UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 10-K


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

For the fiscal ~~year~~years ended December 31, ~~2022~~2023, 2024 and 2025


☐	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: 001-31326

ELOXX PHARMACEUTICALS, INC.

(Exact Name of Registrant as Specified in Its Charter)

     Delaware

     84-1368850

     (State or Other Jurisdiction of
Incorporation or Organization)

     (I.R.S. Employer
Identification No.)

~~480~~P.O. ~~Arsenal~~Box ~~Way~~274

~~Watertown,~~10 ~~Massachusetts~~Court ~~02472~~ Street

Arlington, MA 02476

(Address of Principal Executive Offices and Zip Code)

(781) 577-5300

(Registrant’s Telephone Number, Including Area Code)

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

Title of each class		Trading Symbol(s)		Name of each exchange on which registered
Common Stock, $0.01 par value		ELOX		NASDAQ Capital Market

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

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


Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common Stock, $0.01 par value	ELOX	OTC Expert Market

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

Indicate by check mark if the Registrant is not required to file reports pursuant to Section 13 or 15(d) of the Act. Yes ☐ No ☒

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

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

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


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

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

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

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~~officers during the relevant recovery period pursuant to §240.10D-1(b). ☐

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

The aggregate market value of the voting stock held by non-affiliates of the registrant on June 30, ~~2022~~2025, the last business day of the registrant’s most recently completed second quarter, was $16330.00,~~650,960,~~ based on the closing price for such stock as reported on the ~~NASDAQ~~OTC ~~Capital~~Expert Market on that date.

As of March 2812, ~~2023~~2026, there were 25,~~166~~071,~~356~~935 shares of the Registrant’s common stock, par value $0.01 per share, outstanding.

~~DOCUMENTS~~ELOXX ~~INCORPORATED~~PHARMACEUTICALS, BYINC. ~~REFERENCE~~

Certain information required by Part III, Items 10-14 of this Form 10-K is incorporated by reference to the Registrant’s definitive Proxy Statement for the 2022 Annual Meeting of Stockholders to be filed with the Securities and Exchange Commission pursuant to Regulation 14A not later than 120 days after the end of the fiscal year covered by this Form 10-K, provided that if such Proxy Statement is not filed within such period, such information will be included in an amendment to this Form 10-K to be filed within such 120-day period.

ELOXX PHARMACEUTICALS INC.

TABLE OF CONTENTS

		Page
	Special Note Regarding Forward-Looking Statements	ii
	Market and Industry Data	~~iii~~ii
	Risk Factor Summary	iv
	PART I	1
ITEM 1.	Business	1
ITEM 1A.	Risk Factors	2125
ITEM 1B.	Unresolved Staff Comments	5568
ITEM 2.	Properties	55
ITEM 1C.	Cybersecurity	68
ITEM 3.	Legal Proceedings	55
ITEM 2.	Properties	69
ITEM 4.	Mine Safety Disclosures	55
ITEM 3.	Legal Proceedings	69
	PART II	56
ITEM 4.	Mine Safety Disclosures	69
ITEM 5.	Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities	56
	PART II	70
ITEM 6.	Reserved	56
ITEM 5.	Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities	70
ITEM 7.	Management’s Discussion and Analysis of Financial Condition and Results of Operations	57
ITEM 6.	Reserved	71
ITEM 7A.	Quantitative and Qualitative Disclosure About Market Risk	64
ITEM 7.	Management’s Discussion and Analysis of Financial Condition and Results of Operations	72
ITEM 8.	Financial Statements and Supplementary Data	64
ITEM 7A.	Quantitative and Qualitative Disclosure About Market Risk	83
ITEM 9.	Changes in and Disagreements with Accountants on Accounting and Financial Disclosure	64
ITEM 8.	Financial Statements and Supplementary Data	83
ITEM 9A.	Controls and Procedures	64
ITEM 9.	Changes in and Disagreements with Accountants on Accounting and Financial Disclosure	83
ITEM 9B.	Other Information	65
ITEM 9A.	Controls and Procedures	83
ITEM 9C.	Disclosure Regarding Foreign Jurisdictions that Prevent Inspections	65
ITEM 9B.	Other Information	84
	PART III	66
ITEM 9C.	Disclosure Regarding Foreign Jurisdictions that Prevent Inspections	84
ITEM 10.	Directors, Executive Officers and Corporate Governance	66
	PART III	85
ITEM 11.	Executive and Director Compensation	66
ITEM 10.	Directors, Executive Officers and Corporate Governance	85
ITEM 12.	Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters	66
ITEM 11.	Executive and Director Compensation	90
ITEM 13.	Certain Relationships and Related Transactions, and Director Independence	66
ITEM 12.	Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters	97
ITEM 14.	Principal Accounting Fees and Services	66
ITEM 13.	Certain Relationships and Related Transactions, and Director Independence	98
	PART IV	67
ITEM 14.	Principal Accounting Fees and Services	99
ITEM 15.	Exhibits and Financial Statement Schedules	67
	PART IV	100
ITEM 16.	Form 10-K Summary	67
ITEM 15.	Exhibits and Financial Statement Schedules	100
	SIGNATURES	73
ITEM 16.	Form 10-K Summary	100
	SIGNATURES	107

Explanatory Note

Eloxx Pharmaceuticals, Inc. (“Eloxx”) is filing this comprehensive Annual Report on Form 10-K for the years ended December 31, 2023, 2024 and 2025 (the “Annual Report”) as part of its effort to become current in its filing obligations under the Securities Exchange Act of 1934, as amended (the “Exchange Act”). This Annual Report is Eloxx’s first periodic filing with the Securities and Exchange Commission (the “SEC”) since filing the quarterly report on Form 10-Q for the quarterly period ended September 30, 2023, filed on November 13, 2023. Included in this Annual Report are our audited financial statements for the fiscal years ended December 31, 2023, 2024 and 2025, which have not been previously filed with the SEC.

Special Note Regarding Forward-Looking Statements

Eloxx Pharmaceuticals, Inc., together with its subsidiaries, is collectively referred to herein as “we,” “our,” “us,” “Eloxx” or the “Company”. Hyperlinks and web addresses are provided as a convenience and for informational purposes only. Eloxx bears no responsibility for the security or content of external websites.

This Annual Report ~~on Form 10-K (the “Annual Report”)~~ and the other documents we have filed with the U.S. Securities and Exchange Commission (the “SEC”) that are incorporated herein by reference, contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. We intend such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act of 1933, as amended (the “Securities Act”) and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). All statements other than statements of present and historical facts contained in this Annual Report, including without limitation, statements regarding expected timing of trials and results from our clinical program, strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-looking statements. Without limiting the foregoing, in some cases, you can identify forward-looking statements by terms such as “aim,” “may,” “will,” “would,” “should,” “expect,” “explore,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential,” “seeks,” or “continue” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these words. No forward-looking statement is a guarantee of future results, performance, or achievements, and one should avoid placing undue reliance on such statements.

Forward-looking statements are based on our management’s beliefs and assumptions and on information currently available to us. Such beliefs and assumptions may or may not prove to be correct. Additionally, such forward-looking statements are subject to a number of known and unknown risks, uncertainties and assumptions, and actual results may differ materially from those expressed or implied in the forward-looking statements due to various factors, including, but not limited to, those identified in Part I, Item 1A. “Risk Factors” and Part II. Item 7. “Management’s Discussion and Analysis of Financial Condition and Results of Operations.” ~~These risks and uncertainties include, but are not limited to:~~

risks related to our ability to obtain the capital necessary to fund our operations and continue as a going concern;

risks related to our dependence on our lead product candidate, ELX-02 and our ability to progress any product candidates in preclinical or clinical trials;

risks related to our ability to obtain adequate financing in the future through product licensing, public or private equity or debt financing or otherwise;

the length and expense of preclinical and clinical trial development, the uncertainty of clinical trial results and the fact that positive results from preclinical studies are not always indicative of positive clinical results;

risks related to the scope, rate and progress of our preclinical studies and clinical trials and other research and development activities;

risks related to the competition for patient enrollment from drug candidates in development;

the impact of the global COVID-19 pandemic on our clinical trials, operations, vendors, suppliers and employees;

risks related to regulatory approvals and other requirements applicable to our product candidates;

risks relating to the cost of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights;

general business conditions, regulatory environment, competition and market for our products;

business abilities and judgment of personnel, and the availability of qualified personnel; and

those identified in Part I, Item 1A. "Risk Factors" and Part II, Item 7. "Management's Discussion and Analysis of Financial Condition and Results of Operations" in this Annual Report.

Moreover, we operate in an evolving environment. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risks and uncertainties.

Although we believe the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, level of activity, performance or achievements. You should not rely upon forward-looking statements as predictions of future events. All forward-looking statements speak only as of the date of this Annual Report. Unless required by law, we will not undertake and we specifically disclaim any obligation to release publicly the result of any revisions which may be made to any forward-looking statements to reflect events or circumstances after the date of such statements or to reflect the occurrence of events, whether or not anticipated. In that respect, we wish to caution readers not to place undue reliance on any such forward-looking statements, which speak only as of the date they are made.

Market and Industry Data

This Annual Report and the other documents incorporated herein by reference include statistical and other industry and market data that we obtained from industry publications and research, surveys and studies conducted by third parties. Industry publications and third-party research, surveys and studies generally indicate that their information has been obtained from sources believed to be reliable, although they do not guarantee the accuracy or completeness of such information. While we believe these industry publications and third-party research, surveys and studies are reliable, we have not independently verified such data and disclaim responsibility for its content. Furthermore, management’s estimates are derived from publicly available information, their knowledge of our industry and their assumptions based on such information and knowledge, which we believe to be reasonable. This data involves a number of assumptions and limitations which are necessarily subject to a high degree of uncertainty and risk due to a variety of factors, including those described in this Annual Report under “Forward Looking Statements” and Part I, Item 1A “Risk Factors.” These and other factors could cause our future performance to differ materially from our assumptions and estimates.

and risk due to a variety of factors, including those described in this Annual Report under “Forward Looking Statements” and Part I, Item 1A “Risk Factors.” These and other factors could cause our future performance to differ materially from our assumptions and estimates.

iii

Risk Factor Summary

The following is a summary of the principal risks of an investment in our common stock. This summary does not list all the risks that we face. Additional discussion of the risks summarized below are included in Part I, Item 1A, “Risk Factors” and should be carefully considered, together with other information in this Annual Report and our other filings with the SEC before making an investment decision regarding our common stock.

•

We ~~are~~have ~~heavily~~been ~~dependent~~delinquent onin ~~the~~our ~~success~~public offiling ~~our~~obligations ~~lead~~under ~~product~~the ~~candidate,~~Securities ~~ELX-02.~~Exchange IfAct ~~ELX-02~~of ~~does~~1934, ~~not~~as ~~achieve~~amended, ~~positive~~and ~~results~~there ~~during~~are ~~development~~no orassurances ~~suffers~~that ~~any~~we ~~material~~will ~~development~~be ~~delays,~~successful itin ~~may~~regaining ~~adversely~~compliance ~~impact~~or, ~~the~~if ~~commercial~~regained, ~~viability~~remaining ofcurrent ~~ELX-02~~in ~~and~~ our ~~business.~~public filing obligations.

•

WeOur ~~will~~common ~~need~~stock ~~substantial~~is ~~additional~~currently ~~funding~~listed byon ~~September~~the OTC Expert Market. The Nasdaq Stock Market LLC (“Nasdaq”) suspended trading in our common stock on the Nasdaq Capital Market as of October 16, 2023. IfThough we ~~are~~intend ~~unable~~to seek an uplisting for our common stock to ~~raise~~trade ~~capital~~on ~~when~~the ~~needed~~Nasdaq Capital Market, there are no assurances that we ~~would~~will be ~~forced~~able to ~~delay,~~successfully ~~reduce,~~uplist orto ~~eliminate~~the ~~our~~Nasdaq ~~product~~Capital ~~development~~Market ~~programs~~ or ~~commercialization~~successfully ~~efforts~~maintain compliance with Nasdaq’s listing requirements.

•

~~Preclinical~~We ~~and~~are ~~clinical~~heavily ~~drug~~dependent ~~development~~on isthe asuccess ~~lengthy~~of ~~and~~our ~~expensive~~lead ~~process~~product candidate, ~~with an uncertain outcome~~exaluren. ~~Our~~If ~~preclinical~~exaluren ~~and~~does ~~clinical~~not ~~programs~~achieve ~~may~~positive ~~experience~~results ~~delays~~during ~~or may never advance, which would adversely affect ability to further advance clinical~~ development, ~~obtain regulatory approvals~~ or ~~commercialize~~suffers ~~our~~any ~~product~~material ~~candidates~~development ondelays, ait ~~timely~~may ~~basis~~adversely orimpact atthe ~~all,~~commercial ~~which~~viability ~~could~~of ~~have~~exaluren anand ~~adverse effect on~~ our business.

•

We will need substantial additional funding. If we are unable to raise capital when needed, we would be forced to delay, reduce, or eliminate our product development programs or commercialization efforts.

•

Preclinical and clinical drug development is a lengthy and expensive process, with an uncertain outcome. Our preclinical and clinical programs may experience delays or may never advance, which would adversely affect our ability to further advance clinical development, obtain regulatory approvals or commercialize our product candidates on a timely basis or at all, which could have an adverse effect on our business.

•

We and our collaborating partners may be subject, directly or indirectly, to federal and state healthcare fraud and abuse and false claims laws and regulations. If we or our collaborating partners are unable to comply, or have not fully complied, with such laws, we could face substantial penalties.

•

Our lead product ~~candidates~~candidate, including ~~ELX-02 and ZKN-13~~exaluren, may cause adverse events or have other properties that could delay or prevent their regulatory approval or limit the scope of any approved label or market acceptance.

•

Even though we have received orphan drug designation from the FDA for ~~ELX-02~~exaluren for the treatment of cystic fibrosis, cystinosis, MPS I, AS, and Rett syndrome, we may not be able to maintain the benefits of orphan drug designation or obtain orphan drug marketing exclusivity for ~~ELX-02~~exaluren or any of our other product candidates for ~~Alport~~AS ~~syndrome~~ or other indications.

•

A Fast Track Designation by the FDA, even if granted for any of our product candidates, may not lead to a faster development or regulatory review or approval process, and does not increase the likelihood that our product candidates will receive marketing approval.

We may find it difficult to recruit and enroll patients in our clinical trials, which could cause significant delays in the completion of such trials or may cause us to abandon one or more clinical trials.

•

If we are unable to develop and commercialize our product candidates, our business will be adversely affected.

•

We are a clinical stage biotechnology company and have incurred significant operating losses since our inception and anticipate that we will continue to incur substantial operating losses for the foreseeable future. We may never achieve or maintain profitability.

•

Our recurring losses from operations raise substantial doubt regarding our ability to continue as a going concern.

•

If we fail to adequately protect or enforce our intellectual property rights or secure rights to third party patents, the value of our intellectual property rights would diminish, and our business, competitive position and results of operations would suffer.

•

If we infringe the rights of third parties, we could be prevented from selling products, forced to pay damages and required to defend against litigation which could result in substantial costs and may have a material adverse effect on our business, results of operations and financial condition.

•

Maintaining and improving our financial controls and the requirements of being a public company may strain our resources, divert management’s attention and affect our ability to attract and retain qualified board members.

Our ability to use our net operating losses to offset future taxable income may be subject to certain limitations.

Our stock price may be volatile, and purchasers of our common stock could incur substantial losses.

•

Our ability to use our net operating losses to offset future taxable income may be subject to certain limitations.

PART I

ITEM 1. Business

Company Overview

We are a clinical-stage biopharmaceutical company ~~engaged~~developing innovel, ~~the~~small ~~science~~molecule ofproduct ~~ribosome~~candidates ~~modulation,~~designed ~~leveraging~~to ~~both~~modulate ~~our~~the ~~innovative~~ribosome ~~TURBO-ZM™~~and ~~chemistry~~promote ~~technology~~readthrough ~~platform~~of ~~and~~premature ~~our~~stop ~~library~~codons ofinduced ~~novel~~by ~~aminoglycosides~~nonsense mutations (“NMs”) to ~~develop~~enable ~~novel~~the ~~oral~~production ~~small~~of ~~molecule~~full-length ~~Ribosome~~proteins. ~~Modulating~~Targeting ~~Agents~~ribosome ~~(“RMAs”)~~subunits ~~and~~provides ~~Eukaryotic~~a ~~Ribosome~~therapeutic ~~Selective~~approach ~~Glycosides~~to ~~(“ERSGs”),~~addressing ~~for~~a number of genetic diseases. According to the ~~treatment~~Human ofGene ~~rare~~Mutation ~~and~~Database, ~~ultra-rare~~NMs ~~genetic~~account ~~diseases~~for ~~where~~approximately 10% to 12% of patients ~~have~~with ~~point~~a ~~nonsense~~given genetic ~~mutations~~disease. ~~that~~There ~~result~~are inover ~~premature~~7,000 ~~stop~~inherited ~~codons~~genetic ~~and~~diseases ~~less~~that ~~than~~collectively ~~full~~affect ~~length~~350 ~~proteins.~~million ~~Nonsense~~people ~~mutations~~worldwide. ~~result~~Our inimmediate ~~premature~~focus ~~stop~~is ~~codons~~to inadvance the ~~impacted~~clinical ~~messenger~~development ~~RNA~~of ~~(“mRNA”)~~our ~~which~~lead inproduct ~~turn~~candidate, ~~disrupt~~exaluren, ~~protein~~for ~~synthesis~~the ~~from~~treatment ~~that~~of ~~mRNA~~rare ~~leading~~kidney todiseases ~~less~~and, ~~than~~through ~~full~~our ~~length~~collaboration ~~proteins. Patients~~ with ~~these~~Almirall, ~~mutations~~S.A. ~~have~~(“Almirall”), ~~significantly~~ZKN-013 ~~worse~~for ~~outcomes~~the ~~than~~treatment ~~with~~of ~~missense~~rare ~~mutations~~skin diseases.

WeExaluren ~~have~~is ~~multiple programs in our pipeline including~~ a ~~clinical~~novel ~~program~~eukaryotic ~~for the treatment of Alport syndrome with ELX~~ribosome-02selective ~~(subcutaneous~~glycoside ~~delivery~~(“ERSG”), ~~preclinical~~product ~~programs~~candidate inthat ~~investigational~~is ~~new~~designed ~~drug~~to ~~("IND")~~induce ~~enabling~~premature ~~stages~~termination incodon ~~Recessive Dystrophic~~ (“~~RDEB~~PTC”) ~~and~~readthrough ~~Junctional~~in ~~Epidermolysis~~the ~~Bullosa~~presence ~~(“JEB”)~~of NMs and ~~Familial~~promote ~~Adenomatous~~the ~~Polyposis~~restoration ~~(“FAP”)~~of ~~with ZKN~~full-~~013,~~length ~~and~~proteins. ~~IND~~We ~~enabling~~believe ~~stage~~this ~~program~~mechanism ~~with~~has ~~inhaled~~the ~~delivery~~potential ofto ~~ELX-02~~apply into ~~Class~~all 1genetic ~~cystic~~diseases ~~fibrosis~~caused ~~("CF")~~by NMs. We ~~also~~are ~~have~~initially ~~various~~developing ~~earlier~~exaluren ~~discovery~~to ~~stage~~induce ~~programs~~full-length inCollagen CFIV ~~and~~protein ~~oncology.~~for Asthe ~~our~~treatment ~~programs~~of ~~advance,~~Alport wesyndrome ~~plan~~(“AS”) towith ~~actively~~NMs ~~look~~(“NMAS”). toNMAS, ~~expand~~a ~~our~~subset ~~pipeline~~of byAS, ~~seeking~~is ~~new~~a ~~indications~~genetic inkidney ~~other~~disorder ~~rare~~that ~~diseases~~is ~~for~~caused ~~compounds~~by ~~designed~~the ~~with~~loss ~~our~~of ~~platforms.~~one ~~The~~of ~~U.S.~~three ~~Food~~Collagen ~~and~~IV ~~Drug~~subtypes, ~~Administration~~Collagen IV alpha 3 (“~~FDA~~COL4A3”), ~~has~~alpha ~~granted~~4 ~~Fast~~(“COL4A4”), ~~Track~~or ~~designation~~alpha ~~for~~5 ~~ELX-02~~(“COL4A5”), ~~for~~and the ~~treatment~~resulting loss of CFthe ~~patients~~Collagen ~~with~~IV ~~nonsense~~alpha ~~mutations~~3,4,5 trimer. InThis ~~addition,~~trimer ~~the~~is ~~FDA~~made ~~granted~~in ~~ELX-02~~podocyte ~~Orphan~~cells ~~Drug~~and ~~Designation~~required for the ~~treatment~~functioning of CFthe infiltration ~~July~~structure ~~2020~~of ~~and,~~the ~~based~~kidney oncomprising the ~~European~~glomerular ~~Medicines~~basement ~~Agency’s~~membrane (“~~EMA~~GBM”) ~~positive opinion~~, ~~the~~foot ~~European~~processes ~~Commission~~(“FPs”) ~~granted~~and ~~ELX-02~~slit ~~orphan medicinal product designation in September 2018~~diaphragms.

InWe ~~March~~estimate ~~2022,~~that weNMAS ~~announced~~affects ~~our~~roughly ~~decision~~6% to ~~advance~~7% ~~ELX-02 delivered subcutaneously for the restoration~~ of ~~collagen~~AS IVpatients ~~protein~~or ~~for~~approximately ~~the treatment of Alport syndrome. Alport syndrome with nonsense mutations is a genetic kidney disorder that occurs in 1 in 50~~5,000 ~~newborns~~patients in the United States. Itand isapproximately ~~caused~~14,000 bypatients ~~the~~in ~~loss~~developed ofcountries ~~one~~and ~~of three collagen IV subtypes~~China. ~~This~~NMAS ~~disease~~ is characterized by ~~blood (~~hematuria) and proteinuria, or blood and protein, ~~(proteinuria)~~respectively, in the patient'’s urine and results in progressive kidney disease, hearing loss, and eye abnormalities. InThe ~~November~~median ~~2022,~~age weto ~~began~~kidney afailure ~~Phase~~in 2patients ~~monotherapy~~with ~~clinical~~NMAS ~~trial~~is ~~for~~19 ~~ELX-02~~years ~~for the treatment of Alport syndrome~~ and in30 ~~February~~years ~~2023,~~for ~~we announced that the first~~ patients ~~had~~with ~~been~~NMs ~~enrolled. ELX-02 treatment has demonstrated restoration of full-length protein~~ in ~~multiple~~the ~~preclinical~~COL4A3/4 ~~models,~~genes ~~including collagen IV~~ and ~~collagen~~the ~~VII~~COL4A5 ~~in cells~~gene, ~~and also clinical activity in our Phase 2 cystic fibrosis trial~~respectively. InAlthough ~~February~~angiotensin ~~2023~~converting weenzyme ~~announced~~inhibitor ~~that~~(“ACEi”) ~~the~~and ~~first~~angiotensin ~~patients~~receptor ~~had~~blocker ~~been~~(“ARB”) ~~dosed~~therapies incan ~~this~~slow ~~Phase~~progression 2to ~~trial.~~end-stage Wekidney ~~believe our results~~disease, ~~previously~~they ~~conducted~~do innot ~~vivo~~prevent ~~studies showing improvement of~~ kidney ~~function~~failure, ~~with collagen IV restoration~~ and ~~the~~there ~~ability~~are tono ~~achieve~~therapies ~~high~~approved ~~kidney~~by ~~drug levels at tolerable doses support~~ the ~~clinical development of ELX-02 in Alport syndrome~~U.S. ~~This~~Food ~~Phase~~and 2Drug ~~trial~~Administration ~~is targeting dosing of up to eight Alport syndrome patients with nonsense mutations in the collagen IV~~ (~~COL4~~“FDA”) ~~gene.~~specifically ~~Patients~~indicated ~~will be dosed for two months with a three month follow-up. In addition~~ to ~~the~~address ~~primary endpoint of safety,~~ the ~~key~~underlying ~~secondary~~genetic ~~efficacy~~cause ~~endpoint~~ of ~~proteinuria will be measured every two weeks~~AS. ~~For~~Exaluren ~~eligible~~has ~~patients,~~received ~~induction~~Orphan ofDrug ~~the~~Designation ~~COL~~for ~~IV protein will also be measured at~~ the ~~end~~treatment of ~~two~~AS ~~months.~~from ~~Topline results are expected in~~ the ~~first half of 2023~~FDA.

WeExaluren ~~are~~has ~~also~~been ~~advancing~~tested ~~ZKN-013~~in aseight anclinical ~~oral~~trials ~~agent~~including ~~for~~four ~~the~~Phase ~~treatment~~1 ofstudies ~~RDEB/JEB~~in ~~and~~healthy ~~FAP~~volunteers, ~~patients~~one ~~with~~Phase ~~nonsense~~2a ~~mutations.~~study ~~RDEB~~in ~~and~~NMAS, ~~JEB~~two ~~are~~Phase ~~rare~~2 ~~skin~~studies ~~diseases characterized by mutations~~ in ~~Collagen~~cystic ~~VII~~fibrosis (~~RDEB~~“CF”) ~~and LAMB3(JEB) proteins. We estimate that there are approximately 4,000~~ patients with ~~nonsense mutations in these diseases in the major markets of the United States~~NMs, ~~Japan,~~ and ~~western~~one ~~Europe.~~Phase ~~Patients~~2 ~~suffer~~study ~~from severe skin bruising, wounds and internal lesions resulting~~ in ~~increased~~nephropathic ~~risk~~cystinosis ofpatients ~~skin~~with ~~cancer~~NMs. ~~and~~In ~~severe~~total, ~~malnourishment.~~145 ~~FAP~~subjects ~~patients~~ have ~~mutations~~received inat ~~the~~least ~~APC~~one ~~gene~~dose ~~that result in a proliferation~~ of ~~polyps~~exaluren induring ~~the~~these ~~colon~~clinical ~~that if untreated can lead to colon and other related cancers~~trials. ~~There~~In ~~are currently no approved disease modifying therapies for~~ these ~~diseases. ZKN-013 has demonstrated robust collagen VII restoration in patient cells comparable to 5-10% of protein restoration across a range of mutations. We have also seen in two separate~~ studies, ~~that~~no ~~treatment of APCMin mice, a validated model for evaluating potential treatment effects in FAP patients, with ZKN~~dose-~~013~~limiting ~~for~~toxicities ~~eight~~were ~~weeks reduced polyp number~~reported, ~~polyp size~~ and ~~meaningfully~~no ~~improved~~serious ~~survival.~~adverse Onevents ~~March~~were ~~24,~~attributed ~~2023,~~to ~~we submitted an IND for ZKN-013 for the treatment of RDEB~~exaluren.

InWe ~~September~~conducted ~~2022,~~a proof-of-concept Phase 2a open-label monotherapy trial in ~~consultation~~the United Kingdom in three patients with autosomal recessive AS and a NM in the ~~Cystic~~COL4A4 ~~Fibrosis~~gene. ~~Foundation~~All three patients showed a reduction in podocyte foot process effacement (~~“CFF”~~"FPE"), wewhich ~~terminated~~is the ~~development~~flattening and loss of ~~ELX-02~~specialized ~~delivered~~kidney ~~subcutaneously,~~cell ~~for~~structures that form the ~~treatment~~filtration ofbarrier CFand ~~patients~~attach ~~with~~to atthe ~~least~~podocytes ~~one~~and ~~nonsense~~GBM, ~~(“Class~~in 1transmission CFelectron microscopy (“TEM”) ~~mutation~~images. ~~This~~FPE ~~decision~~is a hallmark of kidney diseases including AS and the severity of FPE has historically been associated with time to kidney failure. TEM images of biopsy samples also showed an improvement in the GBM width in all treated patients. FPE was ~~made~~also ~~after~~measured ~~our~~as ~~Phase~~a 250% ~~trial~~increase in the filtration slit density (“FSD”). These results were consistent with exaluren’s proposed mechanism of ~~ELX~~functional full-02length protein restoration as reflected by improvements in ~~combination~~GBM ~~with~~architecture ~~ivacaftor,~~and anFPE ~~approved~~observed ~~drug~~in ~~currently~~kidney ~~marketed~~biopsies. ~~for~~We plan to initiate a Phase 2b clinical trial in the ~~treatment~~first half of ~~certain~~2026 CFfor exaluren in NMAS patients ~~under~~and anticipate topline data from the ~~trade~~initial ~~name~~16-week ~~“Kalydeco”,~~placebo-controlled ~~did~~part of the study by mid-2027 with the final readout by the end of 2027.

Our pipeline also includes a preclinical program evaluating exaluren for the treatment of autosomal dominant polycystic kidney disease (“ADPKD”) in patients that have NMs (“nmADPKD”). ADPKD is the most common monogenic kidney disease based on genetic diagnosis, affecting approximately 160,000 to 200,000 patients in the United States. The PKD1 gene encodes polycystin-1 (“PC1”) and the PKD2 gene encodes polycystin-2 (“PC2”), these are proteins that regulate cell growth and fluid secretion in kidney tubules. Loss of functional PC1 or PC2 protein leads to uncontrolled cyst formation. Approximately 26% of ADPKD patients have NMs in the PKD1 and PKD2 genes resulting in a prevalence of approximately 40,000 to 50,000 patients in the United States. Patients experience hypertension, kidney stones, urinary tract infections, heart valve abnormalities, hematuria and increased probability of aortic aneurysm. Formation of these cysts eventually leads to nephromegaly (kidney enlargement) and end-stage renal disease. The only approved therapy for ADPKD, tolvaptan, does not address the underlying genetic

~~not~~cause ~~meet~~and ~~the~~carries ~~secondary~~significant ~~efficacy~~tolerability ~~endpoint of reduction from baseline in sweat chloride concentration (SCC) or improvement from baseline in percent forced expiratory volume (FEV1)~~limitations. ~~Encouragingly,~~Preclinical weorganoid ~~continued~~and tocellular ~~see~~models ~~strong~~have ~~evidence~~shown ofincreased ~~biological~~PC1 ~~activity~~and ~~similar~~PC2 togene ~~that~~expression infollowing ~~our previously completed Phase 2 study that reported in November 2021 a reduction in sweat chloride concentration from baseline after one week of~~ treatment with ~~ELX-02~~exaluren. We ~~believe~~plan ~~that the lack of statistically significant clinical benefit in Class 1 CF patients was due~~ to ~~drug~~initiate ~~concentration~~enrollment in ~~the~~a ~~lung tissue being significantly below that required for effect consistent with our preclinical studies. ELX-02 was well tolerated in the~~ Phase 2 trial ~~with~~of noexaluren ~~drug~~for ~~related adverse events even at~~ the ~~clinical~~treatment ~~dose~~ of ~~1.5mg/kg.~~nmADPKD ~~Going~~in ~~forward,~~2027 wefollowing ~~plan~~protocol tofinalization ~~only~~and ~~develop~~clearance ~~ELX-02~~of as an ~~inhaled~~Investigational ~~therapy~~New ~~for~~Drug ~~Class~~application 1(“IND”) CFby ~~patients because~~ the ~~achievable drug concentrations are more than one-hundred times higher in the lung tissue than when given subcutaneously~~FDA. We ~~have~~anticipate ~~completed~~topline ~~the~~data ~~IND~~from ~~enabling~~this ~~studies~~trial ~~for~~by ~~inhaled ELX~~mid-~~02 in Class 1 CF but further clinical development is contingent upon funding from the CFF~~2028.

~~Acquisition~~ We are also developing ZKN-013, an oral ribosome modulating agent (“RMA”) with structural similarity to azithromycin that induces PTC readthrough. In March 2024, we entered into an exclusive global rights agreement with Almirall (the “Almirall License Agreement”) for Almirall to develop and commercialize ZKN-013 for the use in orphan dermatological diseases. Through this collaboration, we are developing ZKN-013 for the treatment of ~~Zikani~~recessive ~~Therapeutics~~dystrophic epidermolysis bullosa (“RDEB”) and junctional epidermolysis bullosa (“JEB”) with NMs. RDEB and JEB are rare skin diseases characterized by mutations in the Collagen VII (RDEB) and LAMB3 (JEB) proteins. We estimate that there are approximately 4,000 ~~Inc~~patients with NMs in these diseases in the major markets of the United States, Japan and Western Europe. Patients with these diseases suffer from severe skin bruising, wounds and internal lesions resulting in increased risk of skin cancer and severe malnourishment. Under the Almirall License Agreement, we received an upfront payment of $3 million and a development milestone of $3 million in 2024. Almirall is responsible for development and commercialization of ZKN-013 and we are eligible to receive up to approximately $470.0 million in additional development, regulatory and commercial milestone payments as well as tiered royalties based on global sales. The agreement may be terminated under specified circumstances, including for convenience by Almirall, in which case rights may revert to us.

OnOur ~~April~~Product 1, 2021, the Company acquired Zikani Therapeutics, Inc. (“Zikani” and such acquisition, the “Zikani Merger”), a company in preclinical development and engaged in the science of ribosome modulation, leveraging its innovative TURBO-ZMTM chemistry technology platform to develop novel RMAs as potential therapeutics for diseases with limited treatment options. The TURBO-ZMTM platform is designed to enable rapid synthesis of novel compounds that can be optimized to modulate the ribosome in a disease specific manner. The TURBO-ZMTM synthetic chemistry platform can design oral novel macrolide-based small molecules that are potent oral modulators with favorable therapeutic indices. Macrolides are antibiotics that inhibit protein synthesis in bacteria. Candidates

~~Our~~We ~~Technology~~are working to unlock the potential of the ribosome in order to transform genetic diseases. Ribosomes form the translation machinery that generates functional proteins from genetic sequences. By modulating ribosome subunits, we believe we have the potential to advance product candidates for the subset of genetic diseases with NMs, such as AS, ADPKD, RDEB, JEB, familial adenomatous polyposis (“FAP”) and CF.

WeOur product candidates, exaluren and ZKN-013, are ~~working~~novel tosmall ~~unlock~~molecules ~~the~~based ~~potential~~on ofantibiotic ~~the~~aminoglycoside ~~ribosome~~and tomacrolide ~~transform~~molecules ~~genetic~~that ~~diseases.~~have ~~Ribosomes~~previously ~~form~~shown ~~the~~potential ~~translation~~for ~~machinery~~PTC ~~that~~readthrough. ~~generates~~Exaluren ~~functional~~and ~~proteins~~ZKN-013 ~~from~~are ~~genetic~~designed ~~sequences;~~to ~~modulating~~promote ~~the~~PTC readthrough with human ribosome ~~subunits~~selectivity, ~~provides~~potentially aoffering ~~therapeutic~~lower ~~approach~~toxicity and positioning them to ~~addressing~~address adefects ~~number~~caused ofby ~~diseases~~NMs. WeWhile ~~are~~antibiotic ~~focused~~macrolides onand ~~modulating~~aminoglycosides ~~the~~have ~~ribosome~~shown toactivity ~~address~~in ~~two~~clinical ~~specific~~and ~~defects:~~preclinical ~~(1)~~studies, ~~nonsense~~significant ~~mutations~~safety, ~~implicated~~tolerability inand ~~many~~delivery ~~rare~~limitations have prevented further development for human diseases. We believe exaluren and ~~(2)~~ZKN-013 ~~ribosomal~~are ~~mutations~~designed ~~driving~~to ~~cancer~~be safer, more potent and easier to deliver than aminoglycoside and macrolide antibiotics.

WeNonsense ~~are~~Mutations using our TURBO-ZM™ chemistry technology platform and our library of novel aminoglycosides to develop novel small molecule RMAs and ERSGs, that are uniquely positioned to correct both nonsense mutations and ribosomal mutations. Clinical and preclinical results for the ability of macrolide and aminoglycoside antibiotics to restore proteins in nonsense mutations have been shown in more than 36 rare diseases. These molecules have also shown an ability to selectively stop protein translation. However, significant safety, tolerability and delivery limitations have prevented further development for human diseases. Our RMA and ERSG molecules are designed to be safer, more potent, and easier to deliver than traditional macrolide and aminoglycoside antibiotics and thus fulfill their clinical promise.

~~Nonsense~~According to the Human Gene Mutation Database, NMs account for approximately 10% to 12% of patients with a given genetic disease. NMs are single point mutations within the DNA sequence which are either inherited or acquired. The disease phenotypes caused by NMs are frequently more severe than those caused by other kinds of mutations because these mutations often lead to a complete loss of protein production or function. The ribosome manufactures proteins one amino acid at a time designated by a series of three nucleotides, called a codon. An NM leads to a PTC in the messenger RNA (“mRNA”) and the production of truncated, non-functional proteins. In simple terms, an NM changes the codon for an amino acid into the codon for a “STOP” signal in mRNA, leading to the formation of a truncated protein with loss of function.

~~Nonsense~~Patients ~~mutations,~~with ~~also~~diagnosed ~~known~~NMs ason ~~premature~~one ~~termination~~ or ~~stop~~both ~~codons,~~alleles ~~are~~represent ~~single~~a ~~point~~high ~~mutations~~unmet ~~within~~medical ~~the~~need. ~~DNA~~NMs ~~sequence which~~ are ~~either~~involved ~~inherited or acquired that result~~ in ~~the~~a ~~premature~~large ~~termination~~number of ~~the~~genetic ~~translational~~diseases ~~process~~such ~~leading~~as toAS, ~~truncated~~ADPKD, orRDEB, ~~absent proteins. The ribosome manufactures protein one amino acid at a time designated by a series of three nucleotides~~JEB, ~~called~~FAP aand ~~codon~~CF. AThere ~~nonsense~~are ~~mutation~~no ~~changes~~FDA-approved ~~the~~small ~~codon~~molecule ~~for~~therapies anspecifically ~~amino~~designed ~~acid into the codon for a “STOP” signal leading~~ to ~~the~~promote ~~formation~~ribosomal ofreadthrough ain ~~truncated~~genetic ~~protein~~kidney ~~with~~diseases ~~loss~~caused ofby ~~function~~NMs.

WeReadthrough ~~believe that the segment~~ of ~~patients~~NMs ~~with~~is ~~diagnosed nonsense mutations on one or both alleles represents~~ a ~~high~~naturally ~~unmet~~occurring ~~medical~~process ~~need~~that ascan ~~there~~be ~~are~~attributed ~~currently~~to nothe ~~approved~~redundancy ~~therapeutics~~in ~~targeting~~ the ~~impairment~~three-nucleotide ~~caused~~codon bystructure. ~~these~~During ~~mutations.~~readthrough, ~~Nonsense~~either ~~mutations~~the ~~are~~typical ~~involved~~healthy inor a ~~large~~near-cognate ~~number~~substitute ofamino ~~genetic~~acid ~~diseases~~occurs ~~such~~resulting asin ~~cystic~~the ~~fibrosis,~~continuation ~~Alport,~~of ~~Polycystic~~translation ~~Kidney~~for ~~disease,~~full-length ~~RDEB,~~proteins. ~~JEB,~~Exaluren and ~~FAP.~~ZKN-013 ~~According~~are designed to enhance the ~~Human~~likelihood ~~Gene~~of ~~Mutation~~readthrough ~~Database,~~by ~~nonsense~~modulating ~~mutations~~the ~~account~~ribosome ~~for~~and ~~approximately~~changing ~~12%~~the oftranslational ~~patients~~equilibrium ~~with~~away afrom ~~given~~release ~~genetic~~factors ~~disease.~~that ~~The~~signal ~~disease~~a ~~phenotypes~~stop ~~caused~~to bytranslational ~~nonsense~~factors ~~mutations~~that ~~are~~signal ~~frequently~~continued ~~more~~amino ~~severe~~acid ~~than~~incorporation. ~~those~~Multiple ~~caused~~compounds bywithin ~~other~~our ~~kinds~~RMA ofand ~~mutations~~ERSG ~~because~~library ~~these~~are ~~mutations~~designed ~~often lead~~ to aevaluate ~~complete~~the ~~loss~~readthrough of ~~protein~~the ~~production~~premature orstop ~~function~~codon. ~~In general, these diseases do not have specific therapies beyond symptomatic and palliative interventions.~~

Read-through of nonsense mutations is a naturally occurring process that can be attributed to the redundancy in the three-nucleotide codon structure. During read-through, either the typical healthy or a near-cognate substitute amino acid occurs resulting in the continuation of translation. Our RMAs and ERSGs (like ELX-02) are designed to

~~enhance~~Exaluren: ~~the~~Novel ~~likelihood of readthrough by modulating the ribosome. Multiple compounds within our RMA and~~ ERSG ~~library~~with ~~are~~Therapeutic ~~designed~~Potential to ~~demonstrate~~Mediate ~~the~~Nonsense ~~readthrough~~Mutation ~~of the premature stop codon.~~Disease

~~Drivers~~Exaluren is a novel ERSG product candidate designed to increase the PTC readthrough mechanism of ~~ribosomal~~aminoglycoside ~~mutations~~antibiotics, insuch ~~cancer~~as gentamicin, with increased selectivity for the human ribosome to make it more suitable for chronic use to treat human genetic diseases with NMs.

~~Loss~~Aminoglycoside orantibiotics, ~~gain~~such as gentamicin, have been extensively studied for their potential to promote the restoration of ~~ribosomal~~full-length proteins ~~and~~by ~~ribosome~~the ~~modifying~~mechanism ~~factors~~of PTC readthrough in ~~cancer~~preclinical ~~can~~studies ~~lead~~in tovarious ~~cancer~~genetic ~~progression~~diseases ~~through~~with ~~translation~~NMs, ofincluding ~~oncogenic~~NMAS, ~~proteins.~~and ~~These~~in ~~altered~~several ~~ribosomes~~clinical ~~are~~studies ~~structurally~~in ~~distinct~~patients ~~and~~with ~~can~~NMs, beincluding ~~selectively~~RDEB, ~~targeted~~JEB, byCF ~~rationally~~and ~~designed~~Duchenne ~~macrolides~~muscular ~~designed~~dystrophy ~~with~~in ~~the~~adult ~~TURBO-ZM™~~and ~~platform~~pediatric patients. ~~Active~~However, ~~screening~~gentamicin ofand ~~compounds~~similar ~~has~~antibiotic ~~identified~~aminoglycosides ~~several~~are ~~leads~~weak binders to the human ribosome and ~~hits~~thus ~~which~~require ~~have~~high ~~shown~~doses ~~promising~~for ~~results~~activity. inThey ~~colon~~are ~~cancer~~also poorly tolerated and ~~small~~cause ~~cell~~heightened ~~lung~~risk ~~cancer~~of ~~patient~~kidney ~~organoids~~damage ~~characterized~~and byhearing ~~over~~loss ~~expression~~from chronic use due to their strong inhibition of ~~cMYC~~mitochondrial protein translation.

~~Current~~Due ~~Data~~to ~~Supporting~~the markedly decreased affinity for the ~~Potential~~bacterial ~~Mechanism~~and mitochondrial ribosomes, ERSG compounds like exaluren have little of ~~Action~~the antibiotic activity associated with aminoglycosides. In in vitro mitochondrial protein translation assays, exaluren showed an approximately 57-fold higher IC50 relative to gentamicin, indicating lower inhibition under the assay conditions tested. In bacterial growth inhibition assays, exaluren showed over a 100-fold higher minimum inhibitory concentration (“MIC”) relative to gentamicin. Additionally, in reporter assays with a PTC, exaluren showed higher read-through activity than gentamicin. We believe this result may reflect higher selectivity towards the human ribosome. ERSGs are selective for the human ribosome and have markedly lower affinity for the mitochondrial ribosome, which we believe may reduce the risk of ~~ELX~~mitochondrial-02associated toxicity with chronic use.

~~ELX-02 is a novel investigational ERSG designed based on aminoglycoside antibiotics~~Exaluren, ~~such~~like ~~as gentamicin, with increased selectivity for the eukaryotic ribosome. The early observations of eukaryotic read-through activity were made in patients treated with~~ aminoglycosides ~~due to bacterial infections. However~~, ~~despite~~is ~~the~~transported ~~promising~~into ~~clinical~~cells ~~observations~~via ~~of read-through activity~~megalin, ~~the~~which ~~use of aminoglycoside antibiotics as a read-through therapy~~ is ~~restricted~~expressed ~~since~~in ~~aminoglycosides~~renal ~~may cause damage to the kidney~~ and ~~ear~~epithelial ~~after~~tissues ~~prolonged administration. The effect of aminoglycoside antibiotics on the hair cells of the ear~~ and ~~the~~supports ~~proximal~~intracellular ~~tubular~~delivery ~~cells~~in of the kidney ~~may~~and beother ~~attributed,~~relevant incell ~~part, to the inhibition of mitochondrial protein production in these cells~~types. ~~Due~~Modeling ~~to the markedly decreased affinity for the prokaryotic and mitochondrial ribosomes, ERSG compounds have little~~ of ~~the~~human ~~antibiotic~~tissue ~~activity~~drug ~~associated~~exposures ~~with~~based ~~aminoglycosides.~~on ~~When~~animal ~~compared~~studies inshowed ~~laboratory~~that ~~tests~~exaluren tocould ~~gentamicin~~achieve (aapproximately ~~classic aminoglycoside antibiotic), ELX-02 showed~~ a ~~100~~50-fold ~~lower antibacterial activity and nine-fold~~ higher ~~read-through~~exposure ~~activity~~in ~~for~~kidney ~~nonsense~~cells ~~mutations.~~compared ~~We believe this result was attributable~~ to ~~higher selectivity towards the eukaryotic cytoplasmic ribosome. Because ERSGs are selective for the eukaryotic cytoplasmic ribosome and have markedly decreased affinity for the mitochondrial ribosome~~plasma, wesupporting ~~believe~~its ~~ERSGs~~evaluation ~~have the potential to show an acceptable safety and tolerability profile~~ for ~~chronic~~treatment ~~use. We believe that our library~~ of ~~ERSG~~kidney ~~compounds has the potential to show improved read-through activity with a reduced potential for impairment of the mitochondrial ribosome and may have an improved safety profile~~diseases.

WeThe ~~evaluated~~mechanism ~~a subset~~ of ~~our~~exaluren ~~compounds~~is ingene ~~the~~agnostic. ~~cell by quantitative polymerase chain reaction (“qPCR”)~~Therefore, ~~western~~models ~~blot protein analysis and for proper localization~~ of ~~the~~comparable ~~restored~~diseases ~~protein~~caused by ~~immunofluorescence.~~NM ~~Consistent~~variants ~~with~~that ~~our~~introduce ~~overall hypothesis~~PTCs, wesuch ~~have~~as ~~found~~ADPKD, ~~that~~CF ~~molecules~~and incystinosis, ~~our~~from ~~library~~NMs, ~~significantly~~can ~~increase~~be ~~both~~used ~~the~~to ~~mRNA~~evaluate ~~(dose-dependent~~the ~~increases~~efficacy of ~~30-fold~~exaluren ~~over~~in ~~vehicle control) and protein of interest (increased normalized full-length protein 4~~vivo.~~7-fold~~ ~~over~~In ~~vehicle~~animal ~~control)~~models, asexaluren ~~well~~has asshown ~~the~~functional ~~protein’s~~readthrough ~~proper~~across ~~sub-cellular~~multiple ~~localization.~~genes Inand ~~addition to supporting our overall mechanism of action hypothesis~~NMs, ~~these~~including ~~studies~~in ~~have enabled us to develop~~ a ~~robust~~CtnsY226X/Y226X ~~(z’~~cystinosis ~~factor~~mouse ~~= 0.88)~~model, ~~high-throughput~~where ~~assay~~treatment ~~within~~resulted ~~this~~in ~~system~~a to30% ~~further~~reduction ~~evaluate~~in ~~compound-mediated~~kidney ~~read-through~~cystine ~~across our library~~levels.

~~Scope~~Development Program for Exaluren for the Treatment of ~~Activities~~NMAS

WeAS, a rare genetic kidney disorder caused by mutations in the COL4A3/4/5 genes, is characterized by podocyte injury and impaired kidney filter function leading to proteinuria and kidney failure. Podocytes are ~~currently~~specialized ~~focused~~cells onthat produce Collagen IV proteins and the ~~following~~Collagen ~~program~~alpha ~~areas~~IV 3,4,5 trimer needed for the functional integrity of the GBM. They bind to the GBM with finger-like extensions called foot processes that enable efficient ultrafiltration. Mutations in Collagen IV genes result in FPE and thus loss of podocytes and proteinuria in all cases of AS. Exaluren is designed to promote restoration of functional protein and showed improvement in FPE in NMAS patients in a small (n=3) open label Phase 2a study.

~~Alport~~Exaluren ~~Syndrome~~has been tested in eight clinical trials, including four Phase 1 studies in healthy volunteers, one Phase 2a study in NMAS, two Phase 2 studies in CF patients with ~~Nonsense~~NMs, ~~Mutations~~and one Phase 2 study in nephropathic cystinosis patients with NMs. In total, 145 subjects received at least one dose of exaluren during these clinical trials, including doses up to 10-fold higher than those planned for the Phase 2b trial in NMAS. In these studies, no dose-limiting toxicities were reported, and no serious adverse events were attributed to exaluren. Exaluren was also not associated with clinically significant nephrotoxicity or ototoxicity. Results from the Phase 2 clinical studies in CF and cystinosis studies highlighted the need for higher tissue exposures to translate biological activity to clinical efficacy. The biological property of exaluren to concentrate in kidney cells supported advancing exaluren in NMAS patients.

~~Alport~~Exaluren ~~syndrome~~has isshown a2-fold ~~major~~to ~~inherited~~10-fold ~~kidney~~full-length ~~diseases~~COL4A5 ~~that~~protein ~~affects~~induction anin ~~estimated~~cell-based ~~155,000~~reporter toassays ~~215,000~~that ~~patients~~measured ~~worldwide~~light ~~and~~levels. These results are consistent with results of exaluren treatment in other cell-based assays with other genes. Protein restoration therapies apart from ~~mutations~~exaluren in ~~the~~AS ~~COL4~~mice ~~gene~~models ~~which~~with ~~cause~~a ~~truncated~~complete loss of Collagen IV protein or ~~missense~~a ~~COLIV~~NM ~~proteins.~~in ItCollagen isIV ~~estimated~~have ~~that~~shown ~~85%~~improvements ofin ~~patients~~the ~~are~~structure, ~~X-linked~~kidney function and ~~15%~~survival ~~have~~with ~~recessive~~3 ~~mutations~~weeks to 16 weeks of treatment.

~~Approximately~~Building ~~6% of Alport patients carry a nonsense mutation~~ on the ~~COL4~~cellular ~~gene~~PTC ~~and~~readthrough ~~have~~results ~~truncated COLIV proteins. More than 70 nonsense mutations have been~~ described. ~~Alport~~above, isthe abreadth ~~progressive~~of ~~disease~~preclinical ~~caused~~results byshowing ~~a fragile (or none) base membrane of~~ the ~~glomeruli~~potential ~~due~~treatment toeffect ~~deficiency~~with inexaluren ~~COLIV protein. Alport patients have high levels of blood (Hematuria)~~ and ~~proteins (Proteinuria) in~~ the ~~urine.~~specific ~~This~~studies in ~~turn~~AS ~~causes~~mice ~~fibrosis,~~with ~~loss~~other ofgenetic ~~kidney~~therapies, ~~function~~we ~~(eGFR)~~advanced ~~and~~exaluren ~~ultimately kidney failure. There are no approved treatments~~ for ~~Alport~~the ~~and~~restoration ~~50%~~ of ~~patients~~the ~~with~~Collagen ~~nonsense~~IV ~~mutations~~protein ~~lose~~for ~~their kidney function by~~ the ~~time~~treatment ~~they~~of ~~are~~AS. 18We ~~years~~have ~~old.~~received Orphan

We are evaluating the treatment effect of ELX-02 delivered subcutaneously in a Phase 2 trial in Alport Patients. This Phase 2 trial is targeting dosing of up to eight Alport syndrome patients with nonsense mutations in the COL4 gene. Patients will be dosed for two months with a three-month follow-up. In addition to the primary endpoint of safety, the key secondary efficacy endpoint of proteinuria will be measured every two weeks. For eligible patients, induction of COL IV will also be measured at the end of two months. Topline results are expected in the first half of 2023.

~~Recessive~~Drug ~~Dystrophic~~Designation ~~Epidermolysis~~for ~~Bullosa~~the ~~(“RDEB”)~~treatment of AS from the FDA. We conducted a Phase 2a trial in patients with NMAS and ~~Junctional~~we ~~Epidermolysis~~plan ~~Bullosa~~to ~~(“JEB”)~~initiate, subject to patient enrollment, a Phase 2b clinical trial in the first half of 2026 for exaluren in NMAS, patients and anticipate topline data from the initial 16-week placebo-controlled part of the study by mid-2027 with the final readout by the end of 2027.

~~Epidermolysis~~Phase ~~bullosa~~2a ~~(“EB”)~~Trial isin aNMAS ~~group~~Patients ~~of rare inherited skin disorders that cause the skin to become very fragile. Any trauma or friction to the skin can cause painful blisters. RDEB and JEB are the two main types of EB.~~

~~RDEB~~We isconducted ~~caused~~a byPhase ~~mutations~~2a trial in the ~~COL7A1~~United Kingdom with three NMAS patients with NMs in the COL4A4 gene ~~that~~aged ~~codes~~12 to 18 years. Patients received a daily dose of exaluren subcutaneously at 0.75 mg/kg for ~~COL7A1~~eight ~~protein~~weeks with a three-month follow-up, with kidney biopsies performed before and after treatment to assess Collagen IV expression and podocyte morphology. ~~The~~This ~~COL7A1~~study ~~gene~~was isnot ~~involved~~powered into ~~coding~~assess statistical significance for ~~the~~changes ~~collagen~~in ~~that~~efficacy ~~helps~~and ~~attach~~the primary objective of the ~~epidermis~~study was to ~~underlying~~assess ~~layers~~safety. The secondary objective of ~~skin.~~this Westudy ~~are~~was ~~targeting~~to ~~nonsense~~evaluate ~~mutations~~exaluren’s mechanism of action through protein restoration of Collagen IV expression and associated structural changes in ~~COL7A1~~kidney biopsies and in clinical markers of kidney function. ~~These~~Efficacy ~~represent~~was ~~approximately~~assessed 30by measuring changes in urine protein-~~40%~~to-creatinine ofratio ~~all~~(“UPCR”) ~~mutations~~and hematuria and by measuring the protein expression change from baseline and structural changes in ~~COL7A1~~kidney biopsies. Structural changes upon Collagen IV restoration were assessed by change in podocyte FPE and its quantitative correlates of FSD and Foot Process Width (“FPW”).

~~JEB~~All isthree ~~most~~patients ~~commonly~~treated ~~caused~~with byexaluren ~~mutations~~showed an improvement in ~~the~~FPE. ~~LAMA3~~TEM images showed a reduction from widespread to moderate segmental FPE, ~~LAMB3~~reduced FPW and ~~LAMC2~~an ~~genes~~improvement in the GBM in all treated patients. ~~The~~These ~~LAMA3,~~changes ~~LAMB3,~~were ~~and~~consistent ~~LAMC2~~with ~~genes~~structural ~~are~~improvement ~~involved~~in components of the kidney filtration architecture as assessed in ~~coding~~biopsy ~~for~~specimens. aCollagen IV also increased in all patients, supporting exaluren’s proposed mechanism of protein ~~that~~restoration ~~plays~~and anassociated ~~important~~structural ~~role~~changes in ~~strengthening~~kidney biopsies. At the end of treatment UPCR reduced by approximately 37% in one patient and ~~stabilizing~~nominally increased in the ~~skin.~~other We2 ~~are~~patients, ~~targeting~~although ~~nonsense~~the ~~mutations~~high variability in ~~LAMB3~~measurements ~~genes~~within ~~that~~each ~~represent~~patient ~~approximately~~at ~~70%~~each oftime ~~all~~point ~~mutations~~limited interpretability. These observations were limited to biopsy-based structural assessments and did not establish long-term functional outcomes.

