. Competitors could purchase our products and replicate some or all of the competitive advantages we derive from our development efforts for technologies on which we do not have patent protection. If any of our trade secrets were to be lawfully obtained or independently developed by a competitor, we would have no right to prevent them, or those to whom they communicate such trade secrets, from using that technology or information to compete with us. If any of our trade secrets were to be disclosed to or independently developed by a competitor, our competitive position would be harmed.

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We may not be able to protect our intellectual property rights throughout the world.

Patents are of national or regional effect, and filing, prosecuting and defending patents on all of our products and technologies throughout the world would be prohibitively expensive. As such, our intellectual property rights in some countries outside the United States can be less extensive than those in the United States and we may not be able to prevent third parties from practicing our inventions in all countries outside the United States, or from selling or importing products made using our inventions in and into the United States or other jurisdictions. Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop their own products or technology and may export otherwise infringing products or technology to territories where we have patent protection, but enforcement rights are not as strong as those in the United States. These products may compete with our products and technologies, and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing. Further, the legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents and other intellectual property protection, particularly those relating to pharmaceuticals or biologics, which could make it difficult for us to stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally. Proceedings to enforce our patent rights in other jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing and could provoke third parties to assert claims against us. We may not prevail in any such lawsuits that we initiate and the damages and other remedies awarded, if any, may not be commercially meaningful. Similarly, if our trade secrets are disclosed in another jurisdiction, competitors worldwide could have access to our proprietary information and we may be without satisfactory recourse. Such disclosure could have a material adverse effect on our business. Moreover, our ability to protect and enforce our intellectual property rights may be adversely affected by unforeseen changes in intellectual property laws of other countries. In addition, certain developing countries, including China and India, have compulsory licensing laws under which a patent owner may be compelled to grant licenses to third parties. In those countries, we and our licensors may have limited remedies if patents are infringed or if we or our licensors are compelled to grant a license to a third party, which could materially diminish the value of those patents. In addition, many countries limit the enforceability of patents against government agencies or government contractors. This could limit our potential revenue opportunities. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.

In 2012, the European Patent Package, or EU Patent Package, regulations were passed with the goal of providing a single pan-European Unitary Patent and a new European Unified Patent Court, or UPC, for litigation involving European patents. The EU Patent Package went into effect June 1, 2023. Under the UPC, all European patents, including those issued prior to ratification of the European Patent Package, will by default automatically fall under the jurisdiction of the UPC. The UPC will provide our competitors with a new forum to centrally revoke our European patents, and allow for the possibility of a competitor to obtain pan-European injunctions. It will be several years before we will understand the scope of patent rights that will be recognized and the strength of patent remedies that will be provided by the UPC. Under the EU Patent Package, we will have the right to opt our patents out of the UPC over the first seven years of the court’s existence, but doing so may preclude us from realizing the benefits of the new unified court.

Our decision to seek approval of our product candidates under certain regulatory pathways, such as the 505(b)(2) NDA pathway for the FDA, may increase the risk that patent infringement suits are filed against us, which would delay FDA or comparable foreign regulatory authorities' approval of such product candidates.

Regarding any NDA that we may submit under the 505(b)(2) NDA pathway, if there are patents that claim the approved drug contained in our product candidates and referenced in our 505(b)(2) NDA, we must certify to the FDA and notify the patent holder that any patents listed for the approved drug in the FDA’s Orange Book publication are invalid, unenforceable or will not be infringed by the manufacture, use or sale of our prodrug. If a patent infringement lawsuit is filed against us within 45 days of its receipt of notice of our certification, the FDA is automatically prevented from approving our 505(b)(2) NDA until the earliest of 30 months, expiration of the patent, settlement of the lawsuit or a court decision in the infringement case that is favorable to us, or such shorter or longer period as may be ordered by a court. Such actions are routinely filed by patent owners. Accordingly, we may invest considerable time and expense in the development of our product candidates only to be subject to significant delay and patent litigation before our product candidates may be commercialized. We may not be successful in defending any patent infringement claim. Even if we are found not to infringe, or a plaintiff’s patent claims are found invalid or unenforceable, defending any such infringement claim would be expensive and time-consuming, and would delay launch of our product candidates and distract management from their normal responsibilities.

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Risks Related to Regulatory Approval of Our Product Candidates and Other Legal Compliance Matters

Failure to obtain marketing approval in international jurisdictions would prevent our approved products, and any of our other product candidates from being marketed abroad.

In order to market and sell our products in the EU and any other jurisdictions, we must obtain separate marketing approvals and comply with numerous and varying regulatory requirements. The approval procedure varies among countries and can involve additional testing. The time required to obtain approval may differ substantially from that required to obtain FDA approval. The regulatory approval process outside the United States generally includes all of the risks associated with obtaining FDA approval. In addition, in many countries outside the United States, it is required that the product be approved for reimbursement before the product can be approved for sale in that country. We may not obtain approvals from regulatory authorities outside the United States on a timely basis, if at all. Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions, and approval by one regulatory authority outside the United States does not ensure approval by regulatory authorities in other countries or jurisdictions or by the FDA. However, failure to obtain approval in one jurisdiction may impact our ability to obtain approval elsewhere. We may not be able to file for marketing approvals and may not receive necessary approvals to commercialize our products in any market.

A variety of risks associated with marketing our approved products and any of our product candidates, if approved, internationally, could affect our business.

We may seek regulatory approval for our approved products and any of our product candidates, if approved, outside of the United States and, accordingly, we expect that we will be subject to additional risks related to operating in foreign countries if we obtain the necessary approvals, including:

● differing regulatory requirements in foreign countries; ● the potential for so-called parallel importing, which is what happens when a local seller, faced with high or higher local prices, opts to import goods from a foreign market with low or lower prices rather than buying them locally; ● unexpected changes in tariffs, trade barriers, price and exchange controls and other regulatory requirements; ● economic weakness, including inflation, labor shortages, supply chain shortages, or other economic or political uncertainties or instability in particular foreign economies and markets; ● compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; ● foreign taxes, including withholding of payroll taxes; ● foreign currency fluctuations, which could result in increased operating expenses and reduced revenue, and other obligations incident to doing business in another country; ● difficulties staffing and managing foreign operations; ● workforce uncertainty in countries where labor unrest is more common than in the United States; ● potential liability under the Foreign Corrupt Practices Act of 1977 or comparable foreign regulations; ● challenges enforcing our contractual and intellectual property rights, especially in those foreign countries that do not respect and protect intellectual property rights to the same extent as the United States; ● production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and ● business interruptions resulting from geo-political actions, including war and terrorism, such as the current situation with Ukraine and Russia.

These and other risks associated with our international operations may compromise our ability to achieve or maintain profitability.

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Our approved products are, and any of our product candidates for which we obtain marketing approval will remain subject to significant post-marketing regulatory requirements and oversight.

Our approved products are, and any of our product candidates for which we obtain marketing approval could be, subject to significant post-marketing regulatory requirements and oversight, including the submission of reports to regulatory authorities and surveillance to monitor the safety and efficacy of the product, significant limitations related to use restrictions for specified age groups, warnings, precautions or contraindications, and burdensome post-approval study or risk management requirements.

For example, we are required to conduct pediatric studies related to AZSTARYS to evaluate its safety and effectiveness for the claimed indication in pediatric patients. Under the AZSTARYS License Agreement, Corium will be responsible for these regulatory activities going forward, and we cannot guarantee they will be complied with.

For OLPRUVA for oral suspension in the U.S. for the treatment of certain patients with UCDs, and for MIPLYFFA for orally-delivered treatment for NPC, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion and recordkeeping for the product will be subject to extensive and ongoing regulatory requirements. These requirements include submissions of safety and other post-marketing information and reports, registration, as well as continued compliance with cGMP and comparable foreign regulations and GCP for any clinical trials that we conduct post-approval.

