Enanta Pharmaceuticals : 2025 Annual Report

About this update from Enanta Pharmaceuticals, Inc.

Annual Report 2025 January 15, 2026 To Our Shareholders, All of us at Enanta are committed to leveraging our expertise in small molecule drug discovery to develop novel, best-in-class medicines to transform the lives of patients with viral infections and immunological diseases. As we reflect on 2025, we made significant progress across our pipeline, laying a strong foundation. Looking to 2026, I am confident that we are poised to achieve meaningful value creation, and I could not be more optimistic for the year ahead. At the core of our efforts in virology is our commitment to delivering the first treatment for respiratory syncytial virus (RSV) to patients. There is a significant unmet need for RSV treatments, despite the availability of vaccines and prophylactic monoclonal antibodies. Our two clinical-stage candidates for the treatment of RSV - zelicapavir, an N-protein inhibitor, and EDP-323, an L-protein inhibitor - hold significant promise to advance patient care in RSV. In September, we reached a major milestone by reporting data for zelicapavir, a culmination of years of dedication and perseverance from our team. These positive data from RSVHR, our Phase 2b study of zelicapavir in a high-risk adult outpatient population, represent the first time an antiviral treatment demonstrated a clinically meaningful benefit in high-risk adult outpatients with RSV. Specifically, zelicapavir demonstrated an improvement of 6.7 days in time to complete resolution of all 13 RSV symptoms compared to placebo, for patients with congestive heart failure, chronic obstructive pulmonary disease or age 75 or older, termed the HR3 population. Additionally, zelicapavir shortened time to complete resolution of the 29-parameter total RiiQ™ symptom scale by 7.2 days in the HR3 population compared to placebo. RSVHR also met key secondary endpoints, including a reduction in hospitalization and antiviral effects. We believe the totality of these data identified multiple potential registration endpoints for a Phase 3 trial. We also presented new data at IDWeek™ building on previously reported positive results from the Phase 2 study of zelicapavir in pediatric patients, demonstrating that treatment with zelicapavir is associated with shortened time to complete resolution of RSV symptoms - defined as all symptoms absent and patient discharged from hospital. Overall, we are proud that zelicapavir has been dosed in more than 700 people and continues to be well-tolerated with a favorable safety profile. Our second RSV candidate, EDP-323, has the potential to be a best-in-disease treatment. We presented new data at IDWeek™ from the previously disclosed successful Phase 2a human challenge study, including a post-hoc post-exposure prophylaxis analysis suggesting that EDP-323 may also be effective in preventing infection after exposure. Among 68 RSV-exposed subjects randomized to receive EDP-323 or placebo, 26% of placebo recipients became infected versus 0% of EDP-323 recipients (p<0.001). These results are highly encouraging and support further clinical development of EDP-323. Looking forward, we are continuing Phase 3-enabling activities, including aligning with the U.S. Food and Drug Administration on an adult Phase 3 trial design and on an overall pathway to registration. In parallel, we are exploring business development opportunities related to our RSV program. With zelicapavir and EDP-323, we have the leading RSV treatment portfolio in the industry and are committed to ensuring these drugs reach patients while maximizing value for our shareholders. Turning to immunology, we are focused on the treatment of type 2 immune driven diseases, in areas with significant unmet need. Our team is leveraging deep expertise in medicinal chemistry to design oral molecules that are highly potent and selective with optimized preclinical profiles. Currently, we are advancing programs targeting KIT, STAT6 and MRGPRX2 inhibition. In November, we announced EDP-978, a novel, potent and selective oral KIT inhibitor, as our clinical candidate for the treatment of chronic spontaneous urticaria and potentially other mast-cell-driven diseases. EDP-978 demonstrates nanomolar potency, sub-nanomolar activity in vivo , high selectivity for KIT versus other kinases, and favorable in vitro and in vivo ADME properties preclinically. We are on track to submit an Investigational New Drug (IND) application in the first quarter of 2026, with topline Phase 1 data expected in the fourth quarter of 2026. In November, we also nominated EPS-3903, a novel, oral STAT6 inhibitor, as our lead development candidate for the treatment of atopic dermatitis and other diseases currently treated by dupilumab. Preclinically, EPS-3903 exhibits nanomolar potency and high selectivity for STAT6, with rapid, continuous and complete (>90%) inhibition of phosphorylated STAT6 after oral dosing in mice. EPS-3903 also demonstrates efficacy comparable to dupilumab in multiple disease models. Currently, we are performing scale-up and IND enabling activities and targeting an IND filing in the second half of 2026. We also expanded our immunology portfolio with our newest program targeting MRGPRX2, a receptor expressed predominantly on mast cells, with the potential to address multiple chronic inflammatory diseases including urticaria, asthma, prurigo nodularis, migraine and others. We are excited about this program and expect to select a development candidate in the second half of 2026. I'm proud of the progress we have made across our immunology portfolio, having introduced three new programs in just two years. With programs in KIT, STAT6 and MRGPRX2 inhibition, we have the potential to treat broad patient populations across numerous diseases and to create meaningful longterm value. Operationally, in August, we filed a suit in the Unified Patent Court (UPC) of the European Union against Pfizer seeking a determination of liability for use and infringement of Enanta's European Patent in the manufacture, use and sale of Pfizer's COVID-19 antiviral, Paxlovid™ (nirmatrelvir tablets; ritonavir tablets). Under UPC procedures, a hearing on the infringement action is expected to occur within the UPC's published 12-month target, with the decision rendered within weeks thereafter, which we understand is closely adhered to by the UPC. By filing suit in the UPC, we will be able to present to a panel of technical judges and seek to obtain a judgment of liability that will apply in the 18 European member states. In the U.S. we are continuing to advance our appeal to the Federal Circuit, having filed our notice of appeal in the first quarter of 2025 and completed the briefing phase in the first half of 2025. Financially, we ended 2025 in a solid position with $188.9 million in cash, cash equivalents and marketable securities, further