~~Infants~~Patients ~~are~~had ~~typically~~an ~~born~~average ~~with~~increase ~~widespread~~of ~~blistering~~50% in FSD (50%, 13.3% and ~~areas~~116%) reaching 80% of ~~missing~~healthy ~~skin,~~levels ~~often~~consistent ~~caused~~with byTEM ~~trauma~~assessments ~~during~~of ~~birth~~FPW. ~~Most~~FSD ~~RDEB~~was ~~patients~~measured ~~develop~~on ~~skin~~an ~~cancer~~automated, blinded and unbiased basis in kidney biopsy tissue by ~~age~~NIPOKA 35using ~~and~~an ~~the~~automated ~~average~~high-resolution ~~mortality~~image ofanalysis ~~patients~~approach. ~~with~~In ~~JEB~~each issample, 18FSD ~~months~~was averaged across individual cells (“glomeruli”). ~~RDEB~~Glomerular ~~affects~~FSD ~~approximately~~distributions 4showed clear,~~000~~ ~~patients~~consistent, ~~worldwide~~upward ~~with~~shifts ~~nonsense~~in ~~mutations~~all ~~and~~participants, ~~there~~consistent ~~are~~with noimprovement ~~approved~~observed ~~treatments;~~across ~~management~~sampled ~~is palliative~~glomeruli.

~~ZKN-013~~Protein isimmunofluorescence ~~our~~staining ~~lead~~analyses ~~TURBO~~also showed a mean 72% (38.5%, 8.3% and 170.8%) increase in the average Collagen IV alpha 3 and alpha 4 proteins, which were consistent with the qualitative assessments of high-~~ZM™~~resolution ~~based~~imaging ~~molecule~~following similar staining. Structural improvements in ~~our~~Collagen ~~program~~IV toalpha ~~address~~5 ~~nonsense~~were ~~mutations~~observed in ~~RDEB/JEB~~independent assays, providing further evidence of the formation of the Collagen IV alpha 3,4,5 trimer. The changes in FSD were proportional to and consistent with these changes in protein expression.

~~Familial~~The ~~Adenomatous~~biopsy ~~Polyposis~~analyses ~~(“FAP”)~~were conducted using multiple complementary methodologies, including TEM, fresh frozen tissue immunofluorescence staining, and formalin-fixed paraffin-embedded tissue analyses. Quantitative image analysis was performed in a blinded manner with respect to treatment timing, and independent laboratories were engaged to assess structural and protein expression endpoints. Improvements in FSD, FPW, and Collagen IV expression were observed consistently across biopsy preparation methods and analytical techniques, supporting the structural findings. Variability in response may reflect differences in baseline disease severity, specific mutation type, or other patient-specific factors; however, the small sample size limits conclusions regarding predictors of response.

~~FAP~~Phase is2b ~~caused~~Trial ~~by a mutation~~ in ~~the~~NMAS ~~APC~~Patients gene coding for APC protein, which acts as a tumor suppressor and keeps cells from growing too fast or in an uncontrolled way. It is characterized by polyps developing in subjects as young as in their teens. These polyps have a high propensity for progression to cancer. Hence patients undergo prophylactic colectomy in adolescence or early adulthood to prevent colorectal cancer development.

~~Our~~Subject ~~program~~to patient enrollment, we plan to ~~address~~initiate ~~FAP~~a ~~includes~~Phase ~~TURBO~~2b clinical trial in the first half of 2026 for exaluren in NMAS and anticipate topline data from the initial 16-~~ZM™~~week ~~based~~placebo-controlled ~~RMAs~~part ~~including~~of ~~ZKN~~the study by mid-~~013~~2027 with the final readout by the end of 2027. The Phase 2b trial is a randomized, double-blind, placebo-controlled, delayed-start study designed to evaluate the efficacy and safety of exaluren. We plan to enroll approximately 24 NMAS patients aged 12 and older with a confirmed genetic diagnosis of a loss-of-function NM in one of the COL4A3/4/5 genes. The study will utilize a 2:1 randomization at screening to either exaluren or placebo. Patients will receive treatment for 16 weeks. At 16 weeks, placebo patients will be switched to exaluren treatment, while patients randomized to exaluren will continue to receive exaluren for an additional ~~undisclosed~~16 ~~compounds~~weeks. Treatment assignment will be double-blind for the entire duration of the treatment period.

Research and Development Programs

Our pipeline of programs is summarized in the following table:

Development Program for ELX-02 for the Treatment of Alport Syndrome

In March 2022, we announced our decision to advance ELX-02 delivered subcutaneously for the restoration of the COL IV protein for the treatment of Alport syndrome, a rare kidney disease, with nonsense mutations, a rare kidney disease. In November 2022, we began a Phase 2 monotherapy clinical trial for ELX-02 for the treatment of Alport syndrome and in January 2023, we announced that the first patients had been enrolled and in February 2023 we announced that the first patients had been dosed. Alport syndrome with nonsense mutations is a genetic kidney disorder that occurs in 1 in 50,000 newborns in the United States. It is caused by the loss of one of three collagen IV subtypes. This disease is characterized by blood (hematuria) and protein (proteinuria) in the patient's urine, and results in progressive kidney disease, hearing loss, and eye abnormalities. ELX-02 treatment has demonstrated restoration of full-length protein in multiple preclinical models, including collagen IV and collagen VII in cells, and also clinical activity in our Phase 2 cystic fibrosis trial. We believe our results, previously conducted in vivo studies

~~showing~~The ~~improvement~~primary ofefficacy ~~kidney~~endpoint ~~function~~for ~~with~~non-U.S. ~~collagen~~pediatric IVpatients ~~restoration~~ and ~~the~~all ~~ability~~adult topatients ~~achieve~~is ~~high~~to ~~kidney~~evaluate ~~drug levels at tolerable doses support~~ the ~~clinical~~effect ~~development~~ of ~~ELX-02~~exaluren inon ~~Alport~~structural ~~syndrome.~~changes ~~In preclinical studies, significant improvement~~ in ~~kidney~~podocyte ~~function~~FPE ~~and~~as ~~survival~~measured ~~has~~by ~~been~~change ~~seen~~ in ~~Alport~~FSD ~~mice~~in ~~that~~kidney ~~lack~~biopsies. ~~full~~In ~~length~~the ~~Collagen~~United IVStates, ~~proteins~~the atFDA ~~very~~did ~~low~~not ~~protein~~support ~~levels~~the ~~when~~use ~~treated~~of ~~with protein restoration therapies. ELX~~protocol-02mandated ~~has~~repeat ~~demonstrated~~kidney 6biopsies ~~to 15% collagen IV restoration~~ in ~~cellular~~pediatric ~~systems.~~patients ~~ELX-02~~for ~~treatment~~efficacy assessment in ~~mice~~this ~~with~~Phase ~~another~~2b ~~rare kidney disease~~study, ~~cystinosis,~~citing ~~also~~the ~~resulted~~absence inof a ~~reduction~~prospect of ~~cystine~~direct ~~levels,~~benefit asufficient ~~marker~~to ~~for~~justify ~~disease improvement. ELX-02 drug levels in~~ the ~~kidney~~risks ~~are~~under ~~approximately~~21 ~~50-fold~~CFR ~~higher than in the plasma~~50.52. ~~As a result~~Accordingly, atfor ~~our~~U.S. ~~targeted~~pediatric ~~dose of 0.75mg/kg~~patients, ~~which is half of~~ the ~~dose~~primary ~~previously~~objective ~~given~~is tosafety ~~patients in our Phase 2 CF trial with ELX-02~~ and ~~ivacaftor~~tolerability, wewhile ~~believe that ELX~~biopsy-02based ~~levels~~structural inendpoints ~~the~~are ~~kidney~~being ~~could~~evaluated ~~result~~ in ~~protein~~non-U.S. ~~restoration~~pediatric ~~levels~~and ~~that~~adult ~~may be sufficient to reduce proteinuria in Alport~~ patients, awhere ~~key~~permitted ~~endpoint~~by ~~for~~local ~~kidney~~regulatory ~~function improvement~~authorities. ~~This~~The ~~Phase~~key 2secondary ~~trial~~objective isfor ~~targeting~~all ~~dosing of up to eight Alport syndrome~~ patients ~~with nonsense mutations in the COL4 gene. Patients~~ will be ~~dosed for two months with a three month follow-up. In addition~~ to assess the ~~primary~~effect ~~endpoint~~ of ~~safety,~~exaluren ~~the~~on ~~key~~reducing ~~secondary efficacy endpoint of~~ proteinuria, ~~will~~as be measured ~~every~~by ~~two~~UPCR ~~weeks.~~in ~~For~~all ~~eligible~~ patients,. ~~induction~~The ofstudy ~~COL~~size IVand ~~will~~randomization ~~also~~were bedetermined ~~measured~~with atconsideration ~~the end~~ of ~~two months. Topline results are expected in~~ the ~~first~~number ~~half~~ of ~~2023~~patients ~~and~~expected ~~we plan~~ to ~~advance~~contribute toevaluable abiopsy ~~pivotal~~data ~~clinical trial if we observe a significant improvement~~ in ~~our~~the ~~efficacy~~patient ~~endpoint~~populations ofwhere ~~proteinuria~~repeat ~~reduction~~biopsies inare ~~the kidney~~permitted.

~~ZKN-013~~The -severity ~~RDEB~~of FPE has been associated with time to kidney failure in a recent study of more than 800 kidney disease patient biopsies. In published studies across multiple kidney diseases, including AS, higher FSD, a quantitative measurement of the degree of FPE has been associated with lower proteinuria. In certain kidney diseases, including IgA nephropathy and ~~JEB~~focal segmental glomerulosclerosis, publicly available approval decisions have reflected the use of proteinuria reduction measures, such as UPCR, as clinically meaningful endpoints. However, while the Phase 2b trial has been submitted and allowed by the FDA and clinical trial authorization has been obtained from the UK Medicines and Healthcare products Regulatory Agency, FSD has not been validated as a surrogate endpoint for clinical benefit in AS, and regulatory authorities have not determined that changes in FSD are sufficient to support approval. However, the FDA has initiated efforts through the Alport Syndrome Surrogate Endpoint Network (ASSENT) working group to assess new surrogate endpoints, including biopsy changes, to support the potential future approval of drugs to treat AS.

~~ZKN-013~~Development isProgram ~~our~~of ~~lead~~Exaluren ~~TURBO-ZM™~~for ~~based molecule in our program to address nonsense mutations in RDEB/JEB. Existing third-party data has paved~~ the ~~way~~Treatment ~~for~~of our development program, including third-party clinical studies evaluating gentamicin. Patients receiving gentamicin in these studies had an approximate 70% increase in wound closure and an approximate 70% decrease in blistering events. ADPKD

~~Preclinical~~ADPKD ~~results~~is ~~support~~a ~~the~~monogenic ~~potential~~cystic ~~for~~tubular ~~RMAs~~disease. toMutations ~~restore~~in ~~functional~~the ~~collagen~~PKD1 ~~protein~~and atPKD2 ~~levels~~genes ~~comparable~~lead to ~~high-dose~~renal ~~gentamicin~~cyst formation, kidney enlargement, and extrarenal organ involvement. ~~IND-enabling~~Patients ~~pre-clinical~~experience ~~studies~~hypertension, ~~have~~kidney ~~been~~stones, ~~completed~~urinary ~~and~~tract oninfections, ~~March~~heart 24valve abnormalities, ~~2023~~hematuria, weand ~~filed~~increased anprobability ~~IND~~of ~~for~~aortic ~~ZKN~~aneurysm. Formation of these cysts eventually leads to nephromegaly and end-~~013~~stage ~~for~~renal ~~the~~disease. ~~treatment~~ADPKD patients with NMs represent approximately 26% of ~~RDEB~~ADPKD patients or approximately 40,000 to 50,000 patients in the United States.

~~FAP~~In preclinical organoid and cellular models of ADPKD with NMs, exaluren showed increased PC1 and PC2 protein expression following treatment, with associated reductions in cyst formation and cyst expansion observed in these experimental systems. In certain organoid models, 14-day treatment resulted in 10% to 75% exposure-dependent increase in PC1 and PC2 protein expression across different PKD1 and PKD2 NM organoid models and experimental conditions. Independent studies in ADPKD mice, conducted using other genetic or therapeutic approaches that did not evaluate exaluren, have also shown that restoration of PC1 and PC2 proteins can shrink cysts and overall kidney size. Independent clinical efforts in ADPKD have explored strategies aimed at increasing PC1 expression, with early-stage studies evaluating the potential relationship between protein restoration and changes in disease-related parameters. These studies are mechanistically distinct from exaluren and remain investigational.

~~ZKN-013~~We ~~has~~believe ~~also~~our ~~shown~~clinical ~~promising~~data in ~~vivo~~NMAS and ~~in vitro~~ preclinical ~~activity~~findings in ~~FAP.~~ADPKD ~~Existing~~models ~~third-party~~provide ~~data~~a ~~has~~scientific ~~paved~~rationale ~~the way~~ for ~~our~~further ~~development program, including results from third-party~~ clinical ~~studies~~evaluation ~~evaluating~~of ~~erythromycin,~~exaluren ain ~~macrolide~~nmADPKD. ~~antibiotic~~We ~~and~~plan ~~Celecoxib.~~to ~~Patients~~initiate ~~receiving~~enrollment ~~erythromycin~~ in ~~these~~a ~~studies~~Phase ~~had~~2 antrial ~~approximate~~of ~~50%~~exaluren ~~reduction~~for inthe ~~polyp~~treatment ~~number and polyp burden (area~~ of ~~polyps)~~nmADPKD ~~after~~in at2027 12following ~~months~~finalization ~~after~~of 6and ~~months~~IND ~~400mg/day~~clearance ~~once~~by ~~daily~~the ~~Celecoxib~~FDA ~~showed~~for anthe ~~approximate 30% reduction (vs~~trial. ~~those~~We ~~treated~~anticipate ~~with~~topline ~~placebo)~~data infrom ~~polyp~~this ~~number~~trial ~~and~~by ~~size after 6 months of treatment~~mid-2028.

~~In a pre-clinical study, evaluating the activity of~~ ZKN-013: inRMA ~~mice~~with ~~models~~Therapeutic ~~known~~Potential ~~as APCmin, that are considered~~ to beMediate ~~representative~~Nonsense ofMutations ~~FAP patients, ZKN-013 showed a 40% reduction~~ in ~~polyp~~Epidermolysis number (vs. untreated mice), an approximately 50% reduction in polyp burden (vs. untreated mice) and 50% survival benefit (vs. untreated mice). We believe that these results support the further development of ZKN-013 for the treatment of FAP patients. We continue to evaluate ZKN-013 and other RMAs for their potential to treat FAP patients with nonsense mutations. Bullosa

~~ELX~~In collaboration with Almirall, we are developing ZKN-02013 –for ~~Class~~the treatment of RDEB, a rare dermatological disease. Under the Almirall License Agreement, Almirall is conducting a Phase 1 CFclinical ~~Program~~trial of ZKN-013 in healthy volunteers to evaluate safety. EB is a group of rare inherited skin disorders that cause the skin to become fragile, where any trauma or friction to the skin can cause painful blisters. RDEB and JEB are the two main types of EB.

RDEB Inis ~~September~~caused ~~2022,~~by mutations in ~~consultation with~~ the ~~Cystic~~COL7A1 ~~Fibrosis Foundation (“CFF”)~~gene, wewhich ~~terminated~~codes ~~the development of ELX-02 delivered subcutaneously,~~ for the ~~treatment~~COL7A1 ~~CF patients with at least one nonsense (“Class 1 CF”) mutations~~protein. ~~This~~NMs ~~decision~~in ~~was~~COL7A1 ~~made~~represent ~~after~~approximately ~~our~~30% ~~Phase~~to 240% ~~trial~~ of ~~ELX-02~~all mutations in ~~combination~~COL7A1. ~~with~~The ~~ivacaftor,~~COL7A1 angene ~~approved~~is ~~drug~~involved ~~currently~~in ~~marketed~~coding for ~~the~~Collagen ~~treatment of certain CF patients under the trade name “Kalydeco”~~VII, ~~did~~which ~~not~~helps ~~meet~~attach the ~~secondary~~epidermis ~~efficacy~~to ~~endpoint~~underlying layers of ~~reduction from baseline in sweat chloride concentration (SCC) or improvement from baseline in percent forced expiratory volume (FEV1)~~skin. ~~Encouragingly~~Worldwide, weRDEB ~~continued~~affects toapproximately ~~see~~4,000 ~~strong~~patients ~~evidence~~with ofNMs, ~~biological~~with ~~activity~~most ~~similar~~RDEB topatients ~~that~~developing inskin ~~our~~cancer ~~previously~~by ~~completed~~age ~~Phase~~35. 2JEB ~~study~~is ~~that~~most ~~reported~~commonly incaused ~~November~~by ~~2021~~mutations ~~a reduction~~ in ~~sweat~~the ~~chloride~~LAMA3, ~~concentration~~LAMB3 ~~from~~and ~~baseline~~LAMC2 ~~after~~genes, ~~one~~which ~~week~~encode ofthe ~~treatment~~protein ~~with ELX~~laminin-~~02.~~332 ~~We believe~~ that ~~the~~plays ~~lack~~an ofimportant ~~statistically~~role ~~significant~~in ~~clinical~~strengthening ~~benefit~~and instabilizing ~~Class~~the 1skin. CFNMs ~~patients~~in ~~was~~LAMB3 ~~due~~genes torepresent ~~drug~~approximately ~~concentration~~70% inof ~~the~~all ~~lung~~mutations ~~tissue~~while ~~being~~those ~~significantly~~in ~~below~~LAMA3 ~~that~~and ~~required~~LAMC2 account for ~~effect~~approximately ~~consistent~~32% ~~with~~and ~~our~~53%, ~~preclinical studies~~respectively. ~~ELX-02~~Infants ~~was~~suffering ~~well~~from ~~tolerated~~EB inare ~~the~~typically ~~Phase~~born ~~2 trial~~ with nowidespread ~~drug~~blistering ~~related~~and ~~adverse~~areas ~~events~~of ~~even~~missing atskin, ~~the~~often ~~clinical dose of 1.5mg/kg.~~

Going forward, we plan to only develop ELX-02 as an inhaled therapy for Class 1 CF patients because the achievable drug concentrations are more than one-hundred times higher in the lung tissue than when given subcutaneously. We have completed the IND enabling studies for inhaled ELX-02 in Class 1 CF but further clinical development is contingent upon funding from the CFF.

~~Ongoing~~caused ~~earlier~~by ~~stage~~trauma ~~discovery~~during ~~programs~~birth. The average mortality of patients with ~~our~~JEB ~~library~~is 18 months. Approved therapies to treat RDEB and JEB include gene-based approaches designed to promote the restoration of ~~RMAs~~Collagen VII expression; however, these therapies only address disease management and ~~ERSGs~~topical wound treatment but not the systemic treatment of the underlying genetic defect.

WeLike ~~continue~~macrolide antibiotics in bacteria, ZKN-013 is postulated to ~~explore~~interact with the ~~potential~~nascent ofpeptide ~~our~~exit ~~libraries~~tunnel ofin ~~RMAs~~the human ribosome and ~~ESRGs,~~incorporate ~~while~~a ~~expanding~~near-cognate ~~our~~amino ~~RMA~~acid ~~library~~at ~~using~~the ~~our~~PTC ~~TURBO-ZMTM~~thus ~~platform,~~preventing topremature ~~expand~~termination ~~into~~of ~~other~~translation. ~~rare~~In ~~diseases~~preclinical models, ZKN-013 showed Collagen VII restoration and ~~cancers~~functional improvement in ~~our~~patient ~~earlier~~cells ~~stage~~across ~~discovery~~a ~~efforts.~~range Weof ~~have~~mutations ~~observed~~comparable ~~promising~~to ~~early~~high-dose ingentamicin, ~~vitro~~which ~~and~~has indemonstrated ~~vivo~~evidence ~~results~~of infunctional ~~various~~improvement ~~cell~~in ~~line~~prior ~~and~~clinical ~~animal~~studies ~~cancer~~conducted ~~models~~at ~~that~~the ~~support~~University ~~our~~of ~~current~~Southern ~~efforts~~California.

We are developing ZKN-013 in collaboration with Almirall to address the NMs that are the underlying cause of RDEB and JEB. Preclinical results supported the potential for RMAs, such as ZKN-013, to promote the restoration of functional collagen protein at levels comparable to gentamicin, which has shown activity in prior RDEB clinical studies.

Our Team and History

We are led by a management team with extensive experience in clinical drug development and commercialization. Sumit Aggarwal, our Chief Executive Officer, has more than 25 years of experience in pharmaceutical and biotechnology commercial operations, investment management, and management consulting. Prior to Eloxx, Mr. Aggarwal was the Chief Executive Officer and a director of Zikani, a company focused on ribosomal modulation for rare diseases. Prior to this, Mr. Aggarwal was interim President and Chief Financial Officer of Progenity, Inc. Our management team also includes Teji Singh, our Head of Clinical Development, Dr. Roger Clark, our Head of Discovery Sciences and Daniel Geffken, our Interim Chief Financial Officer. Dr. Singh has more than 20 years of clinical development experience, including in orphan drug development, with several primary product approvals in gene, oligonucleotide and antibody therapies. Prior to Eloxx, Dr. Singh had various clinical development roles at Sarepta Therapeutics, Shire, and Sanofi-Genzyme. Dr. Clark has more than 25 years of experience in drug design and process development and previously held related roles at Bayer Pharmaceuticals, Critical Therapeutics, Tetraphase Pharmaceuticals, and Zikani Therapeutics. Mr. Geffken has more than 35 years of financial experience across a variety of biotechnology companies.

Shares of our common stock were traded on Nasdaq until October 16, 2023, when our shares were delisted for failing to comply with Nasdaq Listing Rule 5550(b)(2), requiring a market value of listed securities of at least $35.0 million. Following the delisting from Nasdaq, we had limited access to capital and became delinquent in our reporting obligations under the Exchange Act when we were unable to file our Annual Report on Form 10-K for the year ended December 31, 2023. Between October 2023 and August 2025, our primary source of capital was the Almirall License Agreement, which provided $6.0 million in upfront payments and development milestones, and short-term bridge loans from our lender, Domicilium. During this period, while operating with resources and reduced headcount including minimal staffing for our clinical, research and development and finance teams, we continued to collect and analyze data from our Phase 2a trial of exaluren in AS and engaged with the FDA regarding our trial design for our planned Phase 2b trial.

In August 2025, we entered into a securities purchase agreement with Coastlands Capital Partners LP (“Coastlands”), pursuant to which Coastlands invested $15.0 million and Domicilium invested $2.0 million and converted all of the outstanding indebtedness under our Loan and Security Agreement between August 2025 and March 2026. With renewed access to capital, we initiated the process to complete the audits of our consolidated financial statements for the fiscal years ended December 31, 2023, 2024 and 2025 to regain compliance with our Exchange Act reporting obligations, which is required for our planned uplisting to the Nasdaq Capital Market.

Our Strategy

•

Advance exaluren as a novel disease-modifying therapy for NMAS.

•

Further accelerate exaluren’s development as a disease-modifying therapy for ADPKD.

•

Explore the development of exaluren in other rare diseases driven by NMs with high unmet needs.

•

Evaluate and execute strategic partnerships and collaborations to maximize the potential of our compound library.

Intellectual Property

Patent Portfolio

As of December 31, 2025, we owned or licensed 66 issued patents and 101 pending patent applications in the U.S. and abroad, not including U.S. provisional applications. Our licensed and owned patent portfolio includes patents and applications relating to our lead compound, ~~ELX-02~~exaluren (formerly known as NB124), and over 40 other read-through inducing compounds, as well as methods of making and using these compounds. Each of our patent families is described briefly below.

With regard to ~~ELX-02~~exaluren, our primary composition of matter coverage derives from a ~~first~~ patent family that we exclusively ~~license~~in-licensed under the Research and License Agreement (the “Technion Agreement”) with Technion Institute for Research and Development Ltd. (“TRDF”), dated August 29, 2013. As of ~~December~~February 314, ~~2022~~2026, this family included issued patents in the United States, Europe, Canada, Hong Kong, ~~India,~~ Israel, and Japan~~, and a pending application in the United States and Israel~~. Issued patents in this family have claims directed to ~~ELX-02~~exaluren and other read-through inducing compounds, as well as claims directed to pharmaceutical compositions of the disclosed compounds and methods of using the compounds and compositions to treat genetic disorders associated with premature stop codon mutations including cystic fibrosis, ~~neophropathic~~nephropathic cystinosis, DMD, ataxia-telangiectasia, Hurler syndrome, hemophilia A and B, Usher Syndrome, and Tay-Sachs disease. Patents that have issued or which may issue in the future from this family are currently expected to expire in 2031, not including any extensions of term for which we may be eligible and that we may be granted. A second patent family licensed under the Research and License Agreement with TRDF includes one issued U.S. patent with claims directed to the use of ELX-02 and other read-through inducing compounds to treat Rett syndrome.

We own ~~two~~additional patent families that may provide additional protection for specific methods of using or manufacturing ~~ELX-02~~exaluren beyond the anticipated expiration date of the primary composition of matter patents.

The first of these families is directed to methods for large-scale synthesis of ~~ELX-02~~exaluren and other read-through inducing compounds. As of ~~December~~February 314, ~~2022~~2026, this family included issued patents in the United States, Australia, ~~Israel,~~ India, and Japan ~~and pending applications in the United States, Europe, Brazil, Canada, China Hong Kong, and India~~. Patents that have been issued or which may issue in the future from this family are currently expected to expire in 2038, not including any extensions of term for which we may be eligible and that we may be granted.

The second family is directed to methods of using ~~ELX-02~~exaluren and other read-through inducing compounds to treat various ocular conditions associated with ~~nonsense mutations~~NMs, including retinitis pigmentosa, Usher Syndrome, Stickler Syndrome, aniridia, Leber congenital amaurosis, and choroideremia. As of ~~December~~February 314, ~~2022~~2026, this family ~~includes~~included ~~pending~~issued ~~applications~~patents in ~~the United States~~Japan, ~~Europe~~India, ~~Australia,~~and ~~Canada~~Mexico, ~~China,~~and ~~Hong~~pending ~~Kong,~~applications ~~Israel,~~in ~~Japan~~Canada, ~~Mexico, Malaysia, New Zealand,~~ Philippines, Singapore, and South Africa,. ~~and~~Patents ~~South~~that ~~Korea.~~have ~~Any~~issued ~~patents~~or ~~issuing~~which may issue in the future from this family are currently expected to expire in ~~2039~~2038, not including any extensions of term for which we may be eligible and that we may be granted.

~~Three~~The ~~additional~~third patent ~~families~~family ~~licensed~~is ~~under~~directed ~~the~~to ~~Research~~methods ~~and~~of ~~License~~using ~~Agreement~~exaluren ~~with~~and ~~TRDF~~other ~~are directed to additional~~ read-through inducing compounds to treat Rett syndrome. As of February 4, 2026, this family included one issued patent in the United States, which is currently expected to expire in 2038, not including any extensions of term for which we may be eligible and that we may be granted.

~~The~~Two ~~first~~additional ofpatent ~~these~~ families ~~includes claims directed to ELX~~in-03licensed ~~(formerly~~under ~~known as NB84) and other read-through inducing compounds, as well as claims directed to pharmaceutical compositions and methods of using~~ the ~~compounds~~Research and ~~compositions~~License toAgreement ~~treat~~with ~~genetic~~TRDF disorders including cystic fibrosis, DMD, ataxia-telangiectasia, Hurler syndrome, hemophilia A, hemophilia B, Usher Syndrome, and Tay-Sachs. As of December 31, 2022, this family included issued patents in the U.S., Europe, Canada, India, Israel and Japan, and a pending application in the United States. Patents that have issued or which may issue in the future from this family are ~~currently~~directed ~~expected~~ to ~~expire in 2027 and 2028, not including any~~ additional ~~extensions~~read-through ofinducing ~~term for which we may be eligible and that we may be granted~~compounds.

The ~~second~~first ~~family~~of these families includes claims directed to ELX-1003 (formerly known as ~~NB157~~NB84) and other read-through inducing compounds, ~~and~~as well as claims directed to pharmaceutical compositions and ~~uses~~methods ~~thereof.~~of Asusing ofthe ~~December~~compounds ~~31,~~and ~~2022,~~compositions ~~this~~to ~~family~~treat ~~included~~genetic ~~issued~~disorders ~~patents~~including incystic ~~the~~fibrosis, ~~U.S.~~DMD, ~~Australia~~ataxia-telangiectasia, ~~China~~Hurler syndrome, ~~India~~hemophilia A, ~~Israel~~hemophilia ~~and~~B, ~~Japan~~Usher Syndrome, and ~~pending~~Tay-Sachs ~~applications~~disease. inAs ~~the~~of ~~U.S.,~~February ~~Europe~~4, ~~Australia~~2026, ~~Brazil,~~this ~~Canada~~family included issued patents in the United States, ~~China~~Europe, ~~Hong Kong~~India, Israel, and Japan. Patents that have issued ~~or which may issue in the future~~ from this family are currently expected to expire in ~~2036~~2027 and 2028, not including any extensions of term for which we may be eligible and that we may be granted.

6The second family includes claims directed to ELX-10 (formerly known as NB157) and other read-through inducing compounds and pharmaceutical compositions and uses thereof. As of February 4, 2026, this family included issued patents in the United States, Israel and Japan. Patents that have issued from this family are currently expected to expire in 2036, not including any extensions of term for which we may be eligible and that we may be granted.

The third family includes claims directed to additional read-through inducing compounds and pharmaceutical compositions and uses thereof. As of December 31, 2022, this family included an issued patent in Australia and pending applications in the United States, Europe, Australia, Brazil, Canada, China, EAPO, Hong Kong, India, Israel, Japan, Malaysia, Mexico, New Zealand, Singapore, and South Korea. Patents that have issued or which may issue in the future from this family are currently expected to expire in 2038, not including any extensions of term for which we may be eligible and that we may be granted.

Our licensed and owned patent portfolio also includes patents and applications relating to TURBO-ZMTM compounds that can be optimized to modulate the ribosome in a disease specific manner. The TURBO-ZMTM compounds are macrolides. Most commonly known macrolides are antibiotics such as azithromycin, erythromycin and clarithromycin that are delivered orally and have favorable safety profiles that have been shown to inhibit protein synthesis in bacteria. Until Zikani’s TURBO-ZMTM chemistry technology, macrolides were only made semi-synthetically which limited their use to antibiotics.

We have licensed four patent families from the President and Fellows of Harvard College ("Harvard") under the license agreement dated February 10, 2015, and subsequently amended and restated on March 31, 2020, claiming macrolides as well as methods of making and using these macrolides. Patents issuing from these families are expected to expire in 2034, 2035 and 2036, respectively, not including any extensions of term for which we may be eligible and that we may be granted.

We jointly own three patent families with Harvard claiming other macrolides as well as methods of making and using these macrolides. These families include pending applications in the United States, Europe, Australia, Brazil, Canada, China, India, Indonesia, Israel, Japan, Mexico, New Zealand, Singapore, South Africa, and South Korea. Any patents issuing from this family are currently expected to expire in 2038 and 2039, respectively, not including any extensions of term for which we may be eligible and that we may be granted. One of these patent families includes claims directed to ZKN-013, our lead TURBO-ZMTM compound.

Patent Term Extension

The term of a U.S. patent is 20 years from its earliest effective nonprovisional or international patent application filing date, assuming all maintenance fees are paid, the patent has not been terminally disclaimed, and the patent has not been invalidated through administrative and/or court proceedings. The term of foreign patents varies but is generally also 20 years from the earliest effective filing date. In certain instances, the term of U.S. and certain foreign patents may be extended.

In the United States, patent term may be extended in certain instances by patent term adjustment (“PTA”), which compensates for administrative delays by the U.S. Patent & Trademark Office during examination of the patent. We have received a PTA for one of our exclusively licensed patents relating to ELX-01 and other related read-through inducing compounds, extending the expiration date of that patent from 2027 to 2028. However, we do not know whether any PTA will be granted for any of our future patents.

For pharmaceutical products that have received FDA approval, the term of a U.S. patent covering the approved product, a method of manufacturing the approved product, or an approved method of use of the product may be extended under the Drug Price Competition and Patent Term Restoration Act of 1984, referred to as the Hatch-Waxman Act, in certain instances if specific statutory and regulatory requirements are satisfied. The Hatch-Waxman Act provides for a patent term extension, or PTE, of up to five years as compensation for effective patent term lost during product development and the FDA regulatory review process. PTE is only available for the first approval of a particular product, the total patent term including the restoration period must not exceed 14 years from the date of FDA approval, and only one patent may be extended for a particular regulatory review period. In the EU, a similar mechanism exists for extending patent term up to five years through the grant of a Supplementary Protection Certificate (“SPC”) following European Medicines Agency (the “EMA”) approval. Similar regulatory extensions are available or may be available in the future in other jurisdictions. If and when ELX-02 or other of our read-through inducing compounds are approved by the FDA, EMA, or other foreign regulatory authorities, we will apply for these and other patent term extensions on patents covering the approved products, methods of use, or methods of manufacture if the patents are eligible for such extension. However, we cannot provide any assurance that such extensions will be granted for any of our currently issued or future patents.

Trade Secrets and Know-How

~~consultants,~~In ~~scientific~~the ~~advisors~~United ~~and~~States, ~~contractors.~~patent Weterm ~~also~~may ~~seek~~be toextended ~~preserve~~in ~~the~~certain ~~integrity~~instances ~~and~~by ~~confidentiality~~patent ofterm ~~our~~adjustment ~~data~~(“PTA”), ~~know-how~~which ~~and~~compensates ~~trade~~for ~~secrets~~administrative delays by ~~maintaining~~the ~~physical~~U.S. ~~security~~Patent of& ~~our~~Trademark ~~premises~~Office ~~and~~during ~~physical~~the ~~and~~prosecution ~~electronic security~~ of ~~our~~such ~~information technology systems~~patent. ~~While~~We we have ~~confidence~~received ina ~~these~~PTA ~~individuals,~~for ~~organizations~~one ~~and~~of ~~systems,~~our ~~agreements~~exclusively orlicensed ~~security~~patents ~~measures~~relating ~~may~~to beELX-01 ~~breached,~~ and weother ~~may~~related ~~not~~read-through ~~have~~inducing ~~adequate remedies for any breach. In addition~~compounds, ~~our~~extending ~~trade~~the ~~secrets~~expiration ~~may~~date ~~otherwise~~of ~~become~~that ~~known~~patent orfrom be2027 ~~independently~~to ~~discovered by competitors~~2028. ~~To the extent that our consultants~~However, ~~contractors~~we ordo ~~collaborators~~not ~~use~~know ~~intellectual~~whether ~~property~~any ~~owned~~PTA bywill ~~others~~be ingranted ~~their work~~ for ~~us,~~any ~~disputes~~of ~~may~~our ~~arise~~future ~~as to the rights in related or resulting know-how and inventions~~patents.

For pharmaceutical products that have received FDA approval, the term of a U.S. patent covering the approved product, a method of manufacturing the approved product, or an approved method of use of the product may be extended under the Drug Price Competition and Patent Term Restoration Act of 1984, referred to as the Hatch-Waxman Act, in certain instances if specific statutory and regulatory requirements are satisfied. The Hatch-Waxman Act provides for a patent term extension, or PTE, of up to five years as compensation for effective patent term lost during the FDA regulatory review process. PTE is only available for the first approved use of a particular product, the total patent term including the restoration period must not exceed 14 years from the date of FDA approval, and only one patent may be extended for a particular regulatory review period. In the EU, a similar mechanism exists for extending patent term up to five years through the grant of a Supplementary Protection Certificate (“SPC”) following European Medicines Agency (the “EMA”) approval. Similar regulatory extensions are available or may be available in the future in other jurisdictions. If and when exaluren or other of our read-through inducing compounds are approved by the FDA, EMA, or other foreign regulatory authorities, we will apply for these and other patent term extensions on patents covering the approved products, methods of use, or methods of manufacture if the patents are eligible for such extension. However, we cannot provide any assurance that such extensions will be granted for any of our currently issued or future patents.

Trade Secrets and Know-How

With respect to our ERSG-based technology platform, we primarily rely on trade secrets and know-how to protect the proprietary nature of our platform. However, trade secrets and know-how can be difficult to protect. We seek to protect our proprietary technology and processes, in part, by confidentiality agreements with our employees, consultants, scientific advisors, CROs, contract manufacturers and contractors. We also seek to preserve the integrity and confidentiality of our data, know-how and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology systems. While we have confidence in these individuals, organizations and systems, agreements or security measures may be breached, and we may not have adequate remedies for any breach. In addition, our trade secrets may otherwise become known or be independently discovered by competitors. To the extent that our employees, consultants, scientific advisors, CROs, contract manufacturers, contractors or collaborators use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting know-how and inventions.

License Agreements

Research and License Agreement with Technion Research and Development Foundation Ltd. ("TRDF")

On August 29, 2013, we entered into the Technion Agreement with TRDF, which was further amended and ~~addended~~supplemented to reflect, among other things, the assignment of patents and extension of research periods, with respect to certain technology relating to aminoglycosides and the redesign of aminoglycosides for the treatment of human genetic diseases caused by premature stop mutations and further results of the research of the technology, in order to develop and commercialize products based on such technology. The Technion Agreement provides us with an exclusive, worldwide, non-transferrable license, with a right to grant sublicenses, and royalty-bearing licenses tounder the TRDF inventions, TRDF patent rights, TRDF’s interest in the joint inventions and joint patent rights, and certain materials and research results owned by TRDF, solely with respect to products in the field of prevention, diagnosis or treatment of any human disease or condition therefor. In return for the license we will pay TRDF (i) milestone payments with respect to each licensed product upon the achievement of certain pre-defined goals by us or one of our sublicensees as follows: $100,000 upon first dosing of a patient in a Phase 2 clinical study (which we paid to TRDF in 2020 for ELX-02); $1,000,000 upon first dosing of a patient in a pivotal study; and $5,000,000 upon first filing of a new drug application (NDA); (ii) certain royalties in the low- to mid-single-digit percentages of all net sales (subject to change in the case of (a) sublicensing to a big pharmaceutical or biotechnology company, or (b) payment of royalties to third parties, or (c) commercialization by a third party of an authorized generic to a licensed product); and (iii) a low- to mid-double-digit percentage of any non-royalty sublicense income. In addition to the milestone payments, we undertook to annually fund the research activities under the license, currently in the estimated annual amount of $0.1 million per year. The Technion Agreement further provides TRDF with an additional pre-emptive right, in force until the first exit event, to invest an amount equal to up to 5% of the amount contemplated to be raised in a proposed investment. TRDF is also entitled, until the closing of an exit event, to appoint an observer to the board under certain restrictions such as confidentiality or conflict of interest. Furthermore, we will reimburse TRDF for all patent filing expenses as of the effective date of the Technion Agreement and for past patent filing expenses in the amount of several hundred thousand New Israeli Shekels upon the occurrence of certain conditions.

~~Under~~In return for the ~~Technion~~license ~~Agreement,~~we ~~TRDF~~agreed ~~reserved~~to ~~the~~pay ~~right,~~TRDF ~~for~~(i) ~~itself,~~aggregate ~~the~~milestone ~~Technion~~payments ~~and~~of ~~other~~up ~~not-for-profit~~to ~~research~~$6.5 ~~organizations~~million with respect to ~~utilize~~each ~~the~~licensed ~~technology~~product ~~solely~~upon ~~for~~the ~~educational~~achievement ~~purposes.~~of ~~Furthermore,~~certain ~~Professor~~pre-defined ~~Baasov,~~goals ~~the~~by ~~principal~~us ~~investigator,~~or ~~had~~one ~~ongoing~~of ~~research~~our ~~programs~~sublicensees ~~involving~~including ~~covered~~upon ~~compounds~~first ~~(as~~dosing ~~defined~~of ina ~~the~~patient ~~agreement)~~in ~~that~~a ~~are~~Phase ~~being~~2 ~~funded~~clinical bystudy ~~the~~(which ~~National~~we ~~Institute~~paid ofto ~~Health~~TRDF in ~~the~~2020 ~~U.S.,~~for orexaluren); upon ~~the~~first ~~NIH,~~dosing ~~under~~of ~~sub-awards~~a ~~from~~patient ~~the~~in ~~University~~a ofpivotal ~~Alabama~~study; and upon the ~~University~~first approval of ~~Michigan,~~a ~~and~~new itdrug isapplication ~~possible~~(NDA); ~~that~~(ii) ~~such~~certain ~~research~~royalties ~~programs~~in ~~will~~the ~~overlap~~low- ~~with~~to ~~the~~mid-single-digit ~~research~~percentages ~~conducted~~of ~~according~~all tonet ~~the~~sales ~~terms~~(subject ofto ~~our~~change ~~agreement.~~in In the case of ~~any~~(a) ~~such~~sublicensing ~~overlap~~to a pharmaceutical or biotechnology company, ~~the~~or ~~work~~(b) ~~product~~payment of ~~such~~royalties ~~research~~to ~~will~~third beparties, ~~subject~~or to(c) ~~the~~commercialization ~~terms~~by ~~and~~a ~~conditions~~third party of ~~such~~an ~~sub-awards,~~authorized ~~including~~generic ~~certain~~to ~~obligations~~a ~~under~~licensed 35product); ~~U.S.C.~~and §§(iii) ~~200~~a mid-~~212~~single-digit orto 37low-double-digit ~~C.F.R.~~percentage §of ~~401~~any etnon-royalty ~~seq~~sublicense income. inIn addition to the ~~case~~milestone ofpayments, ~~any~~we ~~TRDF~~undertook ~~inventions~~to ~~that~~annually ~~are~~fund ~~also~~the ~~“subject~~research ~~invention”~~activities asunder ~~defined~~the license, currently in 35the Uestimated annual amount of $0.~~S.C.~~1 §million ~~201~~per year.

Under the Technion Agreement, TRDF reserved the right, for itself, to the Technion and other not-for-profit research organizations to utilize the technology solely for educational purposes. Furthermore, Professor Timor Baasov, the principal investigator, had ongoing research programs involving covered compounds (as defined in the agreement) that are being funded by the National Institute of Health in the U.S., or the NIH, under sub-awards from the University of Alabama and the University of Michigan, and it is possible that such research programs will overlap with the research conducted according to the terms of our agreement. In the case of any such overlap, the work product of such research will be subject to the terms and conditions of such sub-awards, including certain obligations under 35 U.S.C. §§ 200-212 or 37 C.F.R. § 401 et seq. in the case of any TRDF inventions that are also “subject invention” as defined in 35 U.S.C. § 201.

The license agreement shall continue in full force and effect on a product-by-product and country-by-country basis until the expiration of all payment obligations for any such licensed product as described above. Upon the expiration, we will have a fully paid-up, worldwide non-exclusive, perpetual, irrevocable license (with the right to grant sublicenses) to use certain materials and the research results, solely with respect to products in the field of prevention, diagnosis or treatment of any human disease or condition.

License Agreement between Zikani and President and Fellows of Harvard College ("Harvard")

On February 10, 2015, Zikani entered into an agreement with the President and Fellows of Harvard to license certain patent rights owned by Harvard. This license agreement was subsequently amended and restated on March 31, 2020 and further amended on July 17, 2024 (the “Harvard Agreement”). Under the Harvard Agreement, Harvard is entitled to receive clinical and regulatory milestone payments totaling up to $3.6 million in the aggregate per licensed product approved in the United States, a major European ~~Union~~country, and Japan. The Company is also obligated to make additional royalty payments to Harvard upon the occurrence of certain sales milestones per licensed product up to a mid-single digit royalty percentage. The royalty percentage depends on the product and whether such licensed product is covered by a valid claim within the certain patent rights that the Company licenses from Harvard. The Company is also obligated to make tiered non-royalty sublicense income payments of mid- to high single digit percentage to low double-digit percentage of any non-royalty sublicense income. Additionally, the Company is obligated to pay Harvard a percentage of income associated with transferring a priority review voucher from the FDA.

8Almirall has agreed to assume responsibility for the payment and performance obligations under the Harvard Agreement as sublicensee which ultimately depends on Almirall’s development and commercialization of ZKN-013.

~~covered~~Under bythis aagreement, ~~valid~~the ~~claim~~Company ~~within~~has ~~the~~an ~~certain~~exclusive, ~~patent~~worldwide, ~~rights~~royalty-bearing ~~that~~license ~~the~~under ~~Company~~Harvard’s ~~licenses~~interest ~~from~~in ~~Harvard.~~the ~~Further~~patent rights, ~~the~~and ~~Company~~a ~~may~~non-exclusive, ~~sub~~worldwide, royalty-bearing license ~~the~~under ~~patent~~Harvard’s ~~rights~~interest ~~and~~in ~~any~~the ~~income~~Harvard know-how, ~~with~~solely ~~the~~to ~~Company~~develop, ~~obligated~~make, tohave ~~remit~~made, touse, ~~Harvard~~offer ~~fees~~for ~~ranging~~sale, ~~from~~sell, ~~20%~~have tosold ~~30%~~and ofimport ~~such~~and ~~sublicense~~export ~~income~~licensed upproducts tosolely for the ~~achievement~~use of ~~certain~~macrolides ~~milestone~~in ~~events.~~humans ~~There~~and ~~were~~non-human noanimals, ~~royalties~~including, ~~recorded~~without inlimitation, ~~2022~~the diagnosis, prevention and/or ~~2021~~treatment of antibacterial infection, inflammation and immunomodulation.

~~Under~~Harvard ~~this~~retains ~~agreement~~the right, ~~the~~for ~~Company~~itself ~~has~~and anfor ~~exclusive,~~other ~~worldwide~~not-for-profit research organizations, ~~royalty-bearing~~to ~~license~~practice ~~under~~the ~~Harvard’s~~patent ~~interest~~rights inwithin the ~~Patent~~scope ~~Rights~~of the license granted above, ~~and~~solely afor non-~~exclusive,~~commercial ~~worldwide~~research, ~~royalty-bearing~~educational ~~license~~and ~~under~~scholarly ~~Harvard’s~~purposes; ~~interest~~however, nothing in the Harvard ~~Know~~Agreement shall be construed as permitting Harvard or any such not-~~How~~for-profit research organization to grant any rights to any third party, ~~solely~~including any for-profit sponsor, to practice or exploit any of the patent rights for any commercial purpose that would be inconsistent with the terms of the exclusive license of the patent rights, including any right to develop, ~~make~~manufacture, ~~have~~market ~~made,~~or sell licensed products for use of macrolides in humans and non-human animals, ~~offer~~including, ~~for~~without ~~sale~~limitation, ~~sell~~the diagnosis, ~~have~~prevention ~~sold~~and/or treatment of antibacterial infection, inflammation and ~~import~~immunomodulation; and ~~export~~the ~~licensed~~United ~~products~~States ~~solely~~federal ~~within~~government retains rights in the ~~field~~patent rights pursuant to 35 U.S.C. §§ 200-212 and 37 C.F.R. § 401 et seq., and any right granted in this agreement greater than that permitted under 35 U.S.C. §§ 200-212 or 37 C.F.R. § 401 et seq. will be deemed modified.

~~Harvard~~License ~~retains~~Agreement ~~the~~between ~~right,~~Eloxx ~~for itself~~ and for other not-for-profit research organizations, to practice the patent rights within the scope of the license granted above, solely for non-commercial research, educational and scholarly purposes; provided, that, nothing herein shall be construed as permitting Harvard or any such not-for-profit research organization to grant any rights to any third party, including any for-profit sponsor, to practice or exploit any of the patent rights for any commercial purpose that would be inconsistent with the terms of the exclusive license of the patent rights, including any right to develop, manufacture, market or sell licensed products for use in the field; and the United States federal government retains rights in the patent rights pursuant to 35 U.S.C. §§ 200-212 and 37 C.F.R. § 401 et seq., and any right granted in this agreement greater than that permitted under 35 U.S.C. §§ 200-212 or 37 C.F.R. § 401 et seq. will be deemed modified. Almirall

On March 11, 2024, the Company entered into the License Agreement with Almirall (the “Almirall License Agreement”). Under the terms of the Almirall License Agreement, Almirall obtained global rights to develop and commercialize ZKN-013 for the potential treatment of rare dermatological and other diseases associated with NMs.

Under the Almirall License Agreement, the Company received an upfront payment and is eligible to receive additional payments throughout the potential development phases, including development and sales milestones of up to approximately $470.0 million and tiered royalties of mid-single to low-double digit percentages of any future global net sales of licensed products during the applicable royalty term. The achievement and timing of the milestones depend on the success of development, approval and sales progress, if any, of commercial products developed through the collaboration in the future.

During the year ended December 31, 2024, we recorded $6.4 million in license and service revenue from the Almirall License Agreement, of which $3.0 million related to the achievement of a development milestone.

In March 2025, Almirall informed us of its decision to not exercise the option for continued research and development services under the Almirall License Agreement, as permitted within the Almirall License Agreement, thereby relieving us of our remaining responsibilities under the Almirall License Agreement. We remain eligible to receive additional payments throughout the potential development phases, including development and sales milestones of up to approximately $470.0 million and tiered royalties based on any potential future global sales.

Royalty and Revenue Sharing Agreement

On July 10, 2024, as a condition of Domicilium’s entry into the Sixth Hercules Amendment and in consideration of the Tranche 2 Advance, the borrowers and the Company entered into a Royalty and Revenue Sharing Agreement, as amended on March 2, 2026 (the “Royalty Agreement”) with Domicilium. Capitalized terms under this heading “Royalty and Revenue Sharing Agreement” not otherwise defined herein have the definitions ascribed to them in the Royalty Agreement.

Under the Royalty Agreement, the Company agreed to pay to Domicilium an amount equal to (i) (x) a low-mid-double-digit percentage of the Development and Launch Milestone Payments for the several next occurring Development and Launch Milestone Events (as defined in the Almirall License Agreement), minus (y) the amounts required to be paid by the Company pursuant to certain vendors as defined in the Royalty Agreement, and (ii) (x) a low-mid-double-digit percentage of (1) each subsequent Development and Launch Milestone Payment plus (2) any Priority Review Voucher Income (as defined in the Almirall License Agreement) realized by Eloxx, less (y) any amount of such Development and Launch Milestone Payments which are due to Harvard University pursuant to the Harvard License Agreement, provided the aggregate amount paid to Domicilium shall not exceed an amount in the mid-double-digit millions. Each Milestone Sharing Payment shall be applied as a repayment or prepayment, as applicable, of the Loans (as defined in the Amended Loan Agreement) (including all interest and fees thereon) owed to Domicilium, if any such Loans remain outstanding.

The Royalty Agreement provides for an amount based on a percentage of the aggregate of (without duplication) the net sales, royalties and any other income or revenue realized by the Company solely related to or arising from the exaluren compound or any exaluren product, calculated in accordance with U.S. GAAP (collectively, the “exaluren Revenue”) (the “exaluren Revenue-Based Payment”). The exaluren Revenue-Based Payment with respect to each fiscal quarter shall be less than one percent of exaluren Revenue during the applicable fiscal quarter. Commencing on the ZKN-013 royalty commencement date, the Company promises to pay to Domicilium an amount based on a percentage of the aggregate of (without duplication) the net sales, royalties and any other income or revenue realized by the Company solely related to or arising from the ZKN-013 compound, calculated in accordance with U.S. GAAP (collectively, the “ZKN-013 Revenue”) (the “ZKN-013 Revenue-Based Payment”). The ZKN-013 Revenue-Based Payment with respect to each fiscal quarter shall be less than one percent of ZKN-013 Revenue during the applicable fiscal quarter.

Cystic Fibrosis Foundation

During 2019, the Company received a funding award (the “2019 CFF Award”) from the Cystic Fibrosis Foundation (“CFF”) for up to $3.6 million to fund the clinical development of exaluren in cystic fibrosis, which award was amended in December 2020 and March 2022 to increase the potential award amounts up to $15.9 million. Additionally, in May 2021, the Company received an additional award from the CFF (the “2021 CFF Award”) pursuant to an award agreement (the "2021 CFF Award Agreement") for up to $2.6 million to help identify optimized oral ribosome modulating agents for further development in the treatment of cystic fibrosis patients with NMs. Payment of award amounts under each of the 2019 CFF Award and the 2021 CFF Award are subject to the achievement of certain development milestones in connection with the Company’s cystic fibrosis development programs. Under the terms of the agreements, the Company was required to repay amounts received from the CFF (or specified multiples of such amounts) in certain circumstances, including as royalties on net sales, and, in the event of a disposition of the underlying asset (as defined in the agreements).

On October 28, 2025, the Company and CFF entered into Amendment No. 3 to Development Program Award Letter Agreement Royalty Repurchase Agreement and Termination Agreement, as amended on February 26, 2026 (the “CFF Omnibus Agreement”), which, upon the completion of certain funding and contractual milestones and a one-time payment to CFF, reduced the Company’s obligations to CFF to less than one percent of net sales of exaluren for the treatment of any disease amenable to treatment of patients with a NM with a read-through agent and terminated the 2021 CFF Award Agreement. As of December 31, 2025, the Company has not made any royalty payments to CFF pursuant to the CFF Omnibus Agreement.

Manufacturing

~~ELX-02~~Exaluren is designed to be manufactured under current Good Manufacturing Practice (“cGMP”) conditions and is formulated as a sterile frozen liquid or lyophilized powder in glass vials. ~~ELX-02~~Exaluren is designed to be administered by parenteral subcutaneous injection after appropriate dilution or reconstitution, as required.

We do not own or operate manufacturing or distribution facilities for the production of clinical quantities of ~~ELX-02~~exaluren or for our other preclinical product candidates. We currently rely, and expect to continue to rely, on third parties for the manufacture, packaging, labeling and distribution of clinical supplies of ~~ELX-02~~exaluren as well as any other candidate that we may develop.

We engage separate manufacturers for drug substance and drug product. We have a relationship with a manufacturer that is capable of providing fill and finish services for our clinical product at the current scale. To support later clinical trials, transfer of the manufacturing and release to a manufacturer with higher lot scale capacity will be needed for our clinical product.

All of our current drug candidates are organic compounds of low molecular weight. We have selected our lead compounds not only on the basis of their potential efficacy and safety but also for their ease of synthesis and reasonable cost of their starting materials. ~~ELX-02~~Exaluren is manufactured in reliable and reproducible synthetic processes. We currently use a single third-party manufacturing source for the production of a key raw material, produced by bacterial fermentation; however, we have identified several other acceptable sources for this production.

We currently obtain clinical supplies of ~~ELX-02~~exaluren from third-party manufacturers pursuant to agreements that include specific supply timelines and volume expectations. If a manufacturer should become unavailable to us for any reason, we would seek to obtain supply from another manufacturer engaged by us for the applicable product or service. In the event that we were unable to procure the applicable supply from a currently qualified manufacturer, we believe that there are a number of potential replacements for each of our outsourced services; however, we would likely experience delays in our ability to supply ~~ELX-02~~exaluren in advancing our clinical trials while we identify and qualify replacement suppliers.

Government Regulation

Government authorities in the United States, at the federal, state and local level, and other countries extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, marketing and export and import of drug products. A new drug must be approved by the FDA through the New Drug Application (“NDA”) process before it may be legally marketed in the United States. We, along with any third-party contractors, will be required to navigate the various preclinical, clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies or seek approval of our products and product candidates. The process of obtaining regulatory approvals and the subsequent compliance with applicable federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources.