In addition, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion, import, export and recordkeeping for any approved drugs are subject to extensive and ongoing regulatory requirements. These requirements include submissions of safety and other post-marketing information and reports, registration and listing requirements, payment of substantial annual product and establishment fees, labeling requirements, promotional, marketing and advertising requirements, requirements related to further development, packaging, storage and distribution requirements, cGMP requirements relating to manufacturing, quality control, quality assurance and corresponding maintenance of records and documents, requirements regarding the distribution of samples to physicians and recordkeeping. If there are any modifications to the drug, including changes in indications, labeling, manufacturing processes or facilities, or new safety issues arise, a new or supplemental NDA, a post-implementation notification or other reporting may be required or requested depending on the change, which may require additional data or additional preclinical studies and clinical trials.

Our approved products are, and if marketing approval of any of our product candidates is granted, such product candidates may be, subject to limitations on the indicated uses for which the product may be marketed or to the conditions of approval, including the requirement to implement a REMS, which could involve requirements for, among other things, a medication guide, special training for prescribers and dispensers, and patient registries. In addition, the FDA or the EMA may also impose requirements for costly post-marketing studies or clinical trials and surveillance to monitor the safety or efficacy of the product.

Products may be approved with a label that limits their approved uses, including more limited subject populations, than we request, and regulatory authorities may require that contraindications, warnings or precautions be included in the product labeling, including a boxed warning, or may approve a product candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of that product candidate, which could limit sales of the product. For instance, the label for AZSTARYS contains black box warnings regarding the risks of abuse and dependence.

Violations of the FFDCA relating to the promotion of prescription drugs may lead to a number of actions and penalties, including warning letters, cyber letters, or untitled letters, adverse publicity, the requirement for dear-health-care-provider letters or other corrective information, fines and other monetary penalties, civil or criminal prosecution, including False Claims Act liability, restrictions on our operations and other operating requirements through consent decrees or corporate integrity agreements, debarment, exclusion from participation in federal health care programs and refusal of government contracts or future orders under existing contracts, among other consequences.

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In addition, later discovery of previously unknown adverse events or other problems with our products, including those related to manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may have negative consequences, including:

● adverse inspectional findings; ● restrictions on such products, distribution, manufacturers or manufacturing processes; ● restrictions on the labeling or marketing of a drug; ● additional warnings or other restrictions on the product’s indicated use, label, or marketing; ● issuance of safety alerts, dear-healthcare-provider letters, press releases or other communications containing warnings regarding the product; ● requirement to establish or modify a REMS or similar risk management programs; ● requirement to conduct post-marketing studies or surveillance; ● restrictions on drug distribution or use; ● requirements to conduct post-marketing studies or clinical trials; ● warning letters; ● recall or withdrawal of the prodrug products from the market; ● refusal to approve pending applications or supplements to approved applications that we submit and other delays; ● clinical holds, or the suspension or termination of ongoing clinical trials; ● fines, restitution or disgorgement of profits or revenue; ● suspension or withdrawal of marketing approvals or other permits or voluntary suspension of marketing; ● refusal to permit the import or export of our products; ● reputational harm; ● refusal of government contracts or future orders under existing contracts, exclusion from participation in federal health care programs, and corporate integrity agreements; ● product seizure or detention; or ● injunctions or the imposition of civil or criminal penalties, including False Claims Act liability.

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Non-compliance with EU requirements regarding safety monitoring or pharmacovigilance, and with requi rements related to the development of drugs for the pediatric population, can also result in significant financial penalties. Similarly, failure to comply with the EU’s requirements regarding the protection of personal information can also lead to significant penalties and sanctions.

The occurrence of any event or penalty described above may inhibit our ability to commercialize our products and generate revenue, and could require us to expend significant time and resources in response and could generate negative publicity. In addition, the policies of the FDA, the EMA and other regulatory authorities may change, and additional government regulations may be enacted that could impair our business. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may be subject to enforcement action, and we may not achieve or sustain profitability.

Our employees, independent contractors, principal investigators, CROs, consultants, commercial collaborators, contract manufacturers, service providers and other vendors may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements.

We are exposed to the risk of misconduct by employees and independent contractors, such as principal investigators, CROs, consultants, commercial collaborators, contract manufacturers, service providers and other vendors. Such misconduct could include failures to comply with FDA, the EMA, or comparable foreign regulations, to provide accurate information to the FDA, the EMA, or comparable foreign authorities, to comply with manufacturing standards that we have established or that are established by regulation, to comply with federal and state contracting and healthcare fraud and abuse laws, to report drug pricing, financial information or data accurately or to disclose unauthorized activities to us. In particular, sales, marketing and other business arrangements in the healthcare industry are subject to extensive laws intended to prevent fraud, kickbacks, self-dealing and other abusive practices. These laws may restrict or prohibit a wide range of business activities, including, but not limited to, research, manufacturing, distribution, pricing, discounting, marketing, advertising and promotion, sales commissions, customer incentive programs and other business arrangements. Employee and independent contractor misconduct could also involve the improper use of individually identifiable information, including, without limitation, information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation. In addition, federal procurement laws impose substantial penalties for misconduct in connection with government contracts and require certain contractors to maintain a code of business ethics and conduct and self-disclose credible evidence of False Claims Act violations.

It is not always possible to identify and deter employee and independent contractor misconduct, and any precautions we take to detect and prevent improper activities may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws. If any such actions are instituted against us, those actions could have a significant impact on our business, including the imposition of warning letters, untitled letters, cyber letters, seizure or recall of products, injunctions, withdrawal of product approval or other permits, clinical holds and termination of clinical trials, FDA or foreign regulatory authorities refusal to approve pending applications, product detentions, FDA, DEA, or comparable foreign regulatory authorities consent decrees, restriction or suspension of manufacturing and distribution, debarment, refusal to allow product import or export, adverse publicity, refusal of government contracts or future orders under existing contracts, dear-health-care-provider letters or other warnings or corrective information, recalls, delays, significant civil, criminal and administrative penalties including False Claims Act liability, damages, monetary fines, disgorgement, restitution, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, corporate integrity agreements, contractual damages, reputational harm, diminished profits and future earnings and curtailment or restructuring of our operations, among other consequences, any of which could adversely affect our ability to operate.

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Our current and future relationships with healthcare professionals, principal investigators, consultants, customers and third-party payors in the United States and elsewhere may be subject, directly or indirectly, to applicable anti-kickback, fraud and abuse, false claims, physician payment transparency, and other healthcare laws and regulations, which could expose us to penalties.