strengthened by $74.5 million in gross proceeds from an upsized public offering in October. Based on our operating plan, we believe our existing financial resources, including cash flows from the retained portion of our royalties from AbbVie's sales of MAVYRET®/ MAVIRET® (glecaprevir/pibrentasvir), will enable us to fund our programs into fiscal 2029. MAVYRET®/ MAVIRET® (glecaprevir/pibrentasvir) remains a leading treatment for hepatitis C virus (HCV). Importantly, AbbVie received FDA approval of an expanded indication for MAVYRET® in June 2025 as the first and only treatment for people with acute HCV. This expanded indication is a heartening reminder of the critical role this drug continues to play in treating millions infected with HCV. I would be remiss if I did not mention the passing of our beloved and respected longtime Chief Financial Officer, Paul J. Mellett, Jr. Since joining Enanta more than two decades ago, Paul's leadership and generosity of spirit have been at the core of the Company. His dedication to Enanta was complete and steadfast as evidenced by the strength of the team he leaves behind. In closing, I would like to recognize the physicians, patients and caregivers involved in our completed RSV studies. I would also like to acknowledge our employees for their hard work and commitment in the past year. And finally, all of us at Enanta owe sincere gratitude to you, our shareholders, for your support throughout the year to execute on our mission and to achieve our vision of transforming the lives of patients with curative therapies. As we look to 2026, I hope you share in our excitement about the opportunities ahead. Sincerely, Jay R. Luly, Ph.D. President and Chief Executive Officer 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 ended September 30, 2025 OR TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 Commission File Number 001-35839 ENANTA PHARMACEUTICALS, INC. (Exact name of registrant as specified in its charter) DELAWARE 04-3205099 (State or other jurisdiction of incorporation or organization) 4 Kingsbury Avenue Watertown, Massachusetts 02472 (617) 607-0800 (I.R.S. Employer Identification Number) (Address, including zip code, and telephone number, including area code, of registrant's principal executive offices) Securities registered pursuant to Section 12(b) of the Act: Title of each class Trading Symbol(s) Name of each exchange on which registered Common Stock, par value $0.01 per share ENTA Nasdaq Securities registered pursuant to Section 12(g) of the Act: None Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒ Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 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 ☐ Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, smaller reporting company, or an emerging growth company. See the definitions of "large accelerated filer," "accelerated filer," "smaller reporting company," and "emerging growth company" in Rule 12b-2 of the Exchange Act: Large accelerated filer ☐ 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 requireda recovery analysis of incentive-based compensation received by any of the registrant's executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐ Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act): Yes ☐ No ☒ The aggregate market value of the registrant's common stock held by non-affiliates of the registrant as of the last business day of the registrant's most recently completed second fiscal quarter, March 31, 2025, based on the last reported sale price of the registrant's common stock of $5.52 per share was $110,592,792. The number of shares of the registrant's Common Stock, $0.01 par value, outstanding as of November 4, 2025 was 28,862,601 shares . DOCUMENTS INCORPORATED BY REFERENCE Information for Part III of this Form 10-K will either (i) be incorporated by reference to portions of the registrant's Definitive Proxy Statement for its 2026 Annual Meeting of Stockholders, or (ii) if the Definitive Proxy is not filed with the Securities and Exchange Commission within 120 days after the registrant's fiscal year end of September 30, 2025, it will be provided by amendment to this Form 10-K. As used in this Form 10-K, "Enanta," "the Company," "we," "our," and "us" refer to Enanta Pharmaceuticals, Inc., and "MAVYRET/MAVIRET" refers to AbbVie's HCV regimen consisting of tablets of glecaprevir/pibrentasvir, except where the context otherwise requires or as otherwise indicated. MAVYRET ® , MAVIRET ® , VIEKIRA PAK ® , VIEKIRAX ® and EXVIERA ® are trademarks of AbbVie, Inc. NOTE REGARDING FORWARD-LOOKING STATEMENTS This Annual Report on Form 10-K contains forward-looking statements concerning our business, operations and financial performance and condition, as well as our plans, objectives and expectations for our business operations and financial performance and condition. Any statements contained herein that are not statements of historical facts may be deemed to be forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as "aim," "anticipate," "assume," "believe," "contemplate," "continue," "could," "due," "estimate," "expect," "goal," "intend," "may," "objective," "plan," "predict," "potential," "positioned," "seek," "should," "target," "will," "would," and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. These forward-looking statements include, but are not limited to, statements about overall trends, royalty revenue trends, research and clinical development plans, liquidity and capital needs and other statements of expectations, beliefs, future plans and strategies, anticipated events or trends and similar expressions. These forward-looking statements are based on our management's current expectations, estimates, forecasts and projections about our business and the industry in which we operate and our management's beliefs and assumptions. These forward-looking statements are not guarantees of future performance or development and involve known and unknown risks, uncertainties and other factors that are in some cases beyond our control. As a result, any or all of our forward-looking statements in this Annual Report on Form 10-K may turn out to be inaccurate. Factors that may cause actual results to differ materially from current expectations include, among other things, those listed under "Risk Factors" and discussed elsewhere in this Annual Report on Form 10-K. These forward-looking statements speak only as of the date of this Annual Report on Form 10-K. Except as required by law, we assume no obligation to update or revise these forward-looking statements for any reason, even if new information becomes available in the future. You should, however, review the factors and risks we describe in the reports we will file from time to time with the SEC after the date of this Annual Report on Form 10-K. ENANTA PHARMACEUTICALS, INC. ANNUAL REPORT ON FORM 10-K For the year ended September 30, 2025 INDEX Item No. Page Summary of Principal Risk Factors .......................................................................................................... 