U.S. Drug Development Process

In the United States, the FDA regulates drugs under the federal Food, Drug, and Cosmetic Act (“FDCA”) and its implementing regulations. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources. Failure to comply with the applicable U.S. requirements at any time during the product development process, approval process or after approval may subject an applicant to administrative or judicial sanctions. These sanctions could include the FDA’s refusal to approve pending applications, withdrawal of an approval, a clinical hold, warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal penalties. The process required by the FDA before a drug may be marketed in the United States generally involves the following:

•

completion of preclinical laboratory tests, animal studies and formulation studies in accordance with FDA’s Good Laboratory Practice (“GLP”) requirements and other applicable regulations;

•

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

•

approval by an independent Institutional Review Board (“IRB”) or ethics committee at each clinical site before each trial may be initiated;

•

performance of adequate and well-controlled human clinical trials in accordance with good clinical practices (“GCPs”) to establish the safety and efficacy of the proposed drug for its intended use;

•

preparation of and submission to the FDA of an NDA after completion of all pivotal trials;

•

a determination by the FDA within 60 days of its receipt of an NDA to file the application for review;

•

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 drug is produced to assess compliance with cGMP requirements to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity, and of selected clinical investigation sites to assess compliance with GCPs; ~~and~~

•

potential FDA audit of the preclinical and/or clinical trial sites that generated the data in support of the
NDA; and

•

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

The preclinical developmental stage generally involves laboratory evaluations of chemistry, formulation and stability, as well as studies to evaluate the product candidate’s toxicity in animals, in an effort to support subsequent clinical testing. The conduct of preclinical studies is subject to federal regulations and requirements, including GLP regulations, where applicable.

Prior to beginning the first clinical trial with a product candidate in the United States, the trial sponsor must submit an IND to the FDA. An IND is a request for authorization from the FDA to administer an investigational drug to humans. The central focus of an IND submission is on the general investigational plan and the protocol(s) for clinical studies. Some preclinical testing may continue after the IND is submitted. The IND also includes results of animal and in vitro studies assessing the toxicology, pharmacokinetics, pharmacology, and pharmacodynamic characteristics of the product candidate, chemistry, manufacturing, and controls information, and any available human data or literature to support the use of the product candidate. An IND must become effective before human clinical trials may begin. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises safety concerns or questions about the proposed clinical trial. In such a case, the IND may be placed on clinical hold and the IND sponsor and the FDA must resolve any outstanding concerns or questions before the clinical trial can begin. Submission of an IND therefore may or may not result in FDA authorization to begin a clinical trial.

Clinical trials involve the administration of the investigational drug to human subjects under the supervision of qualified investigators, generally physicians not employed by or under the trial sponsor’s control, in accordance with GCPs, which include the requirement that all research subjects provide their informed consent for their participation in any clinical study. Clinical trials are conducted under protocols detailing, among other things, the objectives of the study, the parameters to be used in monitoring subject 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.

10Furthermore, an independent IRB or ethics committee for each site proposing to conduct the clinical trial must review and approve the plan for any clinical trial and its informed consent form before the clinical trial begins at that site and must monitor the study until completed. An IRB is charged with protecting the welfare and rights of trial participants and considers such items as whether the risks to individuals participating in the clinical trials are minimized and are reasonable in relation to anticipated benefits. The IRB also approves the informed consent form that must be provided to each clinical trial subject or his or her legal representative and must monitor the clinical trial until completed. Regulatory authorities, the IRB or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the subjects are being exposed to an unacceptable health risk or that the trial is unlikely to meet its stated objectives. Some studies also include oversight by an independent group of qualified experts organized by the clinical study sponsor, known as a data safety monitoring board, which provides authorization for whether or not a study may move forward at designated check points based on access to certain data from the study, and may halt the clinical trial if it determines that there is an unacceptable safety risk for

Furthermore, an independent IRB or ethics committee for each site proposing to conduct the clinical trial must review and approve the plan for any clinical trial and its informed consent form before the clinical trial begins at that site, and must monitor the study until completed. Regulatory authorities, the IRB or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the subjects are being exposed to an unacceptable health risk or that the trial is unlikely to meet its stated objectives. Some studies also include oversight by an independent group of qualified experts organized by the clinical study sponsor, known as a data safety monitoring board, which provides authorization for whether or not a study may move forward at designated check points based on access to certain data from the study, and may halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy. There are also requirements governing the reporting of ongoing clinical studies and clinical study results to public registries, including clinicaltrials.gov.12

subjects or other grounds, such as no demonstration of efficacy. There are also requirements governing the reporting of ongoing clinical studies and clinical study results to public registries, including clinicaltrials.gov.

Human clinical trials are typically conducted in three sequential phases that may overlap or be combined:

•

Phase 1: The product candidate is initially introduced into healthy human subjects or patients with the target disease or condition. These studies are designed to test the safety, dosage tolerance, absorption, metabolism and distribution of the investigational product in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness.

•

Phase 2: The product candidate is administered to a limited patient population with a specified disease or condition to evaluate the preliminary efficacy, optimal dosages and dosing schedule and to identify possible adverse side effects and safety risks. Multiple Phase 2 clinical trials may be conducted to obtain information prior to beginning larger and more expensive Phase 3 clinical trials.

•

Phase 3: The product candidate is administered to an expanded patient population to further evaluate dosage, to provide statistically significant evidence of clinical efficacy and to further test for safety, 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 approval.

In some cases, the FDA may require, or sponsors may voluntarily pursue, additional clinical trials after a product is approved to gain more information about the product. These ~~so-called~~trials, sometimes referred to as Phase 4 studies, may be conducted after initial marketing approval, and may be used to gain additional experience from the treatment of patients in the intended therapeutic indication. In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of an NDA.

The FDA or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients. In addition, some clinical trials are overseen by an independent group of qualified experts organized by the sponsor, known as a data safety monitoring board or committee. Depending on its charter, this group may determine whether a trial may move forward at designated checkpoints based on access to certain data from the trial.

In addition, during the development of a new drug, sponsors are given opportunities to meet with the FDA at certain points. These points may be prior to submission of an IND, at the end of Phase 2, and before an NDA is submitted. Meetings at other times may be requested. These meetings can provide an opportunity for the sponsor to share information about the data gathered to date, for the FDA to provide advice, and for the sponsor and the FDA to reach agreement on the next phase of development. Sponsors typically use the meetings at the end of the Phase 2 trial to discuss Phase 2 clinical results and present plans for the pivotal Phase 3 clinical trials that they believe will support approval of the new drug.

Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the drug and 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, the manufacturer must develop methods for testing the identity, strength, quality and purity of the final drug. In addition, 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.

U.S. Review and Approval Process

Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product development, preclinical and other non-clinical studies and clinical trials, along with descriptions of the manufacturing process, analytical tests conducted on the chemistry of the drug, proposed labeling and other relevant information are submitted to the FDA as part of an NDA requesting approval to market the product. Data can come from company-sponsored clinical studies intended to test the safety and effectiveness of a use of the product, or from a number of alternative sources, including studies initiated by independent investigators. The submission of an NDA is subject to the payment of substantial user fees, unless a waiver or exemption applies.

11In addition, the Pediatric Research Equity Act (“PREA”) requires a sponsor to conduct pediatric clinical trials for most drugs, for a new active ingredient, new indication, new dosage form, new dosing regimen or new route of

In addition, the Pediatric Research Equity Act (“PREA”) requires a sponsor to conduct pediatric clinical trials for most drugs, for a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration. Under PREA, NDAs and supplements must contain a pediatric assessment unless the sponsor has received a deferral or waiver. The required assessment must evaluate the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The sponsor or FDA may request a deferral of pediatric clinical trials for some or all of the pediatric subpopulations. A deferral may be granted for several reasons, including a finding that the drug is ready for approval for use in adults before pediatric clinical trials are complete or that additional safety or effectiveness data needs to be collected before the pediatric clinical trials begin. The FDA must send a non-compliance letter to any sponsor that fails to submit the required assessment, keep a deferral current or fails to submit a request for approval of a pediatric formulation.13

administration. Under PREA, NDAs and supplements must contain a pediatric assessment unless the sponsor has received a deferral or waiver. The required assessment must evaluate the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The sponsor or FDA may request a deferral of pediatric clinical trials for some or all of the pediatric subpopulations. A deferral may be granted for several reasons, including a finding that the drug is ready for approval for use in adults before pediatric clinical trials are complete or that additional safety or effectiveness data needs to be collected before the pediatric clinical trials begin. The FDA must send a non-compliance letter to any sponsor that fails to submit the required assessment, keeps a deferral current or fails to submit a request for approval of a pediatric formulation.

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 NDA must be resubmitted with the additional information. The resubmitted application also is subject to review before the FDA accepts it for filing. Once filed, the FDA has a goal of ten months from the filing date to complete a standard review of an NDA for a drug that is a new molecular entity. The FDA reviews an NDA to determine, among other things, whether a product is safe and effective for its intended use and whether its manufacturing is sufficient to assure and preserve the product’s identity, strength, quality and purity.

The FDA may refer an application for a novel drug to an advisory committee. An advisory committee is a panel of independent experts, including clinicians and other scientific experts, that reviews, evaluates and provides a recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions. Before approving an NDA, the FDA will typically inspect the facility or facilities where the product is manufactured. The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP and adequate to assure consistent production of the product within required specifications. Additionally, before approving aan NDA, the FDA will typically inspect one or more clinical sites to assure compliance with GCPs.

After the FDA evaluates an NDA and conducts inspections 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 (“CRL”). An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications. A CRL will describe all of the deficiencies that the FDA has identified in the NDA, except that where the FDA determines that the data supporting the application are inadequate to support approval, the FDA may issue the CRL without first conducting required inspections and/or reviewing proposed labeling. In issuing the CRL, the FDA may recommend actions that the applicant might take to place the NDA in condition for approval, including requests for new clinical studies or additional information or clarification. Notwithstanding the submission of any requested additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.

If regulatory approval of a product is 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 NDA with a Risk Evaluation and Mitigation Strategy (“REMS”) to ensure the benefits of the product outweigh its risks. A REMS is a safety strategy to manage a known or potential serious risk associated with a medicine and to enable patients to have continued access to such medicines by managing their safe use, and could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries, and other risk minimization tools. The FDA also may condition approval on, among other things, changes to proposed labeling or the development of adequate controls and specifications. Once approved, the 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 also require one or more Phase 4 post- market studies and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization, and may limit further marketing of the product based on the results of these post-marketing studies. In addition, new government requirements, including those resulting from new legislation, may be established, or the FDA’s policies may change, which could impact the timeline for regulatory approval or otherwise impact ongoing development programs.

Expedited Development and Review Programs

The FDA offers a number of expedited development and review programs for qualifying product candidates. For example, the Fast Track program is intended to expedite or facilitate the process for reviewing product candidates that 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. Fast Track designation applies to the combination of the ~~product and the specific indication for which it is being studied. The sponsor of a Fast Track product candidate has~~

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product and the specific indication for which it is being studied. The sponsor of a Fast Track product candidate has opportunities for more frequent interactions with the applicable FDA review team during development and, once an NDA is submitted, the product candidate may be eligible for priority review. A Fast Track product candidate may also be eligible for rolling review, where the FDA may consider for review sections of the NDA 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.

A product 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 marketing application for a drug submitted to the FDA for approval, including a product candidate with a Fast Track designation and/or Breakthrough Therapy designation, may be eligible for other types of FDA programs intended to expedite the FDA review and approval process, such as priority review and accelerated approval. An NDA is eligible for priority review if the product candidate is designed to treat a serious or life-threatening disease or condition, and if approved, would provide a significant improvement in safety or effectiveness compared to available alternatives for such disease or condition. For new-molecular-entity NDAs, priority review designation means the FDA’s goal is to take action on the marketing application within six months of the 60-day filing date, as opposed to ten months under standard review.

Additionally, product candidates studied for their safety and effectiveness in treating serious or life-threatening diseases or conditions may receive accelerated approval upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or 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, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments. As a condition of accelerated approval, the FDA will generally require the sponsor to perform adequate and well-controlled post-marketing clinical studies to verify and describe the anticipated effect on irreversible morbidity or mortality or other clinical benefit. ~~Products~~Under ~~receiving~~the ~~accelerated~~Food ~~approval~~and Drug Omnibus Reform Act of 2022 (“FDORA”), the FDA may require, as appropriate, that such trials be ~~subject~~underway prior to ~~expedited~~approval ~~withdrawal~~or ~~procedures~~within ifa specific time period after the ~~sponsor~~date ~~fails~~of toapproval ~~conduct~~for a product granted accelerated approval . Under FDORA, the ~~required~~FDA ~~post-marketing~~has ~~studies~~increased inauthority afor ~~timely~~expedited ~~manner~~procedures to withdraw approval of a drug or indication approved under accelerated approval if, ~~such~~for ~~studies~~example, ~~fail~~the confirmatory trial fails to verify the predicted clinical benefit of the product. In addition, the FDA currently requires as a condition for accelerated approval pre-approval of promotional materials, which could adversely impact the timing of the commercial launch of the product.

Fast Track designation, 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 drug designation and exclusivity

Under the Orphan Drug Act, the FDA may grant orphan designation to a drug intended to treat a rare disease or condition, defined as a disease or condition with a patient population of fewer than 200,000 individuals in the United States, or a patient population greater than 200,000 individuals in the United States and when there is no reasonable expectation that the cost of developing and making available the drug in the United States will be recovered from sales in the United States for that drug. Orphan drug designation must be requested before submitting an NDA. After the FDA grants orphan drug designation, the generic identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA.

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If a product that has orphan drug designation subsequently receives the first FDA approval for a particular active ingredient for the disease 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, including a full NDA, to market the same drug for the same approved use or indication within such rare disease or condition for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity or if the FDA finds that the holder of the orphan drug exclusivity has not shown that it can assure the availability of sufficient quantities of the orphan drug to meet the needs of patients with the disease or condition for which the drug was designated. Orphan drug exclusivity does not prevent the FDA from approving a different drug for the same ~~disease~~approved indication or ~~condition~~use, or the same drug for a different ~~disease~~indication or ~~condition~~use. Among the other benefits of orphan drug designation are tax credits for certain research and a waiver of the NDA application user fee.

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

Post-approval Requirements

Drug products manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to record-keeping, reporting of adverse experiences, periodic reporting, product sampling and distribution, and advertising and promotion of the product. 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, annual program fees for any marketed products. Drug 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 cGMP, which impose certain procedural and documentation requirements upon us and our 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 cGMP and impose reporting requirements. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMP and other aspects of regulatory compliance.

The FDA may withdraw 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 revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical studies to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program. Other potential consequences include, among other things:

•

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

•

fines, warning letters, or untitled letters;

•

clinical holds on clinical studies;

•

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

•

product seizure or detention, or refusal to permit the import or export of products;

•

consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs;

•

mandated modification of promotional materials and labeling and the issuance of corrective information;

•

the issuance of safety alerts, Dear Healthcare Provider letters, press releases and other communications containing warnings or other safety information about the product; or

•

injunctions or the imposition of civil or criminal penalties.

The FDA closely regulates the marketing, labeling, advertising and promotion of drug products. A company can make only those claims relating to safety and efficacy, purity and potency that are approved by the FDA 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 off-label uses. Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties. Physicians may prescribe, in their independent professional medical judgment, legally available products for uses that are not described in the product’s labeling and that differ from those tested by us and approved by the FDA. Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances. The FDA does not regulate the behavior of physicians in their choice of treatments. The FDA does, however, restrict manufacturer’s communications on the subject of off-label use of their products. However, companies may share truthful and not misleading information that is otherwise consistent with a product’s FDA-approved labelling.16

Marketing Exclusivity

Market exclusivity provisions authorized under the FDCA can delay the submission or the approval of certain marketing applications. The FDCA provides a five-year period of non-patent data exclusivity within the United States to the first applicant to obtain approval of an NDA for a new chemical entity. A drug is a new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule or ion responsible for the action of the drug substance. During the exclusivity period, the FDA may not approve or even accept for review an abbreviated new drug application (“ANDA”) or an NDA submitted under Section 505(b)(2) (505(b)(2) NDA) submitted by another company for another drug based on the same active moiety, regardless of whether the drug is intended for the same indication as the original innovative drug or for another indication, where the applicant does not own or have a legal right of reference to all the data required for approval. However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement to one of the patents listed with the FDA by the innovator NDA holder.

The FDCA alternatively provides three years of marketing exclusivity for an NDA, or supplement to an existing 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, for example new indications, dosages or strengths of an existing drug. This three-year exclusivity covers only the modification for which the drug received approval on the basis of the new clinical investigations and does not prohibit the FDA from approving ANDAs or 505(b)(2) NDAs for drugs containing the active agent for the original indication or condition of use. 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 any preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

Pediatric exclusivity is another type of marketing exclusivity available in the United States. Pediatric exclusivity provides for an additional six months of marketing exclusivity attached to another period of exclusivity or patent term, if a sponsor conducts clinical trials in children in response to a written request from the FDA. The issuance of a written request does not require the sponsor to undertake the described clinical trials.

Foreign Regulation

We conduct clinical trials and plan to market our future products in numerous jurisdictions outside the U.S. Most of these jurisdictions have clinical trial, product approval and post-approval regulatory processes that are similar in principle to those in the U.S. Thus, whether or not we obtain FDA approval for a product candidate, we must obtain approval by the comparable regulatory authorities of foreign countries or economic areas, such as the E.U., before we can commence clinical trials or market products in those countries or areas. The approval process and requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from place to place, and the time may be longer or shorter than that required for FDA approval.

~~Under~~Non-clinical ~~the~~Studies E.U. regulatory system, a company may submit marketing authorization applications either under a centralized or decentralized procedure. The centralized procedure, which is compulsory for orphan medicines, medicines produced by biotechnology, and ~~those~~Clinical ~~medicines~~Trials ~~intended to treat AIDS, cancer, neurodegenerative disorders, or diabetes, and optional for those medicines that are highly innovative, provides for the grant of a single~~

15Similarly to the United States, the various phases of non-clinical and clinical research in the EU are subject to significant regulatory controls.

~~marketing~~Non-clinical ~~authorization~~studies ~~that~~are isperformed ~~valid~~to ~~for~~demonstrate ~~all~~the ~~E.U.~~health ~~member~~or ~~states~~environmental safety of new chemical or biological substances. InNon-clinical ~~addition~~(pharmaco-toxicological) tostudies ~~the~~must ~~centralized~~be ~~procedure,~~conducted in compliance with the ~~E.U.~~principles ~~also~~of ~~has~~good alaboratory ~~nationalized~~practice ~~procedure,~~(“GLP”) ~~which~~as ~~requires~~set aforth ~~separate~~in ~~application~~EU toDirective ~~and~~2004/10/EC ~~approval~~(unless ~~determination~~otherwise byjustified ~~each~~for ~~country;~~certain aparticular ~~decentralized~~medicinal ~~procedure~~products, ~~whereby~~e.g., ~~applicants~~radio-pharmaceutical ~~submit~~precursors ~~identical~~for ~~applications~~radio-labeling topurposes). ~~several~~In ~~countries~~particular, ~~and~~non-clinical ~~receive~~studies, ~~simultaneous~~both ~~approval;~~in vitro and ain ~~mutual~~vivo, ~~recognition~~must ~~procedure~~be planned, ~~where~~performed, ~~applicants~~monitored, ~~submit~~recorded, anreported ~~application~~and toarchived ~~one~~in ~~country~~accordance ~~for~~with ~~review~~the ~~and~~GLP ~~other~~principles, ~~countries~~which ~~may~~define ~~accept~~a orset ~~reject~~of ~~the~~rules ~~initial~~and ~~decision.~~criteria for a quality system for

~~Other U.S. Healthcare Laws and Compliance Requirements~~17

~~Although we currently do not have any products on~~ the ~~market,~~organizational weprocess ~~are~~ and, ~~upon approval and commercialization, will be subject to additional healthcare regulation and enforcement by~~ the ~~federal~~conditions ~~government~~for ~~and~~non-clinical bystudies. ~~authorities~~These inGLP ~~the~~standards ~~states~~reflect ~~and foreign jurisdictions in which we conduct our business. In~~ the ~~United~~Organization ~~States,~~for ~~such~~Economic ~~laws include, without limitation, state and federal anti~~Co-~~kickback,~~operation ~~fraud~~ and ~~abuse,~~Development ~~false claims, price reporting, and transparency laws and regulations regarding payments or other transfers of value made to physicians and other licensed healthcare professionals~~requirements.

~~The~~Clinical ~~federal~~trials ~~Anti-Kickback~~of ~~Statute~~medicinal ~~prohibits,~~products ~~among other things, any person or entity, from knowingly and willfully offering, paying, soliciting, or receiving any remuneration, directly or indirectly, overtly or covertly,~~ in ~~cash~~the orEU inmust ~~kind,~~be toconducted ~~induce or~~ in ~~return~~accordance ~~for~~with ~~purchasing,~~EU ~~leasing,~~and ~~ordering,~~national orregulations ~~arranging~~and ~~for~~ the ~~purchase,~~International ~~lease~~Council orfor ~~order~~Harmonization of ~~any~~Technical ~~item~~Requirements orfor ~~service~~Pharmaceuticals ~~reimbursable~~for ~~under~~Human ~~Medicare,~~Use ~~Medicaid~~(“ICH”) orguidelines ~~other~~on ~~federal~~GCP ~~healthcare~~as ~~programs.~~well ~~The~~as ~~term~~the ~~remuneration~~applicable ~~has~~regulatory ~~been~~requirements ~~interpreted~~and ~~broadly~~the toethical ~~include~~principles ~~anything~~that ~~of value. In addition, a person or entity does not need to~~ have ~~actual~~their ~~knowledge~~origin ofin the ~~statute~~Declaration orof ~~specific intent to violate it in order to have committed a violation~~Helsinki. ~~The~~If ~~Anti-Kickback~~the ~~Statute~~sponsor ~~has~~of ~~been~~the ~~interpreted~~clinical totrial ~~apply~~is tonot ~~arrangements~~established ~~between~~within ~~pharmaceutical manufacturers on~~ the ~~one hand and prescribers~~EU, ~~purchasers,~~it ~~and~~must ~~formulary~~appoint ~~managers~~an onEU ~~the~~entity ~~other.~~to ~~There~~act ~~are~~as aits ~~number~~legal ~~of statutory exceptions and regulatory safe harbors protecting some common activities from prosecution~~representative. The ~~exceptions~~sponsor ~~and~~must ~~safe~~take ~~harbors~~out ~~are~~a ~~drawn~~clinical ~~narrowly~~trial ~~and~~insurance ~~practices~~policy, ~~that~~and ~~involve~~in ~~remuneration~~most ~~that~~EU ~~may~~member ~~be alleged to be intended to induce prescribing~~states, ~~purchasing,~~the orsponsor ~~recommending~~is ~~may~~liable ~~be subject~~ to ~~scrutiny~~provide if‘no ~~they~~fault’ docompensation ~~not qualify for an exception or safe harbor. Failure~~ to ~~meet~~any ~~all~~study ofsubject ~~the~~injured ~~requirements~~in ~~of a particular applicable statutory exception or regulatory safe harbor does not make~~ the ~~conduct~~clinical ~~per se illegal under the Anti-Kickback Statute~~trial. ~~Instead, the legality of the arrangement will be evaluated on a case-by-case basis based on a cumulative review of all of its facts and circumstances.~~

The ~~federal~~regulatory ~~False~~landscape ~~Claims~~related ~~Act~~to ~~prohibits,~~clinical ~~among~~trials ~~other~~in ~~things,~~the ~~any~~EU ~~person~~has orbeen ~~entity~~subject ~~from~~to ~~knowingly~~recent ~~presenting,~~changes. orThe ~~causing~~EU toClinical beTrials ~~presented,~~Regulation a(“CTR”) ~~false~~which ~~claim~~was ~~for~~adopted ~~payment~~in ~~to,~~April or2014 ~~approval~~and ~~by,~~repeals the ~~federal~~EU ~~government~~Clinical orTrials ~~knowingly making~~Directive, ~~using,~~became orapplicable ~~causing~~on toJanuary be31, ~~made~~2022. orUnlike ~~used~~directives, athe ~~false~~CTR ~~record~~is ordirectly ~~statement~~applicable ~~material~~in toall aEU ~~false~~member orstates ~~fraudulent~~without ~~claim to~~ the ~~federal~~need ~~government.~~for Asmember astates ~~result~~to offurther aimplement ~~modification~~it ~~made~~into bynational ~~the~~law. ~~Fraud~~The ~~Enforcement~~CTR ~~and~~notably ~~Recovery~~harmonizes ~~Act~~the ofassessment ~~2009,~~and asupervision ~~claim~~processes ~~includes “any request or demand”~~ for ~~money~~clinical ortrials ~~property~~throughout ~~presented to~~ the ~~U.S.~~EU ~~government.~~via ~~In addition,~~ a ~~claim~~Clinical ~~including~~Trials ~~items~~Information orSystem, ~~services~~which ~~resulting~~contains ~~from~~ a ~~violation~~centralized ofEU ~~the~~portal ~~federal~~and ~~Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the federal False Claims Act~~database.

~~The~~While ~~U.S.~~the ~~federal~~EU ~~Health~~Clinical ~~Insurance~~Trials ~~Portability~~Directive ~~and~~required ~~Accountability~~a ~~Act~~separate ofclinical ~~1996~~trial application (“~~HIPAA~~CTA”), ~~also~~to ~~created~~be ~~new~~submitted ~~federal~~in ~~criminal~~each ~~statutes~~member ~~that~~state ~~prohibit~~in ~~knowingly~~which ~~and~~the ~~willfully~~clinical ~~executing,~~trial ortakes ~~attempting~~place, to ~~execute,~~both athe ~~scheme~~competent tonational ~~defraud~~health orauthority toand ~~obtain,~~an byindependent ~~means~~ethics ofcommittee, ~~false~~much orlike ~~fraudulent~~the ~~pretenses,~~FDA ~~representations~~and orIRB ~~promises~~respectively, ~~any~~the ~~money~~CTR orintroduces ~~property~~a ~~owned~~centralized ~~by,~~process orand ~~under~~only requires the ~~control~~submission orof ~~custody~~a ~~of,~~single ~~any~~application ~~healthcare~~for ~~benefit~~multi-center ~~program,~~trials. ~~including~~The ~~private~~CTR ~~third-party~~allows ~~payors~~sponsors ~~and~~to ~~knowingly~~make ~~and~~a ~~willfully~~single ~~falsifying,~~submission ~~concealing~~to orboth ~~covering~~the upcompetent byauthority ~~trick,~~and ~~scheme~~an orethics ~~device~~committee in each member state, aleading ~~material~~to ~~fact~~a orsingle ~~making~~decision ~~any~~per ~~materially~~member ~~false,~~state. ~~fictitious~~The orCTA ~~fraudulent~~must ~~statement~~include, inamong ~~connection~~other ~~with~~things, ~~the~~a ~~delivery~~copy of orthe ~~payment~~trial ~~for~~protocol ~~healthcare~~and ~~benefits,~~an ~~items,~~investigational ormedicinal ~~services.~~product ~~Similar~~dossier tocontaining ~~the~~information ~~Anti-Kickback~~about ~~Statute,~~the amanufacture ~~person~~and orquality ~~entity~~of ~~does~~the ~~not~~medicinal ~~need~~product tounder ~~have~~investigation. ~~actual~~The ~~knowledge~~assessment procedure of the ~~statute~~CTA orhas ~~specific~~been ~~intent~~harmonized toas ~~violate~~well, itincluding ina ~~order~~joint toassessment ~~have~~by ~~committed~~all amember ~~violation~~states ~~Also~~concerned, ~~many~~and ~~states~~a ~~have~~separate ~~similar~~assessment ~~fraud~~by ~~and~~each ~~abuse~~member ~~statutes~~state orwith ~~regulations~~respect ~~that~~to ~~apply~~specific requirements related to ~~items~~its ~~and~~own ~~services~~territory, ~~reimbursed~~including ~~under~~ethics ~~Medicaid~~rules. ~~and~~Each ~~other~~member state’s ~~programs,~~decision ~~or,~~is incommunicated ~~several~~to ~~states,~~the ~~apply~~sponsor ~~regardless~~via ofthe centralized EU portal. Once the ~~payor~~CTA is approved, clinical study development may proceed.

~~Additionally,~~The ~~the~~CTR ~~federal~~transition ~~Physician~~period ~~Payments~~ended ~~Sunshine~~on ~~Act~~January ~~and its implementing regulations~~31, ~~require that certain manufacturers of drugs~~2025, ~~devices, biological~~ and ~~medical~~all ~~supplies~~clinical ~~for~~trials ~~which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program~~ (~~with~~and ~~certain~~related ~~exceptions~~applications) ~~annually~~are ~~report~~now ~~information~~fully ~~related~~subject to ~~certain~~the ~~payments~~provisions ~~or other transfers~~ of ~~value~~the made or distributed to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain non-physician practitioners (physician assistants, nurse practitioners, clinical nurse specialists, anesthesiologist assistants, certified registered nurse anesthetists and certified nurse midwives) and teaching hospitals, certain ownership and investment interests held by physicians and their immediate family membersCTR.

16Medicines used in clinical trials must be manufactured in accordance with Good Manufacturing Practice (“GMP”). Other national and EU-wide regulatory requirements may also apply.

~~Violation~~Marketing ofAuthorization any of the federal and state healthcare laws described above or any other governmental regulations that apply to us may result in significant penalties, including without limitation, civil, criminal and/or administrative penalties, damages, fines, disgorgement, exclusion from participation in government programs, such as Medicare and Medicaid, injunctions, private “qui tam” actions brought by individual whistleblowers in the name of the government, contractual damages, reputational harm, administrative burdens, diminished profits and future earnings, and the curtailment or restructuring of operations.

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

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

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

Under the centralized procedure the maximum timeframe for the evaluation of an MAA by the EMA is 210 days, excluding clock stops.

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

Data and Marketing Exclusivity

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

Orphan Medicinal Products

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

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

Pediatric Development

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

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

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

Other U.S. and Foreign Healthcare Laws and Compliance Requirements

Pharmaceutical companies and developers and manufacturers of therapeutic biological products 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 and may constrain the financial arrangements and relationships through which we research as well as sell, market, and distribute any products for which we obtain marketing approval. Such laws include, without limitation, federal and state anti-kickback, fraud and abuse, false claims, data privacy and security, and physician and other healthcare provider transparency laws and regulations.

In the EU, the advertising and promotion of medicinal products are also subject to laws concerning promotion of medicinal products, interactions with physicians, misleading and comparative advertising and unfair commercial practices. All advertising and promotional activities for 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.

Violation of any such laws or any other governmental regulations, including foreign regulations, that apply may result in significant penalties, including without limitation, civil, criminal and/or administrative penalties, damages, fines, disgorgement, exclusion from participation in government programs, such as Medicare and Medicaid, injunctions, private “qui tam” actions brought by individual whistleblowers in the name of the government, contractual damages, reputational harm, administrative burdens, diminished profits and future earnings, and the curtailment or restructuring of operations.

Coverage and Reimbursement

Sales of any pharmaceutical product depend, in part, on the extent to which such product will be covered by third-party payors, such as federal, state and foreign government healthcare programs, commercial insurance and managed healthcare organizations, and the level of reimbursement for such product by third-party payors. Significant uncertainty exists as to the coverage and reimbursement status of any newly approved product, particularly for gene therapy products where the Centers for Medicare & Medicaid Services (“CMS”) and other third-party payors in the United States have not yet established a uniform policy of coverage and reimbursement. Therefore, decisions. Decisions regarding the extent of coverage and amount of reimbursement to be provided are made on a plan-by-plan basis. One third-party payor’s decision to cover a particular product does not ensure that other payors will also provide coverage for the product. As a result, the coverage determination process can require manufacturers to provide scientific and clinical support for the use of a product to each payor separately and can be a time-consuming process, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance. 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 for the product itself or the treatment or procedure in which the product is used may not be available, which may impact physician utilization.

In addition, third-party payors are increasingly reducing reimbursements for pharmaceutical products and services. The U.S. government and state legislatures have continued implementing cost-containment programs, including price controls, restrictions on coverage and reimbursement and requirements for substitution of generic products. Third-party payors are more and more challenging the prices charged, examining the medical necessity and reviewing the cost effectiveness of pharmaceutical products, in addition to questioning their 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. Decreases in third-party reimbursement for any product or a decision by a third-party payor not to cover a product could reduce physician usage and patient demand for the product.

In international markets, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies. For example, the European Union provides options for its member states to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use. A member state may approve a specific price for the medicinal product or it may instead adopt a system of direct or indirect controls on the profitability of us placing the medicinal product on the market. Pharmaceutical products may face competition from lower-priced products in foreign countries that have placed price controls on pharmaceutical products and may also compete with imported foreign products. Furthermore, there is no assurance that a product will be considered medically reasonable and necessary for a specific indication, will be considered cost-effective by third-party payors, that an adequate level of reimbursement will be established even if coverage is available or that the third-party payors’ reimbursement policies will not adversely affect the ability for manufacturers to sell products profitably. 20

In international markets, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies. For example, the EU provides options for its member states to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use. A member state may approve a specific price for the medicinal product or it may instead adopt a system of direct or indirect controls on the profitability of us placing the medicinal product on the market. Pharmaceutical products may face competition from lower-priced products in foreign countries that have placed price controls on pharmaceutical products and may also compete with imported foreign products. Furthermore, there is no assurance that a product will be considered medically reasonable and necessary for a specific indication, will be considered cost-effective by third-party payors, that an adequate level of reimbursement will be established even if coverage is available or that the third-party payors’ reimbursement policies will not adversely affect the ability for manufacturers to sell products profitably.

Healthcare Reform

A primary trend in the U.S. healthcare industry and elsewhere is cost containment. Government authorities and other third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medical products and services, implementing reductions in government healthcare programs and other healthcare funding and applying new payment methodologies. For example, in March 2010, the Affordable Care Act, or ACA, was enacted, which affected existing government healthcare programs and resulted in the development of new programs. Among the ACA’s provisions of importance to the pharmaceutical industry, in addition to those otherwise described above, are the following:

•

an annual, nondeductible fee on any entity that manufactures or imports certain specified branded prescription drugs and biologic agents apportioned among these entities according to their market share in some government healthcare programs;

•

an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program to 23.1% and 13% of the average manufacturer price for most branded and generic drugs, respectively, and a cap on the total rebate amount for innovator drugs at 100% of the Average Manufacturer Price, or AMP;

•

a new Medicare Part D coverage gap discount program, in which manufacturers must now agree to offer 70% point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturers’ outpatient drugs to be covered under Medicare Part D;

extension of manufacturers’ Medicaid rebate liability to covered drugs dispensed to individuals who are enrolled in Medicaid managed care organizations;

•

expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to additional individuals, including individuals with income at or below 133% of the federal poverty level, thereby potentially increasing manufacturers’ Medicaid rebate liability;

•

expansion of the entities eligible for discounts under the Public Health Service pharmaceutical pricing program; and

•

a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research.

Since its enactment, there have been judicial, executive and Congressional challenges to certain aspects of the ACA. On June 17, 2021, the U.S. Supreme Court dismissed the most recent judicial challenge to the ACA without specifically ruling on the constitutionality of the ACA. ~~Prior~~Other tolegislative ~~the~~changes ~~Supreme~~have ~~Court’s~~been ~~decision,~~proposed ~~President~~and ~~Biden~~adopted ~~issued~~in anthe ~~executive~~United ~~order~~States ~~initiating~~since athe ~~special~~ACA ~~enrollment~~was ~~period~~enacted. ~~from~~On ~~February~~March 1511, 2021, ~~through~~the ~~August~~American ~~15,~~Rescue ~~2021~~Plan ~~for~~Act ~~purposes~~ of ~~obtaining~~2021 ~~health~~was ~~insurance~~signed ~~coverage~~into ~~through~~law, ~~the~~which ~~ACA~~eliminated ~~marketplace.~~the ~~The~~statutory ~~executive~~cap ~~order~~on ~~also~~drug ~~instructed~~manufacturers’ ~~certain~~Medicaid ~~governmental~~drug ~~agencies~~rebate toliability, ~~review~~which ~~and~~began ~~reconsider~~in ~~their~~2024 ~~existing policies~~ and ~~rules~~was ~~that~~previously ~~limit~~set ~~access~~at to100% ~~healthcare. It is unclear how other healthcare reform measures~~ of ~~the~~a ~~Biden~~drug’s ~~administration,~~average ifmanufacturer ~~any, will impact our business~~price.

InThe ~~addition,~~cost ~~other~~of ~~legislative~~prescription ~~changes~~pharmaceuticals ~~have~~in ~~been proposed and adopted since~~ the ~~ACA~~United ~~was~~States ~~enacted.~~has ~~These~~also ~~changes~~been ~~included~~the ~~aggregate~~subject ~~reductions~~of toconsiderable ~~Medicare~~discussion. ~~payments~~There tohave ~~providers~~been ofseveral 2%Congressional ~~per fiscal year~~inquiries, ~~which~~as ~~went~~well ~~into~~as ~~effect~~legislative onand ~~April~~regulatory 1,initiatives ~~2013~~ and, ~~due~~executive toorders ~~subsequent~~designed ~~legislative amendments~~ to, ~~the~~among ~~statute~~other things, ~~will~~bring ~~remain~~more intransparency ~~effect~~to ~~through~~product ~~2030~~pricing, ~~with~~review the ~~exception~~relationship ofbetween apricing ~~temporary~~and ~~suspension~~manufacturer ~~from~~patient ~~May 1~~programs, ~~2020 through March 31, 2022~~ and areform 1%government ~~reduction~~program ~~from~~reimbursement ~~April~~methodologies 1,for ~~2022~~drug ~~through~~products. ~~June~~In ~~30,~~ 2022, ~~unless~~the ~~additional~~Inflation ~~Congressional~~Reduction ~~action~~Act(IRA) iswas ~~taken.~~signed Ininto ~~addition,~~law. onAmong ~~January~~other 2things, ~~2013,~~ the ~~American~~IRA ~~Taxpayer~~requires ~~Relief~~manufacturers ~~Act~~ of ~~2012~~certain ~~was~~drugs ~~signed~~to ~~into~~engage ~~law,~~in ~~which,~~price ~~among~~negotiations ~~other~~with ~~things~~Medicare, ~~reduced~~with ~~Medicare~~prices ~~payments~~that tocan ~~several~~be ~~providers,~~negotiated ~~including~~subject ~~hospitals,~~to ~~and~~a ~~increased~~cap; ~~the~~imposes ~~statute~~rebates ofunder ~~limitations~~Medicare ~~period~~Part ~~for~~B ~~the~~and ~~government~~Medicare Part D to ~~recover~~penalize ~~overpayments~~price toincreases ~~providers~~that ~~from~~outpace ~~three~~inflation to(first ~~five~~due ~~years.~~in ~~More~~2023); ~~recently,~~redesigns onthe ~~March~~Medicare ~~11,~~Part ~~2021,~~D ~~President~~benefit ~~Biden~~(beginning ~~signed~~in 2024); and replaces the ~~American~~Part ~~Rescue~~D ~~Plan~~coverage ~~Act~~gap ofdiscount ~~2021~~program ~~into~~with ~~law,~~a ~~which~~new ~~eliminates~~manufacturer ~~the~~discount ~~statutory~~program ~~Medicaid~~(beginning ~~drug~~in ~~rebate~~2025). ~~cap,~~CMS ~~currently~~has ~~set~~published atthe ~~100%~~negotiated ofprices afor ~~drug’s~~the ~~average~~initial ~~manufacturer~~ten ~~price~~drugs, ~~beginning~~which ~~January~~became 1effective in 2026, ~~2024.~~and the

The cost of prescription pharmaceuticals in the United States has also been the subject of considerable discussion. There have been several Congressional inquiries, as well as legislative and regulatory initiatives and executive orders designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug products. Members of Congress and the Biden Administration have indicated they will continue to pursue legislative or administrative measures to control prescription drug costs, although the likelihood of such measures being adopted remains uncertain. For example, the Build Back Better Act, if enacted, would introduce substantial drug pricing reforms, including the establishment of a drug price negotiation program within the U.S. Department of Health and Human Services that would require manufacturers to charge a negotiated “maximum fair price” for certain selected drugs or pay an excise tax for noncompliance, and the establishment of rebate payment requirements on manufacturers of certain drugs payable under Medicare Parts B and D. If the Build Back Better Act is not enacted, similar or other drug pricing proposals could appear in future legislation. 21

18subsequent 15 drugs, which will first be effective in 2027. CMS has also published the next set of 15 drugs that will be subject to negotiation, although the Medicare drug price negotiation program is currently subject to legal challenges. The IRA permits the Secretary of the Department of Health and Human Services (HHS) to implement many of these provisions through guidance, as opposed to regulation, for the initial years. HHS has and will continue to issue and update guidance as these programs are implemented. The impact of the IRA on us and the pharmaceutical industry cannot yet be fully determined, but is likely to be significant.

~~Individual~~The ~~states~~One inBig ~~the~~Beautiful ~~United~~Bill ~~States~~Act, ~~have~~which ~~also~~was ~~become~~enacted ~~increasingly~~in ~~active~~July in2025, ~~passing~~imposes ~~legislation~~significant ~~and~~reductions ~~implementing~~in ~~regulations~~the ~~designed~~funding toof ~~control~~the ~~pharmaceutical~~Medicaid ~~product~~program. ~~pricing,~~Such ~~including~~reductions ~~price~~are orexpected ~~patient~~to ~~reimbursement~~decrease ~~constraints,~~the ~~discounts,~~number ~~restrictions~~of onpersons ~~certain~~enrolled ~~product~~in ~~access~~Medicaid and ~~marketing~~reduce ~~cost~~the ~~disclosure~~services ~~and~~covered ~~transparency~~by ~~measures~~Medicaid, ~~and,~~which incould ~~some~~adversely ~~cases,~~affect ~~designed~~our tosales ~~encourage~~of ~~importation~~any ~~from~~product ~~other~~candidate ~~countries~~that ~~and~~we ~~bulk purchasing~~commercialize.

WeThe ~~anticipate~~Trump ~~that~~administration ~~these~~is ~~new~~also ~~laws~~pursuing ~~will~~a ~~result~~two-fold strategy to reduce drug costs in ~~additional~~the ~~downward~~U.S. ~~pressure~~While onit ~~coverage~~is unclear whether and how the ~~price~~Trump ~~that~~proposals wewill be implemented, the Trump policies are likely to have a negative impact on the pharmaceutical industry and on our ability to receive adequate revenues for any ~~approved~~ product, ~~and~~candidate ~~could~~for ~~seriously~~which ~~harm~~we ~~our~~obtain ~~business~~marketing approval. ~~Any~~On ~~reduction~~the inone ~~reimbursement~~hand, ~~from~~President ~~Medicare~~Trump ~~and~~has ~~other~~threatened ~~government~~to ~~programs~~impose ~~may~~significant ~~result~~tariffs on pharmaceutical manufacturers that do not adopt pricing policies such as most favored nation pricing, which would tie the price for drugs in athe ~~similar~~U.S. ~~reduction~~to the lowest price in ~~payments~~a ~~from~~group ~~private~~of ~~payors~~other countries. ~~The~~In ~~implementation~~response, ofmultiple ~~cost~~manufacturers ~~containment~~have ~~measures~~reportedly orentered into confidential pricing agreements with the federal government. On the other ~~healthcare~~hand, ~~reforms~~the ~~may~~Trump ~~prevent~~administration usis ~~from~~pursuing ~~being~~traditional ~~able~~regulatory pathways to ~~generate~~impose ~~revenue~~drug pricing policies, ~~attain~~and ~~profitability~~published two proposed regulations in December 2025, orreferred ~~commercialize~~to ~~our~~as ~~products~~Globe and Guard. If Infinalized, ~~addition~~these regulations would implement mandatory payment models under which manufacturers of eligible drugs would be required to pay rebates to the federal government on a portion of the units of their drugs that are reimbursed by Medicare, with the rebate amount based on most favored nation pricing. While the impact of the Globe and Guard proposed regulations, if finalized, cannot yet be determined, it is ~~possible~~likely ~~that~~to ~~there~~be ~~will~~significant. beEven ~~further~~regulatory ~~legislation~~proposals or ~~regulation~~executive actions that are ultimately deemed unlawful could ~~harm~~negatively impact the U.S. pharmaceutical sector and our business,. ~~financial~~In ~~condition~~addition, pharmaceutical pricing and ~~results~~marketing has long been the subject of ~~operations.~~considerable discussion in Congress and among policymakers, and it is possible that Congress could enact additional laws that negatively affect the pharmaceutical industry.

Individual states in the United States have also become increasingly active in passing legislation and implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access, marketing cost disclosure, drug price reporting and other transparency measures. Some states have enacted legislation creating so-called prescription drug affordability boards, with the goal of imposing price limits on certain drugs in these states, and at least one state board is imposing an upper payment limit. States are also seeking to implement general, across the board price caps for pharmaceuticals, or are seeking to regulate drug distribution. Some measures are designed to encourage importation from other countries.

We anticipate that these new laws will result in additional downward pressure on coverage and the price that we receive for any approved product and could seriously harm our business. Any reduction in reimbursement from Medicare and other government programs may result in a similar reduction in payments from private payors. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize our products. In addition, it is possible that there will be further legislation or regulation that could harm our business, financial condition, and results of operations.

Data Privacy and Security Laws

Numerous state, federal and foreign laws, regulations and standards govern the collection, use, access to, confidentiality and security of health-related and other personal information, and could apply now or in the future to our operations or the operations of our partners. In the U.S., numerous federal and state laws and regulations, including data breach notification laws, health information privacy and security laws and consumer protection laws and regulations govern the collection, use, disclosure, and protection of health-related and other personal information. In addition, certain foreign laws govern the privacy and security of personal data, including health-related data. In particular, the General Data Protection Regulation 2016/679 (“GDPR”) and implementing legislation in individual European countries impose specific compliance obligations relating to the processing and transfer of personal data of natural persons, including certain kinds of clinical trial data. Privacy and security laws, regulations, and other obligations are constantly evolving, may conflict with each other to complicate compliance efforts, and can result in investigations, proceedings, or actions that lead to significant civil and/or criminal penalties and restrictions on data processing.

Competition

~~Our~~We ~~industry~~compete iswith ~~highly~~pharmaceutical, ~~competitive~~biotechnology companies and ~~subject~~academic toresearch ~~rapid~~institutions ~~and~~developing ~~significant~~therapies ~~technological~~for ~~change~~rare genetic kidney and dermatologic diseases. ~~New~~To our knowledge, no FDA-approved or investigational therapies ~~and~~are ~~treatments~~specifically ~~based~~designed onto ~~innovative~~promote ~~discoveries~~ribosomal ~~emerge~~readthrough ~~frequently.~~of NMs in NMAS, nmADPKD, or RDEB.

~~Our~~There ~~potential~~are ~~competitors~~currently ~~are~~no ~~public~~FDA-approved ~~and~~therapies ~~private~~approved ~~companies,~~specifically ~~pharmaceutical~~for ~~companies~~the ~~and~~treatment ~~biotechnology~~of ~~companies~~AS. ~~who~~Disease ~~may~~management betypically ~~engaged~~consists inof ~~targeting~~ACEi ~~the~~and ~~same~~ARB ~~biological~~therapies ~~processes~~to ~~that~~reduce ~~our~~proteinuria ~~compounds~~and slow disease progression. Several investigational programs are ~~designed~~in toclinical ~~impact~~development, ~~and~~including ~~who~~sparsentan ~~may~~(Travere beTherapeutics), ~~developing~~an ~~products~~endothelin ~~for~~and ~~the~~angiotensin ~~same~~receptor ~~indications~~antagonist asin ~~our~~Phase ~~investigational~~3 ~~drug~~for ~~candidates.~~proteinuric ~~Potential~~glomerular ~~competitors~~diseases ~~could~~including ~~also~~AS; ~~include~~R3R01 ~~academic~~(River ~~institutions~~Renal), ~~government~~in ~~agencies,~~clinical ~~other~~development ~~public~~for AS and ~~private~~FSGS; ~~research~~BAY3401016 ~~organizations~~(Bayer), ~~and~~in ~~charitable~~a ~~venture~~clinical ~~philanthropic~~biomarker ~~organizations~~study ~~that~~in ~~conduct~~AS; ~~research~~BI 764198 (Boehringer Ingelheim), ~~seek~~in ~~patent~~clinical ~~protection~~development ~~and/or~~across ~~establish~~multiple ~~collaborative~~kidney ~~arrangements~~diseases ~~for~~including ~~research~~AS. These programs, ~~development~~however, ~~manufacturing~~target ~~and~~downstream ~~commercialization~~pathological processes such as fibrosis, inflammation, or proteinuria rather than the underlying genetic cause of the disease.

Many of our competitors have substantially greater financial resources, technical resources, expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. These competitors 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 a result, our competitors may commercialize products more rapidly or effectively than we do, which would affect our competitive position, the likelihood that our drug candidates, if approved, would achieve and maintain market acceptance and our ability to generate meaningful revenues from our products. nmADPKD

~~Our~~In ~~commercial~~ADPKD, ~~opportunities~~tolvaptan ~~could~~(Otsuka) beis ~~reduced~~approved orin ~~eliminated~~certain ifregions ~~our~~to ~~competitors~~slow ~~develop~~kidney function decline in patients at risk of rapid progression but does not address the underlying genetic cause and ~~commercialize~~carries ~~products~~significant ~~that~~tolerability limitations. Multiple additional programs are ~~safer~~in clinical development, ~~more~~including ~~effective~~AZD1613 (AstraZeneca), ~~have~~in ~~fewer~~Phase ~~side~~1 ~~effects~~for ADPKD; VX-407 (Vertex Pharmaceuticals), ~~are~~in ~~more~~Phase ~~convenient~~2a orfor ~~are~~ADPKD ~~more~~patients ~~affordable~~with ~~than~~a ~~any~~subset ~~products~~of ~~that~~PKD1 wegene ~~develop.~~variants; ~~The~~farabursen ~~key~~(Novartis, ~~competitive~~formerly ~~factors~~Regulus ~~affecting~~Therapeutics), ~~the~~a ~~success~~microRNA-targeting oftherapy ~~ELX~~in Phase 3 for ADPKD; and PYC-02003 (PYC Therapeutics), an RNA-based therapeutic in Phase 1; ABBVCLS-628, Calico (AbbVie) in Phase 2 clinical trials with fast track designation; GSK-4771261 (GSK) in Phase 1a/1b clinical trials; and ~~our~~XRx-008 ~~other~~(XORTX ~~product~~Therapeutics) ~~candidates~~in ~~are~~Phase ~~their~~2 ~~impact~~for onuric ~~the~~acid-lowering ~~targeted~~approach. ~~diseases~~Additionally, ~~superiority~~Maze ~~over~~Therapeutics ~~competing~~and ~~products,~~Vertex ~~long~~Pharmaceuticals are advancing programs for APOL1-~~term~~mediated ~~safety~~kidney disease, ~~convenience~~which represents a broader kidney disease population. These programs generally target pathways involved in cyst growth, ~~price~~fluid ~~and~~secretion, or gene expression rather than specifically addressing NMs. Our approach with exaluren is designed to target the ~~availability~~approximately 26% of ~~coverage~~ADPKD ~~and~~patients ~~reimbursement~~with ~~from~~NMs ~~government~~in ~~and~~PKD1 ~~other~~or ~~third-party~~PKD2 ~~payors~~through ribosomal readthrough to restore functional polycystin protein.

Several companies are involved in researching and developing molecules targeting suppression of nonsense mutations and enhancement of translational read-through. However, we believe that ELX-02 is the only drug candidate in clinical development designed to treat nonsense mutations in CFTR, the underlying cause of cystic fibrosis. Additional competition to ELX-02 may arise from other programs that do not target a specific CFTR mutation class but work via other mechanisms. RDEB

19In RDEB, approved therapies include beremagene geperpavec (Krystal Biotech), a topical gene therapy; prademagene zamikeracel (Abeona Therapeutics), an autologous cell-based gene therapy in which a patient's own skin cells are engineered to express functional COL7A1; Filsuvez (Chiesi) for dystrophic and junctional EB; FCX-007 (Castle Creek ) a gene therapy in Phase 3 development for DEB; Ebesanar (RHEACELL) a stem-cell therapy in Phase 3 development for RDEB; and CORDStrom (Inmune Bio) in Phase 3 development for RDEB. These therapies address the underlying genetic defect in treated tissue through localized or ex vivo genetic modification strategies. We are not aware of any FDA-approved oral small molecule therapies designed to promote ribosomal readthrough of NMs in RDEB or JEB. Our approach with ZKN-013 is designed as a systemic oral small molecule strategy for patients with NMs.

Some of our competitors have significantly greater financial resources than we do and an established presence in the market. Our competitors may have greater expertise in research and development, manufacturing, obtaining regulatory approvals and marketing approved products and may obtain regulatory approvals for their products more rapidly than we can, if at all. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. We also

compete with these companies in recruiting, hiring and retaining qualified scientific and management talent, establishing clinical trial sites and patient registration for clinical trials and obtaining manufacturing slots at contract manufacturing organizations.

If our product candidates do not offer advantages over available products, we may not be able to successfully compete against current and future competitors. The key factors affecting the success of our products, if approved, are likely to be their potential efficacy, safety, convenience and availability of reimbursement.

Employees and Human Capital Management

As of December 31, ~~2022~~2025, we had 15seven employees in the United States and three employees in Israel. We believe that we have a good relationship with our employees. In order to achieve our goals, it is crucial that we continue to attract and retain top talent. To facilitate talent attraction and retention, we strive to make our Company a safe and rewarding workplace, with opportunities for our employees to grow and develop in their careers, supported by strong compensation, benefits, and health and wellness programs.

We ~~strive~~benchmark toour ~~maintain~~compensation anpractices ~~inclusive~~and ~~environment~~benefits ~~free~~programs ~~from~~against ~~discrimination~~those of ~~any~~comparable ~~kind,~~industries ~~including~~and ~~sexual~~peer orcompanies. ~~other~~We ~~discriminatory~~believe ~~harassment.~~that ~~Our~~our compensation and employee benefits are competitive and allow us to attract and retain qualified employees ~~have~~throughout ~~multiple~~our ~~avenues~~organization. ~~available~~In ~~through~~addition ~~which~~to ~~inappropriate~~salaries, ~~behavior~~employee ~~can~~benefits beinclude ~~reported~~annual discretionary bonuses, ~~including~~equity awards, a ~~confidential~~401(k) ~~hotline~~plan for U.S. employees, healthcare and insurance benefits, health savings and flexible spending accounts, paid time off, family leave, and flexible work schedules, among others.

As of December 31, 2022, 44% of our employees were female and 56% were male. We are committed to creating and maintaining a diverse and inclusive workplace in which all employees have an opportunity to participate and contribute to the success of the business and are valued for their skills, experience, and unique perspectives. We seek and respect different perspectives, points of view, backgrounds, and communication styles.

We frequently benchmark our compensation practices and benefits programs against those of comparable industries and peer companies, and in the geographic areas where our facilities are located. We believe that our compensation and employee benefits are competitive and allow us to attract and retain qualified employees throughout our organization. In addition to salaries, employee benefits include annual discretionary bonuses, equity awards, a 401(k) plan for U.S. employees, healthcare and insurance benefits, health savings and flexible spending accounts, paid time off, family leave, and flexible work schedules, among others.