Healthcare providers and third-party payors in the United States and elsewhere play a primary role in the recommendation and prescription of our products, as well as any product candidates for which we obtain marketing approval. Our and our commercial partners' current and future arrangements with healthcare professionals, principal investigators, consultants, customers and third-party payors may expose us to broadly applicable fraud and abuse and other healthcare laws, including, without limitation, the Anti-Kickback Statute and the False Claims Act, that may constrain the business or financial arrangements and relationships through which we and our commercial partners sell, market and distribute any product candidates for which we obtain marketing approval. In addition, we may be subject to transparency laws with respect to drug pricing and transfers of value made to physicians and other healthcare professionals. The applicable federal, state and foreign healthcare laws that may affect our ability to operate include the following:

● the federal Anti-Kickback Statute, which prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, receiving or paying remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, lease, order or arranging for the purchase, lease or order of, any good, facility, item or service, for which payment may be made, in whole or in part, under federal and state healthcare programs such as Medicare and Medicaid. A person or entity does not need to have actual knowledge of this statute or specific intent to violate it in order to have committed a violation; ● federal civil and criminal false claims laws, including the False Claims Act, which impose criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or entities for, among other things, knowingly presenting, or causing to be presented, to the federal government, including the Medicare and Medicaid programs, claims for payment that are false or fraudulent or making or using a false record or statement material to a false or fraudulent claim or to avoid, decrease or conceal an obligation to pay money to the federal government, including erroneous pricing information on which mandatory rebates, discounts and reimbursement amounts are based, or in the case of the False Claims Act, for violations of the federal Anti-Kickback Statute in connection with a claim for payment or for conduct constituting reckless disregard for the truth; ● the civil monetary penalties statute, which imposes penalties against any person or entity who, among other things, is determined to have presented or caused to be presented a claim to a federal health program that the person knows or should know is for an item or service that was not provided as claimed or is false or fraudulent; ● the Health Insurance Portability and Accountability Act, or HIPAA, which created additional federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of whether the payor is public or private, knowingly and willfully embezzling or stealing from a health care benefit program, willfully obstructing a criminal investigation of a health care offense and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters. Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of this statute or specific intent to violate it in order to have committed a violation; ● the federal Physician Payments Sunshine Act and its implementing regulations, impose new annual reporting requirements for manufacturers of drugs, devices, biologicals and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with certain exceptions, to annually report certain payments and transfers of value provided to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other healthcare professionals (physician assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, anesthesiologist assistants and certified nurse-midwives) and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, such providers and teaching hospitals, and to report annually certain ownership and investment interests held by physicians and their immediate family members; and

● analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers; certain state laws which require drug manufacturers to comply with the industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government and may require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; certain state laws that require manufacturers to report information on the pricing of certain drug products; and certain state and local laws require the registration or pharmaceutical sales representatives.

These laws may affect our and our commercial partners' sales, marketing, and other promotional activities by imposing administrative and compliance burdens on us and our commercial partners.

Efforts to ensure that our current and future business arrangements with third parties will comply with applicable healthcare laws and regulations may involve substantial costs. It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws, or that our compliance systems are inadequate to detect and report such conduct or to report accurate pricing information to the government. If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, including, without limitation, damages, fines, imprisonment, exclusion from participation in government healthcare programs, such as Medicare and Medicaid, corporate integrity agreements or similar agreements to resolve allegations of non-compliance with these laws, and the curtailment or restructuring of our operations, which could significantly harm our business. If any of the physicians or other healthcare providers or entities with whom we currently, or expect to, do business, including future collaborators, is found not to be in compliance with applicable laws, they and we may be subject to significant penalties and potential exclusion from participation in healthcare programs as a result of their non-compliance.

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Recently enacted and future legislation may increase the difficulty and cost for us to obtain marketing approval of our product candidates and increase the cost to commercialize our approved products, and any of our product candidates that may be approved in the future and affect the prices thereof.

In the United States and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could, among other things, prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities and affect the ability to profitably sell our approved products and our ability to profitably sell any of our product candidates for which we obtain marketing approval.

Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and/or expanding access. In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives. For example, in March 2010, the ACA was signed into law and was intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add new transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms.

Among the provisions of the ACA of importance to our potential product candidates are the following:

● an annual, nondeductible fee on any entity that manufactures or imports certain branded prescription drugs and biologic agents, apportioned among these entities according to their market share in certain government healthcare programs; ● an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program to 23.1% and 13.0% of the average manufacturer price for branded drugs and generic drugs, respectively; ● expansion of healthcare fraud and abuse laws, including the False Claims Act and the federal Anti-Kickback Statute, new government investigative powers and enhanced penalties for non-compliance; ● establishment of a new and distinct methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected; ● a new Medicare Part D coverage gap discount program (which was replaced in 2025), in which manufacturers were required to offer 70% point-of-sale discounts off negotiated prices (generally as negotiated between the Medicare Part D plan and the pharmacy) of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D; ● extension of manufacturers’ Medicaid rebate liability to covered drugs dispensed to individuals who are enrolled in Medicaid managed care organizations and extension of the inflation percentage applicable to existing branded drugs to new formulations for purposes of computing the inflation penalty component of Medicaid rebates; ● expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to additional individuals and by adding new mandatory eligibility categories for certain individuals with income at or below 133% of the Federal Poverty Level, thereby potentially increasing manufacturers’ Medicaid rebate liability; ● expansion of the entities eligible for discounts under the Public Health Service pharmaceutical pricing program; ● the new requirements under the federal Open Payments program and its implementing regulations; ● a new requirement to annually report drug samples that manufacturers and distributors provide to physicians; and ● a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research.

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Since its enactment, there have been executive, judicial and congressional challenges to certain aspects of the ACA. On June 17, 2021, the U.S. Supreme Court dismissed the most recent judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA. Thus, the ACA will remain in effect in its current form.

In addition, other legislative changes have been proposed and adopted since the ACA was enacted. In August 2011, the Budget Control Act of 2011, among other things, included aggregate reductions to Medicare payments to providers, which went into effect in April 2013, and, due to subsequent legislative amendments, will stay in effect through 2032, In January 2013, the American Taxpayer Relief Act of 2012 was signed into law, which, among other things, further reduced Medicare payments to several providers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. In addition, on March 11, 2021, the American Rescue Plan Act of 2021 was signed into law, which eliminated the statutory Medicaid drug rebate cap, beginning January 1, 2024. The rebate was previously capped at 100% of a drug's average manufacturer price.

Further, there has been increasing legislative and enforcement interest in the United States with respect to specialty drug pricing practices. Specifically, there have been several recent U.S. Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the cost of drugs under Medicare, and reform government program reimbursement methodologies for drugs. On August 16, 2022, the Inflation Reduction Act of 2022, or IRA, was signed into law. Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (beginning in 2026), imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023), and replaces the Part D coverage gap discount program with a new manufacturer discounting program (which began in 2025). The IRA permits the Secretary of the Department of Health and Human Services, or HHS, to implement many of these provisions through guidance, as opposed to regulation, for the initial years. CMS has published the negotiated prices for the initial ten drugs, which will first be effective in 2026, and has published the list of the subsequent 15 drugs that will be subject to negotiation, although the drug price negotiation program is currently subject to legal challenges. For that and other reasons, it is currently unclear how the IRA will be effectuated. At the state level, legislatures are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure, drug price increase reporting and other transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. Some states have enacted legislation creating so-called prescription drug affordability boards, which ultimately may attempt to impose price limits on certain drugs in these states. These new laws may result in additional reductions in Medicare and other healthcare funding, which could negatively impact customers for our product candidates, if approved, and, accordingly, our financial operations

In the EU, on December 13, 2021, Regulation No 2021/2282 on Health Technology Assessment (“HTA”) amending Directive 2011/24/EU, was adopted. The Regulation entered into force in January 2022 and has been applicable since January 2025, with phased implementation based on the type of product, i.e. oncology and advanced therapy medicinal products as of 2025, orphan medicinal products as of 2028, and all other medicinal products by 2030. The Regulation intends to boost cooperation among EU member states in assessing health technologies, including new medicinal products, and provide the basis for cooperation at the EU level for joint clinical assessments in these areas. It will permit EU member states to use common HTA tools, methodologies, and procedures across the EU, working together in four main areas, including joint clinical assessment of the innovative health technologies with the highest potential impact for patients, joint scientific consultations whereby developers can seek advice from HTA authorities, identification of emerging health technologies to identify promising technologies early, and continuing voluntary cooperation in other areas. Individual EU member states will continue to be responsible for assessing non-clinical (e.g., economic, social, ethical) aspects of health technology, and making decisions on pricing and reimbursement. We expect that the healthcare reform measures that have been adopted and may be adopted in the future, may, among other things, result in more rigorous coverage criteria and in additional downward pressure on the price that we receive for any approved product. Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize our prodrug product candidates.