1 1. PART I Business .................................................................................................................................................... 3 1A. Risk Factors .............................................................................................................................................. 32 1B. Unresolved Staff Comments..................................................................................................................... 56 1C. Cybersecurity Risk Management and Strategy......................................................................................... 56 2. Properties .................................................................................................................................................. 57 3. Legal Proceedings..................................................................................................................................... 57 4. Mine Safety Disclosures ........................................................................................................................... 57 5. PART II Market for the Company's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities ....................................................................................................................................... 58 6. Reserved.................................................................................................................................................... 59 7. Management's Discussion and Analysis of Financial Condition and Results of Operations................... 60 7A. Quantitative and Qualitative Disclosures about Market Risk................................................................... 68 8. Consolidated Financial Statements and Supplementary Data .................................................................. 68 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure................... 69 9A. Controls and Procedures ........................................................................................................................... 69 9B. Other Information ..................................................................................................................................... 69 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections...................................................... 69 10. PART III Directors, Executive Officers and Corporate Governance ....................................................................... 70 11. Executive Compensation .......................................................................................................................... 70 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters 70 13. Certain Relationships and Related Transactions, and Director Independence ......................................... 71 14. Principal Accounting Fees and Services................................................................................................... 71 15. PART IV Exhibits and Financial Statement Schedules ............................................................................................ 72 16. Form 10-K Summary................................................................................................................................ 74 Signatures.................................................................................................................................................. 75 SUMMARY OF PRINCIPAL RISK FACTORS This summary briefly states the principal risks and uncertainties facing our business that could affect our common stock, which are onlya select portion of those risks. A more complete statement of those risks and uncertainties is set forth in the Section 1A "Risk Factors" of this report. This summary is qualified in its entirety by that more complete statement. You should carefully read the entire statement and "Risk Factors" when considering the risks and uncertainties as part of your evaluation of an investment in our common stock. We will require substantial additional funding to achieve our goals. If we do not generate sufficient funding from our existing collaboration and any future collaborations, we will need to obtain additional funding to support our operations. A failure to obtain funding when needed could force us to delay, limit, reduce or terminate some or all of our product development efforts. Our revenues for the next several years are substantially dependent upon AbbVie's success selling MAVYRET/MAVIRET, which includes our protease inhibitor, glecaprevir, for the treatment of HCV . AbbVie may experience lower sales volume in future quarters, primarily due to a reduction in diagnoses and treatment rates of HCV. AbbVie's MAVYRET TM /MAVIRET TM regimen will have to continue to compete successfully against other products and therapies for HCV, including competition for exclusive arrangements with third-party payors and governmental entities as well as price competition, both in the U.S. and in other markets worldwide. Beginning after June 30, 2023, 54.5% of our reported revenues represent payments that go directly to OMERS following our April 2023 sale of that portion of our MAVYRET/MAVIRET royalties earned through June 30, 2032, subject to a cap on aggregate payments to OMERS equal to 1.42 times the purchase price. Any further changes in royalty revenue earned under our AbbVie agreement or in the level of expenses associated with our research and clinical development programs, or both, will cause our results of operations to fluctuate from period to period. If AbbVie experiences lower sales volumes in future quarters combined with research and development expenses in support of our advancing programs, we expect to have continuing operating losses for the foreseeable future. Many of the preclinical and clinical development activities required for our product candidates must be contracted out to contract research organizations, or CROs, at significant expense. We expect these expenses to increase substantially in the coming years if we are able to advance any of our compounds into registrational clinical studies, as well as any impact of inflation, the combination of which will likely result in continuing operating losses. There are many companies developing potential therapies for RSV, type 2 immune and mast-cell-driven diseases and other virology and immunology indications, which may result in others discovering, developing or commercializing products before we do or doing so more successfully than we do. In most of the disease areas currently the subject of our research and development efforts, there are other companies with product candidates that are more advanced than ours. If we are not "first to market" or sufficiently