Other Matters

Corporate Information

We were incorporated under the laws of the State of Delaware. ~~Our~~Effective as of June 30, 2024, we became a remotely headquartered company and we do not maintain a principal executive ~~offices~~office. ~~are~~For ~~located~~purposes atof ~~480~~compliance ~~Arsenal~~with ~~Way~~applicable requirements of the Securities Act of 1933, ~~Watertown~~as amended (the “Securities Act”), and ~~Massachusetts~~the ~~02472~~Exchange Act, ~~and~~any stockholder communication required to be sent to our ~~phone~~principal ~~number~~executive isoffices ~~(781)~~may ~~577-5300~~be directed to P.O. ~~Our~~Box ~~common~~274, ~~stock~~10 isCourt ~~listed~~Street, onArlington, ~~the~~Massachusetts ~~Nasdaq~~02476, ~~Capital~~and ~~Market~~our ~~under~~phone ~~the~~number ~~symbol~~is ~~“ELOX~~(617) 515-6033.”

Information Available on the Internet

Our internet address is www.eloxxpharma.com. Our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, proxy statements and all amendments to those reports are available to you free of charge through the “Investors-Financials & Filings” section of our website as soon as reasonably practicable after those materials have been electronically filed with, or furnished to, the SEC. The information contained on, or that can be accessed through, our website is not incorporated by reference into, and is not a part of, this Annual Report. ~~In addition, the SEC maintains a website (www.sec.gov) that contains reports, proxy and information statements, and other information regarding issuers that file electronically.~~

20The SEC maintains a website (www.sec.gov) that contains reports, proxy and information statements, and other information regarding issuers that file electronically. Our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, proxy statements and all amendments to those reports are available to you free of charge on the SEC website as reasonably practicable after those materials have been electronically filed with, or furnished to, the SEC.

ITEM 1A. Risk Factors

~~Investing~~Risks inRelated our common stock involves a high degree of risk. You should carefully consider the risks and uncertainties described below, together with all of the other information in this Annual Report on Form 10-K, before you decide to ~~purchase~~Our ~~our~~Filing common stock. If any of the possible adverse events described below actually occurs, we may be unable to conduct our business as currently planned and our financial condition and operating results could be harmed. In addition, the trading price of our common stock could decline due to the occurrence of any of the events described below, and you may lose all or part of your investment. Additional risks that we currently do not know about, or that we currently believe immaterial, may also impair our business.History

We have been delinquent in our public filing obligations under the Securities Exchange Act of 1934, as amended (the “Exchange Act”), and there are no assurances that we will be successful in regaining compliance or, if regained, remaining current in our public filing obligations.

We were unable to file our Annual Reports on Form 10-K for the years ended December 31, 2023 and 2024 because we lacked sufficient financial resources. Since November 2023, when we made our last quarterly report filing on Form 10-Q for the quarter ended September 30, 2023, we have operated at reduced capacity and with limited personnel, including minimal staffing for our clinical, research and development and administrative and finance teams. Until August 2025, we had minimal access to capital and resources. Since August 2025, we have raised sufficient funds for us to conduct the audit of our consolidated financial statements for the years ended December 31, 2023, 2024 and 2025 and file this Annual Report, which we believe will allow us to regain compliance with our reporting obligations under the Exchange Act. The process of regaining and maintaining compliance with Exchange Act reporting requirements after being delinquent for a meaningful period of time is complex and costly, and there are limited examples of companies successfully completing such a process. There are no assurances that the Securities and Exchange Commission (the “SEC”) will agree with our approach toward regaining compliance with our Exchange Act reporting obligations or, if regained, that we will be able to continue to comply with such reporting obligations.

Our common stock is currently listed on the OTC Expert Market. The Nasdaq Stock Market LLC (“Nasdaq”) suspended trading in our common stock on the Nasdaq Capital Market as of October 16, 2023. Though we intend to seek an uplisting for our common stock to trade on the Nasdaq Capital Market, there are no assurances that we will be able to successfully uplist to the Nasdaq Capital Market or successfully maintain compliance with Nasdaq’s listing requirements.

On October 16, 2023, Nasdaq suspended trading in our common stock on the Nasdaq Capital Market because we were not compliant with Nasdaq Listing Rule 5550(b)(2), which requires a listed company to have at least $35 million in market value of listed securities. Following delisting, our common stock has been listed on the OTC Expert Market, which has limited our access to trading markets. In connection with regaining compliance with our Exchange Act filing obligations, we intend to seek an uplisting of our common stock to trade on the Nasdaq Capital Market, which will require us to meet the initial listing standards for the Nasdaq Capital Market. There are no assurances that we will be able to successfully satisfy the initial listing criteria or, if we are successful, to continue to meet the on-going listing requirements for the Nasdaq Capital Market. In particular, we may face heightened scrutiny from Nasdaq as a result of our history of being unable to meet Nasdaq’s listing requirements and having been a delinquent filer under the Exchange Act, which could delay an uplisting to the Nasdaq Capital Market or prevent us from achieving an uplisting. In addition, we may decide it is not in our stockholders’ best interests to uplist our common stock to the Nasdaq Capital Market once we are current with our SEC reporting requirements.

In addition, as a result of delisting from the Nasdaq Capital Market, we lost an active trading market for our common stock, and the trading market for our common stock on the OTC Expert Market is limited. We face significant material adverse consequences as a result of our common stock not being listed on a national securities exchange, including one or more of the following:

•

a limited availability of market quotations for our common stock;

•

significantly reduced liquidity and efficiency of the trading market for our common stock;

•

a decrease in the price of our common stock and greater volatility as a result of the loss of market efficiencies;

•

holders of our common stock may be unable to sell our common stock and buyers may be unable to purchase our common stock when they wish to do so;

•

we have lost the interest of institutional investors in our common stock;

•

a determination that our shares of common stock are considered a “penny stock,” which requires brokers trading in our common stock to adhere to more stringent rules and could possibly result in a reduced level of trading activity in the secondary trading market for our common stock;

•

limited amount or complete loss of media, news and analyst coverage; and

•

a decreased ability to issue additional securities or obtain additional financing in the future.

Further, the National Securities Markets Improvement Act of 1996, which is a federal statute, prevents or preempts the states from regulating the sale of certain securities, which are referred to as “covered securities.” Our shares of common stock have ceased to qualify as covered securities under such statute because they are no longer listed on a national securities exchange. Accordingly, we and our common stock are subject to state regulation in each state in which we offer our common stock. Whether or not our shares of common stock are covered securities, the states have the power to investigate companies if there is a suspicion of fraud, and, if there is a finding of fraudulent activity, then the states can regulate or bar the sale of covered securities in a particular case.

Moreover, since being delisted from the Nasdaq Capital Market, we are no longer subject to certain rules and regulations of Nasdaq. As a result, an investment in our common stock may be riskier than an investment in securities of a company that is listed on a national securities exchange due to the reduced protections such rules and regulations provide stockholders.

Our failure to timely file periodic reports with the SEC could limit our access to the public markets to raise debt or equity capital.

We have filed this Annual Report in an effort to become current in our filing obligations under the Exchange Act. If we are unable to become current in our filings with the SEC, we will not be able to register the offer and sale of our securities on a registration statement under the Securities Act of 1933, as amended (the “Securities Act”), and will not be able to make public offerings of our securities, which will limit our ability to raise capital. Further, assuming we become current in our filing obligations, we will not be eligible to register the offer and sale of our securities using a shelf registration statement on Form S-3 until we have timely filed all periodic reports required under the Exchange Act for one year. As a result, during this one-year period, our transaction costs could increase and the amount of time required to complete a transaction could increase, making it more difficult to execute any such transaction successfully. We will also not be able to uplist our shares of common stock on the Nasdaq Capital Market or on any national securities exchange until we are current in our SEC reporting requirements. A failure to list our common stock on a national securities exchange could further limit our ability to raise capital. Limitations on our ability to raise capital could adversely affect our business, financial condition and results of operations.

In addition, if we are unable to resolve the delinquency in our reporting obligations, we could be subject to an administrative hearing to revoke the registration of our securities under Section 12(g) of the Exchange Act. If the SEC brought an administrative action against us, it is likely that we would cease being a public company. In that event, our ability to raise capital would be severely affected and we may not be able to continue operations. As a result, holders of our securities might lose their entire investment in our Company.

Risks Related to Financial Position and Need for Additional Capital

Since our inception, we have incurred significant operating losses. Our net losses were $6.0 million, $3.1 million and $17.1 million for the years ended December 31, 2025, 2024 and 2023, respectively. As of December 31, 2025, we had an accumulated deficit of $300.6 million. To date, we have financed our operations primarily through the sale of equity, license and collaboration agreements, debt securities and, to a lesser extent, grants. We have devoted substantially all of our financial resources and efforts to research and development. We expect that it may be several years, if ever, before we receive regulatory approval and have a product candidate ready for commercialization. We expect to continue to incur significant expenses and operating losses for the foreseeable future due to, among other things, costs related to research, development of our product candidates, conducting preclinical studies and clinical trials, and our administrative organization. A successful transition to profitable operations is dependent upon achieving a level of revenue adequate to support our cost structure. Our net losses may fluctuate significantly from quarter to quarter and year to year. We anticipate that our expenses may increase if, and as, we:

•

advance exaluren and/or other product candidates further into clinical development;

•

experience delays in enrollment and completion of our clinical trials;

•

fund preclinical development of our research programs and advance candidates into clinical trials;

•

pursue regulatory authorization to conduct clinical trials of additional product candidates;

•

seek marketing approvals for our product candidates;

•

establish a sales, marketing and distribution infrastructure to commercialize any product candidates for which we obtain marketing approval;

•

maintain, expand and protect our intellectual property portfolio;

•

hire additional clinical, regulatory, management and scientific personnel;

•

add operational, financial and management information systems and personnel;

•

acquire or in-license other product candidates and technologies; and

•

operate as a public company including costs associated with regaining and maintaining Nasdaq compliance.

We may never achieve profitability, and unless and until we do, we will continue to need to raise additional cash to fund our operations. We believe that our cash and cash equivalents as of the date of this Annual Report are not sufficient to maintain our current and planned operations for at least the next twelve months following the filing of this Annual Report. We will need to raise additional capital to finance our operations, which cannot be assured. We have concluded that these conditions, in aggregate, raise substantial doubt about our ability to continue as a going concern through one year after the date these consolidated financial statements are issued. Our independent registered public accounting firm, in its report on our consolidated financial statements for the year ended December 31, 2025, has also expressed substantial doubt about our ability to continue as a going concern. The financial statements included elsewhere in this Annual Report have been prepared assuming we will continue as a going concern and do not include any adjustments that might result from the outcome of this uncertainty.

Management intends to fund future operations through private or public debt or equity financing transactions and may seek additional capital through arrangements with strategic partners or from other sources, including licensing arrangements. The availability of sufficient funding to alleviate the conditions that raise substantial doubt is not within management’s control and cannot be assessed as being probable of occurring. If we are unable to obtain adequate financing, we will evaluate alternatives which may include curtailing expenses contemplated by our current operating plan, and we may be required to delay, limit, reduce or terminate our product development efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves, which may have a material adverse effect on our operations and future prospects.

Prior to filing this Annual Report we did not file any quarterly or annual reports with the SEC since November 2023 as a result of a lack of funds. As described further below, in August 2025, we entered into a securities purchase agreement, as amended, for the offer and sale of up to $20 million of shares and/or pre-funded warrants. We have used the funds received so far to prepare the year-end consolidated financial statements for the years ended December 31, 2025, 2024, and 2023. A goal in this process is to regain compliance with our SEC filing obligations and uplist onto Nasdaq. We anticipate raising additional capital as part of this process.

We will need substantial additional funding. If we are unable to raise capital when needed, we would be forced to delay, reduce or eliminate our product development programs or commercialization efforts.

We expect our expenses to increase in connection with our ongoing activities, particularly as we continue the research and development of, continue and initiate clinical trials of, and seek marketing approval for exaluren, and as we become obligated to make milestone payments pursuant to our outstanding license agreements. We do not have adequate funds to conduct any of our planned clinical trials. This means that if we are unable to raise sufficient funds, we will not be able to conduct our planned Phase 2b clinical trial of exaluren in patients with Alport syndrome (“AS”) or our planned Phase 2 clinical trial of exaluren in patients with nmADPKD. If these trials are significantly delayed or we are unable to conduct them at all due to a lack of funds, our business will be materially adversely affected. We will also require substantial funds to continue research and development, including for any future clinical trials. In addition, if we obtain marketing approval for any of our current or future product candidates, we expect to incur significant commercialization expenses related to sales, marketing, manufacturing and distribution of the approved product. Our future capital requirements will depend on many factors, including:

•

the scope, progress, results and costs of drug discovery, clinical development, laboratory testing and clinical trials for exaluren and other product candidates;

•

the costs, timing and outcome of any regulatory review of exaluren and other product candidates;

•

the cost of any other product candidate programs we pursue;

•

the costs and timing of commercialization activities, including manufacturing, marketing, sales and distribution, and securing coverage and reimbursement for any product candidates that receive marketing approval;

•

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

•

our ability to establish and maintain collaborations on favorable terms, if at all; and

•

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

Identifying potential product candidates and conducting preclinical studies and clinical trials are time consuming, expensive and uncertain processes that take years to complete, and we may never generate the necessary data or results required to obtain marketing approval or achieve product sales for any of our current or future product candidates. In addition, our product candidates, if approved, may not achieve commercial success. Our commercial revenue, if any, will be derived from sales of products that we do not expect to be commercially available for several years, if at all.

Accordingly, despite our prior public equity offerings and debt financings, we will need substantial additional funding in connection with our continuing operations and to achieve our goals. However, our existing cash and cash equivalents are insufficient for these activities. If we are unable to raise capital when needed or on attractive terms, we would be forced to delay, reduce or eliminate our research and development programs, product portfolio expansion or future commercialization efforts. Adequate additional financing may not be available to us on acceptable terms, or at all. In addition, in the future, we may seek additional financing due to favorable market conditions or strategic considerations, even if we believe we have sufficient funds for our operating plans. If we are unable to obtain adequate financing, we will evaluate options, which may include reducing or deferring operating expenses, including by downsizing our workforce and curtailing certain development programs, which could have a material adverse effect on our operations and financial results.

Our recurring losses from operations raise substantial doubt regarding our ability to continue as a going concern.

For the year ended December 31, 2025, our net loss was $6.0 million and, as of December 31, 2025, we had an accumulated deficit of $300.6 million. We anticipate operating losses to continue for the foreseeable future due to, among other things, costs related to research and development of our product candidates, conducting preclinical studies and clinical trials, and our administrative organization. We will require substantial additional financing to fund our operations and to continue to execute our strategy, and we will pursue a range of options to secure additional capital. We believe that our cash and cash equivalents of $4.8 million as of December 31, 2025, along with the $5.0 million received by us in February 2026 and the $2.0 million received in March 2026 in the private placement of our pre-funded warrants, will not be sufficient to maintain our current and planned operations for at least the next twelve months from the date of the consolidated financial statements set forth in this Annual Report. The accompanying consolidated financial statements have been prepared assuming that we will continue as a going concern, which contemplates the realization of assets and settlement of liabilities in the normal course of business. However, based on our current working capital, anticipated operating expenses and net losses and the uncertainties surrounding our ability to raise additional capital as needed, as discussed below, we believe that these conditions, in aggregate, raise substantial doubt about our ability to continue as a going concern for one year after the date these consolidated financial statements were issued.

We are exploring various sources of funding such as equity and debt financings, as well as entering into new collaborations, strategic alliances and licensing arrangements. If we raise additional funds through strategic collaborations and alliances, which may include existing collaboration partners, we may have to relinquish valuable rights to our technologies or product candidates, or grant licenses on terms that are not favorable to us. To the extent that we raise additional capital through the sale of equity, the ownership interest of our existing stockholders will be diluted and other preferences may be necessary that adversely affect the rights of existing stockholders. If we are unable to raise sufficient capital through the transactions discussed above, we will not be able to execute our current operating plan, may need to curtail expenses, and may be required to delay, limit, reduce or terminate our product candidate development efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves. If the foregoing plans are unsuccessful and we are unable to continue as a going concern, you could lose all or part of your investment in our Company.

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

Until such time, if ever, as we can generate substantial product revenue, we expect to finance our cash needs through a combination of equity and debt financings, as well as entering into new collaborations, strategic alliances and licensing arrangements. We do not have any committed external source of funds. To the extent that we raise additional capital through the sale of equity, or convertible debt securities, an investor’s ownership interest will be diluted, and the terms of these securities may include liquidation or other preferences that may adversely affect an investor’s rights as a common stockholder. Debt 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, and may be secured by all or a portion of our assets. Any debt agreements we may enter into in the future may contain similar restrictions on funding. If we raise funds by entering into new collaborations, strategic alliances or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings or through collaborations, strategic alliances or licensing arrangements when needed, we may be required to delay, limit, reduce or terminate our product candidate development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

If in the future we incur indebtedness to fund our operations or strategic initiatives, any future indebtedness could have significant negative consequences, including requiring the dedication of a substantial portion of our expected cash flow to service such indebtedness, thereby reducing the amount of our expected cash flow available for other purposes, limiting our flexibility in planning for, or reacting to, changes in our business and the industry in which we compete, and placing us at a competitive disadvantage compared to our competitors that have less debt. If we incur additional indebtedness in the future and are unable to generate sufficient cash to meet our obligations, we may have to delay or curtail research and development programs.

We do not intend to pay dividends for the foreseeable future.

We have never declared or paid any dividends on our common stock and do not intend to pay any dividends in the foreseeable future. We anticipate that we will retain all of our future earnings for use in the operation of our business and for general corporate purposes. Any determination to pay dividends in the future will be at the discretion of our board of directors.

Risks Related to Drug Discovery, Development, Regulatory Approval and Commercialization

We are heavily dependent on the success of our lead product candidate, ~~ELX-02~~exaluren. If ~~ELX-02~~exaluren does not achieve positive results during development or suffers any material development delays, it may adversely impact the commercial viability of ~~ELX-02~~exaluren and our business.

We currently have no products approved for sale. We have invested substantial efforts and financial resources primarily in the research and development of ~~ELX-02~~exaluren, which is currently our ~~only~~primary product candidate in clinical development. WeExaluren ~~have~~has ~~increased~~been ~~investment~~evaluated in ~~our~~a ~~preclinical~~Phase ~~candidate~~2a ~~portfolio~~trial ~~but~~in ~~have~~AS ~~yet~~patients towith ~~advance~~nonsense ~~other molecules into clinical development. In September 2022~~mutations, and we ~~announced~~plan ~~topline~~to ~~results~~initiate ~~from~~a ~~our~~ Phase 22b ~~combination~~ clinical trial in the first half of ~~ELX-02~~2026 for ~~Class~~exaluren 1in CFNMAS patients ~~with~~and atanticipate ~~least~~topline ~~one~~data ~~nonsense~~from ~~mutation.~~the ~~The~~initial ~~combination~~16-week ~~trial of ELX~~placebo-02controlled ~~with~~part ~~ivacaftor~~of ~~did~~the ~~not~~study ~~achieve~~by ~~statistical~~mid- ~~significance~~2027 ~~for~~with ~~its~~the ~~efficacy~~final ~~endpoints~~readout ~~and~~by asthe aend ~~result~~of we2027. ~~have~~We ~~paused~~also ~~all~~plan ~~development~~to ofinitiate ~~ELX-02~~enrollment in ~~CF.~~a ~~ELX-02~~Phase is2 ~~now~~trial ~~being~~of ~~evaluated~~exaluren infor athe ~~Phase~~treatment 2of ~~trial~~nmADPKD in ~~Alport~~2027 ~~syndrome~~following ~~patients~~protocol ~~with~~finalization ~~nonsense~~and ~~mutations~~regulatory approval. ~~This~~We isanticipate ~~the~~topline ~~first~~data ~~known~~from ~~clinical~~this ~~study~~trial inby ~~Alport~~mid-2028. ~~syndrome~~There ~~and there~~ can be no assurances of its success.

We are heavily dependent on favorable efficacy results from this study in the near term for our continued development and funding for ofexaluren ~~ELX-02~~ and the Company. Our ability to achieve and sustain profitability depends on obtaining regulatory approvals for, and successfully commercializing ~~ELX-02~~exaluren and any future product candidates, either alone or with third parties. The success of ~~ELX-02~~exaluren and any other product candidates will depend on several factors, including the following:

•

our ability to continue our business operations and product candidate research and development, and adapt to any changes in the regulatory approval process, manufacturing supply or clinical trial requirements and timing;

•

successful completion of preclinical studies;

~~receipt of allowances to proceed under INDs and similar applications outside the United States for our planned clinical trials or future clinical trials;~~29

•

receipt of allowances to proceed under Investigational New Drugs (“INDs”) and similar applications outside the United States for our planned clinical trials or future clinical trials;

•

successful patient enrollment in and completion of clinical trials;

•

safety and efficacy data for our product candidates that are satisfactory to the U.S. Food and Drug Administration (“FDA”), European Medicines Agency (“EMA”), or any other comparable foreign regulatory authority for marketing approval;

•

receipt of marketing approvals for our product candidates from applicable regulatory authorities;

•

completion of any required post-marketing approval commitments to applicable regulatory authorities;

•

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

•

making arrangements with third-party manufacturers, or establishing manufacturing capabilities, for both clinical and commercial supplies of our product candidates, if any product candidates are approved;

•

establishing sales, marketing and distribution capabilities and launching commercial sales of our products, if and when approved, whether alone or in collaboration with others;

•

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

•

obtaining and maintaining third-party coverage and adequate reimbursement; and

•

maintaining a continued acceptable safety profile of our products following any approval.

Many of these factors are beyond our control, and it is possible that we may never obtain regulatory approval for ~~ELX-02~~exaluren or any other product candidates even if we expend substantial time and resources seeking their development and approval. If we do not achieve regulatory approval in a timely manner or at all, we could experience significant delays or an inability to commercialize our current or future product candidates, which would materially adversely affect our business.

The success of our business, including our ability to finance ~~our~~the Company and generate revenue from products in the future, which we do not expect will occur for several years, if ever, will depend heavily on the successful development and any eventual commercialization of the product candidates we develop. Our current product candidates, and any future product candidates we develop, will require additional preclinical and clinical development, management of clinical, preclinical and manufacturing activities, marketing approval in the United States and other markets, demonstrating cost-effectiveness to pricing and reimbursement authorities in certain markets, obtaining sufficient manufacturing supply for both clinical development and commercial production in accordance with current Good Manufacturing Practices (“cGMP”) or similar regulatory requirements outside the United States, building of a commercial organization, and substantial investment and significant marketing efforts before we generate any revenue from product sales. We may also experience delays in developing a sustainable, reproducible and scalable manufacturing process or transferring that process to commercial partners, which may prevent us from completing our clinical trials or commercializing our product candidates on a timely or profitable basis, if at all. Changes in the manufacturing process or facilities will require further comparability analysis and approval by the FDA or comparable foreign regulatory authorities before implementation, which could delay our clinical trials and product candidate development, and could require additional clinical trials, including bridging studies, to demonstrate consistent and continued safety and efficacy.

We have not previously submitted a new drug application (“NDA”), to the FDA or similar submissions to a comparable foreign regulatory authority, for any product candidate. An NDA or other relevant regulatory filing must include extensive preclinical and clinical data and supporting information to establish that the product candidate is safe and effective for each desired indication. The NDA or other relevant regulatory filing must also include significant information regarding the chemistry, manufacturing and controls for the product. We cannot be certain that our current or future product candidates will be successful in clinical trials or receive regulatory approval. Further, even if they are successful in clinical trials, our product candidates or any future product candidates may not receive regulatory approval. If we do not receive regulatory approvals for current or future product candidates, we may not be able to continue our operations. Even if we successfully obtain regulatory approval to market a product candidate, our revenue will depend, in part, upon the size of the markets in the territories for which we gain regulatory approval and have commercial rights for each product candidate, as well as the availability of competitive products, whether there is sufficient third-party reimbursement and adoption by physicians.

Before obtaining regulatory approval for the commercial distribution of our therapeutic product candidates, we or a collaborator must conduct extensive preclinical studies and clinical trials to demonstrate the safety and efficacy of our product candidates in humans to the satisfaction of the FDA, EMA and other applicable regulatory agencies in the jurisdictions in which we intend to market our product candidates. Clinical testing is expensive, time-consuming, and subject to uncertainty. Of the large number of drugs in development, only a small percentage successfully complete clinical testing and an even smaller portion obtain FDA or similar foreign regulatory authority approval and are commercialized. Accordingly, even if we are able to obtain the requisite financing to continue to fund our research, development and clinical programs, we cannot assure you that ~~ELX-02~~exaluren, ZKN-013, or any of our future product candidates will be successfully developed or commercialized.

The results of preclinical studies and early clinical trials of our product candidates may not be predictive of the results of later-stage clinical trials. Product candidates in later stages of clinical development may fail to show the desired safety and efficacy traits despite having progressed through preclinical studies and initial clinical trials. A number of companies in the biopharmaceutical industry have suffered significant setbacks in advanced clinical trials due to lack of efficacy or safety profiles, notwithstanding promising results in earlier trials. Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses. Accordingly, we, or any development partners, may ultimately be unable to provide regulatory agencies with satisfactory data on clinical safety and efficacy sufficient to obtain approval for any indication.

22Further, we may experience delays in clinical trials of our product candidates. We do not know whether ongoing clinical trials will be completed on schedule or at all, or whether planned clinical trials will begin on time, need to be redesigned, enroll patients on time or be completed on schedule, if at all. Moreover, issues may arise that could cause regulatory authorities to suspend or terminate such clinical trials. Clinical trials can be delayed for a variety of reasons, including delays related to:

•

trials due to lack of efficacy or safety profiles, notwithstanding promising results in earlier trials. Accordingly, we, or any development partners, may ultimately be unable to provide regulatory agencies with satisfactory data on clinical safety and efficacy sufficient to obtain approval for any indication.

Further, we may experience delays in clinical trials of our product candidates. We do not know whether ongoing clinical trials will be completed on schedule or at all, or whether planned clinical trials will begin on time, need to be redesigned, enroll patients on time or be completed on schedule, if at all. We also cannot be sure that submission of an Investigational New Drug (“IND”) or similar application will result in the FDA, or other regulatory authority allowing clinical trials to begin in a timely manner, if at all. Moreover, issues may arise that could cause regulatory authorities to suspend or terminate such clinical trials. Clinical trials can be delayed for a variety of reasons, including delays related to:

inability to generate sufficient preclinical, toxicology or other in vivo or in vitro data to support the initiation or continuation of clinical trials;

•

reaching a consensus with regulatory authorities on study design or implementation of the clinical trials;

•

failure or delay in obtaining regulatory authorization to commence a clinical trial;

•

reaching agreement on acceptable terms with prospective contract research organizations (“CROs”), and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical trial sites;

•

obtaining institutional review board (“IRB”), or ethics committee approval at each clinical trial site;

•

identifying, recruiting and training suitable clinical investigators;

•

manufacturing, testing, releasing, validating or importing/exporting sufficient stable quantities of our product candidates for use in clinical trials;

•

insufficient or inadequate supply or quality of product candidates or other materials necessary for use in clinical trials;

•

recruiting, screening and enrolling suitable patients to participate in a clinical trial;

•

having patients complete a clinical trial or return for post-treatment follow-up;

•

clinical trial sites deviating from trial protocol or dropping out of a clinical trial;

•

adding new clinical trial sites;

•

failure by our CROs, other third parties or us to adhere to clinical trial protocols;

•

failure to perform in accordance with the FDA’s good clinical practices (“GCPs”), or similar regulatory guidelines in other countries;

•

occurrence of adverse events associated with the product candidate that are viewed to outweigh its potential benefits, or occurrence of adverse events in clinical trials of the same class of agents conducted by other companies;

•

changes in regulatory requirements or guidance that require amending or submitting new clinical trial protocols;

•

changes to the standard of care on which a clinical development plan was based, which may require new or additional studies or clinical trials;

•

selection of clinical endpoints that require prolonged periods of observation or analyses of resulting data;

•

costs of clinical trials of our product candidates being greater than we anticipate;

•

clinical trials of our product candidates producing negative or inconclusive results, which may result in our deciding, or regulators requiring us, to conduct additional clinical trials or abandon development of such product candidates;

•

23transfer of manufacturing processes to larger-scale facilities operated by a contract manufacturing organization (“CMO”) and delays or failure by our CMOs or us to make any necessary changes to such manufacturing processes, or failure of our CMOs to produce clinical trial materials in accordance with current Good Manufacturing Practice, or cGMP, regulations or other applicable requirements; or

•

~~transfer~~third ofparties ~~manufacturing~~being ~~processes~~unwilling ~~to larger-scale facilities operated by a contract manufacturing organization (“CMO”) and delays~~ or ~~failure~~unable ~~by our CMOs or us~~ to ~~make~~satisfy ~~any~~their ~~necessary~~contractual ~~changes~~obligations to ~~such manufacturing processes;~~us.

~~third~~Any ~~parties~~such ~~being~~delays ~~unwilling~~ or ~~unable~~temporary topauses ~~satisfy~~in ~~their~~our ~~contractual~~clinical ~~obligations~~trial enrollment in response to ~~us;~~the factors above have and may in the future increase the likelihood that we encounter such difficulties or delays in initiating, enrolling, conducting or completing our planned and ongoing clinical trials. The design of our Phase 2b clinical trial of exaluren in patients with AS may not achieve efficacy results in patients, and there can be no assurance that the results of our clinical trials will support regulatory approval of exaluren for the treatment of AS or any other indication.

~~unforeseen~~Clinical trials must be conducted in accordance with the FDA and other applicable regulatory authorities’ legal requirements, regulations or guidelines, and are subject to oversight by these governmental agencies and ethics committees or IRBs at the medical institutions where the clinical trials are conducted. We could encounter delays if a clinical trial is suspended or terminated by us, by the data safety monitoring board for such clinical trial or by the FDA or any other regulatory authority, or if the IRBs or ethics committees of the institutions in which such trials are being conducted suspend or terminate the participation of their clinical investigators and sites subject to their review. Such authorities may suspend or terminate a clinical trial due to a number of factors, ~~beyond~~including failure to conduct the clinical trial in accordance with regulatory requirements or our ~~control~~clinical protocols, ~~including~~inspection ~~public~~of ~~health~~the ~~concerns~~clinical ~~such~~trial asoperations or trial site by the ~~COVID-19~~FDA ~~pandemic~~or other regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a product candidate, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial. In addition, changes in regulatory requirements and policies may occur, and we may need to amend clinical trial protocols to comply with these changes. Amendments may require us to resubmit our clinical trial protocols to regulators or to IRBs for reexamination, which may impact the costs, timing or successful completion of a clinical trial.

In addition, ~~disruptions~~significant ~~caused~~adverse byevents ~~the~~with ~~COVID-19~~respect ~~pandemic,~~to ~~including~~individuals ~~temporary~~who ~~pauses~~are not enrolled in any of our clinical ~~trial~~trials ~~enrollment~~but inwho ~~response~~receive toour ~~the~~product ~~COVID-19~~candidate ~~pandemic~~under ~~have~~our ~~and~~compassionate ~~may~~use inpolicy ~~the~~(typically ~~future~~under ~~increase~~a ~~the~~single-patient ~~likelihood~~IND ~~that~~administered weby ~~encounter~~the ~~such~~individual’s ~~difficulties~~treating orphysician) ~~delays~~may result in ~~initiating,~~a ~~enrolling,~~partial ~~conducting~~ or ~~completing~~full ~~our~~clinical ~~planned~~hold ~~and~~on our ongoing clinical trials. ~~The~~A ~~design~~clinical ofhold ~~our~~may ~~Phase~~result 2in ~~Alport~~the ~~syndrome~~inability ~~trial~~to ~~may~~enroll ~~not~~new ~~achieve~~patients ~~efficacy~~in ~~results~~our instudies ~~patients,~~until ~~and~~the wehold ~~cannot~~is ~~provide~~removed ~~assurances~~and asmay tomake ~~whether~~it wemore ~~will~~difficult ~~incur~~to ~~significant~~enroll ~~additional~~patients ~~costs~~thereafter. Additionally, ~~expend~~a ~~additional~~clinical ~~resources~~hold ormay bealso ~~subject~~result toin, ~~additional~~among ~~regulatory~~other ~~requirements~~things, ~~including~~protocol ~~COVID-19~~redesign, ~~related~~changes ~~disruptions~~in eligibility criteria and increased costs, any of which ~~may~~could ~~have~~adversely aaffect ~~material~~our ~~adverse~~projected ~~impact~~development ontimelines ~~our~~and ~~financial~~jeopardize ~~condition~~successful ~~and~~completion ~~results~~ of ~~operations~~our clinical programs.

~~Clinical trials must be conducted in accordance with the FDA and other applicable regulatory authorities’ legal requirements~~Further, ~~regulations~~conducting ~~or guidelines, and are subject to oversight by these governmental agencies and ethics committees or IRBs at the medical institutions where the~~ clinical trials ~~are~~in ~~conducted.~~foreign ~~We could encounter delays if a clinical trial is suspended or terminated by us~~countries, byas ~~the~~we ~~data~~do ~~safety monitoring board~~ for ~~such~~our ~~clinical~~product ~~trial or by the FDA or any other regulatory authority~~candidates, orpresents ifadditional ~~the~~risks ~~IRBs~~that ormay ~~ethics~~delay ~~committees~~completion of ~~the~~our ~~institutions~~clinical ~~in which such~~ trials. ~~are~~These ~~being~~risks ~~conducted~~include ~~suspend or terminate~~ the ~~participation~~failure of ~~their~~enrolled ~~clinical~~patients ~~investigators~~in ~~and~~foreign ~~sites~~countries ~~subject~~ to ~~their~~adhere ~~review.~~to ~~Such authorities may suspend or terminate a~~ clinical ~~trial~~protocol ~~due~~as to a ~~number~~result of ~~factors,~~differences ~~including failure to conduct the clinical trial~~ in ~~accordance~~healthcare ~~with~~services ~~regulatory requirements~~ or ~~our~~cultural ~~clinical protocols~~customs, ~~inspection~~managing ofadditional ~~the~~administrative ~~clinical~~burdens ~~trial~~associated ~~operations~~with orforeign ~~trial site by the FDA or other~~ regulatory ~~authorities resulting in the imposition of a clinical hold~~schemes, ~~unforeseen~~as ~~safety~~well ~~issues~~as orpolitical ~~adverse~~and ~~side~~economic ~~effects,~~risks ~~failure~~relevant to ~~demonstrate~~such aforeign ~~benefit from using a product candidate, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial~~countries.

InIf ~~addition,~~we ~~significant~~experience ~~adverse~~delays ~~events~~in ~~with~~the ~~respect~~completion toof ~~individuals~~any ~~who~~clinical ~~are~~trial ~~not enrolled in any~~ of our ~~clinical~~product ~~trials~~candidates, ~~but~~the ~~who~~commercial ~~receive~~prospects ~~our~~of ~~drug candidate under~~ our ~~compassionate~~product ~~use~~candidates ~~policy~~and ~~(typically~~the ~~under~~ability ato ~~single-patient~~generate ~~IND~~revenues ~~administered~~may bybe ~~the~~impaired. ~~individual’s~~In ~~treating~~addition, ~~physician)~~any ~~may~~delays ~~result~~ in acompleting ~~partial or full clinical hold on~~ our ~~ongoing~~ clinical trials. ~~A clinical hold~~ may ~~result~~increase inour ~~the~~costs, ~~inability~~slow todown ~~enroll new patients in~~ our ~~studies~~product ~~until~~development ~~the~~and ~~hold~~approval isprocess ~~removed~~ and may ~~make~~jeopardize itour ~~more~~ability ~~difficult~~ to ~~enroll~~commence ~~patients~~product ~~thereafter.~~sales ~~Additionally, a clinical hold may also result in, among other things, protocol redesign, changes in eligibility criteria~~ and ~~increased~~generate ~~costs,~~revenues. ~~any~~Any of ~~which~~these ~~could~~occurrences ~~adversely~~may ~~affect~~have ~~our~~an ~~projected development timelines and jeopardize successful completion of our clinical programs.~~

Further, conducting clinical trials in foreign countries, as we may do for our product candidates, presents additional risks that may delay completion of our clinical trials. These risks include the failure of enrolled patients in foreign countries to adhere to clinical protocol as a result of differences in healthcare services or cultural customs, managing additional administrative burdens associated with foreign regulatory schemes, as well as political and economic risks relevant to such foreign countries.32

If we experience delays in the completion of any clinical trial of our product candidates, the commercial prospects of our product candidates and the ability to generate revenues may be impaired. In addition, any delays in completing our clinical trials may increase our costs, slow down our product development and approval process and may jeopardize our ability to commence product sales and generate revenues. Any of these occurrences may have an adverse impact on our business, financial condition and prospects. Further, the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of our product candidates.

In addition, ~~the~~many ~~FDA’s~~of ~~and~~the ~~other~~factors ~~regulatory~~that ~~authorities’~~cause, ~~policies~~or ~~with~~lead ~~respect~~ to, ~~clinical~~the ~~trials~~termination, ~~may~~suspension ~~change~~of, ~~and~~or ~~additional~~a ~~government~~delay ~~regulations~~in ~~may~~the becommencement ~~enacted.~~or ~~For~~completion ~~instance~~of, ~~the regulatory landscape related to~~ clinical trials inmay ~~the~~also ~~European~~ultimately ~~Union~~lead ~~(“EU”)~~to ~~recently~~the ~~evolved.~~denial ~~The~~of EUregulatory ~~Clinical~~approval ~~Trials~~of ~~Regulation~~a ~~(“CTR”)~~product ~~which~~candidate. ~~was~~Any ~~adopted~~resulting indelays ~~April~~to ~~2014~~our ~~and~~clinical ~~repeals~~trials ~~the~~could EUshorten ~~Clinical~~any ~~Trials~~period ~~Directive,~~during ~~became~~which ~~applicable~~we onmay ~~January~~have ~~31,~~the ~~2022.~~exclusive ~~While~~right ~~the~~to ~~Clinical~~commercialize ~~Trials~~our ~~Directive~~product ~~required~~candidates. aIn ~~separate~~such ~~clinical~~cases, ~~trial~~our ~~application~~competitors ~~(“CTA”)~~may to be ~~submitted~~able into ~~each~~bring ~~member~~products ~~state,~~ to ~~both~~market ~~the~~before ~~competent~~we ~~national health authority and an independent ethics committee~~do, ~~the CTR introduces a centralized process~~ and ~~only requires~~ the ~~submission~~commercial viability of aour ~~single~~product ~~application~~candidates tocould ~~all~~be ~~member~~significantly ~~states concerned~~reduced. ~~The~~Any ~~CTR~~of ~~allows~~these ~~sponsors~~occurrences tomay ~~make~~harm aour ~~single~~business, ~~submission~~financial tocondition ~~both the competent authority~~ and ~~an ethics committee in each~~ prospects.

24In addition, the FDA’s and other regulatory authorities’ policies with respect to clinical trials may change and additional government regulations may be enacted. For instance, the regulatory landscape related to clinical trials in the European Union (“EU”) recently evolved. 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. While the EU Clinical Trials Directive required a separate clinical trial application (“CTA”) to be submitted in each member state in which the clinical trial takes place, to both the competent national health authority and an independent ethics committee, the CTR introduces a centralized process and only requires the submission of a single application for multi-center trials. The CTR allows sponsors to make a single submission to both the competent authority and an ethics committee in each member state, leading to a single decision per member state. The assessment procedure of the CTA has been harmonized as well, including a joint assessment by all member states concerned, and a separate assessment by each member state with respect to specific requirements related to its own territory, including ethics rules. Each member state’s decision is communicated to the sponsor via the centralized EU portal. Once the CTA is approved, clinical study development may proceed. The CTR transition period ended on January 31, 2025, and all clinical trials (and related applications) are now fully subject to the provisions of the CTR. Compliance with the CTR requirements by us and our third-party service providers, such as CROs, may impact our developments plans.

member state, leading to a single decision per member state. The assessment procedure of the CTA has been harmonized as well, including a joint assessment by all member states concerned, and a separate assessment by each member state with respect to specific requirements related to its own territory, including ethics rules. Each member state’s decision is communicated to the sponsor via the centralized EU portal. Once the CTA is approved, clinical study development may proceed. The CTR foresees a three-year transition period. The extent to which ongoing and new clinical trials will be governed by the CTR varies. For clinical trials whose CTA was made under the Clinical Trials Directive before January 31, 2022, the Clinical Trials Directive will continue to apply on a transitional basis for three years. Additionally, sponsors may still choose to submit a CTA under either the Clinical Trials Directive or the CTR until January 31, 2023 and, if authorized, those will be governed by the Clinical Trials Directive until January 31, 2025. By that date, all ongoing trials will become subject to the provisions of the CTR. Compliance with the CTR requirements by us and our third-party service providers, such as clinical research organizations (“CROs”), may impact our developments plans.

If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies governing clinical trials, our development plans may also be impacted.

Healthcare providers, healthcare facilities and institutions, physicians, and third-party payors in the United States and elsewhere will play a primary role in the recommendation and prescription of any product candidates for which we obtain marketing approval. Our current and future arrangements with our collaborators, healthcare professionals, healthcare facilities and institutions, principal investigators, consultants, customers, and third-party payors may expose us to broadly applicable fraud and abuse and other healthcare laws, including, without limitation, the federal Anti-Kickback Statute and the federal False Claims Act, that may constrain the business or financial arrangements and relationships through which we research, sell, market, and distribute any product candidates for which we obtain marketing approval. In addition, we may be subject to transparency laws and regulation with respect to drug pricing payments and other transfers of value made to physicians and other health care professionals by the federal government and by the states and foreign jurisdictions in which we conduct our business. The applicable federal, state, and foreign healthcare laws that affect our ability to operate include, but are not limited to, the following:

•

The U.S. federal Anti-Kickback Statute, which prohibits, among other things, persons or entities from knowingly and willfully soliciting, offering, receiving, or providing any remuneration (including any kickback, bribe, or certain rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, lease, order or recommendation of, any good, facility, item or service, for which payment may be made, in whole or in part, under any U.S. federal healthcare program, such as Medicare and Medicaid. The term “remuneration” has been broadly interpreted to include anything of value~~, including stock options~~. In addition, 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. The federal Anti-Kickback Statute has also been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers and formulary managers on the other hand. There are a number of statutory exceptions and regulatory safe harbors protecting some common activities from prosecution, but the exceptions and safe harbors are drawn narrowly and require strict compliance in order to offer protection. Any arrangements with prescribers must be for bona fide services and compensated at fair market value.;

The U.S. federal civil and criminal false claims laws, including without limitation, the civil False Claims Act, which can be enforced by private citizens on behalf of the U.S. federal government through civil whistleblower or qui tam actions, and the federal civil monetary penalties law which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, to the U.S. federal government, claims for payment or approval that are false or fraudulent, knowingly making, using, or causing to be made or used, a false record or statement material to a false or fraudulent claim, or from knowingly making a false statement to avoid, decrease, or conceal an obligation to pay money to the U.S. federal government. Pharmaceutical manufacturers can cause false claims to be presented to the U.S. federal government by, among other things, engaging in impermissible marketing practices, such as the off-label promotion of a product for an indication for 33

•

25The U.S. federal civil and criminal false claims laws, including without limitation, the civil False Claims Act, which can be enforced by private citizens on behalf of the U.S. federal government through civil whistleblower or qui tam actions, and the federal civil monetary penalties law which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, to the U.S. federal government, claims for payment or approval that are false or fraudulent, knowingly making, using, or causing to be made or used, a false record or statement material to a false or fraudulent claim, or from knowingly making a false statement to avoid, decrease, or conceal an obligation to pay money to the U.S. federal government. Further, pharmaceutical manufacturers can be held liable under the civil False Claims Act even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. Pharmaceutical manufacturers can cause false claims to be presented to the U.S. federal government by, among other things, engaging in impermissible marketing practices, such as the off-label promotion of a product for an indication for which it has not received FDA approval. In addition, the government may assert that a claim including items and services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act;

•

~~which~~The itU.S. ~~has~~federal ~~not~~Health ~~received~~Insurance ~~FDA~~Portability ~~approval.~~and ~~Further,~~Accountability ~~pharmaceutical~~Act ~~manufacturers~~of ~~can~~1996 be(“HIPAA”), ~~held~~which ~~liable~~imposes ~~under~~criminal ~~the~~and civil ~~False~~liability ~~Claims~~for, ~~Act~~among ~~even~~other ~~when~~things, ~~they~~knowingly doand ~~not~~willfully ~~submit~~executing, ~~claims~~or ~~directly~~attempting to ~~government~~execute, ~~payors~~a ifscheme ~~they~~to ~~are~~defraud ~~deemed~~any tohealthcare ~~“cause”~~benefit ~~the~~program, ~~submission~~or ofknowingly ~~false~~and willfully falsifying, concealing, or ~~fraudulent~~covering ~~claims.~~up Ina ~~addition~~material fact or making any materially false statement, in connection with the ~~government~~delivery ~~may~~of, ~~assert~~or ~~that~~payment afor, ~~claim~~healthcare ~~including~~benefits, items, ~~and~~or services. ~~resulting~~Similar ~~from~~to ~~a violation of~~ the federal Anti-Kickback Statute, ~~constitutes~~ a ~~false~~person or ~~fraudulent~~entity ~~claim~~does ~~for~~not ~~purposes~~need to have actual knowledge of the ~~civil~~statute ~~False~~or ~~Claims~~specific ~~Act.~~intent to violate it in order to have committed a violation;

•

The U.S. ~~federal~~Physician ~~Health~~Payments ~~Insurance~~Sunshine ~~Portability~~Act and ~~Accountability~~its ~~Act~~implementing ~~of 1996 (“HIPAA”)~~regulations, which ~~imposes~~requires ~~criminal~~certain ~~and~~manufacturers ~~civil~~of ~~liability for~~drugs, ~~among other things~~devices, ~~knowingly~~biologics and ~~willfully~~medical ~~executing,~~supplies orthat ~~attempting~~are toreimbursable ~~execute~~under Medicare, aMedicaid, ~~scheme~~or tothe ~~defraud~~Children’s ~~any~~Health ~~healthcare~~Insurance ~~benefit~~Program, ~~program~~with specific exceptions, orto ~~knowingly~~report ~~and~~annually ~~willfully~~to ~~falsifying,~~Centers ~~concealing,~~for orMedicare ~~covering~~& upMedicaid aServices ~~material~~(“CMS”) ~~fact~~information orrelated ~~making~~to ~~any~~certain ~~materially~~payments ~~false~~and ~~statement,~~other intransfers ~~connection~~of ~~with~~value ~~the~~to ~~delivery~~physicians ~~of,~~(as ordefined ~~payment~~by ~~for~~statute), ~~healthcare~~certain ~~benefits,~~non-physician ~~items,~~practitioners or(including ~~services.~~physician ~~Similar~~assistants, tonurse ~~the~~practitioners, ~~federal~~clinical ~~Anti-Kickback~~nurse ~~Statute~~specialists, acertified ~~person~~nurse oranesthetists, ~~entity~~anesthesiology ~~does~~assistants, ~~not~~and ~~need~~certified tonurse ~~have~~midwives) ~~actual~~and ~~knowledge~~teaching ofhospitals, ~~the~~as ~~statute~~well oras ~~specific~~ownership ~~intent~~and toinvestment ~~violate~~interests itheld inby ~~order~~physicians toand ~~have~~their ~~committed~~immediate afamily ~~violation.~~members;

•

~~The~~Federal ~~U.S.~~laws ~~Physician Payments Sunshine Act and its implementing regulations, which requires certain manufacturers of drugs, devices, biologics and medical supplies~~ that ~~are~~require ~~reimbursable~~pharmaceutical ~~under~~manufactures ~~Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions,~~ to ~~report~~submit ~~annually~~regular toreports ~~CMS~~on ~~information~~drug ~~related~~pricing ~~to certain payments~~ and ~~other~~price ~~transfers~~calculation of value to physicians (as defined by statute), certain non-physician practitioners (including physician assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, anesthesiology assistants, and certified nurse midwives) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family membersmethodologies; and

•

Analogous U.S. state and foreign laws and regulations, including: state anti-kickback and false claims laws, which may apply to our business practices, including but not limited to, research, distribution, sales and marketing arrangements, and claims involving healthcare items or services reimbursed by any third-party payor, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the U.S. federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws and regulations that require drug manufacturers to file reports relating to pricing and marketing information, which requires tracking gifts and other remuneration and items of value provided to healthcare professionals and entities; and state and local laws requiring the registration of pharmaceutical sales representatives, and similar healthcare laws and regulations in foreign jurisdictions, including reporting requirements detailing interactions with and payments to healthcare providers.

Ensuring that our internal operations and future business arrangements with third parties comply with applicable healthcare laws and regulations will involve substantial costs. It is not always possible to identify and deter employee misconduct or business noncompliance, and the precautions we take to detect and prevent inappropriate conduct may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to comply with such laws or regulations.

If our operations are found to be in violation of any of the laws described above or any other governmental laws and regulations that may apply to us, we may be subject to significant penalties, including civil, criminal, and administrative penalties, damages, fines, exclusion from government-funded healthcare programs, such as Medicare and Medicaid, or similar programs in other countries or jurisdictions, integrity oversight and reporting obligations to resolve allegations of noncompliance, disgorgement, imprisonment, contractual damages, reputational harm, diminished profits, and the curtailment or restructuring of our operations. Further, defending against any such actions can be costly, time-consuming and may require significant personnel resources. Therefore, even if we are successful in defending against any such actions that may be brought against us, our business may be impaired.

Our product candidates, including ELX-02 and ZKN-013 may cause adverse events or have other properties that could delay or prevent their regulatory approval or limit the scope of any approved label or market acceptance.34

~~Undesirable~~actions ~~side~~can ~~effects~~be ~~caused by our product candidates~~costly, ~~such as ELX~~time-02consuming and ~~ZKN-013,~~may ~~could~~require ~~cause~~significant uspersonnel orresources. ~~regulatory authorities to interrupt~~Therefore, ~~delay~~even orif ~~halt~~we ~~clinical~~are ~~trials~~successful ~~and could result~~ in ~~the~~defending ~~denial~~against ofany ~~regulatory~~such ~~approval~~actions bythat ~~the~~may ~~FDA~~be orbrought ~~other~~against ~~comparable foreign regulatory authorities. During the conduct of clinical trials~~us, ~~patients~~our ~~report~~business ~~changes~~may inbe ~~their health, including illnesses, injuries, and discomforts, to their study doctor~~impaired. ~~Often, it is not possible to determine whether or not the product candidate being studied caused these conditions. It is possible that as we test~~

26Our lead product candidate, including exaluren, may cause adverse events or have other properties that could delay or prevent their regulatory approval or limit the scope of any approved label or market acceptance.

Undesirable side effects caused by our lead product candidate, exaluren, or any additional product candidates, could cause us or regulatory authorities to interrupt, delay or halt clinical trials and could result in the denial of regulatory approval by the FDA or other comparable foreign regulatory authorities. During the conduct of clinical trials, patients report changes in their health, including illnesses, injuries, and discomforts, to their study doctor. Often, it is not possible to determine whether or not the product candidate being studied caused these conditions. It is possible that as we test our product candidates in larger, longer and more extensive clinical trials, or as use of these product candidates becomes more widespread if they receive regulatory approval, illnesses, injuries, discomforts and other adverse events that were observed in previous trials, as well as conditions that did not occur or went undetected in previous trials, will be reported by patients. Many times, side effects are only detectable after investigational products are tested in large-scale clinical trials or, in some cases, after they are made available to patients on a commercial scale following approval.

It is possible that, during the course of the clinical development of ~~ELX-02,~~exaluren ~~ZKN-013,~~ or ~~other~~any additional product candidates, results of our clinical trials (or significant adverse events experienced by individuals receiving drug under our compassionate use policy) could reveal an unacceptable severity and prevalence of side effects. For example, inexaluren ~~preclinical~~is ~~testing~~a ofeukaryotic ~~ELX~~ribosome-02selective glycoside, wea ~~observed~~non-antibiotic ~~renal~~and ~~toxicities~~human inribosome-selective analogue of aminoglycoside antibiotics. While exaluren has been designed for selectivity toward the ~~animals~~eukaryotic weribosome ~~tested~~and ~~following~~has ~~administration~~demonstrated ofa ~~this~~significantly ~~compound~~differentiated profile from aminoglycoside antibiotics, certain aminoglycosides are associated with nephrotoxicity and ototoxicity. In preclinical studies, renal toxicities were observed in animals at doses in excess of ~~the~~expected clinical doses. weAlthough ~~expect~~clinical studies to ~~administer~~date have not identified nephrotoxicity or ototoxicity in ~~our~~treated ~~clinical~~subjects, ~~trials~~there can be no assurance that such effects will not be observed in future studies or in larger patient populations. As a result of ~~this~~these or any other side effects, our clinical trials could be suspended or terminated or not even allowed to commence, and the FDA or comparable foreign regulatory authorities could order us to cease further development, or deny approval, of our product candidates for any or all targeted indications. The drug-related side effects could affect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims. Even if the side effects do not preclude the product candidate from obtaining or maintaining regulatory approval, undesirable side effects may inhibit market acceptance due to tolerability concerns as compared to other available therapies. If we are required to delay, suspend or terminate any clinical trial or commercialization efforts, the commercial prospects of such product candidates may be harmed, and our ability to generate product revenues from them or other product candidates that we develop may be delayed or eliminated.

Additionally, if one or more of our product candidates receive marketing approval, and we or others later identify undesirable side effects caused by such products, a number of potentially significant negative consequences could result. For example, ~~including~~the FDA could require us to adopt a Risk Evaluation and Mitigation Strategy (“REMS”), to ensure that the benefits of treatment with such product candidate outweigh the risks for each potential patient, which may include, among other things, a communication plan to health care practitioners, patient education, extensive patient monitoring or distribution systems and processes that are highly controlled, restrictive and more costly than what is typical for the industry. We or our collaborators may also be required to adopt a REMS or engage in similar actions, such as patient education, certification of health care professionals or specific monitoring, if we or others later identify undesirable side effects caused by any product that we develop alone. Other potentially significant negative consequences associated with adverse events include:

•

regulatory authorities may withdraw approvals of such product or impose restrictions on its distribution in the form of a new or modified risk evaluation and mitigation strategy;

•

regulatory authorities may require additional labeling, such as additional warnings or contraindications, which may negatively impact sales;

•

regulatory authorities may issue safety alerts, letters to healthcare providers, press releases or other communications containing warnings or other safety information about the product;

•

we may be required to change the way the product is administered or to conduct additional clinical studies;

•

we may be ~~required~~subject to ~~create~~fines, ainjunctions ~~risk~~or ~~evaluation and mitigation strategy (“REMS”) which could include a medication guide outlining~~ the ~~risks~~imposition of ~~such~~criminal ~~side effects for distribution to patients~~penalties;

~~we may be subject to fines, injunctions o the imposition of criminal penalties;~~35

•

we could be sued and held liable for harm caused to patients; and

•

a product may become less competitive, and our reputation may suffer.

Any of these events could prevent us from achieving or maintaining market acceptance of the particular product candidate, if approved, and could significantly harm our business, results of operations and prospects.

Regulatory authorities in some jurisdictions, including the United States ~~(“U.S.”)~~and the EU, may designate drugs for relatively small patient populations as “orphan drugs” in the ~~U.S.~~United States and “orphan medicinal products” in the EU. Under the Orphan Drug Act, the FDA may designate a 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 than 200,000 individuals in the ~~U.S.~~United States, or a patient population greater than 200,000 in the United States where there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the United States. Orphan drug designation must be requested before submitting an NDA.