Legislative and regulatory proposals and enacted statutes have been made to expand post-approval requirements and restrict sales and promotional activities for drugs. For instance, the Drug Supply Chain Security Act imposes obligations on manufacturers of pharmaceutical products, among others, related to product tracking and tracing. Among the requirements of this new legislation, manufacturers are required to provide specified information regarding the drug products they produce to individuals and entities to which product ownership is transferred, label drug products with a product identifier and keep specified records regarding the drug products. The transfer of information to subsequent product owners by manufacturers will eventually be required to be done electronically. Manufacturers are also required to verify that purchasers of products are appropriately licensed. Further, under this legislation, manufacturers have drug product investigation, quarantine, disposition and FDA and trading-partner notification responsibilities related to counterfeit, diverted, stolen and intentionally adulterated products, as well as products that are the subject of fraudulent transactions or which are otherwise unfit for distribution such that they would be reasonably likely to result in serious health consequences or death.

In the EU, the EU pharmaceutical legislation is currently undergoing a complete review process, in the context of the Pharmaceutical Strategy for Europe initiative, launched by the European Commission in November 2020. The European Commission’s proposal for revision of several legislative instruments related to medicinal products (potentially reducing the duration of regulatory data protection, revising the eligibility for expedited pathways, etc.) was published on April 26, 2023. The proposed revisions remain to be agreed and adopted by the European Parliament and European Council and the proposals may therefore be substantially revised before adoption, which is not anticipated before early 2026. The revisions may, however, have a significant impact on the pharmaceutical industry and our business in the long term.

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We cannot be sure whether additional legislative changes will be enacted, or whether the FDA or foreign regulations, guidance or interpretations will be changed, or what the impact of such changes on the marketing approvals of our product candidates, if any, may be. In addition, increased scrutiny by the U.S. Congress of the FDA’s approval process may significantly delay or prevent marketing approval, as well as subject us to more stringent product labeling and post-marketing testing and other requirements.

If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate Program or other governmental pricing programs in which we participate, we could be subject to additional reimbursement requirements, penalties, sanctions and fines, which could have a material adverse effect on our business, financial condition, results of operations and growth prospects.

Medicaid is a joint federal and state program administered by the states for low income and disabled beneficiaries. We participate in and have certain price reporting obligations under the Medicaid Drug Rebate Program, or the MDRP, as a condition of having covered outpatient drugs payable under Medicaid and, if applicable, under Medicare Part B. The MDRP requires us to pay a rebate to state Medicaid programs every quarter for each unit of our covered outpatient drugs dispensed to Medicaid beneficiaries and paid for by a state Medicaid program. The rebate is based on pricing data that we must report on a monthly and quarterly basis to the Centers for Medicare & Medicaid Services, or CMS, the federal agency that administers the MDRP and other governmental healthcare programs. These data include the average manufacturer price (AMP) for each drug and, in the case of innovator products, the best price, which in general represents the lowest price available from the manufacturer to certain entities in the U.S. in any pricing structure, calculated to include all sales and associated rebates, discounts and other price concessions. The Medicaid rebate consists of two components, the basic rebate and the additional rebate, which is triggered if the AMP for a drug increases faster than inflation. If we become aware that our MDRP government price reporting submission for a prior quarter was incorrect or has changed as a result of recalculation of the pricing data, we must resubmit the corrected data for up to three years after those data originally were due. If we fail to provide information timely or are found to have knowingly submitted false information to the government, we may be subject to civil monetary penalties and other sanctions, including termination from the MDRP. In the event that CMS terminates our rebate agreement pursuant to which we participate in the MDRP, no federal payments would be available under Medicaid or Medicare Part B for our covered outpatient drugs. Our failure to comply with our MDRP price reporting and rebate payment obligations could negatively impact our financial results.

The recently-enacted IRA imposes rebates under Medicare Part B and Medicare Part D that are triggered by price increases that outpace inflation (first due in 2023), as described under the risk factor “Recently enacted and future legislation may increase the difficulty and cost for us to obtain marketing approval of our product candidates and increase the cost to commercialize our approved products, and any of our product candidates that may be approved in the future and affect the prices thereof,” above. The Medicare Part D rebate will be calculated on the basis of the AMP figures we report pursuant to the MDRP.

Federal law requires that any company that participates in the MDRP also participate in the Public Health Service’s 340B drug pricing program in order for federal funds to be available for the manufacturer’s drugs under Medicaid and, if applicable, Medicare Part B. We participate in the 340B program, which is administered by the Health Resources and Services Administration, or HRSA, and requires us to charge statutorily defined covered entities no more than the 340B “ceiling price” for our covered outpatient drugs[BP(A4] [TS5] [RC6] . These 340B covered entities include a variety of community health clinics and other entities that receive health services grants from the Public Health Service, as well as hospitals that serve a disproportionate share of low‑income patients. The ACA expanded the list of covered entities to include certain free‑standing cancer hospitals, critical access hospitals, rural referral centers and sole community hospitals, but exempts “orphan drugs,” such as OLPRUVA, from the ceiling price requirements for these covered entities. The 340B ceiling price is calculated using a statutory formula based on the AMP and rebate amount for the covered outpatient drug as calculated under the MDRP, and in general, products subject to Medicaid price reporting and rebate liability are also subject to the 340B ceiling price calculation and discount requirement. We must report 340B ceiling prices to HRSA on a quarterly basis, and HRSA publishes those prices to 340B covered entities. In addition, HRSA has finalized regulations regarding the calculation of the 340B ceiling price and the imposition of civil monetary penalties on manufacturers that knowingly and intentionally overcharge covered entities for 340B‑eligible drugs. HRSA has also finalized a revised regulation implementing an administrative dispute resolution process through which 340B covered entities may pursue claims against participating manufacturers for overcharges, and through which manufacturers may pursue claims against 340B covered entities for engaging in unlawful diversion or duplicate discounting of 340B drugs. Our failure to comply 340B program requirements could negatively impact our financial results. Any additional future changes to the definition of average manufacturer price and the Medicaid rebate amount under legislation or regulation could affect our 340B ceiling price calculations and also negatively impact our financial results.

In order for OLPRUVA or any product candidates, if approved, to be paid for with federal funds under the Medicaid and Medicare Part B programs and purchased by certain federal agencies and grantees, we also participate in the U.S. Department of Veterans Affairs, or VA, Federal Supply Schedule, or FSS, pricing program. As part of this program, we are required to make our products available for procurement on an FSS contract under which we must comply with standard government terms and conditions and charge a price that is no higher than the statutory Federal Ceiling Price, or FCP, to four federal agencies (VA, U.S. Department of Defense, or DOD, Public Health Service, and U.S. Coast Guard). The FCP is based on the Non-Federal Average Manufacturer Price, or Non-FAMP, which we must calculate and report to the VA on a quarterly and annual basis. Pursuant to applicable law, knowing provision of false information in connection with a Non-FAMP filing can subject a manufacturer to significant civil monetary penalties for each item of false information. The FSS pricing and contracting obligations also contain extensive disclosure and certification requirements.

