UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

~~WASHINGTON~~Washington, D.C. 20549

________________________________

FORM 10-K

~~ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d)~~________________________________

OF(Mark ~~THE SECURITIES EXCHANGE ACT OF 1934~~One)

~~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 the fiscal year ended December 31, 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 number 001-36177

~~GlycoMimetics, Inc.~~________________________________

~~(Exact~~Crescent ~~name~~Biopharma, ~~of Registrant as specified in its charter)~~Inc.

(Exact name of registrant as specified in its charter)

Delaware	06-1686563
(State or other jurisdiction ofincorporation or organization)	(IRS EmployerIdentification No.)

________________________________


Cayman Islands			06-1686563
(State or other jurisdiction of incorporation or organization)			(I.R.S. Employer Identification No.)
300 Fifth Avenue
Waltham, MA			02451
(Address of Principal Executive Offices)			(Zip Code)

(617) 460-5595

P.O. Box 65Monrovia, Maryland	21770
(Address of principal executive offices)	(Zip Code)

Registrant’s telephone number, including area code

Registrant’s telephone number, including area code: (240) 243-1201

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

Title of Each Class:	Trading Symbol:	Name of Each Exchange on which Registered
Title of Each Class			Trading Symbol	Name of Each Exchange on which Registered
Common Stock, $0.001 par value	GLYC	The Nasdaq Stock Market
Ordinary Shares, $0.001 par value per share			CBIO	The Nasdaq Capital Market

Securities registered pursuant to section 12(g) of the Act:

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

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~~Yes byo ~~check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐~~ No ☒ x

Indicate by check mark ~~whether~~if the registrant ~~(1) has~~is ~~filed~~not ~~all reports~~ required to befile ~~filed~~reports bypursuant to Section 13 or Section 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 ☒ No ☐~~

~~Indicate~~Yes byo 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 ☒ No ☐ x

Indicate by check mark whether the registrant is(1) ahas ~~large~~filed ~~accelerated~~all ~~filer,~~reports anrequired ~~accelerated~~to ~~filer,~~be afiled ~~non-accelerated~~by ~~filer,~~Section a13 ~~smaller~~or ~~reporting~~15(d) ~~company~~of orthe ~~emerging~~Securities ~~growth~~Exchange ~~company.~~Act ~~See~~of ~~definitions~~1934 ofduring ~~“large~~the ~~accelerated~~preceding ~~filer,”~~12 ~~“accelerated~~months ~~filer”,~~(or ~~“smaller~~for ~~reporting~~such ~~company”~~shorter ~~and~~period ~~“emerging~~that ~~growth~~the ~~company”~~registrant inwas ~~Rule~~required ~~12b-~~to file such reports), and (2) ofhas been subject to such filing requirements for the ~~Exchange~~past ~~Act~~90 days.

~~Large~~Yes ~~Accelerated~~x ~~Filer~~No ~~☐ Accelerated Filer ☐ Non-accelerated Filer ☒ Smaller Reporting Company ☒ Emerging Growth Company ☐~~o

IfIndicate ~~an emerging growth company, indicate~~ by check mark ifwhether the registrant has ~~elected~~submitted ~~not~~electronically every Interactive Data File required to ~~use~~be ~~the~~submitted ~~extended~~pursuant ~~transition~~to ~~period~~Rule ~~for~~405 ~~complying~~of ~~with~~Regulation ~~any~~S-T ~~new~~(§ or232.405 ~~revised~~of ~~financial~~this ~~accounting~~chapter) ~~standards~~during ~~provided~~the ~~pursuant~~preceding to12 ~~Section~~months 13(a)or offor such shorter period that the ~~Exchange~~registrant ~~Act~~was required to submit such files). ☐

~~Indicate~~Yes byx ~~check~~No 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

IfIndicate ~~securities~~by ~~are~~check ~~registered~~mark ~~pursuant~~whether tothe ~~Section~~registrant ~~12(b)~~is ofa ~~the~~large ~~Act~~accelerated filer, ~~indicate~~an byaccelerated ~~check~~filer, ~~mark~~a ~~whether~~non-accelerated ~~the~~filer, ~~financial~~a ~~statements~~smaller ofreporting ~~the~~company, ~~registrant~~or ~~included~~an inemerging ~~the~~growth ~~filing~~company. ~~reflect~~See the ~~correction~~definitions of an“large ~~error~~accelerated tofiler,” ~~previously~~“accelerated ~~issued~~filer,” “smaller ~~financial~~reporting ~~statements.~~company,” ☐and "emerging growth company" in Rule 12b-2 of the Exchange Act.

~~Indicate~~Large byaccelerated ~~check~~filer ~~mark~~o ~~whether~~Accelerated ~~any~~filer ofo ~~those~~Non-accelerated ~~error~~filer ~~corrections~~☒ ~~are~~Smaller ~~restatements~~reporting ~~that~~company ~~required~~☒ aEmerging ~~recovery~~growth ~~analysis~~company ~~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~~If an emerging growth company, indicate by check mark ~~whether~~if the registrant ishas aelected ~~shell~~not ~~company~~to ~~(as~~use ~~defined~~the inextended ~~Rule~~transition ~~12b-2~~period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act). ~~Yes ☐ No ☒~~

As of June 30, 2024, the last business day of the registrant’s last completed second quarter, the aggregate market value of the Common Stock held by non-affiliates of the registrant was approximately $17.5 million based on the closing price of the registrant’s Common Stock, as reported by the Nasdaq Capital Market, on such date.o

AtIndicate ~~February~~by 7,check ~~2025,~~mark ~~64,513,862~~whether ~~shares~~the ofregistrant ~~GlycoMimetics,~~has ~~Inc.~~filed a report on and attestation to its management’s ~~Common~~assessment ~~Stock,~~of ~~$0.001~~the ~~par~~effectiveness ~~value~~of ~~per~~its ~~share,~~internal ~~were~~control ~~outstanding~~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.

~~DOCUMENTS INCORPORATED BY REFERENCE~~o

~~None~~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.

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).

~~Table~~Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of ~~Contents~~the Act).

~~SPECIAL~~Yes ~~NOTE~~o ~~REGARDING~~No ~~FORWARD-LOOKING STATEMENTS~~ x

~~This~~The ~~Annual~~aggregate ~~Report~~market onvalue ~~Form 10-K, or this Annual Report, contains forward-looking statements within the meaning~~ of ~~Section 27A of~~ the ~~Securities~~voting ~~Act of 1933, as amended,~~ and ~~Section 21E~~non-voting ofcommon ~~the~~equity ~~Securities~~held ~~Exchange~~by ~~Act of 1934, as amended, or the Exchange Act, that involve substantial risks and uncertainties. The forward~~non-~~looking~~affiliates ~~statements are contained principally in Part I, Item 1. “Business,” Part I, Item 1A. “Risk Factors,” and Part II, Item 7. “Management’s Discussion and Analysis~~ of ~~Financial Condition and Results of Operations,” but are also contained elsewhere in this Annual Report. In some cases, you can identify forward-looking statements by~~ the ~~words~~Registrant ~~“may,”~~as “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue” and “ongoing,” or the negative of ~~these~~June ~~terms~~30, ~~or other comparable terminology intended to identify statements about the future. These statements involve known and unknown risks~~2025, ~~uncertainties~~was ~~and~~approximately other factors that may cause our actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements$177.2 ~~Although~~million ~~we believe that we have a reasonable basis for each forward-looking statement contained in this Annual Report, we caution you that these statements are~~ based on athe ~~combination~~closing ofprice ~~facts and factors currently known by us and our expectations~~ of the ~~future,~~Registrant’s ~~about~~ordinary ~~which~~shares weon ~~cannot~~The beNasdaq ~~certain.~~Capital ~~Forward-looking~~Market ~~statements~~on ~~include~~such ~~statements about:~~ date.

●The ~~our~~number ~~plans~~of ~~to consummate~~ the ~~proposed~~Registrant’s ~~merger,~~Ordinary orShares ~~the~~outstanding ~~Merger,~~as ~~between~~of usFebruary ~~and~~23, ~~Crescent~~2026 ~~Biopharma,~~was ~~Inc~~27,556,767.

● the sufficiency of our cash resources to continue operating through consummation of the Merger;

● our ability to maintain compliance with Nasdaq listing standards;

● our plans to potentially explore other strategic alternatives or to dissolve or liquidate the Company if the Merger is not consummated;

● the clinical utility of our drug candidates;

● our potential commercialization, marketing and manufacturing capabilities and strategy if we resume the development of our drug candidates;

● our intellectual property position;

● our ability to identify additional drug candidates; and

● our estimates regarding needs for additional financing.

You should refer to Item 1A. “Risk Factors” section of this Annual Report for a discussion of important factors that may cause our actual results to differ materially from those expressed or implied by our forward-looking statements. As a result of these factors, we cannot assure you that the forward-looking statements in this Annual Report will prove to be accurate. Furthermore, if our forward-looking statements prove to be inaccurate, the inaccuracy may be material. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame, or at all. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this Annual Report.

Table of Contents

SELECTED RISKS AFFECTING OUR BUSINESS

Our business is subject to numerous risks. You should carefully consider the following risks, as well as general economic and business risks, and all of the other information contained in this Annual Report, together with any other documents we file with the SEC. Any of the following risks could have a material adverse effect on our business, operating results and financial condition and cause the trading price of our common stock to decline.

Among these important risks are the following:

● Failure to complete, or delays in completing, the potential Merger could materially and adversely affect our results of operations, business, financial results and/or common stock price.

● If the Merger is not completed, our stock price may decline significantly.

● Even if we complete the Merger, the combined company will need to raise additional capital by issuing equity securities or additional debt or through licensing arrangements, which may cause significant dilution to the combined company’s stockholders or restrict the combined company’s operations.

● Our stockholders will experience significant dilution as a consequence of the Merger and related transactions.

● We may fail to realize all of the anticipated benefits of the Merger and may be exposed to other operational and financial risks.

● Our ability to consummate the Merger will depend on our ability to retain our employees required to consummate such transaction.

● If we are unable to consummate the Merger with Crescent, our board of directors may decide to pursue a dissolution and liquidation. In such an event, the amount of cash available for distribution to our stockholders will depend heavily on the timing of such liquidation as well as the amount of cash that will need to be reserved for commitments and contingent liabilities.

● If we fail to comply or regain compliance with Nasdaq’s continued listing standards prior to the consummation of the Merger, our common stock may be delisted and the price of our common stock, our ability to access the capital markets and our financial condition could be negatively impacted.

● We have incurred significant losses since our inception. We expect to continue to incur losses and may never achieve or maintain profitability.

● If we decide to resume development of our drug candidates, we would need substantial additional funding. If we were unable to raise that capital when needed, we may not be able to continue as a going concern and could be forced to delay, reduce or eliminate drug development programs or potential commercialization efforts.

● Raising additional capital may cause dilution to our stockholders, restrict our operations or require us to relinquish rights to our drug candidates.

● If we were to resume development activities, we would need to conduct additional clinical trials. All of our other drug candidates other than uproleselan were in earlier stages or clinical trials or in preclinical development.

● Clinical drug development involves a lengthy and expensive process, with an uncertain outcome. Should we resume development of our drug candidates, we may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of our drug candidates.

● Should we resume development of our drug candidates, serious adverse or unacceptable side effects could be identified, in which case we would need to abandon or limit their development.

● If we were to resume development of our drug candidates, we may expend our limited resources to pursue a particular drug candidate or indication and fail to capitalize on drug candidates or indications that may be more profitable or for which there is a greater likelihood of success.

● Should we resume development activities, our success would depend in part on collaborations. If we are unable to maintain any of these collaborations, or if these collaborations are not successful, our business could

Table of Contents

be adversely affected.

● Should we resume development of our drug candidates, we would expect to rely on third parties to conduct additional clinical trials for our drug candidates, and those third parties may not perform satisfactorily, including failing to meet deadlines for the completion of such trials.

● We previously contracted with third parties for the manufacturing of our drug candidates for preclinical and clinical testing, and if we were to resume development activities and pursue commercialization, we would expect to continue to do so. This reliance on third parties increases the risk that we would not have sufficient quantities of our drug candidates or drugs, or such quantities at an acceptable cost, which could delay, prevent or impair our potential development or commercialization efforts.

● Should we resume development of drug candidates, if any of those drug candidates were to receive marketing approval, it may still fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success.

● Should we resume drug development, we would face substantial competition, which may result in others discovering, developing or commercializing drugs before or more successfully than we do.

● Should we resume drug development activities but are unable to obtain and maintain patent protection for our drug candidates, or if the scope of the patent protection obtained is not sufficiently broad, our competitors could develop and commercialize drug candidates similar or identical to ours, and our ability to successfully commercialize our drug candidates may be impaired.

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

● Should we resume development of our drug candidates but we or our collaborators are not able to obtain, or if there are delays in obtaining, required regulatory approvals, we or they would not be able to commercialize our drug candidates and our ability to generate revenue would be materially impaired.

● If our information technology systems or data, or those of third parties upon which we rely, are or were compromised, we could experience adverse consequences resulting from such compromise, including, but not limited to, regulatory investigations or actions; litigation; fines and penalties; a disruption of our business operations, including our clinical trials; reputational harm; loss of revenue and profits; and other adverse consequences.

● Unfavorable global economic conditions could adversely affect our business, financial condition or results of operations.

Table of Contents

TABLE OF CONTENTS


			Page
PART I			1
	ITEM 1.	BUSINESS	1
	ITEM 1A.	RISK FACTORS	18
	ITEM 1B.	UNRESOLVED STAFF COMMENTS	51
	ITEM 1C.	CYBERSECURITY	51
	ITEM 2.	PROPERTIES	52
	ITEM 3.	LEGAL PROCEEDINGS	53
	ITEM 4.	MINE SAFETY DISCLOSURES	53
PART II			53
	ITEM 5.	MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES	53
	ITEM 6.	[RESERVED]	53
	ITEM 7.	MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS	54
	ITEM 7A.	QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK	59
	ITEM 8.	FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA	59
	ITEM 9.	CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL DISCLOSURE	60
	ITEM 9A.	CONTROLS AND PROCEDURES	60
	ITEM 9B.	OTHER INFORMATION	60
	ITEM 9C.	Disclosure Regarding Foreign Jurisdictions that Prevent Inspections	60
PART III			61
	ITEM 10.	DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE	61
	ITEM 11.	EXECUTIVE COMPENSATION	65
	ITEM 12.	SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED STOCKHOLDER MATTERS	72
	ITEM 13.	CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS, AND DIRECTOR INDEPENDENCE	76
	ITEM 14.	PRINCIPAL ACCOUNTANT FEES AND SERVICES	77
PART IV			77
	ITEM 15.	EXHIBITS AND FINANCIAL STATEMENT SCHEDULES	77
	ITEM 16.	FORM 10-K SUMMARY	81
SIGNATURES			82

Table of Contents

PART I

ITEM 1. BUSINESS

Introduction

We are a biotechnology company that was previously developing a pipeline of proprietary glycomimetics, which are small molecules that mimic the structure of carbohydrates involved in important biological processes, to inhibit disease-related functions of carbohydrates, such as the roles they play in cancers and inflammation. Our previous lead glycomimetic drug candidate, uproleselan, is a specific E-selectin antagonist that we were developing to be used in combination with chemotherapy to treat patients with acute myeloid leukemia, or AML, a life-threatening hematologic cancer, and potentially other hematologic cancers.

We conducted a randomized, double-blind, placebo-controlled Phase 3 pivotal clinical trial to evaluate uproleselan in individuals with relapsed/refractory (R/R) AML. In the second quarter of 2024, we reported results from the Phase 3 trial showing that uproleselan combined with chemotherapy did not achieve a statistically significant improvement in overall survival in the intent to treat (ITT) population versus chemotherapy alone. We have concluded, following subsequent feedback from the U.S. Food and Drug Administration, that the regulatory path forward for uproleselan for the treatment of relapsed and refractory acute myeloid leukemia would require an additional clinical trial. In July 2024, we announced a streamlined operating plan that included the exploration of strategic alternatives focused on maximizing shareholder value and a corporate restructuring that included a reduction in our workforce by 26 employees, or approximately 80% of our headcount. At this time, we do not intend to continue development of uproleselan or any other drug candidates.

Following the strategic review, on October 28, 2024, we, Gemini Merger Sub Corp., a Delaware corporation and our wholly-owned subsidiary (“First Merger Sub”), Gemini Merger Sub II, LLC, a Delaware limited liability company and our wholly-owned subsidiary (“Second Merger Sub” and, together with First Merger Sub, “Merger Subs”), and Crescent Biopharma, Inc., a Delaware corporation (“Crescent”), entered into an Agreement and Plan of Merger and Reorganization (the “Merger Agreement”), pursuant to which, among other matters, and subject to the satisfaction or waiver of the conditions set forth in the Merger Agreement, (i) First Merger Sub will merge with and into Crescent, with Crescent continuing as our wholly owned subsidiary and the surviving corporation of the merger (the “First Merger”) and (ii) immediately following the First Merger and as part of the same overall transaction as the First Merger, Crescent will merge with and into Second Merger Sub (the “Second Merger” and, together with the First Merger, the “Merger”).

Pursuant to the exchange ratio formula in the Merger Agreement, and based on our capitalization as of September 30, 2024 and Crescent’s capitalization as of October 28, 2024 (the date the Merger Agreement was executed), upon the closing of the Merger (and prior to closing of the Private Placement described below), on a pro forma basis and based upon the number of shares of our common stock expected to be issued in the Merger, pre-Merger Crescent stockholders will own approximately 86.21% of the combined company and pre-Merger GlycoMimetics stockholders will own approximately 13.79% of the combined company. After giving further effect to the Private Placement, the pre-Merger Crescent stockholders (inclusive of those investors participating in the Private Placement) are expected to own approximately 96.9% of the combined company and our pre-Merger stockholders are expected to own approximately 3.1% of the combined company. The exchange ratio may be further adjusted as described in the Merger Agreement. We and Crescent have agreed to customary representations, warranties and covenants in the Merger Agreement and the consummation of the Merger is subject to customary closing conditions, including, among other things, approval by our stockholders and the Crescent stockholders of the transaction, Nasdaq and SEC approvals, and completion of a concurrent private placement of at least $100 million (as described below).

Additionally, in connection with the Merger, we will establish the terms of a new series of preferred stock designated as Series A Non-Voting Convertible Preferred Stock, par value $0.001 per share (the “Series A Preferred Stock”). Holders of the Series A Preferred Stock will be entitled to receive dividends on shares of Series A Preferred Stock equal to, on an as-if-converted-to-GlycoMimetics common stock basis, and in the same form as dividends actually paid on shares of the GlycoMimetics common stock. Except as otherwise required by the Certificate of Designation or law, the Series A Preferred Stock will not have voting rights. The Certificate of Designation will provide however that for so long at least 30% of the Series A Preferred Stock remains issued and outstanding, the holders of Series A Preferred Stock exclusively and voting together as a separate class on an as-converted to common stock basis, shall be entitled to

Table of Contents

~~elect~~TABLE ~~two~~OF (2) directors (the “Preferred Directors”); and the holders of record of the shares of common stock and of any other class or series of voting stock (including the Series A Preferred Stock), exclusively and voting together as a single class on an as-converted to common stock basis, shall be entitled to elect the balance of the total number of directors.CONTENTS


		Page No.
Part I

Item 1.	Business	6
Item 1A.	Risk Factors	58
Item 1B.	Unresolved Staff Comments	100
Item 1C.	Cybersecurity	101
Item 2.	Properties	102
Item 3.	Legal Proceedings	102
Item 4 .	Mine Safety Disclosures	102

Part II

Item 5.	Market for Registrant’s Common Equity, Related Shareholder Matters and Issuer Purchases of Equity Securities	103
Item 6.	Reserved	104
Item 7.	Management’s Discussion and Analysis of Financial Condition and Results of Operations	105
Item 7A .	Quantitative and Qualitative Disclosures about Market Risk	119
Item 8.	Financial Statements and Supplementary Data	120
Item 9.	Changes in and Disagreements with Accountants on Accounting and Financial Disclosure	157
Item 9A.	Controls and Procedures	157
Item 9B.	Other Information	157
Item 9C.	Disclosure Regarding Foreign Jurisdictions that Prevent Inspections	157

Part III

Item 10.	Directors, Executive Officers and Corporate Governance	158
Item 11 .	Executive Compensation	164
Item 12 .	Security and Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters	169
Item 13.	Certain Relationships and Related Transactions, and Director Independence	173
Item 14.	Principal Accountant Fees and Services	177

Part IV

Item 15.	Exhibits and Financial Statement Schedules	178
Item 16.	Form 10-K Summary	181
Signatures		182

Upon completion of the Merger, we plan to operate under the name Crescent Biopharma, Inc. The Merger is expected to close in the second quarter of 2025, subject to certain closing conditions, including, among other things, approval by the stockholders of each company and the satisfaction of customary closing conditions. The Merger is intended to qualify for federal income tax purposes as a tax-free reorganization under the provisions of Section 368(a) of the Internal Revenue Code of 1986, as amended. Following the Merger, the current business of Crescent will become the primary business of our company.

Concurrently with the execution and delivery of the Merger Agreement, certain institutional and accredited investors have entered into a securities purchase agreement with us, pursuant to which they have agreed, subject to the terms and conditions of such agreements, to purchase, immediately following the consummation of the Merger, shares of our common stock and pre-funded warrants for an aggregate purchase price of approximately $200.0 million in a private placement (the “Private Placement”). The closing of the Private Placement is conditioned on the satisfaction or waiver of the conditions set forth in the Merger Agreement (in addition to other customary closing conditions) and is expected to occur immediately following the closing of the Merger.

Concurrently with the execution of the Merger Agreement, our directors and officers and certain stockholders of Crescent (solely in their respective capacities as Crescent stockholders) holding approximately 98% of the outstanding shares of Crescent capital stock have entered into support agreements to vote all of their shares in favor of the adoption and approval of the Merger.

Our future operations are highly dependent on the success of the Merger and there can be no assurances that the Merger will be successfully consummated. In the event that we do not complete the Merger, we may explore strategic alternatives, including, without limitation, another strategic transaction and/or pursue a dissolution and liquidation of our business.

Our Historical Platform and Drug Candidates

Our proprietary glycomimetics platform was based on our expertise in carbohydrate chemistry and our understanding of the role carbohydrates play in key biological processes. Most human proteins are modified by the addition of complex carbohydrate structures to the surface of such proteins, which affects the functions of the proteins and their interactions with other molecules. Our prior research and development efforts focused on drug candidates targeting selectins, which are proteins that serve as adhesion molecules and bind to carbohydrates that are involved in the inflammatory component and progression of a wide range of diseases, including hematologic disorders, cancer and cardiovascular disease. For example, we believe that members of the selectin family play a key role in tumor metastasis and resistance to chemotherapy. Inhibiting specific carbohydrates from binding to selectins has long been viewed as a potentially attractive approach for therapeutic intervention. The ability to successfully develop drug-like carbohydrate compounds that inhibit binding with selectins, known as selectin antagonists, has historically been limited by their potency and the complexities of carbohydrate chemistry. We believe our expertise in the rational design of potent glycomimetic antagonists with drug-like properties and in carbohydrate chemistry enabled us to identify highly effective selectin antagonists and other glycomimetics that may inhibit the disease-related functions of certain carbohydrates in order to develop novel drug candidates to address orphan diseases with high unmet medical need.

The status of our drug candidates is summarized below. We are no longer actively pursuing the development of any of these drug candidates. We retained the worldwide development and commercialization rights to each of our drug candidates, except with respect to uproleselan and GMI-1687, for which we have exclusively licensed development and commercialization rights to Apollomics (Hong Kong) Limited, or Apollomics, in Mainland China, Hong Kong, Macau and Taiwan, collectively referred to as Greater China. Although those agreements remain in force, Apollomics has announced its intention to wind down its clinical development program and we do not anticipate those agreements to continue following consummation of the Merger.

Table of Contents

~~Uproleselan~~SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

WeThis ~~were~~Annual ~~previously~~Report ~~developing~~on ~~uproleselan,~~Form a10-K ~~specific~~contains E“forward-~~selectin~~looking ~~antagonist,~~statements” towithin bethe ~~used~~meaning inof ~~combination~~Section ~~with~~27A ~~chemotherapy~~of tothe ~~treat~~Securities ~~patients~~Act ~~with~~of ~~acute~~1933, ~~myeloid~~as ~~leukemia,~~amended or(the ~~AML~~“Securities Act”), aand ~~life-threatening~~Section ~~hematologic~~21E ~~cancer~~of the Securities Exchange Act of 1934, ~~and~~as ~~potentially~~amended ~~other~~(the ~~hematologic~~“Exchange ~~cancers~~Act”).

All statements other than statements of historical facts contained in this Annual Report on Form 10-K, including, without limitation, statements regarding our future results of operations and financial position, business strategy, the length of time that we believe our existing cash resources will fund our operations, our market size, our potential growth opportunities, our preclinical and future clinical development activities, the efficacy and safety profile of our product candidates, the potential therapeutic benefits and economic value of our product candidates, the timing and results of preclinical studies and clinical trials, the expected impact of macroeconomic conditions, the timing of the Option Agreement Termination (as defined herein), and the receipt and timing of potential regulatory designations, approvals and commercialization of product candidates, are forward-looking statements. Forward-looking statements generally relate to future events or our future financial or operating performance. The words “believe,” “may,” “will,” “potentially,” “estimate,” “continue,” “anticipate,” “predict,” “target,” “intend,” “could,” “would,” “should,” “project,” “plan,” “expect,” and similar expressions that convey uncertainty of future events or outcomes are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.

~~Uproleselan~~These ~~received~~forward-looking ~~Orphan~~statements ~~Drug~~are ~~designation~~based ~~from~~on management’s current expectations, estimates, forecasts and projections about our business and the ~~FDA~~industry in ~~2015~~which ~~for~~we ~~treatment~~operate. ofThese ~~patients~~statements ~~with~~are ~~AML.~~neither Inpromises ~~2016~~nor guarantees, ~~uproleselan~~but ~~received~~involve ~~Fast~~known ~~Track~~and ~~designation~~unknown ~~from~~risks, ~~the~~uncertainties ~~FDA~~and ~~for~~other ~~treatment~~important offactors ~~adult~~that ~~patients~~may ~~with~~cause ~~relapsed~~our actual results, performance or ~~refractory~~achievements ~~AML~~to ~~and~~be ~~elderly~~materially ~~patients~~different ~~aged~~from ~~60 years~~any future results, performance or ~~older~~achievements ~~with~~expressed ~~AML~~or implied by the forward-looking statements. InFactors ~~2017,~~that ~~uproleselan~~may ~~received~~cause ~~Breakthrough~~actual ~~Therapy~~results ~~designation~~to differ materially from current expectations include the ~~FDA~~initiation, ~~for~~execution ~~treatment~~and completion of ~~adult~~clinical ~~patients~~trials, ~~with~~uncertainties ~~relapsed~~surrounding orthe ~~refractory~~timing ~~AML.~~of Inavailability ~~2017,~~of ~~the~~data ~~European~~from ~~Commission~~our clinical trials, ~~based~~ongoing ondiscussions awith ~~favorable~~and ~~recommendation~~actions ~~from~~by ~~the~~regulatory ~~EMA~~authorities, ~~Committee~~our ~~for~~development ~~Orphan~~activities ~~Medicinal~~and ~~Products~~those other factors we discuss in Part I, ~~granted~~Item ~~Orphan~~1A. ~~Designation~~“Risk ~~for~~Factors” ~~uproleselan~~in ~~for~~this ~~treatment~~Annual ofReport ~~patients~~on ~~with~~Form ~~AML~~10-K. InYou ~~January~~should ~~2021,~~read ~~the~~these ~~China~~risk ~~National~~factors ~~Medical~~and ~~Products~~the ~~Administration~~other ~~Center~~cautionary ~~for~~statements ~~Drug~~made ~~Evaluation~~in ~~granted~~this ~~Breakthrough~~report ~~Therapy~~as ~~designation~~being applicable to ~~uproleselan~~all ~~for~~related ~~treatment~~forward-looking statements wherever they appear in this report. The risk factors are not exhaustive and other sections of ~~relapsed/refractory~~this ~~AML~~report may include additional factors which could adversely impact our business and financial performance.

Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Preliminary and interim results from any trial and results in early-stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. Moreover, we operate in a very competitive and rapidly changing environment. New risk factors emerge from time to time, and it is not possible for our management to predict all risk factors nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements.

~~E-selectin~~Given ~~plays~~these ~~a critical role in binding cancer cells within vascular niches in the bone marrow~~uncertainties, ~~which~~you ~~prevents~~should ~~the~~not ~~cells~~rely ~~from~~on entering circulation where they can be more readily killed by chemotherapy. In animal studies, uproleselan mobilized AML cancer cells out of the bone marrow, making them more sensitive to chemotherapy. In these ~~studies,~~forward-looking ~~tumor~~statements ~~burden was significantly reduced in the animals treated with a combination of chemotherapy and uproleselan~~ as ~~compared~~predictions ~~to animals treated with chemotherapy alone. In addition, the combination~~ of ~~uproleselan~~future ~~with chemotherapy resulted in improved survival rates for the treated animals compared to chemotherapy alone~~events. InExcept other animal studies, uproleselan appeared to also protect normal cells from some of the side effects of chemotherapy. Common side effects of chemotherapy include bone marrow toxicity resulting in neutropenia, which is an abnormally low number of neutrophils, the white blood cells that serve as ~~the~~required ~~primary~~by ~~defense against infection~~law, ~~and~~we ~~mucositis,~~assume ~~which~~no isobligation the inflammation and sloughing of the mucous membranes lining the digestive tract. Animals treated with uproleselan and chemotherapy had less severe neutropenia and mucositis and lower bone marrow toxicity as compared to ~~animals~~update ~~treated~~or ~~with~~revise ~~chemotherapy~~these ~~alone.~~forward-looking Westatements ~~believe~~for ~~that~~any ~~treatment~~reason, ~~with~~even ~~uproleselan~~if ~~results~~new ininformation ~~lower~~becomes ~~bone~~available ~~marrow toxicity due to its inhibition of E-selectin; this inhibition makes stem cells~~ in the ~~bone marrow divide less frequently, thereby protecting them from chemotherapy agents that target rapidly dividing cells~~future.

As used in this Annual Report on Form 10-K, unless otherwise specified or the context otherwise requires, the terms “we,” “our,” “us,” and the “Company” refer to Crescent Biopharma, Inc. and its subsidiaries. All brand names or trademarks appearing in this Annual Report on Form 10-K are the property of their respective owners.

InSUMMARY ~~2018,~~OF weTHE ~~dosed~~MATERIAL ~~the~~RISK ~~first~~FACTORS ~~patient~~ASSOCIATED inWITH aOUR ~~Phase~~BUSINESS 3 clinical trial to evaluate uproleselan in adults with relapsed/refractory AML. In 2021, we completed enrollment of 388 patients in a randomized, double-blind, placebo-controlled Phase 3 pivotal clinical trial to evaluate uproleselan in individuals with relapsed/refractory AML, the design of which was based on guidance received from the FDA.

Our business is subject to numerous risks and uncertainties, including those described in Part I, Item 1A. “Risk Factors” in this Annual Report on Form 10-K. The principal risks and uncertainties affecting our business include the following:

InRisks ~~September~~Related ~~2022, we submitted a request~~ to ~~the~~Our ~~FDA~~Financial toCondition ~~amend the protocol for the trial to conduct an interim analysis~~ and ~~have~~Capital the findings reviewed by the trial’s Independent Data Monitoring Committee, or IDMC, as blinded pooled survival data showed patients living longer than expected based on the historical benchmarks used to design the trial. The statistical plan agreed to with the FDA was for the IDMC to review efficacy and safety data at 80% of survival events, which was reached at the end of 2022. When designing the interim analysis, we amended the protocol to create the opportunity to achieve unblinding at approximately 80% of survival events while maintaining the statistical integrity of the final analysis should the IDMC recommend the trial continue to the final overall events trigger. The interim analysis plan required a high statistical threshold to be met for the IDMC to recommend unblinding, reserving approximately 95% of the trial’s statistical power for the final analysis. In February 2023, the IDMC reviewed the interim utility analysis and recommended that the pivotal Phase 3 clinical trial continue to the originally planned final overall survival events trigger. Requirements

•We are a clinical-stage biotechnology company with a limited operating history on which to assess our business; we have not completed any clinical trials, and have no products approved for commercial sale.

In•We ~~May~~have ~~2024,~~historically weincurred ~~reported~~losses ~~topline~~and results from the Phase 3 trial, in which uproleselan combined with chemotherapy did not achieve a statistically significant improvement in overall survival in the intent to treat, or ITT, population versus chemotherapy alone. In June 2024, we ~~announced~~anticipate ~~comprehensive~~that ~~results of the Phase 3 trial. Following the announcement of the data from the Phase 3 trial,~~ we ~~requested~~will ~~and~~continue ~~held a meeting with the FDA~~ to ~~discuss~~incur ~~whether~~losses ~~any of the results summarized above could serve as a basis~~ for ~~a submission for regulatory approval. Based on~~ the ~~feedback~~foreseeable received, we concluded that any potential regulatory path for uproleselan in this patient population would require an additional clinical trial, the conduct of which would require capital resources beyond those available to usfuture. ~~The decision~~

•We have never generated revenue from product sales and may never be profitable.

Table of Contents

to•We ~~not~~may ~~conduct an additional clinical trial did~~ not ~~relate~~be able to ~~any~~raise ~~safety~~the orcapital ~~medical~~that ~~issues~~we orneed ~~negative regulatory feedback related~~ to support our ~~programs~~business plans.

•Raising additional capital may cause dilution to our shareholders, restrict our operations, or require us to relinquish rights to our technologies or product candidates.

WeRisks ~~also~~Related ~~entered~~to ~~into~~Clinical aDevelopment ~~Cooperative Research~~ and ~~Development~~Regulatory Agreement, or CRADA, with the National Cancer Institute, or NCI, part of the National Institutes of Health, to conduct a Phase 2/3 randomized, controlled clinical trial evaluating the addition of uproleselan to a standard chemotherapy regimen in older adults with previously untreated AML who are eligible for intensive chemotherapy. On October 29, 2024, we announced data from the Phase 2 portion of the trial showing no statistically significant improvement in event-free survival, or EFS, for patients receiving uproleselan in combination with chemotherapy versus chemotherapy alone.Approval

•Drug development and obtaining and maintaining regulatory approval for drug products is costly, time-consuming, and highly uncertain.

~~GMI~~•We are substantially dependent on the success of our lead program, CR-~~1687~~001, and our current and anticipated clinical trials of such program may not be successful.

•We ~~designed~~may annot ~~innovative antagonist of E-selectin, GMI-1687, that could~~ be aable ~~subcutaneously administered treatment. Initially developed as a potential life-cycle extension~~ to ~~uproleselan,~~meet ~~GMI-1687~~requirements was being developed to broaden the clinical usefulness of an E-selectin antagonist to conditions where outpatient treatment is preferred or required. As described below, we have entered into a collaboration with Apollomics (Hong Kong) Limited for the ~~development of GMI-1687~~chemistry, ~~as well as uproleselan~~manufacturing, ~~in Mainland China, Hong Kong, Macau~~ and ~~Taiwan,~~control ~~also~~of ~~known~~our ~~as Greater China, but we are not otherwise actively developing GMI-1687~~programs.

•We face competition from entities that have developed or may develop programs for the diseases addressed by product candidates developed by us.

~~Our~~•The ~~Collaboration~~United ~~with~~States ~~Apollomics~~Food ~~for~~and ~~Uproleselan~~Drug Administration (“FDA”) and ~~GMI-1687~~comparable foreign regulatory approval processes are lengthy and time consuming and we may not be able to obtain or may be delayed in obtaining regulatory approvals for our product candidates.

In•Disruptions ~~2020,~~at ~~we entered into an exclusive collaboration and license agreement with Apollomics for~~ the ~~development~~FDA and ~~commercialization~~other ofgovernment ~~uproleselan~~agencies ~~and~~could ~~GMI-1687~~negatively ~~for~~affect ~~all fields and all uses in Greater China. We and Apollomics were also collaborating to advance~~ the ~~preclinical~~review ~~and clinical development~~ of ~~GMI-1687.~~our Inregulatory December 2024 Apollomics announced that its Phase 3 bridging trial of uproleselan did not demonstrate favorable benefit and that Apollomics would be winding down the program. We do not expect the collaboration and license agreement to remain in effect following the consummation of the Mergersubmissions, ~~and~~which docould ~~not~~negatively ~~anticipate~~impact ~~having~~our ~~any material ongoing obligations under the agreement for supplying drug for any trials being conducted by Apollomics~~business.

•Even if we obtain regulatory approval, we will be subject to ongoing regulatory obligations.

~~Under~~•We ~~the~~may ~~terms~~fail ~~of the exclusive collaboration and license agreement, which currently remains in effect, we are eligible~~ to ~~receive~~achieve ~~potential~~our ~~milestone~~projected ~~payments totaling approximately $180.0 million based on the achievement of specified~~ development, ~~regulatory~~goals and commercial milestones, as well as tiered royalties ranging from the high single digits to 15% based on net sales. Apollomics will be responsible for all costs related to development, regulatory approvals and commercialization in ~~Greater China for uproleselan and GMI-1687. We retain all rights for both compounds in~~ the ~~rest~~time offrames ~~the~~we ~~world~~announce and ~~have agreed to supply uproleselan and GMI-1687 to Apollomics pursuant to clinical and commercial supply agreements~~expect.

Risks Related to Our Intellectual Property

•We ~~have~~do ~~also~~not ~~entered~~currently ~~into~~own aany ~~clinical~~issued ~~supply~~patents ~~agreement~~and ~~with~~our ~~Apollomics~~patent ~~under~~portfolio ~~which~~is wein-licensed ~~will~~from ~~manufacture~~Paragon ~~and~~Therapeutics, ~~supply~~Inc, ~~uproleselan~~(“Paragon”) ~~product~~and toSichuan ~~Apollomics~~Kelun-Biotech atBiopharmaceutical ~~agreed~~Co., ~~upon prices~~Ltd. ~~Apollomics has the option to begin manufacture after appropriate material transfer requirements are met~~(“Kelun”).

•Our ability to obtain and protect patent rights and protect other proprietary rights is uncertain.

In•We ~~2020,~~may ~~the~~fail China National Medical Products Administration, or NMPA, Center for Drug Evaluation, or CDE, granted IND approval for uproleselan (also referred to as APL-106), enabling the initiation of a Phase 1 PK and tolerability study. The IND approval also included acceptance of a Phase 3 bridging study of APL-106 in ~~combination~~obtaining with chemotherapy in relapsed/refractory AML. In January 2021, APL-106 was granted Breakthrough Therapy designation from the China NMPA CDE for the treatment of relapsed/refractory acute myeloid leukemia. In January 2024, Apollomics announced the completion of enrollment in the Phase 3 bridging study. A total of 140 adult patients across 20 sites in Greater China with primary refractory AML or ~~relapsed~~maintaining ~~AML~~necessary ~~(first~~rights ~~or second untreated relapse) and eligible~~ to ~~receive~~our ~~induction chemotherapy were randomized to receive either uproleselan combined with chemotherapy or placebo plus chemotherapy~~programs. The primary endpoint for the Phase 3 bridging study is overall survival. Secondary outcome measures include the rate and duration of remission and whether uproleselan can reduce the rate of oral mucositis, a chemotherapy-related side effect.

•We may be subject to patent infringement claims or may need to file such claims.

We•Our ~~and~~ability ~~Apollomics established a joint development committee~~ to ~~oversee~~protect ~~activities~~our ~~under~~products ~~the~~may ~~collaboration~~be ~~and~~impaired ~~license agreement. The collaboration and license agreement will terminate on a region-~~by~~-region~~ ~~basis~~changes ~~upon~~to ~~the~~patent laws.

•Our patent protection could be reduced or eliminated for non-compliance with legal requirements.

•We may fail to identify or interpret relevant third-party patents.

•We may become subject to claims challenging the inventorship or ownership of our intellectual property.

•Patent terms may be inadequate to protect our competitive position of our programs.

•Our technology licensed from Paragon and Kelun and any technology licensed from other third-parties in the future may be subject to retained rights.

•We may be unable to protect the confidentiality of our trade secrets and other proprietary information.

•We may become subject to litigation under the Biologics Price Competition and Innovation Act of 2010 (“BPCIA”) in connection with patent rights for our product candidates.

Risks Related to Our Reliance on Third Parties

•We currently and in the future expect to rely on agreements with third parties to develop our product candidates. If we are unable to maintain our current or future collaborations or licensing arrangements, or if our current or future collaborations or licensing arrangements are not successful, our business could be negatively impacted.

Table of Contents

~~expiration~~Additionally, ofin ~~the~~some ~~royalty term for each region~~instances, ~~unless~~our ~~earlier~~agreements ~~terminated~~with bythird ~~either~~parties ~~party. Either party~~ may ~~terminate~~include ~~the~~certain ~~collaboration~~indemnification ~~and~~provisions ~~license agreement upon prior written notice~~which, ~~subject~~if ~~to specified conditions~~triggered, ~~including uncured material breach, or upon bankruptcy or insolvency of the other party. Apollomics~~ may ~~terminate~~negatively ~~the~~impact ~~collaboration~~our ~~and license agreement upon prior written notice for any reason~~business. As noted above, in December 2024 Apollomics announced that its Phase 3 bridging trial of uproleselan did not demonstrate favorable benefit and that Apollomics would be winding down the program. We do not expect the collaboration and license agreement to remain in effect following the consummation of the Merger, and do not anticipate having any material ongoing obligations under the agreement for supplying drug for any trials being conducted by Apollomics.

•Third parties we rely on for the execution of nonclinical studies and clinical trials may fail to carry out their contractual duties.

~~Intellectual~~•We ~~Property~~may be unable to use third-party manufacturing sites, our third-party manufacturers may encounter difficulties in production, or we may need to switch or create third-party manufacturer redundancies.

WeOther ~~strive~~Risk toFactors protect the intellectual property that we believe is important to our business, including seeking and maintaining patent protection intended to cover the composition of matter of our drug candidates and their methods of use. We have issued patents which cover uproleselan and methods of use that are expected to expire between 2032 and 2039. In addition, we have several pending patent applications covering uproleselan and/or methods of using it, the last expiring of which, if issued, currently would be predicted to expire in 2041. We also have two issued patents covering GMI-~~1687~~ ~~that~~Risks ~~are~~Related ~~expected~~ to ~~expire~~Employee ~~in 2037. In addition~~Matters, weManaging ~~have several pending patent applications covering GMI-1687 and/or methods of using it~~Growth, ~~the~~Other ~~last~~Risks ~~expiring~~Related ~~of which, if issued, currently it would be predicted~~ to ~~expire~~Our ~~in 2041. We also have several pending patent applications directed to our lead galectin antagonist compounds and their methods of use~~Business, ~~the last of which, if issued, currently would be predicted to expire in 2042. We have also relied on trade secret protection for our confidential~~ and ~~proprietary~~Owning ~~information~~Our ~~and~~Ordinary careful monitoring of such information to protect aspects of our business, as well as know-how and continuing technological innovation to develop, strengthen and maintain our proprietary position in the field of glycomimetics. Shares

•Our business is dependent on key personnel and we will be harmed if we cannot recruit and retain highly qualified personnel to successfully implement our business strategy.

If•In weorder ~~were~~ to ~~resume~~successfully ~~our~~implement ~~historical business of drug development,~~ our ~~success~~plans ~~would depend significantly on our ability to obtain~~ and ~~maintain~~strategies, ~~patent~~we ~~and~~will ~~other~~need ~~proprietary protection for commercially important inventions and know-how related~~ to ~~our~~grow ~~business,~~the ~~defend~~size ~~and enforce our patents, preserve confidentiality~~ of our ~~trade~~organization ~~secrets~~ and ~~operate~~we ~~without~~may ~~infringing~~experience ~~valid~~difficulties ~~and~~in ~~enforceable~~managing ~~patents~~this ~~and other proprietary rights of third parties~~growth.

•Our estimates of market opportunity and forecasts of market growth may prove to be inaccurate, and even if the markets in which we compete achieve the forecasted growth, our business may not grow at similar rates, or at all.

A•Significant ~~third~~disruptions ~~party may hold intellectual property, including patent rights that are important or necessary to the development~~ of ~~our~~information ~~drug~~technology ~~candidates.~~systems ~~It may be necessary for us to use the patented~~ or ~~proprietary~~breaches ~~technology~~ of ~~third~~data ~~parties~~security tocould ~~commercialize~~adversely ~~our~~affect drug candidates, in which case we would be required to obtain a license from these third parties. If we are not able to obtain such a license, or are not able to obtain such a license on commercially reasonable terms, our business ~~could be materially harmed~~.

•Changes in and failures to comply with United States and foreign privacy and data protection laws, regulations, and standards may adversely affect our business, operations, and consolidated financial performance.

~~The~~•We ~~patent~~may ~~positions~~become ofexposed ~~biotechnology~~to ~~companies~~costly ~~like us are generally uncertain~~ and ~~involve~~damaging ~~complex~~liability ~~legal,~~claims ~~scientific~~ and ~~factual~~our ~~questions.~~insurance In addition, the coverage claimed in a patent application can be significantly reduced before the patent is issued, and its scope can be reinterpreted after issuance, including where a reissue application is filed in relation to an issued patent to correct issues or errors arising during prosecution that may ~~render claims of the issued patent either wholly or partially invalid or unenforceable. Consequently, we do~~ not ~~know~~cover ~~whether~~all ~~any~~damages offrom ~~our~~such drug candidates will be protectable or remain protected by enforceable patents. We cannot predict whether the patent applications we are currently pursuing will issue as patents in any particular jurisdiction or whether the claims ~~of any issued patents will provide sufficient proprietary protection from competitors~~. ~~Any patents that we hold may be challenged, circumvented or invalidated by third parties.~~

•Our business could be adversely affected by macroeconomic conditions, including tariffs.

~~Because~~•We ~~patent~~do ~~applications~~not inanticipate ~~the~~paying ~~United~~any ~~States~~dividends ~~and certain other jurisdictions are maintained~~ in ~~secrecy for 18 months, and since publication of discoveries in scientific or patent literature often lags behind actual discoveries, we cannot be certain of~~ the ~~priority~~foreseeable ~~of inventions covered by pending patent applications~~future. Moreover, we may have to participate in interference proceedings declared by the U.S. Patent and Trademark Office, or USPTO, or a foreign patent office to determine priority of invention or in post-grant challenge proceedings, such as oppositions, that challenge priority of invention or other features of patentability. Such proceedings could result in substantial cost, even if the eventual outcome is favorable to us.

•Future sales of shares by existing shareholders could cause our share price to decline.

•Future sales and issuances of equity and debt could result in additional dilution to our shareholders and could cause our share price to decline.

Table of Contents

Part I

~~Manufacturing~~Item 1. Business

WeCorporate do not have any manufacturing facilities or personnel. We relied on third parties for the manufacturing of our drug candidates for preclinical and clinical testing, as well as for potential commercial manufacturing. Information

We were incorporated under the laws of the State of Delaware in 2003. Our company, formerly known as GlycoMimetics, Inc., is a biotechnology company that is the result of a reverse recapitalization transaction with a private company named Crescent Biopharma, Inc. (“Pre-Merger Crescent”). Prior to the reverse recapitalization transaction, Pre-Merger Crescent was established and incorporated under the laws of the state of Delaware on September 19, 2024. On June 16, 2025, in connection with the reverse recapitalization transaction with Pre-Merger Crescent, we changed our jurisdiction of incorporation from the state of Delaware to the Cayman Islands pursuant to a plan of conversion.

In January 2024, we entered into a project agreement with Patheon Manufacturing Services LLC, part of Thermo Fisher Scientific, or Patheon, for manufacture and supply of uproleselan for commercial sale. Pursuant to the agreement, Patheon was to manufacture commercial supplies of injectable uproleselan from active pharmaceutical ingredients we supply, and was also to be responsible for supplying the other required raw materials and other supportive manufacturing services such as quality control testing for raw materials, packaging components and finished product. The initial term of the agreement is through year-end 2026; however, following our decision to cease the development and potential commercialization of uproleselan we have paused all activities under this project agreement and expect that it may be terminated following the consummation of the Merger with Crescent. Overview

We are a clinical-stage biotechnology company focused on delivering the next wave of transformative therapies to bring a brighter future for people living with cancer. We have a bold vision to build the next leading biotechnology oncology company. We are executing across two distinct strategies to build our portfolio to achieve this vision. First, we are developing CR-001, which we refer to as a PD-1 x VEGF bispecific antibody because it is designed to bind both the PD-1 immune checkpoint (“PD-1”) and Vascular Endothelial Growth Factor (“VEGF”), which has potential to replace pembrolizumab, marketed by Merck as Keytruda®, as the foundational immuno-oncology backbone; second, we are building a robust portfolio of potentially best-in-class antibody drug conjugates (“ADCs”). Importantly, as we execute on these two strategies, we intend to combine CR-001 and ADC therapies to create what we believe will be best-in-class synergistic combinations to transform care for multiple types of cancer. We initiated a global Phase 1/2 trial of CR-001 (the “ASCEND trial”) in February 2026 and we anticipate initiation of CR-002 and CR-003 monotherapy clinical trials in 2026 as well as the first ADC combination trial with CR-001.

~~Commercialization~~Figure 1. Our vision is to create a world-leading oncology company developing products that can be used as monotherapies or in combination

~~Prior~~Immune tocheckpoint ~~entering~~inhibitors ~~into~~have revolutionized the ~~agreement~~treatment ~~with~~landscape ~~Crescent~~ for ~~the~~various ~~Merger,~~solid wetumors ~~had~~by ~~not~~reactivating ~~yet~~the ~~established~~body’s aimmune ~~sales,~~system ~~marketing~~to ortarget ~~drug~~and ~~distribution~~destroy ~~infrastructure~~cancer cells. WeThese ~~generally~~inhibitors, ~~retained~~which ~~commercial~~are ~~rights~~antibodies inagainst ~~the~~targets ~~United~~such ~~States~~as ~~for~~Cytotoxic ~~our~~T-lymphocyte-associated ~~drug~~protein ~~candidates.~~4 If(“CTLA-4”) weand ~~were~~PD-1/Programmed toDeath-Ligand ~~resume~~1 ~~drug development activities~~(“PD-L1”), ~~then~~have ~~subject~~shown tounprecedented ~~receiving~~anti-tumor ~~marketing approvals~~activity, weand ~~believe~~have ~~that~~become itstandard-of-care ~~would~~treatments ~~be possible~~ for usmore tothan ~~access~~40 ~~the~~malignancies, ~~U.S.~~including ~~market~~melanoma, ~~for~~non-small ~~those~~cell ~~drug~~lung ~~candidates~~cancer ~~through~~(“NSCLC”) aand ~~focused,~~microsatellite ~~specialized,~~instability-high ~~key account sales force~~tumors. WeThese ~~believe~~inhibitors ~~that~~have ~~such~~led ~~an organization would be able~~ to ~~target~~significant ~~the~~clinical ~~community~~outcomes, ofwith ~~physicians~~notable ~~who~~improvements ~~are the key specialists~~ in ~~treating~~survival ~~the~~rates ~~patient~~and ~~populations~~durable ~~for~~responses ~~which~~in ~~our~~patients ~~drug~~who ~~candidates~~previously ~~were~~had ~~being~~limited ~~developed~~treatment options. ~~With~~These ~~respect~~products tohave ~~uproleselan~~also ~~and~~been ~~GMI-1687,~~successful wecommercially ~~granted~~with ~~Apollomics~~worldwide ~~exclusive~~annual ~~commercialization~~sales ~~rights~~estimated ~~in Greater China. We would expect~~ to ~~enter~~be ~~into~~in ~~distribution~~excess ~~and~~of ~~other~~$50 ~~marketing~~billion, ~~arrangements~~over ~~with~~half ~~third~~of ~~parties~~which ~~for~~are ~~any~~driven ~~other~~by ~~drug~~sales ~~candidates~~of ~~that obtain marketing approval outside the United States~~Keytruda.

Although immune checkpoint inhibitors are highly effective in some indications, many patients with solid tumors fail to respond to these therapies. Furthermore, patients who do respond do not always achieve long-lasting benefit. There have been broad efforts by the pharmaceutical industry to identify immuno-oncology products able to address this unmet clinical need. Ivonescimab, a PD-1 x VEGF bispecific antibody in development by Akeso Biopharma and Summit Therapeutics Inc., is the first drug candidate to demonstrate significantly improved progression free survival (“PFS”) compared to Keytruda. In the HARMONi-2 trial, a randomized, double-blind, head-to-head Phase 3 clinical trial in naïve, or not

Competition

The biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary products. While we believe that our technology, knowledge, experience and scientific resources have in the past provided us with competitive advantages, we would face potential competition from many different sources, including large pharmaceutical and biotechnology companies, specialty pharmaceutical and generic drug companies, and medical technology companies, in the event that we resume our drug development activities. Any product candidates that we successfully develop and commercialize would compete with existing therapies and new therapies that may become available in the future.

If we resume our development activities and seek any regulatory approvals and pursue commercialization, we believe that the key competitive factors affecting success of our drug candidates are likely to be their safety, efficacy, convenience, price, generic competition, and availability of coverage and reimbursement from government and other third-party payors.

Many of the companies against which we would compete have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved drugs than we do. Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These competitors would also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.

Government Regulation and Product Approval

Government authorities in the United States, at the federal, state and local levels, and in other countries, extensively regulate, among other things, the research, development, testing, manufacture, packaging, storage, recordkeeping, labeling, advertising, promotion, distribution, marketing, import and export of pharmaceutical products,

Table of Contents

~~such~~previously astreated, ~~those~~advanced ~~we are developing. The processes for obtaining regulatory approvals in the United States~~ and inmetastatic ~~foreign countries~~NSCLC, ~~along~~the ~~with~~median ~~subsequent~~PFS ~~compliance~~ with ~~applicable~~ivonescimab ~~statutes~~was ~~and~~11.1 ~~regulations,~~months ~~require~~compared ~~the~~to ~~expenditure~~5.8 ofmonths ~~substantial~~with ~~time and financial resources~~Keytruda.

CR-001 (also referred to as SKB118) is a new molecular entity designed to incorporate the targeting, binding, cooperativity and pharmacokinetics of ivonescimab. Through its ability to bind both PD-1 and VEGF, CR-001 has been shown to have cooperative binding and increased activity of cytotoxic T cell activation. These effects are similar to that observed with ivonescimab in the presence of these ligands which are commonly found in many tumors. We believe the emerging data from the clinical development of ivonescimab supports the rationale for developing CR-001 in light of CR-001 and ivonescimab sharing the same mechanism of action. We do not have any clinical data regarding cancer patients that have been treated with CR-001 and there can be no assurance that the clinical trial of CR-001, which we have initiated and which covers a broader set of indications than in HARMONi-2, will have similar or comparable results.

~~United~~We ~~States~~believe ~~Government~~that ~~Regulation~~CR-001 has the potential to deliver improved clinical efficacy and safety over Keytruda, which is the best-selling drug in the world and is approved for the treatment of numerous cancers. Following the precedents set by traditional PD-1 inhibitors, such as Keytruda and Opdivo®, we plan to seek regulatory approvals for CR-001 to treat multiple solid tumor indications utilizing monotherapies and combination treatment options. We initiated a Phase 1/2 trial of CR-001 in NSCLC and other solid tumors in the first quarter of 2026.