27In April 2024, the FDA granted Orphan Drug Designation to exaluren for the treatment of AS. The FDA has previously granted orphan drug designation for exaluren for the treatment of cystic fibrosis, MPS I, Rett syndrome, AS, and cystinosis. We may seek orphan drug designation for exaluren in other diseases and conditions or for our other product candidates, and other indications. In the United States, orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and application fee waivers. After the FDA grants orphan drug designation, the generic identity of the drug and its potential orphan use are disclosed publicly by the FDA.

~~Similarly,~~In ~~in the EU~~addition, if a ~~medicinal~~drug ~~product~~with ~~may~~an ~~receive~~ orphan drug designation. ~~This~~subsequently ~~applies~~receives tothe ~~products~~first ~~that~~FDA ~~are~~marketing ~~intended~~approval for the ~~diagnosis,~~indication ~~prevention~~for orwhich ~~treatment~~it ofhas asuch ~~life-threatening or chronically debilitating condition and either the condition affects no more than five in 10~~designation,~~000~~ ~~persons in~~ the EUdrug ~~when the application~~ is ~~made,~~entitled orto ~~the~~a ~~product,~~period ~~without~~of ~~the~~marketing ~~benefits derived from orphan status~~exclusivity, ~~would~~which ~~unlikely~~precludes ~~generate sufficient return in~~ the EUFDA tofrom ~~justify~~approving ~~the~~another ~~necessary~~marketing ~~investment. Moreover~~application, inincluding ~~order~~an toNDA, ~~obtain~~for ~~orphan designation in~~ the ~~EU,~~same itdrug isfor ~~necessary~~the tosame approved ~~demonstrate~~use ~~that~~or ~~there~~indication ~~exists~~for noseven ~~satisfactory method of diagnosis~~years, ~~prevention~~except ~~or treatment of the condition authorized for marketing~~ in ~~the~~limited EUcircumstances, ~~or if~~ such as a ~~method~~showing ~~exists, that the product will be~~ of ~~significant~~clinical ~~benefit~~superiority to ~~those affected by~~ the ~~condition.~~product ~~The~~with ~~applicable~~orphan drug exclusivity ~~period~~within ~~is ten years in~~ the ~~EU.~~relevant ~~The~~approved ~~European~~use ~~exclusivity~~or ~~period can be reduced to six years~~indication, ~~if,~~or atwhere the ~~end~~manufacturer ofis ~~the~~unable ~~fifth~~to ~~year~~assure asufficient ~~drug~~product noquantity ~~longer~~to ~~meets~~meet the ~~criteria~~needs ~~for~~relating ~~orphan~~to ~~drug designation or if~~ the ~~drug~~relevant isapproved ~~sufficiently~~indication ~~profitable~~or ~~so that market exclusivity is no longer justified~~use.

~~The~~Even ~~FDA~~if ~~has~~we ~~granted~~obtain orphan drug ~~designation~~exclusivity for ~~ELX-02~~a ~~for~~product ~~the~~candidate, ~~treatment~~we ofmay ~~cystic~~not ~~fibrosis,~~be ~~MPS~~able I,to ~~Rett~~obtain ~~syndrome,~~or ~~and~~maintain ~~cystinosis~~orphan drug exclusivity for that product candidate. WeFurther, ~~may~~even ~~seek~~if we obtain orphan drug ~~designation~~exclusivity for ~~our~~a ~~other~~product, that exclusivity may not effectively protect the product ~~candidates,~~from ~~and~~competition because different drugs with ~~respect~~different toactive ~~Alport~~ingredients ~~syndrome~~may ~~and~~be ~~other~~approved ~~indications.~~for Inthe same approved use or indication within the ~~United~~applicable ~~States,~~rare disease or condition. Even after an orphan drug ~~designation~~is ~~entitles~~approved, athe ~~party~~FDA tocan ~~financial~~subsequently ~~incentives~~approve ~~such~~the assame ~~opportunities~~drug for ~~grant~~the ~~funding~~same ~~towards~~approved ~~clinical~~use ~~trial~~or ~~costs,~~indication ~~tax~~within ~~advantages~~the ~~and~~applicable ~~application~~rare ~~fee~~disease ~~waivers.~~or ~~After~~condition if the FDA ~~grants~~concludes ~~orphan~~that the later drug ~~designation~~is clinically superior in that it is shown to be safer, ~~the~~more ~~generic~~effective ~~identity~~or makes a major contribution to patient care, or the manufacturer of the product with orphan exclusivity is unable to maintain sufficient product quantity. Orphan drug ~~and~~designation ~~its~~neither ~~potential~~shortens ~~orphan~~the ~~use~~development ~~are~~or ~~disclosed~~regulatory ~~publicly~~review bytime of a drug nor gives the ~~FDA~~drug any advantage in the regulatory review or approval process.

~~In addition~~Similarly, ifin the EU, a ~~drug~~medicinal ~~with~~product anmay receive orphan ~~drug~~designation. Orphan designation ~~subsequently~~is ~~receives~~granted by the ~~first~~European ~~FDA~~Commission ~~marketing~~based ~~approval~~on ~~for~~a scientific opinion of the ~~indication~~EMA’s Committee for ~~which~~Orphan itMedicinal ~~has~~Products. ~~such~~A ~~designation,~~medicinal product may be designated as orphan if its sponsor can establish that (i) the ~~drug~~product is ~~entitled~~intended tofor athe ~~period~~diagnosis, prevention or treatment of ~~marketing~~a ~~exclusivity~~life-threatening or chronically debilitating condition; (ii) either (a) such condition affects no more than 5 in 10,000 ~~which~~persons ~~precludes~~in the ~~FDA~~EU ~~from~~when ~~approving~~the ~~another~~application ~~marketing~~is ~~application~~made, ~~for~~or (b) the ~~same~~product, ~~drug~~without ~~for~~the benefits derived from orphan status, would not generate sufficient return in the ~~same~~EU ~~disease~~to justify investment; and (iii) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for ~~that~~marketing ~~time~~in ~~period.~~the ~~The~~EU, ~~applicable~~or ~~period~~if issuch ~~seven~~a ~~years~~method inexists, the Umedicinal product will be of significant benefit to those affected by the condition.S. ~~Orphan~~The ~~drug~~application ~~exclusivity~~for ~~may~~orphan designation must be ~~lost~~submitted inbefore ~~limited~~the ~~circumstances~~application for marketing authorization. In the EU, ~~such~~orphan asdesignation entitles a ~~showing~~party ofto ~~clinical~~financial ~~superiority~~incentives ~~over~~such ~~the~~as ~~product~~reduction ~~with~~of ~~orphan~~fees, ~~exclusivity~~fee waivers, ifprotocol ~~the~~assistance, ~~underlying~~and ~~NDA~~access ~~authorizing~~to the ~~sale~~centralized marketing authorization procedure. Moreover, upon grant of a marketing authorization and assuming the ~~drug~~requirement isfor ~~withdrawn,~~orphan ordesignation ifare also met at the ~~manufacturer~~time the marketing authorization is ~~unable~~granted, orphan medicinal products are entitled to ~~assure~~a ~~sufficient~~ten-year ~~quantity~~period of market exclusivity for the ~~drug~~approved totherapeutic ~~meet~~indication. ~~the~~The ~~needs~~period of ~~patients~~market ~~with~~exclusivity ~~the~~is ~~rare~~extended ~~disease~~by ortwo ~~condition.~~years for orphan

Even if we obtain orphan drug exclusivity for a product candidate, that exclusivity may not effectively protect the drug candidate from competition because different drugs can be approved for the same disease or condition. In addition, even after an orphan drug is approved, the applicable regulatory authority can subsequently approve the same or a similar drug from another sponsor for the same condition if it concludes that the later drug is clinically superior in that it is shown to be safer, more effective or makes a major contribution to patient care. Orphan drug designation neither shortens the development time or regulatory review time of a drug nor gives the drug any advantage in the regulatory review or approval process.36

Amedicinal ~~Fast~~products ~~Track~~that ~~Designation~~have byalso ~~the~~complied ~~FDA,~~with ~~even~~an ifagreed ~~granted~~pediatric ~~for~~investigation ~~any~~plan. ofHowever, ~~our~~during ~~product~~such ~~candidates~~period, marketing authorizations may ~~not~~be ~~lead~~granted to a ~~faster~~similar ~~development~~medicinal product with the same orphan indication if: (i) the applicant can establish that the second medicinal product, although similar to the orphan medicinal product already authorized is safer, more effective or ~~regulatory~~otherwise ~~review~~clinically superior to the orphan medicinal product already authorized; (ii) the marketing authorization holder for the orphan medicinal product grants its consent; or ~~approval~~(iii) ~~process~~if the marketing authorization holder of the orphan medicinal product is unable to supply sufficient quantities of product. The European exclusivity period can be reduced to six years, ~~and~~if, ~~does~~at ~~not~~the ~~increase~~end of the ~~likelihood~~fifth year a medicine no longer meets the criteria for orphan designation (i.e. the prevalence of the condition has increased above the orphan designation threshold or it is judged that ~~our~~the product ~~candidates~~is ~~will~~sufficiently ~~receive~~profitable ~~marketing~~so ~~approval~~as not to justify maintenance of market exclusivity).

On August 27, 2021 we received Fast Track Designation for ELX-02 for the treatment of cystic fibrosis patients with nonsense mutations. If a drug is intended for the treatment of a serious or life-threatening condition and the drug demonstrates the potential to address unmet medical needs for this condition, the drug sponsor may apply to the FDA for Fast Track Designation. 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 an NDA is submitted, the product candidate may be eligible for priority review. A Fast Track product candidate may also be eligible for rolling review, where the FDA may consider for review sections of the NDA 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 has broad discretion whether or not to grant this designation. Even if we believe a particular product candidate is eligible for this designation, we cannot assure you that the FDA would decide to grant it. Even if we do receive Fast Track Designation, we may not experience a faster development process, review or approval compared to conventional FDA procedures. The FDA may withdraw Fast Track Designation if it believes that the designation is no longer supported by data from our clinical development program. Many drugs that have received Fast Track Designation have failed to obtain approval.

Successful and timely completion of clinical trials will require that we enroll a sufficient number of subjects. These trials and other trials we conduct may be subject to delays for a variety of reasons, including as a result of enrollment taking longer than anticipated, subject withdrawal or adverse events. These types of developments could cause us to delay the trial or halt further development. Our clinical trials will compete with other clinical trials that are in the same therapeutic areas as our product candidates, and this competition reduces the number and types of patients available to us, as some patients who might have opted to enroll in our trials may instead opt to enroll in a trial being conducted by one of our competitors. The protocols for our clinical trials generally require that patients may not be enrolled in more than one clinical trial for the same indication, which will limit the pool of available subjects.

In addition to the rarity of some diseases, the eligibility criteria of our clinical studies will further limit the pool of available study participants as we will require that patients have specific characteristics that we can measure and that their disease is not too advanced. Specifically, some of the diseases that our product candidates are designed to treat are rare and ultra-rare and we expect only a subset of the patients with these diseases will be eligible for our clinical trials. Because ~~ELX-02~~exaluren is designed to target small populations and patient numbers have not been determined definitively, we must be able to identify patients in order to complete our development programs, potentially secure regulatory approval for, and if approved, successfully commercialize ~~ELX-02~~exaluren.

We cannot guarantee that any of our programs will identify a sufficient number of patients to complete clinical development, pursue regulatory approval and market our product candidates, if approved. The combined number of patients in the ~~U.S.~~United States, ~~Japan~~the UK and Europe and elsewhere may turn out to be lower than expected, may not be otherwise amenable to treatment with ~~ELX-02~~exaluren, or new patients may become increasingly difficult to identify, all of which would adversely affect our results of operations and our business. An inability to recruit and enroll a sufficient number of patients for any of our current or future clinical trials would result in significant delays or may require us to abandon one or more clinical trials altogether, which could impact our ability to develop our product candidates and may have a material adverse effect on our business, results of operations and financial condition. Patient enrollment depends on many factors, including:

•

the size and nature of the patient population;

•

the severity of the disease under investigation;

•

eligibility criteria for the trial;

•

the proximity of patients to clinical sites;

•

the design of the clinical protocol;

•

the ability to obtain and maintain patient consents;

•

the ability to recruit clinical trial investigators with the appropriate competencies and experience;

•

the risk that patients enrolled in clinical trials will drop out of the trials before the administration of our product candidates or trial completion;

•

the availability of competing clinical trials;

•

the availability of new drugs approved for the indication the clinical trial is investigating; and

•

clinicians’ and ~~patients’~~patient ~~perceptions~~perception as to the potential advantages of the drug being studied in relation to other available therapies.

~~In addition, the ongoing COVID-19 pandemic has and may in the future adversely affect enrollment in our clinical trials.~~ We ~~experienced~~also ~~significant~~rely delays in our recently completed Phase 2 monotherapy study with ELX-02 in CF as a result of having to pause enrollment in response to the COVID-19 pandemic in order to avoid unnecessary exposure in at-risk populationson, ~~to maintain the integrity of our study data~~ and towill ~~support~~continue ~~global healthcare providers in their commitment~~ to ~~ensure~~rely ~~patient safety. On November 1~~on, ~~2022,~~CROs weand ~~announced that enrollment in our Phase 2~~ clinical trial insites ~~Alport~~to ~~syndrome~~ensure ~~commenced.~~proper Weand ~~experienced~~timely ~~delays~~conduct inof ~~starting the trial related to staffing challenges in~~ our clinical ~~trial~~trials ~~sites~~ and ~~related~~preclinical ~~lack of resources at these sites~~studies. ~~Any~~Though ~~future~~we ~~additional costs as a result of delays in enrollment or failure to complete enrollment in accordance with our objectives could be significant and may~~ have aentered ~~material~~into ~~adverse~~agreements ~~impact~~governing ontheir ~~our~~services, ~~financial~~we ~~condition and results of operations.~~

2937

~~Interim,~~will ~~“topline”~~have ~~and~~limited ~~preliminary~~influence ~~data~~over ~~from~~their actual performance. Our inability to enroll a sufficient number of patients for our clinical trials ~~that~~would weresult ~~announce~~in significant delays or ~~publish~~may ~~from~~require ~~time~~us to ~~time~~abandon one or more clinical trials altogether. Enrollment delays in our clinical trials may ~~change~~result asin ~~more~~increased ~~patient~~development ~~data~~costs ~~become~~for ~~available~~our product candidates and jeopardize our ability to obtain regulatory approval for the sale of our product candidates. Furthermore, even if we are ~~subject~~able to ~~audit~~enroll ~~and~~a ~~verification~~sufficient ~~procedures~~number ~~that~~of ~~could~~patients ~~result~~for inour ~~material~~clinical ~~changes~~trials, we may have difficulty maintaining enrollment of such patients in ~~the~~our ~~final~~clinical ~~data~~trials.

We may conduct clinical trials for our product candidates outside of the United States and the FDA may not accept data from such trials, in which case our development plans may be delayed, which could materially harm our business.

We are conducting one or more of our clinical trials or a portion of our clinical trials for our product candidates outside the United States. The acceptance of study data from clinical trials conducted outside the United States or another jurisdiction by the FDA or comparable foreign regulatory authority may be subject to certain conditions or may not be accepted at all. In cases where data from foreign clinical trials are intended to serve as the sole basis for regulatory approval in the United States, the FDA will generally not approve the application on the basis of foreign data alone unless (i) the data are applicable to the U.S. population and U.S. medical practice; (ii) the trials were performed by clinical investigators of recognized competence and pursuant to GCP regulations; and (iii) the data may be considered valid without the need for an on-site inspection by the FDA, or if the FDA considers such inspection to be necessary, the FDA is able to validate the data through an on-site inspection or other appropriate means. In addition, even where the foreign study data are not intended to serve as the sole basis for approval, if the study was not otherwise subject to an IND, the FDA will not accept the data as support for an application for regulatory approval unless the study is well-designed and well-conducted in accordance with GCP requirements and the FDA is able to validate the data from the study through an onsite inspection if deemed necessary. Many foreign regulatory authorities have similar requirements for clinical data gathered outside of their respective jurisdictions. In addition, such foreign trials would be subject to the applicable local laws of the foreign jurisdictions where the trials are conducted. There can be no assurance that the FDA or any comparable foreign regulatory authority will accept data from trials conducted outside of the United States or the relevant jurisdiction. Additionally, recent policy proposals in the United States, if enacted in the future, may make acceptance by the FDA or inclusion in a marketing application of foreign data more difficult or costly. If the FDA or any comparable foreign regulatory authority does not accept such data, it may result in the need for additional trials, which could be costly and time-consuming, and which may result in current or future product candidates that we may develop not receiving approval for commercialization in the applicable jurisdiction.

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

From time to time, we may publicly disclose preliminary or topline data from our preclinical studies and clinical trials, which is based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change following a more comprehensive review of the data related to the particular study or trial. We also make assumptions, estimations, calculations and conclusions as part of our analyses of data, and we may not have received or had the opportunity to fully evaluate all available data. As a result, the topline or preliminary results that we report may differ from future results of the same studies, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated. Topline and preliminary data also remain subject to audit and verification procedures that may result in the final data being materially different from the top-line or preliminary data we previously published. As a result, topline and preliminary data should be viewed with caution until the final data are available.

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

Further, others, including regulatory agencies, may not accept or agree with our assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular product candidate or product and ~~our~~the Company in general. InFor ~~addition~~example, ~~the~~our ~~information~~Phase we2a ~~choose to publicly disclose regarding a particular study or~~ clinical trial isof ~~based~~exaluren ~~on what is typically extensive information, and you or others may not agree with what we determine to be material or otherwise appropriate information to include~~ in ~~our~~patients disclosure. If the interim, topline, or preliminary data that we report differ from actual results, or if others, including regulatory authorities, disagree with the conclusions or interpretations reached, our ability to obtain approval for, and commercialize, our product candidates may be harmed, which could negatively impact our business, operating results, prospects or financial condition.

with AS patients was an open-label clinical trial. An “open-label” clinical trial is one where both the patient and investigator know whether the patient is receiving the investigational product candidate or either an existing approved drug or placebo. Most typically, open-label clinical trials test only the investigational product candidate and sometimes may do so at different dose levels. Open-label clinical trials are subject to various limitations that may exaggerate any therapeutic effect as patients in open-label clinical trials are aware when they are receiving treatment. Open-label clinical trials may be subject to a “patient bias” where patients perceive their symptoms to have improved merely due to their awareness of receiving an experimental treatment. In addition, open-label clinical trials may be subject to an “investigator bias” where those assessing and reviewing the physiological outcomes of the clinical trials are aware of which treatment regimen patients have received and may interpret the information of the treated group more favorably given this knowledge. Accordingly, data from our Phase 2a clinical trial of exaluren in AS patients may not be predictive of data from our planned clinical trials for exaluren, which will be blinded. Further, any data from open-label trials that we may in future conduct may not be predictive of data from blinded clinical trials.

In addition, the information we choose to publicly disclose regarding a particular study or clinical trial is based on what is typically extensive information, and you or others may not agree with what we determine to be material or otherwise appropriate information to include in our disclosure. If the interim, topline, or preliminary data that we report differ from actual results, or if others, including regulatory authorities, disagree with the conclusions or interpretations reached, our ability to obtain approval for, and commercialize, our product candidates may be harmed, which could negatively impact our business, operating results, prospects or financial condition.

The regulatory approval processes of the FDA and comparable regulatory authorities are lengthy, time consuming and inherently unpredictable, and if we are ultimately unable to obtain regulatory approval for our product candidates, our business will be substantially harmed.

The clinical development, manufacturing, labeling, storage, record-keeping, advertising, promotion, import, export, marketing and distribution of our product candidates are subject to extensive regulation by the FDA in the United States and by comparable foreign regulatory authorities in foreign markets. The time required to obtain approval by the FDA and comparable regulatory authorities is unpredictable but typically takes many years following the commencement of clinical trials and depends upon numerous factors, including the substantial discretion of the regulatory authorities. In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions, and the FDA and comparable regulatory have substantial discretion in the approval process, including the ability to delay, limit or deny approval of a product candidate for many reasons. Neither we nor any future collaborator is permitted to market any of our product candidates in the United States until we receive regulatory approval of an NDA from the FDA. Similarly, in the EUEuropean Union, our product candidates can only be placed on the market after obtaining a marketing authorization.

Prior to obtaining approval to commercialize a product candidate in the United States, Europe or other jurisdictions, we or our collaborators must demonstrate with substantial evidence from well-controlled clinical trials, and to the satisfaction of the FDA or other regulatory agencies, that such product candidates are safe and effective for their intended uses. Results from nonclinical studies and clinical trials can be interpreted in different ways. Even if we believe the nonclinical or clinical data for our product candidates are promising, such data may not be sufficient to support approval by the FDA and other regulatory authorities. The FDA or other regulatory authority may also require us to conduct additional preclinical studies or clinical trials for our product candidates either prior to or post-approval, or it may object to elements of our clinical development program.

The FDA or any foreign regulatory authorities or bodies can delay, limit or deny approval of our drug product candidates or require us to conduct additional nonclinical or clinical testing or abandon a program for a variety of reasons, including the following:

•

regulatory authorities may disagree with the design or implementation of our clinical trials;

•

we may be unable to demonstrate to the satisfaction of the applicable regulatory authority that a product candidate is safe or effective for its proposed indication;

•

the results of clinical trials may not meet the level of statistical significance required by regulatory authorities for approval;

•

serious and unexpected drug-related side effects experienced by participants in our clinical trials or by individuals using drugs similar to our product candidates;

•

we may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks;

•

regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials;

•

the data collected from clinical trials of our product candidates may not be acceptable or sufficient to support the submission of an NDA or other submission or to obtain regulatory approval in the United States, the EU, or elsewhere, and we may be required to conduct additional clinical studies;

•

the applicable foreign regulatory authority may disagree regarding the formulation, labeling and/or the specifications of our product candidates;

•

applicable regulatory authorities may fail to approve the manufacturing processes or facilities of third-party manufacturers with which we contract for clinical and commercial supplies; and

•

the approval policies or regulations of the FDA or comparable regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval..

Of the large number of drugs in development, only a small percentage successfully complete the regulatory approval processes and are commercialized. The lengthy approval process as well as the unpredictability of future clinical trial results may result in our failing to obtain regulatory approval to market our product candidates, which would significantly harm our business, results of operations and prospects.

In addition, even if we were to obtain approval, regulatory authorities may approve our product candidates for fewer or more limited indications than we request, may not approve the price we intend to charge for our products, may grant approval contingent on the performance of costly post-marketing clinical trials, including Phase 4 clinical trials, and/or the implementation of a REMS program, which may be required to assure safe use of the drug after approval. Regulatory authorities may also approve a product candidate for a more limited indication or patient population than we originally requested, or may approve a product candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of that product candidate. Any of the foregoing scenarios could materially harm the commercial prospects for our product candidates.

In addition, FDA and foreign regulatory authorities may change their approval policies and new regulations may be enacted. For instance, the EU pharmaceutical legislation has been undergoing a complete review process, in the context of the Pharmaceutical Strategy for Europe initiative, launched by the European Commission in November 2020. The European Commission’s proposal for revision of several legislative instruments related to medicinal products was published on April 26, 2023. The proposed changes were since discussed and negotiated by the European Parliament and the Council of the EU as part of the EU ordinary legislative process. A provisional agreement has been reached by the European Parliament and Council of the EU on the proposed revisions on December 11, 2025. The proposed revisions (affecting the duration of regulatory data protection and market protection, including for orphan medicinal products, revising the eligibility for expedited pathways, etc.) remain to be formally adopted by the two institutions, which is not anticipated before early 2026. The proposed changes are not expected to enter into application before 2028 and may have a significant impact on the biopharmaceutical industry in the long term.

Even if we obtain FDA approval for any of our product candidates in the United States, we may never obtain approval for or commercialize such candidates in any other jurisdiction, which would limit our ability to realize their full market potential.

In order to market any products in any particular jurisdiction, we must establish and comply with numerous and varying regulatory requirements on a country-by-country basis regarding safety and efficacy. Approval by the FDA in the United States does not ensure approval by regulatory authorities in other countries or jurisdictions. However, the failure to obtain approval in one jurisdiction may negatively impact our ability to obtain approval elsewhere. In addition, clinical trials conducted in one country may not be accepted by regulatory authorities in other countries, and regulatory approval in one country does not guarantee regulatory approval in any other country.

Approval processes vary among countries and can involve additional product testing and validation, as well as additional administrative review periods. Seeking foreign regulatory approval could result in difficulties and increased costs for us and require additional preclinical studies or clinical trials which could be costly and time consuming. Regulatory requirements can vary widely from country to country and could delay or prevent the introduction of our products in those countries. We do not have any product candidates approved for sale in any

jurisdiction, including in international markets, and we do not have experience in obtaining regulatory approval in international markets. If we fail to comply with regulatory requirements in international markets or to obtain and maintain required approvals, or if regulatory approvals in international markets are delayed, our target market will be reduced and our ability to realize the full market potential of any product we develop will be unrealized.

If we are unable to establish sales and marketing capabilities or enter into agreements with third parties to market and sell any of our product candidates that obtain regulatory approval, we may be unable to generate any revenue.

We have no experience selling and marketing our product candidates or any other products. To successfully commercialize any products that may result from our clinical development programs and obtain regulatory approval, we will need to develop these capabilities, either on our own or with the assistance of others. We may seek to enter into collaborations with other entities to utilize their marketing and distribution capabilities, but we may be unable to do so on favorable terms, if at all. If any future collaborative partners do not commit sufficient resources to commercialize our future products, if any, and we are unable to develop the necessary marketing capabilities on our own, we will be unable to generate sufficient product revenue to sustain our business. We will be competing with many companies that currently have extensive and well-funded marketing and sales operations. Without an internal team or the support of a third party to perform marketing and sales functions, we may be unable to compete successfully against these more established companies or successfully commercialize any of our product candidates.

31Even if our product candidates receive regulatory approval, they will be subject to significant post-marketing regulatory requirements and oversight.

~~Even~~Any ifregulatory approvals that we may receive for our product candidates ~~receive~~will require the submission of reports to regulatory authorities and surveillance to monitor the safety and efficacy of the product candidate, may contain significant limitations related to use restrictions for specified age groups, warnings, precautions or contraindications, and may include burdensome post-approval study or risk management requirements. For example, ~~they~~the FDA may require a REMS in order to approve our product candidates, which could entail requirements for a medication guide, physician training and communication plans or additional elements to ensure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. In addition, if the FDA, EMA or other regulatory authorities approve our product candidates, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion, import, export and recordkeeping for our product candidates will be subject to ~~significant~~extensive and ongoing regulatory requirements. These requirements include submissions of safety and other post- marketing information and reports, registration, as well as ongoing compliance with cGMP and comparable foreign requirements and GCPs for any clinical trials that we conduct post-approval. In addition, manufacturers of drug products and their facilities are subject to continual review and periodic, unannounced inspections by the FDA and other regulatory authorities for compliance with cGMP regulations and similar standards. Further, manufacturers and other parties involved in the drug supply chain for prescription drug products must also comply with product tracking and tracing requirements and ~~oversight~~for notifying FDA of counterfeit, diverted, stolen and intentionally adulterated products or products that are otherwise unfit for distribution in the United States.

Any regulatory approvals that we may receive for our product candidates will require the submission of reports to regulatory authorities and surveillance to monitor the safety and efficacy of the product candidate, may contain significant limitations related to use restrictions for specified age groups, warnings, precautions or contraindications, and may include burdensome post-approval study or risk management requirements. For example, the FDA may require a REMS in order to approve our product candidates, which could entail requirements for a medication guide, physician training and communication plans or additional elements to ensure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. In addition, if the FDA, EMA or other regulatory authorities approve our product candidates, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion, import, export and recordkeeping for our product candidates will be subject to extensive and ongoing regulatory requirements. These requirements include submissions of safety and other post-marketing information and reports, registration, as well as ongoing compliance with cGMP requirements and GCPs for any clinical trials that we conduct post-approval. In addition, manufacturers of drug products and their facilities are subject to continual review and periodic, unannounced inspections by the FDA and other regulatory authorities for compliance with cGMP regulations and similar standards. If we or a regulatory authority discover previously unknown problems with a product, such as adverse events of unanticipated severity or frequency, or problems with the facilities where the product is manufactured, a regulatory authority may impose restrictions on that product, the manufacturing facility or us, including requiring recall or withdrawal of the product from the market or suspension of manufacturing. In addition, failure to comply with applicable regulatory requirements may subject ~~our~~the ~~company~~Company to administrative or judicially imposed sanctions, including:

•

delays in or the rejection of product approvals;

•

restrictions on our ability to conduct clinical trials, including full or partial clinical holds on ongoing or planned trials;

•

restrictions on the products, manufacturers or manufacturing process;

•

warning or untitled letters;

•

civil and criminal penalties;

•

injunctions;

•

suspension or withdrawal of regulatory approvals;

•

product seizures, detentions or import bans;

•

voluntary or mandatory product recalls and publicity requirements;

•

total or partial suspension of production; and

•

imposition of restrictions on operations, including costly new manufacturing requirements.

The occurrence of any event or penalty described above may inhibit our ability to commercialize our product candidates and generate revenue and could require us to expend significant time and resources in response and could generate negative publicity.

In addition, the FDA’s and other regulatory authorities’ policies may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our product candidates. We also cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, either in the United States or abroad. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may be subject to enforcement action and we may not achieve or sustain profitability.

There is no guarantee that we will receive in a timely fashion or at all the additional milestone or royalty payments under the Almirall License Agreement.

On March 11, 2024, we entered into the License Agreement with Almirall (the “Almirall License Agreement”), pursuant to which we sublicensed to Almirall certain rights we owned under the Harvard Agreement relating to the research, development and commercialization of ZKN-013, and other related assets as described in the Almirall License Agreement. Under the Almirall License Agreement, we received an upfront payment of $3.0 million and are eligible to receive additional payments throughout the potential development phases, including development and sales milestones of up to approximately $470.0 million and tiered royalties of mid-single to low-double digit percentages of any future global sales. The achievement and timing of the milestones depend on the success of development, approval and sales progress, if any, of commercial products developed through the collaboration in the future. In connection with Almirall License Agreement, Almirall has control and broad discretion over all aspects of the development and commercialization of ZKN-013 and we will have little, if any, influence over how such activities will be conducted. Our receipt of any payments related to development milestones or royalties is dependent on Almirall’s ability to successfully develop and commercialize ZKN-013. See section titled “ITEM 1 Business—License Agreements—License Agreement between Eloxx and Almirall.”

The FDA and other regulatory agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses.

If any of our product candidates are approved and we are found to have improperly promoted off-label uses of those products, we may become subject to significant liability. The FDA and other regulatory agencies strictly regulate the promotional claims that may be made about prescription products, such as our product candidates, if approved. These regulations include standards and restrictions for direct-to-consumer advertising, industry-sponsored scientific and educational activities, promotional activities involving the internet and off-label promotion. Any regulatory approval that the FDA grants is limited to those specific diseases and indications for which a product is deemed to be safe and effective by FDA. In particular, a product may not be promoted for uses that are not approved by the FDA or such other regulatory agencies as reflected in the product’s approved labeling. If we receive marketing approval for a product candidate, physicians may nevertheless prescribe it to their patients for uses that are not described in the product’s labeling and for uses that differ from those tested in clinical trials and approved by the regulatory authorities. However, our ability to promote any products will be narrowly limited to those indications that are specifically approved by the FDA.

32If we are found to have promoted such off-label uses, we may become subject to significant liability. The U.S. federal government has levied large civil and criminal fines against companies for alleged improper promotion of off-label use and has enjoined several companies from engaging in off-label promotion. The government has also required companies to enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed and/or subject to additional oversight and monitoring. If we cannot successfully manage the promotion of our product candidates, if approved, we could become subject to significant liability, which would materially adversely affect our business and financial condition.

approved. In particular, a product may not be promoted for uses that are not approved by the FDA or such other regulatory agencies as reflected in the product’s approved labeling. If we receive marketing approval for a product candidate, physicians may nevertheless prescribe it to their patients in a manner that is inconsistent with the approved label. If we are found to have promoted such off-label uses, we may become subject to significant liability. The U.S. federal government has levied large civil and criminal fines against companies for alleged improper promotion of off-label use and has enjoined several companies from engaging in off-label promotion. The FDA has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed. If we cannot successfully manage the promotion of our product candidates, if approved, we could become subject to significant liability, which would materially adversely affect our business and financial condition.42

Disruptions at the FDA and other government agencies and foreign regulatory authorities caused by funding shortages, staffing limitations, or global health concerns could hinder their ability to hire, retain or deploy key leadership and other personnel, or otherwise prevent new or modified products from being developed, approved or commercialized in a timely manner or at all, which could negatively impact our business.

The ability of the FDA and foreign regulatory authorities to review and approve new products can be affected by a variety of factors, including government budget and funding levels, statutory, regulatory, and policy changes, the FDA’s and foreign regulatory authorities’ ability to hire and retain key personnel and accept the payment of user fees, and other events that may otherwise affect the FDA’s and foreign regulatory authorities’ ability to perform routine functions. Average review times at the FDA and foreign regulatory authorities have fluctuated in recent years as a result. In addition, government funding of other government agencies that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable. Disruptions at the FDA and other agencies, ~~such as the EMA relocation to Amsterdam and resulting staff changes~~ may also slow the time necessary for new drugs or modifications to approved drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business. For example, ~~over~~in ~~the~~recent ~~last several~~ years, the U.S. government has shut down several times and certain regulatory agencies, such as the FDA, have had to furlough critical FDA employees and stop critical activities. In addition, the current U.S. Presidential administration has issued certain policies and Executive Orders directed towards reducing the employee headcount and costs associated with U.S. administrative agencies, including the FDA, which have led to substantial personnel changes, and it remains unclear the degree to which these efforts may limit or otherwise adversely affect the FDA’s ability to conduct routine activities.

~~Separately,~~If in response to the COVID-19 pandemic, in March 2020, the FDA temporarily postponed routine surveillance inspections of domestic manufacturing facilities. Subsequently, in July 2020, the FDA resumed certain on-site inspections of domestic and foreign manufacturing facilities subject to a ~~risk-based~~prolonged ~~prioritization~~government ~~system.~~shutdown ~~The FDA utilized this risk-based assessment system to assist in determining when and where it was safest to conduct prioritized domestic inspections. Additionally~~occurs, onor ~~April~~if ~~15,~~funding ~~2021~~shortages, ~~the~~staffing FDA issued a guidance document in which the FDA described its plans to conduct voluntary remote interactive evaluations of certain drug manufacturing facilities and clinical research sites, among other facilities. According to the guidance, the FDA may request such remote interactive evaluations where the FDA determines that remote evaluation would be appropriate based on mission needs and travel limitations. Inor July 2021, the FDA resumed standard inspectional operations of domestic facilities. More recently, the FDA has continued to monitor and implement changes to its inspectional activities to ensure the safety of its employees and those of the firms it regulates as it adapts to the evolving COVID-19 pandemic. Regulatory authorities outside the United States have adopted similar ~~restrictions~~factors orhinder ~~other policy measures in response to the COVID-19 pandemic. If a prolonged government shutdown occurs,~~ or ~~if global health concerns continue to~~ prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews, or other regulatory activities, itsuch events could significantly impact the ability of the FDA or other such regulatory authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business.

Developments by competitors may render our ~~products~~product candidates or technologies obsolete or non-competitive which would have a material adverse effect on our business, results of operations and financial condition.

We compete with pharmaceutical ~~companies~~and ~~that~~biotechnology ~~are collaborating with larger pharmaceutical~~ companies, and academic research institutions, ~~government~~developing ~~agencies~~therapies ~~and~~for ~~other~~rare ~~public~~genetic kidney and ~~private~~dermatologic ~~research organizations~~diseases. Our product candidates will ~~have to~~ compete with existing therapies and potential therapies under development by our competitors. In addition, our commercial opportunities may be reduced or eliminated if our competitors develop and market products that are less expensive, more effective or safer than our product candidates. Other companies have product candidates in various stages of preclinical or clinical development to treat diseases for which we are also seeking to develop product candidates through targeting downstream pathological processes such as fibrosis, inflammation, or proteinuria. Some of these potential competing drugs are further advanced in development than our product candidates and may be commercialized earlier. Even if we are successful in developing effective drugs, our products may not compete successfully with products produced by our competitors.

33Some of our competitors have significantly greater financial resources than we do and an established presence in the market. Our competitors may have greater expertise in research and development, manufacturing, obtaining regulatory approvals and marketing approved products and may obtain regulatory approvals for their products more rapidly than we can, if at all. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. We also compete with these companies in recruiting, hiring and retaining qualified scientific and management talent, establishing clinical trial sites and patient registration for clinical trials and obtaining manufacturing slots at contract manufacturing organizations.

Most of our competitors, either alone or together with their collaborative partners, operate larger research and development programs, staff and facilities, and have substantially greater financial resources than we do, as well as significantly greater experience in:

developing drugs;

undertaking preclinical testing and human clinical trials;

obtaining marketing approvals from the FDA and other regulatory authorities;

formulating and manufacturing drugs; and

launching, marketing and selling drugs.

These organizations also compete with us to attract qualified personnel, for acquisitions and joint venture candidates and for other collaborations.

Efforts to compete and the pursuit of activities of our competitors may impose unanticipated costs on our business, which would have a material adverse effect on our business, results of operations and financial condition.

If we are unable to develop and commercialize our product candidates, our business will be adversely affected.

A key element of our strategy is to develop and commercialize a portfolio of new products. We seek to do so through our internal research programs and strategic collaborations for the development of new products. Research programs to identify new product candidates require substantial technical, financial and human resources, whether or not any product candidates are ultimately identified. Our research programs may initially show promise in identifying potential product candidates, yet fail to yield product candidates for clinical development for many reasons, including:

•

a product candidate is not capable of being produced in commercial quantities at an acceptable cost, or at all;

•

a product candidate that is developed and approved may not be accepted by patients, the medical community or third-party payors;

•

competitors may develop alternatives that render our product candidates obsolete;

•

the research methodology used may not be successful in identifying potential product candidates; or

•

a product candidate may on further study be shown to have harmful side effects or other characteristics that indicate it is unlikely to be safe or effective or otherwise does not meet applicable regulatory approval requirements.

Any failure to develop or commercialize any of our product candidates may have a material adverse effect on our business, results of operations and financial condition.

Even if we are able to commercialize any product candidate, coverage and adequate reimbursement may not be available or such product candidate may become subject to unfavorable pricing regulations or third-party coverage and reimbursement policies, which would harm our business.

The regulations that govern regulatory approvals, pricing, and reimbursement for drug products vary widely from country to country. Some countries require approval of the sale price of a drug product before it can be marketed. In many countries, the pricing review period begins after marketing approval is granted. In some foreign markets, prescription drug product pricing remains subject to continuing governmental control even after initial approval is granted. As a result, we might obtain regulatory approval for a product in a particular country, but then be subject to price regulations that delay our commercial launch of the product, possibly for lengthy time periods, and negatively impact the revenues we are able to generate from the sale of the product in that country. Adverse pricing limitations may hinder our ability to recoup our investment in one or more product candidates, even if our product candidates obtain regulatory approval.

Our ability to commercialize any products successfully also will depend in part on the extent to which coverage and adequate reimbursement for these products and related treatments will be available from third-party payors, such as government authorities, private health insurers, and other organizations. Even if we succeed in bringing one or more products to the market, these products may not be considered cost-effective, and the amount reimbursed for any products may be insufficient to allow us to sell our products on a competitive basis. In the United States, no uniform policy for coverage and reimbursement exists, and coverage and reimbursement can differ significantly from payor to payor. Third-party payors often follow Medicare coverage policy and payment limitations in setting their own reimbursement rates, but also have their own methods and approval process apart from Medicare determinations. As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support 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. Decisions regarding the extent of coverage and amount of reimbursement to be provided for any product candidates that we develop will be made on a payor-by-payor basis. One payor’s determination to provide coverage for a drug does not assure that other payors will also provide coverage and adequate reimbursement for the drug. There may be significant delays in obtaining reimbursement for newly-approved drug products, and coverage may be more limited than the purposes for which the drug product is approved by the FDA or comparable foreign regulatory authorities.

bringing one or more products to the market, these products may not be considered cost-effective, and the amount reimbursed for any products may be insufficient to allow us to sell our products on a competitive basis. In the United States, no uniform policy for coverage and reimbursement exists, and coverage and reimbursement can differ significantly from payor to payor. Third-party payors often follow Medicare coverage policy and payment limitations in setting their own reimbursement rates, but also have their own methods and approval process apart from Medicare determinations. As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support 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. Decisions regarding the extent of coverage and amount of reimbursement to be provided for any product candidates that we develop will be made on a payor-by-payor basis. One payor’s determination to provide coverage for a drug does not assure that other payors will also provide coverage and adequate reimbursement for the drug. There may be significant delays in obtaining reimbursement for newly-approved drug products, and coverage may be more limited than the purposes for which the drug product is approved by the FDA or comparable foreign regulatory authorities.

Moreover, eligibility for reimbursement does not imply that any drugs product will be reimbursed in all cases or at a rate that covers our costs, including research, development, manufacture, sale, and distribution. Increasingly, the third-party payors who reimburse patients or healthcare providers are requiring that drug companies provide them with predetermined discounts from list prices, and are seeking to reduce the prices charged or the amounts reimbursed for drug products. If the price we are able to charge for any products we develop, or the coverage and reimbursement provided for such products, is inadequate in light of our development and other costs, our return on investment could be affected adversely.

Interim reimbursement levels for new drug products, if applicable, may also be insufficient to cover our costs and may not be made permanent. Reimbursement rates may be based on payments allowed for lower cost drug products that are already reimbursed, may be incorporated into existing payments for other services and may reflect budgetary constraints or imperfections in Medicare data. Net prices for drug products may be reduced by mandatory discounts or rebates required by third-party payors and by any future relaxation of laws that presently restrict imports of drug products from countries where they may be sold at lower prices than in the United States. Obtaining coverage and adequate reimbursement for our product candidates may be particularly difficult because of the higher prices often associated with drugs administered under the supervision of a physician. Similarly, because our product candidates are physician-administered injectables, separate reimbursement for the product itself may or may not be available. Instead, the administering physician may or may not be reimbursed for providing the treatment or procedure in which our product is used.

coverage and adequate reimbursement for our product candidates may be particularly difficult because of the higher prices often associated with drugs administered under the supervision of a physician. Similarly, because our product candidates are physician-administered injectables, separate reimbursement for the product itself may or may not be available. Instead, the administering physician may or may not be reimbursed for providing the treatment or procedure in which our product is used.

Our inability to promptly obtain coverage and adequate reimbursement from both third-party payors for the product candidates that we may develop and for which we obtain regulatory approval could have a material and adverse effect on our business, financial condition, results of operations, and prospects.

Current and future healthcare reform and other legislation may increase the difficulty and cost for us and any future collaborators to obtain marketing approval of and commercialize our product candidates and affect the prices we, or they, may obtain and may have a negative impact on our business and results of operations.

In the United States, and some foreign jurisdictions there have been, and continue to be, a number of legislative ~~initiatives~~and toregulatory ~~contain~~changes and proposed changes regarding the healthcare ~~costs.~~system ~~The~~that ~~Patient~~could, ~~Protection~~among other things, restrict or regulate post-approval activities with respect to any product candidate for which we obtain marketing approval, and ~~Affordable~~may ~~Care~~affect ~~Act~~our ability, or ~~ACA~~the ability of any future collaborators, to profitably sell our products for which ~~was~~we ~~passed~~obtain inmarketing ~~2010,~~approval. ~~substantially~~Among ~~changed~~policy makers and payors in the ~~way~~United ~~health~~States ~~care~~and elsewhere, there is ~~financed~~significant byinterest ~~both~~in ~~governmental~~promoting ~~and~~changes ~~private~~in ~~insurers.~~healthcare ~~The~~systems ~~ACA,~~with ~~among~~the ~~other~~stated ~~things,~~goals ~~expanded~~of ~~Medicaid~~containing ~~program~~healthcare ~~eligibility~~costs, improving quality and/or expanding access. toIn ~~commercial~~the ~~health~~United ~~insurance~~States ~~coverage~~and elsewhere, ~~increased~~ the ~~minimum~~pharmaceutical ~~Medicaid~~industry ~~rebates~~has ~~owed~~been bya ~~manufacturers~~particular ~~under~~focus ~~the~~of ~~Medicaid~~these ~~Drug~~efforts ~~Rebate~~and ~~Program~~has been significantly affected by major legislative and ~~extended~~regulatory ~~the~~initiatives. ~~rebate~~We ~~program~~expect tothat ~~individuals~~current ~~enrolled~~laws, inas ~~Medicaid~~well ~~managed~~as ~~care~~other ~~organizations~~healthcare reform measures that may be adopted in the future, ~~established~~may ~~annual~~result ~~fees~~in more rigorous coverage criteria and ~~taxes~~additional ondownward ~~manufacturers~~pressure ofon ~~certain~~the ~~branded~~price ~~prescription~~that ~~drugs~~we, ~~and~~or ~~promoted~~any afuture ~~new~~collaborators, ~~Medicare~~may ~~Part~~receive Dfor ~~coverage~~any ~~gap~~product ~~discount~~candidates ~~program~~approved for sale. ~~The~~New ~~ACA~~and changing laws and regulations may also ~~appropriated~~create ~~funding~~uncertainty toabout ~~comparative~~how ~~clinical~~such ~~effectiveness~~laws ~~research,~~and ~~although~~regulations itwill ~~remains~~be ~~unclear~~interpreted ~~how~~and ~~the~~applied. ~~research~~If ~~will~~we ~~affect~~are ~~Medicare~~found ~~coverage~~to have violated laws and ~~reimbursement~~regulations, orit ~~how~~could ~~new~~materially ~~information~~adversely ~~will~~affect ~~influence~~our ~~other~~business, ~~third-party~~results ~~payer~~of ~~policies~~operations and financial condition.

~~Since~~The ~~its~~Affordable ~~enactment,~~Care ~~there~~Act ~~have~~(the ~~been~~“ACA”) ~~judicial,~~was ~~executive~~signed ~~and~~into ~~Congressional~~law ~~challenges~~in to2010. ~~certain~~The ~~aspects of the~~ ACA. Onsubstantially ~~June~~changed ~~17,~~the ~~2021,~~way ~~the~~healthcare ~~U.S.~~is ~~Supreme~~financed ~~Court~~by ~~dismissed~~both ~~the~~governmental ~~most~~and ~~recent~~private ~~judicial~~insurers, ~~challenge~~and tosignificantly affects the ~~ACA~~U.S. ~~without~~pharmaceutical ~~specifically~~industry. ~~ruling~~Among on the ~~constitutionality~~provisions of the ACA. ~~Prior~~of importance to ~~the~~our ~~Supreme Court’s decision~~business, ~~President Biden issued an executive order initiating a special enrollment period from February 15~~including, ~~2021~~without ~~through August 15~~limitation, ~~2021~~our ~~for~~ability ~~purposes~~to ofcommercialize ~~obtaining~~and ~~health insurance coverage through~~ the ~~ACA~~prices ~~marketplace.~~we ~~The~~may ~~executive~~obtain ~~order~~for ~~also~~any ~~instructed~~product ~~certain~~candidates ~~governmental agencies to review and reconsider their existing policies and rules~~ that ~~limit~~are ~~access~~approved tofor ~~healthcare. It is unclear how other healthcare reform measures of the Biden administration~~sale, ifare ~~any, will impact our business.~~

•

35an annual, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic agents, apportioned among these entities according to their market share in certain government healthcare programs, although this fee does not apply to sales of certain products approved exclusively for orphan indications;

•

Ina ~~addition,~~Patient ~~other~~Centered ~~legislative~~Outcomes ~~changes~~Research ~~have~~Institute ~~been proposed and adopted since the ACA was enacted. These changes included aggregate reductions~~ to ~~Medicare payments to providers of 2% per fiscal year~~oversee, ~~which~~identify ~~went~~priorities ~~into effect on April 1~~in, ~~2013~~ and, ~~due~~conduct tocomparative ~~subsequent~~clinical ~~legislative~~effectiveness ~~amendments to the statute~~research, ~~will~~along ~~remain in effect through 2030,~~ with ~~the~~funding exception of a temporary suspension from May 1, 2020 through March 31, 2022. Under current legislation, the actual reduction in Medicare payments varies from 1% from April 1, 2022 through June 30, 2022, up to 3% in the final fiscal year of this sequester unless additional Congressional action is taken. In addition, on January 2, 2013, the American Taxpayer Relief Act of 2012 was signed into law, which, among other things, reduced Medicare payments to several providers, including hospitals, and increased the statute of limitations period for ~~the~~such ~~government~~research; to recover overpayments to providers from three to five years. More recently, on March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacturer price, beginning January 1, 2024. and

•

~~Similar~~establishment ~~developments have occurred outside~~ of the ~~United~~Center ~~States,~~for ~~including~~Medicare inand ~~the~~Medicaid ~~European~~Innovation ~~Union~~within ~~where~~CMS ~~healthcare~~to ~~budgetary~~test ~~constraints~~innovative ~~have~~payment ~~resulted in restrictions on the pricing~~ and ~~reimbursement of medicines by relevant health~~ service ~~providers.~~delivery Tomodels ~~obtain~~to ~~reimbursement~~lower orMedicare ~~pricing~~and ~~approval~~Medicaid ~~in some European Union member states~~spending, weincluding ~~may~~prescription bedrug ~~required to conduct studies that compare the cost-effectiveness of our product candidates to other therapies that are considered the local standard of care~~spending.

ItSince isits ~~also~~enactment, ~~possible~~certain ~~that~~provisions ~~additional~~of ~~governmental~~the ~~action~~ACA ishave ~~taken~~been insubject ~~response~~ to ~~address the COVID-19 pandemic. We cannot predict the likelihood~~judicial, ~~nature~~executive, orand ~~extent~~legislative ofchallenges ~~government~~and ~~regulation that~~ may ~~arise~~be ~~from~~subject ~~future~~to ~~legislation~~additional orchallenges ~~administrative action~~ in the ~~United~~future. ~~States~~In addition, ~~particularly~~other aslegislative achanges ~~result~~have ofbeen ~~the~~proposed ~~recent~~and ~~presidential~~adopted ~~election,~~since orthe ~~any~~ACA ~~other~~was ~~jurisdiction~~enacted. IfThe wecost orof ~~any~~prescription ~~third~~pharmaceuticals ~~parties~~in wethe ~~may~~United ~~engage~~States ~~are~~has ~~slow~~also orbeen ~~unable~~the tosubject ~~adapt~~of toconsiderable ~~changes~~discussion in ~~existing~~the ~~requirements~~United orStates. ~~the~~There ~~adoption~~have ofbeen ~~new~~several ~~requirements~~Congressional ~~or policies~~inquiries, oras ifwell weas orlegislative ~~such~~and ~~third~~regulatory ~~parties~~initiatives ~~are~~and ~~not~~executive ~~able~~orders designed to, ~~maintain~~among ~~regulatory~~other ~~compliance~~things, ~~our~~bring ~~product~~more ~~candidates~~transparency ~~may~~to ~~lose~~product ~~any~~pricing, ~~regulatory~~review ~~approval~~the ~~that~~relationship ~~may~~between ~~have~~pricing ~~been~~and ~~obtained~~manufacturer patient programs, and wereform ~~may~~government ~~not~~program ~~achieve~~reimbursement ormethodologies ~~sustain~~for ~~profitability~~drug products.

~~Risks~~The ~~Related~~Inflation Reduction Act (the “IRA”) was enacted in 2022. Among other things, the IRA established requirements for manufacturers of certain drugs to ~~Our~~engage ~~Financial~~in ~~Position~~price negotiations with Medicare, with prices that can be negotiated subject to a cap known as the maximum fair price; imposed rebates under the Medicare program, Part B and ~~Need~~Medicare Part D to penalize price increases that outpace inflation (beginning in 2023); redesigned the Medicare Part D benefit (beginning in 2024); and replaced the Part D coverage gap discount program with a new manufacturer discount program (beginning in 2025). CMS has published and negotiated maximum fair price for ~~Additional~~the ~~Capital~~initial ten drugs subject to negotiation, which became effective in 2026, and for a subsequent set of 15 drugs, which will first be effective in 2027. CMS has also published the next set of 15 drugs that will be subject to negotiation. The Medicare drug price negotiation program is currently subject to legal challenges. The IRA permits the Secretary of the Department of Health and Human Services (“HHS”) to implement many of these provisions through guidance, as opposed to regulation, for the initial years. HHS has and will continue to issue and update guidance as

We have incurred significant operating losses since our inception and anticipate that we will continue to incur substantial operating losses for the foreseeable future. We may never achieve or maintain profitability.45

Wethese ~~have~~programs aare ~~history of net losses and negative cash flows from operating activities since inception and, as of December 31, 2022, had an accumulated deficit of $274~~implemented.4 ~~million.~~The Weimpact ~~have financed our operations primarily through equity securities, and to a lesser extent from loans and grants. We have devoted substantially all~~ of ~~our~~the ~~financial~~IRA ~~resources~~on ~~and~~us ~~efforts to research~~ and ~~development.~~the Wepharmaceutical ~~expect~~industry ~~that~~cannot ityet ~~will~~ be ~~several~~fully ~~years~~determined, ifbut ~~ever,~~is ~~before~~likely ~~we receive regulatory approval for commercialization of a product candidate. We expect~~ to ~~continue~~be ~~to incur~~ significant ~~expenses and operating losses for the foreseeable future~~. ~~Our net losses may fluctuate significantly from quarter to quarter and year to year. We anticipate that our expenses will increase substantially if and as we:~~

~~advance~~The ~~ELX-02~~One Big Beautiful Bill Act, ~~ZKN-013~~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~~/or~~ ~~other~~reduce ~~product~~the ~~candidates~~services ~~further~~covered ~~into~~by ~~clinical~~Medicaid, ~~development;~~which could adversely affect our sales of any product candidate that we commercialize.

The ~~experience~~Trump administration is also pursuing strategies reduce drug costs in the United States that are likely to have a negative impact on the pharmaceutical industry and may negatively affect our ability to receive adequate revenues for any ~~further~~product ~~delays~~candidate for which we obtain marketing approval. This includes threats to impose significant tariffs on pharmaceutical manufacturers that do not adopt pricing policies such as most favored nation pricing, which would tie the price for drugs in ~~enrollment~~the United States to the lowest price in a group of other countries. In response, multiple manufacturers have reportedly entered into confidential pricing agreements with the federal government. The Trump administration also published two proposed regulations in December 2025, referred to as GLOBE and ~~completion~~GUARD, that would, if finalized, these regulations would implement mandatory payment models under which manufacturers of ~~our~~eligible ~~clinical~~drugs ~~trials~~would ~~due~~be required to pay rebates to the ~~COVID-19~~federal ~~pandemic~~government on a portion of the units of their drugs that are reimbursed by Medicare, with the rebate amount based on most favored nation pricing. While the impact of the GLOBE and GUARD proposed payment models, if fully implemented, cannot yet be determined, it is likely to be significant. Even if any of these regulatory proposals or ~~otherwise;~~executive actions are ultimately deemed unlawful, they could negatively impact the United States pharmaceutical sector and our business. In addition, pharmaceutical pricing and marketing has long been the subject of considerable discussion in Congress and among policymakers, and it is possible that Congress could enact additional laws that negatively affect the pharmaceutical industry.