We also participate in the Tricare Retail Pharmacy program, under which we are required to pay quarterly rebates on utilization of innovator products that are dispensed through the Tricare Retail Pharmacy network to Tricare beneficiaries. The rebates are calculated as the difference between the annual Non-FAMP and FCP. We are required to list our innovator products on a Tricare Agreement in order for them to be eligible for DOD formulary inclusion. If we overcharge the government in connection with our FSS contract or Tricare Agreement, whether due to a misstated FCP or otherwise, we are required to refund the difference to the government. Failure to make necessary disclosures and/or to identify contract overcharges could result in allegations against us under the False Claims Act and other laws and regulations. Unexpected refunds to the government, and responding to a government investigation or enforcement action, would be expensive and time-consuming, and could have a material adverse effect on our business, financial condition, results of operations and growth prospects.

Individual states continue to consider and have enacted legislation to limit the growth of healthcare costs, including the cost of prescription drugs and combination products. A number of states have either implemented or are considering implementation of drug price transparency legislation. Requirements of pharmaceutical manufacturers under such laws include advance notice of planned price increases, reporting price increase amounts and factors considered in taking such increases, wholesale acquisition cost information disclosure to prescribers, purchasers, and state agencies, and new product notice and reporting. Such legislation could limit the price or payment for certain drugs, and a number of states are authorized to impose civil monetary penalties or pursue other enforcement mechanisms against manufacturers who fail to comply with drug price transparency requirements, including the untimely, inaccurate, or incomplete reporting of drug pricing information.

Pricing and rebate calculations vary among products and programs. The calculations are complex and are often subject to interpretation by us, governmental or regulatory agencies, and the courts. CMS, the Department of Health & Human Services Office of Inspector General, and other governmental agencies have pursued manufacturers that were alleged to have failed to report these data to the government in a timely or accurate manner. Governmental agencies may also make changes in program interpretations, requirements or conditions of participation, some of which may have implications for amounts previously estimated or paid. We cannot assure you that any submissions we are required to make under the MDRP, the 340B program, the VA/FSS program, the Tricare Retail Pharmacy Program, and other governmental drug pricing programs will not be found to be incomplete or incorrect

Governments outside the United States tend to impose strict price controls, which may affect our revenue, if any.

In some countries, particularly the EU member states, the pricing of prescription pharmaceuticals is subject to governmental control. In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt of marketing approval for a product. To obtain coverage and reimbursement or pricing approval in some member states, we may be required to conduct a clinical trial that compares the cost-effectiveness of our product candidate to other available therapies. If reimbursement of our prodrug products is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our business could be harmed, possibly materially.

If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could harm our business.

We are subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. Our operations involve the use of hazardous and flammable materials, including chemicals and biological materials. Our operations also produce hazardous waste products. We generally contract with third parties for the disposal of these materials and wastes. We cannot eliminate the risk of contamination or injury from these materials. In the event of contamination or injury resulting from our use of hazardous materials, we could be held liable for any resulting damages, and any liability could exceed our resources. We also could incur significant costs associated with civil or criminal fines and penalties for failure to comply with such laws and regulations.

Although we maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to injuries to our employees resulting from the use of hazardous materials, this insurance may not provide adequate coverage against potential liabilities. We do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us in connection with our storage or disposal of biological, hazardous or radioactive materials.

In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations. These current or future laws and regulations may impair our research, development or production efforts. Our failure to comply with these laws and regulations also may result in substantial fines, penalties or other sanctions.

If our security measures are compromised now, or in the future, or the security, confidentiality, integrity or availability of, our information technology systems, software, services, communications or data is compromised, limited or fails, this could result in a material adverse impact, including without limitation, a material interruption to our operations, harm to our reputation, significant fines, penalties and liability, breach or a triggering of data protection laws, privacy policies and data protection obligations, loss of customers or sales, or material disruption of our clinical trials or other business activity.

In the ordinary course of our business, we may collect, process, transmit and store proprietary, confidential and sensitive information, including personal information (including key-coded data and health information), intellectual property, trade secrets and proprietary business information (collectively, “Confidential Information”) owned or controlled by ourselves or other parties. It is critical that we do so in a secure manner to maintain the confidentiality and integrity of such Confidential Information.

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There can be no assurance that our cybersecurity risk management program and processes, including our policies, controls or procedures, will be fully implemented, complied with or effective in protecting our systems and information. Despite the implementation of security measures, our information technology systems and data, and those of our CROs and other third parties on which we rely, are vulnerable to system failure, interruption, compromise, attack or damage from several sources, such as data corruption; breakdown; malicious human acts; malware (such as ransomware); misconfigurations, “bugs” or other vulnerabilities,; malicious code (such as computer viruses or worms); fraudulent activity; employee misconduct, theft or error; denial-of-service attacks; public health epidemics; cyber-attacks by sophisticated nation-state and nation-state supported actors; natural disasters; terrorism; war (such as the current situation with Ukraine and Russia); and telecommunication and electrical failures. We have also outsourced elements of our information technology infrastructure, and as a result a number of third-party vendors may or could have access to our confidential information. Our recovery systems (and those of third parties upon whom we rely) are similarly vulnerable. Any of these events could lead to the unauthorized access, disclosure and use of proprietary, confidential, or otherwise non-public information (such as personal information). The techniques used by criminal actors to attack computer systems are sophisticated, change frequently and may originate from less regulated and remote areas of the world. As a result, we may not be able to address these techniques proactively or implement adequate preventative measures. Attacks upon information technology systems are also increasing in their levels of persistence and intensity and are being conducted by sophisticated and organized groups and individuals with a wide range of motives and expertise. As a result of the continued hybrid working environment, we may also face increased cybersecurity risks due to our reliance on internet technology and the number of our employees who are working remotely, which may create additional opportunities for cybercriminals to exploit vulnerabilities. We may also experience security breaches that may remain undetected for an extended period. Even if identified, we may be unable to adequately investigate or remediate incidents or breaches due to attackers increasingly using tools and techniques that are designed to circumvent controls, to avoid detection, and to remove or obfuscate forensic evidence. If we or our third-party vendors were to experience a significant cybersecurity breach of our or their information systems or data, the costs associated with the investigation, remediation and potential notification of the breach to counter-parties and data subjects could be material. We may be required to expend significant resources, fundamentally change our business activities and practices, or modify our operations, including our clinical trial activities, or information technology in an effort to protect against security breaches and to mitigate, detect and remediate actual and potential vulnerabilities. Due to the nature of some of these threats, we may be unable to anticipate threats, and there is a risk that a threat may remain undetected for a period of time. The costs of maintaining or upgrading our cyber-security systems at the level commercially reasonable to keep up with our expanding operations and prevent against potential attacks are increasing, and despite our best efforts, our network security and data recovery measures and those of our vendors may still not be adequate to protect against such security breaches and disruptions, which could cause harm to our business, financial condition and results of operations. In addition, our remediation efforts may not be successful. If we do not allocate and effectively manage the resources necessary to build and sustain the proper technology and cybersecurity infrastructure, we could suffer significant business disruption, including transaction errors, supply chain or manufacturing interruptions, processing inefficiencies, data loss or the loss of or damage to intellectual property or other proprietary information.

We and certain of our service providers are from time to time subject to cyberattacks and security incidents. While we do not believe that we have experienced any significant system failure, accident or security breach to date, if we, our service providers, partners, or other relevant third parties experience any such incident that results in any data loss, deletion or destruction, unauthorized access to, loss of, acquisition or disclosure of, exposure or disclosure of sensitive information, or compromise related to the security, confidentiality, integrity or availability of our (or their) information technology, software, services, communications or data, it may result in a material adverse impact, including without limitation, fines, damages, litigation, enforcement actions, loss of trade secrets, a material disruption of our drug development programs, or other harm to our business. For example, the loss of clinical trial data from completed or ongoing or planned clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. To the extent that any disruption or security breach was to result in a loss of or damage to our data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability and the further development of our product candidates could be delayed. If such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our business. Additionally, applicable data protection laws, privacy policies and data protection obligations (such as contractual obligations) may require us to notify relevant stakeholders of security breaches, including affected individuals, customers and regulators. Such disclosures are costly, and the disclosure or the failure to comply with such requirements, could lead to material adverse impacts, including without limitation, legal claims or proceedings (such as class actions), regulatory investigations and enforcement actions, fines and penalties, negative reputational impacts that cause us to lose existing or future customers, and/or significant incident response, system restoration or remediation and future compliance costs. There can be no assurance that the limitations of liability in our contracts would be enforceable or adequate or would otherwise protect us from liabilities or damages if we fail to comply with applicable data protection laws, privacy policies or data protection obligations related to information security or security breaches.