differentiated with one of our product candidates in one or more of our targeted disease indications, such as CSU, our competitive position could be compromised because it may be more difficult for us to obtain marketing approval for that product candidate and/or market acceptance of that product candidate as a follow-on competitor. Clinical drug development for viral infections and immunology indications involvesa lengthy and expensive process with uncertain timelines, uncertain outcomes and evolving clinical endpoints for regulatory approvals. If clinical trials of any of our proprietary product candidates are prolonged or delayed, we may be unable to commercialize our product candidates on a timely basis . Changes in regulatory requirements, policies and guidelines, including guidelines specifically addressing requirements for the development of treatments for RSV, type 2 immune and mast-cell-driven diseases or other virology and immunology indications could also delay the time required to reach regulatory approval of one or more of our product candidates. The results of clinical trials are inherently uncertain. 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, if any, including sufficient efficacy and an acceptable safety and tolerability profile . Several companies in the disease areas we are seeking to address have suffered significant setbacks in advanced clinical trials due to adverse safety profiles or lack of efficacy, notwithstanding promising results in earlier studies. Clinical trials involving our product candidates may be suspended or terminated at any time fora number of safety-related reasons. For example, administering any product candidate to humans may produce undesirable side effects not identified in preclinical studies. We may choose to test any of our clinical candidates preclinically and/or clinically in combination with other compounds with different mechanisms of action. Any adverse results from such testing may have adverse consequences for the further development potential of not only the combination but also the clinical candidate itself as a monotherapy or in combination with other mechanisms of action. We may delay or terminate the development of a product candidate at any time if we believe the perceived market or commercial opportunity does not justify further investment. We could be unsuccessful in obtaining or maintaining adequate patent protection for one or more of our product candidates. We are competing to develop intellectual property in areas of small-molecule drug development that are highly competitive. We cannot be certain that patents will be issued or granted with respect to our patent applications that are currently pending, or that issued or granted patents will not later be found to be invalid and/or unenforceable, be interpreted in a manner that does not adequately protect our products, or otherwise fail to provide us with any competitive advantage. We cannot be certain that we were the first to file patent applications on our product candidates or for their uses, or that our product candidates will not infringe patents that are currently issued or that are issued in the future. We rely on third parties to manufacture our clinical drug supplies, monitor, support, conduct and/or oversee clinical trials of our product candidates that we develop independently. PART I ITEM 1. BUSINESS BUSINESS Overview We area biotechnology company that uses our robust, chemistry-driven approach and drug discovery capabilities to discover and develop small molecule drugs for virology and immunology indications. Virology: We discovered glecaprevir, the second of two antiviral protease inhibitors developed through our collaboration with AbbVie for the treatment of acute or chronic infection with hepatitis C virus, or HCV. Glecaprevir is co-formulated as part of AbbVie's leading brand of direct-acting antiviral, or DAA, combination treatment for HCV, which has been marketed under the tradenames MAVYRET ® (U.S.) and MAVIRET ® (ex-U.S.) (glecaprevir/pibrentasvir) since 2017 for the treatment of chronic HCV. MAVYRET ® was also approved as the first and only treatment for acute HCV infection in June 2025. Our active development programs in virology are focused on respiratory syncytial virus, or RSV, the most common cause of bronchiolitis and pneumonia and a leading cause of U.S. hospitalization in young children and a significant cause of respiratory illness in older adults. Populations at high risk for severe RSV infection include infants and young children, adults older than 65 years of age, and those with comorbidities such as chronic heart or lung disease. Recent CDC estimates suggest a significant RSV burden in the U.S., with up to 6.5 million outpatient visits, 350,000 hospitalizations and 23,000 deaths annually. We also have clinical-stage programs in virology for SARS-CoV-2, the virus that causes COVID-19, and Hepatitis B virus, or HBV, the most prevalent chronic hepatitis. Immunology In immunology, we are designing and developing highly potent and selective, oral small molecule inhibitors for the treatment of type 2 inflammatory disease by targeting key mechanisms of the immune response. An overactive response is a primary driver of a number of inflammatory diseases for which there is an enduring unmet need including atopic dermatitis, or AD, urticarias, asthma, prurigo nodularis, or PN, chronic rhinosinusitis with nasal polyps, or CRSwNP, as well as some forms of chronic obstructive pulmonary disease, or COPD, and other conditions. Based on industry reports, by 2030 the market is projected to be approximately $5 billion for urticaria, $30 billion for AD and $35 billion for the combined market of asthma, COPD, CRSwNP, and PN. Our initial immunology targets involve the following mechanisms of immune response: The receptor tyrosine kinase, known as KIT, which is critical for regulating mast cell survival and activation, including release of potent inflammatory mediators such as histamine, which is a primary driver of inflammation in the skin and implicated in multiple allergic diseases; and STAT6, a transcription factor uniquely responsible for interleukin-4, or IL-4, and interleukin-13, or IL-13, cell signaling, which drivesa type 2 dominant phenotype and downstream inflammation. These mechanisms are implicated, along with others, in several diseases, and it is not uncommon for an efficacious treatment for one disease to be tested and approved for other immunology indications. We currently plan to focus our initial immunology drug development proof-of-concept efforts on the following disease indications: Chronic spontaneous urticaria, or CSU, a severely debilitating, chronic inflammatory skin disease manifested by hives, angioedema, which is swelling of soft tissues, or both, but with no identified triggers, which has an estimated global prevalence of between 0.5% - 1% of the