~~continue~~Moreover, the ~~preclinical~~individual ~~development~~states in the United States have become increasingly active in developing proposals, passing legislation and implementing regulations designed to control drug pricing, including price or patient reimbursement constraints, discounts, formulary flexibility, marketing cost disclosure, drug price increase reporting, and other transparency measures. Some states have enacted legislation creating so-called prescription drug affordability boards, with the goal of ~~our~~imposing ~~research~~price ~~programs~~limits on certain drugs in these states, and ~~advance~~at ~~candidates~~least ~~into~~one ~~clinical~~state ~~trials;~~board is imposing an upper payment limit. States are also seeking to implement general, across the board price caps for pharmaceuticals, or are seeking to regulate drug distribution. Some measures are designed to encourage importation from other countries. These types of initiatives may result in additional reductions in Medicare, Medicaid, and other healthcare funding, and may otherwise affect the prices we may obtain for any product candidate for which we obtain marketing approval or the frequency with which any product candidate for which we obtain marketing approval is prescribed or used.

~~pursue~~We ~~regulatory~~expect ~~authorization~~that tothese ~~conduct~~and ~~clinical~~other ~~trials~~healthcare reform measures that may be adopted in the future may result in more rigorous coverage and payment criteria and in additional downward pressure on the price that we receive for any approved drug. Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize our drugs. We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for our product candidates; or additional pricing pressures. We cannot predict with certainty what impact any federal or state health reforms will have on us, but such changes could impose new or more stringent regulatory requirements on our activities or result in reduced reimbursement for our products, any of which could adversely affect our business, results of operations and financial condition.

~~seek~~The pricing of prescription pharmaceuticals is also subject to governmental control outside the United States. In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt of marketing ~~approvals~~approval for ~~our~~a product. ~~candidates;~~To obtain reimbursement or pricing approval in some countries, we may be required to conduct a clinical trial that compares the cost effectiveness of any product candidate for which we obtain marketing approval to other available therapies. If reimbursement of our products is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our ability to generate revenues and become profitable could be impaired.

establish a sales, marketing and distribution infrastructure to commercialize any product candidates for which we obtain marketing approval;

maintain, expand and protect our intellectual property portfolio;

hire additional clinical, regulatory, management and scientific personnel;

add operational, financial and management information systems and personnel;

acquire or in-license other product candidates and technologies; and

operate as a public company and maintain our compliance with Nasdaq listing requirements.

We have never generated any revenue from product sales and may never be profitable. To become and remain profitable, we and our collaborators must develop and eventually commercialize one or more product candidates with significant market potential. This will require us to be successful in a range of challenging activities, including completing preclinical studies and clinical trials of our product candidates, obtaining marketing approval for these product candidates, manufacturing, marketing and selling those product candidates for which we may obtain marketing approval, securing coverage and reimbursement for those product candidates for which we may obtain marketing approval, and satisfying any post-marketing requirements. We may never succeed in these activities and, even if we do, may never generate revenue that is significant or large enough to achieve profitability. Our failure to become and remain profitable would decrease the value of the company and could impair our ability to raise capital, maintain our research and development efforts, expand our business or continue our operations. A decline in the value of the company could also cause investors to lose all or part of their investment.

the scope, progress, results and costs of drug discovery, clinical development, laboratory testing and clinical trials for ELX-02, ZKN-013, and other product candidates;

the costs, timing and outcome of any regulatory review of ELX-02, ZKN-013, and other product candidates;

the cost of any other product candidate programs we pursue;

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

our ability to establish and maintain collaborations on favorable terms, if at all; and

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

Accordingly, despite our prior public equity offerings and debt financings, we will need substantial additional funding in connection with our continuing operations and to achieve our goals. However, our existing cash and cash equivalents may prove to be insufficient for these activities. If we are unable to raise capital when needed or on attractive terms, we would be forced to delay, reduce or eliminate our research and development programs, product portfolio expansion or future commercialization efforts. Adequate additional financing may not be available to us on acceptable terms, or at all. In addition, we may seek additional financing due to favorable market conditions or strategic considerations, even if we believe we have sufficient funds for our operating plans. If we are unable to obtain adequate financing, we will evaluate options, which may include reducing or deferring operating expenses, including by downsizing our workforce and curtailing certain development programs, which could have a material adverse effect on our operations and financial results.

Changing circumstances and market conditions, some of which may be beyond the Company's control, could impair our ability to access our existing cash and cash equivalents and investments and to timely pay key vendors and others.

We maintain our cash and cash equivalents in accounts with major financial institutions, and our deposits these institutions can and do exceed insured limits. Market conditions can impact the viability of these institutions. In the event of failure of any of the financial institutions where we maintain our cash and cash equivalents, we could lose our deposits in excess of the federally insured or protected amounts and there can be no assurance that we will be able to access uninsured funds in a timely manner or at all. Any inability to access or delay in accessing these funds could adversely affect our business and financial position.

Our recurring losses from operations raise substantial doubt regarding our ability to continue as a going concern.

For the year ended December 31, 2022, our net losses were $36.1 million and as of December 31, 2022, we had an accumulated deficit of $274.4 million. We anticipate operating losses to continue for the foreseeable future due to, among other things, costs related to research, development of our product candidates, conducting preclinical studies and clinical trials, and our administrative organization. We will require substantial additional financing to fund our operations and to continue to execute our strategy, and we will pursue a range of options to secure additional capital. We believe that our cash and cash equivalents at December 31, 2022 are not sufficient to fund our current and planned operations for at least the next twelve months. These conditions raise substantial doubt about our ability to continue as a going concern within one year after the date of the issuance of the consolidated financial statements included in this Annual Report on Form 10-K.

We are exploring various sources of funding such as strategic collaborations and the issuance of equity to fund our operations. If we raise additional funds through strategic collaborations and alliances, which may include existing collaboration partners, we may have to relinquish valuable rights to our technologies or product candidates, or grant licenses on terms that are not favorable to us. To the extent that we raise additional capital through the sale of equity, the ownership interest of our existing stockholders will be diluted and other preferences may be necessary that adversely affect the rights of existing stockholders. If we are unable to raise sufficient capital through the transactions discussed above, we may need to curtail expenses contemplated by our current operating plan, and we may be required to delay, limit, reduce or terminate our product development efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves. If the foregoing plans are unsuccessful and we are unable to continue as a going concern, you could lose all or part of your investment in the Company.

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

Until such time, if ever, as we can generate substantial product revenue, we expect to finance our cash needs through a combination of equity and debt financings, as well as entering into new collaborations, strategic alliances and licensing arrangements. We do not have any committed external source of funds. To the extent that we raise additional capital through the sale of equity, such as our public offering of shares of our common stock in May 2021 or issuances of common stock under our at-the-market program (“ATM Program”), or convertible debt securities, an investor’s ownership interest will be diluted, and the terms of these securities may include liquidation or other preferences that may adversely affect an investor’s rights as a common stockholder. Debt 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, and may be secured by all or a portion of our assets. Further, the availability of funding under the Hercules Term Loan is conditioned on us meeting certain clinical and equity milestones during defined time periods. For example, because the Company did not meet the milestone requirements for the Tranche 2 Advance under the Hercules Term Loan as of August 15, 2022, this funding was not available to the Company. Any debt agreements we may enter into in the future may contain similar restrictions on funding. If we raise funds by entering into new collaborations, strategic alliances or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings or through collaborations, strategic alliances or licensing arrangements when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

We may not be able to maintain compliance with our debt covenants in the future.

The Hercules Term Loan Agreement contains customary affirmative and negative covenants which, among other things, required the Company to maintain at all times a minimum qualified cash balance equaling amounts ranging from $6.3 million to $10.0 million ($10.0 million effective as of August 15, 2022 and at December 31, 2022) and limits our ability to (i) incur additional indebtedness, (ii) pay dividends or make certain distributions, (iii) dispose of our assets, grant liens or encumber our assets or (iv) fundamentally alter the nature of our business. These covenants are subject to a number of exceptions and qualifications. Subsequent to year end, on March 7, 2023, this minimum qualified cash balance was reduced to $2.25 million as of March 7, 2023 with the amendment of the terms and our repayment of $7.5 million of principal. If we breach these financial covenants and fail to secure a waiver or forbearance from the third-party lender, such breach or failure could accelerate the repayment of the outstanding borrowings under the Hercules Term Loan or the exercise of other rights or remedies the third-party lender may have under applicable law. No assurance can be provided a waiver or forbearance will be granted or the outstanding borrowings under the Hercules Term Loan, will be successfully refinanced on terms that are acceptable to the Company.

We do not intend to pay dividends for the foreseeable future.

We have never declared or paid any dividends on our common stock and do not intend to pay any dividends in the foreseeable future. We anticipate that we will retain all of our future earnings for use in the operation of our business and for general corporate purposes. Further, the terms of the Hercules Term Loan Agreement limit us from paying dividends or making certain distributions. Any determination to pay dividends in the future will be at the discretion of our board of directors.

Our indebtedness and debt service obligations may adversely affect our cash flow.

We intend to fulfill our debt service obligations, including repayment of the principal of the Hercules Term Loan, from cash generated from our future operations, from our existing cash, and potential additional cash proceeds from our ATM Program or other future equity financings. Our indebtedness could have significant additional negative consequences, including requiring the dedication of a substantial portion of our expected cash flow to service our indebtedness, thereby reducing the amount of our expected cash flow available for other purposes and limiting our flexibility in planning for, or reacting to, changes in our business and the industry in which we compete. If we are unable to generate sufficient cash to meet these obligations and need to use existing cash in order to fund our debt service obligations, including repayment of the principal, we may have to delay or curtail research and development programs.

Risks Related to Our Business and Operations

We continue to seek opportunities to expand our business through strategic initiatives. Our efforts to identify opportunities or complete transactions that satisfy our strategic criteria may not be successful, and we may not realize the anticipated benefits of any completed acquisition, collaboration or other strategic transaction.

Our business strategy includes expanding our product candidates and capabilities. We regularly evaluate potential merger, acquisition, partnering and in-license opportunities that we expect will expand our pipeline or product offerings, and enhance our research or development programs.46

Our business strategy includes expanding our product candidates and capabilities. We regularly evaluate potential merger, acquisition, collaboration and in-license opportunities that we expect will expand our pipeline or product offerings, and enhance our research or development programs.

We may engage in future strategic transactions that could cause us to incur additional liabilities, commitments or significant expense. Any such transactions will be dependent on our ability to appropriately evaluate the potential risks and uncertainties, integrate any new technology, product and/or business, and generate revenues (including through up-front payments, milestones and/or royalties) sufficient to meet our underlying objectives.

Any strategic transaction undertaken may result in unforeseen development costs, timeline delays, regulatory approval challenges and uncertainties relating to the commercial market opportunity, any of which could cause us to fail to realize the anticipated value of the transaction and may have a material adverse effect on our business and financial condition.

require significant capital expenditures and management resources, including investments in research, development, sales and marketing, manufacturing and other areas of our operations. The development or expansion of our business, any acquired business or any acquired or in-licensed products may require a substantial capital investment by us. We may not have these necessary funds, or they might not be available to us on acceptable terms or at all. We may also seek to raise funds by selling shares of our capital stock, or securities convertible into our capital stock, which could dilute current stockholders’ ownership interest in our Company.

Our business could be affected by litigation, government investigations and enforcement actions.

We operate in many jurisdictions in a highly regulated industry and we could be subject to litigation, government investigation and enforcement actions on a variety of matters in the ~~U.S.~~United States or foreign jurisdictions, including, without limitation, intellectual property, regulatory, product liability, environmental, whistleblower, Qui Tam, false claims, privacy, anti-kickback, anti-bribery, securities, commercial, employment, and other claims and legal proceedings which may arise from conducting our business. Any of these actions or proceedings may result in significant costs, fines, penalties or imposition of burdensome restrictions on the company, any of which could have a material adverse effect on our business, results of operations and financial condition.

We could be subject to additional tax liabilities.

We are subject to federal, state and local taxes in the United States, Israel, and ~~Israel~~Australia. Significant judgment is required in evaluating our tax positions and our worldwide provision for taxes. During the ordinary course of business, there are many activities and transactions for which the ultimate tax determination is uncertain. In addition, our tax obligations and effective tax rates could be adversely affected by changes in the relevant tax (including tariffs), accounting and other laws, regulations, principles and interpretations, including those relating to income tax nexus, by our earnings being lower than anticipated in jurisdictions where we have lower statutory rates and higher than anticipated in jurisdictions where we have higher statutory rates, by changes in foreign currency exchange rates, or by changes in the valuation of our deferred tax assets and liabilities. Changes to tax laws (which changes may have retroactive application), including with respect to net operating losses and research and development tax credits, could adversely affect us or holders of our common stock. We may be audited in various jurisdictions, and such jurisdictions may assess additional taxes against us. Although we believe our tax estimates are reasonable, the final determination of any tax audits or litigation could be materially different from our historical tax provisions and accruals, which could have a material adverse effect on our operating results or cash flows in the period or periods for which a determination is made.

Material weaknesses in our internal control over financial reporting could have a significant adverse effect on our business and the price of our common stock.

Material weaknesses in our internal control over financial reporting could have a significant adverse effect on our business and the price of our common stock. As a public company, we are required to comply with the rules of the SEC implementing Sections 302 and 404 of the Sarbanes-Oxley Act of 2002 (the “Sarbanes-Oxley Act”), which requires management to certify financial and other information in our quarterly and annual reports and provide an annual management report on the effectiveness of controls over financial reporting. When evaluating our internal control over financial reporting as of December 31, 2025, our management concluded that our disclosure controls and procedures were not effective at December 31, 2025 due to inconsistent execution of certain financial reporting controls during portions of the years ended December 31, 2025, 2024 and 2023, primarily within the financial close and reconciliation processes. Specifically, controls related to timely preparation and review of account reconciliations and period-end review procedures were not consistently performed or documented at a level sufficient to support the completeness and accuracy of financial reporting. These deficiencies also affected certain review controls over complex accounting analyses and technical accounting documentation prepared during the period. As of December 31, 2025, the material weakness has not been remediated by the Company and there can be no assurance that we will not identify additional material weaknesses in the future. If we identify additional material

weaknesses in our internal control over financial reporting or are unable to comply with the requirements of Section 404 in a timely manner or assert that our internal control over financial reporting is effective, investors may lose confidence in the accuracy and completeness of our financial reports and the market price of our common stock could be materially adversely affected, and we could become subject to investigations by the stock exchange on which our securities are listed, the SEC or other regulatory authorities, which could require additional financial and management resources.

Our business could be adversely affected by the effects of widespread public health epidemics and other factors beyond our control.

~~Public~~Our ~~health~~business ~~epidemics or widespread outbreaks of contagious diseases~~ could be adversely ~~impact~~affected ~~our~~by ~~business.~~public ~~Any~~health ~~outbreak~~crises, ofepidemics, ~~contagious diseases~~pandemics, ~~and~~or ~~other~~similar ~~adverse~~events ~~public~~beyond ~~health~~our ~~developments~~control, ~~such~~which ~~as the COVID-19 pandemic,~~ could ~~impact~~disrupt our operations, ~~depending~~clinical ~~on future developments~~trials, ~~which~~supply ~~are highly uncertain~~chains, ~~largely~~and ~~beyond~~the ~~our~~ability ~~control~~of ~~and~~regulatory ~~cannot~~authorities beto ~~predicted~~conduct ~~with~~timely ~~certainty~~reviews. ~~These~~The ~~uncertain~~severity, ~~factors include the~~ duration ~~of the outbreak~~, ~~new~~and ~~information~~broader ~~which~~consequences ~~may~~of ~~emerge~~any ~~concerning~~such ~~the~~event ~~severity~~are ofinherently ~~the~~uncertain ~~disease~~ and ~~the actions to contain or treat its impact,~~ could adversely impact ~~our operations~~, ~~including~~ among ~~others~~other things, the conduct of our clinical trials, employee mobility and ~~productiveness~~productivity, ~~temporary~~the ~~closure~~availability of ~~facilities, including~~ clinical trial sites, our manufacturing capabilities, and ~~third~~the operations of third-party service providers such as CROs, any of which could have an adverse impact on our business and our financial results. The COVID-19 pandemic has also adversely affected the conduct of our clinical trials. For example, on March 25, 2020, we announced that enrollment in our clinical trials had been paused temporarily in response to the COVID-19 pandemic in order to avoid unnecessary exposure in at-risk populations, to maintain the integrity of our study data and to support global healthcare providers in their commitment to ensure patient safety. On June 17, 2020, we announced that enrollment in our Phase 2 clinical trial in cystic fibrosis had resumed in Israel and Europe, and on August 12, 2020, had resumed in the United States. As the COVID-19 pandemic continues in the United States and elsewhere, we may experience additional disruptions that could severely impact our business, preclinical studies and clinical trials.

WeActual ~~may~~or beperceived ~~subject~~failures to ~~numerous~~comply ~~and~~with ~~varying~~applicable data protection, privacy and security laws, ~~and~~regulations, ~~our~~standards ~~failure~~and toother ~~comply~~requirements could ~~result in penalties and reputational damage, and~~ adversely affect our ~~financial~~business, ~~condition and~~ results of operations, and financial condition.

WeThe global data protection landscape is rapidly evolving, and we are or may become subject to numerous state, federal and foreign laws, requirements and regulations ~~covering~~governing ~~data~~the ~~privacy~~collection, ~~and~~use, ~~the~~disclosure, ~~protection~~retention, and security of personal information, ~~including~~such ~~health~~as information. ~~The~~that ~~legislative~~we ~~and~~may ~~regulatory~~collect ~~landscape~~in ~~for~~connection ~~privacy~~with clinical trials in the United States and ~~data~~abroad. ~~protection~~This ~~continues~~evolution may create uncertainty in our business, affect our ability to ~~evolve~~operate in certain jurisdictions or to collect, store, transfer use and ~~there~~share ~~has~~personal ~~been~~information, annecessitate ~~increasing~~the ~~focus~~acceptance of more onerous obligations in our contracts, result in liability or impose additional costs on ~~privacy~~us. The cost of compliance with these laws, regulations and ~~data~~standards ~~protection~~is ~~issues~~high ~~which~~and ~~may~~is ~~affect~~likely ~~our~~to ~~business.~~increase Inin the Ufuture.~~S.,~~ weAny ~~may~~failure beor ~~subject~~perceived failure by us to ~~state~~comply ~~security~~with ~~breach~~federal, ~~notification~~state or foreign laws or regulations, ~~state~~our ~~health~~internal policies and procedures or our contracts governing our processing of personal information ~~privacy~~could ~~laws~~result in negative publicity, government investigations and enforcement actions, claims by third parties and damage to our reputation, any of which could have a material adverse effect on our business, results of operation, and financial condition.

40As our operations and business grow, we may become subject to or affected by new or additional data protection laws and regulations and face increased scrutiny or attention from regulatory authorities. In the United States, HIPAA imposes, among other things, certain standards relating to the privacy, security, transmission and breach reporting of protected health information. We may obtain protected health information from third parties, such as research institutions with which we collaborate, that are subject to privacy and security requirements under HIPAA. Although we do not believe that we are directly subject to HIPAA, other than potentially with respect to providing certain employee benefits, we could be subject to criminal penalties if we knowingly obtain or disclose individually identifiable health information maintained by a HIPAA covered entity in a manner that is not authorized or permitted by HIPAA. We may also face liability from a contractual perspective if we fail to comply with any agreements in place with such entities.

~~federal~~Even ~~and~~when ~~state~~HIPAA ~~consumer~~does ~~protections~~not ~~laws~~apply, ~~which~~according ~~impose~~to ~~requirements~~the ~~for~~Federal ~~the~~Trade ~~collection,~~Commission ~~use~~(“FTC”), ~~disclosure~~failing ~~and~~to ~~transmission~~take ofappropriate steps to keep consumers’ personal information. ~~Each~~secure ofconstitutes ~~these~~unfair ~~laws~~acts isor ~~subject~~practices toin ~~varying~~or ~~interpretations~~affecting bycommerce ~~courts~~in ~~and~~violation ~~government~~of ~~agencies,~~Section ~~creating~~5(a) ~~complex~~of ~~compliance~~the ~~issues~~Federal ~~for~~Trade usCommission Act (“FTCA”). ~~Any~~The ~~actual~~FTC’s orcurrent ~~perceived~~guidance ~~failure~~for byappropriately ussecuring toconsumers’ ~~comply~~personal ~~with~~information ~~applicable~~is ~~laws~~similar ~~and~~to ~~regulations~~what ~~could~~is ~~result~~required inby ~~negative~~the ~~publicity~~HIPAA security regulations, ~~government~~but ~~investigations~~this ~~and~~guidance ~~enforcement~~may ~~actions~~change in the future, ~~claims~~resulting byin ~~third~~increased ~~parties~~complexity and ~~damage~~the need to ~~our~~expend ~~reputation,~~additional ~~any~~resources ofto ~~which~~ensure ~~could~~we ~~have~~are acomplying ~~material~~with ~~adverse~~the ~~effect~~FTCA. onIn ~~our~~addition, ~~business~~in the United States, ~~financial~~certain ~~condition~~state ~~and~~laws ~~results~~impose ofspecific ~~operation~~security requirements for certain personal information.

AsFurther, ~~our~~at ~~operations~~the ~~and~~state ~~business grow~~level, wenumerous ~~may~~states ~~become~~have ~~subject~~also toadopted orcomprehensive ~~affected~~privacy bylaws, ~~new~~adding orcomplexity, ~~additional~~variation ~~data~~in ~~protection~~requirements, ~~laws~~restrictions and ~~regulations~~potential ~~and~~legal ~~face~~risk ~~increased~~requiring ~~scrutiny~~additional orinvestment ~~attention~~of ~~from~~resources ~~regulatory~~in ~~authorities~~compliance programs. InFor example, the ~~U.S.,~~California ~~HIPAA~~Consumer Privacy Act, as amended by the ~~Health~~California ~~Information~~Privacy ~~Technology~~Rights ~~for Economic and Clinical Health~~ Act ~~of 2009, and regulations promulgated thereunder~~ (collectively, the “~~HIPAA~~CCPA”) ~~imposes,~~requires ~~among~~covered ~~other~~businesses ~~things,~~that ~~certain~~process ~~standards relating to~~ the ~~privacy,~~personal ~~security,~~information ~~transmission and breach reporting~~ of ~~individually~~California ~~identifiable~~residents ~~health~~to, ~~information.~~among ~~While~~other wethings: do(i) ~~not~~provide ~~believe~~certain ~~that~~disclosures weto ~~are~~California ~~currently~~residents ~~acting~~regarding asthe ~~a “covered entity” or “~~business’s ~~associate”~~collection, ~~as such terms are defined under HIPAA~~use, and ~~therefore~~disclosure ~~are~~of ~~not~~their ~~directly~~personal ~~regulated~~information; ~~under~~(ii) ~~HIPAA,~~receive weand ~~could~~respond ~~be subject~~ to ~~penalties~~requests orfrom ~~sanctions,~~California ~~including~~residents ~~criminal~~to ~~penalties~~access, ifdelete, weand ~~knowingly~~correct ~~obtain~~their ~~individually~~personal ~~identifiable health~~ information, ~~from a covered entity in a manner that is not authorized~~ or ~~permitted~~to byopt ~~HIPAA~~out ~~or for aiding and abetting the violation~~ of ~~HIPAA.~~certain

Further, certain states have also adopted privacy and security laws and regulations, which govern the privacy, processing and protection of health-related and other personal information. Such laws and regulations will be subject to interpretation by various courts and other governmental authorities, thus creating potentially complex compliance issues for us and our future customers and strategic partners. For example, the California Consumer Privacy Act of 2018 (“CCPA”) went into effect on January 1, 2020. The CCPA creates individual privacy rights for California consumers and increases the privacy and security obligations of entities handling certain personal information. The CCPA provides for civil penalties for violations, as well as a private right of action for data breaches that is expected to increase data breach litigation. Further, the California Privacy Rights Act (“CPRA”) recently passed in California. The CPRA significantly amends the CCPA and will impose additional data protection obligations on covered businesses, including additional consumer rights processes, limitations on data uses, new audit requirements for higher risk data, and opt outs for certain uses of sensitive data. It will also create a new California data protection agency authorized to issue substantive regulations and could result in increased privacy and information security enforcement. The majority of the provisions will go into effect on January 1, 2023, and additional compliance investment and potential business process changes may be required. Similar laws have passed in Virginia, Utah, Connecticut, and Colorado, and have been proposed in other states and at the federal level, reflecting a trend toward more stringent privacy legislation in the United States. The enactment of such laws could have potentially conflicting requirements that would make compliance challenging. In the event that we are subject to or affected by HIPAA, the CCPA, the CPRA or other domestic privacy and data protection laws, any liability from failure to comply with the requirements of these laws could adversely affect our financial condition.48

~~Numerous~~disclosures ~~other countries have also developed, or are developing, laws governing the collection, use and transmission~~ of their personal information.; ~~EU member states~~ and ~~other jurisdictions have adopted data protection laws and regulations, which impose significant compliance obligations. For example, in May 2018, the General Data Protection Regulation~~ (~~“GDPR”~~iii) ~~went~~enter into ~~effect,~~specific ~~which~~contractual ~~imposes~~provisions ~~strict requirements for processing the personal data of individuals within the European Economic Area (“EEA”). Companies that must comply~~ with ~~the~~service ~~GDPR~~providers face increased compliance obligations and risk, including more robust regulatory enforcement of data protection requirements and potential fines for noncompliance of up to €20 million or 4% of the annual global revenues of the noncompliant company, whichever is greater. Among other requirements, the GDPR regulates transfers of personal data subject to the GDPR to third countries that ~~have~~process ~~not~~California ~~been~~resident ~~found to provide adequate protection to such~~ personal ~~data,~~information including the United States; in July 2020, the Court of Justice of the EU (“CJEU”) limited how organizations could lawfully transfer personal data from the EU/EEA to the United States by invalidating the Privacy Shield for purposes of international transfers and imposing further restrictions on the use of standard contractual clauses (“SCCs”). The European Commission issued revised SCCs on June 4, 2021 to account for the decision of the CJEU and recommendations made by the European Data Protection Board. The revised SCCs must be used for relevant new data transfers from September 27, 2021; existing standard contractual clauses arrangements must be migrated to the revised clauses by December 27, 2022. The new SCCs apply only to the transfer of personal data outside of the EEA and not the United Kingdom. The United Kingdombusiness’s ~~Information Commissioner’s Office has published new data transfer standard contracts for transfers from the United Kingdom under the United Kingdom GDPR~~behalf. ~~This~~Additional ~~new~~compliance ~~documentation~~investment ~~will~~and bepotential ~~mandatory~~business ~~for~~process ~~relevant~~changes ~~data~~may ~~transfers~~also ~~from September 21, 2022; existing standard contractual clauses arrangements must~~ be ~~migrated to the new documentation by March 21, 2024~~required. There is some uncertainty around whether the revised clauses can be used for all types of data transfers, particularly whether they can be relied on for data transfers to non-EEA entities subject to the GDPR. As supervisory authorities issue further guidance on

41Furthermore, other states have proposed or enacted legislation that focus on certain categories of data, such as consumer health data. For example, Washington State enacted the Washington My Health My Data Act, which broadly defines consumer health data, creates a private right of action to allow individuals to sue for violations of the law, imposes stringent consent requirements, and grants consumers certain rights with respect to their health data, including to request deletion of their information. Connecticut and Nevada have also passed similar laws regulating consumer health data. The effects of state and federal privacy laws are potentially significant and may require us to modify our data processing practices and policies and to incur substantial costs and potential liability in an effort to comply with such legislation. While such laws generally exempt clinical trial data, in the event that we are subject to or affected by HIPAA, the CCPA, or other domestic privacy and data protection laws, any liability from failure to comply with the requirements of these laws could adversely affect our financial condition.

~~personal~~Our operations abroad may also be subject to increased scrutiny or attention from data ~~export~~protection ~~mechanisms~~authorities. For example, ~~including~~in ~~circumstances~~Europe, ~~where~~the European Union General Data Protection Regulation (the ~~SCCs~~“EU ~~cannot~~GDPR”) beand ~~used~~in the United Kingdom (the “UK”), the United Kingdom General Data Protection Regulation and~~/or~~ ~~start~~Data ~~taking~~Protection ~~enforcement~~Act ~~action~~2018 (the “UK GDPR” and together with the EU GDPR, wereferred ~~could~~to ~~suffer~~as ~~additional~~the ~~costs~~“GDPR”) impose strict requirements for processing the personal data of individuals within the European Economic Area (“EEA”) and the UK. Companies that must comply with the GDPR face increased compliance obligations and risk, ~~complaints~~including more robust regulatory enforcement of data protection requirements and potential fines for noncompliance under both the EU GDPR and UK GDPR of up to €20 million/ GBP 17.5 million or 4% of the annual global revenues of the noncompliant company, whichever is greater. In addition to fines, a breach of the GDPR may result in regulatory investigations, orreputational ~~fines~~damage, orders to cease/ change our data processing activities, enforcement notices, assessment notices (for a compulsory audit) and/ or ifcivil weclaims ~~are~~(including ~~otherwise~~class ~~unable~~actions). toAmong ~~transfer~~other requirements, the GDPR restricts transfers of personal data ~~between~~subject ~~and~~to ~~among~~the GDPR to third countries ~~and~~that ~~regions~~have innot ~~which~~been wefound ~~operate,~~to itprovide ~~could~~adequate ~~affect~~protection ~~the~~to ~~manner~~such inpersonal ~~which~~data, weincluding ~~provide~~the ~~our~~United ~~services~~States, unless a derogation exists or appropriate transfer mechanisms are implemented (such as such as the ~~geographical~~European ~~location~~Commission approved standard contractual clauses (“SCCs”) or ~~segregation~~the ofU.K. ~~our~~International ~~relevant~~Data ~~systems~~Transfer ~~and~~Addendum ~~operations~~(“IDTA”)), and ~~could~~transfer ~~adversely~~impact ~~affect~~assessments ~~our~~are ~~financial~~conducted. ~~results~~The efficacy and longevity of current transfer mechanisms between the EEA/UK, and the United States remains uncertain.

~~Since~~In ~~the~~relation ~~beginning~~to ofsuch ~~2021,~~cross ~~after~~border ~~the~~transfers ~~end~~ of ~~the~~personal ~~transition period following the United Kingdom’s departure from the EU~~data, we ~~are~~expect ~~also subject to~~ the ~~United~~existing ~~Kingdom~~legal ~~GDPR~~complexity ~~(“UK~~and ~~GDPR”),~~uncertainty ~~which~~regarding ~~together~~international ~~with~~personal ~~the~~data ~~amended~~transfers UKto ~~Data Protection Act 2018~~continue, ~~retains~~and ~~the~~international ~~GDPR~~transfers ~~in UK national law. The UK GDPR imposes separate but similar obligations~~ to ~~those under~~ the ~~GDPR~~United ~~and~~States, ~~comparable penalties~~China, ~~including~~and ~~fines of up~~ to ~~£17.5~~other ~~million~~jurisdictions ormore 4%generally ofto acontinue ~~noncompliant~~to ~~company’s~~be ~~global~~subject ~~annual~~to ~~revenue~~enhanced ~~for~~scrutiny ~~the~~by ~~preceding financial year, whichever is greater~~regulators. ~~The~~As ~~relationship between~~ the ~~United~~regulatory ~~Kingdom~~guidance and ~~the~~enforcement EUlandscape in relation to ~~certain aspects of~~ data ~~protection~~transfers ~~law~~continue ~~remains~~to ~~unclear~~develop, ~~and~~we ~~the~~could ~~European~~suffer ~~Commission~~additional ~~adopted~~costs, ancomplaints ~~adequacy~~and/or ~~decision~~regulatory ininvestigations ~~favor~~or offines; ~~the~~we ~~United~~may ~~Kingdom,~~have ~~enabling~~to ~~data~~stop ~~transfers~~using ~~from~~certain EUtools ~~member~~and ~~states~~vendors toand ~~the~~make ~~United~~other ~~Kingdom~~operational ~~without~~changes; ~~additional~~we ~~safeguards.~~may ~~However,~~have ~~the~~to ~~United~~implement ~~Kingdom~~alternative ~~adequacy~~data ~~decision~~transfer ~~will~~mechanisms ~~automatically~~under ~~expire in June 2025 unless~~ the ~~European~~GDPR ~~Commission re-assesses~~ and/ ~~renews~~ or ~~extends~~take ~~that~~additional ~~decision.~~compliance Inand ~~September~~operational ~~2021,~~measures; ~~the~~and/or ~~United~~it ~~Kingdom~~could ~~government~~otherwise ~~launched~~affect athe ~~consultation~~manner onin ~~its~~which ~~proposals~~we ~~for~~operate ~~wide-ranging~~our ~~reform~~business, ofand ~~United~~could ~~Kingdom~~adversely ~~data~~affect ~~protection~~our ~~laws~~business, ~~following~~operations ~~Brexit~~ and ~~the~~financial ~~response~~condition. toAlthough ~~this~~the ~~consultation~~UK ~~was published in June 2022. There~~ is a ~~risk~~third ~~that~~country ~~any~~under ~~material changes which are made to~~ the ~~United~~EU ~~Kingdom data protection regime could result in the European Commission reviewing the United Kingdom adequacy decision~~GDPR, ~~and~~mutual ~~the United Kingdom losing its~~ adequacy ~~decision~~decisions ifpermit the ~~European~~continued ~~Commission~~free ~~deems~~flow ~~the~~of ~~United Kingdom to no longer provide adequate protection for~~ personal data. Asbetween wethe ~~continue~~EEA ~~to expand into other foreign countries~~ and ~~jurisdictions,~~the ~~we may be subject to additional laws and regulations that may affect how we conduct business~~UK.

The EUUK’s ~~has~~data ~~also~~protection ~~proposed~~regime ais ~~Regulation~~separate onfrom, ~~Privacy~~but ~~and~~aligned ~~Electronic Communications~~with, ~~("ePrivacy~~the ~~Regulation"),~~EU ~~which,~~regime. ifFollowing ~~adopted~~Brexit, ~~would~~there ~~impose~~is ~~new~~increasing ~~obligations~~scope onfor divergence in the ~~use~~application, interpretation and enforcement of ~~personal~~UK and EU data inprotection ~~the~~laws, ~~context~~including ofas ~~electronic~~a ~~communications,~~result ~~particularly~~of ~~with~~the ~~respect~~recently toimplemented ~~online~~UK ~~tracking~~Data ~~technologies~~(Use and ~~direct~~Access) ~~marketing~~Act 2025. ~~Additionally,~~Although the EUEuropean ~~adopted~~Commission extended its adequacy decision for the EUUK ~~Clinical~~through ~~Trials~~December ~~Regulation~~2031, ~~which~~uncertainty ~~came~~remains ~~into~~as ~~effect~~to onhow ~~January~~UK 31law will evolve over time, ~~2022.~~which ~~This~~could ~~regulation~~increase ~~imposes~~legal ~~new~~risk, ~~obligations~~complexity onand ~~the~~compliance ~~use~~costs ofand ~~data~~require ~~generated~~different ~~from~~measures ~~clinical~~for ~~trials~~the UK and ~~enables~~EEA. ~~European~~In ~~patients~~addition, toEEA Member States have ~~the~~adopted ~~opportunity~~national tolaws ~~access~~and ~~information~~regulatory ~~about~~approaches ~~clinical~~that ~~trials.~~may ~~Failure~~diverge orin ~~perceived~~certain ~~failure~~respects, toparticularly ~~comply~~in ~~with~~relation ~~the~~to ~~GDPR~~health data, ~~the~~resulting UKin ~~GDPR,~~a ~~the~~fragmented ~~ePrivacy~~compliance ~~Regulation,~~landscape. The European Commission has also proposed reforms under the EU“Digital ~~Clinical~~Omnibus” ~~Trials~~package ~~Regulations~~which, ~~and~~if ~~other~~adopted, ~~countries’~~may ~~privacy~~further ormodify ~~data security~~GDPR-related ~~laws~~requirements, ~~rules~~including orby ~~regulations~~clarifying ~~could~~the ~~result~~scope inof ~~significant~~“personal ~~regulatory~~data” ~~penalties~~ and ~~fines~~the treatment of coded or de-identified data, ~~affect~~potentially requiring further adjustments to our ~~compliance~~European ~~with~~privacy ~~contracts~~compliance ~~entered~~framework. ~~into~~As ~~with~~we ~~our~~continue ~~partners,~~to ~~collaborators~~expand ~~and~~into other ~~third-party~~foreign ~~payors,~~countries and ~~could~~jurisdictions, ~~have~~we anmay ~~adverse~~be ~~effect~~subject onto ~~our~~additional ~~reputation,~~laws ~~business~~ and ~~financial~~regulations ~~condition~~that may affect how we conduct business.

~~Although~~In ~~we work to comply with applicable laws~~2024, ~~regulations~~the ~~and~~National ~~standards,~~Security ~~our~~Division ~~contractual~~of ~~obligations~~the ~~and~~U.S. ~~other~~Department ~~legal~~of ~~obligations,~~Justice ~~these~~(DOJ) ~~requirements~~issued ~~are~~a ~~evolving~~new ~~and~~rule—referred ~~may~~to beas ~~modified,~~the ~~interpreted~~“Data ~~and~~Security ~~applied~~Program” ~~in an inconsistent manner from one jurisdiction~~ (DSP)—to ~~another,~~implement ~~and~~Executive ~~may~~Order ~~conflict~~14117 ~~with~~aimed ~~one~~at ~~another~~preventing oraccess ~~other~~to ~~legal~~“bulk ~~obligations with which we must comply~~U.S. ~~Any~~sensitive ~~failure~~personal ordata” ~~perceived failure by us or our employees, representatives, contractors, consultants, collaborators, or other third parties to comply with such requirements or adequately address privacy~~ and ~~security~~“government-related ~~concerns,~~data” ~~even~~by if“countries ~~unfounded,~~of ~~could~~concern” ~~result~~(including ~~in additional cost and liability to us~~China, ~~damage our reputation~~Russia, ~~and adversely affect our business, financial condition and results of operations.~~

~~Security breaches, cyber-attacks, or other disruptions could expose us to liability and affect our business and reputation.~~49

WeIran, ~~are~~North ~~increasingly~~Korea, ~~dependent~~Cuba, onand ~~our~~Venezuela) ~~information~~and ~~technology~~“covered ~~systems~~persons” ~~and~~(as ~~infrastructure~~all ~~for~~such ~~our~~terms ~~business~~are defined in the DSP). WeEffective ~~collect~~as of April 8, ~~store~~2025, and ~~transmit~~fully ~~sensitive~~enforceable ~~information~~as ~~including~~of ~~intellectual~~July ~~property~~9, ~~proprietary~~2025, ~~business~~the ~~information~~DSP ~~and~~imposes ~~personal~~stringent ~~information~~obligations inon ~~connection~~companies ~~with~~within ~~business~~its ~~operations.~~scope ~~The~~and ~~secure~~prohibits ~~maintenance~~or ofrestricts ~~this~~“covered ~~information~~data istransactions” ~~critical~~that togrant ~~our~~countries ~~operations~~of ~~and~~concern ~~business~~or ~~strategy.~~covered ~~Some~~persons ofaccess ~~this~~to ~~information~~bulk ~~could~~U.S. besensitive anpersonal ~~attractive~~data ~~target~~or any amount of ~~criminal~~government-related ~~attack~~data. byThe ~~third~~DSP ~~parties~~is ~~with~~new, acomplex ~~wide~~and ~~range~~has ofyet ~~motives~~to be enforced, and ~~expertise~~as such, ~~including~~there ~~organized~~is ~~criminal~~a ~~groups,~~risk ~~“hacktivists,”~~that ~~patient~~our ~~groups~~interpretation of its applicability, ~~disgruntled~~scope, ~~current~~and orrequirements ~~former~~is ~~employees~~incorrect, ~~and~~incomplete, ~~others~~or misapplied. ~~Cyber-attacks~~Compliance ~~are~~with ofthe ~~ever-increasing~~DSP ~~levels~~may ofrequire ~~sophistication,~~us ~~and~~to ~~despite~~invest ~~our~~heavily in data security and compliance measures, ~~our~~such ~~information~~as ~~technology~~implementing ~~systems~~ and ~~those~~complying ofwith ~~our~~the ~~third-party~~Cybersecurity ~~service~~and ~~providers,~~Infrastructure ~~strategic~~Security ~~partners~~Agency’s guidelines and other ~~contractors~~burdensome orrecordkeeping, ~~consultants~~reporting, ~~are~~and ~~vulnerable~~auditing torequirements. ~~attack~~It ~~and~~may ~~damage~~also orrequire ~~interruption~~us ~~from~~to ~~computer~~implement ~~viruses~~new ~~and~~processes, ~~malware~~stop ~~(e.g.~~or ~~ransomware),~~restrict ~~malicious~~certain ~~code,~~data ~~natural disasters~~transfers, ~~terrorism,~~alter ~~war,~~the ~~telecommunication~~geographic ~~and~~scope ~~electrical~~of ~~failures,~~our ~~hacking~~operations, ~~cyberattacks,~~cease ~~phishing~~doing ~~attacks~~business ~~and~~with ~~other~~certain ~~social~~third ~~engineering~~parties ~~schemes,~~or ~~employee~~using ~~theft~~certain tools or ~~misuse~~vendors, ~~human~~or ~~error,~~change ~~fraud,~~how ~~denial~~data orflows ~~degradation~~throughout ofour ~~service attacks~~business, ~~sophisticated~~any ~~nation-state~~of ~~and~~which ~~nation-state-supported~~could ~~actors~~materially orimpact ~~unauthorized~~our ~~access~~business operations or ~~use~~hinder byour ~~persons~~ability ~~inside~~to grow our ~~organization~~business. Finally, non-compliance with the DSP could result in significant civil or ~~persons~~criminal ~~with~~penalties, ~~access~~which tocould ~~systems~~materially ~~inside~~adversely affect our ~~organization~~business, results of operations, and financial condition.

42Our employees and personnel use generative artificial intelligence (“AI”) and/or automated decision-making technologies to perform their work, and the disclosure and use of personal data in AI technologies is subject to various privacy laws and other privacy obligations. Governments have passed and are likely to pass additional laws and regulations regulating AI and/or automated decision-making technologies. Our use of this technology could result in additional compliance costs, regulatory investigations and actions, and lawsuits. If we are unable to use AI and/or automated decision-making technologies, it could make our business less efficient and result in competitive disadvantages.

~~The~~Even ~~COVID-19~~though ~~pandemic~~we ~~has~~believe ~~caused~~we usand ~~to modify~~ our ~~business~~vendors ~~practices,~~are ~~including~~generally ~~permitting~~in ~~our~~compliance ~~employees~~with toapplicable ~~work from home. As a result~~laws, werules ~~are~~and ~~increasingly~~regulations ~~dependent~~relating ~~upon our information technology systems~~ to ~~operate~~privacy ~~our business~~ and ~~our~~data ~~ability to effectively manage our business depends on the~~ security, ~~reliability~~these ~~and~~laws ~~adequacy~~are ofin ~~our~~some ~~information~~cases ~~technology~~relatively ~~systems~~new and ~~data,~~the ~~which~~interpretation ~~includes~~and ~~use~~application of ~~cloud~~these ~~technologies.~~laws ~~This~~are ~~increased~~uncertain. ~~remote~~Any ~~usage~~failure ofor ~~information~~perceived ~~systems~~failure ~~increases~~by ~~the~~us ~~risks that our business may be disrupted due~~ to acomply ~~variety~~with ofdata ~~reasons,~~privacy ~~including security breaches~~laws, ~~power outages~~rules, ~~unavailability of employees~~regulations, ~~use~~industry ofstandards ~~non-company~~and ~~secured~~other ~~equipment~~requirements ~~and~~could ~~increased~~result ~~phishing~~in ~~and~~proceedings ~~hack~~or ~~activity.~~actions ~~However,~~against ~~despite~~us ~~these~~by ~~measures~~individuals, ~~and~~government ~~due to the ever-changing information cyber-threat landscape~~agencies, weor ~~may be subject to data breaches through cyber-attacks~~others. ~~Any~~We ~~such~~could ~~breach~~incur ~~could~~significant ~~compromise~~costs ~~our~~in ~~networks~~investigating and ~~the~~defending ~~information~~such ~~stored~~claims ~~there~~and, ~~could~~if befound ~~accessed~~liable, ~~publicly~~pay ~~disclosed,~~significant ~~lost~~damages or ~~stolen.~~fines Ifor ~~our~~be ~~systems~~required ~~become~~to ~~compromised,~~make wechanges ~~may~~to ~~not~~our ~~promptly discover the intrusion~~business. ~~Even~~Further, ifthese aproceedings ~~compromise~~and ~~were~~any ~~identified,~~subsequent weadverse outcomes may besubject ~~unable~~us to ~~adequately~~significant ~~investigate~~negative orpublicity ~~remediate~~and ~~incidents~~an orerosion ~~breaches~~of ~~due~~trust. toIf ~~attackers~~any ~~increasingly~~of ~~using~~these ~~tools~~events ~~and~~were ~~techniques that are designed~~ to ~~circumvent~~occur, ~~controls~~our business, toresults ~~avoid~~of ~~detection~~operations, and tofinancial ~~remove~~condition orcould ~~obfuscate~~be ~~forensic~~materially ~~evidence.~~adversely affected.

~~Like~~Our ~~other~~business ~~companies in our industry, we~~ and our service providers are from time to time subject to cyberattacks and security incidents, including malware and computer viruses. While we do not believe that we have experienced any significant system failure, accident, or security breach to date, if such an event were to occur and cause interruptions in our operations, itmay ~~could result in patient and other data and information becoming compromised, and we could lose sales for approved products, if any, and~~ suffer ~~reputational damage and loss of confidence by patients, investors and business partners. Such incidents may result~~ in ~~notification obligations to affected individuals and government agencies, legal claims or proceedings, and liability under federal and state laws that protect~~ the ~~privacy~~event ~~and security~~ of ~~personal~~ information. ~~Any~~technology ~~one~~system ~~of these events~~failures, cyberattacks or ~~similar~~deficiencies ~~events~~in ~~occurring through one of~~ our ~~vendors that maintain such information on our behalf, could cause our business to be materially harmed and our results of operations to be adversely impacted~~cybersecurity.

~~Our~~We ~~existing~~collect ~~general liability~~ and ~~cyber~~maintain ~~liability~~information ~~insurance~~in ~~policies~~digital ~~may~~form ~~not~~that ~~cover,~~is ornecessary ~~may~~to ~~cover~~conduct ~~only~~our ~~a portion of~~business, ~~any~~and ~~potential claims related to security breaches to which~~ we are ~~exposed~~increasingly ordependent ~~may not be adequate to indemnify us for all or any portion of liabilities that may be imposed. We also cannot be certain that our existing insurance coverage will continue to be available~~ on ~~acceptable~~information ~~terms~~technology orsystems inand ~~amounts~~infrastructure ~~sufficient~~ to ~~cover~~operate ~~the~~our ~~potentially~~business. ~~significant~~In ~~losses that may result from a security incident or breach or that~~ the ~~insurer~~ordinary ~~will~~course ~~not deny coverage~~ of ~~any~~our ~~future~~business, ~~claim.~~we ~~Accordingly~~collect, ifstore ~~our~~and ~~cybersecurity~~transmit ~~measures~~confidential information, ~~and~~including ~~those~~intellectual ofproperty, ~~our~~proprietary ~~service~~business ~~providers~~information, ~~fail~~preclinical toand ~~protect~~clinical ~~against~~trial ~~unauthorized access~~data, ~~attacks~~and ~~(which~~personal ~~may~~information ~~include~~(collectively, ~~sophisticated~~“Confidential ~~cyberattacks~~Information”). ~~and~~It ~~the~~is ~~mishandling~~critical ofthat ~~data~~we bydo ~~our~~so ~~employees~~in ~~and~~a ~~third-party~~secure ~~service~~manner ~~providers,~~to ~~then~~maintain ~~our~~the ~~reputation,~~confidentiality ~~business,~~and ~~results~~integrity of ~~operations~~such ~~and~~Confidential ~~financial condition could be adversely affected~~Information.

Our information technology systems and those of our third-party service providers, strategic partners and other contractors or consultants are vulnerable to attack, damage and interruption from computer viruses and malware (e.g. ransomware), misconfigurations, “bugs” or other vulnerabilities, malicious code, natural disasters, terrorism, war, telecommunication and electrical failures, hacking, cyberattacks, phishing attacks and other social engineering schemes, wrongful or inadvertent conduct by employees or vendors, human error, fraud, denial or degradation of service attacks and sophisticated nation-state and nation-state-supported actors. These attacks and activity are being facilitated or enhanced by evolving technologies, including artificial intelligence. We have also outsourced elements of our information technology infrastructure, and as a result a number of third-party vendors may or could have access to our confidential information.

The risk of a cybersecurity incident, data breach or other disruption, particularly through cyberattacks or cyber intrusion, including by computer hackers, foreign governments and cyber terrorists, has generally increased as the number, intensity and sophistication of attempted attacks and intrusions from around the world have increased and evolved. If we or our third-party vendors were to experience a significant cybersecurity incident or data breach of our or their information systems or data, the costs associated with the investigation, remediation and potential notification of the incident or breach to counter-parties and data subjects could be material. In addition, our remediation efforts may not be successful. If we do not allocate and effectively manage the resources necessary to

build and sustain the proper technology and cybersecurity infrastructure, we could suffer significant business disruption, including data loss or the loss of or damage to intellectual property or other proprietary information. There can also be no assurance that our and our third-party service providers’, strategic partners’, contractors’, consultants’, CROs’ and collaborators’ cybersecurity risk management program and processes, including policies, controls or procedures, will be fully implemented, complied with or effective in protecting our systems, networks and Confidential Information.

Like other companies in our industry, we, and our third party vendors, have experienced threats and cyberattacks relating to our information technology systems and infrastructure. While we do not believe that we have experienced any significant system failure, accident, cybersecurity incident or data breach to date, if such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our development programs and our business operations, whether due to a loss, corruption or unauthorized disclosure of our trade secrets, personal information or other proprietary or sensitive information or other similar disruptions. For example, the loss of clinical trial data from completed or ongoing clinical trials for any of our therapeutic candidates could result in delays in our development and regulatory approval efforts and significantly increase our costs to recover or reproduce the data.

If a cybersecurity incident, data breach or other disruption were to result in the unauthorized access to or unauthorized use, disclosure, release or other processing of personal information, it may be necessary to notify individuals, governmental authorities, supervisory bodies, the media and other parties pursuant to privacy and data security laws. Any security compromise affecting us, our service providers, strategic partners, other contractors, consultants, or our industry, whether real or perceived, could harm our reputation, erode confidence in the effectiveness of our security measures and lead to regulatory scrutiny. To the extent that any disruption, cybersecurity incident or data breach were to result in a loss of, or damage to, our data or systems, or inappropriate disclosure of confidential or proprietary or personal information, we could incur liability, including litigation exposure, penalties and fines, we could become the subject of regulatory action or investigation, our competitive position could be harmed and the further development and commercialization of our products and services could be delayed. If such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our business. Furthermore, any perceived non-compliance with federal, state and international laws and regulations could expose us to enforcement actions and investigations by regulatory authorities, and potentially result in regulatory penalties, fines and significant legal liability, if our information technology security efforts fail. Any adverse impact to the availability, integrity or confidentiality of our or third-party systems or Confidential Information can result in legal claims or proceedings (such as class actions), regulatory investigations and enforcement actions, fines and penalties, negative reputational impacts that cause us to lose existing or future customers, and/or significant incident response, system restoration or remediation and future compliance costs. We may also be exposed to a risk of loss or litigation and potential liability, which could materially and adversely affect our business, results of operations or financial condition.

Attacks upon information technology systems are increasing in their frequency, levels of persistence, sophistication and intensity, and are being conducted by sophisticated and organized groups and individuals with a wide range of motives and expertise. Furthermore, because the techniques used to obtain unauthorized access to, or to sabotage, systems change frequently and often are not recognized until launched against a target, we may be unable to anticipate these techniques or implement adequate preventative measures. We may also experience cybersecurity incidents or data breaches that may remain undetected for an extended period. Even if identified, we may be unable to adequately investigate or remediate incidents or breaches due to attackers increasingly using tools and techniques – including artificial intelligence – that are designed to circumvent controls, to avoid detection, and to remove or obfuscate forensic evidence.

Our contracts may 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 privacy and data security obligations. Further, our existing general liability and cyber liability insurance policies may not cover, or may cover only a portion of, any potential claims related to security breaches to which we are exposed or may not be adequate to indemnify us for all or any portion of liabilities that may be imposed. We also cannot be certain that our existing insurance coverage will continue to be available on acceptable terms or in amounts sufficient to cover the potentially significant losses that may result from a cybersecurity incident or breach or that the insurer will not deny coverage of any future claim. Accordingly, if our cybersecurity measures, and those of our service providers, fail to protect against unauthorized access, attacks (which may include sophisticated cyberattacks) and the mishandling of data by our employees and third-party service providers, then our reputation, business, results of operations and financial condition could be adversely affected.

We currently rely, and plan to rely on in the future, third parties to conduct and support our preclinical studies and clinical trials. If these third parties do not properly and successfully carry out their contractual duties or meet expected deadlines, we may not be able to obtain regulatory approval of or commercialize our product candidates.

We have utilized and plan to continue to utilize and depend upon independent investigators and collaborators, such as medical institutions, CROs, CMOs, consultants and strategic partners to conduct and support our preclinical studies and clinical trials. As a result, we will have less direct control over the conduct, timing and completion of these preclinical studies and clinical trials and the management of data developed. Nevertheless, we are responsible for ensuring that each of our studies is conducted in accordance with applicable protocol, legal and regulatory requirements and scientific standards, and our reliance on third parties does not relieve us of our regulatory responsibilities. We and these third parties are required to comply with GCP requirements, which are regulations and guidelines enforced by the FDA and comparable foreign regulatory authorities for product candidates in clinical development. Regulatory authorities enforce these GCP requirements through periodic inspections of trial sponsors, principal investigators and trial sites. If we or any of these third parties fail to comply with applicable GCP regulations, the clinical data generated in our clinical trials may be deemed unreliable and the FDA or comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing applications. We cannot assure you that, upon inspection, such regulatory authorities will determine that any of our clinical trials comply with the GCP regulations. In addition, our clinical trials must be conducted with pharmaceutical product produced under cGMP and comparable foreign regulations. Our failure or any failure by these third parties to comply with these regulations may require us to repeat clinical trials, which would delay the regulatory approval process. Moreover, our business may be implicated if any of these third parties violates federal or state fraud and abuse or false claims laws and regulations or healthcare privacy and security laws.

Further, these investigators and CROs are not our employees and we will not be able to control, other than by contract, the amount of resources, including time, which they devote to our product candidates and clinical trials. These third parties may also have relationships with other commercial entities, including our competitors, for whom they may also be conducting clinical trials or other product development activities, which could affect their performance on our behalf. If independent investigators or CROs fail to devote sufficient resources to the development of our product candidates, or if CROs do not successfully carry out their contractual duties or obligations or meet expected deadlines, if they need to be replaced or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated and we may not be able to obtain regulatory approval for or successfully commercialize our product candidates. As a result, our results of operations and the commercial prospects for our product candidates would be harmed, our costs could increase and our ability to generate revenues could be delayed or precluded entirely.