InCR-002 ~~the~~is ~~United~~an ~~States,~~ADC ~~the~~that ~~FDA~~delivers ~~regulates~~a ~~drugs~~topoisomerase ~~under~~toxin ~~the~~to ~~Federal~~cancer ~~Food,~~cells ~~Drug,~~that ~~and~~express ~~Cosmetic Act~~PD-L1, ora ~~FDCA,~~cell ~~and~~surface ~~its~~protein ~~implementing~~that ~~regulations.~~suppresses ~~The~~T-cell ~~process~~activation. ofPD-L1 ~~obtaining~~expression ~~regulatory~~is ~~approvals~~elevated ~~and~~in ~~the~~numerous ~~subsequent~~solid ~~compliance~~tumors ~~with~~compared ~~appropriate~~to ~~federal,~~normal ~~state~~tissues, ~~local~~making ~~and~~it ~~foreign~~an ~~statutes~~attractive ~~and~~ADC ~~regulations~~target. ~~requires~~CR-002 ~~the~~is ~~expenditure~~differentiated offrom ~~substantial~~other ~~time~~ADCs ~~and~~through ~~financial~~multiple ~~resources~~properties. ~~Failure~~First, toa ~~comply~~critical ~~with~~feature ~~the~~of ~~applicable~~CR-002 ~~United~~is ~~States~~that ~~requirements~~it atis ~~any~~more ~~time~~efficiently ~~during~~internalized ~~the~~into ~~drug~~cancer ~~development~~cells ~~process,~~than ~~approval~~comparable ~~process~~ADCs. orSecond, ~~after~~the ~~approval,~~chemical ~~may~~linkage ~~subject~~to anits ~~applicant~~toxin is designed to abe ~~variety~~stable ofuntil ~~administrative~~it oris ~~judicial~~internalized. ~~sanctions~~Third, ~~such~~the ascytotoxic ~~the~~payload ~~FDA’s~~is ~~refusal~~a topoisomerase inhibitor that has been shown to ~~approve~~have ~~pending~~higher ~~new~~antitumor ~~drug~~activity ~~applications,~~and orincreased ~~NDAs,~~tolerability ~~withdrawal~~when ofincorporated aninto ~~approval,~~other ~~imposition~~ADCs ofas acompared ~~clinical~~to ~~hold,~~microtubule ~~issuance~~inhibitors. ofWe ~~warning~~believe orthat ~~untitled~~CR-002 ~~letters,~~has ~~product~~the ~~recalls,~~potential ~~product~~to ~~seizures,~~have ~~total~~improved oranti-tumor ~~partial~~activity ~~suspension~~and oftolerability ~~production~~compared orto ~~distribution,~~other ~~injunctions,~~PD-L1 ~~fines,~~directed ~~refusals~~ADCs. ofWe ~~government~~intend ~~contracts,~~to ~~restitution,~~initiate ~~disgorgement~~a orPhase ~~civil~~1/2 ortrial ~~criminal~~of ~~penalties~~CR-002 in the second half of 2026.

We recently announced a partnership with Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (“Kelun”), a leading Chinese biotech company with commercially approved ADCs, to acquire exclusive rights to SKB105 (also referred to as CR-003), an integrin beta-6 (“ITGB6”)-directed ADC, outside of mainland China, Hong Kong, Macau, and Taiwan (collectively, “Greater China”). ITGB6 is overexpressed in many solid tumors and its high expression correlates with tumor size, vascular invasion, metastatic potential, disease recurrence and worse prognosis. We intend to develop SKB105 as CR-003, a product designation which previously referred to a preclinical ADC asset under the ADC Discovery and Option Agreement with Paragon Therapeutics, Inc. (“Paragon”). ITGB6 is a target with emerging clinical data generated by third party ADCs. We believe that CR-003 has the potential to deliver potent antitumor activity based on its improved potency and half-life in preclinical models. A Phase 1/2 trial of CR-003 is anticipated to be initiated in the first quarter of 2026 in China.

~~The~~Combinations ~~process~~of ~~required~~immune bycheckpoint ~~the~~inhibitors ~~FDA~~and ~~before~~ADCs with a ~~drug~~topoisomerase ~~may~~payload beare ~~marketed~~a growing area of interest as third party results have demonstrated improvements in PFS. In the ~~United~~ASCENT-04 ~~States~~trial, ~~generally~~sacituzumab ~~involves:~~govitecan, marketed as Trodelvy® by Gilead Sciences, in combination with pembrolizumab led to a statistically significant and clinically meaningful improvement in PFS versus chemotherapy plus pembrolizumab with durable responses, no new safety concerns and a lower rate of treatment discontinuation due to treatment-emergent adverse events (“TEAEs”) in patients with previously untreated, PD-L1–positive advanced triple negative breast cancer (“TNBC”).

●The ~~completion~~potential to combine CR-001 with ADCs is a key element of ~~preclinical~~our ~~laboratory~~partnership ~~tests~~with Kelun. As part of our agreement, ~~animal~~we ~~studies~~granted ~~and~~Kelun ~~formulation~~exclusive ~~studies~~rights to CR-001 in ~~compliance~~Greater ~~with~~China. With this partnership, we can mutually advance CR-001 and CR-003 globally. Both companies will have the ~~FDA’s~~ability ~~good~~to ~~laboratory~~develop ~~practice,~~both of these molecules as monotherapies or ~~GLP~~in combination with other therapies, ~~regulations;~~including ADCs. We anticipate that clinical results generated by Kelun evaluating CR-001 in combination with their full suite of ADCs will inform and accelerate the development of CR-001 in the rest of the world. This partnership enables parallel generation of clinical data for CR-001 in both Chinese and non-Chinese patient populations and may limit the need for bridging studies across different populations. We anticipate initiating the first CR-001 ADC combination trial in the second half of 2026.

●We ~~submission~~envision multiple opportunities to ~~the~~establish ~~FDA~~and maintain market leadership in oncology through careful selection of anADC ~~IND,~~products ~~which~~based ~~must~~on ~~become~~targets ~~effective~~and ~~before~~payloads. ~~human~~We ~~clinical~~plan ~~trials~~to ~~may~~continue ~~begin;~~to expand our product portfolio through a combination of internal development, our relationship with Paragon and external sources.

● approval by an independent institutional review board, or IRB, at each clinical site before each trial may be initiated;

● performance of human clinical trials, including adequate and well-controlled clinical trials, in accordance with good clinical practices, or GCP, to establish the safety and efficacy of the proposed drug for each indication;

● submission to the FDA of an NDA;

● satisfactory completion of an FDA advisory committee review, if applicable;

● satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the product is produced to assess compliance with current good manufacturing practices, or cGMP, and to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity, as well as satisfactory completion of an FDA inspection of selected clinical sites to determine GCP compliance; and

● FDA review and approval of the NDA.

Preclinical Studies

Preclinical studies include laboratory evaluation of product chemistry, toxicity and formulation, as well as animal studies to assess potential safety and efficacy. An IND sponsor must submit the results of the preclinical studies, together with manufacturing information, analytical data and any available clinical data or literature, among other things, to the FDA as part of an IND. Some preclinical testing may continue even after the IND is submitted. An IND automatically becomes effective 30 days after receipt by the FDA, unless before that time the FDA raises concerns or questions related to one or more proposed clinical trials and places the clinical trial on a clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. As a result, submission of an IND may not result in the FDA allowing clinical trials to commence.

Clinical Trials

Clinical trials involve the administration of the investigational new drug to human subjects under the supervision of qualified investigators in accordance with GCP requirements, which include the requirement that all research subjects provide their informed consent in writing for their participation in any clinical trial. Clinical trials are conducted under protocols detailing, among other things, the objectives of the trial, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. A protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of the IND. In addition, an IRB at each institution participating in the clinical trial must

Table of Contents

~~review~~Our and approve the plan for any clinical trial before it commences at that institution, and the IRB must continue to oversee the clinical trial while it is being conducted. Information about certain clinical trials must be submitted within specific timeframes to the National Institutes of Health, or NIH, for public dissemination on their ClinicalTrials.gov website.Pipeline

Our Strategy

~~Human~~We ~~clinical trials~~ are ~~typically~~focused ~~conducted~~on indelivering ~~three sequential phases, which may overlap or be combined. In Phase 1,~~ the ~~drug~~next iswave ~~initially~~of ~~introduced~~transformative ~~into~~therapies ~~healthy~~to ~~human~~bring ~~subjects~~a orbrighter ~~patients~~future ~~with the target disease or condition and tested~~ for ~~safety,~~people ~~dosage~~living ~~tolerance,~~with ~~absorption, metabolism, distribution, excretion and, if possible, to gain an initial indication of its effectiveness~~cancer. InWe ~~Phase~~have ~~2, the drug typically is administered to~~ a ~~limited~~bold ~~patient~~vision ~~population~~ to ~~identify~~build ~~possible adverse effects and safety risks, to preliminarily evaluate~~ the ~~efficacy~~next ofleading ~~the~~biotechnology ~~product for specific targeted diseases and to determine dosage tolerance and optimal dosage~~company. InOur ~~Phase~~strategy ~~3, the drug~~ is ~~administered~~ to an expanded patient population, generally at geographically dispersed clinical trial sites, in well-controlled clinical trials to generate enough data to statistically evaluate the safety and efficacy of the product for approval, to establish the overall risk-benefit profile of the product and to provide adequate information for the labeling of the product.:

•Obtain clinical proof-of-concept data with CR-001 in a Phase 1/2 trial. We initiated a global Phase 1/2 trial of CR-001 in up to eight solid tumor types in the first quarter of 2026 (the “ASCEND trial”). We believe that, because CR-001 incorporates the targeting, binding, cooperativity and pharmacokinetics of ivonescimab, early clinical data from ivonescimab can serve as important validation of potential effectiveness and tolerability of both ivonescimab and CR-001, thereby allowing us to move quickly into late-stage development with a level of speed and confidence that would not exist if CR-001 did not incorporate the PD-1 and VEGF binding affinity, potency, and cooperative pharmacology of ivonescimab.

~~Progress~~•Develop ~~reports~~CR-001 ~~detailing~~in ~~the~~multiple ~~results~~indications. ofWe ~~the~~have ~~clinical~~identified ~~trials~~a ~~must~~number beof ~~submitted,~~solid attumors ~~least~~in ~~annually,~~which toPD-1 ~~the~~checkpoint ~~FDA,~~inhibitors and ~~more~~VEGF ~~frequently~~inhibitors ifhave ~~serious~~demonstrated ~~adverse~~clinical ~~events occur~~activity. ~~Phase~~We 1,intend ~~Phase~~to 2develop ~~and~~CR-001 ~~Phase~~in 3multiple ~~clinical~~solid ~~trials~~tumors, ~~may~~prioritized ~~not~~based beon ~~completed~~existing ~~successfully~~clinical ~~within~~evidence ~~any~~for ~~specified~~the ~~period,~~potential orof ~~at all. Furthermore~~CR-001, the ~~FDA~~size orof the ~~sponsor~~market ~~may~~opportunity, ~~suspend~~and orthe ~~terminate~~feasibility ato ~~clinical~~streamline ~~trial~~the atgeneration ~~any~~of ~~time~~data ~~on various grounds, including a finding~~ that ~~the~~we ~~research~~believe ~~subjects~~will ~~are~~be ~~being~~sufficient ~~exposed~~ to anobtain ~~unacceptable~~regulatory ~~health risk~~approval. ~~Similarly,~~Our aninitial ~~IRB~~focus ~~can~~will ~~suspend~~be ~~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~~thoracic, orgastrointestinal ifand ~~the~~gynecologic ~~drug has been associated with unexpected serious harm to patients~~cancers.

•Advance our ADC programs into clinical development. We believe that CR-002 and CR-003 have the potential to provide therapeutic benefit both when used as monotherapies and in combination with CR-001. We anticipate initiating monotherapy clinical trials with CR-002 in the second half of 2026 and with CR-003, through our partnership with Kelun, in the first quarter of 2026.

~~Marketing~~•Develop ~~Approval~~CR-001 as a backbone therapy used in combination with ADCs. We believe that, similar to traditional PD-1 checkpoint inhibitors, CR-001 has the potential to elicit meaningful clinical activity both as monotherapy and in combination with other therapies. Our partnership with Kelun is designed to provide us with a competitive advantage by accelerating clinical evaluation of the potential of CR-001 in combination with a broad portfolio of ADCs.

~~Assuming~~•Expand ~~successful~~our ~~completion~~portfolio of ~~the required clinical testing, the results of the preclinical and clinical studies, together with detailed information relating to the~~ product’s ~~chemistry,~~candidates. ~~manufacture,~~We ~~controls~~will ~~and~~consider ~~proposed~~opportunities ~~labeling, among other things, are submitted~~ to ~~the~~expand ~~FDA~~our aspipeline ~~part~~by ofobtaining anaccess ~~NDA requesting approval~~ to ~~market~~best-in-class ~~the~~ product ~~for one or more indications. In most cases~~candidates, ~~the~~including ~~submission of an NDA is subject to a substantial application user fee. Under the Prescription Drug User Fee Act~~ADCs, ~~or PDUFA, guidelines~~ that ~~are~~have ~~currently~~potential inactivity ~~effect,~~against ~~the~~solid ~~FDA~~tumors ~~has~~both ~~agreed~~as tomonotherapy ~~certain~~and ~~performance~~in ~~goals~~combination ~~regarding~~with ~~the timing of its review of an application~~CR-001.

Limitations of current immune checkpoint inhibitors

InImmune ~~addition,~~checkpoint ~~under~~inhibitors ~~the~~have ~~Pediatric~~revolutionized ~~Research~~the ~~Equity~~treatment ~~Act~~of cancer, anoffering ~~NDA~~new orhope ~~supplement~~ to anpatients ~~NDA~~with ~~must~~previously ~~contain~~limited ~~data~~options. ~~that~~These ~~are~~groundbreaking ~~adequate~~therapies towork ~~assess~~by ~~the~~reactivating ~~safety and effectiveness of~~ the ~~drug~~body’s ~~for~~own ~~the~~immune ~~claimed~~system ~~indications in all relevant pediatric subpopulations, and~~ to ~~support~~target ~~dosing~~ and ~~administration~~destroy ~~for~~cancer ~~each~~cells. ~~pediatric~~Checkpoint ~~subpopulation~~inhibitors, ~~for~~such ~~which~~as ~~the~~CTLA-4 ~~product is safe~~ and ~~effective.~~PD-1/PD-L1 ~~The FDA may~~inhibitors, onhave ~~its~~demonstrated ~~own~~unprecedented ~~initiative~~anti-tumor ~~or at the request of the applicant~~activity, ~~grant~~and ~~deferrals~~have ~~for~~become ~~submission~~standard oftreatments ~~some or all pediatric data until after approval of the product~~ for ~~use~~various ~~in adults~~malignancies, orincluding ~~full~~advanced ormetastatic ~~partial~~melanoma, ~~waivers~~NSCLC, ~~from~~renal ~~the~~cell ~~pediatric data requirements. Unless otherwise required by regulation~~carcinoma, ~~the~~and ~~pediatric~~microsatellite ~~data~~instability-high ~~requirements~~tumors. doThese ~~not~~inhibitors ~~apply~~have led to ~~products with orphan designation.~~

The FDA also may require submission of a risk evaluation and mitigation strategy, or REMS, plan to mitigate any identified or suspected serious risks. The REMS plan could include medication guides, physician communication plans, assessment plans and elements to assure safe use, such as restricted distribution methods, patient registries or other risk minimization tools.

The FDA conducts a preliminary review of all NDAs within the first 60 days after submission, before accepting them for filing, to determine whether they are sufficiently complete to permit substantive review. The FDA may request additional information rather than accept an NDA for filing. In this event, the application must be resubmitted with the additional information. The resubmitted application is also subject to review before the FDA accepts it for filing. Once the submission is accepted for filing, the FDA begins an in-depth substantive review. The FDA reviews an NDA to determine, among other things, whether the drug is safe and effective and whether the facility in which it is manufactured, processed, packaged or held meets standards designed to assure the product’s continued safety, quality and purity.

Table of Contents

~~The~~significant ~~FDA~~clinical ~~typically refers questions regarding novel drugs to an external advisory committee. An advisory committee is a panel of independent experts~~outcomes, ~~including~~with ~~clinicians~~notable ~~and~~improvements ~~other~~in ~~scientific~~survival ~~experts,~~rates ~~that reviews, evaluates~~ and ~~provides~~durable aresponses ~~recommendation~~in aspatients towho ~~whether~~previously ~~the~~had ~~application~~only ~~should~~limited betreatment ~~approved and under what conditions~~options. ~~The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.~~

The remarkable impact of immune checkpoint inhibitors on cancer treatment is reflected in their commercial success. For example, Yervoy®, a CTLA-4 inhibitor that was approved in 2011, achieved worldwide sales of $2.2 billion in 2024. Keytruda, a PD-1 inhibitor, has received 40 U.S. Food and Drug Administration (“FDA”) approvals and 30 European Commission approvals in a variety of different indications. Worldwide sales of Keytruda in 2025 were $31.7 billion. Despite the commercial dominance of Keytruda, at least six other PD-1/PD-L1 inhibitors have been approved by the FDA, including two that received initial approvals in 2024. Sales of this class of checkpoint inhibitors continue to grow year-over-year, with worldwide sales in 2025 reaching $59 billion.

~~Before~~Figure ~~approving an NDA, the FDA typically will inspect the facility or facilities where the product is manufactured~~2. ~~The~~Global ~~FDA~~sales ~~will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production~~ of ~~the~~PD-1/PD-L1 ~~product within required specifications. Additionally, before approving an NDA, the FDA will typically inspect one or more clinical trial sites to assure compliance with GCP.~~inhibitors

Despite these therapies’ remarkable success, only a portion of patients treated with checkpoint inhibitors obtain meaningful benefit. For example, treatment of patients with unresectable or metastatic melanoma with pembrolizumab resulted in a six percent complete response (“CR”) rate, and a 27 percent partial response (“PR”) rate. A meta-analysis of 91 clinical trials found that the objective response rate to checkpoint inhibitors was less than 20 percent.

~~The~~Multiple approaches have been taken to improve this response rate, including the clinical testing of potential therapies against other immune checkpoint targets, and ~~approval~~combination ~~process~~therapies. ~~for~~Emerging antargets, ~~NDA~~such ~~requires~~as ~~substantial~~LAG-3, ~~time~~TIM-3, ~~effort~~and TIGIT, are being evaluated in preclinical studies and ~~financial~~clinical ~~resources~~trials, ~~and~~with ~~could~~the ~~take~~hope ~~several~~of ~~years~~providing toadditional ~~complete~~options for patients with refractory or resistant cancers. ~~Data~~However, ~~obtained~~none ~~from~~of ~~preclinical~~these ~~and~~approaches has yet demonstrated clinical ~~testing~~efficacy as a monotherapy that matches, or exceeds, the established success rates of PD-1/PD-L1 inhibitors. More promising results have been obtained when these agents are ~~not~~combined ~~always~~with ~~conclusive~~PD-1/PD-L1 ~~and~~inhibitors. ~~may~~For beexample, ~~susceptible~~Opdualag®, toa ~~varying~~fixed ~~interpretations~~dose combination of relatlimab, ~~which~~a ~~could~~LAG-3 ~~delay~~inhibitor, ~~limit~~and ornivolumab, ~~prevent~~was ~~regulatory~~approved ~~approval~~in 2022 for the treatment of unresectable or metastatic melanoma. The ~~FDA~~overall ~~may~~response ~~not~~rate ~~grant~~with ~~approval~~the combination drug in the RELATIVITY-047 trial was 43 percent versus 33 percent with nivolumab monotherapy. Combination with other agents thus offers new and potentially profound improvement in the ability of ancheckpoint ~~NDA~~inhibitors onto ameaningfully ~~timely~~impact ~~basis,~~more orpatients atand ~~all~~more tumor types.

After evaluating the NDA and all related information, including the advisory committee recommendation, if any, and inspection reports regarding the manufacturing facilities and clinical trial sites, the FDA may issue an approval letter, or, in some cases, a complete response letter. A complete response letter generally contains a statement of specific conditions that must be met in order to secure final approval of the NDA and may require additional clinical or preclinical testing in order for the FDA to reconsider the application. Even with submission of this 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 will typically issue an approval letter. An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications.

Special FDA Expedited Review and Approval Programs

The FDA has various programs, including fast track designation, accelerated approval, priority review, and breakthrough therapy designation, which are intended to expedite or simplify the process for the development and the FDA review of drugs that are intended for the treatment of serious or life-threatening diseases or conditions and demonstrate the potential to address unmet medical needs. The purpose of these programs is to provide important new drugs to patients earlier than under standard FDA review procedures.

To be eligible for a fast track designation, the FDA must determine, based on the request of a sponsor, that a product is intended to treat a serious or life-threatening disease or condition and demonstrates the potential to address an unmet medical need. The FDA will determine that a product will fill an unmet medical need if it will provide a therapy where none exists or provide a therapy that may be potentially superior to existing therapy based on efficacy or safety factors. The FDA may review sections of the NDA for a fast track product on a rolling basis before the complete application is submitted if the sponsor provides a schedule for the submission of the sections of the NDA, the FDA agrees to accept sections of the NDA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the NDA.

The FDA may give a priority review designation to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists. A priority review means that the goal for the FDA to review an application is six months, rather than the standard review of 10 months under current PDUFA guidelines. These six- and ten- month review periods are measured from the “filing” date rather than the receipt date for NDAs for new molecular entities, which typically adds approximately two months to the timeline for review and decision from the date of submission. Most products that are eligible for fast track designation are also likely to be considered appropriate to receive a priority review.

In addition, products studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may be eligible for accelerated approval. Such products may be approved on the basis of adequate and well-controlled clinical trials establishing that the drug product

Table of Contents

~~has~~The anbreakthrough ~~effect~~potential on a surrogate endpoint that is reasonably likely to predict clinical benefit. Alternatively, the approval may be on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit. Approvals may also take into account the severity, rarity or prevalence of ~~the condition and the availability or lack of alternative treatments. As a condition of approval~~ivonescimab, ~~the FDA may require~~ a ~~sponsor of a drug receiving accelerated approval to perform post~~PD-~~marketing~~1 ~~studies~~x toVEGF ~~verify~~bispecific ~~and~~molecule ~~describe the predicted effect on irreversible morbidity or mortality or other clinical endpoint, and the drug may be subject to accelerated withdrawal procedures.~~

Ivonescimab, a cooperative PD-1 x VEGF bispecific molecule, has demonstrated promising clinical results that highlight its breakthrough potential in oncology. Ivonescimab was designed to synergistically combine the mechanisms of angiogenesis inhibition and immune checkpoint blockade in a single molecule by targeting both PD-1 and VEGF pathways. In the HARMONi-2 trial in NSCLC, ivonescimab demonstrated a statistically significant and clinically meaningful improvement in PFS compared to pembrolizumab.

AHARMONi-2 ~~sponsor~~is ~~can~~a ~~also~~randomized, ~~request~~double-blind ~~designation~~Phase of3 atrial ~~product~~across ~~candidate~~55 ashospitals ain ~~“breakthrough~~China ~~therapy.”~~sponsored Aby ~~breakthrough~~Akeso ~~therapy~~Biopharma isto ~~defined~~support asregulatory aapproval ~~drug~~in ~~that~~China iscomparing ~~intended,~~the ~~alone~~efficacy orof inivonescimab ~~combination~~with pembrolizumab as first-line treatment with ~~one~~PD-L1 expressing locally advanced or ~~more~~metastatic ~~other~~NSCLC. ~~drugs,~~398 topatients ~~treat~~were arandomly ~~serious~~assigned orto ~~life-threatening~~receive ~~disease~~ivonescimab or ~~condition,~~pembrolizumab ~~and~~by ~~preliminary~~intravenous ~~clinical~~infusion ~~evidence~~every ~~indicates~~three ~~that~~weeks. ~~the~~A ~~drug~~planned ~~may~~interim ~~demonstrate~~analysis ~~substantial~~found ~~improvement~~that ~~over~~patients ~~existing~~treated ~~therapies~~with onivonescimab ~~one~~had ora ~~more~~statistically ~~clinically~~ significant ~~endpoints,~~improvement ~~such~~in asmedian ~~substantial~~PFS ~~treatment~~of ~~effects~~5.3 ~~observed~~months ~~early~~compared into ~~clinical~~pembrolizumab, ~~development~~with p<0.0001. ~~Drugs~~Ivonescimab-treated ~~designated~~patients ashad ~~breakthrough~~a ~~therapies~~median ~~are~~PFS ~~also~~of ~~eligible~~11.1 ~~for~~months, ~~accelerated~~compared ~~approval~~to 5.8 months with pembrolizumab. The ~~FDA~~median ~~must~~PFS ~~take~~of ~~certain~~pembrolizumab ~~actions,~~in ~~such~~this astrial ~~holding~~is ~~timely~~consistent ~~meetings~~with ~~and~~the ~~providing~~5.4 ~~advice,~~month ~~intended~~PFS toobserved ~~expedite~~in the ~~development~~pembrolizumab ~~and~~monotherapy ~~review~~arm of anthe ~~application~~KEYNOTE-042 ~~for~~trial ~~approval~~conducted ofin a ~~breakthrough~~similar ~~therapy~~patient population, providing additional support for observed improved potential of ivonescimab.

Figure 3. Ivonescimab monotherapy led to an improvement in median progression-free survival (“mPFS”) over pembrolizumab as a first-line treatment in advanced and metastatic NSCLC

Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened. We may explore some of these opportunities for our product candidates as appropriate.

Post-Approval Requirements

Drugs manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to recordkeeping, periodic reporting, product sampling and distribution, advertising and promotion and reporting of adverse experiences with the product. After approval, most changes to the approved product, such as adding new indications, manufacturing changes or other labeling claims, are subject to further testing requirements and prior FDA review and approval. There also are continuing annual user fee requirements for any marketed products, as well as application fees for supplemental applications with clinical data.

Even if the FDA approves a product, it may limit the approved indications for use of the product, require that contraindications, warnings or precautions be included in the product labeling, including a boxed warning, require that post-approval studies, including Phase 4 clinical trials, be conducted to further assess a drug’s safety after approval, require testing and surveillance programs to monitor the product after commercialization, or impose other conditions, including distribution restrictions or other risk management mechanisms under a REMS, which can materially affect the potential market and profitability of the product. The FDA may prevent or limit further marketing of a product based on the results of post-marketing studies or surveillance programs.

In addition, drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and state agencies, and are subject to periodic unannounced inspections by the FDA and these state agencies for compliance with cGMP requirements. Changes to the manufacturing process are strictly regulated and often require prior FDA approval before being implemented. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting and documentation requirements upon the sponsor and any third-party manufacturers that the sponsor may decide to use. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain cGMP compliance.

Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market.

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 mandatory revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical

Table of Contents

~~trials~~In addition to ~~assess~~this ~~new~~improvement ~~safety~~in ~~risks;~~PFS orover ~~imposition~~pembrolizumab, two other observations from this trial highlight the potential of ~~distribution~~ivonescimab. orFirst ~~other~~is ~~restrictions~~that ~~under~~improved abenefits ~~REMS~~were ~~program~~observed in patients where pembrolizumab has historically had modest efficacy. ~~Other~~This ~~potential~~includes ~~consequences~~patients ~~include,~~with ~~among~~low ~~other~~levels ~~things:~~of PD-L1 expression and in squamous cell tumors.

●Figure ~~restrictions~~4. onIvonescimab ~~the~~provided ~~marketing~~improved orPFS ~~manufacturing~~compared to pembrolizumab, including in patients with low levels of PD-L1 expression and in squamous cell cancers, both of which have historically been associated with poor response to pembrolizumab. The benefits of ivonescimab are represented by the ~~product~~hazard ratio, ~~complete~~a ~~withdrawal~~statistical measure of the ~~product~~relative ~~from~~risk of disease progression in patients in separate groups. A hazard ratio of 0.54 means that ivonescimab-treated patients had a 46 percent lower chance of disease progression than those treated with pembrolizumab. PD-L1 expression was assessed by the ~~market~~Tumor Proportion Score, or ~~product~~TPS, ~~recalls;~~which quantifies the percentage of viable tumor cells showing partial or complete membrane staining of PD-L1.

●Second, ~~fines~~treatment with ivonescimab was well-tolerated with the frequency and severity of immune-related adverse events comparable to those observed in the pembrolizumab arm. Clinical experience in NSCLC with anti-VEGF inhibitors, ~~warning~~such ~~letters~~as bevacizumab, identified serious adverse events, including fatal pulmonary hemorrhage, that have limited the number of patients eligible for treatment. Other adverse events associated with bevacizumab include proteinuria and hypertension. The majority of these VEGF-related adverse events were Grade 1 or ~~holds~~Grade on2 ~~post~~in the data presented from the interim analysis of the HARMONi-~~approval~~2 ~~clinical~~trial. ~~trials;~~There were no adverse events greater than Grade 3. The frequency of Grade 3 events were 1 percent hemorrhage, 3 percent proteinuria, and 5 percent hypertension. There were no increases in treatment discontinuation or death associated with ivonescimab compared to pembrolizumab.

●Our ~~refusal of the FDA to approve pending NDAs or supplements to approved NDAs~~solution, ~~or suspension or revocation of product license approvals;~~CR-001

●CR-001 ~~product~~is ~~seizure~~a orbispecific ~~detention,~~antibody ordesigned ~~refusal~~ to ~~permit~~build upon the ~~import~~transformative orclinical ~~export~~efficacy ofobserved ~~products;~~with orivonescimab by incorporating its functional properties in a proprietary new molecule.

●We ~~injunctions~~initiated orASCEND, a global Phase 1/2 trial of CR-001, enrolling patients with solid tumors in the ~~imposition~~first quarter of ~~civil~~2026. orWe ~~criminal~~believe ~~penalties~~that, because CR-001 incorporates the targeting, binding, cooperativity and pharmacokinetics, early clinical data from ivonescimab can serve as important validation of potential effectiveness and tolerability of both CR-001 and ivonescimab, thereby allowing us to move quickly into late-stage development with a level of speed and confidence that would not exist if CR-001 did not incorporate the PD-1 and VEGF binding affinity, potency, and cooperative pharmacology of ivonescimab.

The ~~FDA~~rationale ~~strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market. Although physicians, in the practice of medicine, may prescribe approved drugs~~ for ~~unapproved~~targeting indications, pharmaceutical companies generally are required to promote their drug products only for the approved indications and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of offPD-~~label~~1 ~~uses,~~ and a company that is found to have improperly promoted off-label uses may be subject to significant liability. However, physicians may, in their independent medical judgment, prescribe legally available products for off-label uses. The FDA does not regulate the behavior of physicians in their choice of treatments, but the FDA does restrict manufacturer’s communications on the subject of off-label use of their products.VEGF

Both PD-1 and VEGF are targets of approved drugs for multiple indications. However, the potential for combining the inhibition of both targets is not widely appreciated. Data from The Cancer Genome Atlas indicates that these targets are co-expressed in various human tumors.

InVEGF ~~addition~~is well-recognized for its angiogenesis-inducing activity, promoting the ~~distribution~~formation of ~~prescription~~new ~~pharmaceutical~~blood ~~products~~vessels isto ~~subject~~help totumors overcome oxygen deficits and nutrient starvation. However, it also has an important immunosuppressive role. VEGF can inhibit the ~~Drug~~maturation ~~Supply~~of ~~Chain~~key ~~Security~~immune ~~Act~~cells known as dendritic cells and ~~state~~promote ~~laws~~the accumulation of another key population of immune cells, the myeloid-derived suppressor cells. Other reports indicate that ~~limit~~blocking VEGF signaling may promote antitumor immune responses by inhibiting the ~~distribution~~accumulation of ~~prescription~~regulatory ~~pharmaceutical~~T ~~product~~cells. ~~samples~~Because ~~and~~immunosuppressive ~~impose~~microenvironments ~~requirements~~can toalso ~~ensure~~drive ~~accountability~~angiogenesis, VEGF plays a central role in ~~distribution.~~driving further

Federal and State Fraud and Abuse, Data Privacy and Security, and Transparency Laws and Regulations

In addition to FDA restrictions on marketing of pharmaceutical products, federal and state healthcare laws and regulations restrict business practices in the biopharmaceutical industry. These laws include, but are not limited to, anti-kickback and false claims laws and regulations, data privacy and security, and transparency laws and regulations.

The federal Anti-Kickback Statute prohibits, among other things, knowingly and willfully offering, paying, soliciting or receiving remuneration to induce or in return for purchasing, leasing, ordering or arranging for or recommending the purchase, lease or order of any item or service reimbursable under Medicare, Medicaid or other federal healthcare programs. The term “remuneration” has been broadly interpreted to include anything of value. The Anti-Kickback Statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on one hand and prescribers, purchasers and formulary managers on the other. Although there are a number of statutory exemptions and regulatory safe harbors protecting some common activities from prosecution, the exemptions and safe harbors are drawn narrowly and require strict compliance in order to offer protection. Practices that involve remuneration that may be alleged to be intended to induce prescribing, purchases or recommendations may be subject to scrutiny if they do not qualify for an exemption or safe harbor. Several courts have interpreted the statute’s intent requirement to mean that if any one purpose of an arrangement involving remuneration is to induce referrals of federal healthcare-covered business, the statute has been violated.

The reach of the federal Anti-Kickback Statute was also broadened by the Patient Protection and Affordable Care Act of 2010, as amended by the Health Care and Education Reconciliation Act of 2010, or collectively PPACA, which, among other things, amended the intent requirement of the federal Anti-Kickback Statute such that a person or entity no longer needs to have actual knowledge of this statute or specific intent to violate it in order to have committed a violation. In addition, PPACA provides that the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the federal civil False Claims Act or the civil monetary penalties statute, which imposes penalties against any person or entity who 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.

Table of Contents

immunosuppression. A number of preclinical studies and clinical trials have explored the potential of inhibiting both PD-1 and VEGF.

Federal false claims laws, including the federal civil False Claims Act, prohibit any person or entity from knowingly presenting, or causing to be presented, a false claim for payment to the federal government or knowingly making, using or causing to be made or used a false record or statement material to a false or fraudulent claim to the federal government. A claim includes “any request or demand” for money or property presented to the U.S. government. Pharmaceutical and other healthcare companies have been prosecuted under these laws for, among other things, allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product. Companies also have been prosecuted for causing false claims to be submitted because of the companies’ marketing of products for unapproved, and thus non-reimbursable, uses. The ~~federal~~design ~~Health Insurance Portability and Accountability Act~~ of ~~1996,~~ivonescimab ordrives ~~HIPAA,~~its ~~created~~clinical additional federal criminal statutes that prohibit, among other things, knowingly and willfully executing a scheme to defraud any healthcare benefit program, including private third-party payors and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services. Also, many states have similar fraud and abuse statutes or regulations that apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor.activity

The antitumor activity of ivonescimab observed in the HARMONi-2 trial was higher than expected for the combination treatments containing both an anti-PD-1 and anti-VEGF antibody in NSCLC. For example, in the Lung-MAP S1800A trial, the combination of ramucirumab, a VEGF receptor inhibitor, and pembrolizumab led to a modest median PFS of 4.5 months compared to 5.2 months reported for patients treated with standard of care. In the ImPower150 trial, the addition of atezolizumab, a PD-L1 inhibitor, to a combination of bevacizumab and chemotherapy, led to a modest increase in median PFS from 6.8 months to 8.3 months.

In ~~addition,~~vitro westudies ~~may~~reported beby ~~subject~~scientists toat ~~data~~Akeso ~~privacy~~Biopharma and ~~security~~Summit ~~regulation~~Therapeutics byat ~~both~~ the ~~federal~~Society ~~government~~for ~~and~~Immunotherapy ~~the~~of ~~states~~Cancer conference in ~~which~~2023 wefound ~~conduct~~that ~~our~~ivonescimab ~~business.~~binding ~~HIPAA,~~to asboth ~~amended~~PD-1 ~~by the Health Information Technology for Economic~~ and ~~Clinical~~to ~~Health~~VEGF ~~Act,~~was orcooperative. ~~HITECH,~~Each ~~and~~molecule ~~their~~of ~~respective~~ivonescimab ~~implementing~~is ~~regulations,~~capable ~~imposes specified requirements on certain types~~ of ~~individuals~~binding ~~and entities relating~~ to ~~the~~two ~~privacy,~~PD-1 ~~security~~ and ~~transmission~~two ofVEGF ~~individually identifiable health information~~molecules. ~~Among~~Due ~~other things, HITECH makes HIPAA’s security standards directly applicable~~ to ~~“business~~inherent ~~associates,”~~dimerization ~~defined as independent contractors or agents~~ of ~~covered entities (or other business associates) that create~~VEGF, ~~receive,~~its ~~maintain~~binding orto ~~transmit~~ivonescimab ~~protected~~can ~~health~~lead ~~information~~to inthe ~~connection~~formation ~~with providing a service for or on behalf~~ of aivonescimab ~~covered entity~~complexes, ~~and~~effectively ~~their~~increasing ~~covered subcontractors. HITECH also increased~~ the ~~civil~~local ~~and~~concentration ~~criminal~~of ~~penalties~~anti-PD-1 ~~that~~binding ~~may~~sites. ~~be imposed against covered entities~~Similarly, ~~business~~binding ~~associates~~of ~~and~~ivonescimab ~~possibly~~to ~~other~~PD-1 ~~persons,~~on ~~and~~immune ~~gave~~cells ~~state~~leads ~~attorneys general new authority~~ to ~~file~~a ~~civil~~local ~~actions~~increase ~~for damages or injunctions~~ in ~~federal~~anti-VEGF ~~courts~~binding ~~to enforce the federal HIPAA laws and seek attorney’s fees and costs associated with pursuing federal civil actions~~sites. In ~~addition~~summary, ~~state~~in ~~laws govern~~ the ~~privacy~~presence ~~and security~~ of ~~health information in certain circumstances~~VEGF, ~~many~~ivonescimab ofbinding ~~which~~affinity ~~are~~to ~~not pre~~PD-~~empted~~1 bywas ~~HIPAA,~~enhanced ~~differ~~promoting ~~from~~increased ~~each~~PD-1/PD-L1 ~~other~~signaling ~~in significant ways and may not have the same effect, thus complicating compliance efforts~~blockade.

The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services, or CMS, information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other healthcare professionals (such as physician assistants and nurse practitioners) and teaching hospitals, and applicable manufacturers and applicable group purchasing organizations to report annually to CMS ownership and investment interests held by the physicians and their immediate family members.

We may also be subject to state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, as well as state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures.

Because of the breadth of these laws and the narrowness of available statutory and regulatory exemptions, it is possible that some of our business activities could be subject to challenge under one or more of such laws. If our operations are found to be in violation of any of the federal and state laws described above or any other governmental regulations that apply to us, we may be subject to significant penalties, including administrative, criminal and civil monetary penalties, damages, fines, disgorgement, 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, contractual damages, reputational harm, diminished profits and future earnings, disgorgement, exclusion from participation in government healthcare programs and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations. To the extent that any of our products are sold in a foreign country, we may be subject to similar foreign laws and regulations, which may include, for instance, applicable post-marketing requirements, including safety surveillance, anti-fraud and abuse laws and

Table of Contents

~~implementation~~Figure of5. ~~corporate~~VEGF ~~compliance~~binding ~~programs~~to ~~and~~ivonescimab ~~reporting~~leads ofto ~~payments~~the orformation ~~transfers~~ of ~~value~~ivonescimab-VEGF ~~to healthcare professionals.~~complexes

The presence of both PD-1 and VEGF expressing immune cells in tumors leads to cooperative binding of ivonescimab resulting in increased binding to both targets, which is hypothesized to be the driver of increased clinical activity.

~~Coverage~~The ~~and~~design ~~Reimbursement~~of CR-001

~~The~~CR-001 ~~future~~is ~~commercial~~a ~~success~~new ofmolecular ~~our~~entity ~~drug~~that ~~candidates~~incorporates orthe ~~any~~targeting, ofbinding, ~~our~~cooperativity, ~~collaborators’~~and ~~ability~~pharmacokinetics toof ~~commercialize~~ivonescimab ~~any approved drug candidates successfully will depend~~ in ~~part~~order ~~on the extent~~ to ~~which~~maximize ~~governmental payor programs at~~ the ~~federal~~likelihood ~~and~~of ~~state~~demonstrating ~~levels,~~superior ~~including~~efficacy ~~Medicare~~compared ~~and~~to ~~Medicaid,~~approved ~~private~~PD-1 ~~health insurers~~ and ~~other third~~PD-~~party~~L1 ~~payors~~therapies. ~~provide~~The ~~coverage~~VEGF ~~for~~binding ~~and~~domain ~~establish~~is ~~adequate~~derived ~~reimbursement~~from ~~levels for our drug candidates. Government health administration authorities~~bevacizumab, ~~private~~an ~~health~~FDA-approved ~~insurers~~anti-VEGF ~~and other organizations generally decide which drugs they will pay for and establish reimbursement levels for healthcare~~antibody. InThis ~~particular,~~domain inwas ~~the~~incorporated ~~United~~into ~~States, private health insurers and other third~~CR-~~party~~001 ~~payors~~to ~~often~~match ~~provide reimbursement for products and services based on~~ the ~~level~~VEGF atbinding ~~which~~affinity ~~the~~of ~~government~~ivonescimab, ~~through~~which contains the ~~Medicare~~same ~~or Medicaid programs, provides reimbursement for such treatments~~domain. InThe ~~the~~PD-1 ~~United~~binding ~~States,~~domain ~~the~~of ~~European Union, or EU, and other potentially significant markets for our drug candidates, government authorities and third~~CR-~~party~~001 ~~payors~~is ~~are~~a ~~increasingly~~proprietary ~~attempting~~scFv tosequence ~~limit~~that orincorporates ~~regulate~~ the ~~price~~affinity of ~~medical~~the ~~products~~PD-1 ~~and~~binding ~~services,~~domain ~~particularly~~of ~~for~~ivonescimab ~~new~~while ~~and~~benefiting ~~innovative~~from ~~products~~increased ~~and~~stability ~~therapies,~~engineered ~~which~~by ~~often has resulted in average selling prices lower than they would otherwise be~~Paragon. ~~Further,~~Paragon ~~the~~has ~~increased~~filed ~~emphasis~~composition onof ~~managed~~matter ~~healthcare~~claims infor the ~~United~~CR-001 ~~States~~sequence ~~and~~based ~~on country and regional pricing and reimbursement controls~~ in ~~the~~part ~~EU will put additional pressure~~ on ~~product~~proprietary ~~pricing,~~scFv ~~reimbursement and usage, which may adversely affect our future product sales and results of operations~~engineering. ~~These~~On ~~pressures~~April ~~can arise from rules and practices of managed care groups~~28, ~~judicial decisions and laws and regulations related to Medicare~~2025, ~~Medicaid and healthcare reform, pharmaceutical coverage and reimbursement policies and pricing in general.~~

Third-party payors are increasingly imposing additional requirements and restrictions on coverage and limiting reimbursement levels for medical products. For example, federal and state governments reimburse covered prescription drugs at varying rates generally below average wholesale price. These restrictions and limitations influence the purchase of healthcare services and products. Third-party payors may limit coverage to specific drug products on an approved list, or formulary, which might not include all of the FDA-approved drug products for a particular indication. Third-party payors are increasingly challenging the price and examining the medical necessity and cost-effectiveness of medical products and services, in addition to their safety and efficacy. We may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of our products, in addition to the costs required to obtain the FDA approvals. Our drug candidates may not be considered medically necessary or cost-effective. A payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved. Further, one payor’s determination to provide coverage for a drug product does not assure that other payors will also provide coverage for the drug product. Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in drug development. Legislative proposals to reform healthcare or reduce costs under government insurance programs may result in lower reimbursement for our drugs and drug candidates or exclusion of our drugs and drug candidates from coverage. The cost containment measures that healthcare payors and providers are instituting and any healthcare reform could significantly reduce our revenues from the sale of any approved drug candidates. We cannot provide any assurances that we will be able to obtain and maintain third-party coverage or adequate reimbursement for our drug candidates in whole or in part.

Impact of Healthcare Reform on our Business

The United States and some foreign jurisdictions are considering enacting or have enacted a number of additional legislative and regulatory proposals 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 expanding access. In the United States, the pharmaceutical industry has been a particular focus of these efforts, which include major legislative initiatives to reduce the cost of care through changes in the healthcare system, including limits on the pricing, coverage, and reimbursement of pharmaceutical and biopharmaceutical products, especially under government-funded health care programs, and increased governmental control of drug pricing.

There have been several U.S. government initiatives over the past few years to fund and incentivize certain comparative effectiveness research, including creation of the Patient-Centered Outcomes Research Institute under PPACA. Although the results of the comparative effectiveness studies are not intended to mandate coverage policies for

Table of Contents

~~public~~we orentered ~~private~~into ~~payors, it is not clear what effect, if any, the research will have on the sales of any product, if any such product or the condition that it is intended to treat is the subject of~~ a ~~study.~~License ItAgreement iswith ~~also~~Paragon ~~possible that comparative effectiveness research demonstrating benefits in a competitor’s product could adversely affect~~ (the ~~sales of our product candidates. If third~~“CR-~~party~~001 ~~payors~~License doAgreement”) ~~not~~pursuant ~~consider our drug candidates~~ to bewhich ~~cost-effective~~we ~~compared~~have tolicensed ~~other~~from ~~available~~Paragon ~~therapies,~~these they may not cover our drug candidates, once approved, as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow us to sell our drugs on a profitable basis. The PPACA substantially changed the way healthcare is financed by both governmental and ~~private insurers. Among~~ other ~~measures~~intellectual ~~that~~property ~~may~~rights ~~have~~applicable an impact on our business, PPACA established an annual, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic agents; a new Medicare Part D coverage gap discount program; and a new formula that increases the rebates a manufacturer must pay under the Medicaid Drug Rebate Program. Additionally, PPACA extends manufacturers’ Medicaid rebate liability, expands eligibility criteria for Medicaid programs and expands entities eligible for discounts under the Public Health Service pharmaceutical pricing program. There have been judicial and Congressional challenges to ~~certain aspects of PPACA, as well as efforts by the executive branch at various times to repeal or replace certain aspects of the PPACA~~CR-001.

Figure 6. Structure of CR-001

~~Since~~CR-001 ~~its~~incorporates ~~enactment,~~the ~~there~~pharmacokinetics ~~have~~of ~~been~~ivonescimab. ~~judicial,~~Similar ~~administrative,~~to ~~executive~~ivonescimab, ~~and~~the ~~Congressional~~IgG ~~legislative~~Fc ~~challenges~~domain toof ~~certain~~CR-001 ~~aspects~~was ofmodified ~~the~~to ~~PPACA.~~reduce ~~For~~its ~~example,~~ability into ~~August~~bind ~~2022~~to FcγRIIIA, ~~the~~a ~~Inflation~~receptor ~~Reduction~~on ~~Act~~natural ofkiller ~~2022,~~(“NK”) orcells ~~IRA~~that ~~was~~drives ~~signed~~antibody ~~into~~dependent ~~law,~~cellular ~~which~~cytotoxicity. ~~among~~The ~~other~~resulting ~~things,~~reduction ~~extends~~in ~~enhanced~~antibody-dependent ~~subsidies~~cellular ~~for~~cytotoxicity ~~individuals~~is ~~purchasing~~designed ~~health~~to ~~insurance~~protect ~~coverage~~CR-001 infrom ~~PPACA~~driving ~~marketplaces~~NK ~~through~~cell ~~plan~~dependent ~~year~~destruction ~~2025~~of T cells. The ~~IRA~~affinity ~~also~~of ~~eliminates~~CR-001 for the ~~"donut~~FcRn ~~hole"~~receptor ~~under~~matches ~~the~~that ~~Medicare~~of ~~Part~~ivonescimab, Dhelping ~~program~~to ~~beginning~~prolong inits ~~2025~~half-life byin ~~significantly~~circulation. ~~lowering~~We ~~the~~have ~~beneficiary~~also ~~maximum~~incorporated ~~out-of-pocket~~proprietary ~~cost~~engineering ~~and~~to ~~creating~~stabilize athe ~~new~~scFVs ~~manufacturer~~of ~~discount~~CR-001, ~~program.~~which Itwe isbelieve ~~unclear~~has ~~how~~the ~~any~~potential ~~such~~for ~~challenges~~developing ~~and~~subcutaneous ~~additional~~dosing. ~~reform~~Our ~~measures~~composition of ~~the~~matter ~~second~~claims ~~Trump~~are ~~administration~~based ~~will~~in ~~impact~~part ~~the~~on ~~PPACA.~~this proprietary scFV engineering.

We believe that our decision to incorporate the functional properties of ivonescimab with a proprietary molecule provides us with an advantage over competitors that have designed product candidates with highly differentiated profiles. We believe that the development of CR-001 can directly benefit from clinical results generated with ivonescimab, potentially accelerating timelines and reducing the number of patients in late-stage trials compared to the challenges associated with highly differentiated competitor product candidates.

In ~~addition,~~vitro 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 federal and proposed and enacted state legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drugs. For example, the IRA, among other things (i) directs the U.S. Department of Health and Human Services, or HHS, to negotiate the price of certain high-expenditure, single-source drugs that have been on the market for at least seven years and covered under Medicare, known as the Medicare Drug Price Negotiation Program, and (ii) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation. These provisions began to take effect progressively in fiscal year 2023. In August 2024, HHS announced the agreed-upon prices of the first 10 drugs that were subject to price negotiations, although the Medicare Drug Price Negotiation Program is currently subject to legal challenges. On January 17, 2025, HHS selected fifteen additional drugs covered under Part D for price negotiation in 2025. Each year thereafter more Part B and Part D products will become subject to the Medicare Drug Price Negotiation Program. activity

The ability of VEGF to drive cooperative binding of CR-001 to PD-1 was investigated in cellular assays conducted by Paragon. CR-001 led to the concentration-dependent activation of the nuclear factor of activated T cell, gene by PD-1-expressing cells upon exposure to PD-L1 expressing cells. In the presence of exogenous VEGF, the potency of CR-001, as measured by PD-1/PD-L1 signaling inhibition, was increased by more than 10-fold (p = 0.001 by one-way Analysis of Variance), as reflected in the left graph below. Additionally, binding of CR-001 to PD-1+ cells was enhanced in the presence of exogenous VEGF (not statistically significant due to sample size), as reflected in the right graph below. The activity of CR-001 in this assay closely matched that of ivonescimab.

Further, on December 7, 2023, an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act was announced. On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights. While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework.

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 and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. For example, on January 5, 2024, the FDA approved Florida’s Section 804 Importation Program (SIP) proposal to import certain drugs from Canada for specific state healthcare programs. It is unclear how this program will be implemented, including which drugs will be chosen, and whether it will be subject to legal challenges in the United States or Canada. Other states have also submitted SIP proposals that are pending review by the FDA. Any such approved importation plans, when implemented, may result in lower drug prices for products covered by those programs.

Table of Contents

AsFigure ~~a result of PPACA, Medicare payments are increasingly tied to quality of care and value measures, and reporting of related data by providers such as physicians and hospitals~~6. SoCR-~~called~~001 ~~“value-based~~led reimbursement” measures may present challenges as well as potential opportunities for biopharmaceutical manufacturers. Medicare incentives for providers meeting certain quality measures may ultimately prove beneficial for manufacturers that are able to ~~establish~~cooperative ~~that~~binding ~~their products may help providers~~ to meet such measures. However, manufacturers’ ability to market their drug products based on quality or value is highly regulated and not always permissible. In addition, the potentially decreased Medicare reimbursement to those providers that fail to adequately comply with quality reporting requirements could translate to decreased resources available to purchase products and may negatively impact marketing or utilization of our drug candidates if they are approved for marketing. We cannot predict at this time what impact, if any, the longerPD-~~term~~1 ~~shift towards value-based reimbursement will have on any of our drug candidates~~ in ~~either~~ the ~~Medicare~~presence ~~program,~~of ~~or in any other third party payor programs that may similarly tie payment to provider quality.~~VEGF

A direct measure of CR-001 binding to PD-1 expressed on a Jurkat T cell line showed that the increased sensitivity to T cell activation upon VEGF addition was consistent with higher binding to PD-1. In the presence of VEGF, binding of CR-001 and ivonescimab to PD-1 were both greatly enhanced, directly demonstrating the cooperative binding nature of CR-001 and ivonescimab. CR-001 also showed potent anti-tumor activity in a xenograft mouse model, and was well-tolerated in non-human primates (“NHPs”) after a single intravenous dose with robust PD-1 receptor occupancy. The presence of VEGF creates daisy chains of drug molecules so that multiple drug molecules are bound to each PD-1 molecule, increasing signal amplitude.

~~Additional~~Clinical ~~legislative~~potential ~~proposals~~for to reform healthcare and government insurance programs, along with the trend toward managed healthcare in the United States, could influence the purchase of medicines and reduce reimbursement and/or coverage of our product candidates, if approved.CR-001

Whereas, to date, the superiority of ivonescimab over pembrolizumab has been demonstrated only in treatment-naïve advanced and metastatic NSCLC, clinical experience with checkpoint inhibitors suggests that molecules that enhance checkpoint inhibition, such as ivonescimab and CR-001, may improve antitumor responses in other solid tumors. Ivonescimab has been or is currently being investigated in clinical trials in 16 indications and has been granted marketing approval by the China National Medical Products Administration (“NMPA”) of China for the treatment of EGFR mutated locally advanced or metastatic NSCLC patients who have progressed after EGFR TKI treatment and as monotherapy in first-line treatment of patients with advanced, PD-L1-positive (tumor proportion score ≥1%) NSCLC who do not harbor EGFR or ALK mutations.

~~Exclusivity~~Access to solid tumor indications and ~~Approval~~the lucrative market opportunities they present is a critical objective for our development of ~~Competing~~CR-001. ~~Products~~We intend to prioritize the development of CR-001 in indications for which clinical evidence supports potential efficacy, for which there is an efficient path to market, we believe there are high unmet medical need, and favorable competitive intensity. We believe that there are over 40 indications where CR-001 could be first-in-class outside of China. This may include indications where ivonescimab has demonstrated clinical proof-of-concept for its

Hatch-Waxman Patent Listing

In seeking approval for a drug through an NDA, applicants are required to list with the FDA each patent with claims that cover the applicant’s product or a method of using the product. Upon approval of a drug, each of the patents listed in the application for the drug is then published in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book. Drugs listed in the Orange Book can, in turn, be cited by potential competitors in support of approval of an abbreviated new drug application, or ANDA, or 505(b)(2) NDA. Generally, an ANDA provides for marketing of a drug product that has the same active ingredients in the same strengths, dosage form and route of administration as the listed drug and has been shown to be bioequivalent through in vitro or in vivo testing or otherwise to the listed drug. ANDA applicants are not required to conduct or submit results of preclinical or clinical tests to prove the safety or efficacy of their drug product, other than the requirement for bioequivalence testing. Drugs approved in this way are commonly referred to as “generic equivalents” to the listed drug, and can often be substituted by pharmacists under prescriptions written for the original listed drug. 505(b)(2) NDAs generally are submitted for changes to a previously approved drug product, such as a new dosage form or indication.

The ANDA or 505(b)(2) NDA applicant is required to certify to the FDA concerning any patents listed for the approved product in the FDA’s Orange Book, except for patents covering methods of use for which the ANDA applicant is not seeking approval. Specifically, the applicant must certify with respect to each patent that:

● the required patent information has not been filed;

● the listed patent has expired;

● the listed patent has not expired, but will expire on a particular date and approval is sought after patent expiration; or

● the listed patent is invalid, unenforceable or will not be infringed by the new product.

Generally, the ANDA or 505(b)(2) NDA cannot be approved until all listed patents have expired, except when the ANDA or 505(b)(2) NDA applicant challenges a listed drug. A certification that the proposed product will not infringe the already approved product’s listed patents or that such patents are invalid or unenforceable is called a Paragraph IV certification. If the applicant does not challenge the listed patents or 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 the listed patents claiming the referenced product have expired.

If the ANDA or 505(b)(2) NDA applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to the NDA and patent holders once the application has been accepted for filing by the FDA. The NDA and patent holders may then initiate a patent infringement lawsuit in response to the notice of the Paragraph IV certification. The filing of a patent infringement lawsuit within 45 days after the receipt of

Table of Contents

~~notice~~mechanism of ~~the~~action ~~Paragraph~~and IVmay ~~certification~~also ~~automatically~~include ~~prevents~~indications ~~the~~in ~~FDA~~which ~~from~~ivonescimab ~~approving~~has ~~the~~not ~~ANDA~~been orstudied ~~505(b)(2)~~to ~~NDA~~date. ~~until~~We ~~the~~may ~~earlier~~also ofdevelop 30CR-001 ~~months,~~in ~~expiration~~other ofindications ~~the~~where ~~patent,~~we ~~settlement~~believe ~~of the lawsuit or a decision in the infringement case~~ that isCR-001 ~~favorable~~may tocompete ~~the~~favorably ~~ANDA~~with ~~applicant~~ivonescimab.