population, resulting in approximately 1.75-3.5 million people with this condition at any given time in the U.S. alone or chronic inducible urticaria (CIndU) of various forms with a variety of known triggers; and Atopic dermatitis, or AD, a chronic dermatological disease characterized by dry, red, inflamed, irritated and itchy skin with significant quality of life impacts such as leadinga limited lifestyle, avoidance of social interactions and a reduced range of activities, with AD affecting 7.3% of the US adult population, of whom approximately 40% have moderate to severe disease. As of September 30, 2025, we had $188.9 million in cash, cash equivalents and short-term marketable securities. Based on our operating plan, we believe that our existing cash, cash equivalents, and short-term marketable securities as of September 30, 2025, as well as the cash flows from our retained portion of future HCV royalties and the proceeds from our public offering in October 2025, will enable us to fund our operating expenses and capital expenditure requirements into fiscal 2029. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. See "Liquidity and Capital Resources." Because of the numerous risks and uncertainties associated with clinical development and commercialization, we are unable to accurately predict the timing or amount of increased expenses or when, or if, we will be able to achieve or maintain profitability. Until such time, if ever, as we can generate substantial revenue sufficient to achieve profitability, we expect to finance our operations through a combination of equity offerings, non-dilutive financings, collaborations, strategic alliances or licensing agreements. We may be unable to raise additional funds or enter into such other agreements or arrangements, when needed, on favorable terms, or at all. If we are unable to raise capital or enter into such agreements as, and when, needed, we may have to significantly delay, scale back or discontinue the further development and commercialization efforts of one or more of our products, or may be forced to reduce or terminate our operations. Our Wholly-Owned Programs All of our development programs in virology and immunology are wholly-owned, including our RSV, KIT and STAT6 programs. RSV . We have two clinical stage candidates for RSV- zelicapavir (formerly EDP-938) and EDP-323. Both candidates inhibit viral replication and the production of new virions. These clinical candidates differ from fusion inhibitors, which act only at viral entry. Zelicapavir, which has Fast Track designation from the U.S. Food and Drug Administration, or FDA, is a potent inhibitor of the RSV N-protein for both major subgroups of RSV, referred to as RSV-A and RSV-B. Zelicapavir has been studied in two Phase 2 studies, each in a different high-risk patient population. EDP-323, which also has a Fast Track designation from the FDA, is an inhibitor of the RSV L-protein for both major subgroups of RSV that has completeda Phase 2 challenge study. We are evaluating potential partnership opportunities to advance our RSV programs to the next stage of clinical development. Zelicapavir - N-protein Inhibitor Candidate . Zelicapavir,a once-daily, oral, direct-acting antiviral selectively targeting the N-protein, has demonstrated statistically significant reductions in RSV viral load and symptoms in a human challenge model, Phase 2 clinical study. We believe that zelicapavir has the greatest potential to show optimal efficacy in high-risk populations since these patients have reduced RSV immunity, which manifests in a higher and longer duration of viral load and greater disease severity, allowing a bigger window to realize the full potential of zelicapavir. We are continuing to evaluate zelicapavir in high-risk populations, including pediatric patients and high-risk adults, all of which have significant unmet need: Hi gh-Risk Adults Study of Zelicapavir . In September 2025, we announced positive topline results from a Phase 2b study in high-risk adults, including those who are older than 65 years of age and those who have asthma, chronic obstructive pulmonary disease, or congestive heart failure. Pediatric Study of Zelicapavir . In December 2024, we announced positive topline results from the first-in-pediatrics Phase 2 randomized, double-blind, placebo-controlled study evaluating zelicapavir in hospitalized and non-hospitalized children aged 28 days to 36 months with RSV. In these Phase 2 clinical studies, zelicapavir has demonstrated a favorable safety profile, consistent with that observed in over 700 subjects exposed to zelicapavir to date. EDP-323 - L-protein Inhibitor Candidate . Our second clinical RSV candidate, EDP-323, is an oral, direct-acting antiviral selectively targeting the RSV L-protein, a viral RNA-dependent RNA polymerase enzyme that contains multiple enzymatic activities required for RSV replication. EDP-323 has sub-nanomolar potency against RSV-A and RSV-B in vitro and protected mice in a dose-dependent manner from RSV infection as demonstrated by both virological and pathological endpoints. EDP-323 is not expected to have cross-resistance to other classes of inhibitors and has the potential to be used alone, or in combination with other RSV mechanisms, to broaden the treatment window or addressable patient populations. Phase 2a Study of EDP-323 . In September 2024, we announced positive topline results for EDP-323 in a Phase 2a challenge study of healthy adults infected with RSV. Immunology . We are leveraging our expertise in developing inhibitors to design and develop highly potent and selective oral small molecule inhibitors targeting the following mechanisms of immune response: KIT Inhibitors . We havea preclinical stage program to develop oral KIT inhibitors for the treatment of CSU and potentially other indications by depleting mast cells, thereby addressing a primary driver of these diseases. We have selected EDP-978 as our clinical candidate. EDP-978 demonstrates potent nanomolar activity in both binding and cellular function assays, sub-nanomolar activity in vivo , and high selectivity for KIT versus other kinases. EDP-978 also demonstrates strong in vitro and in vivo absorption, distribution, metabolism and excretion (ADME) properties. We are finalizing the IND-enabling activities for this program in the fourth quarter of 2025 and expect to file an Investigational New Drug application, or IND, in the first quarter of 2026. STAT6 Inhibitors . We havea preclinical stage program to develop oral inhibitors of the signal transducer and activator of transcription6 transcription factor, known as STAT6, for the treatment of type 2 immune driven diseases. We are initially focusing on AD and potentially other indications by blocking the IL-4/IL-13 signaling pathway, thereby addressing a primary driver of these diseases. We have selected EPS-3903 as our lead development candidate. EPS-3903 