Our CROs have the right to terminate their agreements with us in the event of an uncured material breach. In addition, some of our CROs have an ability to terminate their respective agreements with us if it can be reasonably demonstrated that the safety of the subjects participating in our clinical trials warrants such termination, if we make a general assignment for the benefit of our creditors or if we are liquidated. If any of our relationships with these third-party CROs terminate, we may not be able to enter into arrangements with alternative CROs or to do so on commercially reasonable terms. Switching or adding additional CROs involves additional cost and requires management time and focus. In addition, there is a natural transition period when a new CRO commences work. As a result, delays occur, which can materially impact our ability to meet our desired clinical development timelines. Additionally, CROs may lack the capacity to absorb higher workloads or take on additional capacity to support our needs. Though we carefully manage our relationships with our CROs, there can be no assurance that we will not encounter similar challenges or delays in the future or that these delays or challenges will not have a material adverse impact on our business, financial condition and prospects.

We contract with third parties for the manufacture of our product candidates for preclinical studies and our ongoing clinical trials, and expect to continue to do so for additional clinical trials and ultimately for commercialization. This reliance on third parties increases the risk that we will not have sufficient quantities of our product candidates or ~~drugs~~be orable to obtain such ~~quantities~~product candidates at an acceptable cost, which could delay, prevent or impair our development or commercialization efforts. We also rely on a single-source supplier.

We do not currently have the infrastructure or internal capability to manufacture supplies of our product candidates for use in development, or if approved, eventual commercialization. We rely, and expect to continue to rely, on third-party manufacturers for the production of our product candidates for preclinical studies and clinical trials. We do not have long-term supply agreements with these manufacturers. Furthermore, the raw materials for our product candidates are sourced, in some cases, from a single-source supplier. If we were to experience an unexpected loss of supply of any of our product candidates or any of our future product candidates for any reason, whether as a result of manufacturing, supply or storage issues or otherwise, we could experience delays, disruptions, suspensions or terminations of, or be required to restart or repeat, any pending or ongoing clinical trials. For example, the extent to which the COVID-19 pandemic impacts our ability to procure sufficient supplies for the development of our products and product candidates will depend on the severity and duration of the spread of the virus, and the actions undertaken to contain COVID-19 or treat its effects.

our product candidates are sourced from a single-source supplier. Given this reliance on a single-source supplier, we are especially susceptible to supply shortages because we do not have alternate suppliers currently available. If we were to experience an unexpected loss of supply of any of our product candidates or any of our future product candidates for any reason, whether as a result of manufacturing, supply or storage issues or otherwise, we could experience delays, disruptions, suspensions or terminations of, or be required to restart or repeat, any pending or ongoing clinical trials.

We expect to continue to rely on third-party manufacturers for the commercial supply of any of our product candidates for which we obtain marketing approval. We may be unable to maintain or establish required agreements with third-party manufacturers 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:

•

the failure of the third party to manufacture our product candidates according to our schedule;

•

the reduction or termination of production or deliveries by suppliers, or the raising of prices or renegotiation of terms;

•

the termination or nonrenewal of agreements at a time that is costly or inconvenient for us;

•

the failure to comply with contractual obligations;

•

the failure to comply with applicable regulatory requirements;

•

the failure to manufacture our product candidates according to our specifications;

•

clinical supplies not being delivered to clinical sites on time;

•

disruptions to the operations of our third-party manufacturers or suppliers, testing facilities, or research sites caused by conditions unrelated to our business or operations, including unrelated regulatory action against or the bankruptcy of the manufacturer or supplier, testing facility, or research site, or the unavailability of essential personnel to conduct or complete our research or clinical trials, ~~such~~including as, ~~for example,~~ a result of ~~the~~public ~~COVID-19~~health ~~pandemic~~crises, pandemics, or similar events; and

•

the misappropriation of our proprietary information, including our trade secrets and know-how.

We do not have complete control over all aspects of the manufacturing process of, and are dependent on, our contract manufacturing partners for compliance with cGMP or comparable foreign regulations for manufacturing both active drug substances and finished drug products. Third-party manufacturers may not be able to comply with cGMP regulations or similar regulatory requirements outside of the United States. If our contract manufacturers cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA ~~others~~, they will not be able to secure and/or maintain marketing approval for their manufacturing facilities. In addition, we do not have control over the ability of our contract manufacturers to maintain adequate quality control, quality assurance and qualified personnel. If the FDA, ~~EMA~~ or comparable regulatory authority does not approve these facilities for the manufacture of our product candidates or if it withdraws any such approval in the future, we may need to find alternative manufacturing facilities, which would significantly impact our ability to develop, obtain marketing approval for or market our product candidates, if approved. Our failure, or the failure of our third-party manufacturers, to comply with applicable regulations could result in sanctions being imposed on us, including fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of product candidates or drugs, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our product candidates or drugs and harm our business and results of operations. Our current and anticipated future dependence upon others for the manufacture of our product candidates or drugs may adversely affect our future profit margins and our ability to commercialize any product candidates that receive marketing approval on a timely and competitive basis.

We have vendors and third party service providers located outside of the United States that subject us to additional risks that are beyond our control and that could harm our business, financial condition, results of operations, and prospects.

We currently and may in the future rely on foreign CROs and CMOs, such as WuXi AppTec. Such foreign CROs and CMOs may be subject to U.S. legislation, trade restrictions, sanctions, tariffs, and other regulatory requirements by the U.S. government, which could increase the cost or reduce the supply of material available to us or our partners or potential partners, delay the procurement or supply of such material or have an adverse effect on our or our partners’ or potential partners’ ability to secure significant commitments from governments to purchase potential therapies. For example, on December 18, 2025, the National Defense Authorization Act for Fiscal Year

2026 (NDAA) was signed into law, which includes the U.S. BIOSECURE Act which, in its current form, would prohibit federal agencies from procuring or using any biotechnology equipment or services from “biotechnology companies of concern”, or entering into, extending, or renewing any contracts with entities that use such biotechnology equipment or services from “biotechnology companies of concern” or expending loan or granting funds for biotechnology equipment services provided by “biotechnology companies of concern”, whether directly or through a loan or grant recipient. Congress has interpreted a “biotechnology company of concern” as an entity that is under the control of a foreign adversary and that poses a risk to national security based on its research or multiomic data collection (e.g., collection of genomic information). This includes companies identified on the U.S. Department of Defense's “Chinese military companies operating in the United States” list. Congress further authorizes the U.S. government to identify additional entities for inclusion as “biotechnology companies of concern.” While the U.S. BIOSECURE Act has a grandfathering period of five years for existing contracts and has carveouts for manufacture of drugs for supply under Medicaid and Medicare Part B, subject to the Secretary of Veteran Affairs’ discretion, the impact of the U.S. BIOSECURE Act on the biotechnology industry is uncertain. This and similar laws could have the potential to severely restrict the ability of U.S. biopharmaceutical companies like us or our partners to purchase services or products from, or otherwise collaborate with, certain Chinese biotechnology companies “of concern” without losing the ability to contract with, or otherwise receive funding from, the U.S. government. For example, with the U.S. BIOSECURE Act, we may be restricted in our ability to work with certain Chinese biotechnology manufacturing companies to the extent we would contract with, or otherwise receive funding from, the U.S. government. In addition, if we, our suppliers, or our customers were to be designated under the U.S. BIOSECURE Act, this could potentially cause harm to our business and financial condition. Furthermore, any U.S. executive action, legislative action or potential sanctions including the imposition of higher tariffs on imports into the United States and other governmental regulations affecting trade between the United States and China, and any retaliatory actions by China could materially impact our work or potential work in the future with Chinese biotechnology companies. United States executive agencies may designate entities and individuals on various governmental prohibited and restricted parties lists. Depending on the designation, potential consequences can range from a comprehensive prohibition on all transactions or dealings with designated parties, or a limited prohibition on certain types of activities, such as exports and financing activities, with designated parties. Such disruption could have adverse effects on the development of our product candidates. Without an alternative manufacturing plan, there is a risk that, if supplies are interrupted, or the quality of ingredients provided by such alternative sources is not to our specification, it would cause delays in our supply chain and increase the cost of manufacturing our drugs, which could materially harm our business.

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

The success of our business is dependent in large part on our continued ability to attract and retain our senior management, and other highly qualified personnel in our scientific, clinical, manufacturing and commercial organizations. Intense competition exists in the biopharmaceutical industry for these types of personnel. Our business is specialized and global and we must attract and retain highly qualified individuals across many geographies. We may not be able to continue to attract and retain the highly qualified personnel necessary for developing, manufacturing and commercializing our product candidates. If we are unsuccessful in our recruitment and retention efforts, or if our recruitment efforts take longer than anticipated, our business may be harmed. We may face difficulty in attracting and retaining key talent for a number of reasons, including management changes, the underperformance or discontinuation of one or more late-stage programs, recruitment by competitors or delays in the recruiting and hiring process asor aother ~~result~~factors ofbeyond ~~the~~our ~~COVID-19 pandemic or otherwise~~control. We cannot ensure that we will be able to hire or retain the personnel necessary for our operations or that the loss of any such personnel will not have a material impact on our financial condition and results of operations.

We are highly dependent on principal members of our senior management. While we have entered into employment agreements, consulting agreements or offer letters with each of our executive officers, any of them could leave our employment at any time. Recruiting and retaining other qualified employees, consultants and advisors for our business, including scientific and technical personnel, will also be critical to our success. Competition for skilled personnel is intense and the turnover rate can be high. We may not be able to attract and retain personnel on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies for individuals with similar skill sets. In addition, failure to succeed in preclinical studies or clinical trials may make it more challenging to recruit and retain qualified personnel. The inability to recruit or loss of the services of any executive, key employee, consultant or advisor may impede the progress of our research, development and commercialization objectives. If we fail to attract and retain highly qualified personnel, we may not be able to successfully develop, manufacture or commercialize our product candidates.

4554

~~We have experienced recent changes in management and other key personnel in critical functions across our organization, including in connection with the Zikani Merger.~~ Changes in management and other key personnel have the potential to disrupt our business, and any such disruption could adversely affect our operations, programs, growth, financial condition or results of operations. In addition, new members of management may have different perspectives on programs and opportunities for our business, which may cause us to focus on new business opportunities or reduce or change emphasis on our existing business programs. Further, if members of our management and other key personnel in critical functions across our organization are unable to perform their duties, we may not be able to execute on our business strategy and/or our operations may be negatively impacted.

To manage effectively our current and future potential growth, we must also continue to enhance and develop our global employee base, and our operational and financial processes. Supporting our growth strategy will require significant capital expenditures and management resources, including investments in research, development, sales and marketing, manufacturing and other areas of our operations. The development or expansion of our business, any acquired business or any acquired or in-licensed products may require a substantial capital investment by us. We may not have these necessary funds, or they might not be available to us on acceptable terms or at all. We may also seek to raise funds by selling shares of our capital stock, or securities convertible into our capital stock, which could dilute current stockholders’ ownership interest in the Company.

We have a limited number of employees, which could adversely affect our business and operations.

We are a small company with a limited number of employees. As of December 31, 2025, we had ten full-time employees. Because we have a limited number of employees, each employee is responsible for multiple critical functions within our organization. This concentration of responsibilities in a small number of individuals may affect the operation of our business and we may not be able to quickly or adequately replace the experience and expertise of departing personnel.

Our employees and independent contractors, including collaborators, principal investigators, CROs, consultants and vendors, may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements.

We are exposed to the risk that our employees and independent contractors, including collaborators, principal investigators, CROs, consultants and vendors may engage in misconduct or other illegal activity. Misconduct by these parties could include intentional, reckless and/or negligent conduct or disclosure of unauthorized activities to us that violate: (i) the laws and regulations of the FDA and other comparable foreign regulatory requirements, including those laws that require the reporting of true, complete and accurate information to such authorities, (ii) manufacturing standards, including cGMP requirements, (iii) federal and state data privacy, security, fraud and abuse and other healthcare laws and regulations in the United States and abroad, (iv) laws that require the true, complete and accurate reporting of financial information or data, or (v) laws that prohibit insider trading. Activities subject to these laws also involve the improper use or misrepresentation of information obtained in the course of clinical trials, the creation of fraudulent data in our or our collaborators’ preclinical studies or clinical trials, or illegal misappropriation of drug product, which could result in regulatory sanctions and cause serious harm to our reputation. It is not always possible to identify and deter misconduct by employees and other third parties, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations. In addition, we are subject to the risk that a person or government could allege such fraud or other misconduct, even if none occurred. If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business and financial results, including, without limitation, the imposition of significant civil, criminal and administrative penalties, damages, monetary fines, disgorgements, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, imprisonment, contractual damages, reputational harm, diminished profits and future earnings, 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 and curtailment of our operations, any of which could adversely affect our business, financial condition, results of operations and prospects.

We may engage in strategic transactions that could impact our liquidity, increase our expenses, and present significant distractions to our management.

We have in the past, and may in the future consider strategic transactions, such as acquisitions of companies, asset purchases, and out-licensing or in-licensing of intellectual property, products or technologies. Additional potential transactions that we may consider in the future include a variety of business arrangements, including spin-offs, strategic partnerships and collaborations, joint ventures, restructurings, divestitures, business combinations, and investments. We may not be able to find suitable partners or acquisition candidates, and we may not be able to complete such transactions on favorable terms, if at all.

Any future transactions could increase our near and long-term expenditures, result in potentially dilutive issuances of our equity securities, including our common stock, or the incurrence of debt, contingent liabilities, amortization expenses or acquired in-process research and development expenses, any of which could affect our financial condition, liquidity and results of operations. Future acquisitions may also require us to obtain additional financing, which may not be available on favorable terms or at all. These transactions may never be successful and may require significant time and attention of our management. The integration of any business that we may acquire in the future may disrupt our existing business and may be a complex, risky and costly endeavor for which we may never realize the full benefits. Furthermore, we may experience losses related to investments in other companies, including as a result of failure to realize expected benefits or the materialization of unexpected liabilities or risks, which could have a material negative effect on our results of operations and financial condition. Accordingly, although there can be no assurance that we will undertake or successfully complete any additional transactions of the nature described above, any additional transactions that we do complete could have a material adverse effect on our business, financial condition, results of operations and prospects.

Risks Related to Intellectual Property

AsWe ~~of December 31~~rely, ~~2022,~~and wemay ~~owned~~in orthe ~~licensed~~future 66rely, ~~issued~~upon ~~patents~~a ~~and~~combination ~~101~~of ~~pending~~ patent, ~~applications~~trade insecret ~~the U.S.~~ and ~~abroad,~~trademark ~~not~~protection ~~including~~for ~~U.S.~~our ~~provisional~~product ~~applications.~~candidates ~~However,~~and ~~with~~proprietary ~~regard~~technologies to ~~the~~prevent ~~pending~~third ~~applications,~~parties ~~the~~from ~~filing~~exploiting ofour aachievements, ~~patent~~thus ~~application~~eroding ~~does~~our ~~not~~competitive ~~mean~~position ~~that~~in weour ~~will~~market. beThese ~~issued~~legal ameasures ~~patent~~afford only limited protection, orand ~~that~~competitors ~~any~~or ~~patent~~others ~~eventually~~may ~~issued~~gain ~~will~~access beto asor ~~broad~~use asour ~~requested~~intellectual inproperty ~~the~~and ~~patent~~proprietary ~~application~~information. orOur ~~sufficient~~success todepends ~~protect~~in ~~our~~large ~~technology.~~part ~~Any~~on ~~modification~~our ~~required~~ability to aobtain, ~~currently~~maintain, ~~pending~~expand, ~~patent~~enforce, ~~application~~and ~~may~~defend ~~delay~~ the ~~approval~~scope, ofownership ~~such~~or ~~patent~~control, ~~application~~validity ~~which~~and ~~could~~enforceability ~~have~~of aour ~~material~~intellectual ~~adverse~~property ~~effect~~protection onin ~~our~~the ~~business,~~United ~~results~~States ofand ~~operations~~other ~~and~~countries ~~financial~~with ~~condition.~~respect Into ~~addition,~~our ~~there~~product ~~are~~candidates aand ~~number~~other ofproprietary ~~factors~~technologies ~~that~~we ~~could~~may ~~cause~~develop. ~~our~~We ~~current~~generally orseek, ~~future~~and ~~issued~~may ~~patents~~in tothe ~~become~~future ~~invalid~~seek, orto ~~unenforceable~~protect orour ~~that~~proprietary ~~could~~position, ~~cause~~in ~~our~~part, ~~pending~~by filing patent applications toin ~~not~~the beUnited ~~granted,~~States ~~including~~and ~~known~~abroad orrelating ~~unknown~~to ~~prior~~our ~~art,~~product ~~deficiencies~~candidates inand ~~the~~technology, ~~patent~~manufacturing ~~application~~processes orand ~~lack~~methods of ~~originality~~use. ofWe ~~the~~also ~~technology.~~seek, ~~Our~~and ~~competitive~~may ~~position~~in ~~and~~the future ~~revenue~~seek, ~~will~~to ~~depend~~protect inour ~~part~~proprietary onposition ~~our~~by ~~ability~~acquiring ~~and~~or ~~the~~in-licensing ~~ability~~relevant ofissued ~~our~~patents ~~licensors~~or ~~and~~pending ~~collaborators~~patent toapplications ~~obtain~~from ~~and~~third ~~maintain~~parties. ~~patent~~If ~~protection~~we ~~for~~are ~~our~~unable ~~product~~to ~~candidates~~obtain, ~~methods~~maintain, ~~processes and other technologies~~expand, toenforce ~~preserve~~and ~~our~~defend ~~trade~~the ~~secrets~~scope, toownership ~~prevent~~or ~~third~~control, ~~parties~~validity ~~from~~and ~~infringing~~enforceability onof our ~~proprietary~~intellectual ~~rights~~property ~~and~~protection, toour ~~operate~~business, ~~without~~financial ~~infringing~~condition, ~~the~~results ~~proprietary~~of ~~rights~~operations ofand ~~third~~prospects ~~parties.~~could ~~However,~~be wematerially ~~cannot~~harmed. ~~predict:~~

Changes in either the patent laws or their interpretation in the United States and other jurisdictions may diminish our ability to protect, obtain, maintain, expand, enforce and defend our intellectual property rights and, more generally, could affect the value of our intellectual property or narrow the scope of our protection. We cannot predict whether the patent applications we currently pursue or in-license, or may in the future pursue or in-license, will issue as patents in any particular jurisdiction, or whether any patent that eventually issues will be as broad as requested in the patent application or be sufficient to protect our technology. There are a number of factors that could cause our current or future issued patents to become invalid or unenforceable or that could cause our pending patent applications to not be granted, including known or unknown prior art, deficiencies in the patent application or lack of originality of the technology. The existence of unpublished patent applications or future patents owned by third parties could limit our freedom to operate even where our own patent applications issue. Patent applications are commonly kept confidential for a period after filing, and such unpublished applications may later issue with claims that cover aspects of our product candidates, manufacturing processes or methods of use. As a result, we may be required to obtain licenses on terms that are not commercially reasonable, modify or redesign our products or processes, or cease certain activities, any of which could materially and adversely affect our business, prospects and financial condition. Our competitive position and future revenue will depend in part on our ability and the ability of

our licensors and collaborators to obtain and maintain patent protection for our product candidates, methods, processes and other technologies, to preserve our trade secrets, to prevent third parties from infringing on our proprietary rights and to operate without infringing the proprietary rights of third parties. However, we cannot predict:

•

the degree and range of protection any patents will afford us against competitors and those who infringe upon our patents, including whether third parties will find ways to invalidate or otherwise circumvent our licensed patents;

•

if and when patents will issue;

•

whether or not others will obtain patents claiming aspects similar to those covered by our owned or licensed patents and patent applications; or

•

whether we will need to initiate litigation or administrative proceedings, which may be costly, and whether we win or lose.

If patent rights covering our products or technologies are not sufficiently broad, they may not provide us with sufficient proprietary protection or competitive advantages against competitors with similar products and technologies. Furthermore, if the U.S. Patent and Trademark Office or foreign patent offices issue patents to us or our licensors, others may challenge the patents or circumvent the patents, or the patent office or the courts may invalidate the patents. Thus, any patents we own or license from or to third parties may not provide any protection against our competitors and those who infringe upon our patents.

Furthermore, the lives of our patents are limited. With regard to our lead compound ~~ELX-02~~exaluren, patents that have issued or that may issue in the future from our primary composition of matter patent family are currently set to expire in 2031. We ~~have pending patent families directed to specific methods of manufacturing ELX-02 and using ELX-02 to treat various ocular conditions, and any patents that~~ may issue from these families would be expected to expire in 2038 and 2039, respectively. However, these applications may not issue, and even if they do issue the resultant patents may not provide adequate coverage to meaningfully block competitors from launching their products. We will likely pursue additional patent protection relating to ~~ELX-02~~exaluren in the future, including for example additional methods of use or manufacture, specific formulations, or combinations of ~~ELX-02~~exaluren with other therapeutic agents. However, ~~as with our pending patent families,~~ any applications we file in the future may not issue or may not result in adequate coverage to adequately protect our assets.

46Depending upon the timing, duration, and conditions of any FDA marketing approval for exaluren, one or more of our patents may be eligible for patent term extension of up to five years under the Hatch-Waxman Act. However, we may not receive an extension if we fail to exercise due diligence during the testing phase or regulatory review process, fail to apply for an extension within applicable deadlines, fail to apply prior to expiration of relevant patents or otherwise fail to satisfy applicable requirements. Moreover, the length of the extension could be less than we request. Only one patent per approved product can be extended, the extension cannot extend the total patent term beyond 14 years from the date of product approval and only those claims covering the approved drug, an approved method of using the approved drug, or a method of manufacturing the approved drug may be extended. If we are unable to obtain patent term extension or the term of any such extension is less than we request, the period during which we can enforce our patent rights for exaluren will be shortened and our competitors may obtain approval to market competing products sooner. As a result, our revenue from applicable products could be reduced. Further, if this occurs, our competitors may take advantage of our investment in development and clinical trials by referencing our clinical and preclinical data and launch their product earlier than might otherwise be the case, and our business could be harmed.

Depending upon the timing, duration, and conditions of any FDA marketing approval for ELX-02, one or more of our patents may be eligible for patent term extension of up to five years under the Hatch-Waxman Act. However, we may not receive an extension if we fail to exercise due diligence during the testing phase or regulatory review process, fail to apply for an extension within applicable deadlines, or otherwise fail to satisfy applicable requirements. Moreover, the length of the extension could be less than we request. Only one patent per approved product can be extended, the extension cannot extend the total patent term beyond 14 years from approval and only those claims covering the approved drug, an approved method of using the approved drug, or a method of manufacturing the approved drug may be extended. If we are unable to obtain patent term extension or the term of any such extension is less than we request, the period during which we can enforce our patent rights for ELX-02 will be shortened and our competitors may obtain approval to market competing products sooner. As a result, our revenue from applicable products could be reduced. Further, if this occurs, our competitors may take advantage of our investment in development and trials by referencing our clinical and preclinical data and launch their product earlier than might otherwise be the case, and our business could be harmed.

If we cannot obtain new patents, maintain our existing patents and protect the confidentiality and proprietary nature of our trade secrets and other intellectual property, our business and competitive position may be harmed.

Our success will depend in part on our ability to obtain and maintain patent and regulatory protections for our product candidates and their intended uses, to preserve our trade secrets and other proprietary rights, to operate without infringing the proprietary rights of third parties, and to prevent third parties from circumventing our rights. Due to the time and expense of bringing new product candidates through development and regulatory approval to the marketplace, there is particular importance in obtaining patent and trade secret protection for significant new technologies, products and processes. In addition, we may be subject to increased risks of trade secret misappropriation or cyber intrusion by nation-state or state-sponsored actors seeking to obtain proprietary biotechnology or pharmaceutical information. Such actors may possess substantial financial and technological resources, and our security measures may not be sufficient to prevent unauthorized access to our trade secrets or other confidential information. Any such misappropriation could materially harm our competitive position.

We have and may in the future obtain patents or the right to practice patents through ownership or license. Our patent applications may not result in the issue of patents in the U.S. or other countries. Our patents may not afford adequate protection for our products. Third parties may challenge our patents. If any of our patents are narrowed, invalidated or become unenforceable, competitors may develop and market products similar to ours that do not conflict with or infringe our patents rights, which could have a material adverse effect on our financial condition. We may also finance and collaborate in research conducted by government organizations, hospitals, universities or other educational or research institutions. Such research partners may be unwilling to grant us exclusive rights to technology or products developed through such collaborations. There is also a risk that disputes may arise as to the rights to technology or products developed in collaboration with other parties. Our product candidates are expensive and time-consuming to test and develop. Even if we obtain and maintain patents, our business may be significantly harmed if the patents are not broad enough to protect our products from copycat products.57

~~Significant~~We ~~legal~~have ~~questions~~obtained, ~~exist~~and ~~concerning~~may in the ~~extent~~future ~~and~~obtain, ~~scope~~patents ofor rights to practice patents through ownership or license. Our patent ~~protection~~applications ~~for~~may ~~biopharmaceutical~~not ~~products~~result ~~and~~in ~~processes~~the issue of patents in the ~~U.S.~~United ~~and~~States ~~elsewhere~~or other countries. ~~Accordingly,~~Our ~~there~~patents ismay nonot ~~certainty~~afford ~~that~~adequate ~~patent~~protection ~~applications~~for ~~owned~~our orproducts. ~~licensed~~Third byparties usmay ~~will~~challenge ~~issue~~our aspatents. If any of our patents are narrowed, invalidated or become unenforceable, competitors may develop and market products similar to ours that ~~our~~do ~~issued~~not conflict with or infringe our patents ~~will~~rights, ~~afford~~which ~~meaningful~~could ~~protection~~have ~~against~~a ~~competitors.~~material ~~Once~~adverse ~~issued,~~effect ~~patents~~on ~~are~~our ~~subject~~financial tocondition. ~~challenge~~We ~~through~~may ~~both~~also ~~administrative~~finance and ~~judicial~~collaborate ~~proceedings~~ in ~~the~~research ~~U.S.~~conducted ~~and~~by government organizations, hospitals, universities or other ~~countries~~educational or research institutions. ~~Such~~To ~~proceedings~~the ~~include~~extent ~~re-examinations~~any related intellectual property is developed with government funding or under statutory regimes that attach rights to government sponsors, ~~inter~~applicable ~~partes~~laws ~~reviews~~may give governments certain rights in inventions, ~~post~~including non-~~grant~~exclusive ~~reviews~~licenses, ~~and~~march-in ~~interference~~rights ~~proceedings~~or ~~before~~ the Uability to require licensing under specified circumstances.S. ~~Patent~~In ~~and~~addition, ~~Trademark~~government ~~Office~~authorities may impose compulsory licensing, asrequire ~~well~~domestic asmanufacturing ~~opposition~~or ~~proceedings~~take ~~before~~title if disclosure or filing requirements are not satisfied. The exercise of any such governmental rights or remedies, particularly in the ~~European~~context ~~Patent~~of ~~Office~~public ~~and~~health emergencies or other ~~non~~policy-~~U.S.~~driven ~~patent~~actions, ~~offices~~could materially reduce the exclusivity, commercial value or enforceability of our intellectual property rights. ~~Litigation~~Such research partners may be ~~required~~unwilling to ~~enforce,~~grant ~~defend~~us exclusive rights to technology or ~~obtain~~products ~~our~~developed ~~patent~~through ~~and~~such ~~other~~collaborations. ~~intellectual~~There ~~property~~is also a risk that disputes may arise as to the rights to technology or products developed in collaboration with other parties. ~~Any~~Our ~~administrative~~product ~~proceeding~~candidates orare ~~litigation~~expensive ~~could~~and ~~require~~time-consuming ato ~~significant~~test ~~commitment~~and ofdevelop. ~~our~~Even ~~resources~~if we obtain and maintain patents, ~~depending~~our onbusiness ~~outcome,~~may ~~could~~be ~~adversely~~significantly ~~affect~~harmed if the ~~scope,~~patents ~~validity~~are ornot ~~enforceability~~broad ofenough ~~certain~~to ofprotect our ~~patent~~products orfrom ~~other~~copycat ~~proprietary rights~~products.

Significant legal questions exist concerning the extent and scope of patent protection for biopharmaceutical products and processes in the United States and elsewhere. In Europe, the introduction of the Unitary Patent and Unified Patent Court (the “UPC”) regime presents additional uncertainty. Under the UPC, certain European patents may be subject to centralized revocation or infringement proceedings with pan-European effect; an adverse decision in such a proceeding could invalidate or limit our patent rights across multiple European states simultaneously. Patent owners may in some cases elect to opt out of UPC jurisdiction, but failure to comply with applicable timing or procedural requirements may leave patents subject to UPC review. Given the relative novelty of the UPC and its developing jurisprudence, this new regime may materially affect our European patent strategy, enforcement options and the value of our European patent portfolio. Accordingly, there is no certainty that patent applications owned or in-licensed by us will issue as patents, or that our issued patents will afford meaningful protection against competitors. Once issued, patents are subject to challenge through both administrative and judicial proceedings in the United States and other countries. Such proceedings include re-examinations, inter partes reviews, post-grant reviews, interference proceedings and derivation proceedings before the U.S. Patent and Trademark Office, as well as opposition proceedings before the European Patent Office and other non-U.S. patent offices. Litigation may be required to enforce, defend or obtain our patent and other intellectual property rights. Any administrative proceeding or litigation could require a significant commitment of our resources and, depending on outcome, could adversely affect the scope, validity or enforceability of certain of our patent or other proprietary rights.

In addition, our business requires using sensitive technology, techniques and proprietary compounds that we protect as trade secrets. However, we may also rely heavily on collaboration with, or discuss the potential for collaboration with, suppliers, outside scientists and other biopharmaceutical companies. Collaboration and discussion of potential collaboration present a strong risk of exposing our trade secrets. If our trade secrets were exposed, it would help our competitors and adversely affect our business prospects.

If we are found to be infringing on patents owned by others, we may be forced to pay damages to the patent owner and/or obtain a license to continue the ~~manufacture~~development, ~~sale~~manufacture or ~~development~~sale of our product candidates. If we cannot obtain a license, we may be prevented from the ~~manufacture~~development, ~~sale~~manufacture or ~~development~~sale of our product candidates, which would adversely affect our business.

We have not received to date any claims of infringement by any third parties. However, as our product candidates progress into clinical trials and commercialization, if at all, our public profile and that of our product candidates may be raised and generate such claims. Defending against such claims, and occurrence of a judgment adverse to us, could result in unanticipated costs and may have a material adverse effect on our business and competitive position. If our products, methods, processes and other technologies infringe the proprietary rights of other parties, we may incur substantial costs and we may have to:

•

obtain licenses, which may not be available on commercially reasonable terms, if at all;

•

redesign our products or processes to avoid infringement, which could significantly impede development and impair or block our ability to secure regulatory approval of any redesigned product or process;

•

stop using the subject matter claimed in the patents held by others, which could cause us to lose the use of one or more of our product candidates;

•

defend litigation or administrative proceedings that may be costly whether we win or lose, and which could result in a substantial diversion of management resources; or

•

pay damages, including treble damages and attorneys’ fees for willful infringement.

Any costs incurred in connection with such events or the inability to develop or sell our products may have a material adverse effect on our business, results of operations and financial condition.

We rely on confidentiality agreements that could be breached and may be difficult to enforce which could have a material adverse effect on our business and competitive position.

Our policy is to enter agreements relating to the non-disclosure of confidential information with third parties, including our contractors, CROs, contract manufacturers, consultants, advisors and research collaborators, as well as agreements that purport to require the disclosure and assignment to us of the rights to the ideas, developments, discoveries and inventions of our employees and consultants while we employ them. However, these agreements can be difficult and costly to enforce. Moreover, to the extent that our contractors, CROs, contract manufacturers, consultants, advisors and research collaborators apply or independently develop intellectual property in connection with any of our projects, disputes may arise as to the proprietary rights to the intellectual property. If a dispute arises, a court may determine that the rights belong to a third party, and enforcement of our rights can be costly and unpredictable. In addition, we rely on trade secrets and proprietary know-how that we seek to protect in part by confidentiality agreements with our employees, contractors, CROs, contract manufacturers, consultants, advisors and other third parties. Despite the protective measures we employ, we still face the risk that:

•

we may not have entered into applicable agreements with each party that may have or have had access to our trade secrets or proprietary technology and processes;

•

these agreements may be breached;

•

these agreements may not provide adequate remedies for the applicable type of breach; or

•

we may not effectively monitor unauthorized uses and disclosures, and we do not know whether the steps we have taken to protect our proprietary technologies will be effective; or

•

our trade secrets or proprietary know-how will otherwise become known.

Any breach of our confidentiality agreements or our failure to effectively enforce such agreements may have a material adverse effect on our business and competitive position.

If we cannot meet requirements under our license agreement, we could lose the rights to our product candidates, which could have a material adverse effect on our business.

We depend on the license ~~agreement~~agreements with ~~TRDF~~Technion Research and Development Foundation Ltd. and Fellows of Harvard College to maintain the intellectual property rights to certain of our product candidates. Our license agreement requires us to make payments and satisfy performance obligations in order to maintain our rights under this agreement. This agreement lasts either throughout the life of the patents that are the subject of the agreement, or with respect to other licensed technology, for a number of years after the first commercial sale of the relevant product.

In addition, we are responsible for the cost of filing and prosecuting certain patent applications and maintaining certain issued patents licensed to us. If we do not meet our obligations under our license agreement in a timely manner, we could lose the rights to our proprietary technology, which could have a material adverse effect on our business, results of operations and financial condition.

We may become involved in lawsuits to protect or enforce or defend our intellectual property, which could be expensive, time consuming and unsuccessful and have an adverse effect on the success of our business.

Competitors or other third parties may infringe, misappropriate or otherwise violate our patents or other intellectual property. If we or one of our licensors were to initiate legal proceedings against a third party to enforce a patent covering one of our products or product candidates, the defendant could counterclaim that our patent is invalid or unenforceable. In patent litigation in the United States and in Europe, defendant counterclaims alleging invalidity or unenforceability are commonplace. Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, for example, lack of novelty, obviousness, lack of written description, or non-enablement. Third parties might allege unenforceability of our patents because during prosecution of the patent an individual connected with such prosecution withheld relevant information or made a misleading statement. Interference or derivation proceedings provoked by third parties or brought by us or declared by the USPTO may be necessary to determine the priority of inventions with respect to our patents or patent applications. The outcome of proceedings involving assertions of invalidity and unenforceability during patent litigation is unpredictable. If a defendant were to prevail on a legal assertion of invalidity or unenforceability, we would lose at least part, and perhaps all, of the patent protection on our products and product candidates, which may allow third parties to commercialize our technology or products and compete directly with us, without payment to us, or could require us to obtain license rights from the prevailing party in order to be able to manufacture or commercialize our products, product candidates or technologies without infringing third-party patent rights. Even if a defendant does not prevail on a legal assertion of invalidity or unenforceability, our patent claims may be construed in a manner that would limit our ability to enforce such claims against the defendant and others. Moreover, 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 our product candidates. Accordingly, despite our efforts, we may not be able to prevent third parties from infringing upon, misappropriating or otherwise violating our intellectual property rights. Thus, even if we were to ultimately prevail, or to settle at an early stage, such litigation could burden us with substantial unanticipated costs. Our patents and other intellectual property rights also will not protect our technology if competitors design around our protected technology without infringing our patents or other intellectual property rights.59

WeCompetitors or other third parties may beinfringe, ~~subject~~misappropriate or otherwise violate our patents or other intellectual property. If we or one of our licensors were to initiate legal proceedings against a third- party ~~claims~~to ~~including~~enforce ~~infringement,~~a ~~interference~~patent covering one of our products or ~~derivation~~product ~~proceedings~~candidates, ~~post-grant~~the ~~review~~defendant ~~and~~could ~~inter~~counterclaim ~~partes~~that ~~review~~such ~~before~~patent ~~the~~is ~~USPTO~~invalid or ~~similar~~unenforceable. ~~adversarial~~In ~~proceedings~~patent or litigation in ~~other~~the ~~jurisdictions.~~United ~~Even~~States ifand wein ~~believe~~Europe, ~~such~~defendant ~~claims~~counterclaims alleging invalidity or unenforceability are ~~without~~commonplace. ~~merit,~~Grounds for a ~~court~~validity challenge could ~~hold~~be ~~that~~an ~~these~~alleged ~~third-party~~failure ~~patents~~to ~~are~~meet ~~valid,~~any ~~enforceable~~of ~~and~~several ~~infringed~~statutory requirements, ~~and~~for ~~the~~example, ~~holders~~lack of ~~any~~novelty, ~~such~~obviousness, ~~patents~~lack ~~may~~of bewritten ~~able~~description, non-enablement, failure to ~~block~~claim patent-eligible subject matter or obviousness-type double patenting. Third parties might allege unenforceability of our ~~ability~~patents tobecause ~~commercialize~~during prosecution of the ~~applicable~~patent ~~product~~an orindividual ~~product~~connected ~~candidates~~with ~~unless~~such weprosecution ~~obtained~~withheld arelevant ~~license~~information ~~under~~from the ~~applicable~~USPTO ~~patents,~~or made a misleading or ~~until~~inconsistent ~~such~~statement. ~~patents~~Interference ~~expire~~or derivation proceedings provoked by third parties or ~~are~~brought ~~finally~~by ~~determined~~us toor declared by the USPTO may be ~~invalid~~necessary to determine the priority of inventions with respect to our patents or ~~unenforceable~~patent applications. ~~Because~~The outcome of proceedings involving assertions of invalidity and unenforceability during patent ~~applications~~litigation ~~can~~is ~~take~~unpredictable. ~~many~~If ~~years~~a defendant were to ~~issue~~prevail on a legal assertion of invalidity or unenforceability, ~~there~~we ~~may~~would belose ~~currently~~at ~~pending~~least part, and perhaps all, of the patent ~~applications~~protection on our products and product candidates, which may ~~later~~allow ~~result~~third parties to commercialize our technology or products and compete directly with us, without payment to us, or could require us to obtain license rights from the prevailing party in ~~issued~~order ~~patents~~to ~~that~~be able to manufacture or commercialize our products, product candidates or technologies ~~may~~without ~~infringe~~infringing third-party patent rights. InEven ~~addition~~if a defendant does not prevail on a legal assertion of invalidity or unenforceability, ~~third~~our ~~parties~~patent claims may ~~obtain~~be ~~patents~~construed in a manner that would limit our ability to enforce such claims against the ~~future~~defendant and ~~claim~~others. ~~that~~Moreover, ~~use~~if the breadth or strength of protection provided by our ~~technologies~~patents ~~infringes~~and ~~upon~~patent ~~these~~applications ~~patents.~~is Ifthreatened, ~~any~~it ~~third-party~~could ~~patents~~dissuade ~~were~~companies ~~held~~from bycollaborating awith ~~court~~us to ~~cover~~license, ~~aspects~~develop ofor commercialize our ~~products,~~ product candidates. Accordingly, despite our efforts, we may not be able to prevent third parties from infringing upon, misappropriating or ~~technologies~~otherwise violating our intellectual property rights. Thus, ~~the~~even ~~holders~~if ofwe ~~any~~were to ultimately prevail, or to settle at an early stage, such litigation could burden us with substantial unanticipated costs. Our patents ~~may~~and beother ~~able~~intellectual toproperty ~~prohibit~~rights also will not protect our ~~commercialization~~technology if competitors design around our protected technology without infringing our patents or other intellectual property rights. Further, geopolitical developments, including actions taken by certain countries in connection with regional conflicts, may affect the enforceability of intellectual property rights. For example, governmental measures in certain jurisdictions have limited the ~~applicable~~enforcement ~~product~~of orpatents ~~product~~owned ~~candidate~~by ~~until~~entities ~~such~~from ~~patent~~particular ~~expires~~countries. orIf issimilar ~~finally~~measures ~~determined~~are adopted in jurisdictions relevant to beour ~~invalid~~business, orour ~~unenforceable~~ability orto ~~unless~~enforce weour ~~obtained~~intellectual aproperty ~~license~~rights could be materially impaired.

InWe ~~addition,~~may ~~defending~~be ~~such~~subject to third-party claims ~~would~~including ~~cause~~infringement, usinterference toor ~~incur~~derivation ~~substantial~~proceedings, ~~expenses~~post-grant review and, ifinter ~~successful,~~partes ~~could~~review ~~cause~~before usthe toUSPTO ~~pay~~or ~~substantial~~similar ~~damages~~adversarial proceedings or litigation in other jurisdictions. Even if we ~~are~~believe ~~found~~such toclaims beare ~~infringing~~without merit, a ~~third~~court ~~party’s~~could ~~patent~~hold ~~rights.~~that ~~These~~these ~~damages~~third-party ~~potentially~~patents ~~include~~are ~~royalties~~valid, ~~increased~~enforceable ~~damages~~and ~~(possibly~~infringed ~~treble~~by ~~damages)~~us, and ~~attorneys’~~the ~~fees~~holders ifof weany ~~are~~such ~~found~~patents may be able to ~~have~~block ~~infringed~~our ~~such~~ability ~~rights~~to ~~willfully.~~commercialize ~~Further,~~the ifapplicable aproduct ~~patent~~or ~~infringement~~product ~~suit~~candidates isunless ~~brought~~we ~~against~~obtained ~~us,~~a ~~our~~license ~~development~~under the applicable patents, ~~manufacturing~~or until such patents expire or ~~sales~~are ~~activities~~finally ~~relating~~determined to ~~the~~be ~~product,~~invalid ~~product~~or ~~candidate~~unenforceable. orBecause ~~technology~~patent ~~that~~applications iscan ~~the~~take ~~subject~~many ofyears ~~the~~to ~~suit~~issue, there may be ~~delayed~~currently orpending ~~terminated,~~patent asapplications ~~parties~~which ~~making~~may ~~claims~~later ~~against~~result usin ~~may~~issued ~~obtain~~patents ~~injunctive~~that our products, product candidates or ~~other~~technologies ~~equitable~~may ~~relief~~infringe. AsIn aaddition, ~~result~~third ofparties ~~patent~~may ~~infringement~~obtain ~~claims,~~patents or in ~~order~~the tofuture ~~avoid~~and ~~potential~~claim ~~infringement~~that ~~claims,~~use weof ~~may~~our ~~choose~~technologies toinfringes ~~seek,~~upon orthese bepatents. ~~required~~If toany ~~seek,~~third-party apatents ~~license~~were ~~from~~held ~~the~~by ~~third~~a ~~party,~~court ~~which~~to ~~may~~cover ~~require~~aspects ~~payment~~ of ~~substantial~~our ~~royalties~~products, product candidates or ~~fees~~technologies, orthe ~~require~~holders usof toany ~~grant~~such apatents ~~cross-license~~may ~~under~~be ~~our~~able ~~intellectual~~to ~~property~~prohibit ~~rights.~~our ~~These~~commercialization ~~licenses~~of ~~may~~the ~~not~~applicable beproduct ~~available~~or onproduct ~~reasonable~~candidate ~~terms~~until orsuch atpatent ~~all.~~expires Ifor weis ~~are~~finally ~~unable~~determined to ~~enter~~be ~~into~~invalid aor ~~license~~unenforceable onor ~~acceptable~~unless ~~terms,~~ we ~~could~~obtained bea ~~prevented~~ license.

49In addition, defending such claims, regardless of their merit, would cause us to incur substantial expenses and, if unsuccessful, could cause us to pay substantial damages if we are found to be infringing a third party’s patent rights. These damages potentially include royalties, increased damages (possibly treble damages) and attorneys’ fees if we are found to have infringed such rights willfully. Further, if a patent infringement suit is brought against us, our development, manufacturing or sales activities relating to the product, product candidate or technology that is the subject of the suit may be delayed or terminated, as parties making claims against us may obtain injunctive or other equitable relief. As a result of patent infringement claims, or in order to avoid potential infringement claims, we may choose to seek, or be required to seek, a license from the third party, which may require payment of substantial royalties or fees, or require us to grant a cross-license under our intellectual property rights. These licenses may not be available on reasonable terms or at all and obtaining them may require substantial time and monetary expenditure. If we are unable to enter into a license on acceptable terms, we could be prevented from commercializing one or more of our products or product candidates, or forced to modify such products or product candidates, or to cease some aspect of our business operations, which could harm our business significantly. We might also be forced to redesign or modify our products, product candidates or technologies so that we no longer

from commercializing one or more of our products or product candidates, or forced to modify such products or product candidates, or to cease some aspect of our business operations, which could harm our business significantly. We might also be forced to redesign or modify our products, product candidates or technologies so that we no longer infringe the third-party intellectual property rights, which may result in significant cost or delay to us, or which redesign or modification could be impossible or technically infeasible.60

~~Even~~infringe ifthe wethird-party ~~were~~intellectual ~~ultimately to prevail, any of these events could require us to divert substantial financial and management resources that we would otherwise be able to devote to our business. Intellectual~~ property ~~litigation~~rights, ~~regardless~~which ~~of its outcome,~~ may ~~cause~~result ~~negative~~in ~~publicity,~~significant ~~adversely~~cost ~~impact prospective customers, cause product shipment delays,~~ or ~~prohibit~~delay usto ~~from manufacturing~~us, ~~importing, marketing~~ or ~~otherwise~~which ~~commercializing~~redesign ~~our products~~ or ~~product~~modification ~~candidates. Such litigation or proceedings~~ could substantially increase our operating losses and reduce our resources available for development activities. We may not have sufficient financial or other resources to adequately conduct such litigation or proceedings. Some of our competitors may be ~~able~~impossible ~~to sustain the costs of such litigation~~ or ~~proceedings~~technically ~~more effectively than we can because of their substantially greater financial resources~~infeasible. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could have an adverse effect on our ability to compete in the marketplace and could have an adverse impact on our business and financial condition.

Even if we were ultimately to prevail, any of these events could require us to divert substantial financial and management resources that we would otherwise be able to devote to our business. Intellectual property litigation, regardless of its outcome, may cause negative publicity, adversely impact prospective customers, cause product shipment delays, or prohibit us from manufacturing, importing, marketing or otherwise commercializing our products or product candidates. Such litigation or proceedings could substantially increase our operating losses and reduce our resources available for development activities. We may not have sufficient financial or other resources to adequately conduct such litigation or proceedings. Some of our competitors may be able to sustain the costs of such litigation or administrative proceedings more effectively than we can because of their substantially greater financial resources. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could have an adverse effect on our ability to compete in the marketplace and could have an adverse impact on our business and financial condition.

Risks Related to Our Regional Operations

Potential political and economic instability in regions where we conduct business may adversely affect our results of operations.

In addition to our operations in the United States, we currently conduct certain research and clinical development activities through our regional operations located in Israel. We also maintain a legal presence and contract with vendors located in Australia. We may, in the future, expand our presence and operations to other locations as circumstances require. Accordingly, political and economic conditions in any other country or region where we do business may directly affect our operations. As of December 31, 2025, three of our ten employees are based in Israel, and the loss or unavailability of these employees due to geopolitical events or other disruptions could adversely affect our research and development activities.

In October 2023, Hamas terrorists infiltrated Israel’s southern border from the Gaza Strip and conducted a series of attacks on civilian and military targets. Hamas also launched extensive rocket attacks on Israeli population and industrial centers located along Israel’s border with the Gaza Strip and in other areas within the State of Israel. These attacks resulted in extensive deaths, injuries and kidnapping of civilians and soldiers. Following the attack, Israel’s security cabinet declared war against Hamas and a military campaign against these terrorist organizations commenced in parallel to their continued rocket and terror attacks. In January 2025, Israel and Hamas entered into a ceasefire agreement, which remained in effect until March 18, 2025, when hostilities resumed. As of October 9, 2025, Israel and Hamas entered into a renewed ceasefire agreement calling for a permanent end of the war. However, there are no assurances that such as agreement will hold. While the conflict has created heightened security concerns, disruptions to business operations, and economic instability, the ceasefire may contribute to improved regional stability. However, the security situation remains fluid, and any renewed military actions, restrictions, or government-imposed measures could adversely affect our operations, supply chains, and financial condition.

Since the commencement of these events, there have been continued hostilities along Israel’s northern border with Lebanon (with the Hezbollah terror organization) and on other fronts from various extremist groups in region, such as the Houthis in Yemen and various rebel militia groups in Syria and Iraq. In October 2024, Israel began limited ground operations against Hezbollah in Lebanon, and in November 2024, a ceasefire was brokered between Israel and Hezbollah, but there are no guarantees as to whether the agreement will hold or whether further hostilities will resume.

In addition, in April 2024 and October 2024, Iran launched direct attacks on Israel involving hundreds of drones and missiles and has threatened to continue to attack Israel and is widely believed to be developing nuclear weapons. In June 2025, Israel launched a strike against Iran, aimed to disrupt Iran’s capacity to coordinate or launch hostilities against Israel. Iran has retaliated in response, firing missiles and drones at Israeli military and civilian infrastructure. In February 2026, Israel launched air attacks on Iran and Iran retaliated firing missiles targeted at Israel. Ongoing political instability, widespread protests, and heightened geopolitical tensions involving Iran, including the potential for military escalation and broader regional conflict, may adversely affect economic conditions, disrupt markets, and create uncertainty that could negatively impact our business, financial condition and results of operations. A broader regional conflict involving additional state and non-state actors remains a significant risk. Iran is also believed to have a strong influence among extremist groups in the region, such as Hamas in Gaza, Hezbollah in

Lebanon, the Houthi movement in Yemen and various rebel militia groups in Syria and Iraq. These situations may potentially escalate in the future to more violent events which may affect Israel and us.

In connection with the Israeli security cabinet’s declaration of war against Hamas and possible hostilities with other organizations, several hundred thousand Israeli military reservists were drafted to perform immediate military service. None of our employees or consultants were drafted. Although many of such military reservists have since been released, they may be called up for additional reserve duty, depending on developments in the war in Gaza and along Israel’s other borders. Military service call ups that result in absences of personnel from us for an extended period of time may materially and adversely affect our business, prospects, financial condition and results of operations. As of the date of this Annual Report, none of our directors, officers or employees are serving in active or reserve duty.

Since the war broke out on October 7, 2023, our operations have not been adversely affected by this situation, and we have not experienced disruptions to our clinical studies, facilities or the manufacturing or supply of our drug candidates. While the intensity and duration of the security situation in Israel have been difficult to predict, as were the economic implications on our business and operations and on Israel’s economy in general, the ceasefire marks a potential shift towards stability in the region. If sustained, this could reduce the risk of disruptions to our business and the Israeli economy in general. However, if the war is renewed or expands to other fronts, such as Lebanon, Syria and the West Bank, our operations may be harmed.

In particular, regional instability in the Middle East may lead to a deterioration in the political and trade relationship that exists between countries in the region, making it more difficult to conduct operations. In addition, our insurance does not cover losses that may occur as a result of an event associated with the security situation in the Middle East or for any resulting disruption in our operations. Although the Israeli government has in the past covered the reinstatement value of direct damages that were caused by terrorist attacks or acts of war, we cannot provide assurance that this government coverage will be maintained or, if maintained, will be sufficient to compensate us fully for damages incurred.

Furthermore, in the past, Israel and Israeli companies have been subjected to economic boycotts. Several countries still restrict business with Israel and with Israeli companies. These restrictive laws and policies, even though we are a U.S.-based company, may have an adverse impact on our operating results, financial conditions or the expansion of our business.

We received Israeli government grants for our research and development activities and programs. The terms of such grants may require us, in the future, to pay royalties and under certain circumstances, penalties in addition to payment of royalties.

Our research and development efforts were initially financed, in part, through royalty-bearing grants from the Israel Innovation Authority, or (“IIA”). We received an aggregate of $2.6 million from the IIA for the development of our technologies. With respect to such grants we are required to pay certain royalties (including accrued interest) up to $2.8 million. We are required to comply with the requirements of the Israeli Encouragement of Research, Development and Technological Innovation in the Industry Law, 5744-1984, as amended, and related regulations ("the “R&D Law"”) with respect to these past grants. If we fail to comply with the R&D Law, we may be required to refund certain grants previously received and/or to pay interest and penalties and we may become subject to criminal charges.

With respect to such grants we are obligated to pay royalties at a rate in the low to middle single -digit percentage from the revenue generated from the sale of any products or services developed using IIA grants up to a maximum amount equal to repayment of the grant proceeds received plus accrued interest. We have not commenced the payment obligation of these royalties since we have not yet generated revenue, and we have a contingent obligation with respect to such future royalty payments including interest, of $2.8 million.

50The R&D Law and terms of the prior grants restrict the transfer of certain know-how, and the transfer of manufacturing or manufacturing rights of products developed with grant funds, outside of Israel, without the prior approval of the IIA. Therefore, if aspects of our technologies are deemed to have been developed with IIA funding according to the R&D Law, the discretionary approval of the IIA may be required for any assignment and/or transfer to third parties inside or outside of Israel of know-how or transfer outside of Israel of manufacturing or manufacturing rights and may result in payment of increased royalties and/or payment of additional amounts to the IIA. Furthermore, the IIA may impose certain conditions on any arrangement under which it permits us to transfer

~~the payment obligation of these royalties since we have not yet generated revenue, and we have a contingent obligation with respect to such future royalty payments including interest, of $2.8 million.~~62

The R&D Law and terms of the prior grants restrict the transfer of certain know-how, and the transfer of manufacturing or manufacturing rights of products developed with grant funds, outside of Israel, without the prior approval of the IIA. Therefore, if aspects of our technologies are deemed to have been developed with IIA funding according to the R&D Law, the discretionary approval of the IIA may be required for any assignment and/or transfer to third parties inside or outside of Israel of know-how or transfer outside of Israel of manufacturing or manufacturing rights and may result in payment of increased royalties and/or payment of additional amounts to the IIA. Furthermore, the IIA may impose certain conditions on any arrangement under which it permits us to transfer technology or development outside of Israel. Such approvals may not be granted by the IIA and any conditions imposed may not be acceptable to the Company.

The R&D Law and the regulations promulgated thereunder provide that the transfer of IIA-supported technology or know-how outside of Israel may involve the payment of additional amounts depending upon the value of the transferred technology or know-how, the amount of IIA support, the time of completion of the IIA-supported research project and other factors, up to a maximum of six times the amount of grants received. These restrictions and requirements for payment may impair our ability to sell our technology assets outside of Israel or to outsource or transfer development or manufacturing activities with respect to any product or technology outside of Israel. Furthermore, the consideration available to our stockholders in a transaction involving the transfer outside of Israel of technology or know-how developed with IIA funding may be reduced by any amounts that we are required to pay to the IIA. Our obligations and limitations pursuant to the R&D Law are not limited in time and may not be terminated by us at will. As of the date hereof, we have not been required to pay any royalties with respect to the IIA grants.

We may become subject to claims for remuneration or royalties for assigned service invention rights by our employees, which could result in litigation and adversely affect our business.