Figure 7. PD-1/PD-L1 checkpoint inhibitors and anti-VEGF antibodies have demonstrated antitumor activity across multiple solid tumors, both as a monotherapy and in combination.

~~Hatch-Waxman~~Planned ~~Non-Patent~~clinical ~~Exclusivity~~development of CR-001

~~Market~~We ~~and~~initiated ~~data~~a ~~exclusivity~~global ~~provisions~~Phase ~~under~~1/2 ~~the~~clinical ~~FDCA~~trial ~~also~~of ~~can~~CR-001 ~~delay~~in the ~~submission~~first orquarter ~~the approval~~ of ~~certain~~2026. ~~applications~~The ~~for~~ASCEND ~~competing~~trial ~~products.~~will ~~The~~enroll ~~FDCA~~patients ~~provides~~with aup ~~five-year~~to ~~period~~eight types of ~~non-patent~~solid ~~data~~tumors: ~~exclusivity~~hepatocellular ~~within~~carcinoma. ~~the~~biliary ~~United~~tract ~~States~~cancer, togastric ~~the~~cancer, ~~first~~colorectal ~~applicant~~cancer, toendometrial ~~gain~~carcinoma, ~~approval~~cervical ofcancer, anovarian ~~NDA~~cancer, ~~for~~and aNSCLC. ~~new~~The ~~chemical~~trial ~~entity.~~is Aexpected ~~drug~~to isenroll aup ~~new~~to ~~chemical~~290 ~~entity~~patients ifin ~~the~~dose-escalation, ~~FDA~~backfill ~~has~~and ~~not~~dose-optimization ~~previously~~cohorts ~~approved~~at ~~any~~centers ~~other~~across ~~new~~multiple ~~drug~~regions, ~~containing~~including the ~~same~~United ~~active moiety~~States, ~~which~~Europe isand ~~the~~Asia ~~molecule~~Pacific. orThe ~~ion~~initial ~~responsible~~part ~~for~~of ~~the~~this ~~activity~~trial ofwill ~~the~~follow ~~drug~~a ~~substance.~~traditional ~~During~~dose-escalation ~~the~~design ~~exclusivity~~in ~~period,~~previously ~~the~~treated ~~FDA~~patients. ~~may~~The ~~not~~backfill ~~accept~~portion ~~for~~of ~~review~~the antrial ~~ANDA~~will orexpand aenrollment ~~505(b)(2)~~to ~~NDA~~include ~~submitted~~first-line bypatients. ~~another~~Our ~~company~~dose ~~that~~optimization ~~contains~~cohorts ~~the~~will ~~previously~~be ~~approved~~focused ~~active~~on ~~moiety.~~enrolling ~~However,~~first-line anpatients ~~ANDA~~to orunderstand ~~505(b)(2)~~CR-001’s ~~NDA~~clinical ~~may~~profile bein ~~submitted~~the ~~after~~landscape ~~four~~of ~~years~~other ifbispecifics, itespecially ~~contains~~its aefficacy ~~certification~~and ofsafety ~~patent~~in ~~invalidity~~treatment-naïve ~~or noninfringement~~patients.

The FDCA also provides three years of marketing exclusivity for an NDA, 505(b)(2) NDA or supplement to an existing NDA or 505(b)(2) NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant, are deemed by the FDA to be essential to the approval of the application or supplement. Three-year exclusivity may be awarded for changes to a previously approved drug product, such as new indications, dosages, strengths or dosage forms of an existing drug. This three-year exclusivity covers only the conditions of use associated with the new clinical investigations and, as a general matter, does not prohibit the FDA from approving ANDAs or 505(b)(2) NDAs for generic versions of the original, unmodified drug product. Five-year and three-year exclusivity will not delay the submission or approval of a full NDA; however, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

Orphan Drug Exclusivity

Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biological product intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals in the United States, or more than 200,000 individuals in the United States and for which there is no reasonable expectation that the cost of developing and making a drug or biological product available in the United States for this type of disease or condition will be recovered from sales of the product. Orphan designation must be requested before submitting an NDA or biologics license application. Orphan designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.

If a product that has orphan designation subsequently receives the first FDA approval for such drug for the disease or condition for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications to market the same drug or biological product for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity. Competitors, however, may receive approval of different products for the indication for which the orphan product has exclusivity or obtain approval for the same product but for a different indication for which the orphan product has exclusivity. If a drug or biological product designated as an orphan product receives marketing approval for an indication broader than what is designated, it may not be entitled to orphan product exclusivity. Orphan drug status in the EU has similar, but not identical, benefits.

Pediatric Exclusivity

Pediatric exclusivity is another type of non-patent marketing exclusivity in the United States and, if granted, provides for the attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity, including the non-patent and orphan drug exclusivity periods described above. This six-month exclusivity may be granted if an NDA sponsor submits pediatric data that fairly respond to a written request from the FDA for such data. The data do not need to show the product to be effective in the pediatric population studied; rather, if the clinical trial is deemed to fairly respond to the FDA’s request, the additional protection is granted. If reports of requested pediatric studies are submitted to and accepted by FDA within the statutory time limits, whatever statutory or regulatory periods of exclusivity or Orange Book listed patent protection cover the drug are extended by six months. This is not a

Table of Contents

~~patent~~We ~~term~~believe ~~extension,~~that ~~but~~the itsimilarity ~~effectively~~between ~~extends~~CR-001 ~~the~~and ~~regulatory~~ivonescimab ~~period~~will ~~during~~enable ~~which~~it to apply insights from the ~~FDA~~clinical ~~cannot~~development ~~approve~~of anivonescimab ~~ANDA~~to orthat ~~505(b)(2)~~of ~~application~~CR-001. ~~owing~~Specifically, towe ~~regulatory~~believe ~~exclusivity~~this orprior ~~listed~~experience ~~patents.~~will Ifhelp ~~any~~it to obtain early proof-of-concept ~~our~~data ~~drug~~in ~~candidates~~the isinitial ~~approved,~~Phase we1/2 ~~anticipate~~trial ~~seeking~~as ~~pediatric~~well ~~exclusivity~~as ~~when~~to itaccelerate isits ~~appropriate~~development in later-stage trials.

Figure 8. Outline of the clinical development plan for CR-001. 1Hepatocellular carcinoma. biliary tract cancer, gastric cancer, colorectal cancer, endometrial carcinoma, cervical cancer, ovarian cancer, and NSCLC 2 Dose regimens for backfill cohorts will be determined by emerging data and doses deemed adequately tolerated per the safety review committee. Each dose level may have up to 8 different tumor-specific cohorts that can enroll up to 12 participants each for a maximum of approximately 150 participants in backfill. 3 Dose escalation is conducted according to 3+3 design. 4 Selected dose expansion tumor types may include tumor types from backfill or other solid tumor indications not previously evaluated, Abbreviations: DL = dose level; RP2D = recommended Phase 2 dose

~~Foreign~~We ~~Regulation~~anticipate reporting proof-of-concept clinical data from the ASCEND trial in the first quarter of 2027, including initial safety, pharmacokinetic, pharmacodynamic and early anti-tumor activity from dose escalation and backfill cohorts in first-line and previously treated patients. Because CR-001 incorporates the cooperative pharmacology of ivonescimab, we believe that the data generated in this trial will be highly validating. Along with data we generate, we anticipate data generated by Kelun in clinical trials of CR-001 in Greater China to substantially contribute to our understanding of the clinical potential of CR-001. We believe positive data from early clinical trials using CR-001 will provide us with the opportunity to accelerate its development and efficiently move into registration-enabling studies of monotherapy and in combinations. This has the potential to put us in a strong position in a competitive field.

InThe ~~order~~importance ~~to market any product outside~~ of ~~the~~combination ~~United~~therapies States, we would need to comply with numerous and varying regulatory requirements of other countries regarding safety and efficacy and governing, among other things, clinical trials, marketing authorization, commercial sales and distribution of our drug candidates. For example, in the EU, we must obtain authorization of a clinical trial application, or CTA, in each member state in which we intend to conduct a clinical trial. Whether or not we obtain FDA approval for a drug, we would need to obtain the necessary approvals by the comparable regulatory authorities of foreign countries before we can commence clinical trials or marketing of the drug in those countries. The approval process varies from country to country and can involve additional product testing and additional administrative review periods. The time required to obtain approval in other countries might differ from and be longer than that ~~required~~include toADCs ~~obtain FDA approval. Regulatory approval~~ in ~~one country does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country may negatively impact the regulatory process in others.~~cancer

Cancer treatment often depends on the use of combination therapies. Traditionally, these have been combinations of cytotoxic drugs. However, new treatment modalities are transforming the treatment landscape resulting in combinations of biologics. Drug candidates such as ivonescimab and CR-001 not only have the potential to improve efficacy, but they can also do so with good tolerability. This provides the opportunity to combine these drug candidates with other antitumor drugs. Ivonescimab has already demonstrated in multiple clinical trials that it can be safely dosed in combination with other anticancer drugs to deliver meaningful antitumor activity.

~~Employees~~A promising advancement in cancer therapy is the use of ADCs, which are designed to combine the targeting capabilities of antibodies with the cell-killing power of cytotoxic drugs. By specifically targeting cancer cells and ~~Human~~delivering ~~Capital~~the ~~Resources~~cytotoxic agent directly to them, ADCs can minimize damage to healthy cells and reduce side effects. An emerging therapeutic approach combines the use of ADCs and checkpoint inhibitors. Examples of synergistic activity between these two classes of biologics have been reported in cancers such as NSCLC and urogenital cancers. In December 2023, the FDA approved the combination of enfortumab vedotin, a nectin-4 directed ADC, and pembrolizumab for patients with locally advanced or metastatic urothelial cancer.

InWe ~~July~~intend ~~2024,~~to develop CR-001 in ~~connection~~combination with ~~our~~CR-002 ~~streamlined~~and ~~operating plan~~CR-003, ~~we announced a corporate restructuring that included a reduction in~~ our ~~workforce~~internal byADC 26product ~~employees,~~candidates. orWe ~~approximately~~anticipate ~~80%~~the offirst ~~our~~ADC ~~headcount.~~combination Wetrial ~~substantially~~with ~~completed~~CR-001 ~~the~~to ~~reduction~~begin in the ~~third~~second ~~quarter~~half of ~~2024~~2026.

As of January 31, 2025, we had four full-time employees, all of whom are located in the United States. None of our employees is represented by a labor union or covered by a collective bargaining agreement. We consider our relationship with our employees to be good.

Prior to our corporate restructuring and the ceasing of our drug development activities, our human capital resources objectives included, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and new employees. The principal purposes of our equity incentive plans were to attract, retain and reward high performing employees through the granting of equity-based compensation awards in order to motivate employees to perform to the best of their abilities and achieve our objectives.

Corporate Information

We were incorporated under the laws of the State of Delaware in 2003. Our executive officers and employees work remotely, and our mailing address is P.O. Box 65, Monrovia, Maryland 21770, and our telephone number is (240) 243-1201.

“GlycoMimetics,” the GlycoMimetics logo and other trademarks or service marks of GlycoMimetics, Inc. appearing in this Annual Report are the property of GlycoMimetics, Inc. This Annual Report contains additional trade names, trademarks and service marks of others, which are the property of their respective owners.

Available Information

Our internet website address is www.glycomimetics.com. In addition to the information contained in this Annual Report, information about us can be found on our website. Our website and information included in or linked to our website are not part of this Annual Report.

Our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended, are available free of charge through our website as soon as reasonably practicable after they are electronically filed with or furnished to the Securities and Exchange Commission, or SEC. Additionally the SEC maintains an internet site that contains reports, proxy and information statements and other information. The address of the SEC’s website is www.sec.gov.

Table of Contents

~~ITEM 1A.~~Limitations ~~RISK~~of ~~FACTORS~~current ADCs

~~Our~~ADCs ~~business~~are isanticancer ~~subject~~agents tothat ~~numerous~~selectively ~~risks.~~attack ~~You~~cancer ~~should~~cells ~~carefully~~while ~~consider~~leaving ~~the~~normal ~~following~~cells ~~risks,~~unharmed. asThe ~~well~~ADC asmarket ~~general~~is ~~economic~~rapidly ~~and~~expanding ~~business~~with ~~risks,~~2025 ~~and~~sales ~~all~~ of ~~the~~close ~~other~~to ~~information~~$13 ~~contained~~billion inand ~~this~~a ~~Annual~~projected ~~Report,~~market ~~together~~of ~~with~~over ~~any~~$41 ~~other~~billion ~~documents~~by ~~we file with the SEC~~2035. ~~Any~~There ~~of the following risks could~~ have abeen ~~material~~at ~~adverse~~least ~~effect~~21 onADCs ~~our~~approved ~~business~~worldwide, ~~operating~~including ~~results~~two ~~and~~approved ~~financial~~by ~~condition and cause~~ the ~~trading~~FDA ~~price~~in ~~of our common stock to decline~~2025.

~~Risks~~ADCs ~~Related~~have tothree ~~Our~~components ~~Proposed~~that ~~Merger~~drive ~~with~~their ~~Crescent~~safety and efficacy.

~~Failure~~1.The Antibody. The ability of an ADC to ~~complete,~~target ortumor ~~delays~~cells inis ~~completing,~~dependent on the ~~potential~~identification ~~merger,~~of ~~announced~~an onantibody ~~October~~that ~~29,~~can ~~2024,~~selectively ~~could~~bind ~~materially~~to ~~and~~tumor ~~adversely~~cells. ~~affect~~These ~~our~~antibodies ~~results~~typically bind to antigens that are overexpressed on the surface of ~~operations~~tumor cells compared to normal cells. Examples include HER2 in breast cancer, ~~business~~EGFR in head and neck cancers, ~~financial~~nectin-4 ~~results~~in urothelial cancer and~~/or~~ ~~common~~TROP2 ~~stock~~in ~~price~~various tumors.

On2.The ~~October~~Payload. ~~28,~~The ~~2024,~~cell wekilling ~~entered~~activity ~~into~~of ~~the~~ADCs ~~Merger~~is ~~Agreement,~~driven ~~pursuant~~by toa ~~which,~~cytotoxic ~~among~~molecule ~~other~~that ~~matters,~~is ~~and~~covalently ~~subject~~attached to the ~~satisfaction or waiver of the conditions set forth in the Merger Agreement~~antibody, ~~First~~often ~~Merger~~also ~~Sub~~referred ~~will merge with and into Crescent. Upon consummation of the First Merger, First Merger Sub will cease~~ to ~~exist~~as ~~and~~ the ~~Crescent will become our wholly owned subsidiary~~payload. ~~Immediately~~These ~~following~~molecules ~~the~~are ~~First~~typically ~~Merger~~inhibitors ~~and~~that asblock ~~part~~critical ofcell ~~the~~processes ~~same~~such ~~overall transaction~~ as ~~the~~DNA ~~First~~replication. ~~Merger,~~Coupling ~~Crescent~~them ~~will~~to ~~merge~~antibodies ~~with~~enables ~~and into Second Merger Sub with Second Merger Sub being~~ the ~~surviving~~delivery ~~entity~~ of ~~the~~higher ~~Second~~concentrations ~~Merger. Consummation~~ of ~~the Merger is subject to certain closing conditions, a number of which are not within our control. Any failure to satisfy~~ these ~~required~~toxins ~~conditions~~ to ~~closing~~tumors ~~may~~than ~~prevent,~~can ~~delay~~be orachieved otherwise ~~materially~~as ~~adversely affect~~ the ~~completion~~unconjugated ofcytotoxic ~~the~~molecules ~~transaction.~~are Wetoxic ~~cannot predict with certainty whether or when any of the required closing conditions will be satisfied or if another uncertainty may arise and cannot assure you that we will be able~~ to ~~successfully~~healthy ~~consummate the Merger as currently contemplated under the Merger Agreement or at all~~cells.

3.The Linker. Critical for an ADC to have the desired safety and efficacy is the ability of the payload to remain attached to the antibody until it is delivered to the tumor whereupon it must be released. One of the most effective ways to ensure that the payload is not released prematurely is to use a linker that is cleaved only after the ADC has been localized into the tumor.

~~Our~~Historically, ~~efforts~~ADCs tohad ~~complete~~limited ~~the~~efficacy ~~Merger~~due ~~could~~to ~~cause~~systemic ~~substantial~~toxicities. ~~disruptions~~Recently ~~and~~approved ~~uncertainty,~~ADCs ~~which~~have ~~may~~addressed ~~materially~~some ~~adversely~~of ~~affect~~the ~~our~~limitations ~~results~~ of ~~operations~~early ~~and~~generations ~~business.~~of ~~Uncertainty~~these asdrugs tothrough ~~whether~~improvements ~~the Merger will be completed~~ in aall ~~timely~~three ~~manner~~ADC orcomponents. atMore ~~all~~stable ~~may~~linkers ~~affect~~have ~~our~~led ~~ability~~ to ~~retain~~reduced ~~and~~systemic ~~motivate~~toxicities ~~our~~while ~~remaining~~at ~~employees. Uncertainty as to whether~~ the ~~Merger~~same ~~will~~time bemultivalent ~~completed~~linkers inhave aincreased ~~timely~~the ~~manner~~number orof atpayload ~~all~~molecules ~~could~~that ~~adversely~~can ~~affect~~be ~~our~~delivered ~~relationships~~by ~~with~~a ~~collaborators,~~single ~~suppliers,~~antibody. ~~vendors,~~Antibodies ~~regulators~~that ~~and~~can ~~other~~target ~~business~~a ~~partners.~~wider ~~The~~range ~~adverse effects~~ of ~~the~~tumors ~~pendency~~have ofbeen ~~the~~identified ~~transaction~~and ~~could~~payloads bethat ~~exacerbated~~lead byto ~~any~~more ~~delays~~efficient incell ~~completion~~killing ofhave ~~the~~been ~~transaction~~incorporated orinto ~~termination of the Merger Agreement~~ADCs.

Examples of the impact that switching the cytotoxic payload can have on clinical efficacy include HER2 directed ADCs Enhertu® versus Kadcyla® and TROP2 directed ADCs Dato-DXd versus PF-06664178. ADCs directed at each of these targets have higher overall response rates (“ORR”) when a topoisomerase inhibitor is the cytotoxic payload compared to a microtubule inhibitor payload. Furthermore, ADCs that deliver a topoisomerase inhibitor have been associated with lower rates of peripheral neuropathy (“PN”), an adverse event that can drive dose reductions and discontinuations.

IfFigure ~~the~~9. ~~conditions~~ADCs that have topoisomerase inhibitor payloads have higher efficacy and improve tolerability than those containing microtubule inhibitor payloads. Notes: Caution should be exercised when analyzing cross-trial comparisons due to ~~the~~differences ~~Merger~~in subject characteristics, trial designs and other factors. Abbreviations: GEJ: Gastroesophageal junction. A. Approved. R: In registration . PN rates are ~~not~~weighted ~~satisfied~~averages orby ~~waived~~number of patients across indications / trials and include PN, ~~the~~PSN. ~~Merger~~PMN, ~~may~~and ~~not~~PSMN ~~occur~~when separately measured. Disitamab vedotin is approved in China and is in Phase 3 development globally.

~~Even~~Data ifpresented ~~the~~at ~~Merger is approved by our stockholders, specified conditions must be satisfied or, to~~ the ~~extent~~2025 ~~permitted~~European bySociety ~~applicable~~for ~~law,~~Medical ~~waived~~Oncology to(“ESMO”) ~~complete~~conference ~~the~~showed ~~Merger. We cannot assure you~~ that ~~all~~sacituzumab oftirumotecan ~~the~~(“Sac-TMT”), ~~conditions~~a toTROP2-directed ~~the~~ADC ~~consummation~~with ofa ~~the~~topoisomerase ~~Merger will be satisfied or waived. If the conditions are not satisfied or waived~~payload, ~~the~~significantly ~~Merger~~improved ~~may~~PFS ~~not~~in ~~occur~~patients ~~or the closing may be delayed.~~

The exchange ratio for the Merger will not change or otherwise be adjusted based on the market price of GlycoMimetics common stock.

Applying the exchange ratio based on GlycoMimetics’ capitalization as of September 30, 2024 and Crescent’s capitalization as of October 28, 2024 (the date the Merger Agreement was executed), our current securityholders are expected to own approximately 3% of the aggregate number of shares of the combined company's capital stock following the Merger (on a fully-diluted basis), subject to certain assumptions, including, but not limited to, GlycoMimetics' net cash as of closing being equal to $1.8 million. In the event GlycoMimetics' net cash is below $1.725 million, the exchange ratio will be adjusted such that the number of shares issued to Crescent's pre-closing securityholders will be increased, and our stockholders will own a smaller percentage of the combined company following the consummation of the Merger.

Any changes in the market price of our stock before the completion of the First Merger will not affect the number of shares our stockholders will be entitled to receive pursuant to the Merger Agreement. Therefore, if before the completion of the First Merger, the market price of our common stock increases from the market price on the date of the Merger Agreement, then our stockholders could receive merger consideration with substantially more value for their shares than the parties had negotiated when they established the exchange ratio. Similarly, if before the completion of the First Merger, the market price of our common stock declines from the market price on the date of the Merger Agreement, then our

Table of Contents

~~stockholders~~with ~~could~~EGFR-mutated ~~receive~~NSCLC ~~merger~~compared ~~consideration~~to ~~with~~platinum-based ~~substantially~~standard ~~lower~~of ~~value~~care. ~~The~~To ~~Merger~~the ~~Agreement~~best ~~does~~of ~~not~~our ~~include~~knowledge, this is the first randomized phase 3 study with a ~~price~~TROP2-~~based~~directed ~~termination~~ADC ~~right~~that showed meaningful improvements over standard of care in this population.

Evidence for the potential of combination therapy of an ADC with a topoisomerase payload and an immune checkpoint inhibitor was presented at the 2025 American Society of Clinical Oncology (“ASCO”) conference. Sacituzumab govitecan, a TROP2-directed ADC marketed as Trodelvy by Gilead, plus pembrolizumab resulted in a median PFS of 11.2 months versus 7.8 months when pembrolizumab was given in combination with chemotherapy. These data highlight the potential of topoisomerase ADCs to synergize with checkpoint inhibitors and deliver best-in-class outcomes for patients.

IfFigure ~~the~~10. ~~Merger~~Topoisomerase isADCs ~~not~~led ~~completed,~~to ~~our~~significant ~~stock~~improvements ~~price~~in ~~may~~PFS ~~decline~~compared ~~significantly~~to chemotherapy.

~~The~~In ~~market~~addition ~~price of our common stock is subject~~ to ~~significant~~increasing ~~fluctuations. Market prices for securities of pharmaceutical~~efficacy, ~~biotechnology~~topoisomerase ~~and~~ADCs ~~other~~also ~~life~~reduced ~~science companies have historically been particularly volatile. In addition,~~ the ~~market~~frequency ~~price~~ of ~~our~~TEAEs ~~common stock will likely be volatile based on whether stockholders and other investors believe~~ that weled ~~can~~to ~~complete~~treatment ~~the~~discontinuations ~~Merger~~ or ~~otherwise~~death ~~raise~~compared ~~additional capital~~ to ~~support~~standard ~~our operations if the Merger is not consummated and another strategic transaction cannot be identified, negotiated and consummated in a timely manner, if at all. The volatility~~ of ~~the~~care ~~market price of our common stock has been and may be exacerbated by low trading volume~~chemotherapy. ~~Additional factors that may cause the market price of our common stock to fluctuate include:~~

•Figure ~~announcements~~11. ofTopoisomerase ~~the~~ADCs ~~results~~were ofassociated ~~our~~with ~~clinical~~lower ~~trials,~~frequencies ~~discussions~~of ~~with~~TEAEs ~~regulators,~~leading ~~and~~to ~~regulatory~~discontinuation ~~approvals~~or ~~decisions;~~death

~~• the entry into~~CR-002, ora ~~termination~~PD-L1 ~~of,~~directed ~~key agreements, including commercial partner agreements;~~ADC

•We ~~announcements~~are developing CR-002, a PD-L1-directed ADC with a topoisomerase payload for the treatment of PD-L1 expressing tumors. PD-L1 is a surface protein that is overexpressed by ~~commercial~~over ~~partners~~35 orpercent ~~competitors~~of certain types of ~~new~~cancer, ~~commercial~~such ~~products~~as melanoma, ~~clinical~~hepatocellular ~~progress~~carcinoma, orcolorectal ~~lack~~cancer, ~~thereof~~and NSCLC. Binding of PD-L1 to its receptor, ~~significant~~PD-1, ~~contracts~~on immune T cells leads to suppression of cytotoxic CD8+ T cells, ~~commercial~~preventing ~~relationships~~immune orattack ~~capital~~of ~~commitments;~~the tumor. While inhibitors that interfere with the binding of PD-L1 to PD-1 have resulted in remarkable clinical efficacy across multiple cancer types, their

• the loss of key employees;

• future sales of common stock;

• general and industry-specific economic conditions; and

• period-to-period fluctuations in financial results.

Moreover, the stock markets in general have experienced substantial volatility that has often been unrelated to the operating performance of individual companies. These broad market fluctuations may also adversely affect the trading price of our common stock. In the past, following periods of volatility in the market price of a company’s securities, stockholders have often instituted class action securities litigation against such companies.

Even if we complete the Merger, the combined company will need to raise additional capital by issuing equity securities or additional debt or through licensing arrangements, which may cause significant dilution to the combined company’s stockholders or restrict the combined company’s operations.

On October 28, 2024, we entered into the Private Placement with certain investors pursuant to which the investors agreed to purchase, in the aggregate, $200.0 million in shares of our common stock and pre-funded warrants immediately following the closing of the Merger. The closing of the Private Placement is conditioned upon the satisfaction or waiver of the conditions to the closing of the Merger as well as certain other conditions. Our shares of common stock and pre-funded warrants to be issued in the Private Placement will result in dilution to all securityholders of the combined company.

Additional financing may not be available to the combined company when it is needed or may not be available on favorable terms. To the extent that the combined company raises additional capital by issuing equity securities, such financing will cause additional dilution to all securityholders of the combined company. It is also possible that the terms of any new equity securities may have preferences over the combined company’s common stock. Any debt financing the combined company enters into may involve covenants that restrict its operations. These restrictive covenants may include limitations on additional borrowing and specific restrictions on the use of the combined company’s assets, as well as prohibitions on its ability to create liens, pay dividends, redeem its stock or make investments. In addition, if the combined company raises additional funds through licensing arrangements, it may be necessary to grant licenses on terms that are not favorable to the combined company.

Some of our directors and executive officers have interests in the Merger that are different from yours and that may influence them to support or approve the Merger without regard to your interests.

Our directors and executive officers may have interests in the Merger that are different from, or in addition to, the interests of our other stockholders generally. These interests with respect to our directors and executive officers may

Table of Contents

~~include~~efficacy, ~~among~~even ~~others,~~in ~~retention~~tumors ~~bonus~~with ~~payments~~high immunogenicity, ~~extension~~is oflimited ~~exercisability~~to ~~periods~~approximately of20 ~~previously~~percent ~~issued~~to ~~stock~~30 ~~option~~percent ~~grants,~~of ~~severance~~patients. ~~payments~~Rather ifthan ~~employment~~inhibiting isthe ~~terminated~~interaction inof aPD-L1 ~~qualifying termination in connection~~ with ~~the~~PD-1, ~~Merger~~CR-002 ~~and~~is ~~rights~~designed to ~~continued~~directly ~~indemnification,~~kill ~~expense~~tumor ~~advancement~~cells ~~and~~that ~~insurance~~express ~~coverage~~PD-L1.

CR-002 builds on clinical validation from PD-L1 directed ADC molecules from Henlius and Pfizer while differentiating via choice of antibody, linker, payload, and ability to combine with other therapies.

~~Our~~Figure board of directors was aware of and considered those interests, among other matters, in reaching their decisions to approve and adopt the Merger Agreement, approve the Merger, and recommend the approval of the Merger Agreement to our stockholders12. ~~These~~Design ~~interests, among other factors, may have influenced the directors and executive officers~~ of ~~each company to support or approve the Merger.~~CR-002

CR-002 was designed with a DXd topoisomerase inhibitor as the payload which we believe will impart high antitumor activity while minimizing the frequency of serious TEAEs. By contrast, SGN-PDL1V, a PD-L1 directed ADC in development by Pfizer, has a microtubule inhibitor as its payload.

~~Certain~~The ~~provisions~~linker ofused to attach the ~~Merger~~payload ~~Agreement~~to ~~may~~the ~~discourage~~antibody ~~third~~in ~~parties~~CR-002 ~~from~~is ~~submitting~~a ~~competing~~peptide ~~proposals,~~referred ~~including~~to ~~proposals~~as ~~that~~GGFG ~~may~~which bewas ~~superior~~selected tobased on its stability in circulation. Release of the ~~transactions~~payload ~~contemplated~~from byADCs created using this linker requires internalization of the ~~Merger~~ADC ~~Agreement~~into lysosomes. This linker was also used to create Enhertu, a HER2 directed ADC approved in over 70 countries.

~~While~~CR-002 ~~the~~was ~~Merger~~created ~~Agreement~~using isa inproprietary ~~effect,~~anti-PD-L1 each party is generally prohibited from, among other things, soliciting, initiating or knowingly encouraging, inducing or facilitating the communication, making, submission or announcement of any acquisition proposal or acquisition inquiryantibody. InThis ~~addition,~~antibody ~~our~~was ~~current~~specifically ~~directors~~selected ~~and~~based ~~executive~~on ~~officers~~its ~~have~~superior ~~entered~~ability ~~into support agreements pursuant~~ to ~~the~~be ~~terms~~internalized. ofCR-002 ~~the~~was ~~Merger~~more ~~Agreement,~~potent ~~and~~in as an ~~inducement to GlycoMimetics willingness to enter into the Merger Agreement, by which they have agreed to vote all of their shares of our capital stock~~ in ~~favor~~vitro ofcytotoxicity ~~the~~assay Merger Agreement and the transactions contemplated thereby and against any competing proposals, subject to certain limited exceptions. These provisions could discourage a potential competing acquirer from considering or proposing an acquisition or merger, even if it were prepared to pay consideration with a higher value than ~~that~~ADCs ~~implied~~containing by the ~~merger consideration in the combination.~~

Our stockholders will experience significant dilution as a consequence of the Merger and related transactions.

The ownership of current stockholders of our company is expected to decrease from 100% of our common stock to approximately 3% of the combined company following the Merger and related private placement financing. This reduced ownership interest in the combined company will significantly reduce the influence that our current stockholders will have on the management of the combined company.

If the combined company is unable to realize the full strategic and financial benefits currently anticipated from the Merger, our stockholders will have experienced substantial dilution of their ownership interests without receiving any commensurate benefit, or only receiving part of the commensurate benefit to the extent the combined company is able to realize only part of the strategic and financial benefits currently anticipated from the Merger.

We may fail to realize all of the anticipated benefits of the Merger and may be exposed to other operational and financial risks.

The consummation of our proposed Merger with Crescent will require significant time on the part of the Company, and the diversion of the Company’s attention may disrupt our business.

Our ability to realize the anticipated benefits of the Merger are highly uncertain. Any anticipated benefits will depend on a number of factors, including our ability to integrate our business with that of Crescent and our ability to generate future value for the stockholders of the combined company. The expected benefits may not be achieved within the anticipated time frame, or at all.

The consummation of the Merger may also require more time or greater cash resources than we anticipate and expose us to other operational and financial risks, including:

● increased near-term and long-term expenditures;

● exposure to unknown liabilities;

● higher than expected acquisition or integration costs;

● incurrence of substantial debt or dilutive issuances of equity securities to fund future operations;

● write-downs of assets or goodwill or incurrence of non-recurring, impairment or other charges;

Table of Contents

●same ~~increased~~DXd ~~amortization~~payload ~~expenses;~~created from other anti-PD-L1 antibodies. A non-intuitive finding was that cytotoxicity was inversely correlated with PD-L1 binding potency.

●Figure ~~difficulty~~13. ~~and~~CR-003 ~~cost~~demonstrated inmore ~~combining~~potent ~~Crescent’s~~cell ~~operations~~toxicity than DXd ADCs created using antibodies with ~~ours;~~higher affinities for PD-L1

●A ~~impairment~~single dose of ~~relationships~~CR-002 ~~with~~at ~~key~~1 ~~suppliers~~mg/kg orled ~~customers~~to ~~due~~complete toresponses ~~changes~~in eight of eight mice evaluated in ~~management~~a ~~and~~Karpas-299 ~~ownership;~~Non-Hodgkins Leukemia (“NHL”) model. CR-002 performed favorably in this model compared with benchmark antibodies incorporated into ADCs with identical DXd payloads.

●Figure ~~inability~~14. toCR-002 ~~retain~~performed ~~employees;~~favorably versus opoucolimab-DXd (antibody in Henlius' PD-L 1 ADC HLX43), SG-559-01-DXd (antibody in Pfizer's PD-L 1 ADC SGN-PDL 1V), and BMS-936559-DXd (PD-L1 antibody)

●Clinical ~~possibility~~development ofplans ~~future~~for ~~litigation.~~CR-002

We plan to submit an Investigational New Drug application (“IND”) to the FDA for CD-002 in mid-2026 and initiate a Phase 1/2 trial in the second half of 2026.

If we are unable to consummate the Merger with Crescent, our board of directors may decide to pursue a dissolution and liquidation. In such an event, the amount of cash available for distribution to our stockholders will depend heavily on the timing of such liquidation as well as the amount of cash that will need to be reserved for commitments and contingent liabilities.

There can be no assurance that we will be able to complete the proposed Merger with Crescent. If the Merger is not completed, our board of directors may decide to pursue a dissolution and liquidation. In such an event, the amount of cash available for distribution to our stockholders will depend heavily on the timing of such decision and, with the passage of time the amount of cash available for distribution will be reduced as we continue to fund our operations. In addition, if our board of directors were to approve and recommend, and our stockholders were to approve, a dissolution and liquidation, we would be required under Delaware corporate law to pay our outstanding obligations, as well as to make reasonable provision for contingent and unknown obligations, prior to making any distributions in liquidation to our stockholders.

As a result of this requirement, a portion of our assets may need to be reserved pending the resolution of such obligations and the timing of any such resolution is uncertain. In addition, we may be subject to litigation or other claims related to a dissolution and liquidation. If a dissolution and liquidation were pursued, our board of directors, in consultation with our advisors, would need to evaluate these matters and make a determination about a reasonable amount to reserve. Accordingly, holders of our common stock could lose all or a significant portion of their investment in the event of a liquidation, dissolution or winding up. A liquidation would be a lengthy and uncertain process with no assurance of any value ever being returned to our stockholders.

We may become involved in litigation, including securities class action litigation, that could divert management’s attention and harm our business, and insurance coverage may not be sufficient to cover all costs and damages.

In the past, litigation, including securities class action litigation, has often followed certain significant business transactions, such as the sale of a company or announcement of any other strategic transaction, or the announcement of negative events, such as negative results from clinical trials. These events may also result in investigations by the SEC. We may be exposed to such litigation, even if no wrongdoing occurred. Litigation is usually expensive, uncertain, and diverts management’s attention and resources, which could adversely affect our business and cash resources and our ability to consummate the Merger with Crescent.

If we fail to comply or regain compliance with Nasdaq’s continued listing standards prior to the consummation of the Merger, our common stock may be delisted and the price of our common stock, our ability to consummate the Merger, our access the capital markets and our financial condition could be negatively impacted.

Our common stock was previously listed on the Nasdaq Global Market, and we were required to meet certain listing requirements, including with respect to minimum closing bid prices, market value of publicly held shares, stockholders’ equity and market value of listed securities.

In June 2024, we received notice from the Listing Qualifications Department of The Nasdaq Stock Market, or Nasdaq, that we were not in compliance with the minimum bid price requirement for continued listing on the Nasdaq Global Market. Pursuant to Nasdaq listing rules, we were provided an initial compliance period until December 18, 2024 to regain compliance. In order to qualify for additional time to regain compliance, we transferred the listing of our common stock from the Nasdaq Global Market to the Nasdaq Capital Market, which became effective as of December 20, 2024. In connection with that transfer, on December 19, 2024, we received notice from Nasdaq that we had been

Table of Contents

~~granted~~CR-003, an ~~additional~~ITGB6 ~~180~~directed ~~calendar days, or until June 16, 2025, to regain compliance with the minimum closing bid price requirement for continued listing on The Nasdaq Capital Market under Nasdaq Listing Rule 5550(a)(2).~~ ADC

CR-003, also known as SKB105, is an ADC that is designed to deliver a topoisomerase inhibitor payload to tumors expressing ITGB6. We have obtained an exclusive license outside of Greater China to develop CR-003. In January 2026, Kelun received IND approval to initiate a Phase 1/2 trial for SKB105 from the Center for Drug Evaluation of the National Medical Products Administration of China with initial data expected in the first quarter of 2027, followed quickly by the initiation of a CR-001 and CR-003 combination trial in early 2027 with first data expected by year-end 2027.

IfITGB6 ~~necessary~~is toan ~~regain~~attractive ~~compliance~~target ~~with~~for Nasdaq listing standards, we may, subject to approval of our board of directors and stockholders, implement a reverse stock split. However, there can be no assurance that a reverse stock split, or any other alternatives we may consider to regain compliance with the minimum bid price requirement, would be approved or would result in a sustained higher stock price that would allow us to meet the Nasdaq stock price listing requirements. In addition, pursuant to the terms of the Merger Agreement we are required to use commercially reasonable efforts to maintain our listing on Nasdaq until the effective time of the First Merger.ADCs

ITGB6 is a member of the integrin family of integral membrane proteins that anchor cells and respond to the extracellular matrix. Integrins mediate cell-to-cell and cell-to-matrix communication. ITGB6, which encodes a component of the adhesion receptor alpha-v/beta-6, is overexpressed in numerous solid tumors. ITGB6 is highly expressed in a broad range of tumors including lung, head and neck, pancreatic, breast and cervical cancers, among others. Expression of ITGB6 is a negative prognostic indicator associated with reduced survival in multiple tumors. ITGB6 expression can also promote metastasis through stimulation of epithelial to mesenchymal transition. ITGB6 expressed at low levels in healthy epithelial cells compared to high expression in numerous solid tumors, which makes it an attractive ADC target.

~~Separately,~~Our ~~Nasdaq listing rules requires companies listed on the Nasdaq Capital Market to maintain a stockholders’ equity of at least $2.5 million. As of December 31~~solution, 2024, we had stockholders’ equity of $5.3 million. As a result of our expected decrease in stockholders’ equity prior to the Merger due to continued net losses, there can be no assurance that we will be able to maintain the minimum required stockholders’ equity under the Nasdaq continued listing standards.CR-003

CR-003 was created by Kelun using a proprietary Fc silenced fully human antibody to a specific epitope on ITGB6. A topoisomerase inhibitor payload is coupled to the antibody using a clinically validated peptide linker. CR-003 has been shown to be well-tolerated in NHPs.

~~Risks~~Figure ~~Related~~15. toStructural ~~Our~~model ~~Financial~~of ~~Position and Capital Needs~~ CR-003

WePreclinical ~~have~~studies ~~incurred~~showed ~~significant~~that ~~losses~~the ~~since~~CR-003 ~~our~~antibody ~~inception.~~demonstrated Wesuperior ~~expect~~cell tointernalization ~~continue~~in low antigen density cancer cell lines compared to ~~incur~~the ~~losses~~anti-ITGB6 ~~and~~antibody ~~may~~utilized ~~never~~in ~~achieve~~the orSeagen ~~maintain~~ADC ~~profitability~~SGN-B6A. SGN-B6A is now in

We have incurred significant losses since our inception and, as of December 31, 2024, we had an accumulated deficit of $494.4 million. In recent years, we have financed our operations primarily with proceeds from public offerings of our common stock.

We have devoted substantially all of our financial resources and efforts to research and development, including preclinical studies and clinical trials. However, we have not completed development of any drugs, and in July 2024, following the announcement of the data from our Phase 3 pivotal trial and our discussions with the FDA, we announced that we would initiate a review of strategic alternatives focused on maximizing stockholder value. We also reduced our workforce by approximately 80% in order to conserve our cash resources as part of a streamlined operating plan while we undertook our strategic review. Following the strategic review, we entered into an acquisition agreement with Crescent to consummate the proposed Merger.

In connection with the termination of our clinical programs, our research and development expenses have decreased. We expect to continue to incur costs and expenditures in connection with the merger process. Based on our current operating plan, which includes the ceasing of our clinical development programs, we expect that our current cash and cash equivalents will fund our operations until the closing of the Merger; however, we have based this estimate on assumptions that may prove to be wrong, and we could use our capital resources sooner than we expect. There can be no assurance that the proposed Merger with Crescent, or any other course of action, business arrangement or transaction, or series of transactions, will be pursued, successfully consummated or lead to increased stockholder value. If we are unable to close the Merger or raise additional capital, we will need to eliminate some or all of our operations or liquidate our company.

We expect to continue to incur significant expenses in connection with our ongoing activities, including continuing to operate as a public company. If we were to resume clinical development activities in the future, we would expect to incur significant additional expenses and operating losses.

To become and remain profitable, we must succeed in developing and eventually commercializing drugs that generate significant revenue. This would require us to be successful in a range of challenging activities, including completing preclinical testing and clinical trials of our drug candidates, obtaining regulatory approval for these drug candidates and manufacturing and commercializing any drugs for which we may obtain regulatory approval, as well as discovering additional drug candidates. If we were to resume our development programs, we may never succeed in these activities and, even if we did, we may never generate revenue that is significant enough to achieve profitability.

Table of Contents

~~Even~~development ifas wesigvotatug ~~achieve~~vedotin ~~profitability,~~by ~~we may not be able to sustain or increase profitability on a quarterly or annual basis~~Pfizer. ~~Our~~Compared ~~failure~~ to ~~become~~SGN-B6A, ~~and~~the ~~remain~~enhanced ~~profitable~~internalization ~~would~~by ~~depress~~ the ~~value~~CR-003 ofantibody ~~our~~may ~~company~~potentially ~~and~~enhance ~~could~~cell-killing ~~impair~~activity ~~our~~of ~~ability~~cells toexpressing ~~raise~~lower ~~capital,~~levels ~~expand our business, maintain our research and development efforts or even continue our operations. A decline in the value~~ of ~~our company could also result in significant harm to our financial position and adversely affect our stock price~~ITGB6.

Figure 16. The antibody used to create CR-003 was more rapidly internalized in cells expressing low levels of ITGB6 than the SGN-B6A antibody

IfCR-003 weled ~~decide~~ to ~~resume~~potent ~~development~~in ofvivo ~~our~~antitumor ~~drug~~activity ~~candidates,~~in wetwo ~~would~~cell-line ~~need~~derived ~~substantial~~(“CDX”) ~~additional~~tumor ~~funding~~models. IfIn weboth ~~were~~the ~~unable~~NCIH358 toNSCLC ~~raise~~model ~~that~~and ~~capital~~the ~~when~~CFPAC-1 ~~needed~~pancreatic model, wea ~~may~~single ~~not~~dose beof ~~able~~CR-003 led to ~~continue~~tumor asshrinkage. aBy ~~going~~contrast, ~~concern~~treatment ~~and~~with ~~could~~SGN-B6A beled ~~forced~~at best to a delay, ~~reduce~~in ortumor ~~eliminate drug development programs or potential commercialization efforts~~growth.

IfFigure we17. ~~were~~CR-003 todemonstrated ~~resume~~superior ~~development~~antitumor ofresponses ~~drug~~in ~~candidates,~~multiple ~~our~~CDX ~~capital~~models ~~requirements~~compared ~~would~~to ~~depend on many factors, including:~~SGN-B6a

●Additionally, CR-003 demonstrated a superior PK profile versus SGN-B6A. The superimposable PK profiles of the ~~scope,~~CR-003 ~~progress,~~ADC ~~results~~and total antibody curves demonstrate high stability in circulation and ~~costs~~suggest that there are low levels of ~~preclinical~~free ~~development~~payload in circulation, ~~laboratory~~creating ~~testing~~an opportunity for a differentiated safety profile. As expected based on its linker and payload, the SGN-B6A PK profile demonstrates instability in circulation indicative of payload release. The higher exposure of CR-003 as measured by the area under the curve (“AUC”) creates an opportunity for enhanced efficacy, which could be a compelling advantage in the clinical ~~trials;~~setting.

● the number and development requirements of other drug candidates that we may pursue;

● the costs, timing and outcome of regulatory review of our drug candidates;

● the costs and timing of future commercialization activities, including product manufacturing, marketing, sales and distribution, for any of our drug candidates for which we receive marketing approval;

● the revenue, if any, received from commercial sales of our drug candidates for which we receive marketing approval;

● the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims; and

● the extent to which we acquire or in-license other drug candidates and technologies.

Identifying potential drug candidates and conducting preclinical testing and clinical trials is a time-consuming, expensive and uncertain process that takes years to complete, and we or any current or future collaborators may never generate the necessary data or results required to obtain regulatory approval and achieve product sales. In addition, drug candidates, if approved, may not achieve commercial success. Accordingly, if we were to resume development activities, our ability to fund our operations would be dependent upon management’s plans, which could include raising additional capital through a combination of equity and debt financings, collaborations and strategic alliances. However, there can be no assurances that new financings or other transactions will be available to us on commercially acceptable terms, or at all. Our ability to raise additional capital could also be adversely impacted by global economic conditions and disruptions to and volatility in the credit and financial markets in the United States and worldwide. If we are unable to raise capital to fund our operations when needed or on attractive terms, we could be forced to delay, reduce the scope of or eliminate our research and development programs or any future commercialization efforts.

Raising additional capital may cause dilution to our stockholders, restrict our operations or require us to relinquish rights to our drug candidates.

If we were to resume our development activities, we would expect to finance our cash needs through a combination of equity offerings, debt financings and license and development agreements until such time, if ever, as we could generate substantial commercial revenues. To the extent that we raise additional capital through the sale of equity or convertible debt securities, your ownership interest would be diluted, and the terms of these securities may include liquidation or other preferences that could adversely affect your rights as a common stockholder. Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends.

If we were to raise additional funds through collaborations, strategic alliances or marketing, distribution or licensing arrangements with third parties, we may be required to relinquish valuable rights to our research programs or drug candidates or grant licenses on terms that may not be favorable to us or that may be at less than the full potential value of such rights. If we are unable to raise additional funds through equity or debt financings or other arrangements with third parties when needed, we may be required to delay, limit, reduce or terminate our drug development or future

Table of Contents

~~commercialization~~Figure ~~efforts~~18. orCR-003 ~~grant~~had ~~rights~~enhanced tostability ~~third parties to develop~~ and ~~market~~superior ~~drug~~half-life ~~candidates~~compared ~~that we would otherwise prefer~~ to ~~develop~~SGN-B6A ~~and~~in ~~market ourselves.~~mice

Clinical development plans for CR-003

~~Risks~~Our ~~Related~~partnership with Kelun was designed to ~~the~~accelerate ~~Discovery~~clinical development of both CR-001 and ~~Development~~CR-003. ofKelun ~~Our~~received IND approval to initiate a Phase 1/2 trial for SKB105 from the Center for Drug ~~Candidates~~Evaluation of the National Medical Products Administration of China with initial data expected in the first quarter of 2027, followed quickly by the initiation of a CR-001 and CR-003 combination trial in early 2027 with first data expected by year-end 2027.

~~Should~~Clinical weand ~~resume~~market ~~development~~potential of our ~~drug~~product candidates~~, our focus on discovering and developing novel glycomimetic drugs and our approach to discovering and developing drugs may never lead to marketable drugs.~~

AOur ~~key~~vision ~~element~~is ~~of our prior development strategy was~~ to ~~use~~transform ~~and~~cancer ~~expand~~treatment ~~our~~by ~~platform~~advancing ~~to build~~ a ~~pipeline~~portfolio of ~~novel~~best-in-class ~~glycomimetic~~ drug candidates ~~and progress these drug candidates~~ through clinical development ~~for the treatment of a variety of diseases~~. ~~The~~To ~~discovery~~this ~~of therapeutic drugs based on molecules that mimic the structure of carbohydrates is an emerging field~~end, ~~and~~we ~~the scientific discoveries that form the basis for our past efforts to discover and develop drug candidates~~ are ~~relatively~~actively ~~new.~~evaluating ~~The scientific evidence to support the feasibility of developing drug~~ candidates ~~based on these discoveries is both preliminary and limited. Although our research and development efforts resulted~~ in ~~a pipeline of glycomimetic drug candidates, we were unable to successfully progress those drug candidates through clinical trials. If we were to resume~~ our ~~development~~CR-004 ~~activities,~~program ~~the drug candidates that we identify may not be suitable for clinical development, including as a result of being shown~~ to ~~have~~further ~~harmful~~expand side effects or other characteristics that indicate that they are unlikely to be drugs that will receive marketing approval and achieve market acceptance. If we do not successfully develop and commercialize drug candidates based upon our ~~glycomimetics platform, we will not be able to obtain product revenue in future periods~~pipeline.

We anticipate the initiation of four clinical trials of our product candidates in 2026 including the first trial of CR-001 in combination with an ADC.

IfFigure we19. ~~were~~Multiple ~~to resume development activities, we would need to conduct additional~~ clinical ~~trials.~~trial ~~All~~initiations ~~of our other drug candidates other than uproleselan were~~ in ~~earlier~~2026 ~~stages~~and ofdata ~~clinical~~readouts ~~trials or~~ in ~~preclinical~~2027 ~~development.~~are anticipated

Uproleselan is our only drug candidate that was recently in a Phase 2 or Phase 3 clinical trial. In the second quarter of 2024, we announced results of our pivotal Phase 3 clinical trial of uproleselan in R/R AML. The study of uproleselan combined with chemotherapy did not meet its primary endpoint of overall survival in the intent to treat population. Following the announcement of the data from the Phase 3 trial, we requested and held a meeting with the FDA to discuss whether any of the results summarized above could serve as a basis for a submission for regulatory approval. Based on the feedback received, we concluded that any potential regulatory path for uproleselan in this patient population would require an additional clinical trial, the conduct of which would require capital resources beyond those available to us.

Our other drug candidates were in earlier stages of clinical trials or in preclinical development. We have not completed the development of any drug candidates, we currently generate no revenue from the sale of any drugs, and even if we were to resume our development activities, we may never be able to develop a marketable drug. As a company, we have no experience in submitting and obtaining FDA approval for an NDA. We previously invested substantially all of our efforts and financial resources in the development of our glycomimetics platform, the identification of potential drug candidates using that platform and the development of our drug candidates. If we were to resume development, our ability to generate revenue from our other drug candidates, would depend heavily on their successful development and eventual commercialization. The success of those drug candidates would depend on several factors, including:

● successful completion of preclinical studies and clinical trials;

● receipt of marketing approvals from applicable regulatory authorities;

● obtaining and maintaining patent and trade secret protection and regulatory exclusivity for our drug candidates;

● making arrangements with third-party manufacturers for, or establishing, commercial manufacturing capabilities;

● launching commercial sales of the drugs, if and when approved, whether alone or in collaboration with others;

● acceptance of the drugs, if and when approved, by patients, the medical community and third-party payors;

● effectively competing with other therapies;

● obtaining and maintaining healthcare coverage and adequate reimbursement;

Table of Contents

●Our ~~protecting~~candidates were chosen based on their potential to each treat a broad spectrum of tumors, both as monotherapies and in combinations. We intend to continue to expand our ~~rights~~pipeline with promising product candidates that have the potential to work in synergy with our ~~intellectual~~existing ~~property~~candidates ~~portfolio;~~as ~~and~~well as to address areas in which there is high unmet need.

●Figure ~~maintaining~~20. aOur ~~continued~~product ~~acceptable~~candidates ~~safety~~are ~~profile~~positioned to address $B market opportunities in a broad range of ~~the~~tumors ~~drugs~~with ~~following~~high ~~approval.~~unmet need

Paragon Collaboration

~~Clinical~~Pre-Merger Crescent was launched to research and develop antibody and ADC candidates licensed from Paragon, an antibody discovery engine founded by Fairmount Funds Management LLC (“Fairmount”), and led by industry veterans with extensive experience in drug ~~development~~discovery. ~~involves~~Pre-Merger aCrescent ~~lengthy~~entered into the Antibody Discovery and ~~expensive~~Option ~~process~~Agreement, dated September 19, 2024 (the “Antibody Paragon Option Agreement”), and the Amended and Restated ADC Discovery and Option Agreement, dated April 28, 2025 (the “ADC Paragon Option Agreement” and together with the Antibody Paragon Option Agreement, the “Paragon Option Agreements”), each by and among Pre-Merger Crescent, Paragon Therapeutics, Inc. (“Paragon”) and Parascent Holding LLC (“Parascent”), pursuant to which Paragon agreed to perform certain research activities to discover, generate, identify, and characterize antibody or ADC candidates, as applicable, directed to the selected targets PD-1 and VEGF for CR-001, an ~~uncertain~~undisclosed ~~outcome~~target for CR-002, and three undisclosed targets for the product candidate formerly referred to as CR-003 (“Former CR-003”). ~~Should~~On February 24, 2026, we ~~resume~~provided ~~development~~notice to Paragon of our ~~drug~~intention ~~candidates,~~to terminate the ADC Paragon Option Agreement and we ~~may~~expect ~~incur~~that ~~additional~~the ~~costs~~agreement orwill ~~experience~~terminate ~~delays~~on inor ~~completing~~about March 26, or2026 ~~ultimately~~(the be“Option ~~unable~~Agreement Termination”). Pursuant to ~~complete~~the Paragon Option Agreements, we have licensed intellectual property rights with respect to CR-001 and CR-002 and have held an option to acquire intellectual property rights with respect to Former CR-003 from Paragon. Following the exercise of the options under the Paragon Option Agreements and execution of the respective license agreements, we have exclusive worldwide development and commercialization ofrights to our ~~drug~~programs. ~~candidates~~Pre-Merger Crescent exercised the option with respect to CR-001 in March 2025 and entered into the related license agreement in April 2025 pursuant to the Antibody Paragon Option Agreement. We exercised the option with respect to CR-002 in September 2025 and entered into the related license agreement in November 2025 pursuant to the ADC Paragon Option Agreement. We will no longer license intellectual property rights with respect to CR-003 following the Option Agreement Termination. See the sections titled “—CR-001 License Agreement” and “—CR-002 License Agreement” below. Our option to acquire the intellectual property rights to Former CR-003 under the ADC Paragon Option Agreement will terminate in connection with the Option Agreement Termination and we will no longer seek to license intellectual property rights with respect to Former CR-003.

~~The~~Paragon ~~risk~~Option ofAgreements failure of our drug candidates is high. It is impossible to predict when or if any of our drug candidates will prove safe or effective in humans or will receive regulatory approval. Before obtaining marketing approval from regulatory authorities for the sale of any drug candidate, we or a collaborator must complete preclinical development and then conduct extensive clinical trials to demonstrate the safety and efficacy of the drug candidate in humans. Clinical testing is expensive, difficult to design and implement, can take many years to complete and is uncertain as to outcome. For example, in May 2024, we announced results of our pivotal Phase 3 clinical trial of uproleselan in R/R AML. Even though we observed favorable results in earlier trials of uproleselan, uproleselan combined with chemotherapy did not meet the primary endpoint of overall survival in the intent to treat population in our Phase 3 trial. A failure of one or more clinical trials can occur at any stage of development. The outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final results. In addition, changes in patient treatment options over time may make the relevance of historical control data for a given indication less relevant to the drug candidate being studied, which could impact the success of the trial or, even if successful, the desirability of a successful drug candidate versus other available treatment options. Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their drug candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain marketing approval of their drugs.