Further, failures or significant downtime of our information technology or telecommunication systems or those used by our third-party service providers could cause significant interruptions in our operations and adversely impact the confidentiality, integrity and availability of sensitive or confidential information, including preventing us from conducting clinical trials, tests or research and development activities and preventing us from managing the administrative aspects of our business.

We cannot be sure that our insurance coverage will be adequate or otherwise protect us from or adequately mitigate liabilities or damages with respect to claims, costs, expenses, litigation, fines, penalties, business loss, data loss, regulatory actions or materially adverse impacts arising out of our privacy and cybersecurity practices, processing or security breaches that we may experience, or that such coverage will continue to be available on acceptable terms at all. The successful assertion of one or more large claims against us that exceeds our available insurance coverage, or results in changes to our insurance policies (including premium increases or the imposition of a large deductible or co-insurance requirements), could have an adverse effect on our business. In addition, we cannot be sure that our existing coverage and coverage for errors and omissions will continue to be available on acceptable terms or that our insurers will not deny coverage as to any future claim.

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Failure or perceived failure to comply with existing or future laws, regulations, contracts, self-regulatory schemes, policies, standards and other obligations related to data privacy or security could lead to government enforcement actions (which could include civil or criminal fines or penalties), a disruption of our clinical trials or commercialization of our products, private litigation, other liabilities, and/or adverse publicity. Compliance or the failure to comply with such obligations could increase the costs of our products, could limit their use or adoption, and could otherwise negatively affect our operating results and business.

Regulation of data (including personal data) is evolving, as federal, state, and foreign governments continue to adopt new, or modify existing, laws and regulations addressing data privacy and security, and the collection, processing, storage, transfer, and use of data. We and our collaborators may be subject to current, new, or modified federal, state, and foreign data protection laws and regulations. These new or proposed laws and regulations are subject to differing interpretations and may be inconsistent among jurisdictions, and guidance on implementation and compliance practices are often updated or otherwise revised, which adds to the complexity of processing personal data. Moreover, we are subject to the terms of our privacy and security policies, representations, certifications, standards, publications, contracts and other obligations to third parties related to data privacy, security and processing. These and other requirements could require us or our collaborators to incur additional costs to achieve compliance, limit our competitiveness, necessitate the acceptance of more onerous obligations in our contracts, restrict our ability to use, store, transfer, and process data, impact our or our collaborators’ ability to process or use data in order to support the provision of our products, affect our or our partners’ ability to offer our products or operate in certain locations, cause regulators to reject, limit, or disrupt our clinical trial activities, result in increased expenses, reduce overall demand for our products and services and make it more difficult to meet expectations of or commitments to customers or collaborators. Any failure or perceived failure by us to comply with federal, state or foreign laws or regulations, our internal policies and procedures or our contracts governing our processing of personal information could result in negative publicity, government investigations and enforcement actions, claims by third parties and damage to our reputation, any of which could have a material adverse effect on our business, results of operation, and financial condition.

Furthermore, the Federal Trade Commission, or the FTC, also has authority to initiate enforcement actions against entities that mislead customers about HIPAA compliance, make deceptive statements about privacy and data sharing in privacy policies, fail to limit third-party use of personal health information, fail to implement policies to protect personal health information or engage in other unfair practices that harm customers or that may violate Section 5 of the FTC Act. Even when HIPAA does not apply, failing to take appropriate steps to keep consumers’ personal information secure can constitute unfair acts or practices in or affecting commerce in violation of Section 5(a) of the FTC Act. The FTC expects a company’s data security measures to be reasonable and appropriate in light of the sensitivity and volume of consumer information it holds, the size and complexity of its business, and the cost of available tools to improve security and reduce vulnerabilities. Additionally, federal and state consumer protection laws are increasingly being applied by FTC and states’ attorneys general to regulate the collection, use, storage, and disclosure of personal or personally identifiable information, through websites or otherwise, and to regulate the presentation of website content.

Certain states have also adopted laws and regulations that govern the privacy, processing and protection of health-related and other personal information. Such laws and regulations will be subject to interpretation by various courts and other governmental authorities, thus creating potentially complex compliance issues for us and our future customers and strategic partners. For example, the California Consumer Privacy Act of 2018, as amended by the California Privacy Rights Act, collectively the CCPA, requires businesses that process the personal information of the California residents to, among other things, (i) provide certain disclosures to California residents regarding the business's collection, use, and disclosure of their personal information (ii) receive and respond to requests from California residents to access, delete, and correct their personal information or opt out of certain disclosures of their personal information; and (iii) enter into specific contractual provisions with service providers that process California resident personal information on the business’s behalf. Additional compliance investment and potential business process changes may also be required. Similar laws have been passed in other states and are continuing to be proposed at the state and federal level, reflecting a trend toward more stringent privacy legislation in the United States. As we expand our operations, these and similar laws may increase our compliance costs and potential liability. The enactment of such laws could have potentially conflicting requirements that would make compliance challenging. In the event that we are subject to or affected by HIPAA, the CCPA, or other domestic privacy and data protection laws, any liability from failure to comply with the requirements of these laws could adversely affect our financial condition.

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Foreign data protection laws, such as the GDPR and member state data protection laws, may also apply to health-related and other personal data that we process, including personal data relating to clinical trial participants. European data protection laws impose strict obligations on the ability to process health-related and other personal data of data subjects in Europe, including standards relating to the privacy and security of personal data. For example, in Europe, the European Union General Data Protection Regulation, or the GDPR, went into effect in May 2018 and imposes strict requirements for processing the personal data of individuals within the European Economic Area, or the EEA. Companies that must comply with the GDPR face increased compliance obligations and risk, including more robust regulatory enforcement of data protection requirements and potential fines for noncompliance of up to €20 million or 4% of the annual global revenues of the noncompliant company, whichever is greater. In addition to fines, a breach of the GDPR may result in regulatory investigations, reputational damage, orders to cease/ change our data processing activities, enforcement notices, assessment notices (for a compulsory audit) and/ or civil claims (including class actions). Among other requirements, the GDPR regulates transfers of personal data subject to the GDPR to third countries that have not been found to provide adequate protection to such personal data, including the United States, and the efficacy and longevity of current transfer mechanisms between the EEA and the United States remains uncertain.

We expect the existing legal complexity and uncertainty regarding international personal data transfers to continue. As a result, we may have to make certain operational changes and we will have to implement revised standard contractual clauses and other relevant documentation for existing data transfers within required time frames As supervisory authorities issue further guidance on personal data export mechanisms, including circumstances where the standard contractual clauses cannot be used, and/or start taking enforcement action, we could suffer additional costs, complaints and/or regulatory investigations or fines, and/or if we are otherwise unable to transfer personal data between and among countries and regions in which we operate, it could affect the manner in which we provide our services, the geographical location or segregation of our relevant systems and operations, and could adversely affect our financial results. Additionally, other countries have passed or are considering passing laws requiring local data residency and/or restricting the international transfer of data. As we continue to expand into other foreign countries and jurisdictions, we may be subject to additional laws and regulations regarding personal data protection and international personal data transfers that may affect how we conduct business.