inhibits STAT6 with nanomolar potency in both binding and cellular assays and is highly selective for STAT6 versus other STATs. EPS-3903 also demonstrates a rapid, continuous and complete (>90%) inhibition of phosphorylated STAT6 after oral dosing in mice. Importantly, EPS-3903 shows in vivo efficacy comparable to dupilumab, or an anti-mouse IL-4/IL-13 antibody, in multiple disease models of asthma (ovalbumin, house dust mite) and AD (MC903). EPS-3903 displays favorable in vitro and in vivo ADME properties, supportive of once-daily dosing potential. We have initiated IND-enabling activities with the goal of filing an IND in the second half of 2026. We plan to expand our presence in immunology with the introduction of a third program in the fourth quarter of 2025. We have utilized our internal chemistry and drug discovery capabilities to generate all of our development-stage programs. We continue to invest substantial resources in research programs to discover compounds targeting new disease areas. Our Out-Licensed Products HCV . Two protease inhibitors developed through our Collaborative Development and License Agreement with AbbVie have been clinically tested, manufactured, and commercialized by AbbVie as part of its combination regimens for HCV. We have received the full $330.0 million of contractual milestone payments under the agreement related to clinical development and commercialization regulatory approvals of these regimens in major markets, and we continue to earn royalties on sales of the second generation regimen. Glecaprevir is the HCV protease inhibitor we discovered that was developed by AbbVie in a fixed-dose combination with its NS5A inhibitor, pibrentasvir, for the treatment of chronic HCV. In June 2025 it was also approved by the FDA as the first and only treatment for acute HCV infection. This patented combination, currently marketed under the brand names MAVYRET®(U.S.) and MAVIRET® (ex-U.S.), is referred to in this report as MAVYRET/MAVIRET. This regimen is a once-daily, all-oral, fixed-dose, ribavirin-free treatment for HCV genotypes 1-6, or GT1-6, which is referred to as being pan-genotypic. In the U.S., EU and Japan it is approved as an 8-week treatment for patients with and without compensated cirrhosis and new to treatment. Today, these patients are estimated to represent the majority of HCV patients in over 50 countries where MAVYRET/MAVIRET is sold by AbbVie and where MAVYRET/MAVIRET remains the only 8-week pan-genotypic HCV treatment. The first protease inhibitor developed through this collaboration, paritaprevir, is part of AbbVie's initial HCV regimens, which have been almost entirely replaced by MAVYRET/MAVIRET. Since August 2017, substantially all of our royalty revenue has been derived from AbbVie's net sales of MAVYRET/MAVIRET. Our ongoing royalty revenues from this regimen consist of annually tiered, double-digit, per-product royalties on 50% of the calendar year net sales of the glecaprevir/pibrentasvir combination in MAVYRET/MAVIRET. The annual royalty tiers return to the lowest tier for sales on and after each January 1. In April 2023, we sold 54.5% of our future MAVYRET/MAVIRET royalties to an affiliate of OMERS, a Canadian public employee pension fund, fora $200.0 million cash payment, subject to a cap of total royalties sold equal to 1.42 times the cash payment. Our Strategy Our primary objective is to becomea leader in the discovery and development of small molecule drugs with an emphasis on first-in-disease treatments for RSV and best-in-class small molecule treatments for diseases with significant unmet medical needs in immunology. Our strategy includes the following key elements: Advance clinical development of novel virology product candidates for RSV. We have completed clinical studies of two compounds discovered in our research program for RSV, a viral infection for which there is currently no safe and effective treatment and as such there exists a substantial unmet medical need. We are evaluating potential partnership opportunities to advance our RSV programs to the next stage of clinical development. Advance our preclinical immunology portfolio of novel, oral inhibitors. We have ongoing discovery and preclinical efforts targeting multiple mechanisms of the immune response, including KIT, addressing mast cell driven diseases, with an initial focus on CSU. We also have a preclinical program targeting the STAT6 pathway, with an initial focus on AD. Invest in research and development of compounds against other immunology targets . We are continuing to invest resources in our research programs to identify and advance additional novel compounds that have the potential to address significant unmet medical needs in immunology. We may also seek to augment our product candidate pipeline through the acquisition or in-licensing of external assets and/or technologies in one or more of our disease areas of focus. Collaborate or out-license, where and when appropriate, with pharmaceutical partners to accelerate the development and commercialization of our proprietary compounds and/or create combination therapies . We may choose to collaborate with other companies to accelerate the global clinical development of one or more of our product candidates. We are also prepared to join forces, where and when appropriate, with collaborators where there is the potential for better treatments with combination therapies, as we did in HCV. Our decisions regarding our proprietary programs will be based on the results of our studies and the potential for collaborations, including combinations with one or more drugs targeting other mechanisms of action in these diseases. Continue to use our existing resources and future cash flow from our AbbVie collaboration to fund our research and development activities . Based on our operating plan, we believe our existing financial resources, as well as the cash flows from our retained portion of future HCV royalties and the proceeds from our October 2025 public offering, will enable us to fund our operating expenses and capital expenditure requirements into fiscal 2029. These resources will allow us to continue to advance compounds in clinical development and to progress the most promising candidates at least through proof-of-concept trials. Further development of any compound as a monotherapy or in combinations with other therapeutic agents when we believe such combinations will provide the most promising opportunities will require additional financial resources. Our Research and Development Pipeline The following table summarizes our product development pipeline in our virology and immunology programs: *Fixed-dose antiviral combination contains glecaprevir and AbbVie's NS5A inhibitor, pibrentasvir. Marketed by AbbVie as MAVYRET® (U.S.) and MAVIRET® (ex-U.S.). **Continued development dependent on partnering. ***Initial indications. Potential future indications include