We are party to the Paragon Option Agreements with Paragon and Parascent. At the time of entry into the Paragon Option Agreements, Paragon and Parascent each beneficially owned more than 5% of a class of Pre-Merger Crescent’s voting securities through their respective holdings of Pre-Merger Crescent common stock, although neither own more than 5% of our common stock currently. Fairmount beneficially owns more than 5% of a class of our voting securities, two of

If we were to resume development activities, we or our current or future collaborators may experience numerous unforeseen events during, or as a result of, clinical trials that could delay or prevent our or their ability to receive marketing approval or commercialize our drug candidates, including:

● regulators or institutional review boards may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site;

● we may experience delays in reaching, or fail to reach, agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites;

● clinical trials of our drug candidates may produce negative or inconclusive results, including failure to demonstrate statistical significance, and we may decide, or regulators may require us, to conduct additional clinical trials or abandon drug development programs as we have done with respect to uproleselan following the Phase 3 pivotal clinical trial;

● the number of patients required for clinical trials of our drug 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 meet their contractual obligations to us in a timely manner, or at all;

● regulators or institutional review boards 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 drug candidates may be greater than we anticipate;

● the supply or quality of our drug candidates or other materials necessary to conduct clinical trials of our drug candidates may be insufficient or inadequate; and

● our drug candidates may have undesirable side effects or other unexpected characteristics, causing us or our investigators, regulators or institutional review boards to suspend or terminate the trials.

Table of Contents

~~Our~~our ~~drug~~directors ~~development~~are ~~costs~~or ~~would~~were ~~also~~recently ~~increase~~affiliated ifwith weFairmount ~~experience~~(Peter ~~delays~~Harwin inand ~~testing~~Jonathan orViolin) ~~marketing~~and ~~approvals.~~Fairmount ~~Preclinical~~beneficially ~~studies~~owns ormore ~~clinical~~than ~~trials~~5% ~~may~~of ~~not~~Paragon. ~~begin~~Fairmount asappointed ~~planned,~~Paragon’s ~~could~~board ~~need~~of todirectors beand ~~restructured~~has orthe ~~may~~contractual ~~not~~right beto ~~completed~~approve onthe ~~schedule,~~appointment orof atany ~~all.~~executive ~~Significant~~officers ~~preclinical~~of ~~study~~Paragon. orParascent ~~clinical~~is ~~trial~~an ~~delays~~entity ~~also~~formed ~~could~~by ~~shorten~~Paragon ~~any~~as ~~periods~~a ~~during~~vehicle ~~which~~to wehold ~~may~~equity ~~have~~in ~~the~~Crescent ~~exclusive~~in ~~right~~order to ~~commercialize~~share ~~our~~profits ~~drug~~with ~~candidates~~certain oremployees ~~allow~~of ~~our~~Paragon ~~competitors~~and towill ~~bring~~not ~~drugs~~perform toany ~~market~~substantive ~~before~~role weunder ~~do,~~the ~~and~~Paragon ~~thereby~~Option ~~impair~~Agreements ~~our~~other ~~ability~~than to ~~successfully~~receive ~~commercialize~~warrants ~~our~~granted ~~drug~~to ~~candidates~~Parascent under the Paragon Option Agreements.

On September 19, 2024, Pre-Merger Crescent entered into the Antibody Paragon Option Agreement with Paragon and Parascent. On October 28, 2024, Pre-Merger Crescent entered into the ADC Paragon Option Agreement with Paragon and Parascent, which was subsequently amended and restated on April 28, 2025. Under the terms of the Paragon Option Agreements, Paragon agreed to perform certain research activities to discover, generate, identify, and characterize one or more antibody candidates, in the case of the Antibody Paragon Option Agreement, directed to certain mutually agreed therapeutic targets of interest to us (each, a “Research Program”). The Antibody Paragon Option Agreement includes two selected targets for CR-001: PD-1 and VEGF.

~~Should~~The weAntibody ~~resume~~Paragon Option Agreement requires us, Paragon, and Parascent to develop a research plan for each target that includes design, modeling, synthesis, evaluation, and other mutually agreed activities (each, a “Research Plan”), which activities primarily include performing preclinical studies. Paragon will perform the activities set forth in each Research Plan on the timelines set forth in such Research Plan and in compliance with a mutually agreed budget. Each Research Program will be overseen and coordinated by a joint development committee consisting of ~~our~~two ~~drug~~employees ~~candidates~~from us and two employees from Paragon, ~~serious~~with ~~adverse~~us orand ~~unacceptable~~Paragon ~~side~~each ~~effects~~having ~~could~~one bevote ~~identified~~with respect to decisions of the committee. When Paragon and Parascent have produced an antibody against a selected target, inand ~~which~~upon ~~case~~the wecompletion ~~would~~of ~~need~~each Research Program, Paragon and Parascent will deliver to ~~abandon~~us ora ~~limit~~data ~~their~~package ~~development~~that includes sequence information for all then-existing antibodies and information directed to such target. We, Paragon, and Parascent have developed a Research Plan for CR-001 and CR-002 consistent with the foregoing, and Paragon and Parascent have delivered an antibody against PD-1 and VEGF in accordance with such Research Plan.

IfUnder the Paragon Option Agreements, we ~~were~~have an “Option”, on a Research Program-by-Research Program basis, to ~~resume~~enter ~~the~~into ~~development~~a separate agreement with Paragon consistent with a set of ~~our~~pre-negotiated ~~drug~~terms ~~candidates~~(a ~~and~~“License ~~those~~Agreement”). ~~candidates~~Each ~~are~~License ~~associated~~Agreement ~~with~~will ~~undesirable~~include ~~side~~(a) ~~effects~~an inexclusive, ~~clinical~~worldwide ~~trials~~license orto ~~have~~all ~~characteristics~~of ~~that~~Paragon’s ~~are~~right, ~~unexpected~~title, weand ~~may~~interest ~~need~~in and to ~~abandon~~the ~~their~~intellectual ~~development~~property orresulting ~~limit~~from ~~their~~the ~~development~~applicable Research Program to ~~more~~develop, ~~narrow~~manufacture, ~~uses~~and commercialize the monospecific antibodies or ~~subpopulations~~ADCs, as applicable, and products directed to the selected target(s), and (b) an exclusive (in ~~which~~the case of the ~~undesirable~~Antibody ~~side~~Paragon ~~effects~~Option orAgreement) ~~other~~worldwide ~~characteristics~~license ~~are~~to ~~less~~all ~~prevalent~~of Paragon’s right, ~~less~~title, ~~severe~~and orinterest ~~more~~in ~~acceptable~~and to the intellectual property resulting from the applicable Research Program to develop, manufacture, and commercialize multispecific antibodies, as applicable, and products directed to the selected target(s). The Option with respect to the Antibody Paragon Option Agreement is exercisable at our sole discretion at any time during the period beginning on the initiation of activities under the associated Research Program and ending a ~~risk-benefit~~specified ~~perspective~~number of days following the delivery of the data package from Paragon related to the results of the Research Program (an “Option Period”). ~~Many~~There ~~drug~~is ~~candidates~~no ~~that~~payment ~~initially~~due ~~showed~~upon ~~promise~~exercise of an Option pursuant to the Paragon Option Agreements. Activities under a Research Plan may continue past the exercise of an Option or entry into a License Agreement. Pre-Merger Crescent exercised the Option with respect to CR-001 in ~~early~~March 2025 and entered into the related License Agreement in April 2025 pursuant to the Antibody Paragon Option Agreement. We exercised the option with respect to CR-~~stage~~002 ~~testing~~in ~~have~~September ~~later~~2025 ~~been~~and ~~found~~entered into the related license agreement in November 2025 pursuant to ~~cause~~the ~~side~~ADC ~~effects~~Paragon ~~that~~Option ~~prevented~~Agreement. See ~~their~~the ~~further~~sections ~~development~~titled “—CR-001 License Agreement” and “—CR-002 License Agreement” below.

Upon exercise of an Option with respect to a Research Program, the parties are obligated to use reasonable efforts to finalize and execute a License Agreement within 30 days. Under the terms of a License Agreement, we expect that we will have sole authority over and control of the development, regulatory approval, manufacturing and commercialization of such in-licensed intellectual property worldwide. In addition, we expect to have sole authority over and control of the application for and issuance of all regulatory approvals related to such in-licensed intellectual property. Prior to entry into a License Agreement, Paragon is responsible for the prosecution, defense, maintenance and enforcement of patents related to the Research Program. Following entry into a License Agreement, we expect to control prosecution, defense, maintenance and enforcement of patents in-licensed under such License Agreement. However, there is no assurance that we will successfully negotiate future License Agreements with Paragon or that the terms will not differ from those described in this Annual Report on Form 10-K.

IfUnless weterminated ~~were~~earlier, tothe ~~resume~~Antibody ~~development~~Paragon Option Agreement shall continue in force on a Research Program-by-Research Program basis until the later of: ~~our~~(i) ~~drug~~the ~~candidates~~end of the Option Period for such Research Program, weas ~~may~~applicable, ~~expend~~if ~~our~~such ~~limited~~Option ~~resources~~is tonot ~~pursue~~exercised aby ~~particular~~us; ~~drug~~(ii) ~~candidate~~if orwe ~~indication~~exercise ~~and~~our ~~fail~~Option with respect to ~~capitalize~~a onResearch ~~drug~~Program, ~~candidates~~but orthe ~~indications~~parties ~~that~~are ~~may~~unable beto ~~more~~finalize ~~profitable~~and orexecute ~~for~~a ~~which~~License ~~there~~Agreement iswithin a30 ~~greater~~days, ~~likelihood~~the expiration of ~~success.~~such 30-day period (subject to any mutually

Even if we resume our drug development activities, we would have limited financial and management resources and as a result would need to focus on a limited number of research programs and drug candidates. As a result, we may forego or delay pursuit of opportunities with other drug candidates or for other indications that later prove to have greater commercial potential. Our resource allocation decisions could cause us to fail to capitalize on viable commercial drugs or profitable market opportunities. Our spending on research and development programs and drug candidates for specific indications may not yield any commercially viable drugs. If we do not accurately evaluate the commercial potential or target market for a particular drug candidate, we may relinquish valuable rights to that drug candidate through collaboration, licensing or other arrangements in cases in which it would have been more advantageous for us to retain sole development and commercialization rights.

Risks Related to Our Dependence on Third Parties

Should we resume development activities, our success would depend in part on collaborations. If we are unable to maintain any of these collaborations, or if these collaborations are not successful, our business could be adversely affected.

Even before our decision to cease development activities, we had limited capabilities for drug development and do not have any capabilities for sales, marketing or distribution. If we were to resume drug development, we expect that we would need to engage collaborators to support our operations. We cannot assure you that collaborators will develop our drug candidates in a timely manner, or at all, or, if regulatory approval for a drug candidate is achieved, that such collaborator will successfully commercialize the candidate.

Any collaborations we might enter into may pose a number of risks, including:

● collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations;

● collaborators may not perform their obligations as expected;

● collaborators may not pursue the commercialization of any drug candidates that achieve regulatory approval or may elect not to pursue, continue or renew development or commercialization of drug candidates based on clinical trial results, changes in such collaborators’ strategic focus or available funding or external factors, such as an acquisition, that divert resources or create competing priorities;

● collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a drug candidate, repeat or conduct new clinical trials or require a new formulation of a drug candidate for clinical testing;

Table of Contents

●agreed ~~collaborators~~extension ~~could~~of ~~experience~~such ~~delays~~period); inand ~~initiating~~(iii) the expiration of the applicable Research Term (as defined under the Antibody Paragon Option Agreement). We may terminate the Antibody Paragon Option Agreement or ~~conducting~~any ~~clinical~~Research ~~trials~~Program at any time for any or no reason upon 30 days’ prior written notice to Paragon; provided, that we must pay certain unpaid fees due to Paragon upon such termination, as well as any non-cancellable obligations reasonably incurred by Paragon in connection with its activities under any terminated Research Program. Paragon may terminate the Antibody Paragon Option Agreement or any Research Program immediately upon written notice to us if, as a result of any action or failure to act by us or our affiliates, such Research Program or all material activities under the applicable Research Plan are suspended, discontinued or otherwise delayed for a certain consecutive number of ~~reasons;~~months. Each party has the right to terminate the Antibody Paragon Option Agreement or any Research Program upon (i) 30 days’ prior written notice of the other party’s material breach that remains uncured for the 30-day period and (ii) the other party’s bankruptcy.

●Upon ~~collaborators~~signing ~~could~~of ~~independently~~the ~~develop~~Antibody Paragon Option Agreement, orPre-Merger ~~develop~~Crescent ~~with~~was ~~third~~required ~~parties~~to reimburse Paragon $1.5 million for upfront research and development costs related to CR-001 and other general and administrative costs incurred by Paragon prior to September 19, ~~drugs~~2024. ~~that~~Contemporaneously, ~~compete~~Pre-Merger ~~directly~~Crescent oralso ~~indirectly~~issued ~~with~~an ~~our~~aggregate ~~drugs~~of or5,000,000 ~~drug~~shares ~~candidates~~of ifPre-Merger Crescent common stock to Paragon for aggregate non-cash upfront consideration of Paragon’s entry into the Antibody Paragon Option Agreement, valued at $0.20 per share, for a total of $1.0 million. Paragon subsequently contributed 2,500,000 of such ~~collaborators~~shares ~~believe~~to ~~that~~Parascent. ~~competitive~~The ~~products~~$1.5 million of research and development costs related to CR-001 reflects the actual historical direct costs incurred by Paragon as well as a 20% mark-up on the direct costs to approximate the indirect costs incurred by Paragon from the inception of the CR-001 program to the entry into the Antibody Paragon Option Agreement. All of the costs reflected in the upfront amount were incurred by Paragon between January 1, 2024 and the parties’ entry into the Paragon Option Agreement. Such direct costs were related to development activities. Of these upfront development costs related to CR-001 incurred by Paragon prior to September 19, 2024, a total of $1.5 million was recognized as research and development expense and less than $0.1 million was recognized as general and administrative expense during the period from September 19, 2024 (inception) to December 31, 2024. Pre-Merger Crescent paid $1.5 million to Paragon in November 2024. The non-cash upfront consideration was recorded as research and development expense in Pre-Merger Crescent’s consolidated statement of operations and comprehensive loss during the period from September 19, 2024 (inception) to December 31, 2024 as related IP license fees associated with entering into the Option Agreement. We are ~~more~~also ~~likely~~required to bepay ~~successfully~~Paragon ~~developed~~for certain development fees and costs on a Research Program-by-Research Program basis. Paragon had no investments, intangibles, debt, or ~~can~~other beassets ~~commercialized~~or ~~under~~liabilities ~~terms~~related to the CR-001 program aside from standard operating liabilities that ~~are~~were ~~more~~included ~~economically~~in ~~attractive~~the ~~than~~upfront ~~ours;~~amount paid by Crescent to Paragon. Paragon’s cash flows related to the CR-001 program were operating cash flows and this categorization is consistent with the presentation of research and development expense-related cash flows, as presented on our consolidated statement of cash flows.

●We ~~drug~~are ~~candidates~~also ~~discovered~~required into ~~collaboration~~pay ~~with~~Paragon usfor ~~may~~certain bedevelopment ~~viewed~~fees and costs on a Research Program-by-Research ~~our~~Program ~~collaborators~~basis. asUnder ~~competitive~~the ~~with~~Paragon ~~their~~Option ~~own~~Agreements, ~~drug~~Pre-Merger ~~candidates~~Crescent orwas ~~drugs~~required to pay Paragon a one-time, non-refundable research initiation fee within 30 days following finalization of a Research Plan in the amount of $1.3 million for CR-001, $2.5 million for CR-002, and $2.5 million for Former CR-003, which ~~may~~amounts ~~cause~~were ~~such~~paid ~~collaborators~~by Pre-Merger Crescent in December 2024 for each of CR-001 and CR-002. On a Research Program-by-Research Program basis, we are required to ~~cease~~make one-time non-refundable milestone payments to ~~devote~~Paragon ~~resources~~of up to a total of $22.0 million for CR-001 and $46.0 million for CR-002 upon the ~~commercialization~~achievement of ~~our~~certain ~~drug~~clinical ~~candidates;~~development and regulatory milestones. Pre-Merger Crescent paid a $1.5 million milestone payment to Paragon in connection with the achievement of a development candidate for CR-001, which was expensed as development costs for the fiscal year ended December 31, 2024 and paid in January 2025.

●Upon aexercise ~~collaborator~~of the Option with ~~marketing~~respect to a Research Program, the parties are obligated to use reasonable efforts to finalize and ~~distribution~~execute ~~rights~~a License Agreement within 30 days. Any License Agreement entered into with respect to ~~one~~a orgiven ~~more~~Research ofProgram ~~our~~shall ~~drug~~contain ~~candidates~~the same milestone payment obligations as the applicable Paragon Option Agreement, provided that ~~achieve~~any ~~regulatory~~milestone ~~approval~~set ~~may~~in such Paragon Option Agreement that has not ~~commit~~yet ~~sufficient~~been ~~resources~~achieved toand is duplicated in such License Agreement shall no longer be achievable and payable under the ~~marketing~~terms of such Paragon Option Agreement and ~~distribution~~shall only be achievable under the terms of the License Agreement. For the avoidance of doubt, if a milestone is achieved and paid by us pursuant to a Paragon Option Agreement for a certain Research Program, then there shall be no milestone payment due for the achievement of such ~~drug~~milestone under a subsequently executed License Agreement for such Research Program. Further, under a License Agreement, we would also be required to make royalty payments to Paragon in the low single-digit percentage range based on net sales of products, subject to certain reductions. The royalty term will terminate on a product-by-product and country-by-country basis upon the later of the expiration of the last-to-expire valid claim within the relevant patent rights or ~~drugs;~~the twelfth anniversary of the first commercial sale of such product in such country.

~~● disagreements with collaborators~~Additionally, ~~including~~under ~~disagreements over proprietary rights, contract interpretation or~~ the ~~preferred~~ADC ~~course~~Paragon ofOption ~~development~~Agreement, ~~might~~on ~~cause~~December ~~delays~~31, ~~or termination of the research~~2025, ~~development~~we orgranted ~~commercialization~~Parascent ofwarrants ~~drug candidates, might lead~~ to ~~additional~~purchase ~~responsibilities~~a ~~for~~number usof ~~with~~shares ~~respect~~equal to ~~drug~~1.00% ~~candidates~~of orour ~~might~~outstanding ~~result~~ordinary inshares ~~litigation~~as orof ~~arbitration,~~the ~~any~~date of ~~which~~the ~~would~~grant beon ~~time~~a ~~consuming~~fully-diluted ~~and expensive;~~

● collaborators 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;

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

● collaborations may be terminated for the convenience of the collaborator and, if terminated, we could be required to raise additional capital to pursue further development or commercialization of the applicable drug candidates.

If any collaborations we might enter into do not result in the successful development and commercialization of drugs, or if one of our collaborators terminates its agreement with us, we may not receive any future research funding or milestone or royalty payments under the collaboration. For example, in 2020, our former collaborator Pfizer terminated its license agreement with us for the worldwide development and commercialization of our prior drug candidate rivipansel, thereby eliminating our right to receive any future development or commercialization milestones or royalty payments for sales of that drug candidate. In addition, even if we are eligible to receive any such payments from a collaborator, they could be substantially delayed. If we do not receive the funding we expect under these agreements, the development of our drug candidates could be delayed and we may need additional resources to develop our drug candidates. All of the risks relating to drug development, regulatory approval and commercialization described in this report also apply to the activities of our collaborators.

If a current or future collaborator of ours is involved in a business combination, the collaborator might deemphasize or terminate development or commercialization of any drug candidate licensed to it by us. If one of our collaborators terminates its agreement with us, we may find it more difficult to attract new collaborators and our reputation in the business and financial communities could be adversely affected. We may in the future determine to collaborate with pharmaceutical and biotechnology companies for their development and potential commercialization of our drug candidates. We face significant competition in seeking appropriate collaborators. Our ability to reach a definitive agreement for a collaboration will depend, among other things, upon our assessment of a collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of a number of factors. If we are unable to reach agreements with suitable collaborators on a timely basis, on acceptable terms, or at all, we may have to curtail the development of a drug candidate, reduce or delay its development or one or more of our other development programs, delay its potential commercialization or reduce the scope of any sales or marketing activities or increase our expenditures and undertake development or commercialization activities at our own expense. If we elect to fund and undertake development or commercialization activities on our own, we may need to obtain additional expertise and additional capital, which may not be available to us on acceptable terms or at all. If we fail to enter into collaborations and do not have sufficient funds or expertise to undertake the necessary development and

Table of Contents

~~commercialization~~basis, ~~activities~~or an aggregate of 402,731 ordinary shares, with an exercise price equal to the fair market value of our underlying shares on each respective grant date. In addition, in connection with terminating the ADC Paragon Option Agreement, effective March 26, 2026, we ~~may~~will ~~not~~grant beParascent ~~able~~warrants to ~~further~~purchase ~~develop~~34,566 of our ~~drug~~ordinary ~~candidates~~shares orwith ~~bring~~an ~~them~~exercise price equal to the fair market, ~~which~~value ~~would~~of ~~impair~~our underlying shares on the grant date as settlement in full of our ~~business~~remaining ~~prospects~~obligation to issue warrants to Parascent under the ADC Paragon Option Agreement. Parascent is an entity formed by Paragon as a vehicle to hold equity in Crescent in order to share profits with certain employees of Paragon and will not perform any substantive role under the Paragon Option Agreements other than to receive such warrants.

As of December 31, 2025, we have paid Paragon (i) $16.7 million under the Antibody Paragon Option Agreement and CR-001 License Agreement for development costs related to PD-1 and VEGF incurred by Paragon through the effective date of the agreement, including pre-development costs, (ii) $13.9 million under the ADC Paragon Option Agreement and CR-002 License Agreement for development costs related to the CR-002 target incurred by Paragon through the effective date of the agreement, and (iii) $2.2 million under the ADC Paragon Option Agreement for development costs related to the three undisclosed Former CR-003 targets incurred by Paragon through the effective date of the agreement.

~~Should~~CR-001 weLicense ~~resume~~Agreement development of our drug candidates, we would expect to rely on third parties to conduct additional clinical trials for our drug candidates, and those third parties may not perform satisfactorily, including failing to meet deadlines for the completion of such trials.

WeOn ~~previously~~April ~~engaged~~28, a2025, ~~third~~we entered into the CR-~~party~~001 ~~contract~~License ~~research~~Agreement ~~organization~~for all antibodies discovered, generated, identified or ~~CRO,~~characterized toby ~~conduct~~Paragon ~~our~~in ~~clinical~~the ~~trials~~course ~~for~~of ~~uproleselan.~~performing Ifthe weCR-001 ~~were~~research program directed to ~~resume~~PD-1 ~~clinical~~and ~~development~~VEGF, weantibodies ~~would~~created ~~expect~~by us derived from the licensed antibodies and directed to ~~engage~~PD-1 ~~CROs~~and VEGF, and products that comprise the foregoing with ~~respect~~Paragon, toconsistent ~~any~~with ~~further~~the ~~clinical~~pre-negotiated ~~trials~~terms ofagreed ~~uproleselan~~to orupon ~~any~~execution of ~~our~~the ~~other~~Antibody ~~drug~~Paragon ~~candidates~~Option ~~that~~Agreement, ~~may~~pursuant ~~progress~~ to ~~clinical~~which ~~development.~~Paragon Wegranted ~~would~~us ~~also~~a ~~expect~~royalty-bearing, worldwide, exclusive and sublicensable license with respect to ~~rely~~certain oninventions, ~~third~~patent ~~parties~~rights, ~~such~~sequence asinformation ~~CROs~~and other intellectual property rights related to bispecific and multispecific antibodies directed at PD-1 and VEGF (the “Licensed Antibody Technology”) to develop, ~~clinical~~manufacture, ~~data~~commercialize ~~management~~and ~~organizations~~otherwise exploit certain bispecific and multispecific antibodies and products targeting PD-1 and VEGF in the field of prophylaxis, ~~medical~~palliation, ~~institutions~~treatment and ~~clinical~~diagnosis ~~investigators~~of human disease and disorders in all therapeutic areas (the “field”) and worldwide (the “territory”). Under the terms of the CR-001 License Agreement, we are obligated to ~~conduct~~pay ~~those~~Paragon ~~clinical~~up ~~trials~~to $22.0 ~~Agreements~~million ~~with~~based ~~such~~on ~~third~~specific ~~parties~~development ~~might~~and ~~terminate~~regulatory ~~for~~milestones, including a ~~variety~~$1.5 million fee for the nomination of ~~reasons,~~a ~~including~~development candidate and a ~~failure~~further tomilestone ~~perform~~payment byof $2.5 million upon the ~~third~~first ~~parties~~dosing of a human patient in a Phase 1 trial. IfFollowing wethe ~~need~~execution toof ~~enter~~the ~~into~~CR-001 ~~alternative~~License ~~arrangements~~Agreement, ~~that~~we ~~would~~are ~~delay~~solely ~~our~~responsible ~~drug~~for, and have sole authority and control over, all aspects of the development, manufacturing and commercialization of CR-001, including regulatory strategy, communications, filings and activities (including clinical trials). In addition, the following summarizes other key terms of the CR-001 License Agreement.

•We will pay Paragon a low-to-mid single-digit percentage royalty based on annual net sales of the products in the field and in the territory, subject to a 30% reduction if there is no valid patent covering the product in the country.

~~Our~~•The ~~reliance~~royalty onterm ~~these~~ends ~~third~~on ~~parties~~the ~~for~~later ~~research and development activities would reduce our control over these activities, but would not relieve us~~ of ~~our~~(i) ~~responsibilities.~~the ~~For~~twelfth ~~example,~~anniversary ~~we would remain responsible for ensuring that each~~ of ~~our~~such ~~clinical~~date trials is conducted in accordance with the general investigational plan and protocols for the trial. Moreover, the FDA requires us to comply with standards, commonly referred to as good clinical practices, or ~~GCPs,~~(ii) ~~for conducting, recording and reporting~~ the ~~results~~expiration of ~~clinical trials to assure that data and reported results are credible and accurate and that~~ the ~~rights, integrity and confidentiality of trial participants are protected. We also are required~~ last-to-expire ~~register~~valid ~~ongoing~~patent ~~clinical~~covering ~~trials and post~~ the ~~results~~product ~~of completed clinical trials on a government-sponsored database, ClinicalTrials.gov, within specified timeframes. Failure to do so can result~~ in ~~fines,~~the ~~adverse~~country ~~publicity~~at ~~and significant civil and criminal sanctions~~issue.

•The CR-001 License Agreement may be terminated on 60 days’ notice by us; on material breach without cure; and to the extent permitted by law, on a party’s insolvency or bankruptcy.

~~Furthermore,~~•With ~~these~~respect ~~third~~to ~~parties~~patents ~~may~~licensed ~~also~~to ~~have~~us ~~relationships~~under ~~with~~the ~~other~~CR-001 ~~entities,~~License ~~some~~Agreement ofthat ~~which~~have ~~may~~been befiled ~~our~~as ~~competitors.~~of Ifthe ~~these~~effective ~~third~~date ~~parties~~of dothe ~~not~~CR-001 ~~successfully~~License ~~carry~~Agreement, ~~out~~we ~~their~~will ~~contractual~~control ~~duties~~the preparing, ~~meet~~filing, ~~expected~~prosecuting ~~deadlines~~and ormaintenance ~~conduct~~of ~~our~~such ~~clinical~~patents. ~~trials~~With inrespect ~~accordance~~to ~~with~~patents ~~regulatory~~filed ~~requirements~~after orthe ~~our~~effective ~~stated~~date ~~protocols~~of the CR-001 License Agreement, weParagon will ~~not~~control bethe ~~able~~preparing, ~~to obtain~~filing, orprosecuting ~~may~~and bemaintaining ~~delayed~~of insuch ~~obtaining,~~patents ~~marketing~~until ~~approvals~~the ~~for~~final ~~our~~deliverable ~~drug~~for ~~candidates~~the ~~and~~relevant ~~will~~research ~~not~~program beis ~~able~~delivered to us, orafter ~~may~~which bewe ~~delayed~~will incontrol ~~our~~the ~~efforts~~preparing, tofiling, ~~successfully~~prosecuting ~~commercialize~~and ~~our~~maintain ~~drug~~of ~~candidates~~such patents.

•We shall have the right to grant sublicenses under the CR-001 License Agreement, provided that (i) any sublicense agreement is consistent with all relevant terms, conditions and restrictions of the CR-001 License Agreement, (ii) we provide Paragon with a copy of each sublicense agreement and any amendments thereto within 30 days following execution thereof and (iii) we remain responsible for all payments and obligations due under the CR-001 License Agreement.

WeOn ~~also~~December ~~expect~~2, to2025, ~~rely~~we onentered ~~other~~into ~~third~~Amendment ~~parties~~No. to1 ~~store~~(the ~~and~~“Amendment”) ~~distribute~~to ~~drug~~the ~~supplies~~CR-001 ~~for~~License ~~any~~Agreement. ~~further~~The ~~clinical~~purpose ~~trials~~of ~~that~~the weAmendment ~~were~~was to ~~conduct.~~amend ~~Any~~certain ~~performance~~terms ~~failure~~of on the ~~part~~CR-001 ofLicense ~~our~~Agreement ~~distributors~~for ~~could~~the ~~delay~~sole ~~clinical~~purpose ~~development or marketing approval~~ of ~~our~~accommodating ~~drug~~and ~~candidates~~aligning orwith ~~commercialization~~the ofsublicense ~~our~~for ~~drugs,~~the ~~producing~~CR-001 ~~additional~~License ~~losses~~Agreement ~~and~~with ~~depriving~~Sichuan usKelun-Biotech ofBiopharmaceutical ~~potential~~Co. ~~revenue~~Ltd.

We previously contracted with third parties for the manufacturing of our drug candidates for preclinical and clinical testing, and if we were to resume development activities and pursue commercialization, we would expect to continue to do so. This reliance on third parties increases the risk that we would not have sufficient quantities of our drug candidates or drugs, or such quantities at an acceptable cost, which could delay, prevent or impair our potential development or commercialization efforts.

We do not have any manufacturing facilities or personnel. We have in the past relied on third parties for the manufacturing of our drug candidates for preclinical and clinical testing, as well as for potential commercial manufacture. If we were to resume our drug development activities, we would need to re-engage those third parties. Our reliance on third parties would increase the risk that we will not have sufficient quantities of our drug candidates or drugs, or such quantities at an acceptable cost or quality, which could delay, prevent or impair our ability to timely conduct clinical trials or our other potential development or commercialization efforts.

We would also expect to rely on third-party manufacturers or third-party collaborators for the manufacturing of commercial supply of any other drug candidates for which we or our collaborators obtain marketing approval. For example, in January 2024 we entered into an agreement with Patheon Manufacturing Services LLC, or Patheon, for manufacture and supply of uproleselan for commercial sale. Pursuant to the agreement, Patheon was to manufacture commercial quantities of injectable uproleselan from active pharmaceutical ingredient we were to supply.

Table of Contents

~~If we were to resume our development activities, we may be unable to establish any agreements with third~~CR-~~party~~002 ~~manufacturers~~License ~~or to do so on acceptable terms. Even if we are able to establish agreements with third-party manufacturers, reliance on third-party manufacturers entails additional risks, including:~~Agreement

●On ~~reliance~~November 5, 2025, we entered into a License Agreement for all ADCs discovered, generated, identified or characterized by Paragon in the course of performing the CR-002 research program directed to PD-L1, ADCs created by us derived from the licensed ADCs and directed to PD-L1, and products that comprise the foregoing with Paragon (the “CR-002 License Agreement”) consistent with the pre-negotiated terms agreed to upon execution of the ADC Paragon Option Agreement, pursuant to which Paragon granted us a royalty-bearing, worldwide, exclusive and sublicensable license with respect to certain inventions, patent rights, sequence information and other intellectual property rights related to ADCs directed at PD-1 and VEGF (the “Licensed Antibody Technology”) to develop, manufacture, commercialize and otherwise exploit certain ADCs and products targeting PD-L1 in the field of prophylaxis, palliation, treatment and diagnosis of human disease and disorders in all therapeutic areas (the “field”) and worldwide (the “territory”). Under the terms of the CR-002 License Agreement, we are obligated to pay Paragon up to $46.0 million based on specific development and regulatory milestones, including a $5.0 million fee for the ~~third~~nomination ~~party~~of a development candidate and a further milestone payment of $5.0 million upon the first dosing of a human patient in a Phase 1 trial. Following the execution of the CR-002 License Agreement, we are solely responsible for, and have sole authority and control over, all aspects of the development, manufacturing and commercialization of CR-002, including regulatory ~~compliance~~strategy, communications, filings and ~~quality~~activities ~~assurance;~~(including clinical trials). In addition, the following summarizes other key terms of the CR-002 License Agreement.

●•We ~~the~~will ~~possible~~pay ~~breach~~Paragon a low-to-mid single-digit percentage royalty based on annual net sales of the ~~manufacturing~~products ~~agreement~~in bythe field and in the ~~third~~territory, ~~party;~~subject to a 30% reduction if there is no valid patent covering the product in the country.

●•The royalty term ends on the ~~possible~~later ~~misappropriation~~of (i) the twelfth anniversary of ~~our~~such ~~proprietary~~date ~~information,~~or ~~including~~(ii) ~~our~~the ~~trade~~expiration ~~secrets~~of ~~and~~the ~~know~~last-~~how;~~to-expire ~~and~~valid patent covering the product in the country at issue.

●•The ~~the~~CR-002 ~~possible~~License ~~termination~~Agreement ormay ~~non-renewal~~be ofterminated ~~the~~on ~~agreement~~60 days’ notice by ~~the~~us; ~~third~~on ~~party~~material atbreach awithout ~~time~~cure; ~~that~~and isto ~~costly~~the orextent ~~inconvenient~~permitted ~~for~~by uslaw, on a party’s insolvency or bankruptcy.

•With respect to patents licensed to us under the CR-002 License Agreement that have been filed as of the effective date of the CR-002 License Agreement, we will control the preparing, filing, prosecuting and maintenance of such patents. With respect to patents filed after the effective date of the CR-002 License Agreement, Paragon will control the preparing, filing, prosecuting and maintaining of such patents until the final deliverable for the relevant research program is delivered to us, after which we will control the preparing, filing, prosecuting and maintain of such patents.

~~Third-party~~•We ~~manufacturers~~shall ~~may~~have ~~not~~the beright ~~able~~ to ~~comply~~grant ~~with~~sublicenses ~~current~~under ~~good~~the ~~manufacturing~~CR-002 ~~practices,~~License ~~or cGMP~~Agreement, ~~regulations~~provided orthat ~~similar~~(i) ~~regulatory~~any ~~requirements~~sublicense ~~outside~~agreement ~~the~~is ~~United~~consistent ~~States.~~with ~~Our~~all ~~failure~~relevant terms, orconditions ~~the~~and ~~failure~~restrictions of ~~our~~the ~~third~~CR-~~party~~002 ~~manufacturers,~~License ~~to comply with applicable regulations could result in sanctions being imposed on us~~Agreement, ~~including~~(ii) ~~clinical~~we ~~holds,~~provide ~~fines,~~Paragon ~~injunctions,~~with ~~civil~~a ~~penalties,~~copy ~~delays, suspension or withdrawal~~ of ~~approvals,~~each ~~license~~sublicense ~~revocation,~~agreement ~~seizures~~and orany ~~recalls~~amendments ofthereto ~~drug~~within ~~candidates~~30 ordays ~~drugs,~~following ~~operating~~execution ~~restrictions~~thereof and ~~criminal~~(iii) ~~prosecutions,~~we ~~any~~remain ofresponsible ~~which~~for ~~could~~all ~~significantly~~payments and ~~adversely~~obligations ~~affect~~due ~~supplies~~under ofthe ~~our~~CR-002 ~~drugs~~License Agreement.

License and Collaboration Agreement with Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

InOn ~~addition~~December 2, in2025, ~~the~~we ~~event~~entered ~~that~~into ~~any~~a ofLicense ~~our~~and ~~third-party~~Collaboration ~~manufacturers~~Agreement ~~fails~~(the to“Kelun ~~comply~~Collaboration Agreement”) with ~~such~~Sichuan ~~requirements~~Kelun-Biotech orBiopharmaceutical toCo., ~~perform~~Ltd. ~~its~~(“Kelun”) ~~obligations~~pursuant to uswhich inKelun ~~relation~~granted tous ~~quality~~an exclusive, ~~timing or otherwise~~royalty-bearing, orsublicensable iflicense ~~our~~under ~~supply~~certain ofintellectual ~~components~~property orrights ~~other~~controlled ~~materials~~by ~~becomes~~Kelun ~~limited~~to ~~or interrupted for other reasons~~develop, ~~we may be forced to~~ manufacture ~~the materials ourselves~~, ~~for~~commercialize ~~which~~and weotherwise ~~currently~~exploit docertain ~~not~~products ~~have~~comprising ~~the~~SKB105 ~~capabilities~~and orany ~~resources,~~backups orto ~~enter~~SKB105 ~~into~~that anare ~~agreement~~directed ~~with~~to ~~another~~integrin ~~third~~beta-6 ~~party,~~and ~~which~~controlled weby ~~may~~Kelun ~~not~~(“Licensed ~~be able to do on commercially reasonable terms~~Products”), iffor at all. Iftherapeutic, ~~our~~prophylactic ~~contract~~and ~~manufacturers~~diagnostic ~~cannot~~uses ~~perform~~in ashumans ~~agreed~~worldwide, weexcept ~~may~~mainland beChina, ~~required~~Hong toKong, ~~replace~~Macau ~~such manufacturers~~ and weTaiwan ~~may~~(the ~~incur~~“Crescent ~~added~~Territory”). ~~costs~~Kelun ~~and~~granted ~~delays~~us ina ~~identifying~~non-exclusive ~~and~~license ~~qualifying~~to ~~any~~develop ~~such~~(but ~~replacement.~~only ~~Any~~with ~~replacement~~Kelun’s ofprior ~~our~~written ~~manufacturers~~consent) ~~could require significant effort~~ and ~~expertise~~manufacture ~~because~~Licensed ~~there~~Products ~~may~~in bemainland aChina, ~~limited~~Hong ~~number~~Kong, ofMacau ~~qualified~~and ~~replacements.~~Taiwan If(the we“Kelun ~~are~~Territory”), ~~required~~solely ~~to change manufacturers~~ for ~~any~~the ~~reason,~~purpose weof ~~will~~exploiting bethe ~~required~~Licensed toProducts ~~verify~~in ~~that~~ the ~~new~~Crescent ~~manufacturer~~Territory. ~~maintains~~We ~~facilities~~granted ~~and~~to ~~procedures~~Kelun ~~that~~an ~~comply~~exclusive, ~~with~~royalty-free, ~~quality~~sublicensable ~~standards~~license ~~and~~under ~~with~~certain ~~all~~intellectual ~~applicable~~property ~~regulations~~rights ~~and~~controlled ~~guidelines.~~by ~~The~~us ~~delays~~for ~~associated~~Kelun ~~with~~to ~~the~~(a) ~~verification~~fulfill ofits aobligations ~~new~~under ~~manufacturer~~the ~~could~~Kelun ~~negatively~~Collaboration ~~affect~~Agreement, ~~our~~and ~~ability~~(b) to develop, ~~our~~manufacture, ~~drug~~commercialize ~~candidates~~and inotherwise aexploit ~~timely~~Licensed ~~manner~~Products orin ~~within~~the ~~budget~~Kelun Territory.

During the term of the Kelun Collaboration Agreement, both we and Kelun are restricted from developing, manufacturing, commercializing or otherwise exploiting any product containing any antibody-drug conjugate that is linked to a single small molecule cytotoxin and specifically directed to integrin beta-6 (subject to certain exceptions in the event of a change of control or similar transaction of either us or Kelun), except for Licensed Products.

Our dependence upon others for the manufacturing of our drug candidates or drugs may adversely affect our ability to commercialize any drugs that receive marketing approval on a timely and competitive basis.

Risks Related to the Potential Commercialization of Drug Candidates

Should we resume development of drug candidates, if any of those drug candidates were to receive marketing approval, it may still fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success.

We do not intend to continue development of uproleselan or any of our other product candidates. However, should we decide to resume development activities and any of our drug candidates receives marketing approval, it may nonetheless fail to gain sufficient market acceptance by physicians, patients, third-party payors and others in the medical community. If our drug candidates do not achieve an adequate level of acceptance, we may not generate significant revenue from drug sales and we may not become profitable. The degree of market acceptance of our drug candidates, even if approved for commercial sale, would depend on a number of factors, including:

● the efficacy and potential advantages compared to alternative treatments;

● our ability to offer our drugs for sale at competitive prices;

● the convenience and ease of administration compared to alternative treatments;

● the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies;

● the strength of marketing and distribution support;

Table of Contents

●We are obligated to use commercially reasonable efforts to develop, including by achieving certain regulatory milestone obligations within specified timelines, obtain regulatory approval for, manufacture, and commercialize at least one Licensed Product in United States and at least three major European markets. As partial consideration for the ~~availability~~license granted to us by Kelun, we paid Kelun an upfront payment of $80 million. We are obligated to pay Kelun (a) clinical and regulatory milestone payments of up to an aggregate of $345 million, (b) commercial milestone payments of up to an aggregate of $902.5 million, and (c) tiered royalties ranging from a mid-single-digit to low double-digit percentages of net sales of Licensed Products by us, our affiliates or sublicensees, subject to certain customary reductions. Our obligation to pay Kelun royalties will commence, on a Licensed Product-by-Licensed Product and country-by-country basis, on the first commercial sale of such Licensed Product in such country and expire on the latest of the expiration of the last-to-expire Kelun licensed patent covering the manufacture, use or sale of such Licensed Product in such country, expiration of all regulatory exclusivity for such Licensed Product in such country, and twelve years following the first commercial sale of such Licensed Product in such country (the “Royalty Term”). If we sublicense, assign, sell or otherwise divest our rights to develop or commercialize any Licensed Product under the Kelun Collaboration Agreement to a third party, we are obligated to pay Kelun either a low double-digit (if such transaction occurs prior to a specified milestone event) or mid-double digit percentage (if such transaction takes place after a specified milestone event) of all the consideration we receive from such third party ~~coverage~~within ~~and~~a ~~adequate~~certain ~~reimbursement;~~period of time. In addition, if we enter into or undergo a change of control within a certain period following the effective date of the Kelun Collaboration Agreement, we are obligated to pay Kelun a low single-digit to low double-digit percentage (depending how long after the effective date the change of control occurs) of all payments our equity holders receive in connection with the change of control.

●Unless earlier terminated, the ~~prevalence~~Kelun Collaboration Agreement will expire upon the expiration of the final Royalty Term with respect to all Licensed Products. We may terminate the Kelun Collaboration Agreement in its entirety without cause upon advanced written notice to Kelun. Either we or Kelun may terminate the Kelun Collaboration Agreement, in its entirety or on a Product-by-Product and ~~severity~~country-by-county basis, in the event of ~~any~~the ~~side~~other ~~effects;~~party’s material breach, subject to certain notice and cure periods. Either we or Kelun may terminate the Kelun Collaboration Agreement upon written notice to the other party upon the occurrence of certain insolvency events regarding such other party. Kelun may terminate the Kelun Collaboration Agreement if we or our sublicensees challenge the patents licensed to us by Kelun, subject to certain exceptions.

●Upon termination of the Kelun Collaboration Agreement for any ~~restrictions~~reason, onall rights and licenses granted to us will terminate, subject to certain exceptions, and we are obligated to deliver and assign to Kelun all regulatory filings and registrations for the ~~use~~Licensed Products in the Crescent Territory, and disclose to Kelun all data generated by us in any clinical trials related to the Licensed Products. In addition, upon termination of the Kelun Collaboration Agreement by us without cause or by Kelun for our ~~drugs~~material ~~together~~breach, patent challenge or insolvency, we grant to Kelun a non-exclusive, royalty-free, perpetual, sublicensable license under certain intellectual property rights controlled by us for Kelun to develop, manufacture and commercialize Licensed Products worldwide, and upon Kelun’s request, we are obligated to exclusively negotiate in good faith with ~~other~~Kelun ~~medications~~commercially reasonable financial terms upon which we would grant to Kelun an exclusive license under certain of our intellectual property rights to develop, manufacture and commercialize Licensed Products worldwide or within the countries designated by Kelun.

License Agreement with Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

~~Should~~On December 2, 2025, we ~~resume~~entered ~~development~~into ofa ~~our~~License ~~drug~~Agreement ~~candidates~~(the “Kelun License Agreement”) with Kelun, pursuant to which we ~~would~~granted ~~need~~Kelun (a) an exclusive, worldwide, royalty-bearing, sublicensable license under certain intellectual property rights controlled by us for Kelun to ~~establish~~develop, ~~sales~~manufacture and commercialize and otherwise exploit products comprising CR-001 and any backup bispecific antibodies that are directed to both VEGF and PD-1 that are controlled by us (the “Licensed Products”), ~~marketing~~for the treatment, prevention, or diagnosis of human diseases in the Kelun Territory and ~~distribution~~(b) ~~capabilities~~a non-exclusive, royalty-free, sublicensable license to develop Licensed Products outside of the Kelun Territory solely for the purpose of supporting exploitation of Licensed Products in the Kelun Territory, subject to our ~~drug~~prior ~~candidates~~written consent, and to manufacture Licensed Products in the Kelun Territory solely to develop, commercialize and otherwise exploit the Licensed Products in the Kelun Territory. During the term of the Kelun License Agreement, neither we nor Kelun may ~~not~~develop, bemanufacture, ~~successful~~commercialize or otherwise exploit any product containing a bi-specific antibody directed to both PD-1 and VEGF anywhere in ~~commercializing~~the ~~those~~world, ~~drug~~other ~~candidates~~than ifLicensed ~~approved~~Products.

~~Even~~Kelun ~~prior~~is toobligated ~~our decision~~ to ~~cease~~use ~~drug~~commercially ~~development~~reasonable ~~and~~efforts ~~commercialization~~to ~~activities~~develop, weand ~~did~~following ~~not~~regulatory ~~have~~approval, acommercialize ~~sales~~at orleast ~~marketing~~one ~~infrastructure~~Licensed ~~and~~Product ~~had no experience~~ in the ~~sale,~~Kelun ~~marketing or distribution of pharmaceutical drugs~~Territory. IfAs wepartial ~~were~~consideration tofor ~~resume~~the ~~development,~~license wegranted ~~would~~by ~~need~~us to ~~establish~~Kelun, aKelun ~~sales~~paid ~~and~~an ~~marketing~~upfront ~~organization~~payment toof ~~market~~$20 ormillion ~~co-promote~~in ~~any~~January ~~drugs that achieve marketing approval~~2026. ~~There~~Kelun ~~are~~is ~~risks~~obligated ~~involved~~to ~~with~~pay ~~establishing~~us ~~sales,~~development ~~marketing~~milestones ~~and~~of ~~distribution~~up ~~capabilities.~~to ~~For~~an ~~example,~~aggregate ~~recruiting~~of ~~and~~$30 ~~training a sales force is expensive and time consuming and could delay any product launch~~million. IfWe ~~the~~may ~~commercial~~also ~~launch~~be ofobligated ato ~~drug~~pay ~~candidate~~Kelun ~~for~~$5 ~~which~~million weas ~~recruit~~ a ~~sales~~milestone ~~force~~payment ~~and establish marketing capabilities is delayed or does not occur~~ for ~~any~~Kelun’s ~~reason,~~initiation weof ~~would~~certain ~~have~~clinical ~~prematurely~~trials orof ~~unnecessarily~~a ~~incurred~~Licensed ~~these commercialization expenses. This may be costly~~Product, ~~and~~including ~~our~~a ~~investment~~combination ~~would~~clinical betrial ~~lost~~with ifa wespecific ~~cannot retain or reposition our sales and marketing personnel.~~

Other factors that could inhibit our efforts to commercialize drugs on our own include:

● our inability to recruit, train and retain adequate numbers of effective sales and marketing personnel;

● the inability of sales personnel to obtain access to physicians or our failure to educate adequate numbers of physicians on the benefits of any future drugs;

● the lack of complementary drugs to be offered by sales personnel, which could put us at a competitive disadvantage relative to companies with more products; and

● unforeseen costs and expenses associated with creating an independent sales and marketing organization.

If we are unable to establish our own sales, marketing and distribution capabilities and therefore enter into arrangements with third parties to perform these services, our revenue and our profitability, if any, would likely be lower than if we were to sell, market and distribute any drugs that we develop ourselves. In addition, we may not be successful in entering into arrangements with third parties to sell, market and distribute our drug candidates or may be unable to do so on terms that are favorable to us. We likely would have little control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market our drugs effectively. Even if we were to resume drug development, in the event that we do not establish sales, marketing and distribution capabilities successfully, either on our own or in collaboration with third parties, we would not be successful in commercializing our drug candidates.

Even if we were to resume drug development, we would face substantial competition, which may result in others discovering, developing or commercializing drugs before or more successfully than we do.

The development and commercialization of new drugs is highly competitive. We have faced competition with respect to our drug candidates, and should we resume drug development we would face competition with respect to any drug candidates that we may seek to develop or commercialize in the future, from major pharmaceutical companies, specialty pharmaceutical companies, biotechnology companies, academic institutions, governmental agencies and public and private research institutions. Should any competitors’ drug candidates receive regulatory or marketing approval prior to ours, they may establish a strong market position and diminish the need for our drug candidates.

The key competitive factors affecting the success of all of our drug candidates, if approved, are likely to be their safety, efficacy, convenience, price, the level of generic competition and the availability of coverage and reimbursement from government and other third-party payors. To the extent that competitive drugs or drug candidates developed by others are successful in treating our target indications, it would reduce the market opportunity for our drug candidates.

Many of the companies against which we may compete in the future, have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved drugs than we do. Mergers and acquisitions in the pharmaceutical and

Table of Contents

~~biotechnology~~compound, ~~industries~~in ~~may~~each ~~result~~case, insubject ~~even~~to ~~more~~approval ~~resources~~by ~~being~~us. ~~concentrated~~In ~~among~~addition, aKelun ~~smaller~~is ~~number~~obligated to pay us tiered royalties on net sales of ~~our~~Licensed ~~competitors.~~Product ~~Smaller~~by orKelun, ~~early-stage~~its ~~companies~~affiliates ~~may~~and ~~also~~sublicensees, ~~prove~~subject to becustomary ~~significant~~royalty ~~competitors~~offsets, ~~particularly~~ranging ~~through~~from ~~collaborative~~low ~~arrangements~~single-digit ~~with~~to ~~large~~mid-single ~~and~~-digit ~~established~~percentages ~~companies~~of such net sales of Licensed Products. ~~These~~Kelun’s ~~competitors~~obligation ~~also~~to ~~compete~~pay ~~with~~royalties uswill incommence, ~~recruiting~~on ~~and~~a ~~retaining~~Licensed-Product-by ~~qualified~~Licensed ~~scientific~~Product and ~~management~~region-by-region ~~personnel~~basis, ~~and~~on ~~establishing~~the ~~clinical~~first ~~trial~~commercial ~~sites~~sale ~~and~~of ~~patient~~such ~~registration~~Licensed ~~for~~Product ~~clinical~~in ~~trials,~~such asregion ~~well~~and asexpire inon ~~acquiring~~the ~~technologies~~later ~~complementary~~of: (A) the last-to-expire valid claim of a patent that covers the manufacture, use or ~~necessary~~sale ~~for~~of Licensed Product in the applicable region, ~~our~~(B) ~~programs~~the expiration of all regulatory exclusivity for such Licensed Product in such region or (C) the date that is twelve years after the first commercial sale of such Licensed Product in such region (the “Royalty Term”).

Unless earlier terminated, the Kelun License Agreement will expire upon the expiration of the final Royalty Term with respect to all Licensed Products. Either we or Kelun may terminate the Kelun License Agreement, in its entirety or on a Product-by-Product and region-by-region basis, in the event of the other party’s material breach, subject to certain notice and cure periods. Either we or Kelun may terminate the Kelun License Agreement upon written notice to the other party upon the occurrence of certain insolvency events regarding the other party, and we may terminate the Kelun License agreement if Kelun, its affiliates or sublicensees challenge the patents licensed to Kelun by us, subject to certain exceptions. Kelun may terminate the agreement in its entirety for any reason or no reason at all upon prior written notice.

~~Our~~Upon ~~commercial~~termination ~~opportunity~~of ~~could~~the beKelun ~~reduced~~License orAgreement ~~eliminated~~for ifany ~~our~~reason, ~~competitors~~all ~~develop~~rights and ~~commercialize~~licenses ~~drugs~~granted ~~that~~to ~~are~~Kelun ~~safer~~will terminate, ~~more~~subject ~~effective~~to certain exceptions, ~~have~~and ~~fewer~~Kelun oris ~~less~~obligated ~~severe~~to ~~side~~deliver ~~effects~~and assign to us all regulatory filing and registrations for the Licensed Products in the Kelun Territory, ~~are~~and ~~more~~disclose ~~convenient~~to orus ~~are~~all ~~less~~data ~~expensive~~generated ~~than~~under ~~any~~certain ~~drugs~~clinical ~~that~~trials werelated ~~may~~to ~~develop~~the Licensed Products. ~~Our~~In ~~competitors~~addition, ~~also~~upon ~~may~~termination ~~obtain~~of ~~FDA~~the Kelun License Agreement by Kelun without cause, or ~~other~~upon ~~regulatory~~our ~~approval~~termination of the Kelun License Agreement for ~~their~~Kelun’s ~~drugs~~material ~~more~~breach, ~~rapidly~~patent ~~than~~challenge weor ~~may~~insolvency, ~~obtain~~Kelun ~~approval~~grants ~~for~~to ~~ours~~us a non-exclusive, ~~which~~royalty-free, ~~could~~perpetual, ~~result~~sublicensable inlicense under certain intellectual property rights controlled by Kelun to develop, manufacture and commercialize Licensed Products worldwide, and upon our ~~competitors~~request, ~~establishing~~Kelun ais ~~strong~~obligated ~~market~~to ~~position~~exclusively ~~before~~negotiate wein ~~are~~good ~~able~~faith with us commercially reasonable financial terms upon which Kelun would grant to ~~enter~~us ~~the~~an ~~market~~exclusive license under certain of Kelun’s intellectual property rights to develop, manufacture or commercialize Licensed Products.

WuXi Biologics Master Services Agreement

InOn ~~addition~~October 31, ~~because~~2024, we ~~have~~entered nointo ~~patents~~a biologics master services agreement (the “WuXi Biologics MSA”) with ~~respect~~WuXi toBiologics ~~our~~(Hong ~~glycomimetics~~Kong) ~~platform,~~Limited ~~our~~(“WuXi ~~competitors~~Biologics ~~may~~(Hong ~~use~~Kong)”). ~~our~~The ~~methods~~WuXi Biologics MSA governs certain development activities and good manufacturing practice (“GMP”) manufacturing and testing for the CR-001, orCR-002 ~~acquire~~and ~~similar~~CR-003 ~~expertise~~programs, inas well as potential future programs, on a work order tobasis. ~~develop~~Under ~~glycomimetic~~the ~~drug~~WuXi ~~candidates~~Biologics ~~and~~MSA, ~~progress~~we ~~these~~are ~~drug~~obligated ~~candidates~~to ~~through~~pay ~~clinical~~WuXi ~~development~~Biologics (Hong Kong) a service fee and ~~commercialization,~~all ~~which~~non-cancellable ~~could~~obligations ~~impair~~in ~~our~~the ~~ability~~amount tospecified ~~successfully~~in ~~commercialize~~each ~~our~~work ~~drug~~order ~~candidates~~associated orwith ~~otherwise~~the ~~limit~~agreement ~~our~~for ~~commercial~~the ~~opportunities~~provision of services.

The WuXi Biologics MSA terminates on the later of (i) October 31, 2029 or (ii) the completion of services under all work orders executed by the parties prior to October 31, 2029, unless terminated earlier. The term of each work order terminates upon completion of the services under such work order, unless terminated earlier. We can terminate the WuXi Biologics MSA or any work order (i) at any time upon 30 days’ prior written notice, or (ii) immediately upon written notice if WuXi Biologics (Hong Kong) fails to obtain or maintain required material governmental licenses or approvals. Either party may terminate a work order (i) at any time upon six months’ prior notice with reasonable cause, provided however that if WuXi Biologics (Hong Kong) terminates a work order in such manner, no termination or cancellation fees shall be paid by us and (ii) immediately for cause upon (a) the other party’s material breach that remains uncured for 30 days after notice of such breach, (b) the other party’s bankruptcy, or (c) a force majeure event that prevents performance for a period of at least 90 days.