Failure, or perceived failure, to comply with the GDPR, the UK GDPR, and other countries' data protection laws and regulations, privacy policies, contracts and other data protection obligations could result in government investigations and enforcement actions (which could include civil or criminal penalties, fines, or sanctions), private litigation, a diversion of management’s attention, adverse publicity and other negative effects on our operating results and business. There can be no assurance that the limitations of liability in our contracts would be enforceable or adequate or would otherwise protect us from liabilities or damages if we fail to comply with applicable data protection laws, privacy policies or data protection obligations related to information security or security breaches. Moreover, clinical trial participants or subjects about whom we or our collaborators obtain information, as well as the providers who share this information with us, may contractually limit our ability to use and disclose the information. Claims that we have violated individuals’ privacy rights or failed to comply with data protection laws, contracts, privacy notices or other obligations even if we are not found liable, could be expensive and time-consuming to defend and could result in adverse publicity that could harm our business.

Although we work to comply with applicable laws, regulations and standards, our contractual obligations and other legal obligations, these requirements are evolving and may be modified, interpreted and applied in an inconsistent manner from one jurisdiction to another, and may conflict with one another or other legal obligations with which we must comply. Any failure or perceived failure by us or our employees, representatives, contractors, consultants, collaborators, or other third parties to comply with such requirements or adequately address privacy and security concerns, even if unfounded, could result in additional cost and liability to us, damage our reputation, and adversely affect our business and results of operations.

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We are subject to complex and changing laws and regulations, which exposes us to potential liabilities, increased costs and other adverse effects on our business.

We are subject to complex and changing laws, regulations, and executive orders, and compliance with these laws and regulations and executive orders, as well as changing interpretations and enforcement priorities related to such laws, regulations, and executive orders, which are onerous and expensive. Compliance with such laws, regulations, and executive orders can adversely affect our business by increasing our costs, limiting our ability to pursue or offer a product candidate or product, and requiring changes to our business. New and changing laws, regulations, and executive orders can also create uncertainty about how such laws and regulations will be interpreted and applied. Regulatory changes and other actions that materially adversely affect our business may be announced with little or no advance notice we may not be able to effectively mitigate all adverse impacts from such measures. Differing interpretations of such legal obligations and changes in enforcement priorities can expose us to significant fines, government investigations, litigation and reputational harm. If we are found to have violated laws, regulations, or executive orders, it could materially adversely affect our business, reputation, results of operations and financial condition.

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Risks Related to Employee Matters and Managing Our Growth

Our future success depends on our ability to retain key executives and to attract, retain and motivate qualified personnel.

We are highly dependent on the management, research and development, clinical, financial and business development expertise of our senior leadership team, as well as the other members of our scientific and clinical teams. Although we have employment agreements with each of our executive officers, these agreements do not obligate them to continue working for our company and they may terminate their employment with us at any time. Our future performance will depend, in part, the successful transitions and integration of new senior level executives into their roles and the continuity of leadership among the larger workforce. If we do not successfully manage executive transitions, it could be viewed negatively by our customers, employees, investors, and other third-party partners, and could have an adverse impact on our business and results of operations.

Recruiting and retaining qualified scientific and clinical personnel and, if we progress the development of our product candidate pipeline toward scaling up for commercialization, manufacturing and sales and marketing personnel, will also be critical to our success. The loss of the services of our executive officers or other key employees could impede the achievement of our research, development and commercialization objectives and seriously harm our ability to successfully implement our business strategy. Furthermore, replacing executive officers and key employees may be difficult and may take an extended period of time because of the limited number of individuals in our industry with the breadth of skills and experience required to successfully develop, gain regulatory approval of and commercialize our prodrug product candidates. Competition to hire from this limited pool is intense, and we may be unable to hire, train, retain or motivate these key personnel on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies for similar personnel. We also experience competition for the hiring of scientific and clinical personnel from universities and research institutions. In addition, we rely on consultants and advisors, including scientific and clinical advisors, to assist us in formulating our research and development and commercialization strategy. Our consultants and advisors may have commitments under consulting or advisory contracts with other entities that may limit their availability to us. If we are unable to continue to attract and retain high quality personnel, our ability to pursue our growth strategy will be limited.

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Risks Related to Ownership of Our Common Stock and Our Status as a Public Company

The trading price of the shares of our common stock is likely to be volatile, and purchasers of our common stock could incur substantial losses.

Our stock price has been, and is likely to continue to be, volatile. Since shares of our common stock were sold in our initial public offering in April 2015 at a price of $176.00 per share (adjusted to give effect to the 1-for-16 reverse stock split), our stock price has ranged from a low of $1.94 to a high of $418.40 through March 12, 2025. In addition, the stock market in general and the market for pharmaceutical companies, in particular, have experienced extreme volatility that has often been unrelated to the operating performance of particular companies. As a result of this volatility, investors may not be able to sell their common stock at or above the price paid for the shares. The market price for our common stock may be influenced by many factors, including:

● •actual or anticipated variations in our operating results; ● changes in financial estimates by us or by any securities analysts who might cover our stock; ● conditions or trends in our industry, including without limitation changes in the structure of healthcare payment systems; ● stock market price and volume fluctuations of comparable companies and, in particular, those that operate in the pharmaceutical industry; ● announcements by us or our competitors of significant acquisitions, strategic partnerships or divestitures; ● announcements of investigations or regulatory scrutiny of our operations or lawsuits filed against us; ● adverse regulatory announcements or determinations regarding our product candidates; ● capital commitments; ● investors’ general perception of us and our business; ● global macroeconomic conditions, including inflation, tariffs, labor shortages, supply chain shortages, or other economic, political or legal changes, uncertainties or adverse developments; ● political unrest, terrorism and wars, such as the current situation with Ukraine and Russia or Israel and Hamas, which could delay or disrupt our business, and if such political unrest escalates or spills over to or otherwise impacts additional regions it could heighten many of the other risk factors included in this Item 1A; ● other events or factors, including those resulting from system failures and disruptions, earthquakes, hurricanes, other natural disasters, pandemics, or responses to these events; ● recruitment, retention, or departure of key personnel; and ● sales of our common stock, including sales by our directors and officers or specific stockholders.

Many of the factors described above are not within our control and we cannot guarantee that future instances of these influencing factors will not have effects on the trading price of our common stock.49

In addition, in the past, stockholders have initiated class action lawsuits against pharmaceutical and biotechnology companies following periods of volatility in the market prices of these companies’ stock. For instance, in December 2016, we received notice of a class action suit filed against us in the Iowa District Court in Johnson County by a stockholder alleging that we, certain of our senior executives and directors who signed the registration statement in connection with our initial public offering, and each of the investment banks that acted as underwriters for the offering negligently issued untrue statements of material facts and omitted to state material facts required to be stated in the registration statement and incorporated offering materials that we filed with the U.S. Securities and Exchange Commission, or the SEC, in support of the offering. In June 2018, the case was dismissed without prejudice to members of the putative class. Future litigation could cause us to incur substantial costs and divert management’s attention and resources from our business. Further, biotechnology and pharmaceutical companies, in particular, have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies. Broad market and industry factors may negatively affect the market price of our common stock, regardless of our actual operating performance.