asthma, chronic inducible urticaria (CIndU), eosinophilic esophagitis (EoE), prurigo nodularis (PN) and others. Our RSV Program Background and Overview of RSV Respiratory syncytial virus, or RSV, is a virus that infects the lungs and is the most common cause of bronchiolitis and pneumonia in young children and a significant cause of respiratory illness in older adults, with estimates in the United States of up to 350,000 hospitalizations and up to 6.5 million outpatient visits during the 2024-2025 season. Populations at high risk for severe RSV infection include infants and young children, adults older than 65 years of age, and those with comorbidities such as chronic heart or lung disease. There are currently no safe and effective therapies for RSV infection. There are two long-acting monoclonal antibody products recently approved for prophylaxis use in all infants from AstraZeneca/Sanofi (BEYFORTUS ® ) and Merck (ENFLONSIA™), with BEYFORTUS also approved for those at risk up to 24 months of age. A maternal vaccine (ABRYSVO ® /Pfizer) has been approved for women and is recommended at 32-36 weeks (U.S.)& 24-36 weeks (EU) of pregnancy during the RSV season. In addition, two RSV vaccines have been approved in high-risk adults age 18-59 years and for all adults aged 60 years and above (ABRYSVO ® /Pfizer and Moderna/mRESVIA ® ) and a third RSV vaccine has been approved for high-risk adults age 50-59 years and for all adults age 60 years old and above (GSK/AREXVY ® ). While prophylaxis options have recently become available, there is still a significant unmet need for safe and effective antiviral treatments in patients at high-risk for serious RSV outcomes. The adoption of RSV vaccines has declined year over year, especially as the CDC recommendation for a single RSV vaccine dose is now restricted to high-risk adults age 50-74 years and for all adults 75 years and above, which is narrower than the FDA-approved labeling. Even with adoption, breakthrough infections will still occur, as vaccine efficacy is not complete. In the pediatric population, both the maternal vaccine and the prophylactic antibody approaches provide only passive immunity, which lasts for a limited period of time (approximately 4-5 months) and will generally shift the time of first RSV infection to the next season. Similarly, uptake of these options will not be optimal and breakthrough infections will still occur in the population that does receive them. Finally, the antibody approach hasa low barrier to the development of viral resistance. Thus, despite these options for prophylaxis, antiviral treatments are urgently needed. Scientific Background RSV is a single-stranded, negative-sense RNA virus. There are two major subgroups of RSV, designated RSV-A and RSV-B, each of which contains numerous genotypes. Both groups are viewed as capable of causing RSV infections that can result in hospitalization. The RSV genome consists of ten genes that encode for 11 proteins, namely NS1, NS2, N, P, M, SH, G, F, M2-1, M2-2, and L. The F and G proteins are the predominant target proteins for RSV vaccines. Similarly, small molecule therapeutics have focused primarily on theF (or fusion) protein, while some efforts have targeted the N (nucleocapsid) and L (contains viral RNA polymerase) proteins. Fusion inhibitors work by blocking viral entry,a mechanism that may be less ideal when treatment begins at a time when massive amounts of viral replication is already ongoing. Additionally, fusion inhibitors have been generally shown to have a lower barrier to the development of viral resistance when in clinical use. Replication inhibitors (e.g., N and L inhibitors) work by blocking viral replication at its source, stopping production on new virions. They have demonstrated a higher bar to the emergence of viral resistance. While certain companies are developing potential approaches geared toward the F-protein (or fusion protein, responsible for mediating viral entry of RSV into host cells), we are focused on mechanisms, such as the N-protein and L-protein inhibitors, that target the replication process of RSV directly. Competitive Landscape Several companies are seeking to develop antiviral treatments for RSV infection in adult and pediatric patients. Ark Biosciences and Shionogi have compounds in clinical development. There are several prophylaxis options on the market or in development. AstraZeneca/Sanofi (BEYFORTUS ® ) and Merck (ENFLONSIA™) have approved long-acting monoclonal antibodies for prophylaxis use in infants, and Pfizer has an approved maternal vaccine (ABRYSVO ® ), all of which provide passive, short-term immunity to infants. There are also two approved RSV vaccines for high-risk adults age 18-59 years and for all adults age 60 years and above (Pfizer/ABRYSVO ® and Moderna/mRESVIA ® ) and one approved RSV vaccine for high-risk adults age 50-59 years and in adults age 60 years and older (GSK/AREXVY ® ). Zelicapavir, Our N-Protein Inhibitor Through our internal chemistry efforts, we identified our lead clinical candidate, zelicapavir (formerly EDP-938). During preclinical studies, zelicapavir demonstrated a greater than 4-log reduction in viral load in an animal model challenged with RSV. Further, zelicapavir maintained nanomolar antiviral potency across all clinical isolates tested in vitro , as well as virus that was resistant to fusion inhibitors. The compound inhibited RSV at a post-entry replication step and maintained its activity in vitro when given 24 hours post infection. It was also shown to have a high barrier to viral resistance. In addition, combination studies of zelicapavir with other types of RSV inhibitors, such as L-protein and fusion inhibitors, showed synergistic antiviral effects. We have studied zelicapavir in Phase 2 studies that were designed to be proof-of-concept and exploratory studies to understand the viral response better in the context of RSV infection. These studies were conducted in otherwise healthy adults (not at high-risk for serious outcomes with RSV) infected with RSV. Data from these studies demonstrated that zelicapavir was safe and well-tolerated. Based on the growing safety profile of zelicapavir and differences in the range of the course of RSV infection in higher risk populations, which have always been our target populations, we continued the development of zelicapavir in patients at high-risk for developing severe infection leading to hospitalization or death. We believe zelicapavir has the greatest potential to show optimal efficacy in these high-risk populations with significant unmet need, since these patients have reduced RSV immunity, which manifests in a higher and longer duration of viral replication and greater disease severity, allowing a bigger window to realize the full potential of zelicapavir. High-Risk Adults Study of Zelicapavir On September 29, 2025, we announced positive topline results from our Phase 2b