~~Even~~WuXi ifCell weLine orLicense ~~our collaborators are able to commercialize any of our drug candidates, the drugs may become subject to unfavorable pricing regulations or third-party coverage and reimbursement policies.~~Agreement

~~Our~~On ~~and~~October ~~our collaborators’ ability to commercialize any of our drug candidates successfully would depend~~31, ~~in part~~2024, onwe ~~the~~entered ~~extent~~into toa ~~which~~cell ~~coverage~~line ~~and~~license ~~adequate~~agreement ~~reimbursement~~(the ~~for~~“Cell ~~these~~Line ~~drugs~~License ~~and~~Agreement”) ~~related~~with ~~treatments~~WuXi ~~will~~Biologics beIreland ~~available~~Limited ~~from~~(“WuXi ~~government~~Biologics ~~payor~~Ireland”). ~~programs~~Under at the ~~federal~~Cell ~~and~~Line ~~state~~License ~~levels authorities~~Agreement, ~~including~~we ~~Medicare~~received ~~and~~a ~~Medicaid~~non-exclusive, ~~private health insurers~~worldwide, ~~managed~~sublicensable ~~care~~license ~~plans~~to ~~and~~certain ~~other~~of ~~organizations.~~WuXi ~~Government~~Biologics ~~authorities~~Ireland’s ~~and third~~know-~~party payors~~how, ~~such~~cell ~~as private health insurers and health maintenance organizations~~line, ~~decide~~biological ~~which~~materials ~~medications they will pay for~~ and ~~establish~~media ~~reimbursement levels. A primary trend in the U.S. healthcare industry~~ and ~~elsewhere~~feeds isto ~~cost~~make, ~~containment.~~have ~~Government~~made, ~~authorities~~use, ~~and~~sell, ~~third-party payors~~ have ~~attempted~~sold, tooffer ~~control costs by limiting coverage and the amount of reimbursement~~ for ~~particular~~sale, ~~medications. Increasingly~~import, ~~third-party~~keep ~~payors are requiring that drug companies provide them with predetermined discounts from list prices~~ and ~~are~~otherwise ~~challenging~~deal ~~the~~in ~~prices charged for drugs. Coverage~~ and ~~reimbursement~~further ~~may not be available for any drug that we or our collaborators~~ commercialize ~~and,~~certain ~~even~~therapeutic ifproducts ~~these~~produced ~~are~~through ~~available,~~ the ~~level~~use of ~~reimbursement~~the ~~may~~cell ~~not~~line belicensed ~~satisfactory.~~by ~~Inadequate~~WuXi ~~reimbursement~~Biologics ~~levels~~Ireland ~~may~~under ~~adversely affect~~ the ~~demand~~Cell ~~for,~~Line orLicense ~~the~~Agreement price of, any drug candidate for which we or our collaborators obtain marketing approval. Obtaining and maintaining adequate reimbursement for our drugs may be difficult. We may be required to conduct expensive pharmacoeconomic studies to justify coverage and reimbursement or (the ~~level~~“WuXi ofBiologics ~~reimbursement~~Ireland ~~relative~~Licensed ~~to other therapies~~Products”). IfCR-001 ~~coverage~~ and ~~adequate~~CR-002 ~~reimbursement~~ are ~~not~~manufactured ~~available~~using orcell ~~reimbursement~~lines islicensed ~~available~~under ~~only~~Cell toLine ~~limited~~License ~~levels, we or our collaborators may not be able to successfully commercialize any drug candidates for which marketing approval is obtained~~Agreement.

In consideration for the license, we incurred a non-refundable license fee of $0.15 million. Additionally, if we manufacture all of our commercial supplies of bulk drug product for a particular product with a manufacturer other than

There may be significant delays in obtaining coverage and reimbursement for newly approved drugs, and coverage may be more limited than the indications for which the drug is approved by the FDA or similar regulatory authorities outside the United States. Moreover, eligibility for coverage and reimbursement does not imply that a drug 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 drugs, if applicable, may also not be sufficient to cover our costs and may not be made permanent. Reimbursement rates may vary according to the use of the drug and the clinical setting in which it is used, 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 drugs may be reduced by mandatory discounts or rebates required 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. Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement policies. However, one payor’s determination to provide coverage for a drug does not assure that other payors will also provide coverage for the drug. Our or our collaborators’ inability to promptly obtain coverage and adequate reimbursement rates from both government-funded and private payors for any approved drugs that we develop could adversely affect our operating results, our ability to raise capital needed to commercialize drugs and our overall financial condition.

The regulations that govern marketing approvals, pricing, coverage and reimbursement for new drugs vary widely from country to country. Current and future legislation may significantly change the approval requirements in ways that

Table of Contents

~~could~~WuXi ~~involve~~Biologics ~~additional~~Ireland ~~costs~~or ~~and~~its ~~cause~~affiliates, ~~delays~~we inare ~~obtaining~~required ~~approvals.~~to ~~Some~~make ~~countries~~royalty ~~require~~payments ~~approval~~to ofWuXi ~~the~~Biologics ~~sale~~Ireland ~~price~~in ofan aamount ~~drug~~equal ~~before~~to ita ~~can~~fraction beof ~~marketed.~~a Insingle ~~many~~digit ~~countries,~~percentage ~~the~~of ~~pricing~~global ~~review~~net ~~period~~sales ~~begins~~of ~~after~~the ~~marketing~~WuXi orBiologics ~~licensing~~Ireland ~~approval~~Licensed isProducts ~~granted.~~manufactured Inby ~~some~~a ~~foreign~~third-party ~~markets,~~manufacturer ~~prescription~~(the ~~pharmaceutical~~“Royalty”). ~~pricing~~If ~~remains~~we ~~subject~~manufacture topart ~~continuing~~of ~~governmental~~our ~~control~~commercial ~~even~~supplies ~~after~~of ~~initial~~the ~~approval~~WuXi isBiologics ~~granted.~~Ireland AsLicensed aProducts ~~result,~~with weWuXi orBiologics ~~our~~Ireland ~~collaborators~~or ~~might~~its ~~obtain~~affiliates, ~~marketing~~then ~~approval~~the ~~for~~Royalty awill ~~drug in a particular country, but then~~ be ~~subject~~reduced toaccordingly ~~price~~on ~~regulations~~a ~~that~~pro ~~delay~~rata ~~commercial~~basis. ~~launch~~We ofhave the ~~drug~~option, ~~possibly~~at ~~for~~any ~~lengthy~~ time ~~periods~~, ~~and~~to ~~negatively~~pay ~~impact~~WuXi ~~our~~Biologics ~~ability~~Ireland toa ~~generate~~non-refundable ~~revenue~~lump-sum ~~from~~royalty ~~the~~buyout ~~sale~~payment ofon ~~the~~a drug inproduct-by-drug ~~that~~product ~~country.~~basis ~~Adverse~~to ~~pricing~~extinguish ~~limitations~~future ~~may~~Royalty ~~hinder~~obligations ~~our~~with ~~ability~~respect to ~~recoup~~such ~~our investment in one or more~~ drug ~~candidates, even if our drug candidates obtain marketing approval~~product.

The Cell Line License Agreement will continue indefinitely unless terminated (i) by us upon six months’ prior written notice and our payment of all undisputed amounts due to WuXi Biologics Ireland through the effective date of termination, (ii) by WuXi Biologics Ireland for a material breach by us that remains uncured for 60 days after written notice, (iii) by WuXi Biologics Ireland if we fail to make a payment and such failure continues for 30 days after receiving notice of such failure, or (iv) by either party upon the other party’s bankruptcy.

~~There~~Charles ~~can~~River beMaster noServices assurance that our drug 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 our ability to sell our drug candidates profitably if they are approved for sale.Agreement

On December 6, 2024, we entered into a master services agreement (the “Charles River MSA”) with Charles River Laboratories, Inc. (“Charles River”). The Charles River MSA governs certain clinical development activities and GMP manufacturing and testing for the CR-001 and CR-002 programs on a non-exclusive, work order basis (each, a “Statement of Work”). Under the Charles River MSA, we are obligated to pay Charles River a service fee in the amount specified in each Statement of Work associated with the agreement for the provision of services. Charles River is obligated to, among other things, (i) perform manufacturing services in accordance with applicable standards and law using personnel with appropriate qualifications, and to manufacture product in accordance with cGMP, (ii) comply with confidentiality and invention assignment provisions, (iii) notify us of regulatory contact or communication and consult with us regarding the response to any inquiry or observation from any regulatory authority and (iv) assign to us all right, title and interest in and to all intellectual property created or developed in connection with the provision of the services, and all intellectual property relating to such inventions, subject to certain exceptions.

~~Product~~The ~~liability~~Charles ~~lawsuits~~River ~~against~~MSA usterminates ~~could~~on ~~cause~~the uslater toof ~~incur~~(i) ~~substantial~~December ~~liabilities~~6, ~~and~~2029, or (ii) the completion of services under all Statement of Works executed by the parties prior to ~~limit~~December ~~commercialization~~6, 2029, unless terminated earlier. The term of each Statement of Work terminates upon completion of the services under such Statement of Work, unless terminated earlier. We can terminate the Charles River MSA or any ~~drugs~~Statement ~~that~~of weWork ~~may~~(i) ~~develop~~at any time upon 30 days’ prior written notice, or (ii) for material breach of the Charles River MSA by Charles River, (x) upon 30 days’ prior written notice if such breach is not remedied within the 30 day notice period or (y) upon 15 days’ prior written notice if such breach is not capable of cure within such 30 day period. Charles River can terminate the Charles River MSA or any Statement of Work upon 30 days’ prior written notice for material breach of the Charles River MSA by us if such breach is not remedied within the 30 day notice period or if such breach is not capable of cure within such 30 day notice period. Charles River can terminate any Statement of Work at any time upon 30 days’ prior written notice.

We ~~face~~have anentered ~~inherent~~into ~~risk~~various Statements of ~~product~~Work ~~liability~~pursuant ~~exposure related~~ to the ~~testing~~Charles ofRiver ~~our~~MSA ~~drug~~for ~~candidates~~certain inassay ~~human~~development ~~clinical trials,~~ and ~~will~~toxicology ~~face~~work anrelated ~~even~~to ~~greater~~CR-001 ~~risk~~and ~~if we commercially sell any drugs that we may develop~~CR-002. If we cannot successfully defend ourselves against claims that our drug candidates or drugs caused injuries, we will incur substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:

●Intellectual ~~decreased~~Property ~~demand for any drug candidates or drugs that we may develop;~~

●We ~~injury~~strive to protect the proprietary programs and technologies that we believe are important to our ~~reputation~~business, including seeking and ~~significant~~maintaining ~~negative~~patent ~~media~~protection ~~attention;~~intended to cover the composition of matter of our programs, their methods of use and manufacture, related technologies, diagnostics, and other inventions.

●Paragon, ~~withdrawal~~jointly with Crescent in some instances, has filed U.S. provisional and non-provisional patent applications directed to antibodies that target PD-1 and VEGF, including applications covering composition of ~~clinical~~matter, ~~trial~~pharmaceutical ~~participants;~~formulations, and methods of using such antibodies, including CR-001. In addition, Paragon has filed U.S. provisional patent applications, and intends to file one or more additional U.S. provisional patent applications directed to ADCs against various oncology targets, including applications covering composition of matter, pharmaceutical formulations, and methods of using such ADCs, including CR-002. Pursuant to each of the CR-001 and CR-002 License Agreements, we have exclusively licensed the rights to such PD-1 or VEGF patent applications and ADC patent applications, respectively. If the existing non-provisional and provisional patent applications (if pursued non-provisionally) mature into one or more issued patents covering CR-001 or CR-002, we would expect those patents to expire between 2045 and 2046, absent any applicable patent term adjustments or extensions. In addition, Crescent, alone or jointly with Paragon, may opt to file one or more additional patent applications covering pharmaceutical formulations, dosing, and methods of using antibodies that target PD-1 and VEGF, including CR-001.

● significant costs to defend the related litigation;

● substantial monetary awards paid to trial participants or patients;

● loss of revenue;

● reduced resources of our management to pursue our business strategy; and

● the inability to commercialize any drugs that we may develop.

We have carried clinical trial insurance coverage in an amount that we believe was sufficient in relation to our clinical trials that were conducted in the United States and in foreign countries where we had sites. The use of our drug candidates in clinical trials may result in liability claims for which our insurance would not be adequate to cover all liabilities that we may incur. In addition, if we were to resume drug development activities, we may need to increase our insurance coverage as we expand our clinical trials or if we commence commercialization of our drug candidates. Insurance coverage is increasingly expensive. 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.

Table of Contents

~~Risks~~Kelun ~~Related~~has filed patent applications in certain jurisdictions directed to ~~Our~~antibodies ~~Intellectual~~and ~~Property~~ADCs that target ITGB6, including applications covering composition of matter and methods of using such antibodies and ADCs, including CR-003. In addition, Crescent, alone or jointly with Kelun, may opt to file one or more additional patent applications covering pharmaceutical formulations, dosing, and methods of using ADCs, including CR-003. Pursuant to the CR-003 License Agreement, Crescent has exclusively licensed the rights to such ITGB6 antibody patent applications and ADC patent applications outside of Greater China (including mainland China, Hong Kong, Macau, Taiwan). If the patent applications filed by Kelun mature into one or more issued patents covering CR-003, we would expect those patents to expire between 2042 and 2046, absent any applicable patent term adjustments or extensions.

~~Should~~Our wecommercial ~~resume~~success ~~drug~~will ~~development~~depend ~~activities~~in ~~but~~significant ~~are~~part ~~unable~~upon toobtaining ~~obtain~~ and ~~maintain~~maintaining patent protection and trade secret protection for our ~~drug~~targeted ~~candidates~~therapeutics and the methods used to develop and manufacture them, oras ifwell as successfully defending these patents against third-party challenges and operating without infringing on the ~~scope~~proprietary rights of ~~the~~others. ~~patent~~Our ~~protection~~ability ~~obtained~~to isstop ~~not~~third ~~sufficiently~~parties ~~broad~~from making, using, selling, offering to sell, or importing our ~~competitors~~products ~~could~~depends ~~develop~~on the extent to which we have rights under valid and ~~commercialize~~enforceable ~~drug~~patents ~~candidates~~or ~~similar~~trade secrets that cover these activities. We cannot be sure that patents will be granted with respect to any of our pending patent applications or ~~identical~~with respect to ~~ours~~any patent applications filed by us in the future, ~~and~~nor can we be sure that any of our ~~ability~~existing patents, or any patents granted to ~~successfully~~us ~~commercialize~~in the future, will be commercially useful in protecting our ~~drug~~targeted ~~candidates~~therapeutics, ~~may~~current beprograms ~~impaired~~and processes.

IfThe weterm ~~elect~~of toindividual ~~resume~~patents ~~our~~depends ~~drug~~upon ~~development~~the ~~activities,~~legal ~~our~~term ~~success~~of ~~would~~the ~~depends~~patents in ~~large~~the ~~part~~countries onin ~~our~~which ~~ability~~they toare ~~obtain~~obtained. ~~and~~In ~~maintain~~most countries in which we file, including the United States, the patent ~~protection~~term inis 20 years from the earliest date of filing a non-provisional patent application. In the United States, a patent’s term may potentially be lengthened by patent term adjustment (“PTA”), which compensates a patentee for administrative delays by the USPTO in examining and ~~other~~granting ~~countries~~a ~~with~~patent. ~~respect~~In tothe ~~our~~United States, the patent term of a patent that covers an FDA-approved drug ~~candidates~~may also be eligible for PTE, which permits patent term restoration as compensation for the patent term lost during the FDA regulatory review process. WeThe ~~have~~Hatch-Waxman inAct permits PTE of up to five years beyond the ~~past~~expiration ~~sought~~of the patent. The length of the PTE accorded a patent is related to ~~protect~~the ~~our~~length ~~proprietary~~of ~~position~~time the drug is under regulatory review by ~~filing~~the FDA. PTE cannot extend the remaining term of a patent ~~applications~~beyond ina total of 14 years from the ~~United~~date ~~States~~of ~~and~~product ~~abroad~~approval. ~~related~~Further, only one patent applicable to ~~our~~an approved drug ~~candidates~~may be extended, and ~~would~~only ~~need~~those toclaims ~~maintain~~covering the approved drug, a method for using it, or a method for manufacturing it may be extended. Similar provisions for extending the term of a patent that covers an approved drug are available in multiple European countries and other foreign jurisdictions. In the future, if and when our ~~intellectual~~products ~~property~~receive ~~rights~~FDA ~~should~~approval, we ~~decide~~expect to ~~further~~apply ~~pursue~~for ~~the~~patent ~~development~~term extensions on patents covering those products. We expect to seek patent term extensions to all of our issued patents in any jurisdiction where these are available; however, there is no guarantee that the applicable authorities, including the FDA in the United States, will agree with our assessment of ~~those~~whether ~~drug~~such ~~candidates~~extensions should be granted, and if granted, the length of such extensions. Patent term in the U.S. may be shortened if a patent is terminally disclaimed over an earlier-filed patent.

In some instances, we file provisional patent applications directly in the USPTO. Provisional patent applications are designed to provide a lower-cost first patent filing in the United States. Corresponding non-provisional patent applications must be filed not later than 12 months after the provisional application filing date. The corresponding non-provisional application benefits in that the priority date(s) of the non-provisional patent application is/are the earlier provisional application filing date(s), and the patent term of the finally issued patent is calculated from the earliest non-provisional application filing date. This system allows us to obtain an early priority date, obtain a later start to the patent term and to delay prosecution costs, which may be useful in the event that we decide not to pursue examination in a subsequent non-provisional application. While we intend, as appropriate, to timely file non-provisional patent applications relating to our provisional patent applications, we cannot predict whether any such non-provisional patent applications will result in the issuance of patents that provide us with any competitive advantage.

~~The~~We ~~patent~~intend ~~prosecution~~to ~~process~~file isU.S. ~~expensive~~non-provisional applications and/or ~~time~~international ~~consuming~~Patent Cooperation Treaty (“PCT”) applications that claim the benefit of the priority date of earlier filed provisional or non-provisional applications, ~~and~~when weapplicable. ~~may~~The ~~not~~PCT besystem ~~able~~allows for a single PCT application to ~~file~~be ~~and~~filed ~~prosecute~~within ~~all~~12 ~~necessary~~months orof ~~desirable~~the priority filing date of a corresponding priority patent ~~applications~~application, atsuch as a ~~reasonable~~U.S. ~~cost~~provisional or non-provisional application, and to designate all of the 158 PCT contracting states in awhich ~~timely~~national ~~manner~~phase patent applications can later be pursued based on the PCT application. ItThe isPCT ~~also~~International ~~possible~~Searching ~~that~~Authority weperforms ~~will~~a ~~fail~~patentability search and issues a non-binding patentability opinion, which can be used to ~~identify~~evaluate ~~patentable~~the ~~aspects~~chances of ~~our~~success ~~research~~for ~~and~~the ~~development~~national ~~output~~applications ~~before~~in itforeign iscountries ~~too~~prior ~~late~~to having to ~~obtain~~incur ~~patent~~the ~~protection~~filing fees. WeAlthough ~~may~~a PCT application does not ~~have~~issue as a patent, it allows the ~~right~~applicant to ~~control~~establish ~~the~~a ~~preparation,~~patent application filing ~~and~~date ~~prosecution~~in any of ~~patent~~the member states and then seek patents through later-filed national-phase applications,. No later than either 30 or to31 ~~maintain~~months from the ~~rights~~earliest topriority ~~patents~~date ~~licensed~~of tothe ~~third~~PCT ~~parties. Therefore~~application, ~~these~~separate ~~patents~~national ~~and~~phase patent applications ~~may~~can ~~not~~ be ~~prosecuted~~pursued ~~and~~in ~~enforced~~any inof athe ~~manner~~PCT ~~consistent~~member ~~with~~states, ~~the~~depending ~~best~~on ~~interests~~the ofdeadline ~~our~~set ~~business.~~by

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 vice versa. For example, European patent law restricts the patentability of methods of treatment of the human body more than U.S. law does. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing or, in some cases, not at all. Therefore, we cannot know with certainty whether we were the first to make the inventions claimed in our 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, validity, enforceability and commercial value of our patent rights are highly uncertain. Our patent applications may not result in patents being issued that protect our drug candidates, in whole or in part, or which effectively prevent others from commercializing competitive drug candidates. 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.

Recent patent reform legislation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents. 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 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, became effective on March 16, 2013. Accordingly, it is not clear what, if any, impact the Leahy-Smith Act will have on the operation of our business if we were to continue the development of our drug candidates. However, 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, all of which could have a material adverse effect on our business and financial condition.

Moreover, we may be subject to a third-party preissuance submission of prior art to the U.S. Patent and Trademark Office, or become involved in opposition, 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 drug candidates 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 license, develop or commercialize current or future drug candidates.

Table of Contents

~~Even~~individual ifcontracting ~~our~~states. ~~patent~~National ~~applications~~phase ~~issue~~entry ascan ~~patents,~~generally ~~they~~be ~~may~~accomplished ~~not~~through ~~issue~~direct national filing or, in some cases, through a ~~form~~regional ~~that~~patent ~~will~~organization, ~~provide~~such usas ~~with~~the ~~any~~European ~~meaningful~~Patent ~~protection~~Organization. The PCT system delays application filing expenses, ~~prevent~~allows ~~competitors~~a ~~from~~limited ~~competing~~evaluation ~~with~~of usthe orchances ~~otherwise~~of ~~provide~~success usfor ~~with~~national/regional ~~any~~patent ~~competitive~~applications ~~advantage.~~and ~~Our~~allows ~~competitors~~for ~~may~~substantial besavings ~~able~~in comparison to ~~circumvent~~having ~~our~~filed ~~patents~~individual bycountries ~~developing~~rather ~~similar~~than ora ~~alternative~~PCT ~~drug~~application ~~candidates~~ in athe ~~non-infringing~~event ~~manner~~that no national phase applications are filed.

For all patent applications, we determine claiming strategy on a case-by-case basis. Advice of counsel and our business model and needs are always considered. We file patent applications containing claims for protection of all commercially relevant uses of our proprietary technologies and any products, as well as all new applications and/or uses we discover for existing technologies and products, assuming these are strategically valuable. We may periodically reassess the number and type of patent applications, as well as the pending and issued patent claims to ensure that coverage and value are obtained for our processes, and compositions, given existing patent law and court decisions. Further, claims may be modified during patent prosecution to meet our intellectual property and business needs.

InWe ~~addition,~~recognize that the ~~issuance~~ability ofto aobtain patent isprotection ~~not~~and ~~conclusive~~the asdegree toof ~~its~~such ~~inventorship,~~protection ~~scope,~~depends ~~validity~~on ora ~~enforceability~~number of factors, ~~and~~including ~~our~~the ~~patents~~extent ~~may~~of bethe ~~challenged~~prior inart, the ~~courts~~novelty orand ~~patent~~non-obviousness ~~offices~~of in the ~~United~~invention, ~~States~~ and ~~abroad.~~the ~~Such~~ability ~~challenges~~to ~~may~~satisfy ~~result~~subject inmatter, ~~loss~~written ofdescription, ~~exclusivity~~and orenablement ~~freedom~~requirements toof ~~operate~~the orvarious in patent ~~claims~~jurisdictions. ~~being~~In ~~narrowed~~addition, ~~invalidated~~the orcoverage ~~held~~claimed ~~unenforceable,~~ in ~~whole~~a orpatent inapplication ~~part,~~can ~~which~~be ~~could~~significantly ~~limit~~reduced ~~our~~before ~~ability~~the topatent ~~stop~~is ~~others~~issued, ~~from~~and ~~using~~its orscope ~~commercializing~~can ~~similar~~be reinterpreted or ~~identical~~further ~~drug~~altered ~~candidates~~even after patent issuance. Consequently, orwe ~~limit~~may ~~the~~not ~~duration~~obtain ofor ~~the~~maintain adequate patent protection for any of our ~~drug~~targeted ~~candidates~~therapeutics. ~~Given~~We ~~the~~cannot ~~amount~~predict ofwhether ~~time required for~~ the ~~development,~~patent ~~testing~~applications ~~and~~we ~~regulatory~~are ~~review~~currently ofpursuing ~~new~~will ~~drug~~be ~~candidates,~~issued as patents ~~protecting~~in ~~such~~any ~~candidates~~particular ~~might~~jurisdiction ~~expire before~~ or ~~shortly~~whether ~~after~~the ~~such~~claims ~~candidates~~of ~~are~~any ~~commercialized.~~issued Aspatents awill ~~result,~~provide ~~our~~sufficient ~~patent~~proprietary ~~portfolio~~protection ~~may~~from ~~not~~competitors. ~~provide~~Any uspatents ~~with~~that ~~sufficient~~we ~~rights~~hold tomay ~~exclude~~be ~~others~~challenged, ~~from~~circumvented ~~commercializing drugs similar~~ or ~~identical~~invalidated toby ~~ours~~third parties.

In addition to patents, we rely upon unpatented trade secrets, know-how and continuing technological innovation to develop and maintain our competitive position. However, trade secrets and know-how can be difficult to protect. We seek to protect our proprietary information, in part by executing confidentiality agreements with our collaborators and scientific advisors, and non-competition, non-solicitation, confidentiality and invention assignment agreements with our employees and consultants. We have also executed agreements requiring assignment of inventions with selected scientific advisors and collaborators. The confidentiality agreements we enter into are designed to protect our proprietary information and the agreements or clauses requiring assignment of inventions to us are designed to grant us ownership of technologies that are developed through our relationship with the respective counterparty. We cannot guarantee, however, that we have executed such agreements with all applicable counterparties, that such agreements will not be breached, or that these agreements will afford us adequate protection of our intellectual property and proprietary rights.

WeThe ~~may~~patent ~~become~~positions ~~involved~~of biotechnology companies like us are generally uncertain and involve complex legal, scientific and factual questions. Our commercial success will also depend in ~~lawsuits~~part on not infringing upon the proprietary rights of third parties. It is uncertain whether the issuance of any third-party patent would require us to ~~protect~~alter our development or ~~enforce~~commercial strategies, or our ~~patents~~products or ~~other~~processes, ~~intellectual~~obtain ~~property,~~licenses or cease certain activities. Our breach of any license agreements or our failure to obtain a license to proprietary rights required to develop or commercialize our future products may have a material adverse impact on us. If third parties prepare and file patent applications in the United States that also claim technology to which ~~could~~we behave ~~expensive~~rights, ~~time~~we ~~consuming~~may ~~and~~have ~~unsuccessful~~to participate in interference or derivation proceedings in the USPTO to determine priority of invention.

~~Competitors~~When ~~may~~available ~~infringe~~to ~~our~~expand ~~issued~~market ~~patents or other intellectual property. To counter infringement or unauthorized use~~exclusivity, weour ~~may~~strategy beis ~~required~~ to ~~file infringement claims~~obtain, ~~which~~or ~~can~~license beadditional ~~expensive~~intellectual ~~and~~property ~~time~~related ~~consuming. Any claims we assert against perceived infringers could provoke these parties~~ to ~~assert~~current ~~counterclaims~~or ~~against~~contemplated usdevelopment ~~alleging that we infringe their patents. In addition~~platforms, incore aelements ~~patent infringement proceeding, a court may decide that a patent~~ of ~~ours is invalid or unenforceable, in whole or in part, construe the patent’s claims narrowly or refuse to stop the other party from using the~~ technology ~~at issue on the grounds that our patents do not cover the technology. An adverse result in any litigation proceeding could put one~~ and/or ~~more~~programs ofand ~~our~~targeted ~~patents at risk of being invalidated or interpreted narrowly~~therapeutics.

For more information regarding the risks related to our intellectual property, see the section titled “Risk Factors - Risks Related to Our Intellectual Property.”

WeCommercial ~~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.~~

AShould ~~third~~any ~~party~~of ~~may~~our ~~hold~~product ~~intellectual~~candidates ~~property,~~be ~~including~~approved ~~patent~~for commercialization, ~~rights~~we ~~that~~intend ~~are~~to ~~important~~develop ora ~~necessary~~plan to commercialize them in the ~~development~~United ofStates ~~our~~and ~~drug~~other ~~candidates~~key ~~should~~markets, wethrough ~~elect~~internal toinfrastructure ~~resume~~and/or ~~such~~external ~~activities.~~partnerships Itin ~~may~~a bemanner ~~necessary~~that ~~for~~will enable us to ~~use~~realize ~~patented~~the orfull ~~proprietary~~commercial ~~technology~~value of ~~third~~our ~~parties~~programs. toGiven ~~commercialize~~ our ~~drug~~stage ~~candidates~~of development, ~~in which case~~ we ~~would~~have benot ~~required~~yet toestablished ~~obtain~~ a ~~license~~commercial ~~from~~organization ~~these third parties on commercially reasonable terms,~~ or ~~our~~distribution ~~business could be harmed, possibly materially~~capabilities.

Manufacturing

Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could have a material adverse effect on the success of our business.

If we were to resume drug development, our commercial success would depend upon our ability, and the ability of our collaborators, to develop, manufacture, market and sell our drug candidates without infringing the proprietary rights of third parties. There is considerable intellectual property litigation in the biotechnology and pharmaceutical industries. We may become party to, or threatened with, future adversarial proceedings or litigation regarding intellectual property rights with respect to our drug candidates, including 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 drug candidates. 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 drug. 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 drug candidates or force us to cease some of our business operations. Claims that we have misappropriated the confidential information or trade secrets of third parties could have a similar negative impact on our business.

Table of Contents

We ~~may~~do benot ~~subject~~currently own or operate facilities for product manufacturing, testing, storage, and distribution. We have contracted and expect to ~~claims~~continue byto contract with third parties ~~asserting~~for ~~that~~the wemanufacture orand ~~our~~distribution ~~employees~~of ~~have~~our ~~misappropriated~~product ~~their~~candidates. ~~intellectual~~For ~~property~~additional information, orsee ~~claiming~~the ~~ownership~~description of ~~what~~the WuXi Biologics Master Services Agreement, WuXi Cell Line License Agreement, and Charles River Master Services Agreement above. Because we ~~regard~~rely ason ~~our~~contract ~~own~~manufacturers, ~~intellectual~~we ~~property~~employ personnel with extensive technical, manufacturing, analytical, and quality experience. Our team has deep knowledge and understanding of the regulations that govern manufacturing, documentation, quality assurance, and quality control of drug supply that are required to support our regulatory filings.

~~Many~~Competition of our current and former employees were previously employed at universities or other biotechnology or pharmaceutical companies. Although we have tried to ensure that our employees do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that these employees or we have used or disclosed intellectual property, including trade secrets or other proprietary information, of any such employee’s former employer. Litigation may be necessary to defend against these claims.

The biotechnology and biopharmaceutical industries are characterized by continuing technological advancement and significant competition. While we believe that our programs, technology, development experience and scientific knowledge provide us with competitive advantages, we face competition from major pharmaceutical and biotechnology companies, academic institutions, governmental agencies, and public and private research institutions, among others. Any product candidates that we successfully develop and commercialize will compete with existing therapies and new therapies that may become available in the future. Many of the companies with which we are currently competing or will compete against in the future have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals, and marketing approved products than we do. Mergers and acquisitions in the pharmaceutical and biotechnology industry may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel, establishing clinical trial sites, patient enrollment for clinical trials as well as in acquiring technologies complementary to, or necessary for, our programs.

InKey ~~addition,~~competitive ~~while~~factors itaffecting isthe ~~our~~success ~~policy~~of toall ~~require~~of our ~~employees~~product ~~and~~candidates ~~contractors~~that ~~who~~we ~~may~~develop, beif ~~involved~~approved, inare ~~the~~likely ~~development~~to ofbe ~~intellectual~~efficacy, ~~property~~safety, toconvenience, ~~execute~~presentation, ~~agreements~~price, ~~assigning~~the ~~such~~level ~~intellectual~~of ~~property~~generic ~~to us~~competition, weand ~~may~~the beavailability ~~unsuccessful~~of inreimbursement ~~executing~~from ~~such~~government anand ~~agreement~~other ~~with each~~ third-party ~~who in fact develops intellectual property that we regard as our own~~payors. Our ~~assignment~~competitors ~~agreements~~ may ~~not~~also beobtain ~~self-executing~~FDA or ~~may~~other beregulatory ~~breached,~~approval ~~and~~for wetheir ~~may~~products bemore ~~forced~~rapidly tothan ~~bring~~we ~~claims~~may ~~against~~obtain ~~third~~approval ~~parties,~~for orour ~~defend~~products, ~~claims~~which ~~they~~could ~~may~~result ~~bring~~in ~~against~~our ~~us,~~competitors toestablishing ~~determine~~a ~~the~~strong ~~ownership~~market ofposition ~~what~~before we ~~regard~~are asable ~~our~~to ~~intellectual~~enter ~~property~~the market.

Specifically, there are several companies developing or marketing treatments that may be approved for the same indications and/or diseases as our most advanced program, CR-001, including major pharmaceutical companies, and our other programs, CR-002 and CR-003. We do not yet have clinical data for any of our programs and there can be no assurance that our programs will have similar or comparable results, or that our results will support regulatory approval.

IfThere weare ~~fail~~several inapproved ~~prosecuting~~immuno-oncology orbiologic ~~defending~~therapies ~~any~~for ~~such~~the ~~claims~~treatment of solid tumor indications, inincluding, ~~addition~~but not limited to, ~~paying~~anti-PD-1 ~~monetary~~therapies ~~damages,~~Keytruda we(pembrolizumab; ~~may~~Merck) ~~lose~~and ~~valuable~~Opdivo ~~intellectual~~(nivolumab; ~~property~~Bristol ~~rights~~Myers orSquibb), ~~personnel.~~as ~~Even~~well ifas weapproved ~~are~~anti-PD-L1 ~~successful~~therapies inTecentriq® ~~prosecuting~~(atezolizumab; orGenentech) ~~defending~~and ~~against~~Imfinzi® ~~such~~(durvalumab; ~~claims,~~AstraZeneca). ~~litigation~~Future ~~could~~biosimilars ~~result~~and other therapies in ~~substantial~~development ~~costs~~may ~~and~~also beserve aas ~~distraction~~competition tofor ~~management~~our product candidates.

In addition, we are aware of several anti-PD-(L)1/VEGF bispecific product candidates in clinical development for solid tumor indications, including, but not limited to, ivonescimab (Summit Therapeutics Inc.), pumitamig (co-developed by BioNTech SE and Bristol Myers Squibb), LM-299 (LaNova Medicines Ltd.; in-licensed by Merck), SSGJ-707 (3SBio Inc.; in-licensed by Pfizer), and CTX-10726 (Compass Therapeutics, Inc.).

~~Intellectual~~Regarding ~~property~~ADC ~~litigation~~development, ~~could~~we ~~cause~~are usaware toof ~~spend~~other ~~substantial~~ADC ~~resources~~product ~~and~~candidates ~~distract~~in ~~our~~clinical ~~personnel~~development ~~from~~for ~~their~~solid ~~normal~~tumor ~~responsibilities~~indications, including, but not limited to, PDL1V (Pfizer), HLX-43 (Henlius), sigvotatug vedotin (Pfizer).

~~Even~~Government ifRegulation 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, and if securities analysts or investors perceive these results to be negative it could have a substantial adverse effect on the price of our common stock. Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for potential 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.

The FDA and other regulatory authorities at federal, state and local levels, as well as in foreign countries, extensively regulate, among other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring and post-approval reporting of biologics such as those we are developing. We, along with our third-party contractors, will be required to navigate the various preclinical, clinical and commercial approval requirements of the governing regulatory authorities of the countries in which we wish to conduct studies or seek approval or licensure of our product candidates. Generally, before a new therapeutic product can be marketed, considerable data demonstrating a biological product candidate’s quality, safety, purity and potency, or a small molecule drug candidate’s quality, safety and

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

In addition to seeking patents for our drug candidates, we have also relied on trade secrets, including unpatented know-how, technology and other proprietary information, to maintain our historical competitive position. For example, our platform was based on trade secrets that consist largely of expertise in carbohydrate chemistry and knowledge of carbohydrate biology. We do not believe that we can obtain patent protection for our platform. Thus, our competitors may use our methods, or acquire similar expertise, in order to develop glycomimetic drug candidates and progress these drug candidates through clinical development and commercialization, which could impair our ability to successfully commercialize our drug candidates.

We have sought 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 have also entered into confidentiality and invention or patent assignment agreements with our current and former employees and consultants. Despite these efforts, any of these parties may breach the agreements and disclose our proprietary information, including our trade secrets, and we may not be able to obtain adequate remedies for 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. 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 it, from using that technology or information to compete with us. If any of

Table of Contents

~~our~~efficacy, ~~trade~~must ~~secrets~~be ~~were~~obtained, organized into a format specific for each regulatory authority, submitted for review and approved by the regulatory authority. For biological product candidates, potency is similar to beefficacy ~~disclosed~~and is interpreted to mean the specific ability or ~~independently~~capacity ~~developed~~of the product, as indicated by aappropriate ~~competitor,~~laboratory ~~our~~tests ~~competitive~~or ~~position~~by ~~would~~adequately becontrolled ~~harmed~~clinical data obtained through the administration of the product in the manner intended, to effect a given result.

Failure to comply with the applicable U.S. requirements at any time during the product development process, approval process or post-marketing may subject an applicant to administrative or judicial sanctions. These sanctions could include, among other actions, the FDA’s refusal to approve pending applications from the sponsor, withdrawal of an approval, a clinical hold, untitled or warning letters, product recalls or market withdrawals, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement and civil or criminal penalties. Any agency or judicial enforcement action could have a material adverse effect on us and our products or product candidates.

~~Risks~~U.S. ~~Related~~Biologics toRegulation ~~Regulatory Approval of Our Drug Candidates and Other Legal Compliance Matters~~

~~Should~~In wethe ~~resume~~United ~~development~~States, ofbiological ~~our~~products ~~drug~~(or ~~candidates~~“biologics”) ~~but~~are wesubject orto ~~our~~regulation ~~collaborators~~under ~~are~~the ~~not~~FDCA, ~~able~~the toPublic ~~obtain,~~Health orService ifAct ~~there~~(“PHSA”) ~~are~~and ~~delays~~other infederal, ~~obtaining~~state, ~~required~~local, and foreign statutes and regulations. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, westate, orand ~~they~~local ~~would~~statutes ~~not~~and beregulations ~~able~~requires tothe ~~commercialize~~expenditure ~~our~~of ~~drug~~substantial ~~candidates~~time and ~~our~~financial ~~ability~~resources. Failure to ~~generate~~comply ~~revenue~~with ~~would~~the beapplicable ~~materially~~U.S. ~~impaired~~requirements at any time during the product development process, approval process or following approval may subject an applicant to administrative action and judicial sanctions. The process required by the FDA before biologic product candidates may be marketed in the United States generally involves the following:

In•completion ~~the event that we resume development~~ of ~~our~~certain ~~drug~~preclinical ~~candidates,~~laboratory ~~the~~tests ~~activities associated with their development~~ and ~~commercialization,~~animal ~~including~~studies ~~their~~performed design, testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale and distribution, would be subject to comprehensive regulation by the FDA and other regulatory agencies in ~~the~~accordance ~~United~~with ~~States and by~~ the EMA and similar regulatory authorities outside the United States. Failure to obtain marketing approval for a drug candidate would prevent us or our collaborators from commercializing the drug candidate. We have not received approval to market any of our drug candidates from regulatory authorities in any jurisdiction. We have only limited experience in filing and supporting the applications necessary to gain marketing approvals and would expect to rely on third-party CROs to assist us in this process. Securing marketing approval requires the submission of extensive preclinical and clinical data and supporting information to regulatory authorities for each therapeutic indication to establish the drug candidateFDA’s ~~safety~~current ~~and~~Good ~~efficacy.~~Laboratory ~~Securing~~Practices ~~marketing~~(“GLP”) ~~approval~~regulations; also requires the submission of information about the product manufacturing process to, and inspection of manufacturing facilities by, applicable regulatory authorities. Our drug candidates may not be effective, may be only moderately effective or may prove to have undesirable or unintended side effects, toxicities or other characteristics that may preclude our ability to obtain marketing approval or prevent or limit commercial use. If any of our drug candidates receives marketing approval, the accompanying label may limit the approved use of our drug, which could limit sales of the drug.

•submission to the FDA of an IND, which must become effective before clinical trials may begin;

~~The process of obtaining marketing approvals, both in the United States and abroad, is expensive and may take many years if additional clinical trials are required, if~~ •approval isby ~~obtained~~an atindependent ~~all,~~institutional ~~and~~review ~~can~~board ~~vary substantially based upon a variety of factors~~(“IRB”), ~~including the type, complexity and novelty of the drug candidates involved. Changes in marketing approval policies during the development period, changes in~~ or ~~the~~ethics ~~enactment~~committee ofat ~~additional statutes or regulations or changes in regulatory review for~~ each submitted drug application may cause delays in the approval or rejection of an application. Regulatory authorities have substantial discretion in the approval process and may refuse to accept any application, or may decide that our data are insufficient for approval and require additional preclinical, clinical orsite ~~other~~before ~~studies. In addition, varying interpretations of~~ the ~~data~~trial ~~obtained~~is ~~from~~commenced; preclinical and clinical testing could delay, limit or prevent marketing approval of a drug candidate. Any marketing approval we ultimately obtain may be limited or subject to restrictions or post-approval commitments that render the approved drug not commercially viable.

•manufacture of the proposed biologic candidate in accordance with current good manufacturing practices (“cGMPs”);

If•performance weof ~~resume~~adequate ~~development~~and ~~activities~~well-controlled ~~but~~human ~~experience~~clinical ~~delays~~trials in ~~obtaining~~accordance ~~approval~~with orGCP ifrequirements ~~we fail~~ to ~~obtain~~establish ~~approval~~the ~~of our drug candidates~~safety, ~~the~~purity ~~commercial~~and ~~prospects~~potency ~~for~~of ~~our~~the ~~drug~~proposed ~~candidates~~biologic ~~may~~product becandidate ~~harmed~~for ~~and~~its ~~our~~intended ~~ability~~purpose; ~~to generate revenue will be materially impaired.~~

•preparation of and submission to the FDA of a BLA;

~~Even~~•satisfactory ~~though~~completion weof ~~previously~~an ~~obtained~~FDA ~~Orphan~~Advisory ~~Drug~~Committee ~~designation for several of our drug candidates~~review, weif ~~may~~applicable; ~~not be able to obtain orphan drug marketing exclusivity for these or any of our other drug candidates should we resume their development.~~

~~Regulatory~~•a ~~authorities~~determination inby ~~some jurisdictions, including~~ the ~~United States and the European Union, or EU, may designate drugs for relatively small patient populations as orphan drugs. Under the Orphan Drug Act, the~~ FDA ~~may~~within ~~designate~~60 adays ~~drug as an orphan drug if it is intended to treat a rare disease or condition, which is generally defined as a patient population~~ of ~~fewer~~its ~~than~~receipt ~~200,000 individuals annually in the United States. We previously obtained Orphan Drug designation from the FDA for some~~ of ~~our~~a ~~drug~~BLA ~~candidates. However, in order~~ to ~~obtain~~file ~~marketing exclusivity in a particular jurisdiction, we must receive~~ the ~~first~~application ~~marketing approval of the drug~~ for ~~its intended indication. In addition, the orphan designation does not convey any advantage in, or shorten the duration of, the regulatory~~ review; ~~or approval process.~~

•satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the proposed product is produced to assess compliance with cGMPs, and to assure that the facilities, methods and controls are adequate to preserve the biological product’s continued safety, purity and potency;

~~Generally,~~•satisfactory ifcompletion aof ~~drug~~potential ~~with~~audit anof ~~orphan~~selected ~~designation~~clinical ~~subsequently~~investigation ~~receives~~sites ~~the first marketing approval for the indication for which it has such designation, the drug is entitled~~ to aassess ~~period~~compliance ofwith ~~marketing~~GCPs; ~~exclusivity,~~and ~~which precludes the~~

•FDA review and approval of a BLA to permit commercial marketing of the product for particular indications for use in the United States.

Preclinical and Clinical Development

Prior to beginning any clinical trial with a product candidate, in the United States, the sponsor must submit an IND to the FDA. An IND is a request for authorization from the FDA to administer an investigational drug product to humans. The central focus of an IND submission is on the general investigational plan and the protocol or protocols for preclinical studies and clinical trials. The IND also includes results of animal and in vitro studies assessing the toxicology, pharmacokinetics, pharmacology and pharmacodynamic characteristics of the product, chemistry, manufacturing and controls information, and any available human data or literature to support the use of the investigational product. An IND must become effective before human clinical trials may begin. The IND automatically becomes effective 30 days after

Table of Contents

~~FDA~~receipt orby the ~~EMA~~FDA, ~~from~~unless ~~approving another marketing application for~~ the ~~same~~FDA, ~~drug~~within ~~for~~ the ~~same~~30-day ~~indication for that time~~ period., ~~The~~raises ~~applicable~~safety ~~period~~concerns isor ~~seven~~questions ~~years~~about in the ~~United~~proposed ~~States~~clinical ~~and 10 years in the EU~~trial. ~~The~~In EUsuch ~~exclusivity period can be reduced to six years if~~ a ~~drug~~case, ~~no longer meets~~ the ~~criteria~~IND ~~for orphan designation or if the drug is sufficiently profitable so that market exclusivity is no longer justified. Orphan drug exclusivity~~ may be ~~lost~~placed ifon ~~the~~clinical ~~FDA~~hold orand the ~~EMA~~IND ~~determines~~sponsor, ~~that~~and the ~~request~~FDA ~~for~~must ~~designation~~resolve ~~was~~any ~~materially~~outstanding ~~defective~~concerns or ifquestions before the ~~manufacturer~~clinical istrial ~~unable~~can tobegin. ~~assure~~Submission ~~sufficient~~of ~~quantity~~an ofIND ~~the~~therefore ~~drug~~may toor ~~meet~~may ~~the~~not ~~needs~~result ofin ~~patients~~FDA ~~with~~authorization ~~the~~to ~~rare~~begin ~~disease~~a orclinical ~~condition~~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, among other things, 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 and for any subsequent protocol amendments. While the IND is active, progress reports summarizing the results of the clinical trials and nonclinical studies performed since the last progress report, among other information, must be submitted at least annually to the FDA, and written IND safety reports must be submitted to the FDA and 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 or investigator brochure.

~~Even~~Furthermore, ~~though~~an weindependent ~~have~~IRB ~~obtained~~for ~~orphan~~each ~~drug~~site ~~exclusivity~~proposing to conduct the clinical trial must review and approve the plan for aany ~~drug~~clinical ~~candidate,~~trial and its informed consent form before the clinical trial begins at that ~~exclusivity~~site, and must monitor the study until completed. Regulatory authorities, the IRB or the sponsor may ~~not~~suspend ~~effectively~~a ~~protect~~clinical trial at any time on various grounds, including a finding that the ~~candidate~~subjects ~~from~~are ~~competition~~being ~~because~~exposed ~~different~~to ~~drugs~~an ~~can~~unacceptable behealth ~~approved~~risk ~~for~~or that the ~~same~~trial ~~condition~~is unlikely to meet its stated objectives. ~~Even~~Some ~~after~~studies also include oversight by an ~~orphan~~independent ~~drug~~group isof ~~approved,~~qualified experts organized by the ~~FDA~~clinical ~~can~~study ~~subsequently~~sponsor, ~~approve~~known ~~another~~as ~~drug~~a ~~with~~data ~~the~~safety ~~same~~monitoring ~~active~~board, ~~moiety~~which provides authorization for ~~the~~whether ~~same~~or ~~condition~~not ifa ~~the~~study ~~FDA~~may ~~concludes~~move ~~that~~forward at designated check points based on access to certain data from the ~~later~~study ~~drug~~and ismay ~~clinically~~halt ~~superior~~the inclinical ~~that~~trial if it determines that there is ~~shown~~an tounacceptable besafety ~~safer,~~risk ~~more~~for ~~effective~~subjects or ~~makes~~other agrounds, ~~major~~such ~~contribution~~as no demonstration of efficacy. There are also requirements governing the reporting of ongoing preclinical studies and clinical trials and clinical study results to ~~patient~~public ~~care~~registries.

For purposes of BLA approval, human clinical trials are typically conducted in three sequential phases that may overlap.

~~Even~~•Phase if1. weThe ~~were~~investigational toproduct ~~resume~~is initially introduced into healthy human subjects or patients with the ~~development~~target ofdisease ~~uproleselan,~~or condition. These studies are designed to test the ~~FDA~~safety, ~~fast~~dosage ~~track~~tolerance, ~~designation~~absorption, metabolism and ~~additional~~distribution ~~breakthrough~~of ~~therapy~~the ~~designation~~investigational ~~for~~product ~~uproleselan~~in ~~may~~humans, ~~not~~the ~~actually~~side ~~lead~~effects toassociated awith ~~faster~~increasing ~~development~~doses, orand, ~~regulatory~~if ~~review~~possible, orto ~~approval~~gain ~~process~~early evidence on effectiveness.

If•Phase a2. ~~drug~~The isinvestigational ~~intended~~product ~~for~~is ~~the~~administered ~~treatment~~to of a ~~serious~~limited orpatient ~~life-threatening~~population ~~disease~~with ora ~~condition~~specified ~~and the drug demonstrates the potential to address unmet medical needs for this~~ disease or condition, ~~the~~to ~~drug~~evaluate ~~sponsor may apply for~~ the ~~FDA~~preliminary ~~fast track designation. If fast track designation is obtained~~efficacy, ~~the~~optimal ~~FDA~~dosages ~~may~~and ~~initiate~~dosing ~~review~~schedule ofand ~~sections~~to ofidentify apossible ~~NDA~~adverse ~~before~~side ~~the~~effects ~~application~~and issafety ~~complete~~risks. ~~This~~Multiple ~~“rolling~~Phase ~~review”~~2 isclinical ~~available~~trials ifmay ~~the~~be ~~applicant~~conducted ~~provides,~~to ~~and~~obtain ~~the~~information ~~FDA~~prior ~~approves,~~to abeginning ~~schedule~~larger ~~for~~and ~~submission~~more ofexpensive ~~the~~Phase ~~individual~~3 ~~sections~~clinical ~~of the application~~trials.

•Phase 3. The investigational product is administered to an expanded patient population to further evaluate dosage, to provide substantial evidence of clinical efficacy and to further test for safety, generally at multiple geographically dispersed clinical trial sites. These clinical trials are intended to establish the overall risk/benefit ratio of the investigational product and to provide an adequate basis for product labeling.

~~Although~~In wesome ~~previously~~cases, ~~obtained a fast track designation from~~ the FDA ~~for~~may ~~uproleselan to treat AML and breakthrough therapy designation for uproleselan to treat AML~~require, ~~even~~or ifcompanies wemay ~~were~~voluntarily ~~to continue to advance uproleselan toward potential regulatory approval~~pursue, weadditional ~~may~~clinical ~~not~~trials ~~experience~~after a ~~faster~~product ~~development~~is ~~process,~~approved ~~review or approval compared~~ to ~~conventional~~gain ~~FDA~~more ~~procedures.~~information ~~Our~~about ~~fast track designation may be withdrawn by~~ the ~~FDA~~product ifin ~~it believes that~~ the ~~designation~~approved ~~is no longer supported by data from our clinical development programs~~indication. ~~Our~~These ~~fast~~so-called ~~track~~Phase ~~designation~~4 ~~does~~studies ~~not~~may ~~guarantee~~be ~~that~~made wea ~~will~~condition ~~qualify for or be able~~ to ~~take~~approval ~~advantage~~ of the ~~expedited review procedures or obtain regulatory approval~~BLA.

Concurrent with clinical trials, companies may complete additional animal studies and develop additional information about the biological characteristics of the product candidate, and must 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 product candidate and, among other things, must develop methods for testing the identity, strength, quality and purity of the final product, or for biologics, the safety, purity and potency. Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

Failure to obtain marketing approval in international jurisdictions would prevent our drug candidates from being marketed abroad.

In order to market and sell our drugs in the EU and any other jurisdictions, we or our collaborators 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 drug be approved for reimbursement before it can be approved for sale in that country. If we resume development activities, we or our collaborators 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 or our collaborators may not be able to file for marketing approvals and may not receive necessary approvals to commercialize our drugs in any market.

Should we resume drug development activities, a variety of risks associated with developing and marketing our drug candidates internationally could hurt our business.

If we were to continue the development of our drug candidates, we or our collaborators may seek regulatory approval for our other drug candidates 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;

Table of Contents

●A ~~the~~sponsor ~~potential~~may ~~for~~choose, ~~so-called~~but ~~parallel~~is ~~importing~~not required, ~~which~~to isconduct ~~what~~a ~~happens~~foreign ~~when~~clinical study under an IND. When a ~~local~~foreign ~~seller~~clinical study is conducted under an IND, ~~faced~~all IND requirements must be met unless waived. When the foreign clinical study is not conducted under an IND, the sponsor must ensure that the study complies with ~~high~~certain FDA regulatory requirements in order to use the study as support for an IND or ~~higher~~application ~~local~~for ~~prices~~marketing approval or licensure, ~~opts~~including that the study was conducted in accordance with GCP, including review and approval by an independent ethics committee and use of proper procedures for obtaining informed consent from subjects, and the FDA must be able to ~~import~~validate ~~goods~~the data from athe ~~foreign~~study ~~market~~through ~~with~~an ~~low~~onsite orinspection ~~lower~~if ~~prices~~the ~~rather~~FDA ~~than~~deems ~~buying~~such ~~them~~inspection ~~locally;~~necessary.

●BLA ~~unexpected~~Submission ~~changes in tariffs, trade barriers, price~~ and ~~exchange~~Review ~~controls and other regulatory requirements;~~

●Assuming ~~economic~~successful ~~weakness~~completion of all required testing in accordance with all applicable regulatory requirements, the results of product development, including ~~inflation~~results from nonclinical studies and clinical trials, are submitted to the FDA as part of a BLA requesting approval to market the product for one or ~~political~~more ~~instability~~indications. inThe ~~particular~~BLA ~~foreign~~must ~~economies~~include all relevant data available from pertinent preclinical studies and ~~markets;~~clinical trials, including negative or ambiguous results as well as positive findings, together with detailed information relating to the product’s chemistry, manufacturing, controls, and proposed labeling, among other things. Data can come from company-sponsored clinical studies intended to test the safety and effectiveness of the product, or from a number of alternative sources, including studies initiated and sponsored by investigators. The submission of a BLA requires payment of a substantial application user fee to the FDA, unless a waiver or exemption applies.

●Within ~~compliance~~60 days following submission of the application, the FDA reviews a BLA submitted to determine if it is substantially complete before the FDA accepts it for filing. The FDA may refuse to file any BLA that it deems incomplete or not properly reviewable at the time of submission and may request additional information. In this event, the BLA must be resubmitted with ~~tax~~the additional information. Once a BLA has been accepted for filing, ~~employment~~the FDA’s goal is to review standard review applications within 10 months after the filing date, ~~immigration~~or, if the application qualifies for priority review, six months after the FDA accepts the application for filing. In both standard and ~~labor~~priority ~~laws~~reviews, the review process may also be extended by FDA requests for ~~employees~~additional ~~living~~information or ~~traveling~~clarification. ~~abroad;~~The FDA reviews a BLA to determine, among other things, whether a product is safe, pure and potent and the facility in which it is manufactured, processed, packed or held meets standards designed to assure the product’s continued safety, purity and potency.

●The ~~foreign~~FDA ~~taxes,~~may ~~including~~convene ~~withholding~~an advisory committee to provide clinical insight on application review questions. The FDA is not bound by the recommendations of ~~payroll~~an ~~taxes;~~advisory committee, but it considers such recommendations carefully when making decisions.