We enter into agreements with our employees pursuant to which they agree that any inventions created inwithin the scope of their employment or engagement are assigned to us or owned exclusively by us,. ~~without~~These ~~the~~agreements ~~employee~~generally ~~retaining~~include ~~any~~provisions ~~rights.~~pursuant Ato ~~significant~~which ~~portion~~employees ofassign ~~our~~all ~~intellectual~~rights ~~property~~to ~~has~~such ~~been~~inventions ~~developed~~and bywaive ~~our~~any ~~employees~~claim infor ~~the~~royalties ~~course~~or ofother ~~their~~consideration ~~employment~~in ~~for~~respect usof service inventions. Under the Israeli Patent Law, 5727-1967 (the “Patent Law”), inventions conceived by an employee during the scope of his or her employment with a company are regarded as “service inventions,” which belong to the employer, absent a specific agreement ~~between~~providing ~~the employee and employer giving the employee service invention rights~~otherwise. The Patent Law ~~also~~further provides that if there is no ~~such~~ agreement addressing renumeration between an employer and an employee, the Israeli Compensation and Royalties Committee (the “Committee”), a body constituted under the Patent Law, ~~shall~~may determine whether the employee is entitled to remuneration for ~~his~~such ~~or her~~ inventions. ~~Previous~~Israeli ~~decisions~~case bylaw ~~the~~indicates ~~Committee~~that ~~have~~an ~~created~~employee ~~uncertainty~~may inwaive ~~this area regarding whether~~ the right to receive remuneration for service inventions, ~~can~~and bethe ~~voluntarily~~Committee ~~waived~~typically byexamines anthe ~~employee~~contractual ~~and~~framework ~~whether~~between ~~such~~the ~~waiver~~parties iswhen ~~enforceable.~~evaluating Insuch ~~addition~~claims. However, previous decisions by the Committee ~~determined~~have ~~that~~created ~~even~~uncertainty ifregarding such ~~right~~claims. toAlthough ~~receive~~we ~~compensation~~include assignment and ~~royalties~~waiver ~~for~~provisions ~~service~~in ~~inventions~~our employment agreements, we may benevertheless ~~waived,~~face ~~the~~claims ~~waiver~~seeking ~~should~~remuneration bein ~~specific~~respect of service inventions. ~~Subsequent~~Responding ~~court~~to ~~cases~~or ~~have~~defending ~~not~~against ~~provided~~such ~~significant~~claims ~~clarity~~could onresult ~~these~~in ~~matters~~legal costs and the diversion of management resources, which could adversely affect our business.

Risks Related to Our Common Stock

Our stock price may be volatile, and purchasers of our common stock could incur substantial losses.

The trading price of our common stock has been volatile and may continue to be volatile and subject to wide fluctuations in the future, especially following our delisting from the Nasdaq Capital Market in October 2023. Many factors could have an impact on our stock price, including fluctuations in our or our competitors’ operating results, clinical trial results or adverse events associated with our product candidates, product development by us or our competitors, changes in laws, including healthcare, regulatory, tax or intellectual property laws, intellectual property developments, acquisitions or other strategic transactions, changes in financial or operational estimates or projections and the perceptions of our investors that we are not performing or meeting expectations. The trading price of the common stock of many biopharmaceutical companies, including ours, has experienced extreme price and volume fluctuations, which have at times been unrelated to the operating performance of the companies whose stocks were affected. In addition, the securities market has from time-to-time experienced significant price and volume fluctuations that are not related to the operating performance of particular companies. These market fluctuations may also materially and adversely affect the market price of shares of our common stock.

51We are a smaller reporting company, and the reduced disclosure requirements applicable to smaller reporting companies may make our common stock less attractive to investors.

~~Our~~We ~~failure~~are a smaller reporting company as defined in the Exchange Act and expect to ~~meet~~remain a smaller reporting company for the ~~continued~~near ~~listing~~future. ~~requirements~~We may take advantage of ~~The~~certain ~~Nasdaq~~of ~~Capital~~the ~~Market~~scaled ~~could~~disclosures ~~result~~available into asmaller ~~delisting~~reporting companies and will be able to take advantage of these scaled disclosures for so long as our voting and non-voting common stock held by non-affiliates is less than $250.0 million measured on the last business day of our second fiscal quarter, or our annual revenue is less than $100.0 million during the most recently completed fiscal

~~If we fail to satisfy the continued listing requirements of The Nasdaq Capital Market, such as the minimum closing bid price requirement, Nasdaq may take steps to delist our common stock.~~ 63

~~For~~year ~~example,~~and onour ~~January~~voting 3,and ~~2022,~~non-voting we received a letter from the Listing Qualifications Department of The Nasdaq Stock Market ("Nasdaq Listing Qualifications") notifying us that, for the last 30 consecutive business days, the closing bid price for our common stock ~~has~~held ~~been~~by ~~below~~non-affiliates ~~the~~is ~~minimum~~less than $1700.000 ~~per~~million ~~share~~measured ~~required for continued listing~~ on ~~The Nasdaq Global Market pursuant to Nasdaq Listing Rule 5450(a)(1) (~~the ~~“Minimum~~last Bid Price Requirement”). Under Nasdaq Listing Rule 5810(c)(3)(A), the Company was granted a 180 calendar day grace period, or until July 5, 2022, to regain compliance with the minimum bid price requirement. The minimum bid price requirement will be met if our common stock has a minimum closing bid price of at least $1.00 per share for a minimum of 10 consecutive business ~~days during the 180 calendar~~ day grace period. Because the Company did not regain compliance with the Minimum Bid Price Requirement before July 5, 2022, the Company applied to transfer its listing to the Nasdaq Capital Market and for an extension of ~~an additional 180 calendar days, or until January 2, 2023 to regain compliance with the Minimum Bid Price Requirement. On July 7, 2022, Nasdaq notified us that~~ our ~~application~~second ~~for~~fiscal ~~listing on the Nasdaq Capital Market was approved and that Nasdaq had approved the Company’s extension request~~quarter.

OnWe ~~December~~cannot 1,predict ~~2022,~~whether weinvestors ~~effected~~will afind ~~1-for-40 reverse stock split of~~ our common stock ~~(the~~less ~~“Reverse~~attractive ~~Stock~~if ~~Split”).~~we Atrely ~~a special meeting of stockholders held~~ on ~~November~~this ~~30,~~exemption. ~~2022~~If ~~(the~~some ~~“Special~~investors ~~Meeting”),~~find ~~the~~our ~~stockholders~~common ofstock ~~the~~less ~~Company~~attractive ~~approved~~as a ~~proposal to authorize the Company’s Board of Directors~~result, inthere ~~its~~may ~~discretion~~be ~~following the Special Meeting to amend the Company’s Amended and Restated Certificate of Incorporation, as amended (the “Certificate of Incorporation”), to effect~~ a ~~reverse~~less ~~stock~~active ~~split~~trading ofmarket ~~all~~for ofour ~~the outstanding shares of the Company’s~~ common stock. Onand ~~November~~our ~~30,~~stock ~~2022,~~price ~~following~~may ~~the~~be ~~Special~~reduced ~~Meeting,~~or ~~the~~more ~~Company’s Board of Directors approved the Reverse Stock Split at a ratio of 1-for-40~~volatile. On December 1, 2022, the Company filed with the Secretary of State of the State of Delaware a certificate of amendment (the “Certificate of Amendment”) with the Secretary of State of the State of Delaware to amend the Company’s Certificate of Incorporation to effect the Reverse Stock Split. The Reverse Stock Split became effective at 5:00 p.m., Eastern Time, on December 1, 2022.

OnProvisions ~~December~~in ~~19, 2022, we were notified by Nasdaq Listing Qualifications that the closing bid price of the~~ our ~~common~~charter ~~stock~~documents ~~had been at $1.00 per share or greater for the 11 consecutive business days, from December 2, 2022 to December 16, 2022. Accordingly, the Company has regained compliance with Listing Rule 5550(a)(2)~~ and ~~this~~under ~~matter~~Delaware islaw ~~now~~could ~~closed.~~discourage ~~Although we regained compliance with Listing Rule 5550(~~a~~)(2)~~ ~~there~~takeover ~~can~~that bestockholders nomay ~~guarantee~~consider ~~that~~favorable weand ~~can~~may ~~continue~~lead to ~~remain~~entrenchment ~~compliant~~of management.

Our ~~Further,~~amended onand ~~October~~restated ~~11,~~certificate ~~2022,~~of weincorporation ~~received~~and aour ~~letter~~amended ~~from~~and ~~Nasdaq~~restated ~~Listing~~bylaws ~~Qualifications~~contain ~~notifying~~provisions us that ~~for~~could ~~the~~significantly ~~last~~reduce ~~30 consecutive business days,~~ the ~~Company’s~~value ~~Minimum Value~~ of ~~Listed~~our ~~Securities,~~shares asto ~~defined~~a bypotential ~~Nasdaq~~acquiror ~~(“MVLS”),~~or ~~has~~delay ~~been~~or ~~below~~prevent ~~the~~changes ~~minimum~~in ~~$35~~control million requirement for continued listing on The Nasdaq Capital Market under Nasdaq Listing Rule 5500(b)(2) (the “Minimum Market Value Requirement”). Under Nasdaq Listing Rule 5810(c)(3)(C), the Company has 180 calendar days, or ~~until~~changes ~~April~~in ~~10,~~our ~~2023,~~management towithout ~~regain compliance with~~ the ~~Minimum~~consent ~~Market~~of ~~Value Requirement. The Minimum Market Value Requirement will be met if~~ our ~~minimum~~board ~~MVLS closes at $35 million or more for a minimum~~ of ~~ten (10) consecutive business days during the compliance period ending April 10, 2023~~directors. IfThe weprovisions doin not regain compliance with the Minimum Market Value Requirement during the compliance period ending April 10, 2023, Nasdaq will provide written notification that the Company’s common stock will be subject to delisting. At that time, the Company may appeal any such delisting determination to the Panel. We are actively monitoring our ~~MVLS~~charter ~~and~~documents ~~evaluating~~include ~~available options to regain compliance with~~ the ~~Minimum Market Value Requirement. However, there is no assurance that we will be able to regain compliance with the Minimum Market Value Requirement during the 180-day compliance period.~~following:

•

~~The~~the ~~delisting~~ability of our ~~common~~board ~~stock~~of ~~from~~directors ~~Nasdaq may make it more difficult for us~~ to ~~raise~~authorize ~~capital on favorable terms in~~ the ~~future.~~issuance ~~Such~~of ashares ~~delisting would likely have a negative effect on the price~~ of ~~our~~preferred ~~common~~ stock and ~~would impair your ability~~ to ~~sell~~determine orthe ~~purchase~~price ~~our~~and ~~common~~other ~~stock~~terms ~~when~~of ~~you~~those ~~wish to do so. Further~~shares, ifincluding wepreferences ~~were~~and tovoting berights, ~~delisted~~without ~~from~~stockholder ~~Nasdaq~~approval, ~~our~~which ~~common~~could ~~stock would cease to~~ be ~~recognized~~used ~~as covered securities and we would be subject~~ to ~~regulation~~significantly indilute ~~each state in which we offer our securities. Moreover, there is no assurance that any actions that we take to restore our compliance with~~ the ~~Minimum~~ownership Market Value Requirement required for continued listing or prevent future non-compliance with Nasdaq’s listing requirements. There is also no assurance that we will maintain compliance with the other listing requirements of ~~The~~a ~~Nasdaq~~hostile ~~Capital Market.~~acquiror;

•

52the ability of our board of directors to alter our amended and restated bylaws without obtaining stockholder approval; and

•

advance notice procedures that stockholders must comply with in order to nominate candidates to our board of directors or to propose matters to be acted upon at a stockholders’ meeting, which may discourage or deter a potential acquiror from conducting a solicitation of proxies to elect the acquiror’s own slate of directors or otherwise attempting to obtain control of us.

We are also subject to the anti-takeover provisions contained in Section 203 of the Delaware General Corporation Law. Under Section 203, a corporation may not, in general, engage in a business combination with any holder of 15% or more of its capital stock unless the holder has held the stock for three years or, among other exceptions, the board of directors has approved the transaction.

Our current amended and restated bylaws provide that the Court of Chancery of the State of Delaware will be

the exclusive forum for substantially all disputes between us and our stockholders and that the federal district

courts shall be the exclusive forum for the resolution of any complaint asserting a cause of action arising

under the Securities Act, which could limit our stockholders’ ability to obtain a favorable judicial forum for

disputes with us or our directors, officers or employees or the underwriters or any offering giving rise to such

claim.

Our amended and restated bylaws provide that the Court of Chancery of the State of Delaware is the exclusive forum for any derivative action, suit or proceeding brought on our behalf, any action, suit or proceeding asserting a breach of fiduciary duty, any action, suit or proceeding asserting a claim against us arising pursuant to the Delaware General Corporation Law, our amended and restated certificate of incorporation or our amended and restated bylaws, or any action, suit or proceeding asserting a claim against us that is governed by the internal affairs doctrine; provided, that, this provision would not apply to suits brought to enforce a duty or liability created by the Exchange Act or any other claim for which the federal courts have exclusive jurisdiction. These choice of forum provisions may result in increased costs to stockholders to bring a claim, limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, officers or other employees, and may generally have the effect of discouraging lawsuits against us and our directors, officers and other employees. By agreeing to this provision, however, stockholders will not be deemed to have waived our compliance with the federal securities laws and the rules and regulations thereunder. Furthermore, the enforceability of similar choice of forum provisions in other companies’ certificates of incorporation or bylaws has been challenged in legal proceedings, and it is possible that a court could find these types of provisions to be inapplicable or unenforceable. If a court were to find the choice of forum provisions in our amended and restated bylaws to be inapplicable or unenforceable in an action, we may incur additional costs associated with resolving such action in other jurisdictions, which could adversely affect our business and financial condition.

Our common stock constitutes “penny stock” within the meaning of the rules of the SEC and may be subject to greater opportunity for manipulation.

The SEC has adopted a number of rules to regulate “penny stocks” that restrict transactions involving stock which is deemed to be penny stock. These rules may have the effect of reducing the liquidity of penny stocks. “Penny stocks” generally are equity securities with a price of less than $5.00 per share (other than securities registered on certain national securities exchanges or quoted on the Nasdaq Stock Market if current price and volume information with respect to transactions in such securities is provided by the exchange or system). Our securities have in the past constituted, and may again in the future constitute, “penny stock” within the meaning of the rules. The additional sales practice and disclosure requirements imposed upon U.S. broker-dealers may discourage such broker-dealers from effecting transactions in shares of our common stock, which could severely limit the market liquidity of such shares and impede their sale in the secondary market.

A U.S. broker-dealer selling penny stock to anyone other than an established customer or “accredited investor” (generally, an individual with net worth in excess of $1,000,000 or an annual income exceeding $200,000, or $300,000 together with his or her spouse) must make a special suitability determination for the purchaser and must receive the purchaser’s written consent to the transaction prior to sale, unless the broker-dealer or the transaction is otherwise exempt. In addition, the “penny stock” regulations require the U.S. broker-dealer to deliver, prior to any transaction involving a “penny stock”, a disclosure schedule prepared in accordance with SEC standards relating to the “penny stock” market, unless the broker-dealer or the transaction is otherwise exempt. A U.S. broker-dealer is also required to disclose commissions payable to the U.S. broker-dealer and the registered representative and current quotations for the securities. Finally, a U.S. broker-dealer is required to submit monthly statements disclosing recent price information with respect to the “penny stock” held in a customer’s account and information with respect to the limited market in “penny stocks”.

The market for “penny stocks” has suffered from patterns of fraud and abuse. Such patterns include (i) control of the market for the security by one or a few broker-dealers that are often related to the promoter or issuer; (ii) manipulation of prices through prearranged matching of purchases and sales and false and misleading press releases; (iii) “boiler room” practices involving high-pressure sales tactics and unrealistic price projections by inexperienced sales persons; (iv) excessive and undisclosed bid-ask differentials and markups by selling broker-dealers; and (v) the wholesale dumping of the same securities by promoters and broker-dealers after prices have been manipulated to a desired level, resulting in investor losses.

General Risk Factors

As a public company, we are subject to the reporting requirements of the Exchange Act, the Sarbanes-Oxley Act ~~of 2002 (the “Sarbanes-Oxley Act”)~~, and Nasdaq stock market rules. The requirements of these rules and regulations have increased and will continue to significantly increase our legal and financial compliance costs, including costs associated with the hiring of additional personnel, making some activities more difficult, time-consuming or costly, and may also place undue strain on our personnel, systems and resources. The Exchange Act requires, among other things, that we file annual, quarterly and current reports with respect to our business and financial condition.

The Sarbanes-Oxley Act requires, among other things, that we maintain disclosure controls and procedures and internal control over financial reporting. Ensuring that we have adequate internal financial and accounting controls and procedures in place, as well as maintaining these controls and procedures, is a costly and time-consuming effort that needs to be re-evaluated frequently. Section 404 of the Sarbanes-Oxley Act, or Section 404, requires that we annually evaluate our internal control over financial reporting to enable management to report on the effectiveness of those controls. In connection with the Section 404 requirements, we test our internal controls and could, as part of that documentation and testing, identify material weaknesses, significant deficiencies or other areas for further attention or improvement.

Implementing any appropriate changes to our internal controls may require specific compliance training for our directors, officers and employees, require the hiring of additional finance, accounting and other personnel, entail substantial costs to modify our existing accounting systems, and take a significant period of time to complete. These changes may not, however, be effective in maintaining the adequacy of our internal controls, and any failure to maintain that adequacy, or consequent inability to produce accurate financial statements on a timely basis, could increase our operating costs and could materially impair our ability to operate our business. Moreover, adequate internal controls are necessary for us to produce reliable financial reports and are important to help prevent fraud. As a result, our failure to satisfy the requirements of Section 404 could result in the loss of investor confidence in the reliability of our financial statements, which in turn could cause the market value of our common stock to decline.

Our ability to use our net operating losses to offset future taxable income may be subject to certain limitations.

As of December 31, ~~2022~~2025, we had U.S. federal and state net operating loss carryforwards (“NOLs”), of $~~159~~190.21 million ~~and $25.9 million~~, ~~respectively,~~ and federal research tax credit carryforwards of $811.19 million. Certain U.S. NOLs will begin to expire, beginning in 2023 through 2037, and research tax credits will expire beginning in 2026 through 2041. Included in these U.S. federal NOLs are $84101.1 million of NOLs generated after the effective date of the Tax Cuts and Jobs Act of 2017 ("“TCJA"”) which are not subject to expiration. Under the TCJA, Federal NOLs generated in 2018 and future years may be carried forward indefinitely but may not be carried back and are only eligible to offset up to a maximum of 80% of taxable income generated in a given year. It is uncertain if and to what extent various U.S. states will conform their net operating loss rules to the TCJA.

In general, under Section 382 of the U. S. Internal Revenue Code of 1986, as amended, (the “Code”), a corporation that undergoes an “ownership change” is subject to limitations on its ability to utilize its pre-ownership change NOLs to offset future taxable income. We may have experienced ownership changes in the past. We may experience additional ownership changes in the future as a result of subsequent shifts in our stock ownership, some of which may be outside of our control. Although we have not completed our analysis, it is reasonably possible that our federal NOLs available to offset future taxable income could materially decrease. This reduction will be offset by an adjustment to the existing valuation allowance for an equal and offsetting amount. Additionally, our state NOLs available to offset future state income could similarly decrease which would also be offset by an equal and offsetting adjustment to the existing valuation allowance. Given the offsetting adjustments to the existing valuation allowance, any ownership change is not expected to have a material adverse effect on our consolidated financial statements. As of December 31, 2022, we had Israeli NOLs of $101.0 million, which carry forward indefinitely.65

2018 and future years may be carried forward indefinitely but generally may not be carried back and are only eligible to offset up to a maximum of 80% of taxable income generated in a given year.

In general, under Section 382 of the U. S. Internal Revenue Code of 1986, as amended, a corporation that undergoes an “ownership change” is subject to limitations on its ability to utilize its pre-ownership change NOLs to offset future taxable income. We may have experienced ownership changes in the past. We may experience additional ownership changes in the future as a result of subsequent shifts in our stock ownership, some of which may be outside of our control. Although we have not completed our analysis, it is reasonably possible that our federal NOLs available to offset future taxable income could materially decrease. This reduction will be offset by an adjustment to the existing valuation allowance for an equal and offsetting amount. Additionally, our state NOLs available to offset future state income could similarly decrease which would also be offset by an equal and offsetting adjustment to the existing valuation allowance. Given the offsetting adjustments to the existing valuation allowance, any ownership change is not expected to have a material adverse effect on our consolidated financial statements. As of December 31, 2025, we had Israeli NOLs of $126.2 million, which carry forward indefinitely.

Our ability to utilize our NOLs is dependent on attaining profitability sufficient to offset such available NOLs prior to their expiration. In addition, we may not be able to utilize a portion of the NOLs even if we attain profitability.

Our directors, executive officers, principal stockholders and affiliated entities own a significant percentage of our capital stock, and they may make decisions that an investor may not consider to be in the best interests of our stockholders.

Our directors, executive officers, principal stockholders and affiliated entities beneficially own, in the aggregate, a significant percentage of our common stock, giving effect to options and other derivative securities that are held by such persons. As a result, if some or all of them acted together, they would have the ability to exert substantial influence over the election of our board of directors and the outcome of issues requiring approval by our stockholders. This concentration of ownership may have the effect of delaying or preventing a change in control of our company that may be favored by other stockholders. This could prevent the consummation of transactions favorable to other stockholders, such as a transaction in which stockholders might otherwise receive a premium for their shares over current market prices.

Future sales and issuances of our securities or rights to purchase securities, including pursuant to our equity incentive plans, could result in additional dilution of the percentage ownership of our stockholders and could cause the prices of our securities to fall.

Additional capital will be needed in the future to continue our planned operations. To the extent we raise additional capital by issuing equity ~~securities~~ or ~~our~~debt ~~ATM Program pursuant to which we may sell up to $50.0 million of our common stock~~securities, our stockholders may experience substantial dilution. We may sell common stock, convertible securities or other equity securities in one or more transactions at prices and in a manner, we determine from time to time. If we sell common stock, convertible securities or other equity securities in one or more transactions, existing investors may be materially diluted by subsequent sales, and new investors could gain rights superior to our existing stockholders.

~~Pursuant~~We tocould ~~our~~be ~~2018~~subject ~~Equity Incentive Plan, our management is authorized~~ to ~~grant~~securities ~~stock~~class ~~options~~action ~~and other equity-based awards to our employees, directors and consultants~~litigation. As of December 31, 2022, individuals held share awards to purchase or receive an aggregate of 249,403 shares of our common stock. If our board of directors elects to increase the number of shares available for future grant by the maximum amount each year (5% of the outstanding common stock), our stockholders may experience additional dilution, which could have a negative effect on our share price.

54In the past, securities class action litigation has often been brought against a company following a decline in the market price of its securities. This risk is especially relevant for us because biotechnology and biopharmaceutical companies have experienced significant stock price volatility in recent years. If we face such litigation, even if ultimately decided in our favor, it could result in substantial costs and a diversion of our management’s attention and resources, which could harm our business.

Changing circumstances and market conditions, some of which may be beyond our control, could impair our ability to access our existing cash and cash equivalents and to timely pay key vendors and others.

We maintain our cash and cash equivalents in accounts with major financial institutions, and our deposits with these institutions can and do exceed insured limits. Market conditions can impact the viability of these institutions. In the event of failure of any of the financial institutions where we maintain our cash and cash equivalents, we could lose our deposits in excess of the federally insured or protected amounts and there can be no assurance that we will be able to access uninsured funds in a timely manner or at all. Any inability to access or delay in accessing these funds could adversely affect our business and financial position.

Our insurance policies protect us from only some business risks, which will leave us exposed to significant uninsured liabilities.

We do not carry insurance for all categories of risk that our business may encounter. We do not know, however, if we will be able to maintain insurance with adequate levels of coverage. No assurance can be given that an insurance carrier will not seek to cancel or deny coverage after a claim has occurred. Any significant uninsured liability may require us to pay substantial amounts, which would adversely affect our business, financial condition, results of operations and prospects.

We are subject to governmental export and import controls, economic sanctions, anti-corruption laws and regulations of the United States and other jurisdictions. We can face criminal liability and other serious consequences for violations of these laws and regulations, which could harm our business.

We are subject to and required to comply with various export control, import and trade and economic sanctions laws and regulations, including the U.S. Export Administration Regulations, U.S. Customs regulations and sanctions regulations administered by the U.S. Treasury Department’s Office of Foreign Assets Controls. These laws may prohibit or restrict our ability to transfer, sell or supply, our products to certain governments, persons, entities, countries, and territories, including those that are the target of comprehensive sanctions or an embargo.

We are also subject to anti-corruption and anti-bribery laws, including the U.S. Foreign Corrupt Practices Act of 1977, as amended (the “FCPA”), the U.S. domestic bribery statute contained in 18 U.S.C. § 201, the U.S. Travel Act, and other state and national anti-bribery and anti-money laundering laws in the countries in which we conduct activities. Anti-corruption laws, including the FCPA, generally prohibit companies and their employees, agents, CROs, contractors and other partners from offering, promising, giving, soliciting or authorizing others to give or receive anything of value, either directly or indirectly, to or from a non-U.S. government official in order to influence official action, or otherwise obtain or retain business. The FCPA also requires public companies to make and keep books and records that accurately and fairly reflect the transactions of the corporation and to devise and maintain an adequate system of internal accounting controls. We can be held liable for the corrupt or other illegal activities of our employees, agents, CROs, contractors, and other partners, even if we do not explicitly authorize or have actual knowledge of such activities. Any violation of the laws and regulations described above may result in substantial civil and criminal fines and penalties, imprisonment, the loss of export or import privileges, debarment, tax reassessments, breach of contract and fraud litigation, reputational harm, and other consequences.

Coastlands and Domicilium own prefunded warrants to purchase a significant percentage of our capital stock and have board designation and certain consent rights, which allow them to exert meaningful influence on our company.

Following the final closing under the securities purchase agreement, dated as of August 20, 2025 and as amended on September 25, 2025, December 11, 2025, and February 20, 2026 (the “Coastlands Securities Purchase Agreement”), Coastlands owned prefunded warrants to purchase 30,615,243 shares of our common stock and Domicilium owned prefunded warrants to purchase 21,423,618 shares of our common stock, at an exercise price of $0.01 per share. Additionally, pursuant to the terms of the Coastlands Securities Purchase Agreement, each of Coastlands and Domicilium have the right to designate one member of our Board of Directors until immediately prior to the effectiveness of a registration statement on Form S-1. Further, until immediately prior to the effectiveness of a registration statement on Form S-1, without the consent of Coastlands and Domicilium we cannot: (i) amend, alter or repeal any provision of our certificate of incorporation or bylaws; (ii) increase or decrease the size of the Board of Directors or appoint or remove any member of the Board of Directors; (iii) issue any shares of Common Stock or securities convertible into shares of common stock (other than in connection with the exercise or vesting of outstanding securities); (iv) amend the compensation of any executive officer; (v) consummate a Liquidation Event (as defined in the Amended and Restated Certificate of Incorporation), or effect any other merger, statutory conversion, transfer, domestication continuance, liquidation, dissolution, or wind up the business affairs of the Company, or consolidation; (vi) sell, assign, license, pledge or encumber any material asset (including intellectual property); or (vii) incur any indebtedness (other than ordinary course credit or trade payables incurred in the ordinary course of business); provided, that Coastlands and Domicilium agree to consent to any act or transaction that is reasonably necessary to support an uplisting to Nasdaq, as reasonably determined by our Board of Directors. These rights allow Coastlands and Domicilium to exert meaningful influence over the Company. These rights could discourage a takeover of the company, could limit our ability to raise additional funds, whether through offerings of our securities or indebtedness, could limit our ability to retain or attractive executive officers, and could result in Coastland and Domicilium controlling the composition of our Board of Directors.

ITEM 1B. Unresolved Staff Comments

None.

ITEM 1C. CYBERSECURITY

Risk Management and Strategy

We have implemented and 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 intellectual property and confidential information that is proprietary, strategic or competitive in nature (“Information Systems and Data”).

We retain a third-party security management vendor to help identify, assess and manage our cybersecurity threats and risks. This partner identifies and assesses risks from cybersecurity threats by monitoring and evaluating our threat environment using various methods, including, for example, automated tools, cybersecurity threat subscription services, threat report analysis, internal and external audits, and threat and vulnerability assessments.

Depending on the environment, we implement and maintain various technical, physical, and organizational measures, processes, standards and policies designed to manage and mitigate material risks from cybersecurity threats to our Information Systems and Data, including, for example, incident detection and response policy, route risk assessments, data encryption, network security controls, data segregation, access controls, physical security, asset management, tracking and disposal, systems monitoring, penetration testing, and cybersecurity insurance.

Our assessment and management of material risks from cybersecurity threats are integrated into our overall risk management processes. For example, our security management partner works with our Interim Chief Financial Officer to prioritize our risk management processes and mitigate cybersecurity threats that are more likely to lead to a material impact to our business. In addition, our Interim Chief Financial Officer evaluates material risks from cybersecurity threats against our overall business objectives and reports to the audit committee of the board of directors, which evaluates our overall enterprise risk.

We use third-party service providers to assist us from time to time to identify, assess, and manage material risks from cybersecurity threats, including for example, professional services firms, cybersecurity software providers and penetration testing firms. These third-parties also provide application and hosting services. We have a vendor management program to manage cybersecurity risks associated with our use of these providers. The program includes risk assessments and audits for each vendor and a review of each such vendor's written security program.

For a description of the risks from cybersecurity threats that may materially affect us and how they may do so, see our risk factors under Part I. Item 1A. Risk Factors in this Annual Report, including "If our information technology systems or those third parties upon which we rely or our data, 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, disruptions of our business operations, reputational harm, loss of revenue or profits and other adverse consequences.”

Governance

Our Board addresses our cybersecurity risk management as part of its general oversight function. The Audit Committee is responsible for overseeing our cybersecurity risk management processes, including oversight and mitigation of risks from cybersecurity threats. Our cybersecurity risk assessment and management processes are implemented and maintained by our Interim Chief Financial Officer who oversees the work performed by our information security consultant and third-party managed service provider. Our information security consultant has over 40 years of experience in pharmaceutical information technology, including many years as a chief information officer.

Our Interim Chief Financial Officer is responsible for hiring appropriate personnel, helping to integrate cybersecurity risk considerations into our overall risk management strategy, and communicating key priorities to relevant personnel. Our Interim Chief Financial Officer, with support from our information security partners, is responsible for approving budgets, helping prepare for cybersecurity incidents, approving cybersecurity processes, and reviewing security assessments and other security-related reports.

Our cybersecurity incident response policy is designed to escalate certain cybersecurity incidents to members of management depending on the circumstances, including our Interim Chief Financial Officer and legal department. Our Interim Chief Financial Officer works with our incident response team to help mitigate and remediate

cybersecurity incidents of which they are notified. In addition, our incident response policy includes reporting to the Audit Committee for certain cybersecurity incidents.

ITEM 2. Properties

Our principal executive offices ~~are~~were ~~currently~~previously located at 480 Arsenal Way, Watertown, Massachusetts~~, and consist of approximately 9,000 square feet of office space under lease until February 2024, with an option to extend the lease period for an additional three years~~. We also ~~lease~~previously ~~additional~~leased office space in ~~Rehovot~~Ness Ziona, Israel. We ~~believe that our existing facilities~~ are ~~adequate~~now toa ~~meet~~remotely ~~current~~headquartered ~~business needs, and that suitable additional or substitute space will be available as needed to accommodate our future office space needs~~company.

ITEM 3. Legal Proceedings

From time to time, we may become involved in various lawsuits and legal proceedings, which arise in the ordinary course of business, which may include, without limitation, actions related to or based on our intellectual property and its use, customer claims, employment practices and employee complaints and other events arising out of our operations. We are currently unaware of any material pending legal proceedings to which we are party or of which our property is the subject. However, we may at times in the future become involved in litigation in the ordinary course of business. When appropriate in management’s estimation, we will record adequate reserves in our financial statements for pending litigation. Litigation is subject to inherent uncertainties, and an adverse result in any such matters could adversely impact our reputation, operations, and our financial operating results or overall financial condition. Additionally, any litigation to which we may become subject could also require significant involvement of our senior management and may divert management’s attention from our business and operations.

ITEM 4. Mine Safety Disclosures

None.

5569

PART II

ITEM 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities

Market Information for Common Stock

Since October 16, 2023, our common stock has traded on the OTC markets, most recently on the OTC Expert Market, under the symbol “ELOX”. Any over-the-counter market quotations reflect inter-dealer prices, without retail mark-up, mark-down or commission, and may not necessarily represent actual transactions. From July 7, 2022 until October 15, 2023, our common stock ~~has~~was traded on The NASDAQ Capital Market under the symbol “ELOX.” From April 26, 2018 to July 6, 2022, our common stock traded on The NASDAQ Global Market under the symbol “ELOX.” Prior to April 26, 2018, our common stock traded on the OTCQB market under the symbol “ELOX”.

Holders

As of March 2116, ~~2023~~2026 , there were approximately 90117 holders of record of our common stock. This number does not include “street name” or beneficial holders, whose shares are held of record by banks, brokers, financial institutions and other nominees.

Recent Sales of Unregistered Securities

~~None~~On January 9, 2024, the Company entered into a securities purchase agreement (the “Domicilium Securities Purchase Agreement”) with SD MF 4, LLC (“Domicilium”) providing for the issuance by the Company of: (i) 157,138 shares of the Company’s common stock; (ii) a pre-funded warrant (the “January 2024 Pre-Funded Warrant”) to purchase up to 471,508 shares of common stock; and (iii) an additional warrant to purchase up to 150,000 shares of common stock at a price per share of $1.18, as consideration for Domicilium’s assumption of the Tranche 1B Advance under the Company’s outstanding term loan agreement with Hercules. The Company did not receive any proceeds in connection with the Equity Issuance.

On August 20, 2025, the Company entered into a securities purchase agreement (the “Coastlands Securities Purchase Agreement”), as amended on September 25, 2025, December 11, 2025, and February 20, 2026, with Coastlands Capital Partners LP (“Coastlands”) and Domicilium. Pursuant to the Coastlands Securities Purchase Agreement, the Company issued and sold prefunded warrants to purchase up to an aggregate of 30,612,243 shares of common stock to Coastlands and prefunded warrants to purchase up to an aggregate of 21,423,618 shares of common stock to Domicilium, at a sale price of $0.49 per underlying share, for an aggregate purchase price of $17.0 million of investment and the conversion of approximately $9.5 million of outstanding indebtedness.

Since January 1, 2024, the registrant has granted (i) stock options to purchase an aggregate of 9,838,008 shares of its common stock with exercise prices ranging from $0.0001 to $0.24 per share, (ii) 1,230,000 shares of Restricted Stock and (iii) Restricted Stock Units exchangeable into up to 106,500 shares of common stock upon vesting, to employees, consultants and directors in connection with services provided to the registrant by such parties. The issuances of such equity awards and the shares of common stock issuable upon the exercise or vesting of such awards was pursuant to written compensatory plans or arrangements.

Since January 1, 2024, the registrant issued 465,407 shares of common stock in connection with exercise of outstanding options held by executive officers, directors and employees.

All of these unregistered securities were issued pursuant to Section 4(a)(2) under the Securities Act, relative to transactions by an issuer not involving any public offering, to the extent an exemption from such registration was required.

Purchases of Equity Securities by the Issuer or Affiliated Purchaser

There were no repurchases of shares of our common stock during the fourth quarter ended December 31, ~~2022~~2025.

Dividend Policy

We have not paid dividends on our common stock since inception and we do not intend to pay any dividends in the foreseeable future. We expect that any earnings which we may realize will be retained to finance the growth of our Company. The declaration of dividends in the future will be at the election of our board of directors and will depend upon our earnings, capital requirements, financial position, general economic conditions, and other factors the board of directors deems relevant.

ITEM 6. [rESERVED]

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ITEM 7. MANAGEMENT’S Discussion and analysis of financial condition and results of operationS

You should read the following discussion and analysis of our financial condition and results of operations together with our consolidated financial statements and related notes and other financial information appearing elsewhere in this Annual Report ~~on Form 10-K~~. Some of the information contained in this discussion and analysis or set forth elsewhere in this Annual Report ~~on Form 10-K~~, including information with respect to our plans and strategy for our business, includes forward-looking statements that involve risks and uncertainties. Please see “Special Note Regarding Forward-Looking Statements.” As a result of many factors, including those factors set forth in the “Part I, Item 1A - Risk Factors” section of this Annual Report ~~on Form 10-K~~, our actual results could differ materially from the results described in, projected or implied by the forward-looking statements contained in the following discussion and analysis. Our discussion and analysis of our financial condition and results of operations for 2025, 2024, and 2023 are discussed below.

Our discussion and analysis of our financial condition and results of operations for 2022 as compared to 2021 are discussed below. For a discussion of our financial condition and results of operations for 2021 as compared to 2020, please refer to Item 7, “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in our 2021 Annual Report on Form 10-K, except as set forth below.

Company Overview

We are a clinical-stage biopharmaceutical company ~~engaged~~developing innovel, ~~the~~small-molecule ~~science~~product ofcandidates ~~ribosome~~designed ~~modulation,~~to ~~leveraging~~modulate ~~both~~the ~~our~~ribosome ~~innovative~~and ~~TURBO-ZM™~~promote ~~chemistry~~readthrough ~~technology~~of ~~platform~~premature ~~and~~stop ~~our~~codons ~~library~~induced ofby ~~novel~~nonsense ~~aminoglycosides~~mutations (“NMs”) to ~~develop~~enable ~~novel~~the ~~oral~~production ~~small~~of ~~molecule~~full-length ~~Ribosome~~proteins. ~~Modulating~~Targeting ~~Agents~~ribosome ~~(“RMAs”)~~subunits ~~and~~provides ~~Eukaryotic~~a ~~Ribosome~~therapeutic ~~Selective~~approach ~~Glycosides~~to ~~(“ERSGs”),~~addressing ~~for~~a number of genetic diseases. According to the ~~treatment~~Human ofGene ~~rare~~Mutation ~~and~~Database, ~~ultra-rare~~NMs ~~genetic~~account ~~diseases~~for ~~where~~approximately 10% to 12% of patients ~~have~~with ~~point~~a ~~nonsense~~given genetic ~~mutations~~disease. ~~that~~There ~~result~~are inover ~~premature~~7,000 ~~stop~~inherited ~~codons~~genetic ~~and~~diseases ~~less~~that ~~than~~collectively ~~full~~affect ~~length~~350 ~~proteins.~~million ~~"Nonsense~~people ~~mutations~~worldwide. ~~result~~Our inimmediate ~~premature~~focus ~~stop~~is ~~codons~~to inadvance the ~~impacted~~clinical ~~messenger~~development ~~RNA~~of ~~(“mRNA”)~~our ~~which~~lead inproduct ~~turn~~candidate, ~~disrupt~~exaluren, ~~protein~~for ~~synthesis~~the ~~from~~treatment ~~that~~of ~~mRNA~~rare ~~leading~~kidney todiseases ~~less~~and, ~~than~~through ~~full~~our ~~length~~collaboration ~~proteins. Patients~~ with ~~these~~Almirall, ~~mutations~~S.A. ~~have~~(“Almirall”), ~~significantly~~ZKN-013 ~~worse~~for ~~outcomes~~the ~~than~~treatment ~~with~~of ~~missense~~rare ~~mutations.~~skin diseases.

We ~~have~~conducted ~~multiple~~a ~~programs~~proof-of-concept inPhase ~~our~~2a ~~pipeline~~open-label ~~including~~monotherapy atrial ~~clinical~~in ~~program for~~ the ~~treatment~~United ofKingdom ~~Alport~~in ~~syndrome~~three patients with ~~ELX-02~~autosomal ~~(subcutaneous~~recessive ~~delivery),~~AS ~~preclinical~~and ~~programs~~a NM in ~~investigational~~the ~~new~~COL4A4 ~~drug~~gene. ~~("IND")~~All ~~enabling~~three ~~stages~~patients inshowed ~~Recessive~~a ~~Dystrophic~~reduction ~~(“RDEB”)~~in ~~and~~podocyte ~~Junctional~~foot ~~Epidermolysis~~process ~~Bullosa~~effacement (“~~JEB~~FPE”), which is the flattening and ~~Familial~~loss ~~Adenomatous~~of ~~Polyposis~~specialized ~~(“FAP”)~~kidney ~~with~~cell ~~ZKN-013,~~structures ~~and~~that ~~IND~~form ~~enabling~~the ~~stage~~filtration ~~program~~barrier ~~with~~and ~~inhaled~~attach ~~delivery~~to ofthe ~~ELX-02~~podocytes inand ~~Class~~GBM, 1in ~~cystic~~transmission ~~fibrosis~~electron microscopy (~~"CF"~~“TEM”) images. WeFPE ~~also~~is ~~have~~a ~~various~~hallmark ~~earlier~~of ~~discovery~~kidney ~~stage~~diseases ~~programs~~including inAS ~~Cystic~~and ~~fibrosis~~the ~~and~~severity ~~oncology.~~of AsFPE ~~our~~has ~~programs~~historically ~~advance,~~been weassociated ~~plan~~with time to ~~actively~~kidney ~~look~~failure. toTEM ~~expand~~images ~~our~~of ~~pipeline~~biopsy bysamples ~~seeking~~also ~~new~~showed ~~indications~~an improvement in ~~other~~the ~~rare~~GBM ~~diseases~~width ~~for~~in ~~compounds~~all ~~designed~~treated ~~with~~patients. ~~our~~FPE ~~platforms.~~was ~~The~~also ~~U.S.~~measured ~~Food~~as ~~and~~a ~~Drug~~50% ~~Administration~~increase in the filtration slit density (“~~FDA~~FSD”). ~~has~~These ~~granted~~results ~~Fast~~were ~~Track~~consistent ~~designation~~with ~~for~~exaluren’s ~~ELX~~proposed mechanism of functional full-02length ~~for~~protein ~~the~~restoration ~~treatment~~as ofreflected CFby ~~patients~~improvements ~~with~~in ~~nonsense~~GBM ~~mutations~~architecture and FPE observed in kidney biopsies. InWe ~~addition,~~plan ~~the~~to ~~FDA~~initiate ~~granted~~a ~~ELX-02~~Phase ~~Orphan~~2b ~~Drug~~clinical ~~Designation~~trial ~~for~~in the ~~treatment~~first half of CF2026 for exaluren in ~~July~~NMAS ~~2020~~patients and ~~based~~anticipate ontopline ~~the~~data ~~European~~from ~~Medicines~~the ~~Agency’s~~initial ~~(“EMA”)~~16-week ~~positive~~placebo-controlled ~~opinion,~~part of the ~~European~~study ~~Commission~~by ~~granted ELX~~mid-02 ~~orphan~~2027 ~~medicinal~~with ~~product~~the ~~designation~~final inreadout ~~September~~by ~~2018.~~the end of 2027.

InOur ~~March~~pipeline ~~2022,~~also weincludes ~~announced~~a ~~our~~preclinical ~~decision~~program toevaluating ~~advance~~exaluren ~~ELX-02 delivered subcutaneously~~ for the ~~restoration~~treatment of ~~Collagen~~autosomal IVdominant ~~protein~~polycystic ~~for~~kidney ~~the~~disease ~~treatment~~(“ADPKD”) ofin ~~Alport syndrome~~ patients. ~~Alport~~that ~~syndrome~~have ~~with~~NMs ~~nonsense~~(“nmADPKD”). ~~mutations~~ADPKD is athe ~~genetic~~most common monogenic kidney ~~disorder~~disease ~~that~~based ~~occurs~~on ingenetic 1diagnosis, inaffecting 50approximately 160,000 ~~newborns~~to 200,000 patients in the United States. ItThe isPKD1 ~~caused~~gene byencodes ~~the~~polycystin-1 ~~loss~~(“PC1”) ofand ~~one~~the ofPKD2 ~~three~~gene ~~collagen~~encodes IVpolycystin-2 ~~subtypes. This disease is characterized by blood~~ (~~hematuria~~“PC2”), ~~and~~these ~~protein~~are ~~(proteinuria)~~proteins inthat ~~the~~regulate ~~patient's~~cell ~~urine,~~growth and ~~results~~fluid secretion in ~~progressive~~ kidney ~~disease, hearing loss, and eye abnormalities~~tubules. InLoss ~~November~~of ~~2022,~~functional wePC1 ~~began~~or aPC2 ~~Phase~~protein 2leads ~~monotherapy~~to ~~clinical~~uncontrolled ~~trial~~cyst ~~for~~formation. ~~ELX-02~~Approximately ~~for~~26% ~~the potential treatment~~ of ~~Alport~~ADPKD ~~syndrome~~patients ~~and~~have NMs in ~~January 2023, we announced that~~ the ~~first~~PKD1 ~~patients~~and ~~had~~PKD2 ~~been~~genes ~~enrolled.~~resulting ~~ELX-02~~in ~~treatment~~a ~~has~~prevalence ~~demonstrated restoration~~ of ~~full-length~~approximately ~~protein~~40,000 into ~~multiple preclinical models~~50,000 ~~including~~patients ~~collagen~~in IVthe ~~and~~United ~~collagen~~States. ~~VII~~Patients inexperience ~~cells~~hypertension, ~~and~~kidney ~~also~~stones, ~~clinical~~urinary ~~activity~~tract ininfections, ~~our~~heart ~~Phase~~valve ~~2 cystic fibrosis trial. We believe our results~~abnormalities, ~~previously~~hematuria ~~conducted~~and inincreased ~~vivo~~probability ~~studies showing improvement~~ of ~~kidney~~aortic ~~function~~aneurysm. ~~with~~Formation ~~collagen~~of IVthese ~~restoration~~cysts ~~and~~eventually ~~the~~leads ~~ability~~ to ~~achieve~~nephromegaly ~~high~~ (kidney ~~drug~~enlargement) ~~levels~~and atend-stage ~~tolerable~~renal ~~doses~~disease. ~~support~~The ~~the~~only ~~clinical~~approved ~~development~~therapy offor ~~ELX-02~~ADPKD, intolvaptan, ~~Alport~~does ~~syndrome.~~not ~~This~~address ~~Phase~~the 2underlying ~~trial~~genetic iscause ~~targeting~~and ~~dosing~~carries ofsignificant uptolerability tolimitations. ~~eight~~Preclinical ~~Alport~~organoid ~~syndrome~~and ~~patients~~cellular ~~with~~models ~~nonsense~~have ~~mutations~~shown inincreased ~~the~~PC1 ~~COL4~~and PC2 gene. ~~Patients~~expression ~~will~~following betreatment ~~dosed for two months~~ with ~~a three month follow-up~~exaluren. InWe ~~addition~~plan to ~~the~~initiate ~~primary~~enrollment ~~endpoint~~in ofa ~~safety,~~Phase ~~the~~2 ~~key~~trial ~~secondary~~of ~~efficacy~~exaluren ~~endpoint~~for ofthe ~~proteinuria~~treatment ~~will~~of benmADPKD ~~measured~~in ~~every~~2027 ~~two~~following ~~weeks.~~protocol ~~For~~finalization ~~eligible~~and ~~patients,~~clearance ~~induction~~ of ~~COL~~an IVInvestigational ~~will~~New ~~also~~Drug beapplication ~~measured~~(“IND”) atby the ~~end of two months~~FDA. ~~Topline~~We ~~results~~anticipate ~~are~~topline ~~expected~~data infrom ~~the~~this ~~first~~trial ~~half~~by ~~of 2023~~mid-2028.

We are also ~~advancing~~developing ZKN-013, as an oral ribosome modulating agent (“RMA”) with structural similarity to azithromycin that induces PTC readthrough. In March 2024, we entered into an exclusive global rights agreement with Almirall (the “Almirall License Agreement”) for Almirall to develop and commercialize ZKN-013 for the use in orphan dermatological diseases. Through this collaboration, we are developing ZKN-013 for the treatment of recessive dystrophic epidermolysis bullosa (“RDEB~~/JEB~~”) and ~~FAP~~junctional ~~patients~~epidermolysis ~~with~~bullosa ~~nonsense~~(“JEB”) ~~mutations~~with NMs. RDEB and JEB are rare skin diseases characterized by mutations in the Collagen VII (RDEB) and LAMB3 (JEB)

5772

~~LAMB3(JEB)~~ proteins. We estimate that there are approximately 4,000 patients with ~~nonsense~~NMs ~~mutations~~ in these diseases in the major markets of the USUnited States, Japan and Western Europe. Patients with these diseases suffer from severe skin bruising, wounds and internal lesions resulting in increased risk of skin cancer and severe malnourishment. ~~FAP~~Under ~~patients have mutations in~~ the ~~APC~~Almirall ~~gene~~License ~~that~~Agreement, ~~result~~we inreceived aan ~~proliferation~~upfront payment of ~~polyps~~$3 inmillion ~~the~~and ~~colon~~a ~~that~~development ifmilestone ~~untreated~~payment ~~can~~of ~~lead~~$3 tomillion ~~colon~~in ~~and other related cancers~~2024. ~~There~~Almirall ~~are~~is ~~currently~~responsible nofor ~~approved~~development ~~disease~~and ~~modifying~~commercialization ~~therapies~~of ~~for these diseases.~~ ZKN-013 ~~has~~and ~~demonstrated~~we ~~robust~~are ~~collagen~~eligible ~~VII~~to ~~restoration~~receive inup ~~patient cells comparable~~ to ~~5-10%~~approximately ~~of protein restoration across a range of mutations~~$470.0 Wemillion ~~have also seen~~ in ~~two~~additional ~~separate studies~~development, ~~that~~regulatory ~~treatment~~and ofcommercial ~~APCMin~~milestone ~~mice,~~payments aas ~~validated~~well ~~model~~as ~~for~~tiered ~~evaluating~~royalties ~~potential~~based ~~treatment~~on ~~effects~~global insales. ~~FAP~~The ~~patients,~~agreement ~~with~~may ~~ZKN-013~~be ~~for~~terminated ~~eight~~under ~~weeks~~specified ~~reduced polyp number~~circumstances, ~~polyp~~including ~~size and meaningfully improved survival. We submitted an IND~~ for ~~ZKN-013~~convenience onby ~~March 24~~Almirall, ~~2023~~in ~~for~~which ~~the~~case ~~treatment~~rights ofmay ~~RDEB~~revert to us.

In September 2022, in consultation with the Cystic Fibrosis Foundation (“CFF”), we terminated the development of ELX-02 delivered subcutaneously, for the treatment of cystic fibrosis (“CF”) patients with at least one nonsense (“Class 1 CF”) mutations. This decision was made after our Phase 2 trial of ELX-02 in combination with ivacaftor, an approved drug currently marketed for the treatment of certain CF patients under the trade name “Kalydeco”, did not meet the secondary efficacy endpoint of reduction from baseline in sweat chloride concentration (SCC) or improvement from baseline in percent forced expiratory volume (FEV1). Encouragingly, we continued to see strong evidence of biological activity similar to that in our previously completed Phase 2 study that reported in November 2021 a reduction in sweat chloride concentration from baseline after one week of treatment with ELX-02. We believe that the lack of statistically significant clinical benefit in Class 1 CF patients was due to drug concentration in the lung tissue being significantly below that required for effect consistent with our preclinical studies. ELX-02 was well tolerated in the Phase 2 trial with no drug related adverse events even at the clinical dose of 1.5mg/kg. Going forward, we plan to only develop that ELX-02 as an inhaled therapy for Class 1 CF patients because the achievable drug concentrations are more than one-hundred times higher in the lung tissue than when given subcutaneously. We have completed the IND enabling studies for inhaled ELX-02 in Class 1 CF but further clinical development is contingent upon funding from the CFF.

Acquisition of Zikani Therapeutics, Inc.

On April 1, 2021, the Company acquired Zikani Therapeutics, Inc. (“Zikani” and such acquisition, the “Zikani Merger”), a company in preclinical development and engaged in the science of ribosome modulation, leveraging its innovative TURBO-ZMTM chemistry technology platform to develop novel RMAs as potential therapeutics for diseases with limited treatment options. The TURBO-ZMTM platform is designed to enable rapid synthesis of novel compounds that can be optimized to modulate the ribosome in a disease specific manner. The TURBO-ZMTM synthetic chemistry platform can design oral novel macrolide-based small molecules that are potent oral modulators with favorable therapeutic indices. Macrolides are antibiotics that inhibit protein synthesis in bacteria.

Under the terms of the Agreement and Plan of Merger, the Company issued 189,920 shares of common stock in exchange for all of the issued and outstanding equity interests of Zikani (the “Merger Consideration”). The Zikani Merger was accounted for as an asset acquisition with acquired in-process research and development which was immediately expensed.

Results of Operations

~~Comparison~~For discussion of 2022 results and comparison with 2021 results, refer to Part II, Item 7, “Management's Discussion and Analysis of Financial Condition and Results of Operations” in our Annual Report on Form 10-K for the ~~Years~~fiscal ~~Ended~~year ended December 31, 2022. ~~and 2021~~

Comparison of the Years Ended December 31, 2025, 2024 and 2023

Dollar amounts in the following table are in thousands:

	Year ended December 31,						~~2022 / 2021~~				2025 / 2024							2024 / 2023
	2022			2021			$ Change			% Change
	2025			2024			2023				$ Change			% Change				$ Change			% Change
Operating expenses:
License and service revenue:	$	-		$	6,359		$	-			$	(6,359	)		(100	)	%	$	6,359		100			%
Research and development	$	23,727		$	22,899		$	828			4		%
Operating expenses:
General and administrative		10,692			20,449			(9,757	)		(48	)	%
Research and development		3,056			3,577			8,598				(521	)		(15	)	%		(5,021	)		(58	)	%
In process research and development		-			22,670			(22,670	)		(100	)	%
General and administrative		3,382			5,250			8,690				(1,868	)		(36	)	%		(3,440	)		(40	)	%
Total operating expenses		346,~~419~~438			668,~~018~~827			~~(31~~17,~~599~~288	)		~~(48~~	)(2,389	%)		(27	)	%		(8,461	)		(49	)	%
Loss from operations		(346,~~419~~438	)		(662,~~018~~468	)		(3117,~~599~~288	)		~~(48~~	)(3,970	%)		(161	)	%		14,820			86		%
Other expense, net		1,646			709			937			132		%
Other (income) expense, net		(443	)		675			(234	)			1,118		NM			%		(909	)	NM			%
Net loss	$	(365,~~065~~995	)	$	(663,~~727~~143	)	$	(3017,~~662~~054	)		~~(46~~$	)(2,852	%)		(91	)	%	$	13,911			82		%

58License and service revenue

License and service revenue for 2024 was $6.4 million, of which $3.0 million related to the achievement of a development milestone as a result of the Almirall License Agreement that was entered into in March 2024. There was no license and service revenue during the years ended December 31, 2025 and 2023. In March 2025, Almirall informed us of its decision to not exercise the option for continued research and development services under the Almirall License Agreement, as permitted within the Almirall License Agreement, thereby relieving us of our remaining responsibilities under the Almirall License Agreement. We remain eligible to receive additional payments throughout the potential development phases, including development and sales milestones of up to approximately $470.0 million and tiered royalties based on any potential future global sales. No further license and service revenue is expected from the Almirall License Agreement unless and until the development and sales milestones are achieved, and the timing of the achievement of the development and sales milestones is uncertain.

Research and development expenses

Research and development expenses were $233.71 million for the year ended December 31, ~~2022~~2025 compared to $223.96 million for the year ended December 31, ~~2021~~2024, ana ~~increase~~decrease of $0.85 million. The ~~increase~~decrease was primarily related to a $0.18 million ~~increase~~decrease in clinical trial expenses related primarily to Alport ~~and~~related ~~CFF~~activities, ~~funded~~partially ~~activities~~offset ~~and~~by a $0.82 million net increase in ~~facility~~salaries and ~~research~~other ~~and~~personnel ~~development~~ related ~~overhead expenses~~costs, ~~offset~~including by a ~~$0.1 million~~ decrease in ~~expenses~~stock-based ~~related~~compensation toexpense ~~subcontractors,~~of ~~advisors,~~$0.1 ~~and lab supplies in connection with preclinical research and development activities~~million.

Research and development expenses were $3.6 million for the year ended December 31, 2024 compared to $8.6 million for the year ended December 31, 2023, a decrease of $5.0 million. The decrease was primarily related to a $1.0 million decrease in clinical trial expenses related primarily to Alport related activities, a $2.2 million decrease in salaries and other personnel related costs, including a decrease in stock compensation expense of $0.5 million, and a decrease of $1.8 million in expenses related to subcontractors, advisors, and lab supplies in connection with preclinical research and development activities.

General and administrative expenses

Filing Compare · Eloxx Pharmaceuticals, Inc.