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~~Future~~•changes ~~sales~~in ~~and~~financial ~~issuances~~estimates ofby ~~equity~~us ~~and~~or ~~debt~~by ~~could~~any ~~result~~securities inanalysts ~~additional~~who ~~dilution~~might tocover our ~~stockholders.~~stock;

We•conditions ~~may~~or ~~need~~trends ~~additional capital~~ in ~~the future to fund~~ our ~~planned future operations~~industry, including towithout ~~complete~~limitation ~~potential~~changes clinical trials for our product candidates or for successful commercialization of our approved products. To raise capital, we may sell or issue common stock, convertible securities or other equity securities in one or more transactions at prices and in a manner we determine from time to time. The issuance of additional shares of our common stock or equity securities convertible into shares of our common stock may cause your ownership interest to be diluted, and the ~~market~~structure ~~price~~ of ~~our~~healthcare ~~common~~payment ~~stock may fall or be materially and adversely affected. Examples of such issuances of equity securities include the following:~~systems;

●•stock ~~The~~market ~~holders~~price ~~of any of the warrants described elsewhere in this Annual Report on Form 10-K may elect to exercise such warrants~~ and ~~receive~~volume ~~shares~~fluctuations of ~~common~~comparable ~~stock.~~companies;

●•announcements Inby ~~connection~~us ~~with~~or ~~the Merger and its related transactions, we issued shares of~~ our ~~common~~competitors ~~stock pursuant to the Loan and Note Purchase Agreements and the cancellation~~ of ~~the~~significant ~~Acer~~acquisitions, ~~warrants.~~strategic ~~See~~partnerships ~~“Liquidity~~or ~~and Capital Resources.”~~divestitures;

●•announcements Inof ~~July~~investigations ~~2021, the Company entered into the Equity Distribution Agreement with JMP Securities LLC,~~ or ~~JMP,~~regulatory ~~and~~scrutiny ~~RBC~~of ~~Capital~~our ~~Markets,~~operations ~~LLC,~~ or ~~RBCCM,~~lawsuits ~~under~~filed ~~which~~against ~~the Company may offer and sell, from time to time at its sole discretion, shares of its common stock having an aggregate offering price of up to $75,000,000 through JMP and RBCCM as its sales agents.~~us;

In•adverse ~~June~~regulatory ~~2021,~~announcements at the annual meeting of stockholders, the stockholders approved the Amended and Restated 2014 Equity Incentive Plan, which, among other things, added 4,900,000 shares to the equity plan pool, and the employee stock purchase plan, or ~~the 2021~~determinations ~~ESPP,~~regarding ~~which allows eligible employees to purchase up to an aggregate of 1,500,000 shares of stock through the plan. Pursuant to~~ our ~~equity~~product incentive plan, we may grant equity awards and issue additional shares of our common stock to our employees, directors and consultants, and the number of shares of our common stock reserved for future issuance under this plan will be subject to automatic annual increases in accordance with the terms of the plans.candidates;

In•capital February 2024, our Board approved the Amended and Restated 2023 Employment Inducement Award Plan, (the “2023 Plan”), under which we may grant equity awards to certain new employees. The maximum number of shares of common stock to be issued under the 2023 Plan is 4,500,000.commitments;

71 •investors’ general perception of us and our business;

~~Table~~•global ofmacroeconomic ~~Contents~~ conditions, including inflation, tariffs, labor shortages, supply chain shortages, or other economic, political or legal changes, uncertainties or adverse developments;

~~Sales~~•political ofunrest, aterrorism ~~substantial~~and ~~number~~wars, ofsuch ~~shares~~as ~~of our common stock in~~ the ~~public~~current ~~market~~situation ~~could~~with ~~cause~~Ukraine ~~the~~and ~~market~~Russia ~~price~~or ofIsrael ~~our~~and ~~common stock to drop significantly, even if our business is doing well.~~Hamas;

~~Sales~~•other ofevents aor ~~substantial~~factors, ~~number~~including ofthose ~~shares~~resulting offrom ~~our~~system ~~common~~failures ~~stock~~and indisruptions, ~~the~~earthquakes, ~~public~~hurricanes, ~~market~~other ~~could~~natural ~~occur~~disasters, ~~at any time. If our stockholders sell~~pandemics, or ~~the~~responses ~~market perceives that our stockholders intend~~ to ~~sell,~~these ~~substantial amounts of our common stock in the public market, the market price of our common stock could decline significantly.~~events;

•recruitment, retention, or departure of key personnel; and

•sales of our common stock, including sales by our directors and officers or specific stockholders.

Anti-takeover provisions in our amended and restated certificate of incorporation and amended and restated bylaws, as well as provisions of Delaware law and the terms of some or our contracts, might discourage, delay or prevent a change in control of our company or changes in our board of directors or management and, therefore, depress the price of our common stock.

Our amended and restated certificate of incorporation and amended and restated bylaws and Delaware law contain provisions that may discourage, delay or prevent a merger, acquisition or other change in control that stockholders may consider favorable, including transactions in which you might otherwise receive a premium for your shares of our common stock or transactions that our stockholders might otherwise deem to be in their best interests. These provisions may also prevent or frustrate attempts by our stockholders to replace or remove members of our board of directors or our management. Therefore, these provisions could adversely affect the price of our stock. Our corporate governance documents include provisions:

● •establishing a classified board of directors with staggered three-year terms so that not all members of our board of directors are elected at one time; ● providing that directors may be removed by stockholders only for cause; ● preventing the ability of our stockholders to call and bring business before special meetings and to take action by written consent in lieu of a meeting; ● requiring advance notice of stockholder proposals for business to be conducted at meetings of our stockholders and for nominations of candidates for election to our board of directors; ● permitting the board of directors to issue up to 10,000,000 shares of preferred stock with any rights, preferences and privileges they may designate; ● limiting the liability of, and providing indemnification to, our directors and officers; ● providing that vacancies may be filled by remaining directors; ● preventing cumulative voting; and ● providing for a supermajority requirement to amend our amended and restated bylaws.

•providing that directors may be removed by stockholders only for cause;

•preventing the ability of our stockholders to call and bring business before special meetings and to take action by written consent in lieu of a meeting;

•requiring advance notice of stockholder proposals for business to be conducted at meetings of our stockholders and for nominations of candidates for election to our board of directors;

•permitting the board of directors to issue up to 10,000,000 shares of preferred stock with any rights, preferences and privileges they may designate;

•limiting the liability of, and providing indemnification to, our directors and officers;

•providing that vacancies may be filled by remaining directors;

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•preventing cumulative voting; and

•providing for a supermajority requirement to amend our amended and restated bylaws.

As a Delaware corporation, we are also subject to provisions of Delaware law, including Section 203 of the General Corporation Law of the State of Delaware, which prohibits a Delaware corporation from engaging in a broad range of business combinations with any “interested” stockholder for a period of three years following the date on which the stockholder became an “interested” stockholder.

In addition, the provisions of our termination agreement with Aquestive Therapeutics ("“Aquestive"”) may delay or prevent a change in control of our company. For example, if we enter into a merger, an asset sale or any other change of control transaction, then Aquestive will be entitled to a royalty equal to 10% of the price being paid to us and our stockholders in such transaction which is attributable to the value of AZSTARYS or KP1077.

Any provision of our amended and restated certificate of incorporation, amended and restated bylaws or Delaware law or any term of our contracts that has the effect of discouraging, delaying or preventing a change in control could limit the opportunity for our stockholders to receive a premium for their shares of our common stock and could also affect the price that some investors are willing to pay for our common stock.

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If we engage in acquisitions to grow our business, we will incur a variety of costs and may potentially face numerous risks that could adversely affect our business and operations and cause our stock price to decline.

If appropriate opportunities become available, we may seek to acquire businesses or assets to enhance our business. In connection with any acquisitions, we could issue additional equity securities, which would dilute our stockholders, incur substantial debt to fund the acquisitions or assume significant liabilities.

Acquisitions involve many and diverse risks and uncertainties, including problems integrating the purchased operations or assets as well as unanticipated costs, liabilities, and economic, political, legal and re

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