●Before ~~foreign~~approving ~~currency~~a ~~fluctuations~~BLA, ~~which~~the ~~could~~FDA ~~result~~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 are in ~~increased~~compliance ~~operating~~with ~~expenses~~cGMP requirements and ~~reduced~~adequate ~~revenues~~to assure consistent production of the product within required specifications. Additionally, ~~and~~before ~~other~~approving ~~obligations~~a ~~related~~BLA, the FDA will typically inspect one or more clinical sites to ~~doing~~assure ~~business~~compliance inwith ~~another~~GCPs. ~~country;~~

●After ~~difficulties~~the ~~staffing~~FDA evaluates a BLA and ~~managing~~conducts ~~foreign~~inspections ~~operations;~~of manufacturing facilities where the investigational product and/or its drug substance will be produced, the FDA may issue an approval letter or a Complete Response letter. An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications. A Complete Response letter will describe all of the deficiencies that the FDA has identified in the BLA, except that where the FDA determines that the data supporting the application are inadequate to support approval, the FDA may issue the Complete Response letter without first conducting required inspections, testing submitted product lots and/or reviewing proposed labeling. In issuing the Complete Response letter, the FDA may recommend actions that the applicant might take to place a resubmitted BLA in condition for approval, including among other things, requests for additional information or clarification, or requirements to conduct additional clinical or nonclinical studies. If a FDA issues a Complete Response Letter, the sponsor must resubmit the BLA addressing all of the deficiencies identified in the letter, or withdraw the application. Even if such data and information are submitted, the FDA may decide that the resubmitted BLA does not satisfy the criteria for approval.

●If ~~workforce~~regulatory ~~uncertainty~~approval inof ~~countries~~a ~~where~~product ~~labor~~is ~~unrest~~granted, such approval will be granted for particular indications and may entail limitations on the indicated uses for which such product may be marketed. For example, the FDA may approve the BLA with a REMS to ensure the benefits of the product outweigh its risks. A REMS is ~~more~~a ~~common~~safety ~~than~~strategy into manage a known or potential serious risk associated with a product 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. The FDA also may condition approval on, among other things, changes to proposed labeling or the ~~United~~development ~~States;~~of adequate controls and

● potential liability under the Foreign Corrupt Practices Act or comparable foreign regulations;

● challenges enforcing our contractual and intellectual property rights, especially in 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 pandemic, epidemic or disease outbreaks or geo-political actions, including war and terrorism.

Any drug candidate for which we obtain marketing approval could be subject to post-marketing restrictions or recall or withdrawal from the market, and we may therefore be subject to penalties if we fail to comply with regulatory requirements or if we experience unanticipated problems with our drug candidates, when and if any of them are approved.

Any drug candidate for which we obtain marketing approval, along with manufacturing processes, post-approval clinical data, labeling, advertising and promotional activities for such drug candidate, will be subject to continual requirements of and review by the FDA and other regulatory authorities. These requirements include submissions of safety and other post-marketing information and reports, registration and listing 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. Even if marketing approval of a drug candidate is granted, the approval may be subject to limitations on the indicated uses for which the drug may be marketed or to the conditions of approval, including the requirement to implement a risk evaluation and mitigation strategy. If any of our drug candidates receives marketing approval, the accompanying label may limit the approved use of our drug, which could limit its sales.

The FDA may also impose requirements for costly post-marketing studies or clinical trials and surveillance to monitor the safety or efficacy of the drug. The FDA closely regulates the post-approval marketing and promotion of drugs to ensure drugs are marketed only for the approved indications and in accordance with the provisions of the approved labeling. The FDA imposes stringent restrictions on manufacturers’ communications regarding off-label use, and if we do not market our drugs for their approved indications, we may be subject to enforcement action for off-label marketing. Violations of the Federal Food, Drug, and Cosmetic Act relating to the promotion of prescription drugs may lead to investigations alleging violations of federal and state healthcare fraud and abuse laws, as well as state consumer protection laws.

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

● restrictions on such drugs, manufacturers or manufacturing processes;

Table of Contents

●specifications. ~~restrictions~~Once onapproved, the ~~labeling~~FDA may withdraw the product approval if compliance with pre- and post-marketing requirements is not maintained or if problems occur after the product reaches the marketplace. The FDA may require one or more post-market studies and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization, and may limit further marketing of athe ~~drug;~~product based on the results of these post-marketing studies.

●Expedited ~~restrictions~~development onand ~~product~~review ~~distribution or use;~~programs

●The ~~requirements~~FDA has a number of programs intended to ~~conduct~~expedite ~~post-~~the development or review of a marketing ~~studies~~application for an investigational biologic. For example, the fast track designation program is intended to expedite or ~~clinical~~facilitate ~~trials;~~the process for developing and reviewing product candidates that meet certain criteria. Specifically, investigational biologics are eligible for fast track designation if they are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition. The sponsor of a fast track product candidate has opportunities for more frequent interactions with the applicable FDA review team during product development and, once a BLA is submitted, the application may be eligible for priority review. With regard to a fast track product candidate, the FDA may consider for review sections of the BLA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the BLA, the FDA agrees to accept sections of the BLA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the BLA.

●A ~~warning~~product ~~letters;~~candidate intended to treat a serious or life-threatening disease or condition may also be eligible for breakthrough therapy designation to expedite its development and review. A product candidate can receive breakthrough therapy designation if preliminary clinical evidence indicates that the product candidate, alone or in combination with one or more other drugs or biologics, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. The designation includes all of the fast track program features, as well as more intensive FDA interaction and guidance beginning as early as Phase 1 and an organizational commitment to expedite the development and review of the product candidate, including involvement of senior managers.

●Any ~~recall~~product candidate submitted to the FDA for approval, including a product candidate with a fast track designation or ~~withdrawal~~breakthrough designation, may also be eligible for other types of FDA programs intended to expedite development and review, such as priority review. A BLA is eligible for priority review if the ~~drugs~~product ~~from~~candidate is designed to treat a serious condition, and if approved, would provide a significant improvement in safety or efficacy compared to available therapies. The FDA will attempt to direct additional resources to the ~~market;~~evaluation of a BLA designated for priority review in an effort to facilitate the review. The FDA endeavors to review applications with priority review designations within six months of the filing date as compared to ten months for review of original BLAs under its current PDUFA review goals.

●In ~~refusal~~addition, depending on the design of the applicable clinical trials, a product candidate may be eligible for accelerated approval. Specifically, biologics intended to ~~approve~~treat ~~pending~~serious ~~applications~~or life-threatening diseases or ~~supplements~~conditions may be eligible for accelerated approval upon a determination that the product candidate has an effect on a surrogate endpoint that is reasonably likely to ~~approved~~predict ~~applications~~clinical benefit, or on a clinical endpoint that wecan ~~submit;~~be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments. As a condition of approval, the FDA generally requires that a sponsor of a drug or biologic receiving accelerated approval perform adequate and well-controlled confirmatory clinical trials, and may require that such confirmatory trials be underway prior to granting accelerated approval. Biologics receiving accelerated approval may be subject to expedited withdrawal procedures if the sponsor fails to conduct the required confirmatory trials in a timely manner or if such trials fail to verify the predicted clinical benefit. In addition, the FDA requires as a condition of accelerated approval pre-approval of promotional materials, which could adversely impact the timing of the commercial launch of the product.

●Fast ~~clinical~~track ~~holds;~~designation, breakthrough therapy designation, priority review, and accelerated approval do not change the standards for approval but may expedite the development or approval process. Even if a product candidate qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.

●Orphan ~~fines,~~drug ~~restitution or disgorgement of revenue or profit;~~designation

●Under ~~suspension~~the Orphan Drug Act, the FDA may grant orphan designation to a biologic intended to treat a rare disease or ~~withdrawal~~condition, which is a disease or condition that affects fewer than 200,000 individuals in the United States or, if it affects more than 200,000 individuals in the United States, there is no reasonable expectation that the cost of ~~marketing~~developing ~~approvals;~~and

● refusal to permit the import or export of our drugs;

● product seizure; or

● injunctions or the imposition of civil or criminal penalties.

Non-compliance with the 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. Similarly, failure to comply with the EU’s requirements regarding the protection of personal information can also lead to significant penalties and sanctions.

Our business and relationships with 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, transparency, health information privacy and security and other healthcare laws and regulations, which could expose us to significant penalties, including criminal sanctions, civil penalties, contractual damages, reputational harm, administrative burdens and diminished profits and future earnings.

Healthcare providers and third-party payors in the United States and elsewhere will play a primary role in the recommendation and prescription of any drug candidates for which we obtain marketing approval. Our current and future arrangements with third-party payors and customers may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations, including, without limitation, the federal Anti-Kickback Statute and the federal False Claims Act, which may constrain the business or financial arrangements and relationships through which we conduct clinical research, sell, market and distribute any drugs for which we obtain marketing approval. In addition, we may be subject to transparency laws and patient data privacy and security regulation by the U.S. federal and state governments and by governments in foreign jurisdictions in which we conduct our business. The applicable federal, state and foreign healthcare laws and regulations that may affect our ability to operate include:

● the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or providing 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, order or recommendation of, any good or service, for which payment may be made under federal healthcare programs, such as Medicare and Medicaid;

● federal civil and criminal false claims laws, including the federal False Claims Act, which impose criminal and civil penalties, including civil whistleblower or qui tam actions, and civil monetary penalty laws that prohibit individuals or entities for 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 a false statement to avoid, decrease or conceal an obligation to pay money to the federal government;

Table of Contents

●making the ~~federal~~product ~~Health~~available ~~Insurance~~in ~~Portability~~the ~~and~~United ~~Accountability~~States ~~Act~~for this type of ~~1996,~~disease or ~~HIPAA~~condition will be recovered from sales of the product. Orphan designation must be requested before submitting a BLA. After the FDA grants orphan designation, ~~which~~the ~~imposes~~identity ~~criminal~~of the therapeutic agent and ~~civil~~its ~~liability~~potential ~~for~~orphan ~~executing~~use aare ~~scheme~~disclosed topublicly ~~defraud~~by ~~any~~the ~~healthcare~~FDA. ~~benefit~~Orphan ~~program~~designation does not convey any advantage in or ~~making~~shorten ~~false~~the ~~statements~~duration ~~relating~~of tothe ~~healthcare~~regulatory ~~matters;~~review and approval process.

●If ~~HIPAA,~~a asproduct ~~amended~~that byhas orphan designation subsequently receives the ~~Health~~first ~~Information~~FDA ~~Technology~~approval for ~~Economic~~the ~~and~~disease ~~Clinical~~or ~~Health~~condition ~~Act~~for ofwhich ~~2009,~~it orhas ~~HITECH~~such designation, ~~and~~the ~~their~~product ~~respective~~is ~~implementing~~entitled ~~regulations~~to orphan product exclusivity, which ~~impose~~means ~~obligations~~that onthe ~~covered~~FDA ~~healthcare~~may ~~providers,~~not ~~health~~approve ~~plans~~any other applications – including full BLAs – to market the same drug for the same approved indication or use within such disease or condition for seven years, ~~and~~except ~~healthcare~~in ~~clearinghouses~~limited circumstances, such as ~~well~~a showing of clinical superiority to the product with orphan exclusivity for the relevant indication or use or inability to manufacture the product in sufficient quantities to meet the needs relating to the approved indication or use for the patients with the relevant disease or condition. The designation of such biologic also entitles a party to financial incentives such as ~~their~~opportunities ~~business~~for ~~associates~~grant funding towards clinical trial costs, tax advantages and ~~covered~~user-fee ~~subcontractors~~waivers. ~~that~~However, ~~create~~competitors, may receive, ~~maintain~~approval of different products for the same indication or ~~transmit~~use ~~individually~~for ~~identifiable~~which ~~health~~the ~~information~~orphan product has exclusivity, or obtain approval for the same product but for a different indication or onuse ~~behalf~~than the one for which the orphan product has exclusivity. Orphan exclusivity also could block the approval of a ~~covered~~competing ~~entity~~product for the approved orphan indication or use for seven years if a competitor obtains approval of the “same drug,” ~~with~~as ~~respect~~defined by the FDA, or if the active ingredient of the product candidate is determined to ~~safeguarding~~be contained within the ~~privacy~~competitor’s product. In addition, ~~security~~if ~~and~~an ~~transmission~~orphan ofdesignated ~~individually~~product ~~identifiable~~receives ~~health~~marketing ~~information;~~approval for a disease or condition broader than what is designated, it may not be entitled to orphan exclusivity.

●Post-Approval ~~the~~Requirements federal Open Payments program, pursuant to the Physician Payments Sunshine Act, which requires manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services, or CMS, information related to “payments or other transfers of value” made to physicians, which is defined to include doctors, dentists, optometrists, podiatrists and chiropractors, other healthcare professionals (such as physician assistants and nurse practitioners) and teaching hospitals, and applicable manufacturers and applicable group purchasing organizations to report annually to CMS ownership and investment interests held by the physicians and their immediate family members, with disclosure of such information to be made by CMS on a publicly available website; and

●Any ~~analogous~~products ~~state~~manufactured ~~and~~or ~~foreign~~distributed ~~laws~~pursuant ~~and~~to ~~regulations,~~FDA ~~such~~approvals asare ~~state~~subject ~~anti-kickback~~to pervasive and ~~false~~continuing ~~claims~~regulation ~~laws~~by the FDA, ~~which~~including, ~~may~~among ~~apply~~other things, requirements relating to ~~sales~~record-keeping, orreporting ~~marketing~~of ~~arrangements~~adverse ~~and~~experiences, ~~claims~~periodic ~~involving~~reporting, ~~healthcare~~product ~~items~~sampling orand ~~services~~distribution, ~~reimbursed~~and byadvertising ~~non-governmental~~and ~~third-party~~promotion ~~payors,~~of ~~including~~the ~~private~~product. ~~insurers;~~As ~~state~~part ~~and~~of ~~foreign~~the ~~laws~~manufacturing ~~that~~process, ~~require~~the ~~pharmaceutical~~manufacturer ~~companies~~is required to ~~comply~~perform ~~with~~certain ~~the~~tests ~~pharmaceutical~~on ~~industry’s~~each ~~voluntary~~lot ~~compliance~~of ~~guidelines~~the ~~and~~product ~~the~~before ~~relevant~~it ~~compliance~~is ~~guidance~~released ~~promulgated~~for bydistribution. ~~the~~After ~~federal~~a ~~government~~BLA oris ~~otherwise~~approved ~~restrict~~for ~~payments~~a ~~that~~biological product, the product also may be ~~made~~subject to ~~healthcare~~official ~~providers;~~lot ~~state~~release. ~~and~~If ~~foreign~~the ~~laws~~product ~~that~~is ~~require~~subject ~~drug manufacturers~~ to ~~report~~official ~~information~~release ~~related~~by tothe ~~payments~~FDA, ~~and~~the ~~other~~manufacturer ~~transfers~~submits samples of ~~value~~each tolot ~~physicians~~of ~~and~~product ~~other~~to ~~healthcare~~the ~~providers~~FDA ortogether ~~marketing~~with ~~expenditures;~~a ~~state~~release ~~and~~protocol ~~local~~showing ~~laws~~a ~~requiring~~summary of the ~~registration~~history of ~~pharmaceutical~~manufacture ~~sales~~of ~~representatives;~~the lot and ~~state~~the ~~and~~results ~~foreign~~of ~~laws~~all ~~governing~~of the ~~privacy~~manufacturer’s ~~and~~tests ~~security~~performed ofon ~~health~~the ~~information~~lot. inThe FDA also may perform certain ~~circumstances,~~confirmatory ~~many~~tests on lots of ~~which~~some ~~differ~~products ~~from~~before ~~each~~releasing ~~other~~the inlots ~~significant~~for ~~ways~~distribution ~~and~~by ~~often~~the ~~are~~manufacturer. ~~not~~In ~~preempted~~addition, bythe ~~HIPAA~~FDA conducts laboratory research related to the regulatory standards on the safety, ~~thus~~purity, ~~complicating~~and ~~compliance~~potency ~~efforts~~or effectiveness of biologics.

After approval, most changes to the approved product, such as adding new indications or other labeling claims, are subject to prior FDA review and approval. There also are continuing user fee requirements, under which the FDA assesses an annual program fee for each product identified in an approved BLA. Biologic manufacturers and their subcontractors are required to register their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMPs, which impose certain procedural and documentation requirements upon product sponsors and their third-party manufacturers. Changes to the manufacturing process are strictly regulated, and, depending on the significance of the change, may require prior FDA approval before being implemented. FDA regulations also require investigation and correction of any deviations from cGMPs and impose reporting requirements upon sponsors and any third-party manufacturers they may decide to use. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMPs and other aspects of regulatory compliance.

~~Efforts~~The toFDA ~~ensure~~may ~~that~~withdraw ~~our~~approval ~~business~~if ~~arrangements~~compliance with ~~third~~regulatory ~~parties~~requirements ~~will comply with applicable healthcare laws~~ and ~~regulations~~standards ~~may involve substantial costs. It~~ is ~~possible that governmental authorities will conclude that our business practices may~~ not ~~comply~~maintained ~~with current~~ or ~~future~~if ~~statutes,~~problems ~~regulations~~occur orafter ~~case~~the ~~law~~product ~~involving~~reaches ~~applicable~~the ~~fraud and abuse or other healthcare laws and regulations~~market. IfLater ~~our~~discovery ~~operations are found to be in violation~~ of ~~any~~previously ofunknown ~~these~~problems ~~laws~~with ora ~~any other governmental regulations that may apply to us~~product, weincluding ~~may~~adverse beevents ~~subject~~of tounanticipated ~~significant~~severity ~~civil,~~or ~~criminal and administrative penalties~~frequency, ~~including,~~or ~~without~~with ~~limitation,~~manufacturing ~~damages~~processes, ~~fines, individual imprisonment, additional reporting requirements and oversight if we become subject to a corporate integrity agreement~~ or ~~similar~~failure ~~agreement~~ to ~~resolve~~comply ~~allegations of non-compliance~~ with ~~these~~regulatory ~~laws~~requirements, ~~contractual~~may ~~damages,~~result ~~reputational harm, diminished profits and future earnings, disgorgement, exclusion from participation~~ in ~~government~~revisions ~~healthcare~~to ~~programs, such as Medicare and Medicaid, and~~ the ~~curtailment~~approved orlabeling ~~restructuring~~to ofadd ~~our~~new ~~operations,~~safety ~~which~~information; ~~could~~imposition ~~have a material adverse effect on our business. If any~~ of ~~the~~post-market ~~physicians~~studies or ~~other~~clinical ~~healthcare~~studies ~~providers or entities with whom we expect~~ to doassess ~~business,~~new ~~including~~safety ~~our~~risks; ~~collaborators,~~or isimposition ~~found~~of ~~not~~distribution torestrictions ~~be in compliance with applicable laws, it may be subject to criminal, civil~~ or ~~administrative~~other ~~sanctions,~~restrictions ~~including~~under ~~exclusions~~a ~~from~~REMS ~~participation~~program. inOther ~~government~~potential ~~healthcare~~consequences ~~programs~~include, ~~which~~among ~~could~~other ~~also~~things: ~~materially affect our business.~~

•restrictions on the marketing or manufacturing of a product, complete withdrawal of the product from the market or product recalls;

•fines, warning letters or holds on post-approval clinical studies;

•refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of existing product approvals;

Table of Contents

~~Even~~•product ifseizure weor ~~were to resume drug development activities~~detention, ~~recently~~or ~~enacted~~refusal ~~and~~of ~~future~~the ~~legislation~~FDA ~~may~~to ~~increase~~permit the ~~difficulty~~import ~~and~~or ~~cost~~export ~~for us to obtain marketing approval~~ of ~~and~~products; ~~commercialize our drug candidates and affect the prices we may obtain.~~

In•consent ~~the United States and some foreign jurisdictions~~decrees, ~~there~~corporate ~~have~~integrity ~~been a number of enacted and proposed legislative and regulatory changes regarding the healthcare system that could prevent or delay marketing approval of our drug candidates~~agreements, ~~restrict~~debarment or ~~regulate~~exclusion ~~post-approval~~from ~~activities~~federal ~~and~~healthcare ~~affect~~programs; ~~our ability to profitably sell any drug candidates for which we obtain marketing approval.~~

•mandated modification of promotional materials and labelling and the issuance of corrective information;

~~Among policy makers and payors in~~ •the ~~United~~issuance ~~States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals~~ of ~~containing~~safety ~~healthcare costs~~alerts, ~~improving~~Dear ~~quality~~Healthcare ~~and~~Provider ~~expanding access. In the United States~~letters, ~~the~~press ~~pharmaceutical~~releases industry has been a particular focus of these efforts, which include major legislative initiatives to reduce the cost of care through changes in the healthcare system, including limits on the pricing, coverage, and ~~reimbursement~~other ofcommunications ~~pharmaceutical~~containing ~~and~~warnings biopharmaceutical products, especially under government-funded health care programs, and increased governmental control of drug. The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively the PPACA, is a sweeping law intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, improve quality of care, 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. The PPACA, among other ~~things,~~safety ~~increased~~information ~~the~~about minimum level of Medicaid rebates payable by manufacturers of brand name drugs; required collection of rebates for drugs paid by Medicaid managed care organizations; required manufacturers to participate in a coverage gap discount program, under which they must agree to offer point-of-sale discounts off negotiated prices 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~~product; ~~imposed a non-deductible annual fee on pharmaceutical manufacturers~~ or importers who sell certain “branded prescription drugs” to specified federal government programs, implemented a new 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; expanded the types of entities eligible for the 340B drug discount program; expanded eligibility criteria for Medicaid programs; created a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research; and established a Center for Medicare Innovation at CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending.

•injunctions or the imposition of civil or criminal penalties.

~~There~~The ~~have~~FDA ~~been~~closely ~~amendments~~regulates ~~and~~the ~~judicial~~marketing, ~~and~~labeling, ~~Congressional~~advertising ~~challenges~~and topromotion ~~certain aspects~~ of ~~PPACA~~biologics. ~~For~~A ~~example,~~company incan ~~2022,~~make ~~the~~only ~~Inflation~~those ~~Reduction~~claims ~~Act~~relating ofto ~~2022,~~safety orand ~~IRA~~efficacy, ~~was~~purity ~~signed~~and ~~into~~potency ~~law,~~that ~~which~~are ~~among~~approved ~~other~~by ~~things,~~the ~~extends~~FDA ~~enhanced~~and ~~subsidies~~in ~~for~~accordance ~~individuals~~with ~~purchasing~~the ~~health~~provisions ~~insurance~~of ~~coverage~~the inapproved ~~PPACA marketplaces through plan year 2025~~label. The ~~IRA~~FDA ~~also~~and ~~eliminates~~other ~~the~~agencies ~~"donut~~actively ~~hole"~~enforce ~~under~~ the ~~Medicare~~laws ~~Part~~and Dregulations ~~program~~prohibiting ~~beginning in 2025 by significantly lowering~~ the ~~beneficiary~~promotion ~~maximum~~of ~~out~~off-~~of-pocket~~label ~~cost and creating a new manufacturer discount program~~uses. ItFailure isto ~~possible~~comply ~~that~~with ~~the~~these ~~PPACA~~requirements ~~will~~can beresult ~~subject to judicial or Congressional challenges~~ in, ~~the~~among ~~future.~~other Itthings, isadverse ~~unclear~~publicity, ~~how~~warning ~~any~~letters, ~~such~~corrective ~~challenges~~advertising and ~~additional~~potential ~~reform~~civil ~~measures~~and ofcriminal ~~the second Trump administration will impact the PPACA~~penalties. ~~Additional~~Physicians ~~legislative~~may ~~proposals~~prescribe tolegally ~~reform~~available ~~healthcare~~products ~~and~~for ~~government~~uses ~~insurance~~that ~~programs,~~are ~~along~~not ~~with~~described ~~the trend toward managed healthcare~~ in the ~~United~~product’s ~~States,~~labeling ~~could~~and ~~influence~~that ~~the~~differ ~~purchase~~from ofthose ~~medicines~~approved ~~and~~by ~~reduce~~the ~~reimbursement~~FDA. ~~and/or~~Such ~~coverage~~off-label ofuses ~~our~~are ~~product~~common ~~candidates,~~across ifmedical ~~approved~~specialties. ~~Current~~Physicians ~~and~~may ~~future~~believe ~~healthcare~~that ~~reform~~such ~~measures~~off-label ~~may~~uses ~~result~~are inthe ~~more~~best ~~rigorous~~treatment ~~coverage~~for ~~criteria~~many ~~and~~patients in ~~additional~~varied ~~downward~~circumstances. ~~pressure~~The onFDA ~~the~~does ~~price~~not ~~that~~regulate wethe ~~receive~~behavior ~~for~~of ~~any~~physicians ~~approved~~in ~~drug.~~their ~~Any~~choice ~~reduction~~of intreatments. ~~reimbursement~~The ~~from~~FDA ~~Medicare~~does, orhowever, ~~other~~restrict ~~government-funded~~manufacturer’s ~~programs~~communications ~~may~~on ~~result~~the insubject aof ~~similar~~off-label ~~reduction~~use inof ~~payments~~their ~~from private payors~~products.

Biosimilars and Reference Product Exclusivity

InThe ~~addition,~~BPCIA ~~there~~created ~~has~~an ~~been~~abbreviated ~~increasing~~approval ~~legislative~~pathway ~~and~~for ~~enforcement~~biological ~~interest~~products inthat ~~the~~are ~~United~~highly ~~States~~similar, ~~with~~or ~~respect~~“biosimilar,” to ~~specialty~~or ~~drug~~interchangeable ~~pricing~~with ~~practices.~~an ~~Specifically,~~FDA-approved ~~there~~reference ~~have~~biological ~~been several recent U~~product.S. ~~Congressional~~The ~~inquiries~~FDA ~~and~~has ~~proposed~~issued ~~bills~~several ~~designed~~guidance ~~to,~~documents ~~among~~outlining ~~other~~an ~~things,~~approach ~~bring more transparency~~ to ~~drug pricing,~~ review ~~the relationship between pricing~~ and ~~manufacturer~~approval ~~patient programs, and reform government program reimbursement methodologies for drugs. For example, the IRA, among other things (i) directs HHS to negotiate the price~~ of certain high-expenditure, single-source drugs that have been on the market for at least seven years and covered under Medicare, known as the Medicare Drug Price Negotiation Program, and (ii) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflationbiosimilars. ~~These provisions began to take effect progressively in fiscal year 2023. In August 2024,~~

Biosimilarity, which requires that there be no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency, is generally shown through analytical studies, animal studies, and a clinical study or studies. Interchangeability requires that a product is biosimilar to the reference product and the product must demonstrate that it can be expected to produce the same clinical results as the reference product in any given patient and, for products that are administered multiple times to an individual, the biologic and the reference biologic may be alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic. A product shown to be biosimilar or interchangeable with an FDA-approved reference biological product may rely in part on the FDA’s previous determination of safety and effectiveness for the reference product for approval, which can potentially reduce the cost and time required to obtain approval to market the product.

Under the BPCIA, an application for a biosimilar product may not be submitted to the FDA until four years following the date that the reference product was first licensed by the FDA. In addition, the approval of a biosimilar product may not be made effective by the FDA until 12 years from the date on which the reference product was first licensed. During this 12-year period of exclusivity, another company may still market a competing version of the reference product if the FDA approves a full BLA for the competing product containing that applicant’s own preclinical data and data from adequate and well-controlled clinical trials to demonstrate the safety, purity and potency of its product. The BPCIA also created certain exclusivity periods for biosimilars approved as interchangeable products.

A reference biologic is granted 12 years of exclusivity from the time of first licensure of the reference product. The first biologic product submitted under the abbreviated approval pathway that is determined to be interchangeable with the reference product has exclusivity against other biologics submitted under the abbreviated approval pathway for the lesser of (i) one year after the first commercial marketing, (ii) 18 months after approval if there is no legal challenge, (iii) 18 months after the resolution in the applicant’s favor of a lawsuit challenging the biologics’ patents if an application has been submitted, or (iv) 42 months after the application has been approved if a lawsuit is ongoing within the 42-month period.

A biological product can also obtain pediatric market exclusivity in the United States. Pediatric exclusivity, if granted, adds six months to existing exclusivity periods and patent terms. This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric study in accordance with an FDA-issued “Written Request” for such a study.

The BPCIA is complex and continues to be interpreted and implemented by the FDA.

Table of Contents

~~HHS~~Patent ~~announced~~Term ~~the~~Extension agreed-upon prices of the first 10 drugs that were subject to price negotiations, although the Medicare Drug Price Negotiation Program is currently subject to legal challenges. On January 17, 2025, HHS selected fifteen additional drugs covered under Part D for price negotiation in 2025. Each year thereafter more Part B and Part D products will become subject to the Medicare Drug Price Negotiation Program.

In the United States, after a BLA is approved, owners of relevant drug patents may apply for up to a five-year patent extension, which permits patent term restoration as compensation for the patent term lost during the FDA regulatory process. The allowable patent term extension is typically calculated as one-half the time between (1) the latter of (a) the effective date of an IND and (b) issue date of the patent for which extension is sought, and (2) the submission date of a BLA, plus the time between BLA submission date and the BLA approval date, up to a maximum of five years. The time can be shortened if the FDA determines that the applicant did not pursue licensure with due diligence. The total patent term after the extension may not exceed 14 years from the date of product licensure. Only one patent applicable to a licensed biological product is eligible for extension and only those claims covering the product, a method for using it, or a method for manufacturing it may be extended, and the application for the extension must be submitted prior to the expiration of the patent in question. However, a sponsor may not be granted an extension because of, for example, failing to exercise due diligence during the testing phase or regulatory review process, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements. Some, but not all, foreign jurisdictions possess patent term extension or other additional patent exclusivity mechanisms that may be more or less stringent and comprehensive than those of the United States.

~~Further,~~Other onHealthcare ~~December~~Laws ~~7, 2023, an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act was announced. On December 8, 2023, the National Institute of Standards~~ and ~~Technology~~Compliance ~~published~~Requirements for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights. While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework. At the state level, legislatures are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability or commercialize our drugs.

Pharmaceutical companies are subject to additional healthcare regulation and enforcement by the federal government and by authorities in the states and foreign jurisdictions in which they conduct their business. Such laws include, without limitation: the federal Anti-Kickback Statute (“AKS”); the federal False Claims Act (“FCA”); HIPAA and similar foreign, federal and state fraud, abuse and transparency laws.

~~Legislative~~The ~~and~~AKS ~~regulatory~~prohibits, ~~proposals~~among ~~have~~other ~~been~~things, ~~made~~persons toand ~~expand~~entities ~~post-approval~~from ~~requirements~~knowingly and ~~restrict~~willfully ~~sales~~soliciting, ~~and~~receiving, ~~promotional~~offering ~~activities~~or ~~for~~paying ~~drugs.~~remuneration, Weto ~~cannot~~induce, beor ~~sure~~in ~~whether~~return ~~additional~~for, ~~legislative~~either ~~changes~~the ~~will~~referral beof ~~enacted~~an individual, or ~~whether~~ the ~~FDA~~purchase ~~regulations,~~or ~~guidance~~recommendation of an item or ~~interpretations~~service ~~will~~for which payment may be ~~changed,~~made orunder ~~what~~any ~~the~~federal ~~impact~~healthcare program. The term remuneration has been interpreted broadly to include anything of ~~such~~value. ~~changes~~The AKS has been interpreted to apply to arrangements between pharmaceutical manufacturers on one hand, and prescribers and purchasers on the ~~marketing~~other. ~~approvals~~The government often takes the position that to violate the AKS, only one purpose of ~~our~~the ~~drug~~remuneration ~~candidates~~need be to induce referrals, even if ~~any~~there are other legitimate purposes for the remuneration. There are a number of statutory exceptions and regulatory safe harbors protecting some common activities from AKS prosecution, but they are drawn narrowly and practices that involve remuneration that may be. Inalleged ~~addition~~to be intended to induce prescribing, ~~increased~~purchasing or recommending may be subject to scrutiny byif ~~the~~they Udo not qualify for an exception or safe harbor.S. ~~Congress~~Failure to meet all of the ~~FDA’s~~requirements ~~approval~~of ~~process~~a ~~may~~particular ~~significantly~~applicable ~~delay~~statutory exception or ~~prevent~~regulatory ~~marketing~~safe ~~approval,~~harbor asdoes ~~well~~not asmake ~~subject~~the usconduct toper ~~more~~se ~~stringent~~illegal ~~product~~under ~~labeling~~the ~~and~~AKS. ~~post~~Instead, the legality of the arrangement will be evaluated on a case-~~marketing~~by-case ~~testing~~basis based on a cumulative review of all of its facts and ~~other~~circumstances. ~~requirements~~A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.

Civil and criminal false claims laws, including the FCA, which can be enforced through civil whistleblower or qui tam actions, prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment of federal government funds, including in federal healthcare programs, that are false or fraudulent. Pharmaceutical and other healthcare companies have been prosecuted under these laws for engaging in a variety of different types of conduct that caused the submission of false claims to federal healthcare programs. Under the AKS, for example, a claim resulting from a violation of the AKS is deemed to be a false or fraudulent claim for purposes of the FCA.

~~Governments~~HIPAA ~~outside~~created ~~the~~additional ~~United~~federal ~~States~~criminal ~~tend~~statutes tothat ~~impose~~prohibit, ~~strict~~among ~~price~~other ~~controls~~things, ~~which~~executing ~~may~~a ~~adversely~~scheme ~~affect~~to ~~our~~defraud ~~revenue~~any healthcare benefit program, ifincluding ~~any~~private third-party payors, ~~from~~and ~~the~~making ~~potential~~false ~~commercialization~~statements relating to healthcare matters. A person or entity does not need to have actual knowledge of ~~drug~~the ~~candidates~~healthcare fraud statute implemented under HIPAA or specific intent to violate the statute in order to have committed a violation.

InThe ~~some~~U.S. ~~countries,~~federal ~~particularly~~Physician inPayments ~~the~~Sunshine ~~EU,~~Act ~~the~~requires ~~pricing~~certain manufacturers of ~~prescription~~drugs, ~~pharmaceuticals~~devices, isbiologics ~~subject~~and tomedical ~~governmental~~supplies ~~control.~~for Inwhich ~~these~~payment ~~countries~~is available under Medicare, ~~pricing~~Medicaid ~~negotiations~~or ~~with~~the ~~governmental~~Children’s ~~authorities~~Health ~~can~~Insurance ~~take~~Program, ~~considerable~~with ~~time~~specific ~~after~~exceptions, ~~the~~to ~~receipt~~annually ofreport ~~marketing~~to ~~approval~~the Centers for aMedicaid ~~drug.~~& ToMedicare ~~obtain~~Services ~~coverage~~(“CMS”) ~~and~~information ~~reimbursement~~related orto ~~pricing~~payments ~~approval~~or inother ~~some~~transfers ~~countries,~~of wevalue ~~may~~to bephysicians ~~required~~(defined to ~~conduct~~include adoctors, ~~clinical~~dentists, ~~trial~~optometrists, ~~that~~podiatrists, ~~compares~~and ~~the~~chiropractors), ~~cost~~certain non-~~effectiveness~~physician ofproviders ~~our~~(physician ~~drug~~assistants, ~~candidate~~nurse topractitioners, ~~other~~clinical ~~available~~nurse ~~therapies.~~specialists, Ifcertified ~~reimbursement~~nurse ofanesthetists, ~~our~~anesthesiologist ~~drugs~~assistants, isand ~~unavailable~~certified ornurse-midwives), ~~limited~~and inteaching ~~scope~~hospitals, oras ~~amount,~~well oras ifownership ~~pricing~~and isinvestment ~~set~~interests atheld ~~unsatisfactory~~by ~~levels,~~physicians ~~our~~and ~~business~~their ~~could~~immediate befamily ~~harmed,~~members. ~~possibly~~Beginning ~~materially~~on January 1, 2023, California Assembly Bill 1278 requires California physicians and surgeons to notify patients of the ~~extent~~Open ~~that~~Payments wedatabase ~~seek~~established tounder ~~commercialize~~the ~~drugs~~federal Physician Payments Sunshine Act.

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 prior operations involved the use of hazardous and flammable materials, including chemicals and biological materials. Our prior operations also produced hazardous waste products. We have generally contracted 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 have historically maintained 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, to the extent we resume significant drug development activities, 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.

Table of Contents

~~Our~~Pharmaceutical ~~employees~~manufacturers are also subject to federal price reporting laws and ~~employees~~federal ofconsumer ~~our~~protection ~~collaborators~~and unfair competition laws. Federal price reporting laws require manufacturers to calculate and report complex pricing metrics to government programs, where such reported prices may ~~engage~~be used in ~~misconduct~~the calculation of reimbursement and/ or ~~other~~discounts ~~improper~~on ~~activities,~~approved ~~including~~products. ~~non-compliance~~Federal ~~with~~consumer ~~regulatory~~protection ~~standards~~and unfair competition laws broadly regulate marketplace activities and ~~requirements~~activities that potentially harm consumers.

WeIn ~~and~~addition, ~~our~~we ~~collaborators~~ are ~~exposed~~also subject to ~~the~~additional ~~risk~~similar ~~of employee fraud or other misconduct~~U.S. ~~Misconduct~~state byand ~~employees~~foreign ~~could~~law ~~include~~equivalents ~~intentional~~of ~~failures~~each toof ~~comply with FDA regulations, to provide accurate information to~~ the ~~FDA,~~above ~~to comply with manufacturing standards we have established, to comply with~~ federal ~~and state healthcare fraud and abuse~~ laws, ~~and regulations~~which, toin ~~report~~some ~~financial~~cases, ~~information~~differ orfrom ~~data~~each ~~accurately~~other orin tosignificant ~~disclose unauthorized activities to us. In particular~~ways, ~~sales, marketing~~ and ~~business~~may ~~arrangements~~not inhave the ~~healthcare~~same ~~industry are subject to extensive laws and regulations intended to prevent fraud~~effect, ~~kickbacks,~~thus ~~self-dealing~~complicating ~~and~~compliance ~~other abusive practices~~efforts. ~~These~~Violations ~~laws~~of ~~and~~any ~~regulations~~of ~~may~~such ~~restrict~~laws or ~~prohibit~~any ~~a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and~~ other ~~business~~governmental ~~arrangements.~~regulations ~~Employee~~that ~~misconduct~~apply could ~~also~~result ~~involve~~in ~~the~~significant ~~improper use of individually identifiable information~~penalties, including, without limitation, ~~information obtained in the course of clinical trials~~civil, ~~which~~criminal ~~could result in regulatory sanctions~~ and ~~serious~~administrative ~~harm~~penalties, todamages, ~~our reputation. We have adopted a code of business conduct and ethics~~fines, ~~but~~exclusion itfrom isgovernment-funded ~~not~~healthcare ~~always possible to identify and deter employee misconduct~~programs, ~~and~~such ~~the~~as ~~precautions~~Medicare ~~we take to detect~~ and ~~prevent~~Medicaid ~~improper activities may not be effective in controlling unknown~~ or ~~unmanaged~~similar ~~risks~~programs ~~or losses or~~ in ~~protecting us from governmental investigations or~~ other ~~actions~~countries or ~~lawsuits~~jurisdictions, ~~stemming~~integrity ~~from~~oversight aand ~~failure~~reporting obligations to beresolve inallegations of non-compliance, ~~with~~disgorgement, ~~such~~individual ~~laws or regulations. If any such actions are instituted against us~~imprisonment, ~~and~~contractual ~~we are not successful in defending ourselves or asserting our rights~~damages, orreputational ~~any such actions are instituted against any of our collaborators~~harm, ~~those~~diminished ~~actions~~profits ~~could~~and ~~have~~the acurtailment ~~significant~~or ~~impact~~restructuring ~~on our business, including the imposition~~ of ~~significant~~its ~~fines or other sanctions~~operations.

Data Privacy and Security

IfNumerous ~~our~~state, ~~information~~federal, ~~technology~~and ~~systems~~foreign orlaws ~~data~~govern the collection, ordissemination, ~~those~~use, ofaccess ~~third~~to, ~~parties~~confidentiality, ~~upon~~and ~~which~~security weof ~~rely~~personal information, ~~are~~including orhealth-related ~~were~~information. ~~compromised,~~In wethe ~~could~~United ~~experience~~States, ~~adverse~~numerous ~~consequences~~federal ~~resulting~~and ~~from~~state ~~such~~laws ~~compromise~~and regulations, including, ~~but~~state ~~not~~data ~~limited~~breach tonotification laws, ~~regulatory~~state ~~investigations~~health orinformation ~~actions;~~privacy ~~litigation;~~laws, ~~fines~~ and ~~penalties;~~federal aand ~~disruption~~state ofconsumer ~~our~~protection ~~business~~laws ~~operations~~and regulations, ~~including~~govern ~~our~~the ~~clinical~~collection, ~~trials;~~use, ~~reputational~~disclosure, ~~harm;~~and ~~loss~~protection of ~~revenue~~health-related and ~~profits;~~other ~~and~~personal ~~other~~information ~~adverse~~could ~~consequences~~apply to our operations or the operations of our partners.

InFor example, HIPAA, as amended by the ~~ordinary~~HITECH ~~course~~Act, ofand ~~our~~their ~~business~~respective implementing regulations imposes data privacy, wesecurity, and ~~the~~breach ~~third~~notification ~~parties~~obligations ~~upon~~on ~~which~~certain wehealth ~~have~~care ~~relied collect~~providers, ~~receive,~~health ~~store~~plans, ~~process,~~and ~~generate,~~health ~~use,~~care ~~transfer~~clearinghouses, ~~disclose,~~known ~~make~~as ~~accessible,~~covered ~~protect~~entities, ~~secure,~~as ~~dispose~~well ~~of,~~as ~~transmit,~~their business associates and ~~share~~their ~~(collectively,~~covered ~~process)~~subcontractors ~~proprietary~~that perform certain services that involve using, ~~confidential~~disclosing, ~~and~~creating, ~~sensitive~~receiving, ~~data~~maintaining, ~~including~~or ~~personal~~transmitting ~~data~~individually ~~(such~~identifiable asprotected health~~-related~~ ~~data~~information (“PHI”), ~~intellectual~~for ~~property,~~or ~~and~~on ~~trade~~behalf ~~secrets.~~of Wesuch ~~have~~covered ~~also~~entities. ~~relied~~These ~~upon~~requirements ~~third~~imposed ~~parties,~~by ~~such~~HIPAA asand ~~service~~the ~~providers,~~HITECH ~~for~~Act ~~our~~on ~~data~~covered ~~processing–related~~entities ~~activities~~ and ~~have~~business ~~shared~~associates orinclude ~~received~~entering ~~sensitive~~into ~~data~~agreements ~~with~~that orrequire ~~from~~business ~~third~~associates ~~parties.~~protect ToPHI provided by the ~~extent~~covered weentity ~~resume~~against ~~our~~improper ~~drug~~use ~~development~~or ~~activities~~disclosure, weamong ~~will~~other bethings; ~~increasingly~~following ~~dependent~~certain onstandards ~~information~~for ~~technology~~the ~~systems~~privacy ~~and~~of ~~infrastructure~~PHI, ~~including~~which ~~mobile~~limit ~~technologies,~~the todisclosure ~~operate~~of ~~our~~a ~~business.~~patient’s ~~Cyberattacks~~past, ~~malicious internet-based activity~~present, ~~and~~or ~~online~~future ~~and~~physical ~~offline~~or ~~fraud~~mental ~~are~~health ~~prevalent~~or ~~and~~condition ~~continue~~or toinformation ~~increase.~~about ~~These~~a ~~threats~~patient’s ~~are~~receipt ~~becoming~~of ~~increasingly~~health ~~difficult~~care toif ~~detect.~~the ~~These~~information ~~threats~~identifies, ~~come~~or ~~from~~could areasonably ~~variety~~be ofused ~~sources~~to identify, ~~including~~the ~~traditional~~individual; ~~computer~~ensuring ~~“hackers~~the confidentiality,” ~~threat actors~~integrity, ~~personnel~~and ~~(such~~availability asof ~~through~~all ~~theft~~PHI orcreated, ~~misuse)~~received, ~~sophisticated nation states~~maintained, ~~and~~or ~~nation-state-supported~~transmitted ~~actors.~~in ~~Some~~electronic ~~actors~~form, ~~now~~to ~~engage~~identify and ~~are~~protect ~~expected~~against toreasonably ~~continue~~anticipated tothreats ~~engage~~or inimpermissible ~~cyber-attacks,~~uses ~~including~~or ~~without~~disclosures ~~limitation~~to ~~nation-state~~the ~~actors~~security ~~for~~and ~~geopolitical~~integrity ~~reasons~~of such PHI; and inreporting ~~conjunction~~of ~~with~~breaches ~~military~~of ~~conflicts~~PHI ~~and~~to ~~defense~~individuals ~~activities~~and regulators.

Entities that are found to be in violation of HIPAA may be subject to significant civil, criminal, and administrative fines and penalties and/or additional reporting and oversight obligations if required to enter into a resolution agreement and corrective action plan with HHS to settle allegations of HIPAA non-compliance. A covered entity or business associate is also liable for civil money penalties for a violation that is based on an act or omission of any of its agents, which may include a downstream business associate, as determined according to the federal common law of agency. HITECH also increased the civil and criminal penalties applicable to covered entities and business associates and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce HIPAA and seek attorneys’ fees and costs associated with pursuing federal civil actions. To the extent that we submit electronic healthcare claims and payment transactions that do not comply with the electronic data transmission standards established under HIPAA and HITECH, payments to us may be delayed or denied.

~~During~~In ~~times of war and other major conflicts~~addition, westate ~~and~~health ~~the~~information ~~third~~privacy ~~parties upon which we may rely could be vulnerable to a heightened risk of these attacks~~laws, including cyber-attacks that could materially disrupt our systems and operations, supply chain, and ability to operate clinical trials and develop our drug candidates. We and the third parties upon which we may rely could also be subject to a variety of evolving threats, including but not limited to social-engineering attacks (including through deep fakes, which may be increasingly more difficult to identify as fake, and phishing attacks), malicious code (such as ~~viruses~~California’s ~~and~~Confidentiality ~~worms), malware (including as a result~~ of ~~advanced~~Medical ~~persistent~~Information ~~threat~~Act intrusions), denial-of-service attacks (such as credential stuffing), personnel misconduct or error, ransomware attacks, supply-chain attacks, software bugs, server malfunctions, software or hardware failures, loss of data or other information technology assets, adware, attacks enhanced or facilitated by artificial intelligence (AI), telecommunications failures, earthquakes, fires, floods, and ~~other~~Washington’s ~~similar~~My ~~threats.~~Health ~~Ransomware~~My ~~attacks,~~Data ~~including those perpetrated by organized criminal threat actors~~Act, ~~nation-states,~~govern ~~and~~the ~~nation-state-supported~~privacy ~~actors, are becoming increasingly prevalent~~ and ~~severe~~security ~~and can lead to significant interruptions in our operations, loss~~ of ~~data~~health-related ~~and income~~information, ~~reputational harm~~specifically, ~~and diversion of funds. Extortion payments~~ may ~~alleviate~~apply ~~the~~even ~~negative~~when ~~impact~~HIPAA ofdoes anot ~~ransomware~~and ~~attack,~~impose ~~but~~additional ~~we may be unwilling or unable to make such payments due to, for example, applicable laws or regulations prohibiting such payments~~requirements.

Even when HIPAA and state health information privacy laws do not apply, according to the FTC and state Attorneys General, violating consumers’ privacy rights or failing to take appropriate steps to keep consumers’ personal information secure may constitute unfair acts or practices in or affecting commerce in violation of Section 5(a) of the Federal Trade Commission Act and state consumer protection laws.

IfIn weaddition, ~~resume~~certain ~~our~~state ~~drug~~laws, ~~development~~such ~~activities~~as the California Consumer Privacy Act of 2018, weas ~~expect~~amended ~~that~~by wethe ~~would~~California ~~need~~Privacy toRights ~~rely~~Act onof ~~third~~2020 ~~parties~~(“CCPA”), ~~and~~govern ~~technologies~~the toprivacy ~~operate~~and ~~critical~~security ~~business~~of ~~systems~~personal toinformation, ~~process~~including ~~sensitive~~health-related information in acertain ~~variety~~circumstances, some of ~~contexts,~~which ~~including,~~are more stringent than HIPAA in various ways. Numerous other

Table of Contents

~~without~~states ~~limitation,~~have ~~cloud-based~~passed ~~infrastructure,~~similar ~~data center facilities~~laws, ~~encryption~~but ~~and~~many ~~authentication~~differ ~~technology,~~from ~~employee~~each ~~email,~~other ~~content~~in ~~delivery~~significant toways ~~customers,~~ and ~~other~~may ~~functions.~~not Wehave ~~would~~the ~~also~~same ~~rely~~effect, onthus ~~CROs~~complicating ~~and~~compliance ~~CMOs~~efforts. ~~Our~~The ~~ability~~CCPA applies to ~~monitor~~personal ~~these~~data ~~third~~of ~~parties’~~consumers, ~~information~~business ~~security~~representatives, ~~practices~~and ~~is limited~~employees, and ~~these~~imposes ~~third~~obligations ~~parties~~on ~~may~~certain ~~not~~businesses ~~have~~that ~~adequate~~do ~~information~~business ~~security measures~~ in ~~place.~~California, Ifincluding ~~the~~to ~~third~~provide ~~parties~~specific wedisclosures ~~may~~in ~~rely~~privacy ~~upon~~notices, ~~experience~~and aaffords ~~security~~rights ~~incident~~to orCalifornia ~~other~~residents ~~interruption,~~in werelation ~~could~~to ~~experience~~their ~~adverse~~personal ~~consequences~~information. ~~While~~Health weinformation ~~may~~falls beunder ~~entitled~~the toCCPA’s ~~damages~~definition ifof ~~the~~personal ~~third~~information ~~parties~~where weit ~~rely~~identifies, ~~upon~~relates ~~fail~~ to, ~~satisfy~~describes, ~~their~~or ~~privacy~~is orreasonably ~~security-related~~capable ~~obligations~~of tobeing ~~us,~~associated ~~any~~with ~~award~~or ~~may~~could reasonably be ~~insufficient~~linked, todirectly ~~cover~~or ~~our damages~~indirectly, orwith wea ~~may~~particular beconsumer ~~unable~~or tohousehold - unless ~~recover~~it ~~such~~is ~~award.~~subject ~~Similarly,~~to ~~supply~~HIPAA -~~chain~~ and ~~attacks~~is ~~have~~included ~~increased~~under ina ~~frequency~~new ~~and~~category ~~severity~~of personal information, ~~and~~“sensitive wepersonal ~~cannot~~information,” ~~guarantee~~which ~~that~~is ~~third~~offered ~~parties~~greater ~~and~~protection. ~~infrastructure~~The innumerous ~~our~~other ~~potential~~comprehensive ~~supply~~privacy ~~chain~~laws orthat ~~our~~have ~~third-party~~passed ~~partners’~~or ~~supply~~are ~~chains~~being ~~have~~considered ~~not~~in ~~been~~other ~~compromised~~states, oras ~~that~~well ~~they~~as doat ~~not~~the ~~contain~~federal ~~exploitable~~and ~~defects~~local orlevels, ~~bugs~~also ~~that~~exempt ~~could~~some ~~result~~data processed in athe ~~breach~~context of orclinical ~~disruption~~trials; but others exempt covered entities and business associates subject to ~~our~~HIPAA ~~information~~altogether, ~~technology~~further ~~systems~~complicating orcompliance ~~the~~efforts, ~~third-party~~and ~~information~~increasing ~~technology~~legal ~~systems~~risk ~~that~~and ~~would~~compliance ~~support~~costs for us and ~~our~~the ~~services~~third parties upon whom we rely.

Failure to comply with these laws, where applicable, can result in the imposition of significant civil and/or criminal penalties and private litigation. 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.

~~Remote~~Coverage ~~work has also increased risks to our information technology systems~~ and ~~data,~~Reimbursement as our current and former employees have utilized network connections, computers and devices outside our premises or network, including working at home, while in transit and in public locations. Future or past business transactions could expose us to additional cybersecurity risks and vulnerabilities, as our systems could be negatively affected by vulnerabilities present in acquired or integrated entities’ systems and technologies. Furthermore, we may discover security issues that were not found during due diligence of such acquired or integrated entities, and it may be difficult to integrate companies into our information technology environment and security program.

In the U.S. and markets in other countries, patients generally rely on third-party payors to reimburse all or part of the costs associated with their treatment. Adequate coverage and reimbursement from governmental healthcare programs, such as Medicare and Medicaid, and commercial payors is critical to new product acceptance. Our ability to successfully commercialize our product candidates will depend in part on the extent to which coverage and adequate reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations. Even if coverage is provided, the approved reimbursement amount may not be high enough to allow it to establish or maintain pricing sufficient to realize a sufficient return on its investment. Government authorities and third-party payors, such as private health insurers and health maintenance organizations, decide which medications they will pay for and establish reimbursement levels.

~~While~~Significant uncertainty exists as to the coverage and reimbursement status of any pharmaceutical or biological product for which we ~~previously~~obtain ~~implemented~~regulatory ~~security~~approval. ~~measures~~Sales ~~designed~~of toany ~~protect~~product, ~~against~~if ~~security~~approved, ~~incidents~~depend, ~~there~~in ~~can~~part, beon nothe ~~assurance~~extent ~~that~~to ~~these~~which ~~measures~~such product will be ~~effective.~~covered Weby ~~have~~third-party ~~taken~~payors, ~~steps~~such ~~designed~~as ~~to detect~~federal, ~~mitigate~~state, and ~~remediate~~foreign ~~vulnerabilities~~government inhealthcare ~~our~~programs, ~~information~~commercial ~~systems~~insurance ~~(such~~and asmanaged ~~our~~healthcare ~~hardware~~organizations, and~~/or~~ ~~software~~the level of reimbursement, ~~including~~if ~~that~~any, offor such product by third-party ~~parties~~payors. ~~upon~~Decisions ~~which~~regarding wewhether ~~have~~to ~~relied).~~cover Weany ~~may~~of ~~not~~our product candidates, ~~however~~if approved, ~~have~~the ~~detected~~extent of coverage and ~~remediated~~amount ~~all~~of ~~such~~reimbursement ~~vulnerabilities~~to be provided are made on a ~~timely~~plan-by-plan basis. WeFurther, ~~may~~no ~~experience~~uniform ~~further~~policy ~~delays~~for coverage and reimbursement exists in ~~developing~~the ~~and~~United ~~deploying~~States, ~~remedial~~and ~~measures~~coverage and ~~patches~~reimbursement ~~designed~~can todiffer ~~address~~significantly ~~identified~~from ~~vulnerabilities~~payor to payor. ~~Vulnerabilities~~Third-party ~~could~~payors beoften ~~exploited~~rely upon Medicare coverage policy and ~~result~~payment limitations in setting their own reimbursement rates, but also have their own methods and approval process apart from Medicare determinations. As a ~~security~~result, ~~incident~~the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of our product candidates to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance. Factors payors consider in determining reimbursement are based on whether the product is:

•a covered benefit under its health plan;

~~Any of the previously identified or similar threats could cause a security incident. A security incident could result in unauthorized~~•safe, ~~unlawful,~~effective ~~or accidental acquisition, modification, destruction, loss, alteration, encryption, disclosure of, or access to data. A security incident could disrupt our ability (~~and ~~that~~medically of third parties upon whom we rely) to conduct our business. For example, the loss of clinical trial data from completed or future clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. We may expend significant resources or modify our business activities (including our clinical trial activities) in an effort to protect against security incidents. Certain data privacy and security obligations may require us to implement and maintain specific security measures, industry-standard or reasonable security measures to protect our information technology systems and data. Applicable data privacy and security obligations may require us to notify relevant stakeholders of security incidents, including affected individuals, customers, regulators, and investors. Such disclosures are costly, and the disclosures or the failure to comply with such requirements could lead to adverse consequences. If we (or a third party upon whom we rely) experience a security incident or are perceived to have experienced a security incident, we may experience adverse consequences. These consequences may include government enforcement actions (for example, investigations, fines, penalties, audits, and inspections)necessary; interruptions in our operations, including disruption of our development programs, if any; additional reporting requirements and/or oversight; interruptions or restrictions on processing sensitive data (which could result in delays in obtaining, or our inability to obtain, regulatory approvals and significantly increase our costs to recover or reproduce the data); litigation (including class claims); indemnification obligations; negative publicity; reputational harm; monetary fund diversions; diversion of management attention; interruptions in our operations (including availability of data); financial loss; and other similar harms. Security incidents and attendant consequences may negatively impact our ability to grow and operate our business.

•cost-effective; and

~~Our~~•neither ~~contracts~~experimental ~~may~~nor not contain limitations of liability, and even where they do, there can be no assurance that limitations of liability in our contracts are sufficient to protect us from liabilities, damages, or claims related to our data privacy and security obligationsinvestigational. Additionally, we cannot be sure that our insurance coverage will be adequate or sufficient to protect us from or to mitigate liabilities arising out of our privacy and security practices, that such coverage will continue to be available on commercially reasonable terms or at all, or that such coverage will pay future claims.

Third-party payors are increasingly challenging the prices charged for medical products and services, examining the medical necessity and reviewing the cost effectiveness of pharmaceutical or biological products, medical devices and medical services, in addition to questioning safety and efficacy. Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit sales of any product that receives approval. Decreases in third-party reimbursement for any product or a decision by a third-party not to cover a product could reduce physician usage and patient demand for the product.

For products administered under the supervision of a physician, obtaining coverage and adequate reimbursement may be particularly difficult because of the higher prices often associated with such drugs. Additionally, separate reimbursement

Table of Contents

Infor ~~addition~~the toproduct ~~experiencing~~itself aor ~~security~~the ~~incident,~~treatment ~~third~~or ~~parties~~procedure ~~may~~in ~~gather,~~which ~~collect,~~the orproduct ~~infer~~is ~~sensitive~~used ~~information~~may ~~about~~not usbe ~~from~~available, ~~public~~which ~~sources,~~may ~~data~~impact ~~brokers,~~physician orutilization. ~~other~~In ~~means~~addition, ~~that~~companion ~~reveals~~diagnostic ~~competitively~~tests ~~sensitive~~require ~~details~~coverage ~~about~~and ~~our~~reimbursement ~~organization~~separate and ~~could~~apart befrom ~~used~~the tocoverage ~~undermine~~and ~~our~~reimbursement ~~competitive~~for ~~advantage~~their companion pharmaceutical or ~~market~~biological ~~position~~products. ~~Additionally,~~Similar ~~sensitive~~challenges ~~information~~to ofobtaining ~~ours~~coverage ~~could~~and ~~be leaked~~reimbursement, ~~disclosed,~~applicable orto ~~revealed~~pharmaceutical ~~as a result of~~ or inbiological ~~connection~~products, ~~with~~will ~~use~~apply ofto ~~generative~~companion ~~AI technologies by our employees, personnel or vendors~~diagnostics.

In addition, net prices for drugs may be reduced by mandatory discounts or rebates required 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 U.S. Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for medical products. We cannot be sure that reimbursement will be available for any product candidate that we may commercialize and, if reimbursement is available, the level of reimbursement. In addition, many pharmaceutical manufacturers must calculate and report certain price reporting metrics to the government, such as average sales price and best price. Penalties may apply in some cases when such metrics are not submitted accurately and timely. Further, these prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs.

WeFinally, ~~and~~in ~~the~~some ~~third parties with whom we have worked are subject to stringent and changing U.S. and~~ foreign ~~laws~~countries, ~~regulations,~~the ~~rules,~~proposed ~~contractual~~pricing ~~obligations,~~for ~~industry~~a ~~standards,~~drug ~~policies~~must ~~and~~be ~~other~~approved ~~obligations~~before ~~related~~it tomay ~~data~~be ~~privacy~~lawfully ~~and security~~marketed. ~~Our~~The ~~actual~~requirements orgoverning ~~perceived~~drug ~~failure~~pricing tovary ~~comply~~widely ~~with~~from ~~such~~country ~~obligations could lead~~ to regulatory investigations or actions; litigation (including class claims) and mass arbitration; fines and penalties; disruptions of our business operations; reputational harm; loss of revenue and profits; and other adverse business impactscountry.

InHealthcare ~~the~~Reform ordinary course of our business, we have processed personal data and other sensitive data, including proprietary and confidential business data, trade secrets, intellectual property, clinical trial participant data, and other sensitive third-party data. The data processing activities related to our work subject us and the third parties with whom we have worked to numerous data privacy and security obligations, such as federal, state, local and foreign laws, regulations, guidance, industry standards, external and internal privacy and security policies, contracts, and other obligations governing the processing and security of personal data. These obligations may change, are subject to differing interpretations and may be inconsistent among jurisdictions or conflict. The global data protection landscape is rapidly evolving, and implementation standards and enforcement practices are likely to remain uncertain for the foreseeable future. This evolution may create uncertainty in our business; affect our (or the third parties upon which we rely) ability to operate in certain jurisdictions or to collect, store, transfer, use and share personal data; necessitate the acceptance of more onerous obligations in our contracts; result in liability; or impose additional costs on us. These obligations may necessitate changes to our information technologies, systems, and practices and to those of any third parties that process personal data on our behalf.

~~Outside~~The ~~the~~United ~~U.S.,~~States anand ~~increasing~~some ~~number~~foreign ofjurisdictions ~~laws,~~are ~~regulations,~~considering ~~and~~or ~~industry~~have ~~standards~~enacted ~~apply~~a tonumber ~~data~~of ~~privacy~~reform ~~and~~proposals ~~security.~~to ~~For~~change ~~example,~~ the ~~European~~healthcare ~~Union’s~~system. ~~General~~There ~~Data~~is ~~Protection~~significant ~~Regulation~~interest ~~(GDPR)~~in ~~(EU)~~promoting ~~2016/679,~~changes orin ~~the~~healthcare EUsystems ~~GDPR~~with ~~and~~ the ~~United~~stated ~~Kingdom’s~~goals ~~GDPR~~of ~~(UK~~containing ~~GDPR),~~healthcare ~~or collectively GDPR~~costs, ~~impose~~improving ~~strict~~quality ~~requirements~~or onexpanding ~~the processing of personal data~~access. ~~Under~~In the ~~GDPR,~~United ~~government regulators may impose temporary or definitive bans on data processing~~States, ~~as well as fines in~~ the ~~event~~pharmaceutical ofindustry ~~violations.~~has ~~Under~~been ~~the~~a ~~GDPR,~~particular ~~companies~~focus ~~may~~of ~~face~~these ~~temporary~~efforts orand ~~definitive~~has ~~bans~~been onsignificantly ~~data~~affected ~~processing~~by federal and ~~other~~state ~~corrective~~legislative ~~actions;~~initiatives, ~~fines~~including ofthose updesigned to 20limit ~~million Euros under~~ the EUpricing, ~~GDPR~~coverage, ~~17.5~~and ~~million~~reimbursement ~~pounds~~of ~~sterling~~pharmaceutical ~~under~~and ~~the~~biopharmaceutical ~~UK GDPR or~~products, inespecially ~~each~~under ~~case,~~government-funded 4%health ofcare ~~annual global revenue~~programs, ~~whichever~~and isincreased ~~greater;~~governmental orcontrol ~~private litigation related to processing~~ of ~~personal~~drug ~~data brought by classes of data subjects or consumer protection organizations authorized at law to represent their interests~~pricing.

WeFor ~~may~~example, ~~transfer personal data from Europe and other jurisdictions to~~ the ~~United~~ACA, ~~States~~which orwas ~~other countries. Europe and other jurisdictions have~~ enacted ~~laws~~in ~~requiring~~March ~~data~~2010, tosubstantially bechanged ~~localized or limiting~~ the ~~transfer~~way ofhealthcare ~~personal~~is ~~data~~financed toby ~~other~~both ~~countries.~~governmental ~~In particular, the European Economic Area (EEA)~~ and ~~the~~private UKinsurers ~~have~~in ~~significantly restricted~~ the ~~transfer of personal data to the~~ United States, and ~~other~~significantly ~~countries~~affected ~~whose~~the ~~privacy~~pharmaceutical ~~laws it generally believes are inadequate~~industry. ~~Other~~The ~~jurisdictions~~ACA ~~have~~contains ~~adopted~~a ornumber ~~may~~of ~~adopt~~provisions ~~similarly~~of ~~stringent~~particular ~~data~~import ~~localization and cross-border data transfer laws. Although there are currently various mechanisms that may be used~~ to ~~transfer personal data from~~ the ~~EEA~~pharmaceutical and UKbiotechnology toindustries, ~~the~~including, ~~U.S.~~but innot ~~compliance~~limited ~~with law~~to, ~~such~~those asgoverning ~~the~~enrollment ~~EEA~~in ~~standard~~federal ~~contractual~~healthcare ~~clauses~~programs, ~~the~~a ~~UK’s~~new ~~International~~methodology ~~Data~~by ~~Transfer~~which ~~Agreement~~rebates /owed ~~Addendum,~~by ~~and~~manufacturers ~~the~~under ~~EU-U.S. Data Privacy Framework and~~ the UKMedicaid ~~extension~~Drug ~~thereto~~Rebate ~~(which~~Program ~~allows~~are calculated for ~~transfers~~drugs tothat ~~relevant~~are ~~U.S.-based~~inhaled, ~~organizations~~infused, ~~who self-certify compliance and participate in the Framework)~~instilled, ~~these~~implanted ~~mechanisms~~or ~~are subject to legal challenges~~injected, and ~~there~~annual isfees nobased ~~assurance~~on ~~that~~pharmaceutical wecompanies’ ~~can~~share ~~satisfy~~of orsales ~~rely on these measures~~ to ~~lawfully~~federal ~~transfer~~health ~~personal~~care ~~data~~programs. toSince ~~the~~its ~~U.S.~~enactment, If there ishave nobeen ~~lawful~~judicial ~~manner~~and ~~for~~Congressional uschallenges to ~~transfer~~certain ~~personal~~aspects ~~data~~of ~~from~~ the ~~EEA~~ACA, ~~the~~and ~~UK,~~we orexpect ~~other~~there ~~jurisdictions~~will tobe ~~the~~additional ~~U.S.,~~challenges orand ifamendments to the ~~requirements~~ACA ~~for~~in athe ~~legally-compliant~~future. ~~transfer~~For ~~are too onerous~~example, ~~we could face significant adverse consequences, including~~ the ~~interruption or degradation of our operations~~IRA, ~~the~~among ~~need to relocate part of or all of our business or data processing activities to~~ other ~~jurisdictions (such as Europe) at significant expense~~things, ~~increased~~extended ~~exposure~~enhanced tosubsidies ~~regulatory~~for ~~actions,~~individuals ~~substantial~~purchasing ~~fines~~health ~~and~~insurance ~~penalties,~~coverage ~~the~~in ~~inability~~ACA tomarketplaces ~~transfer~~through ~~data~~plan ~~and~~year ~~work~~2025. ~~with~~The ~~partners,~~IRA ~~vendors~~also ~~and~~eliminated ~~other~~the ~~third~~“donut ~~parties,~~hole” ~~and~~under ~~injunctions~~the ~~against~~Medicare ~~our~~Part ~~processing~~D orprogram ~~transferring~~beginning ofin ~~personal~~2025 ~~data~~by ~~necessary~~significantly tolowering ~~operate~~the ~~our~~beneficiary ~~business.~~maximum ~~Some EEA regulators have prevented companies from transferring personal data~~ out -of-pocket ~~the~~cost ~~EEA~~and ~~for~~creating ~~allegedly~~a ~~violating~~new ~~the~~manufacturer ~~GDPR’s~~discount ~~cross-border data transfer limitations~~program.

Other legislative changes have been proposed and adopted since the ACA was enacted, including automatic aggregate reductions of Medicare payments to providers as part of the federal budget sequestration under the Budget Control Act of 2011. These reductions went into effect in April 2013 and, due to subsequent legislative amendments, will remain in effect until 2032 unless additional action is taken by Congress. 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.

Moreover, there has recently been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed and enacted federal and state measures designed to, among other things, reduce the cost of prescription drugs, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug products. By way of example, the IRA provides CMS with significant new authorities intended to curb drug costs and to encourage market competition. For the first time, CMS will be able to directly negotiate prescription drug prices and to cap out-of-pocket costs. Each year, CMS will select and negotiate a preset number of high-spend drugs and biologics that are covered under Medicare Part B and Part D that do not have generic or biosimilar competition. CMS published the negotiated prices for the initial ten drugs, which went into effect in 2026, and the subsequent 15 drugs, which will first be effective in 2027, although the IRA’s drug price negotiation program provisions are currently subject to ongoing litigation. The IRA also provides a new “inflation rebate” covering Medicare patients that took effect in 2023 and is intended to counter certain price increases in prescriptions drugs. The inflation rebate provision requires drug manufacturers to pay a rebate to the federal government if the price for a drug or biologic under Medicare

Table of Contents

InPart ~~the~~B ~~United~~and ~~States,~~Part ~~federal,~~D ~~state,~~increases ~~and~~faster ~~local~~than ~~governments~~the ~~have~~rate ~~enacted~~of ~~numerous~~inflation. ~~data~~To ~~privacy~~support ~~and~~biosimilar ~~security laws~~competition, ~~including~~beginning ~~data~~in ~~breach~~October ~~notification laws~~2022, ~~personal~~qualifying ~~data~~biosimilars ~~privacy~~may ~~laws,~~receive ~~consumer~~a ~~protection~~Medicare ~~laws~~Part ~~(e.g.,~~B ~~Section~~payment 5increase offor ~~the~~a ~~Federal~~period ~~Trade~~of ~~Commission~~five ~~Act)~~years. Separately, ~~and~~if ~~other~~a ~~similar~~biologic ~~laws~~drug ~~(e.g.,~~for ~~wiretapping~~which ~~laws). For~~no ~~example,~~biosimilar ~~HIPAA,~~exists asdelays ~~amended~~a bybiosimilar’s ~~HITECH~~market entry beyond two years, ~~imposes~~CMS ~~specific~~will ~~requirements~~be ~~relating~~authorized to subject the ~~privacy,~~biologics ~~security,~~manufacturer ~~and~~to ~~transmission~~price ofnegotiations ~~individually~~intended ~~identifiable~~to ~~health~~ensure ~~data~~fair competition. ~~See~~Notwithstanding ~~the~~these ~~risk~~provisions, ~~factor~~the ~~captioned~~IRA’s ~~“Our~~impact ~~business~~on commercialization and ~~relationships~~competition ~~with~~remains ~~customers~~largely uncertain. Continued legislative and ~~third-party~~enforcement ~~payors~~interest exists in the United States ~~and~~with ~~elsewhere~~respect ~~may~~to bespecialty ~~subject,~~drug ~~directly~~pricing orpractices. ~~indirectly,~~We toexpect ~~applicable~~regulators ~~anti-kickback,~~to ~~fraud~~continue ~~and~~pushing ~~abuse,~~for ~~false claims,~~ transparency, ~~health~~to ~~information~~drug ~~privacy~~pricing, ~~and~~reducing ~~security~~the ~~and~~cost ~~other~~of ~~healthcare~~prescription ~~laws~~drugs ~~and~~under ~~regulations~~Medicare, ~~which~~reviewing ~~could~~the ~~expose~~relationship usbetween topricing ~~significant~~and ~~penalties,~~manufacturer ~~including~~patient ~~criminal sanctions~~programs, ~~civil~~and ~~penalties,~~reforming ~~contractual~~government ~~damages,~~program ~~reputational~~reimbursement ~~harm,~~methodologies ~~administrative~~for ~~burdens and diminished profits and future earnings~~drugs.”

More recently, the One Big Beautiful Bill Act, which was enacted in July 2025, imposes significant reductions in the funding of the Medicaid program. Such reductions are expected to decrease the number of persons enrolled in Medicaid and reduce the services covered by Medicaid, which could adversely affect our sales of any product candidate that we commercialize.

~~Numerous~~The ~~U.S.~~current ~~states~~Presidential ~~have~~administration is also ~~enacted~~pursuing ~~comprehensive~~a ~~privacy~~two-fold ~~laws~~strategy ~~that~~to ~~impose~~reduce ~~certain~~drug ~~obligations~~costs onin ~~covered~~the ~~businesses,~~U.S. ~~including~~While ~~providing~~it ~~specific~~is ~~disclosures~~unclear inwhether ~~privacy notices~~ and ~~affording~~how ~~residents~~the ~~with~~Trump ~~certain~~proposals ~~rights~~will ~~concerning~~be ~~their personal data. As applicable~~implemented, ~~such~~the ~~rights~~Trump ~~may~~policies ~~include~~are ~~the~~likely ~~right~~ to ~~access,~~have ~~correct,~~a ornegative ~~delete~~impact ~~certain~~on ~~personal~~the ~~data,~~pharmaceutical industry and toon ~~opt-out~~our ofability ~~certain~~to ~~data~~receive ~~processing~~adequate ~~activities,~~revenues ~~such~~for asour ~~targeted~~product ~~advertising~~candidates, ~~profiling,~~if ~~and automated decision-making~~approved. ~~The~~On ~~exercise~~the ofone ~~these~~hand, ~~rights~~President ~~may~~Trump ~~impact~~has ~~our~~threatened ~~business and ability~~ to ~~provide our products and services. Certain states also~~ impose ~~stricter~~significant ~~requirements~~tariffs ~~for~~on ~~processing~~pharmaceutical ~~certain~~manufacturers ~~personal~~that ~~data,~~do ~~including~~not ~~sensitive~~adopt ~~information,~~pricing policies such as ~~conducting~~most ~~data~~favored ~~privacy~~nation ~~impact~~pricing, ~~assessments.~~which ~~These~~would ~~state~~tie ~~laws~~the ~~allow~~price for ~~statutory~~drugs ~~fines~~in ~~for~~the ~~noncompliance~~U.S. ~~For~~to ~~example,~~ the ~~California~~lowest ~~Consumer~~price ~~Privacy~~in ~~Act~~a ofgroup ~~2018, as amended by the California Privacy Rights Act~~ of ~~2020,~~other orcountries. ~~CPRA,~~In ~~collectively CCPA~~response, ~~applies~~multiple tomanufacturers ~~personal~~have ~~data~~reportedly ofentered ~~consumers,~~into ~~business~~confidential ~~representatives,~~pricing ~~and~~agreements ~~employees~~with ~~who~~the ~~are~~federal ~~California residents~~government. ~~These~~On ~~obligations~~the ~~include,~~other ~~but are not limited to~~hand, ~~providing~~the ~~specific~~Trump ~~disclosures~~administration inis ~~privacy~~pursuing ~~notices~~traditional ~~and~~regulatory ~~honoring~~pathways ~~requests of such individuals certain rights related~~ to ~~their~~impose ~~personal~~drug ~~data.~~pricing ~~The~~policies, ~~CCPA~~although ~~provide~~final ~~for~~regulations ~~fines~~have ofnot upyet tobeen ~~$7,500~~published. ~~per~~Even ~~intentional~~regulatory ~~violation~~proposals ~~and~~or ~~allows~~executive ~~private~~actions ~~litigants~~that ~~affected~~are byultimately ~~certain~~deemed ~~data~~unlawful ~~breaches~~could tonegatively ~~recover~~impact ~~significant~~the ~~statutory damages~~U.S. ~~While~~pharmaceutical ~~the~~sector ~~CCPA~~ and ~~other~~our ~~comprehensive~~business. ~~state~~In ~~privacy laws contain limited exceptions for clinical trial data~~addition, ~~these~~pharmaceutical ~~developments~~pricing ~~may further complicate compliance efforts,~~ and ~~increase~~marketing ~~legal~~has ~~risk~~long ~~and~~been ~~compliance costs for us and~~ the ~~third~~subject ~~parties~~of ~~upon~~considerable ~~whom~~discussion ~~we rely. Similar laws are being considered~~ in ~~several~~Congress ~~other states, as well as at the federal~~ and ~~local~~among ~~levels~~policymakers, and weit ~~expect~~is ~~more~~possible ~~states~~that toCongress ~~pass~~could ~~similar~~enact additional laws inthat negatively affect the ~~future~~pharmaceutical industry.

Further, on December 7, 2023, the Biden administration announced an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act. On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights. While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework.

InIndividual ~~addition~~states toin ~~data~~the ~~privacy~~U.S. ~~and~~have ~~security~~also ~~laws,~~become weincreasingly ~~may~~active bein ~~contractually~~passing ~~subject~~legislation toand ~~industry~~implementing ~~standards~~regulations ~~adopted~~designed byto ~~industry~~control ~~groups~~pharmaceutical and ~~may~~biological ~~become~~product ~~subject~~pricing, toincluding ~~such~~price ~~obligations~~or inpatient ~~the~~reimbursement ~~future.~~constraints, Wediscounts, ~~are~~restrictions ~~also~~on ~~bound~~certain bydrug ~~other~~access, ~~contractual~~marketing ~~obligations~~cost ~~related~~disclosure, todrug ~~data~~price ~~privacy~~reporting and ~~security~~other transparency measures, and ~~our~~in ~~efforts~~some cases, designed to ~~comply~~encourage ~~with~~importation ~~such~~from ~~obligations~~other ~~may~~countries ~~not~~and bebulk ~~successful~~purchasing. ~~For~~Some ~~example,~~states ~~clinical~~have ~~trial~~enacted ~~participants~~legislation orcreating ~~research~~so-called ~~subjects~~prescription ~~about~~drug ~~whom~~affordability weboards orwith ~~our~~the ~~vendors~~goal ~~obtain~~of ~~information,~~imposing asprice ~~well~~limits ason ~~the~~certain ~~providers~~drugs ~~who~~in ~~share~~these ~~this information with us~~states, ~~may~~while ~~contractually~~some ~~limit~~states ~~our~~are ~~ability~~also seeking to ~~use~~implement ~~and~~general, ~~disclose~~across the ~~information. We~~board ~~have~~price ~~published~~caps ~~privacy~~for ~~policies~~pharmaceuticals, ~~marketing~~or ~~materials,~~are ~~and~~seeking ~~other~~to ~~statements,~~regulate ~~such~~drug asdistribution. ~~compliance~~Legally ~~with~~mandated ~~certain~~price ~~certifications~~controls oron ~~self~~payment amounts by third-~~regulatory~~party ~~principles~~payors or other restrictions could harm our business, ~~regarding~~financial ~~data~~condition, ~~privacy~~results of operations and ~~security~~prospects. IfIn ~~these policies~~addition, ~~materials~~regional orhealthcare ~~statements~~authorities and individual hospitals are ~~found~~increasingly using bidding procedures to bedetermine ~~deficient,~~what ~~lacking~~pharmaceutical products and which suppliers will be included in ~~transparency,~~their ~~deceptive,~~prescription ~~unfair,~~drug orand ~~misrepresentative~~other ofhealthcare ~~our~~programs. ~~practices,~~This wecould ~~may~~reduce bethe ~~subject~~ultimate todemand ~~investigation~~for its drugs or put pressure on its drug pricing, ~~enforcement~~which ~~actions~~could bynegatively ~~regulators~~affect our business, orfinancial ~~other~~condition, ~~adverse~~results ~~consequences~~of operations and prospects.

Other Government Regulation Outside of the United States

~~Obligations~~In ~~related~~addition to ~~data~~regulations ~~privacy~~in ~~and~~the ~~security~~United ~~(and~~States, ~~consumers’~~we ~~data~~are ~~privacy~~subject ~~expectations)~~to ~~are~~a ~~quickly~~variety ~~changing,~~of ~~becoming~~regulations ~~increasingly~~in ~~stringent,~~other jurisdictions regarding safety and ~~creating~~efficacy ~~uncertainty.~~and ~~Additionally~~governing, ~~these~~among ~~obligations~~other ~~may~~things, beresearch ~~subject~~and todevelopment, ~~differing~~clinical ~~applications~~trials, ~~and~~testing, ~~interpretations~~manufacturing, ~~which~~safety, ~~may~~efficacy, bequality ~~inconsistent~~control, orlabeling, ~~conflict~~packaging, ~~among~~storage, ~~jurisdictions.~~record ~~Preparing~~keeping, ~~for~~distribution, reporting, export and ~~complying~~import, ~~with~~advertising, ~~these~~marketing ~~obligations~~and ~~requires~~other uspromotional topractices ~~devote~~involving ~~significant~~biological ~~resources,~~products ~~which~~as ~~may~~well ~~necessitate~~as ~~changes~~authorization, toapproval ~~our~~as ~~services,~~well ~~information~~as ~~technologies,~~post-approval ~~systems,~~monitoring and ~~practices~~reporting ~~and~~of toits ~~those~~products. ofBecause ~~any~~biologically ~~third~~sourced ~~parties~~raw ~~that~~materials ~~process~~are ~~personal~~subject ~~data~~to onunique ~~our~~contamination ~~behalf~~risks, their use may be restricted in some countries.

ItWhether isor ~~possible~~not ~~that, in the future,~~ we ~~may~~obtain ~~fail~~FDA orapproval befor ~~perceived~~a ~~to have failed to comply with applicable data privacy and security obligations. Moreover~~product, ~~despite~~we ~~our~~must ~~best~~obtain ~~compliance~~the ~~efforts,~~requisite ~~our~~approvals ~~personnel~~from orregulatory ~~third~~authorities ~~parties~~in ~~whom~~foreign wecountries ~~rely~~prior ~~on could fail~~ to ~~comply with such obligations, which could negatively impact our business operations and compliance posture. If we or~~ the ~~third~~commencement ~~parties~~of onclinical ~~which~~trials ~~we rely fail,~~ or ~~are~~marketing ~~perceived~~of tothe ~~have~~product ~~failed,~~in tothose ~~address or comply with data privacy and security obligations, we could face significant consequences~~countries. ~~These~~Approval ~~consequences~~by ~~may~~one ~~include,~~regulatory ~~but~~authority ~~are~~does not ~~limited~~ensure ~~to,~~approval ~~government~~by ~~enforcement~~regulatory ~~actions;~~authorities litigation (including class claims) and mass arbitration demands; additional reporting requirements and/or oversight; bans on processing personal data; orders to destroy or not use personal data; and imprisonment of company officials. In particular, plaintiffs have become increasingly more active in ~~bringing~~other ~~privacy-related claims against companies, including class claims and mass arbitration demands~~jurisdictions. ~~Some~~Certain ~~of these claims allow for the recovery of statutory damages on a per violation basis, and, if viable, carry the potential for~~

Table of Contents

~~monumental~~countries ~~statutory~~outside ~~damages, depending on the volume~~ of ~~data and~~ the ~~number~~United ofStates ~~violations. Any of these events could~~ have a ~~material~~similar ~~adverse~~process ~~effect~~that onrequires ~~our~~the ~~reputation,~~submission ~~business,~~of ora ~~financial condition, including but not limited to: interruptions or stoppages in our business operations including, as relevant,~~ clinical ~~trials;~~trial ~~inability~~application tomuch ~~process~~like ~~personal~~the ~~data~~IND orprior to ~~operate~~the incommencement ~~certain jurisdictions; limited ability to develop or commercialize uproleselan; expenditure~~ of ~~time~~human ~~and~~clinical ~~resources to defend any claim or inquiry; adverse publicity; or revision or restructuring of our operations~~trials.

The requirements and process governing the conduct of clinical trials, including requirements to conduct additional clinical trials, product licensing, safety reporting, post-authorization requirements, marketing and promotion, interactions with healthcare professionals, pricing and reimbursement may vary widely from country to country. No action can be taken to market any product in a country until an appropriate approval application has been approved by the regulatory authorities in that country. The current approval process varies from country to country, and the time spent in gaining approval varies from that required for FDA approval. In certain countries, the sales price of a product must also be approved. The pricing review period often begins after market approval is granted. Even if a product is approved by a regulatory authority, satisfactory prices may not be approved for such product, which would make launch of such products commercially unfeasible in such countries.

~~General~~Regulation ~~Risk~~in ~~Factors~~the European Union

~~Unfavorable~~Non-clinical ~~global~~Studies ~~economic~~and ~~conditions~~Clinical ~~could~~Trials ~~adversely affect our business, financial condition or results of operations.~~

~~Our~~Similarly ~~results~~to ~~of operations could be adversely affected by general conditions in~~ the ~~global~~United ~~economy and in the global financial markets. A severe or prolonged economic downturn~~States, ~~or additional global financial crises, including related to health epidemics or armed conflicts and geopolitical tensions around~~ the ~~world,~~various ~~could~~phases ~~result in a variety~~ of ~~risks~~non-clinical to our business, including weakened demand for our product candidates, if approved, or our ability to raise additional capital when needed on acceptable terms, if at all. A weak or declining economy could also strain our suppliers, possibly resulting in supply disruption. Any of the foregoing could harm our business and weclinical ~~cannot~~research ~~anticipate all of the ways~~ in ~~which~~ the ~~economic~~European ~~climate~~Union ~~and~~(“EU”), ~~financial~~are ~~market~~subject ~~conditions~~to ~~could~~significant ~~adversely~~regulatory ~~impact our business~~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.

InClinical ~~addition,~~trials ~~our~~of ~~available~~medicinal ~~cash~~products ~~and~~in ~~cash~~the ~~equivalents~~EU ~~are~~must ~~held~~be conducted in ~~accounts~~accordance ~~managed~~with byEU ~~third-party~~and ~~financial~~national ~~institutions~~regulations and ~~consist~~the ofInternational ~~cash~~Council infor ~~our~~Harmonization ~~operating~~of ~~accounts~~Technical ~~and~~Requirements ~~cash~~for ~~invested~~Pharmaceuticals infor ~~U.S.~~Human ~~Government~~Use, ~~money~~or ~~market~~ICH, ~~funds.~~guidelines Aton ~~any~~Good ~~point~~Clinical inPractices ~~time~~(“GCP”), ~~the~~as ~~funds~~well inas ~~our~~the ~~operating~~applicable ~~accounts~~regulatory ~~may~~requirements ~~exceed~~and the ~~Federal~~ethical ~~Deposit~~principles ~~Insurance~~that ~~Corporation~~have ~~insurance~~their ~~limits.~~origin ~~While~~in wethe ~~monitor~~Declaration ~~the~~of ~~cash~~Helsinki. ~~balances~~If inthe ~~our~~sponsor ~~operating~~of ~~accounts~~the ~~and~~clinical ~~adjust~~trial ~~the~~is ~~cash~~not ~~balances~~established aswithin ~~appropriate~~the EU, ~~these~~it ~~cash~~must ~~balances~~appoint ~~could~~an beEU ~~impacted~~entity ifto ~~the~~act ~~underlying~~as ~~financial~~its ~~institutions~~legal ~~fail~~representative. WeThe ~~can~~sponsor ~~provide~~must notake ~~assurances~~out ~~that~~a ~~access~~clinical totrial ~~our~~insurance ~~operating~~policy, ~~cash~~and orin ~~invested~~most ~~cash~~EU ~~and~~member ~~cash~~states, ~~equivalents~~the ~~will~~sponsor ~~not~~is beliable ~~impacted~~to byprovide ~~adverse~~‘no ~~conditions~~fault’ compensation to any study subject injured in the ~~financial~~clinical ~~markets~~trial.

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 (“CTIS”), which contains a centralized EU portal and database.

IfWhile wethe ~~fail~~EU Clinical Trials Directive required a separate clinical trial application (“CTA”), to ~~comply~~be orsubmitted ~~regain~~in ~~compliance~~each ~~with~~member ~~Nasdaq’s~~state ~~continued~~in ~~listing~~which ~~standards~~the ~~prior~~clinical trial takes place, to both the ~~consummation~~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 ~~Merger~~competent authority and an ethics committee in each member state, ~~our~~leading ~~common~~to ~~stock~~a ~~may~~single bedecision ~~delisted~~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 ~~price~~manufacture and quality of ~~our~~the ~~common~~medicinal ~~stock~~product under investigation. The assessment procedure of the CTA has been harmonized as well, ~~our~~including ~~ability~~a joint assessment by all member states concerned, and a separate assessment by each member state with respect to ~~access~~specific requirements related to its own territory, including ethics rules. Each member state’s decision is communicated to the ~~capital~~sponsor ~~markets~~via ~~and~~the ~~our~~centralized ~~financial~~EU ~~condition~~portal. ~~could~~Once bethe ~~negatively~~CTA ~~impacted~~is approved, clinical study development may proceed.

~~Our~~The ~~common~~CTR ~~stock~~transition ~~was~~period ~~previously~~ended ~~listed~~ on ~~the~~January ~~Nasdaq~~31, ~~Global Market~~2025, and weall ~~were~~clinical ~~required~~trials to(and ~~meet~~related ~~certain~~applications) ~~listing~~are ~~requirements,~~now ~~including~~fully ~~with~~subject ~~respect~~ to ~~minimum~~the ~~closing~~provisions ~~bid prices, market value~~ of ~~publicly~~the ~~held shares, stockholders’ equity and market value of listed securities~~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.

If necessary to regain compliance with Nasdaq listing standards, we may, subject to approval of our board of directors and stockholders, implement a reverse stock split. However, there can be no assurance that a reverse stock split, or any other alternatives we may consider to regain compliance with the minimum bid price requirement, would be approved or would result in a sustained higher stock price that would allow us to meet the Nasdaq stock price listing requirements.

Separately, Nasdaq listing rules requires companies listed on the Nasdaq Capital Market to maintain a stockholders’ equity of at least $2.5 million. As of December 31, 2024, we had stockholders’ equity of $5.3 million. As a result of our expected decrease in stockholders’ equity prior to the Merger due to continued net losses, there can be no assurance that we will be able to maintain the minimum required stockholders’ equity under the Nasdaq continued listing standards.

Table of Contents

IfMarketing weAuthorization are not able to maintain compliance within the compliance periods allotted by Nasdaq, our common stock could be delisted, which would have a further material adverse effect on the market price of our common stock and on stockholder liquidity. We intend to actively monitor the bid price of our common stock and will consider available options to regain compliance with the listing requirement; however, there can be no assurance that we will be able to regain compliance with the listing requirement or will otherwise be in compliance with the other Nasdaq listing criteria. If Nasdaq delists our common stock for failure to meet its listing standards, and our common stock is not eligible for quotation or listing on another market or exchange, we and our stockholders could face significant negative consequences, including:

●In ~~trading~~the EEA, after completion of ~~our~~all ~~common~~required ~~stock~~clinical ~~being~~testing, ~~conducted~~pharmaceutical products may only inbe ~~the~~placed ~~over-~~on the~~-counter~~ market orafter onobtaining a marketing authorization (“MA”). To obtain an ~~electronic~~MA ~~bulletin~~of ~~board~~a ~~established~~medicinal ~~for~~product ~~unlisted~~candidate ~~securities,~~under ~~such~~EU asregulatory ~~the~~systems, ~~Pink~~an ~~Sheets~~applicant orcan ~~the~~submit ~~OTC~~an ~~Bulletin~~MA ~~Board~~application (“MAA”) through, ~~which~~amongst ~~could~~others, ~~result~~a incentralized ~~limited~~or ~~availability~~decentralized ofprocedure. ~~market~~The ~~quotations~~process for ~~our~~doing ~~common~~this ~~stock~~depends, ~~and~~among ~~increased~~other ~~difficulty~~things, ofon ~~disposing~~the ofnature ~~shares~~ of ~~common~~the ~~stock;~~medicinal product.

●•“Centralized aMAs” ~~determination~~are ~~that~~issued by the ~~common~~European ~~stock~~Commission isthrough athe centralized procedure based on the opinion of the Committee for Medicinal Products for Human Use (“~~penny~~CHMP”), ~~stock~~of the European Medicine 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”) ~~which~~(such ~~would~~as ~~require~~gene ~~brokers~~therapy, ~~trading~~somatic incell therapy and tissue engineered products) and (iv) medicinal products containing a new active substance indicated for the ~~common~~treatment ~~stock~~of tocertain ~~adhere~~diseases, tosuch ~~more~~as ~~stringent~~HIV/AIDS, ~~rules~~cancer, ~~possibly~~diabetes, ~~resulting~~neurodegenerative indiseases or autoimmune diseases and other immune dysfunctions, and viral diseases. The centralized procedure is optional for products containing a ~~reduced~~new ~~level~~active ofsubstance ~~trading~~not ~~activity~~yet authorized in the ~~secondary~~EU, ~~trading~~or ~~market~~ for ~~shares~~products that constitute a significant therapeutic, scientific or technical innovation or which are in the interest of ~~our~~public ~~common~~health ~~stock;~~in the EU.

●•“National aMAs” ~~limited~~are ~~amount~~issued by the competent authorities of ~~analyst~~the ~~coverage;~~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 athe ~~decreased~~centralized ~~ability~~procedure tothe ~~issue~~maximum ~~additional~~timeframe ~~securities~~for orthe ~~obtain~~evaluation ~~additional~~of ~~financing~~an inMAA by the ~~future~~EMA is 210 days, excluding clock stops. In exceptional cases, the CHMP might perform an accelerated review of a MAA in no more than 150 days (not including clock stops).

Moreover, in the EU, a “conditional” MA may be granted in cases where all the required safety and efficacy data are not yet available. The conditional MA is subject to conditions to be fulfilled for generating the missing data or ensuring increased safety measures. It is valid for one year and has to be renewed annually until fulfillment of all the conditions. Once the pending studies are provided, it can become a “standard” MA. However, if the conditions are not fulfilled within the timeframe set by the EMA, the MA ceases to be renewed.

AnFurthermore, ~~active~~MA ~~trading~~may ~~market~~also ~~for~~be ~~our~~granted ~~common~~“under ~~stock~~exceptional circumstances” when the applicant can show that it is unable to provide comprehensive data on the efficacy and safety under normal conditions of use even after the product has been authorized and subject to specific procedures being introduced. This may arise in particular when the intended indications are very rare and, in the present state of scientific knowledge, it is not possible to provide comprehensive information, or when generating data may be ~~sustained~~contrary to generally accepted ethical principles. This MA is close to the conditional MA as it is reserved to medicinal products to be approved for rare diseases or unmet medical needs and the applicant does not hold the complete data set legally required for the grant of a MA. However, unlike the conditional MA, the applicant does not have to provide the missing data and will never have to. Although the MA “under exceptional circumstances” is granted definitively, the risk-benefit balance of the medicinal product is reviewed annually and the MA is withdrawn in case the risk-benefit ratio is no longer favorable.

~~Although~~Under ~~our~~the ~~common~~above-described ~~stock~~procedures, isin ~~listed~~order onto ~~The~~grant ~~Nasdaq~~the ~~Capital Market~~MA, wethe ~~cannot~~EMA ~~assure~~or ~~you~~the ~~that~~competent anauthorities ~~active~~of ~~trading~~the ~~market~~EU ~~for~~member ~~our~~states ~~shares~~make ~~will~~an beassessment ~~sustained.~~of Ifthe anrisk ~~active~~benefit ~~market~~balance ~~for~~of ~~our~~the ~~common~~product ~~stock~~on isthe ~~not~~basis ~~sustained~~of scientific criteria concerning its quality, itsafety ~~may~~and beefficacy. ~~difficult~~MAs ~~for~~have ~~investors~~an ininitial ~~our~~duration ~~common~~of ~~stock~~five toyears. ~~sell~~After ~~shares~~these ~~without~~five ~~depressing~~years, the ~~market~~authorization ~~price~~may ~~for~~be renewed on the ~~shares~~basis orof toa ~~sell~~reevaluation of the ~~shares~~risk-benefit ~~at all~~balance.

Data and Marketing Exclusivity

~~The~~In ~~trading~~the ~~price~~EU, new products authorized for marketing (i.e., reference products) generally receive eight years of ~~our~~data ~~common~~exclusivity ~~stock~~and ~~has~~an ~~been~~additional two years of market exclusivity upon MA. If granted, the data exclusivity period prevents generic and isbiosimilar ~~likely~~applicants tofrom ~~continue~~relying toon bethe ~~volatile~~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

Our stock price from time to time has been volatile. The stock market in general and the market for biopharmaceutical 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:

● expectations regarding the consummation of the Merger with Crescent;

● announcements relating to development, regulatory approvals or commercialization of our drug candidates;

● 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;

● changes in laws or other regulatory actions affecting us or our industry, such as drug pricing and reimbursement;

● stock market price and volume fluctuations of comparable companies and, in particular, those that operate in the biopharmaceutical 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;

● capital commitments;

● investors’ general perception of our company and our business;

● disputes concerning our intellectual property or other proprietary rights;

Table of Contents

●biosimilar ~~recruitment~~applicant orfrom ~~departure~~commercializing its product in the EU until ten years have elapsed from the initial MA of ~~key~~the ~~personnel;~~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.

●There ~~sales~~is a special regime for biosimilars, or biological medicinal products that are similar to a reference medicinal product but that do not meet the definition of ~~our~~a ~~common~~generic ~~stock~~medicinal product, ~~including~~for ~~sales~~example, bybecause ~~our~~of ~~directors~~differences in raw materials or manufacturing processes. For such products, the results of appropriate preclinical or clinical trials must be provided, and ~~officers~~guidelines from the EMA detail the type of quantity of supplementary data to be provided for different types of biological product. There are no such guidelines for complex biological products, such as gene or ~~specific~~cell ~~stockholders~~therapy medicinal products, and so it is unlikely that biosimilars of those products will currently be approved in the EU. However, guidance from the EMA states that they will be considered in the future in light of the scientific knowledge and regulatory experience gained at the time.

Pediatric Development

In ~~addition~~the EU, ~~the~~companies ~~stock~~developing ~~markets~~a ~~have~~new ~~experienced~~medicinal ~~extreme~~product ~~price~~are ~~and~~obligated ~~volume~~to ~~fluctuations~~study ~~that~~their ~~have~~product ~~affected~~in children and ~~continue~~must totherefore ~~affect~~submit a pediatric improvement plan (“PIP”) agreed with the ~~market~~EMA’ ~~prices~~Pediatric ofCommittee ~~equity~~(“PDCO”). ~~securities~~The ofPIP ~~many~~sets ~~companies,~~out ~~which~~the ~~has~~timing ~~resulted~~and inmeasures ~~volatile~~proposed ~~stock~~to ~~prices~~generate ~~for~~data ~~many~~to ~~companies~~support ~~notwithstanding~~a ~~the~~pediatric ~~lack~~indication of the product candidate for which MA is being sought. The PDCO can grant a ~~fundamental~~deferral ~~change~~of inthe ~~their~~obligation ~~underlying~~to ~~business~~implement ~~models~~some or ~~prospects.~~all ~~These~~of ~~fluctuations~~the ~~have~~measures ~~often~~of ~~been~~the ~~unrelated~~PIP oruntil ~~disproportionate~~there are sufficient data to demonstrate the ~~operating~~efficacy ~~performance~~and safety of ~~those~~the ~~companies~~product in adults. ~~Broad~~Further, ~~market~~the ~~and~~obligation ~~industry~~to ~~factors,~~provide ~~including~~pediatric ~~worsening~~clinical ~~economic~~trial ~~conditions~~data ~~and~~can ~~other~~be ~~adverse~~waived ~~effects~~by the PDCO when these data are not needed or ~~developments~~appropriate ~~relating~~because the product is likely to ~~political~~be ineffective or unsafe in children, ~~regulatory~~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 ~~other~~study ~~market~~results ~~conditions~~are included in the product information, ~~may~~even ~~negatively~~when ~~affect~~negative, the ~~market~~product ~~price~~is eligible for six months’ supplementary protection certificate extension (if any is in effect at the time of ~~shares~~approval) or, in the case of ~~our~~orphan ~~common~~medicinal ~~stock~~products, ~~regardless~~a two year extension of ~~our~~the ~~actual~~orphan ~~operating~~market ~~performance~~exclusivity is granted.

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.

InOrphan ~~addition~~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, inprotocol assistance, and access to the ~~past,~~centralized ~~stockholders~~procedure. ~~have~~Upon ~~initiated~~grant ~~class~~of ~~action~~a ~~lawsuits~~MA, ~~against~~orphan ~~pharmaceutical~~medicinal ~~and~~products ~~biotechnology~~are ~~companies~~entitled ~~following~~to ~~periods~~ten years of ~~volatility~~market inexclusivity for the ~~market~~approved ~~prices~~indication, ofwhich ~~these~~means ~~companies’~~that ~~stock.~~the ~~Such~~competent ~~litigation~~authorities cannot accept another MAA, ifor ~~instituted~~grant ~~against~~a usMA, ~~could~~or ~~cause~~accept usan application to ~~incur~~extend ~~substantial~~a ~~costs~~MA ~~and~~for ~~divert~~a ~~management’s~~similar ~~attention~~medicinal ~~and~~product ~~resources~~for ~~from~~the ~~our~~same ~~business~~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 PIP. No extension to any supplementary protection certificate can be granted on the basis of 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 designation, 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.

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.

The trading market for our common stock is influenced by the research and reports that equity research analysts publish about us and our business. We have only limited research coverage by equity research analysts. Equity research analysts may elect not to initiate or continue to provide research coverage of our common stock, and such lack of research coverage may adversely affect the market price of our common stock. Even if we have equity research analyst coverage, we will not have any control over the analysts or the content and opinions included in their reports. The price of our stock could decline if one or more equity research analysts downgrade our stock or issue other unfavorable commentary or research. If one or more equity research analysts ceases coverage of our company or fails to publish reports on us regularly, demand for our stock could decrease, which in turn could cause our stock price or trading volume to decline.

The issuance of additional stock in connection with financings, acquisitions, investments, our stock incentive plan, our employee stock purchase plan or otherwise will dilute all other stockholders.

Our certificate of incorporation authorizes us to issue up to 150,000,000 shares of common stock and up to 5,000,000 shares of preferred stock with such rights and preferences as may be determined by our board of directors. Subject to compliance with applicable rules and regulations, we may issue our shares of common stock or securities convertible into our common stock from time to time in connection with a financing, acquisition, investment, our stock incentive plan, our employee stock purchase plan or otherwise. Any such issuance could result in substantial dilution to our existing stockholders and cause the trading price of our common stock to decline.

If a substantial number of our total outstanding shares are sold into the market, or if the market perceives that such sales may occur, it could cause the market price of our common stock to drop significantly.

Sales of a substantial number of shares of our common stock in the public market could occur at any time. If our stockholders sell, or if the market perceives that our stockholders intend to sell, substantial amounts of our common stock in the public market, the market price of our common stock could decline significantly. All of our outstanding shares of common stock are available for sale in the public market, subject only to the restrictions of Rule 144 under the Securities Act in the case of our affiliates.

In addition, we have filed registration statements on Form S-8 registering the issuance of shares of common stock subject to options or other equity awards issued or reserved for future issuance under our equity incentive plans. Shares registered under these registration statements are available for sale in the public market subject to vesting arrangements and exercise of options, as well as Rule 144 in the case of our affiliates. If these additional shares are sold, or if it is perceived that they will be sold, in the public market, the trading price of our common stock could decline.

Table of Contents

~~Provisions~~PRIME inDesignation our corporate charter documents and under Delaware law may prevent or frustrate attempts by our stockholders to change our management and hinder efforts to acquire a controlling interest in us, and the market price of our common stock may be lower as a result.

~~Provisions~~Innovative inproducts ~~our~~that ~~certificate~~target ofan ~~incorporation~~unmet medical need and ~~bylaws~~are ~~that~~expected ~~could~~to ~~make~~be itof ~~difficult~~major public health interest may be eligible for a ~~third~~number ~~party~~of toexpedited ~~acquire~~development and review programs, orsuch ~~attempt~~as the PRIority MEdicines (“PRIME”) scheme, which provides incentives similar to ~~acquire~~the breakthrough therapy designation in the U.S. In March 2016, ~~control~~the ofEMA ~~our~~launched ~~company~~an initiative, ~~even~~the ifPRIME scheme, a ~~change~~voluntary inscheme ~~control~~aimed ~~was~~at ~~considered~~enhancing ~~favorable~~the byEMA’s ~~some~~support orfor ~~all~~the development of ~~our~~medicines ~~stockholders~~that target unmet medical needs. ~~For~~It ~~example,~~is ~~our~~based ~~board~~on ofincreased ~~directors~~interaction ~~has~~and ~~the~~early ~~authority~~dialogue with companies developing promising medicines, to ~~issue~~optimize their product development plans and speed up their evaluation to ~~5,000,000~~help ~~shares~~them ofreach ~~preferred~~patients ~~stock~~earlier. ~~The~~Product ~~board~~developers ofthat ~~directors~~benefit from PRIME designation can ~~fix~~expect ~~the~~to ~~price,~~be ~~rights,~~eligible ~~preferences,~~for ~~privileges~~accelerated ~~and~~assessment ~~restrictions~~but this is not guaranteed. Many benefits accrue to sponsors of ~~the~~product ~~preferred~~candidates ~~stock~~with ~~without~~PRIME ~~any~~designation, ~~further~~including ~~vote~~but ornot ~~action~~limited byto, ~~our~~early ~~stockholders.~~and ~~The~~proactive ~~issuance~~regulatory ofdialogue ~~shares~~with ofthe ~~preferred~~EMA, ~~stock~~frequent ~~may~~discussions ~~delay~~on orclinical ~~prevent~~trial designs and other development program elements, and accelerated MAA assessment once a ~~change~~dossier inhas ~~control~~been ~~transaction~~submitted. AsImportantly, a ~~result,~~dedicated ~~the~~contact ~~market~~and ~~price~~rapporteur offrom ~~our~~the ~~common~~CHMP ~~stock~~is ~~and~~appointed early in the ~~voting~~PRIME ~~and~~scheme ~~other~~facilitating ~~rights~~increased understanding of ~~our~~the ~~stockholders~~product ~~may~~at beEMA’s ~~adversely~~committee ~~affected~~level. An ~~issuance~~initial ofmeeting ~~shares~~initiates ofthese ~~preferred~~relationships ~~stock~~and ~~may~~includes ~~result~~a inteam ~~the~~of ~~loss~~multidisciplinary ofexperts ~~voting~~at ~~control~~the EMA to ~~other~~provide ~~stockholders~~guidance on the overall development and regulatory strategies.

Post-Approval Regulation

~~Our~~Similar ~~charter~~to ~~documents~~the ~~also~~United ~~contain~~States, ~~other~~both ~~provisions~~MA ~~that~~holders ~~could~~and ~~have~~manufacturers of medicinal products are subject to comprehensive regulatory oversight by the EMA,, the European Commission and/or the competent regulatory authorities of the EU member states. The holder of a MA must establish and maintain a pharmacovigilance system and appoint an ~~anti-takeover~~individual ~~effect~~qualified person for pharmacovigilance (“QPPV”), ~~including:~~who is responsible for the establishment and maintenance of that system, and oversees the safety profiles of medicinal products and any emerging safety concerns. Key obligations include expedited reporting of suspected serious adverse reactions and submission of periodic safety update reports (“PSURs”).

●All ~~only~~new ~~one~~MAA must include a risk management plan, or RMP, describing the risk management system that the company will put in place and documenting measures to prevent or minimize the risks associated with the product. The RMP must be updated any time new information on the medicinal product becomes available which has a significant impact on the content of ~~our~~the ~~three~~RMP. ~~classes~~The regulatory authorities may also impose specific obligations as a condition of ~~directors~~the isMA. ~~elected~~Such ~~each~~risk-minimization ~~year;~~measures or post-authorization obligations may include additional safety monitoring, more frequent submission of PSURs, or the conduct of additional clinical trials or post-authorization safety studies.

●The ~~stockholders~~advertising and promotion of medicinal products are ~~not~~also ~~entitled~~subject to ~~remove~~laws ~~directors~~concerning ~~other~~promotion ~~than~~of bymedicinal aproducts, 66interactions ~~2/3%~~with ~~vote~~physicians, misleading and ~~only~~comparative advertising and unfair commercial practices. All advertising and promotional activities for ~~cause;~~the product must be consistent with the approved summary of product characteristics, and therefore all off-label promotion is prohibited. Direct-to-consumer advertising of prescription medicines is also prohibited in the EU. Although general requirements for advertising and promotion of medicinal products are established under EU directives, the details are governed by regulations in each member state and can differ from one country to another.

●The ~~stockholders~~aforementioned EU rules are ~~not~~generally ~~permitted~~applicable toin ~~take~~the ~~actions~~European byEconomic ~~written~~Area ~~consent;~~(“EEA”), which consists of the 27 EU member states plus Norway, Liechtenstein and Iceland.

●Failure ~~stockholders~~to ~~cannot~~comply ~~call~~with aEU ~~special~~and ~~meeting~~member state laws that apply to the conduct of ~~stockholders;~~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

●Regulation ~~stockholders~~of ~~must~~Combination ~~give~~Products ~~advance~~in ~~notice~~the ~~to nominate directors or submit proposals for consideration at stockholder meetings.~~EU

The EU regulates medical devices and medicinal products separately, through different legislative instruments, and the applicable requirements will vary depending on the type of drug-device combination product. EU guidance has been published to help manufacturers select the right regulatory framework.

InDrug-delivery ~~addition,~~products weintended ~~are subject~~ to ~~the~~administer ~~anti-takeover~~a ~~provisions~~medicinal ofproduct ~~Section~~where ~~203 of~~ the ~~Delaware~~medicinal ~~General~~product ~~Corporation~~and ~~Law,~~the ~~which~~device ~~regulates~~form ~~corporate~~a ~~acquisitions~~single byintegral ~~prohibiting~~product ~~Delaware~~are ~~corporations~~regulated ~~from~~as ~~engaging~~medicinal products in ~~specified~~the ~~business~~EU. ~~combinations~~The ~~with~~EMA ~~particular~~is ~~stockholders~~responsible offor ~~those~~evaluating ~~companies.~~the ~~These~~quality, ~~provisions~~safety ~~could discourage potential acquisition proposals~~ and ~~could~~efficacy ~~delay~~of orMAAs ~~prevent~~submitted athrough ~~change in control transaction. They could also have~~ the ~~effect~~centralized ~~of discouraging others from making tender offers for our common stock~~procedure, including ~~transactions~~the ~~that~~safety ~~may~~and beperformance inof ~~your best interests. These provisions may also prevent changes in our management or limit~~ the ~~price that investors are willing to pay for our stock.~~

Our certificate of incorporation also provides that the Court of Chancery of the State of Delaware will be the exclusive forum for substantially all disputes between us and our stockholders.

If we fail to maintain proper and effective internal controls, our ability to produce accurate financial statements on a timely basis could be impaired.

We are subject to the reporting requirements of the Securities Exchange Act of 1934, the Sarbanes-Oxley Act of 2002, the Dodd-Frank Wall Street Reform and Consumer Protection Act of 2010 and the rules and regulations of The Nasdaq Capital Market. The Sarbanes-Oxley Act requires, among other things, that we maintain effective disclosure controls and procedures and internal control over financial reporting and perform system and process evaluation and testing of our internal control over financial reporting to allow management to report on the effectiveness of our internal control over financial reporting. This requires that we incur substantial additional professional fees and internal costs to expand our accounting and finance functions and that we expend significant management efforts.

We may discover areas of our internal financial and accounting controls and procedures that need improvement. Our internal control over financial reporting will not prevent or detect all errors and all fraud. A control system, no matter how well designed and operated, can provide only reasonable, not absolute, assurance that the control system’s objectives will be met. Because of the inherent limitations in all control systems, no evaluation of controls can provide absolute assurance that misstatements due to error or fraud will not occur or that all control issues and instances of fraud will be detected.

If we are unable to maintain proper and effective internal controls in the future, we may not be able to produce timely and accurate financial statements, and we may conclude that our internal controls over financial reporting are not

Table of Contents

~~effective.~~medical Ifdevice ~~that~~in ~~were~~relation to ~~happen,~~its use with the ~~market~~medicinal ~~price~~product. ofThe ~~our~~EMA ~~stock~~or ~~could~~the ~~decline~~EU member state national competent authority will assess the product in accordance with the rules for medicinal products described above but the device part must comply with the Medical Devices Regulation (including the general safety and weperformance ~~could~~requirements beprovided ~~subject~~in toAnnex ~~sanctions~~I). MAA must include—where available—the results of the assessment of the conformity of the device part with the Medical Devices Regulation contained in the manufacturer’s EU declaration of conformity of the device or ~~investigations~~the relevant certificate issued by ~~Nasdaq~~a notified body. If the MAA does not include the results of the conformity assessment and where for the conformity assessment of the device, if used separately, the ~~SEC~~involvement orof ~~other~~a ~~regulatory~~notified ~~authorities~~body is required, the competent authority must require the applicant to provide a notified body opinion on the conformity of the device.

By contrast, in case of drug-delivery products intended to administer a medicinal product where the device and the medicinal product do not form a single integral product (but are e.g. co-packaged), the medicinal product is regulated in accordance with the rules for medicinal products described above while the device part is regulated as a medical device and will have to comply with all the requirements set forth by the Medical Devices Regulation.

WeThe docharacteristics ~~not~~of ~~anticipate~~non-integral ~~paying~~devices ~~any~~used ~~cash~~for ~~dividends~~the onadministration ~~our~~of ~~common~~medicinal ~~stock~~products may impact the quality, safety and ~~our~~efficacy ~~stock~~profile of the medicinal products. To the extent that administration devices are co-packaged with the medicinal product or, in exceptional cases, where the use of a specific type of administration device is specifically provided for in the product information of the medicinal product, additional information may ~~not~~need ~~appreciate~~to be provided in ~~value~~the MAA for the medicinal product on the characteristics of the medical device(s) that may impact on the quality, safety and/or efficacy of the medicinal product.

WeThe ~~have~~requirements ~~never~~regarding ~~declared~~quality ordocumentation ~~paid~~for ~~cash~~medicinal ~~dividends~~products onwhen ~~our~~used ~~common~~with ~~stock.~~a Wemedical ~~intend~~device, toincluding ~~retain~~single ~~all~~integral ~~available~~products, ~~funds~~co-packaged ~~to continue our operations through the Merger~~ and doreferenced ~~not~~products, ~~anticipate~~are ~~declaring~~outlined orin ~~paying any cash dividends on our common stock. Any return to stockholders will therefore be limited to~~ the ~~appreciation~~EMA guideline of ~~their~~July ~~stock~~22, if2021, ~~any.~~which ~~There~~became isapplicable noas ~~guarantee that shares~~ of ~~our~~January ~~common~~1, ~~stock will appreciate in value or that the price at which our stockholders have purchased their shares will be able to be maintained~~2022.

The aforementioned EU rules are generally applicable in the EEA.

~~Our~~Coverage, ~~ability~~Pricing toand ~~use net operating loss carryforwards may be subject to limitations.~~Reimbursement

AsIn ofaddition, ~~December~~in ~~31,~~many ~~2024~~countries, wethe ~~had~~proposed ~~federal~~pricing for a drug must be approved before it may be lawfully marketed. The requirements governing drug pricing and ~~state~~reimbursement ~~net~~vary ~~operating~~widely ~~loss~~from ~~carryforwards~~country ofto ~~$351~~country.8 ~~million~~In the EU, ~~research~~governments influence the price of products through their pricing and ~~development~~reimbursement ~~tax~~rules ~~credit~~and ~~carryforwards~~control of ~~$10~~national healthcare systems that fund a large part of the cost of those products to consumers.9 ~~million~~Member states are free to restrict the range of pharmaceutical products for which their national health insurance systems provide reimbursement, and ~~$44.1~~to ~~million~~control the prices and reimbursement levels of ~~orphan~~pharmaceutical ~~drug~~products ~~tax~~for ~~credit~~human ~~carryforwards~~use. ~~The~~Some ~~federal~~jurisdictions operate positive and ~~state~~negative ~~net~~list ~~operating~~systems ~~loss~~under ~~carryforwards~~which ~~will~~products ~~begin~~may only be marketed once a reimbursement price has been agreed to ~~expire,~~by ifthe ~~not~~government. ~~utilized,~~Member ~~beginning~~states inmay ~~2025~~approve a specific price or level of reimbursement for the pharmaceutical product, or alternatively adopt a system of direct or indirect controls on the ~~research~~profitability ~~and~~of ~~development~~the ~~tax~~company ~~credits~~responsible infor ~~2025~~placing the pharmaceutical product on the market, including volume-based arrangements, caps and reference pricing mechanisms. To obtain reimbursement or pricing approval, some of these countries may require the ~~orphan~~completion ~~drug~~of ~~tax~~clinical ~~credit~~trials inthat ~~2033~~compare the cost effectiveness of a particular product to currently available therapies. ~~These~~Other ~~net~~member ~~operating~~states ~~loss~~allow ~~and~~companies ~~tax~~to ~~credit~~fix ~~carryforwards~~their ~~could~~own ~~expire~~prices ~~unused~~for medicines, but monitor and control company profits. There can be ~~unavailable~~no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products. The downward pressure on healthcare costs in general, particularly prescription products, has become very intense. As a result, increasingly high barriers are being erected to ~~offset~~the ~~future~~entry ~~income~~of ~~tax~~new ~~liabilities~~products. In addition, in some countries, cross-border imports from low priced markets exert a commercial pressure on pricing within a country.

Other Healthcare Laws

~~Under~~Moreover, ~~federal~~analogous ~~income~~state ~~tax~~and foreign laws, ~~federal~~and ~~net~~regulations ~~operating~~may ~~losses~~be ~~incurred~~broader in ~~2018~~scope ~~and~~than inthe ~~future~~provisions ~~years~~described above and may beapply ~~carried~~regardless ~~forward~~of ~~indefinitely,~~payor. ~~but~~These ~~the~~laws ~~deductibility~~and ofregulations ~~such~~may ~~federal~~differ ~~net~~from ~~operating~~one ~~losses~~another isin ~~limited. In~~significant ~~addition~~ways, ~~under~~thus ~~Section~~further ~~382~~complicating ofcompliance ~~the~~efforts. ~~Internal~~For ~~Revenue~~instance, ~~Code~~in ofthe ~~1986~~EU, asmany ~~amended,~~EU ~~and~~member ~~corresponding~~states ~~provisions~~have ofadopted ~~state~~specific ~~law,~~anti-gift ifstatutes athat ~~corporation~~further ~~undergoes~~limit ancommercial ~~“ownership~~practices ~~change~~for medicinal products,” ~~which~~in isparticular ~~generally~~vis-à-vis ~~defined~~healthcare asprofessionals and organizations. Additionally, there has been a ~~greater~~recent ~~than~~trend ~~50%~~of ~~change,~~increased byregulation of payments and transfers of value, inprovided ~~its~~to ~~equity~~healthcare ~~ownership~~professionals ~~over~~or aentities ~~three-year~~and ~~period,~~many ~~the~~EU ~~corporation’s~~member ~~ability~~states tohave ~~use~~adopted ~~its~~national ~~pre-change~~“Sunshine ~~net~~Acts” ~~operating~~which ~~loss~~impose ~~carryforwards~~reporting and ~~other~~transparency ~~pre-change~~requirements ~~tax~~(often ~~attributes~~on an annual basis), similar to ~~offset~~the ~~its~~requirements ~~post-change~~in ~~income~~the orUnited ~~taxes~~States, ~~may~~on bepharmaceutical ~~limited~~companies. ~~The~~Certain ~~Merger~~countries ~~with~~also ~~Crescent,~~mandate ifimplementation ~~consummated~~of commercial compliance programs, ~~could~~or ~~result~~require indisclosure anof ~~ownership~~marketing ~~change~~expenditures ~~that~~and ~~would~~pricing ~~limit~~information. ~~the~~Violation ~~ability~~of any of ~~the~~such ~~combined~~laws ~~company~~or toany ~~use~~other ~~our~~governmental ~~net~~regulations ~~operating~~that ~~loss~~apply ~~carryforwards.~~may result in penalties, including, without limitation, significant administrative, civil

ITEM 1B. UNRESOLVED STAFF COMMENTS

None.

ITEM 1C. CYBERSECURITY

Risk management and strategy

We operate in the biopharmaceutical sector, which is a highly regulated sector subject to various cybersecurity risks that could adversely affect our business, financial condition, and results of operations, including intellectual property theft; fraud; extortion; harm to employees or customers; disruption of our clinical trials, manufacturing or supply chain; violation of privacy laws and other litigation and legal risk; and reputational risk. Prior to our decision to streamline our operations, we implemented and still maintain various information security processes designed to identify, assess and manage material risks from cybersecurity threats to our critical computer networks, third party hosted services, communications systems, hardware and software, and our critical data, including clinical trial data, intellectual property, confidential information that is proprietary, strategic, financial or competitive in nature, and personal data (“Information Systems and Data”).

With the assistance of outside consultants, our Information Technology personnel help identify, assess and manage cybersecurity threats and risks that could affect our business and Information Systems and Data, and support our efforts to identify and assess risks from cybersecurity threats by monitoring and evaluating our threat environment. We use various methods and tools to identify, assess and manage our cybersecurity threats and risks, including, for example, automated tools, industry reports about cybersecurity risks and threats to our industry, third party threat assessments, and penetration testing. In addition, we utilize encryption for certain data at rest and maintain certain network security controls, such as firewalls and virtual private networks. We also conduct monitoring for certain systems and access controls in place for certain environments and systems, as well as asset management, tracking and disposal associated with onboarding and offboarding of personnel.

Table of Contents

~~Depending on the environment, we implement~~ and ~~maintain~~criminal ~~various technical~~penalties, ~~physical~~damages, ~~and organizational measures~~fines, ~~processes~~disgorgement, ~~standards~~additional ~~and~~reporting ~~policies~~obligations ~~designed to manage~~ and ~~mitigate~~oversight ~~material~~if ~~risks~~a ~~from~~manufacturer ~~cybersecurity~~becomes ~~threats~~subject to ~~our~~a ~~Information~~corporate ~~Systems~~integrity ~~and~~agreement ~~Data. For~~or ~~example,~~other weagreement ~~have implemented and maintain an incident response plan, and we utilize automated tools designed~~ to ~~help~~resolve ~~maintain~~allegations ~~email~~of ~~security. We~~non-compliance ~~also~~with ~~have~~these ~~certain system and password policies for computer systems managed and controlled by us~~laws, ~~and~~the ~~procedures~~curtailment ~~for~~or ~~incident~~restructuring ~~management~~of ~~to address incidents that could impact subject safety~~operations, ~~product~~exclusion ~~quality,~~from ~~and~~participation ~~data integrity~~ in ~~relation~~governmental tohealthcare ~~our~~programs ~~clinical trials~~ and ~~product development~~imprisonment. ~~We also periodically conduct cybersecurity incident tabletop training exercises.~~

Healthcare Reform

~~Our~~Similar ~~assessment~~political, economic and ~~management~~regulatory ofdevelopments ~~material~~are ~~risks~~occurring ~~from~~in ~~cybersecurity~~the ~~threats~~EU isand ~~integrated~~may ~~into~~affect ~~various~~the ~~aspects~~ability of ~~our~~pharmaceutical ~~overall~~companies ~~risk~~to ~~management~~profitably ~~process~~commercialize their products. ~~For~~ ~~example~~In addition to continuing pressure on prices and cost containment measures, ~~our~~legislative ~~head~~developments ofat ~~Information~~the ~~Technology~~EU ~~evaluates~~or ~~material~~EU ~~risks~~member ~~from~~state ~~cybersecurity~~level ~~threats~~may ~~and~~result ~~reports~~in ~~periodically~~significant toadditional ~~our~~requirements ~~Board~~or obstacles. The delivery of ~~Directors’~~healthcare ~~Audit~~in ~~Committee~~the EU, ~~which~~including ~~committee~~the establishment and operation of health services and the pricing and reimbursement of medicines, is ~~responsible~~almost exclusively a matter for ~~evaluation~~national, ofrather ~~our~~than ~~overall~~EU, ~~enterprise~~law ~~risk~~and policy. We ~~use~~National ~~third-party~~governments and health service providers tohave ~~assist~~different uspriorities ~~from~~and ~~time~~approaches to ~~time~~the todelivery ~~identify,~~of ~~assess,~~health care and ~~manage~~the ~~material~~pricing ~~risks~~and ~~from~~reimbursement ~~cybersecurity~~of ~~threats~~products in that context. In general, ~~including~~however, ~~for~~the ~~example,~~healthcare ~~cybersecurity~~budgetary ~~software~~constraints ~~providers,~~in ~~penetration~~most ~~testing~~EU ~~firms,~~member ~~auditors,~~states have resulted in restrictions on the pricing and ~~professional~~reimbursement ~~services~~of ~~firms,~~medicines ~~including~~by ~~legal~~relevant ~~counsel~~health service providers. ~~These~~ ~~relationships~~Coupled ~~enable~~with usever-increasing toEU ~~leverage~~and ~~specialized~~national ~~knowledge~~regulatory burdens on those wishing to develop and ~~insights~~market products, ~~enabling~~this ~~our~~could ~~cybersecurity~~restrict ~~strategies~~or regulate post-approval activities and ~~processes~~affect the ability of pharmaceutical companies to ~~remain~~commercialize ~~consistent~~their ~~with~~products. ~~industry~~In ~~best~~international ~~practices~~markets, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies.

In the EU, potential reductions in prices and changes in reimbursement levels could be the result of different factors, including reference pricing systems, parallel distribution and parallel trade. It could also result from the application of external reference pricing mechanisms, which consist of arbitrage between low-priced and high-priced countries. Reductions in the pricing of our medicinal products in one EU member state could affect the price in other EU member states and, thus, have a negative impact on our financial results.

WeHealth ~~rely~~Technology onAssessment ~~third-party~~(“HTA”), ~~service providers to perform a variety~~ of ~~functions~~medicinal ~~throughout~~products ~~our~~in ~~business,~~the ~~such~~EU asis ~~contract~~an ~~manufacturing~~essential ~~organizations,~~element ~~contract~~of ~~research~~the ~~organizations,~~pricing ~~suppliers~~ and ~~consultants. We~~reimbursement ~~also~~decision-making ~~rely~~process onin ~~third parties who operate~~ a ~~cloud-based~~number ~~infrastructure~~of ~~for~~EU ~~our~~member ~~information technology systems~~states. WeThe ~~have~~outcome ~~in the past conducted quality audits~~ of ~~certain~~HTA ~~regulated~~has ~~vendors,~~a ~~which~~direct ~~typically~~impact ~~include~~on anthe ~~assessment~~pricing ~~of such vendor’s information technology systems,~~ and wereimbursement ~~may~~status ~~also~~granted ~~impose~~to ~~appropriate~~the ~~contractual~~medicinal ~~obligations~~product. onA ~~certain~~negative ~~vendors~~HTA ~~pertaining~~by toa ~~information~~leading ~~security. Depending~~and onrecognized ~~the~~HTA ~~nature~~body ofconcerning ~~the~~a ~~services~~medicinal ~~provided,~~product ~~the~~could ~~sensitivity~~undermine of the ~~Information~~prospects ~~Systems~~to ~~and~~obtain ~~Data~~reimbursement atfor ~~issue,~~such ~~and~~product ~~the~~not ~~identity~~only ofin the ~~provider,~~EU ~~our~~member ~~efforts~~state ~~may~~in ~~involve~~which ~~different~~the ~~levels~~negative of assessment ~~designed~~was toissued, ~~help~~but ~~identify~~also ~~cybersecurity~~in ~~risks~~other ~~associated~~EU ~~with~~member ~~a provider and impose contractual obligations related to cybersecurity on the provider~~states.

In 2011, Directive 2011/24/EU was adopted at the EU level. This Directive establishes a voluntary network of national authorities or bodies responsible for HTA in the individual EU member states. The network facilitates and supports the exchange of scientific information concerning HTAs. Further to this, 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 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 new 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.

~~For~~European aData ~~description of the risks from cybersecurity threats that may materially affect us and how they may do so, see our risk factors under Part 1. Item 1A. Risk Factors in this Annual Report on Form 10-K.~~Laws

The collection and use of personal health data and other personal data in the EU is governed by the provisions of the European General Data Protection Regulation (EU) 2016/679 (GDPR), which came into force in May 2018, and related data protection laws in individual EU Member States. The GDPR imposes a number of strict obligations and restrictions on the ability to process, including collecting, analyzing and transferring, personal data of individuals, in particular with respect to health data from clinical trials and adverse event reporting. The GDPR includes requirements relating to the legal basis of the processing (such as consent of the individuals to whom the personal data relates), the information provided to the individuals prior to processing their personal data, the personal data breaches which may have to be notified to the national data protection authorities and data subjects, the measures to be taken when engaging processors, and the security and confidentiality of the personal data. EU Member States may also impose additional requirements in relation to health, genetic and biometric data through their national legislation.

Risk Management Personnel

Our Information Technology personnel responsible for cybersecurity risk assessment and management processes are managed by certain members of our executive management, including our Chief Financial Officer. Together with our executive management, our Information Technology personnel are responsible for hiring appropriate personnel, helping to integrate cybersecurity risk considerations into our overall risk management strategy, and communicating key priorities to relevant personnel.

Governance

Our Board of Directors addresses our cybersecurity risk management as part of its general oversight function. The Audit Committee of our Board is responsible for overseeing our cybersecurity risk management processes, including oversight and mitigation of risks from cybersecurity threats.

Our Audit Committee and other members of our executive management, as appropriate, receive periodic reports from our Chief Financial Officer concerning significant cybersecurity threats and risk and the processes we have implemented to address them. The Audit Committee also receives various periodic presentations related to cybersecurity threats, risk and mitigation.

ITEM 2. PROPERTIES

Our principal offices occupied approximately 30,000 square feet of leased office space in Rockville, Maryland, pursuant to a lease agreement that expired on January 31, 2025. In anticipation of the consummation of the Merger, we no longer maintain a physical office or laboratory space, and all remaining employees work remotely.

Table of Contents

~~ITEM~~In 3addition, the GDPR imposes specific restrictions on the transfer of personal data to countries outside of the European Economic Area (EEA) that are not considered by the European Commission (EC) to provide an adequate level of data protection. ~~LEGAL~~Appropriate ~~PROCEEDINGS~~safeguards are required to enable such transfers. Among the appropriate safeguards that can be used, the data exporter may use the standard contractual clauses (“SCCs”). When relying on SCCs, data exporters are also required to conduct a transfer risk assessment to verify if anything in the law and/or practices of the third country may impinge on the effectiveness of the SCCs in the context of the transfer at stake and, if so, to identify and adopt supplementary measures that are necessary to bring the level of protection of the data transferred to the EU standard of essential equivalence. Where no supplementary measure is suitable, the data exporter should avoid, suspend or terminate the transfer. With regard to the transfer of data from the EEA to the United States, on July 10, 2023, the EC adopted its adequacy decision for the EU-US Data Privacy Framework. On the basis of the new adequacy decision, personal data can flow from the EEA to U.S. companies participating in the framework. With regard to the transfer of data from the EU to the United Kingdom (UK), personal data may freely flow from the EEA to the UK since the UK is deemed to have an adequate data protection level. However, the adequacy decisions include a ‘sunset clause’ which entails that the decisions will automatically expire four years after their entry into force, unless renewed.

~~From~~Failure ~~time~~ to ~~time,~~comply wewith ~~are~~the ~~subject~~requirements toof ~~litigation~~the GDPR and ~~claims~~the ~~arising~~related innational ~~the~~data ~~ordinary~~protection ~~course~~laws of ~~business.~~the WeEU ~~are~~Member ~~not~~States ~~currently~~may aresult ~~party~~in tosignificant ~~any~~monetary ~~material~~fines ~~legal~~for ~~proceedings~~noncompliance ~~and~~of weup ~~are~~to ~~not~~€20 ~~aware~~million or 4% of ~~any~~the ~~pending~~annual orglobal ~~threatened~~revenues ~~legal~~of ~~proceeding~~the ~~against~~noncompliant uscompany, ~~that~~whichever weis ~~believe~~greater, ~~could~~other ~~have~~administrative penalties and a ~~material~~number ~~adverse~~of ~~effect~~criminal onoffenses ~~our~~for ~~business~~organizations and, ~~operating~~in ~~results~~certain cases, ~~cash~~their ~~flows~~directors orand ~~financial~~officers, ~~condition~~as well as civil liability claims from individuals whose personal data was processed.

~~ITEM~~Data 4.protection ~~MINE~~authorities ~~SAFETY~~from ~~DISCLOSURES~~the different EU Member States may still implement certain variations, enforce the GDPR and national data protection laws differently, and introduce additional national regulations and guidelines, which adds to the complexity of processing personal data in the EU.

~~Not~~Furthermore, ~~applicable~~there are specific requirements relating to processing health data from clinical trials, including public disclosure obligations provided in the EU Clinical Trials Regulation No. 536/2014 (CTR), EMA disclosure initiatives and voluntary commitments by industry. Failure to comply with these obligations could lead to government enforcement actions and significant penalties against us, harm to our reputation, and adversely impact our business and operating results.

~~PART~~Additionally, IIfollowing the UK’s withdrawal from the EU and the EEA, companies also have to comply with the UK’s data protection laws (including the UK GDPR (as defined in section 3(10) (as supplemented by section 205(4)) of the Data Protection Act 2018 (the DPA 2018)), the DPA 2018, and related data protection laws in the UK). Separate from the fines that can be imposed by the GDPR, the UK regime has the ability to fine up to the greater of £17.5 million or 4% of global turnover. Companies are subject to specific transfer rules under the UK regime which broadly mirror the GDPR rules. On February 2, 2022, the UK Secretary of State laid before the UK Parliament the international data transfer agreement (IDTA) and the international data transfer addendum to the EC’s standard contractual clauses for international data transfers (Addendum) and a document setting out transitional provisions. The IDTA and Addendum came into force on March 21, 2022 and replaced the old SCCs for the purposes of the UK regime. Regarding transfers from the UK to the EEA, personal data may flow freely since the EEA is deemed to have an adequate data protection level for purposes of the UK regime. With regard to the transfer of personal data from the UK to the United States, the UK government has adopted an adequacy decision for the United States, the UK-US Data Bridge, which came into force on October 12, 2023. The UK-US Data Bridge recognizes the United States as offering an adequate level of data protection where the transfer is to a U.S. company participating in the EU-US Data Privacy Framework and the UK Extension.

~~ITEM~~Anti-Corruption 5.Legislation ~~MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES~~

~~Market~~In ~~Information~~the ~~for~~EU, ~~Common~~interactions ~~Stock~~between pharmaceutical companies and physicians are also governed by strict laws, regulations, industry self-regulation codes of conduct and physicians’ codes of professional conduct both at EU level and in the individual EU Member States. The provision of benefits or advantages to physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order or use of medicinal products is prohibited in the European Union. The provision of benefits or advantages to physicians is also governed by the national anti-bribery laws of the EU Member States. Violation of these laws could result in substantial fines and imprisonment.

~~Our~~Payments ~~common~~made ~~stock~~to isphysicians ~~listed~~in oncertain ~~The~~EU ~~Nasdaq~~Member ~~Capital~~States ~~Market~~also ~~under~~must be publicly disclosed. Moreover, agreements with physicians must often be the ~~symbol~~subject ~~“GLYC~~of prior notification and approval by the physician’s employer, his/her regulatory professional organization, and/or the competent authorities of the individual EU Member States.” These requirements are provided in the national laws, industry codes, or professional codes of conduct, applicable in the individual EU Member

Dividend Policy

We have never declared or paid any dividends on our common stock. We do not anticipate paying cash dividends in the foreseeable future.

Stockholders

As of February 7, 2025, we had 64,513,862 shares of common stock outstanding held by approximately 20 holders of record. The actual number of stockholders is greater than this number of record holders and includes stockholders who are beneficial owners but whose shares are held in street name by brokers and other nominees. This number of holders of record also does not include stockholders whose shares may be held in trust by other entities.

Recent Sales of Unregistered Securities

None.

Purchases of Equity Securities by the Issuer and Affiliated Parties

None.

ITEM 6. [RESERVED]

Table of Contents

~~ITEM 7~~States. ~~MANAGEMENT’S~~Failure ~~DISCUSSION~~to ~~AND~~comply ~~ANALYSIS~~with OFthese ~~FINANCIAL~~requirements ~~CONDITION~~could ~~AND~~result ~~RESULTS~~in OFreputational ~~OPERATIONS~~risk, public reprimands, administrative penalties, fines or imprisonment.

~~You~~In ~~should~~the ~~read~~UK, the ~~following~~pharmaceutical ~~discussion~~sector ~~and~~is ~~analysis~~recognized as being particularly vulnerable to corrupt practices, some of ~~our~~which ~~financial~~fall ~~condition~~within ~~and~~the ~~results~~scope of ~~operations~~the ~~together~~Bribery ~~with~~Act ~~our~~2010. ~~consolidated~~Due ~~financial~~to ~~statements~~the ~~and~~Bribery Act 2010’s far-reaching territorial application, the ~~related~~potential ~~notes~~penalized ~~and~~act ~~other~~does ~~financial~~not ~~information~~have ~~included~~to ~~elsewhere~~occur in ~~this~~the ~~Annual~~UK ~~Report.~~to ~~Some~~become ofwithin its scope. If the ~~information~~act ~~contained~~or omission does not take place in ~~this~~the ~~discussion~~UK, ~~and~~but ~~analysis~~the person’s act or ~~set~~omission ~~forth~~would ~~elsewhere~~constitute inan ~~this~~offense ~~Annual~~if ~~Report,~~carried ~~including~~out ~~information~~there ~~with~~and ~~respect~~the toperson ~~our~~has ~~plans~~a ~~and~~close ~~strategy~~connection ~~for~~with ~~our~~the ~~business~~UK, ~~includes~~an ~~forward-looking~~offense ~~statements~~will still have been committed. The Bribery Act 2010 is comprised of four offenses that ~~involve~~cover ~~risks~~(i) individuals, companies and ~~uncertainties.~~partnerships ~~You~~that ~~should~~give, ~~review~~promise ~~Item 1A.~~or ~~“Risk~~offer ~~Factors”~~bribes, ~~and~~(ii) ~~“Special~~individuals, ~~Note~~companies ~~Regarding~~and ~~Forward-Looking~~partnerships ~~Statements”~~that inrequest, ~~this~~agree ~~Annual~~to ~~Report~~receive ~~for~~or aaccept ~~discussion~~bribes, of(iii) ~~important~~individuals, ~~factors~~companies and partnerships that ~~could~~bribe ~~cause~~foreign ~~actual~~public ~~results~~officials, and (iv) companies and partnerships that fail to ~~differ~~prevent ~~materially~~persons ~~from~~acting ~~the~~on ~~results~~their ~~described~~behalf infrom orpaying ~~implied~~bribes. byThe penalties imposed under the ~~forward-looking~~Bribery ~~statements~~Act ~~contained~~2010 independ on the ~~following~~offence ~~discussion~~committed, harm and ~~analysis~~culpability and penalties range from unlimited fines to imprisonment for a maximum term of 10 years and in some cases both.

~~Overview~~Regulations ~~and~~in ~~Recent~~the ~~Developments~~UK

WeFollowing ~~are~~the aend ~~biotechnology company that was previously developing a pipeline~~ of ~~proprietary glycomimetics, which are small molecules that mimic~~ the ~~structure~~Brexit oftransition ~~carbohydrates~~period ~~involved~~on inJanuary ~~important biological processes~~1, to2021 ~~inhibit~~and ~~disease-related~~the ~~functions~~implementation of ~~carbohydrates such as~~ the ~~roles~~Windsor ~~they~~Framework ~~play~~on inJanuary ~~cancers and inflammation. Our previous lead glycomimetic drug candidate~~1, ~~uproleselan~~2025, isthe aUK ~~specific~~is ~~E-selectin~~not ~~antagonist~~generally ~~that~~subject ~~we were developing~~ to beEU ~~used~~laws in ~~combination~~respect ~~with~~of ~~chemotherapy~~medicines. toThe ~~treat~~EU ~~patients~~laws ~~with~~that ~~acute~~have ~~myeloid~~been ~~leukemia,~~transposed orinto ~~AML,~~UK alaw ~~life-threatening~~through ~~hematologic~~secondary ~~cancer,~~legislation ~~and~~remain ~~potentially~~applicable ~~other~~in ~~hematologic~~the ~~cancers. We conducted a randomized~~UK, ~~double-blind~~however, ~~placebo-controlled~~new ~~Phase~~legislation 3such ~~pivotal~~as ~~clinical~~the ~~trial to evaluate uproleselan in individuals with relapsed/refractory~~ (~~R/R~~EU) ~~AML.~~CTR Inis ~~May 2024, we reported topline results from the Phase 3 trial, in which uproleselan combined with chemotherapy did~~ not ~~achieve~~applicable ~~a statistically significant improvement~~ in ~~overall survival in~~ the ~~intent to treat (ITT) population versus chemotherapy alone~~UK. ~~In June 2024, we announced comprehensive results of the Phase 3 trial.~~

As of January 1, 2021, the Medicines and Healthcare products Regulatory Agency (“MHRA”) is the UK’s standalone medicines and medical devices regulator. As a result of the Northern Ireland Protocol, different rules applied in Northern Ireland than in England, Wales, and Scotland (together, “Great Britain”), which continued to follow the EU regulatory regime for a period of time after Brexit. However, on January 1, 2025 a new arrangement called the “Windsor Framework” came into effect and reintegrated Northern Ireland under the regulatory authority of the MHRA with respect to medicines. The Windsor Framework removes EU licensing processes and EU labeling and serialization requirements in relation to Northern Ireland and introduces a UK-wide licensing process for medicines.

~~Following~~The ~~the~~UK ~~announcement~~regulatory offramework ~~the~~in ~~data~~relation ~~from~~to ~~the~~clinical ~~Phase~~trials 3is ~~trial,~~governed weby ~~requested~~the ~~and~~Medicines ~~held~~for aHuman ~~meeting~~Use ~~with~~(Clinical ~~the~~Trials) ~~FDA~~Regulations to2004, ~~discuss~~as ~~whether~~amended, ~~any~~which ofis ~~the~~derived ~~results~~from ~~summarized~~the ~~above~~EU ~~could~~Clinical ~~serve~~Trials Directive, as aimplemented ~~basis~~into ~~for~~UK anational ~~submission~~law ~~for~~through ~~regulatory~~secondary ~~approval~~legislation. ~~Based~~In onApril ~~the feedback received~~2025, wethe ~~concluded~~UK ~~that~~introduced ~~any~~the ~~potential~~Medicines ~~regulatory path~~ for ~~uproleselan~~Human inUse ~~this~~(Clinical ~~patient~~Trials) ~~population~~(Amendment) ~~would~~Regulations ~~require~~2025. anThese ~~additional clinical trial~~changes, ~~the conduct of~~ which ~~would~~will ~~require~~take ~~capital~~full ~~resources~~effect ~~beyond~~from ~~those~~April ~~available~~2026, toaim ~~us. The decision~~ to ~~not~~create ~~conduct~~a anstreamlined, ~~additional~~risk-proportionate ~~clinical~~system ~~trial~~that ~~did~~accelerates ~~not~~approvals ~~relate~~while tomaintaining ~~any~~robust safety ~~or medical issues or negative regulatory feedback related to our programs~~standards.

Marketing authorizations in the UK are governed by the Human Medicines Regulations (SI 2012/1916), as amended. In order to use the centralized procedure to obtain a marketing authorization that will be valid throughout the EEA, companies must be established in the EEA. Therefore, after Brexit, companies established in the UK can no longer use the EU centralized procedure and instead an EEA entity must hold any centralized marketing authorizations. In order to obtain a UK marketing authorization to commercialize products in the UK, an applicant must follow one of the UK national authorization procedures or one of the remaining post-Brexit international cooperation procedures. The MHRA has introduced changes to national licensing procedures, including procedures to prioritize access to new medicines that will benefit patients, a 150-day assessment (subject to clock-stops) and a rolling review procedure. In addition, since January 1, 2024, the MHRA may rely on the International Recognition Procedure (“IRP”) when reviewing certain types of MAAs. Pursuant to the IRP, the MHRA will take into account the expertise and decision-making of trusted regulatory partners (e.g. the medicines regulatory authorities in Australia, Canada, Switzerland, Singapore, Japan, the U.S.A. and the EMA in the EU). The MHRA will conduct a targeted assessment of IRP applications but retain the authority to reject applications if the evidence provided is considered insufficiently robust.

In ~~July~~the ~~2024~~UK, ~~following~~ the ~~announcement~~initial duration of ~~the~~a ~~data~~marketing ~~from~~authorization ~~our~~is ~~Phase~~five 3years ~~pivotal trial~~ and ~~our~~following ~~discussions~~renewal ~~with~~will ~~the~~be ~~FDA,~~valid wefor ~~announced~~an ~~that~~unlimited weperiod ~~would~~unless ~~initiate~~the aMHRA ~~review~~decides ~~of strategic alternatives focused~~ on ~~maximizing~~justified ~~stockholder~~grounds ~~value,~~relating ~~which~~to ~~could~~pharmacovigilance ~~include, but are not limited~~ to, aproceed ~~merger,~~with ~~sale,~~only ~~divestiture~~one ofadditional ~~assets,~~five-year ~~licensing, or other strategic transaction~~renewal. Any Weauthorization ~~also~~which ~~reduced~~is ~~our~~not ~~workforce~~followed by ~~approximately 80% in~~ the ~~third~~actual ~~quarter~~placing of ~~2024~~the inmedicine ~~order~~on tothe ~~conserve~~market ~~our~~in ~~cash~~the ~~resources~~UK aswithin ~~part~~three ofyears ashall ~~streamlined~~cease ~~operating~~to ~~plan~~be ~~while~~in ~~we undertook our strategic review~~force.

There is no pre-marketing authorization orphan designation in the UK. Instead, the MHRA reviews applications for orphan designation in parallel to the corresponding MAA. The criteria are essentially the same as in the EU, but have been tailored for the market, i.e., the prevalence of the condition in the UK, rather than the EU, must not be more than five in 10,000. Should an orphan designation be granted, the period or market exclusivity will be set from the date of first approval of the product in the UK.

We also previously entered into a Cooperative Research and Development Agreement, or CRADA, with the National Cancer Institute, or NCI, part of the National Institutes of Health, to conduct a Phase 2/3 randomized, controlled clinical trial testing the addition of uproleselan to a standard chemotherapy regimen. On October 29, 2024 we announced data from the Phase 2 portion of the trial showing no statistically significant improvement in event-free survival (EFS) for patients receiving uproleselan in combination with chemotherapy versus chemotherapy alone.

Following these outcomes of our clinical trials and regulatory discussions we do not currently intend to continue development of uproleselan or any of our other drug candidates. We currently do not have any ongoing clinical trials.

The Merger Agreement

Following the strate

gic review described above, on October 28, 2024 we entered into the Merger Agreement with Crescent, a privately held biotechnology company advancing a pipeline of oncology therapeutics designed to treat solid tumors, pursuant to which Crescent will become a wholly owned subsidiary of us and we will operate under the name Crescent Biopharma, Inc. following the Merger. We anticipate that the Merger will close in the late second quarter of 2025, subject to certain closing conditions, along with the concurrent Private Placement. For additional information about the Merger and the

Table of Contents

~~concurrent~~Regulation ~~Private~~of ~~Placement,~~Medicinal ~~see~~Products ~~Note 1 to the financial statements included~~ in ~~this~~Australia ~~report. Following the Merger, the current business of Crescent will become the primary business of our company.~~

The Australian Therapeutic Goods Administration (“TGA”) and the National Health and Medical Research Council (“NHMRC”) set the GCP requirements for clinical research in Australia.

~~Based~~Compliance onwith ~~our~~the ~~current operating plan~~regulations, westandards ~~expect~~and ~~that~~codes ~~our~~set ~~current~~by ~~cash~~the TGA and ~~cash~~NHMRC ~~equivalents~~is ~~will~~mandatory. ~~fund~~Under ~~our~~the ~~operations~~Therapeutic ~~until~~Goods ~~the~~Act ~~closing~~1989 of(Cth) and the ~~contemplated~~Therapeutic ~~Merger~~Goods Regulations 1990 (Cth), ~~which~~it is ~~subject~~a condition (amongst other conditions) of all clinical trials involving investigational medicinal products to ~~approval~~comply with the National Statement on Ethical Conduct in Research Involving Humans, published by ~~our~~the ~~stockholders~~NHMRC (the “National Statement”), and the ~~stockholders~~Guideline for Good Clinical Practice published by the International Council for Harmonization of ~~Crescent~~Technical ~~and~~Requirements ~~other~~for ~~customary~~Registration ~~closing~~of ~~conditions;~~Pharmaceuticals ~~however,~~for weHuman Use (“ICH Guidelines”). The ICH Guidelines have ~~based~~been ~~this~~adopted ~~estimate~~in onAustralia ~~assumptions~~and ~~that~~must ~~may~~be ~~prove~~complied with across all fields of clinical research involving therapeutic goods, including those related to bepharmaceutical ~~wrong~~quality, nonclinical and weclinical ~~could~~data ~~use~~requirements ~~our~~and ~~capital~~trial ~~resources~~designs. ~~sooner~~The ~~than~~basic werequirements ~~expect.~~for Ifpreclinical ~~the~~data ~~contemplated~~to ~~Merger~~support ~~and~~a ~~Private~~first-in-human ~~Placement~~trial ~~does~~under ~~not~~ICH ~~close~~Guidelines byare ~~the~~applicable ~~second~~in ~~quarter~~Australia. ofRequirements ~~2025,~~related ~~the~~to ~~Company~~adverse ~~may~~event ~~seek~~reporting in Australia are generally similar to those required in other ~~strategic~~major ~~alternatives~~jurisdictions, oralthough ~~liquidate~~reporting timeframes may differ to other jurisdictions.

Clinical trials conducted using “unapproved therapeutic goods” in Australia, being those which have not yet been evaluated by the TGA for quality, safety and efficacy (and including unapproved indications of therapeutic goods which have otherwise been approved for use in Australia) must occur pursuant to either the Clinical Trial Notification Scheme (“CTN Scheme”) or the Clinical Trial Approval Scheme (“CTA Scheme”). In each case, the trial is supervised by a Human Research Ethics Committee (“HREC”), an independent review committee constituted in accordance with the National Statement that ensures the protection of rights, safety and well-being of human subjects involved in a clinical trial. An HREC reviews, approves and provides continuing oversight of trial protocols (including any amendments), methods and materials intended to be used in obtaining and documenting informed consent of the clinical trial subjects.

~~Critical~~The ~~Accounting~~CTN ~~Policies~~Scheme ~~and~~broadly ~~Significant~~involves: ~~Judgments and Estimates~~

~~Our~~•submission ~~management’s~~to ~~discussion~~an ~~and analysis of our financial condition and results of operations is based on our financial statements~~HREC, ~~which have been prepared in accordance with generally accepted accounting principles in the United States, or GAAP. The preparation~~ of ~~these~~all ~~financial~~material ~~statements~~relating ~~requires us~~ to ~~make estimates, judgments and assumptions that affect~~ the ~~reported~~proposed ~~amounts~~clinical ~~of assets and liabilities~~trial, ~~disclosure~~including ~~of contingent assets and liabilities as of~~ the ~~dates~~trial ofprotocol; the balance sheets and the reported amounts of revenue and expenses during the reporting periods. In accordance with GAAP, we base our estimates on historical experience and on various other assumptions that we believe are reasonable under the circumstances at the time such estimates are made. Actual results may differ materially from our estimates and judgments under different assumptions or conditions. We periodically review our estimates in light of changes in circumstances, facts and experience. The effects of material revisions in estimates are reflected in our financial statements prospectively from the date of the change in estimate.

•the HREC reviews the scientific validity of the trial design, the balance of risk versus harm of the therapeutic good, the ethical acceptability of the trial process, and approves the trial protocol. The HREC is also responsible for monitoring the conduct of the trial;

We•the ~~define~~institution ~~our~~or ~~critical~~organization ~~accounting~~at ~~policies~~which asthe ~~those~~trial ~~accounting~~will ~~principles~~be ~~generally~~conducted ~~accepted in~~ (the ~~United~~“Approving ~~States~~Authority”) ~~that~~giving ~~require~~final usapproval tofor ~~make~~the ~~subjective~~conduct ~~estimates and judgments about matters that are uncertain and are likely to have a material impact on our financial condition and results~~ of ~~operations,~~the astrial ~~well~~at as the ~~specific~~site, ~~manner~~ in ~~which~~terms weno ~~apply~~less ~~those~~restrictive ~~principles. While our significant accounting policies are more fully described in Note 3~~ to ~~our~~those ~~financial~~advised ~~statements~~by ~~appearing elsewhere in this Annual Report, we believe~~ the ~~following~~HREC; ~~are the critical accounting policies used in the preparation of our financial statements that require significant judgments~~ and ~~estimates.~~

•the investigator submitting a ‘Notification of Intent to Conduct a Clinical Trial’ form (“CTN Form”) to the TGA. The CTN Form must be signed by the sponsor, the principal investigator, the chairman of the HREC and a person responsible from the Approving Authority. The TGA does not review any data relating to the clinical trial however CTN trials cannot commence until the trial has been notified to the TGA. It is the responsibility of the sponsor to ensure that all relevant approvals are in place before supplying the “unapproved” therapeutic goods in clinical trials in Australia.

~~Stock-Based~~Under ~~Compensation~~the CTA Scheme:

We•a ~~have~~sponsor ~~issued~~submits ~~stock-based~~an ~~compensation~~application ~~awards~~ to ~~our~~conduct ~~employees~~a ~~and~~clinical ~~non-employee~~trial ~~directors, including stock options. We measure stock-based compensation expense related~~ to ~~these awards based on~~ the ~~fair~~TGA ~~value~~for ofevaluation ~~the award, utilizing the Black-Scholes-Merton option pricing model, on the date of grant~~ and ~~recognize stock-based compensation expense on a straight-line basis over the requisite service period of the awards~~comment, which ~~generally~~includes ~~equals~~payment ~~the vesting period. We account for forfeitures as they occur. We previously granted stock options with exercise prices equal to the estimated fair value~~ of ~~our~~relevant ~~common~~fees; stock on the date of grant. The Black-Scholes-Merton option pricing model requires the input of various assumptions that require management to apply judgment and make assumptions and estimates, including:

~~Risk-Free~~•the ~~Interest~~TGA ~~Rate—The~~will ~~risk-free~~undertake ~~interest~~a ~~rate~~preliminary ~~assumption~~assessment isto ~~based~~ensure onthat ~~observed~~there ~~interest~~is ~~rates~~sufficient ~~for~~data ~~constant~~to ~~maturity~~begin Uevaluation.S. ~~Treasury~~If ~~securities~~critical ~~consistent~~data ~~with~~is missing, the ~~expected~~TGA ~~life~~may ofrequest ~~our~~further ~~employee~~information; ~~stock options.~~

~~Expected~~•a ~~Term—The~~sponsor ~~expected~~must ~~life~~forward ~~represents~~any ~~the~~comments ~~period~~made ofby ~~time~~ the ~~stock~~TGA ~~options~~delegate ~~are expected~~ to ~~be outstanding and is based on~~ the ~~simplified~~HREC(s) ~~method.~~at ~~Under~~ the ~~simplified~~sites ~~method,~~where the ~~expected~~trial ~~life~~will ~~of an option is presumed to~~ be ~~the~~conducted; midpoint between the vesting date and the end of the contractual term. We used the simplified method due to the lack of sufficient historical exercise data to provide a reasonable basis upon which to otherwise estimate the expected life of the stock options.

~~Expected Volatility— Volatility is a measure of~~ •the ~~amount~~HREC ~~by which a financial variable such as share price has fluctuated (historical volatility) or~~ is ~~expected~~responsible tofor ~~fluctuate~~considering ~~(expected volatility) during a period. We based~~ the ~~expected~~scientific ~~volatility~~and onethical ~~the~~issues ~~historical volatility~~ of ~~our~~the ~~publicly~~proposed ~~traded~~trial ~~common stock~~protocol.

~~Expected~~A ~~Dividend~~sponsor ~~Yield—We~~cannot ~~have~~commence ~~assumed~~a notrial ~~dividend~~under ~~yield~~the ~~because~~CTA weScheme dountil ~~not~~written ~~expect~~advice tohas ~~pay~~been ~~dividends~~received infrom the ~~future,~~TGA ~~which~~regarding isthe ~~consistent~~application ~~with~~and ~~our~~approval ~~history~~for the conduct of ~~not~~the ~~paying~~trial ~~dividends~~has been obtained from an ethics committee and the institution at which the trial will be conducted.

Table of Contents

~~Components~~Approval for inclusion in the Australian Register of ~~Operating~~Therapeutic ~~Results~~Goods (“ARTG”) is required before a therapeutic good (including pharmaceutical product) may be marketed (or supplied, imported, exported or manufactured) in Australia. Exceptions apply to therapeutic goods/pharmaceutical products that are supplied, imported, and exported to and from Australia for the purposes of a clinical trial, on the basis that certain conditions are met (e.g., the trial is conducted in accordance with the CTN or CTA Scheme).

~~Revenue~~Once a sponsor decides to register a therapeutic good/pharmaceutical product in Australia, in order to obtain registration of the product on the ARTG, it is required that (amongst others):

We•the ~~have~~sponsor ~~not~~submits ~~generated~~appropriate ~~any~~documentation, ~~revenue~~including ~~from~~ the ~~sale~~outcomes of ~~our~~clinical ~~drug~~trials ~~candidates~~ and dostudies, ~~not expect~~ to ~~generate~~allow ~~any revenue from~~ the ~~sale~~TGA ofto ~~drugs~~assess in the ~~near~~quality, ~~future.~~safety ~~Substantially~~and ~~all~~efficacy of ~~our~~the ~~historical~~therapeutic ~~revenue~~product/ ~~consisted~~pharmaceutical ofproduct; ~~upfront~~ and ~~milestone payments under license and collaboration agreements. We do not expect to recognize revenue in the future under any current license or collaboration agreement.~~

~~Research~~•the ~~and~~sponsor ~~Development~~submits evidence which demonstrates that the manufacture of the therapeutic product/ pharmaceutical product complies with the applicable GMP requirements.

~~Research~~The ~~and~~TGA ~~development~~has ~~expenses~~the ~~have~~ultimate ~~consisted~~discretion of expenses incurred in performing research and development activities, including compensation and benefits for full-time research and development employees, facilities expenses, overhead expenses, cost of laboratory supplies, clinical trial and related clinical manufacturing expenses, fees paid to ~~CROs~~decide ~~and~~whether ~~other consultants and other outside expenses. Other preclinical research and platform programs have included activities related~~ to ~~exploratory~~include ~~efforts,~~the ~~target~~therapeutic ~~validation,~~product/ ~~lead~~pharmaceutical ~~optimization~~product ~~for~~in ~~our~~the ~~earlier programs and our proprietary glycomimetics platform~~ARTG.

Regulation of Medical Products in New Zealand

WeClinical ~~have~~trials ~~not~~in ~~utilized~~New aZealand ~~formal~~are ~~time~~regulated ~~allocation~~under ~~system~~the toMedicines ~~capture~~Act ~~expenses~~1981 on(“Medicines aAct”) ~~project-by-project basis because we were organized~~ and ~~recorded~~Medicines ~~expense~~Regulations ~~by functional department and our employees allocated time to more than one development project~~1984. ~~Accordingly, we have only allocated a portion of our research and development expenses by functional area and by drug candidate.~~

Clinical Trial Requirements

~~Research~~The ~~and~~New ~~development~~Zealand ~~costs~~Medicines ~~are~~and ~~expensed~~Medical asDevices ~~incurred.~~Safety ~~Non-refundable~~Authority ~~advance~~(“Medsafe”) ~~payments~~is ~~for~~the ~~goods~~regulatory orauthority ~~services~~that toadministers bethe ~~received~~application inand ~~the~~approval ~~future~~process for ~~use~~medicines ~~in research~~ and ~~development~~clinical ~~activities~~trials ~~were~~in ~~deferred~~New ~~and~~Zealand ~~capitalized.~~(under ~~The~~delegation ~~capitalized~~from ~~amounts~~the ~~are~~Director-General ~~expensed~~of asHealth). ~~the~~Approval ~~related~~from ~~goods~~Medsafe ~~are~~is ~~delivered~~required orin the ~~services~~following ~~are~~two ~~performed.~~circumstances:

•before a medicine can be distributed in New Zealand - see “Approval for Distribution” below; however, there is an exemption from this approval requirement for medicines that are imported or manufactured for the sole purpose of use in a clinical trial (including pharmacokinetic, bioequivalence and first-in-human studies); and

~~General~~•for ~~and~~all ~~Administrative~~clinical trials involving unapproved medicines carried out in New Zealand; however, if a medicine is already approved by Medsafe for distribution in New Zealand, then there is no separate requirement to obtain approval for clinical trials with that medicine (including if the medicine is being tested for a use not provided for under its existing authorization).

~~General~~Medsafe ~~and~~also ~~administrative~~expects ~~expenses~~all ~~have~~clinical ~~consisted~~trials ~~primarily~~to ofbe ~~salaries~~carried ~~and~~out ~~other~~in ~~related~~accordance ~~costs,~~with ~~including~~internationally ~~stock-based~~accepted ~~compensation,~~standards for ~~personnel~~good inclinical ~~executive,~~practice ~~finance,~~as ~~accounting,~~published ~~business~~by ~~development~~the ~~and~~EMA ~~human~~in ~~resources~~its ~~functions.~~Guideline ~~Other~~for ~~significant~~Good ~~costs~~Clinical ~~include facility costs not otherwise included in research and development expenses~~Practice, ~~legal fees relating~~ to ~~patent~~the ~~and~~extent ~~corporate~~that ~~matters~~these ~~and~~standards ~~fees~~are ~~for~~compatible ~~accounting~~with ~~and~~the ~~consulting~~Medicines ~~services~~Act.

Clinical Trial Approval Process

~~Interest~~The ~~Income~~clinical trial approval process requires submission of an online application to Medsafe. The application must include information about the nature of the medicine, the purpose of the trial, details of the investigators conducting the trial, written consent to nomination from each investigator, copies of information supplied to the investigators, a protocol of the trial, and details of the sites and facilities used. The application must be made by the actual or intended importer, manufacturer, packer, or supplier of the medicine in New Zealand. Once approved, the applicant becomes the “sponsor” and assumes responsibility and legal liability for the trial in New Zealand.

~~Other~~Once ~~income~~an ~~consists~~application is received, Medsafe provides it to the Health Research Council of ~~interest~~New ~~income~~Zealand ~~earned~~(“HRC”). One of two HRC standing committees will consider the application and make a recommendation to Medsafe as to whether the clinical trial should be approved (with or without conditions) or declined. The Standing Committee on ~~our~~Therapeutic ~~cash~~Trials considers pharmaceutical medicine trial applications, while the Gene Technology Advisory Committee considers applications for trials involving gene and ~~cash~~other ~~equivalents~~biotechnology therapies. Both standing committees undertake a similar scientific assessment process, and consider factors such as trial protocol and design, data collection, and general compliance with the Guideline for Good Practice before making a recommendation to Medsafe.

Results of Operations

The following table sets forth our results of operations:


	Year Ended December 31,				Increase/(Decrease)
(dollars in thousands)	2024		2023
Revenue	$	—	$	10	$	(10)	(100)	%
Costs and expenses:
Research and development expense		14,260		20,072		(5,812)	(29)	%
General and administrative expense		18,249		19,213		(964)	(5)	%
Restructuring and asset impairment charges		7,530		—		7,530	100	%
Total costs and expenses		40,039		39,285		754	2	%
Loss from operations		(40,039)		(39,275)		(764)	(2)	%

Other income
Gain on sale of asset		1,225		—		1,225	100	%
Interest income		935		2,376		(1,441)	(61)	%
Total other income		2,160		2,376		(216)	(9)	%
Net loss and comprehensive loss	$	(37,879)	$	(36,899)	$	(980)	(3)	%

Table of Contents

~~Revenue~~Ethical Requirements

~~During~~Medsafe ~~the~~expects ~~years~~all ~~ended~~clinical ~~December~~trials ~~31,~~to ~~2024~~be approved by the Health and ~~2023~~Disability Ethics Committee (“HDEC”), weregardless ~~recognized~~of $0whether Medicines Act approval is required. HDEC reviews and ~~$10~~approves applications and provides ongoing oversight of clinical trials to ensure alignment with good ethical practice. HDEC approval can be sought before,~~000,~~ ~~respectively~~during, inor ~~revenue~~after ~~from~~Medicines ~~our~~Act ~~license~~approval ~~agreements~~is ~~with~~sought ~~Apollomics~~from Medsafe.

Registration

~~Research~~A clinical trial’s sponsor may register a trial with the Australian New Zealand Clinical Trials Registry (“ANZCTR”), an online public registry of clinical trials undertaken in New Zealand, Australia, and ~~Development~~elsewhere. ~~Expense~~While not mandatory, the ANZCTR is a recognized part of the World Health Organisation Registry Network and registration is encouraged by the World Health Organisation.

~~The~~Approval ~~following~~for ~~table~~Distribution ~~summarizes our research and development expense by functional area:~~

If a sponsor decides to distribute the new medicine product in New Zealand after the clinical trial, the sponsor must apply for distribution approval. This is separate to the approval process for clinical trials and involves submitting an application to Medsafe for consideration. Medsafe assesses the safety, efficacy, quality and risk profile of the medicine, and makes a recommendation to the Minister of Health as to whether the medicine should be approved for distribution (in practice, the Minister follows Medsafe’s recommendation).


	Year Ended December 31,				Increase/(Decrease)
(dollars in thousands)	2024		2023
Clinical development	$	3,090	$	6,533	$	(3,443)	(53)	%
Manufacturing and formulation		4,145		1,702		2,443	144	%
Contract research services, consulting and other costs		1,184		1,792		(608)	(34)	%
Laboratory costs		780		1,548		(768)	(50)	%
Personnel-related		3,789		7,587		(3,798)	(50)	%
Stock-based compensation		1,272		910		362	40	%
Research and development expense	$	14,260	$	20,072	$	(5,812)	(29)	%

Employees and Human Capital Resources

~~The~~As ~~following~~of ~~table~~December ~~summarizes~~31, ~~our~~2025, ~~research~~we had 44 full-time employees. We also engage temporary employees and ~~development~~consultants ~~expense~~to augment our existing workforce. None of our employees are represented by ~~drug~~a ~~candidate:~~labor union or covered under a collective bargaining agreement. We consider our relationship with our employees to be good.

We recognize that attracting, motivating, and retaining talent at all levels is vital to continuing our success. We invest in our employees through high-quality benefits, professional development opportunities, and various health and wellness initiatives and offers competitive compensation packages (base salary and incentive plans), ensuring fairness in internal compensation practices. The principal purposes of our incentive plans (bonus and equity) are to align with the long-term interests of its stakeholders and shareholders.


	Year Ended December 31,				Increase/(Decrease)
(dollars in thousands)	2024		2023
Uproleselan	$	7,471	$	7,587	$	(116)	(2)	%
GMI-1687		313		1,742		(1,429)	(82)	%
Other research and development		1,416		2,246		(830)	(37)	%
Personnel-related and stock-based compensation		5,060		8,497		(3,437)	(40)	%
Research and development expense	$	14,260	$	20,072	$	(5,812)	(29)	%

Available Information

~~Our~~We ~~research~~file ~~and~~annual, ~~development~~quarterly, ~~expense~~and ~~for~~current ~~the~~reports, ~~year~~proxy ~~ended~~statements, ~~December~~and ~~31,~~other ~~2024~~information ~~decreased~~with bythe $5U.8S. ~~million~~Securities ~~compared~~and toExchange ~~2023~~Commission ~~primarily~~(“SEC”). ~~due~~Our toSEC ~~our~~filings ~~winding~~are ~~down~~available ofto ~~operations~~the ~~beginning~~public inover ~~June~~the ~~2024~~Internet ~~following~~at the ~~results~~SEC’s ~~from~~website ~~our~~at ~~clinical trials~~www. ~~During~~sec.gov. ~~2023,~~Our weSEC ~~accrued~~filings ~~amounts~~are ~~for~~also ~~the~~available ~~expected~~free ~~payments~~ of ~~year-end~~charge ~~bonuses~~under tothe ~~employees;~~Investors assection noof ~~bonuses~~our ~~are~~website ~~payable~~at ~~for~~www.crescentbiopharma.com ~~the~~as ~~year~~soon ~~ended~~as ~~December~~reasonably ~~31,~~practicable ~~2024,~~after wethey ~~did~~are ~~not~~filed ~~recorded~~with

Filing Compare · CRESCENT BIOPHARMA, INC.