high-risk adults study of zelicapavir for the treatment of RSV. This Phase 2b study wasa randomized, double-blind, placebo-controlled study of RSV infection in non-hospitalized adults who are at high risk of complications, including the elderly and/or those with congestive heart failure, or CHF, chronic obstructive pulmonary disease, or COPD, or asthma. The proportion of patients aged 65-74 years or those with asthma was capped at 20% of the total population. Patients were enrolled within 72 hours of symptom onset and received 800mg of zelicapavir or placebo once daily for5 days. The goal of this proof-of-concept, signal finding study was to inform the design of a Phase 3 trial, including populations and endpoints, as well as give an indication of a treatment effect on symptoms that could be confirmed in a larger registrational study. Symptoms were measured using the Respiratory Infection Intensity and Impact Questionnaire, or RiiQ TM , scale, which evaluates a total of 29 parameters, including 13 RSV symptoms, four of which are lower respiratory tract disease, or LRTD, symptoms, and three other impact of disease components (daily activities, emotions, and social relationships). The primary endpoint evaluated the time to resolution of the LRTD subset of four symptoms to mild. Predefined analyses of complete resolution, defined by all symptoms absent, were also conducted. Multiple secondary endpoints, including all 13 RSV symptoms, total RiiQ TM score, additional patient reported outcomes (e.g., PGI-S), virology, safety, and hospitalization rate, were assessed. A total of 186 subjects received 800mg of zelicapavir (n=121) or placebo (n=65) orally, once daily for5 days and were evaluated for 28 days thereafter (safety population). An efficacy population of 175 patients was further defined as those who were polymerase chain reaction, or PCR, positive for RSV at a central laboratory. An HR3 population was defined as those who had CHF, COPD, or were age 75 or older, which represented 81% of the efficacy population. Demographics and baseline characteristics were balanced across treatment groups, with the majority of patients being enrolled within 48 hours of symptom onset. Zelicapavir demonstrated a favorable safety profile over the initial 5-day dosing period and through 28 days of follow-up, with adverse events, or AEs, being similar between zelicapavir and placebo. No AEs led to treatment discontinuation or study withdrawal in the zelicapavir group. The majority of AEs were mild with diarrhea and asthma being the most common AEs on zelicapavir at 3.3% and 2.5%, respectively. A clinically meaningful improvement in time to complete resolution (defined as all symptoms absent) of all 13 RSV symptoms was observed for zelicapavir compared to placebo, with a benefit of 2.2 days for the overall efficacy population and 6.7 days for the HR3 population. Zelicapavir also showed an improvement in time to complete resolution on the 29-parameter total RiiQ™ symptom scale of 3.6 days for the efficacy population and 7.2 days for the HR3 population compared to placebo. Additionally, there wasa 3.0-day faster time to complete resolution of lower respiratory tract disease (LRTD) symptoms in the HR3 population. No effect was observed on the time to partial resolution of symptoms (defined as mild or absent), including the primary endpoint of time to resolution of the LRTD subset of four symptoms in the efficacy population. A statistically significant improvement in RiiQTM RSV 13-symptom score in the HR3 population at Days9 (p=0.0403) and 14 (p=0.0247) was observed in a post hoc analysis for zelicapavir compared to placebo. Furthermore, the study meta key secondary endpoint with zelicapavir treatment resulting in a statistically significant 2-day faster improvement in a Patient Global Impression of Severity, or PGI-S, score compared to placebo in both the efficacy population (p=0.0446) and the HR3 population (p=0.0465). Importantly,a lower hospitalization rate was observed for patients treated with zelicapavir (1.7%) compared to placebo (5.0%). Blinded attribution by investigators judged none (0%) of the hospitalizations on zelicapavir and all (5.0%) of the hospitalization on placebo to be related to RSV. Post hoc attribution suggested RSV-relatedness of 0.9% for the patients on zelicapavir compared to 5.0% on placebo. The study met key secondary virology endpoints showing a robust antiviral effect, with a statistically significantly greater proportion of zelicapavir patients having an undetectable viral load at the end of treatment compared with placebo. In the efficacy population undetectable viral load at the end of treatment was 23.5% vs. 10.0% in placebo (p=0.0198), and in the HR3 population was 23.9% vs. 10.0% in placebo (p=0.0292). Treatment with zelicapavir resulted in a 4- or 5-day faster median time to undetectable viral load and a 0.6 or 0.7 log decline in viral load at the end of treatment compared to placebo for the efficacy and HR3 populations, respectively. Pediatric Study of Zelicapavir In December 2024, we announced positive topline results from the first-in-pediatrics Phase 2 randomized, double-blind, placebo-controlled study evaluating zelicapavir in 96 hospitalized and non-hospitalized children aged 28 days to 36 months with RSV. The first part of the study included dose ranging in two different age cohorts, focused on safety and pharmacokinetics (PK), and the second part of the study focused on virology outcomes from a single dose selected from the first part of the study. Zelicapavir demonstrated a favorable safety profile over the 5-day dosing period and through 23 days of followup. There were no adverse effects leading to treatment discontinuation or study withdrawal. Zelicapavir achieved target drug exposure levels across all age groups and dosing cohorts. Exposure was similar across cohorts and doses, and all patients receiveda therapeutic dose. A dose of 5 mg/kg was selected for patients aged ≥28 days to <12 months, and a dose of 7.5 mg/kg was selected for patients aged ≥12 months to ≤36 months. An antiviral effect was observed for the primary and secondary virology endpoints in the overall pooled efficacy population, with the viral load decline peaking at 0.7 log on Day 9 compared to placebo. The primary endpoint for Part 2 of the study showed a more pronounced effect, with a viral load decline of 1.0 log at Day 3 and 1.4 log at Day5 compared to placebo. Additionally,a rapid and robust antiviral effect was observed in the prespecified subset of patients who were randomized within 3 days of symptom onset, which represents about 40% of patients in the study (n=38/96). In these patients, a viral load decline of 0.9 log at Day 3 and 1.2 log at Day 5 was observed compared to placebo. Furthermore, zelicapavir treatment resulted in a greater proportion of patients having undetectable viral load at Days5 and 9 compared to placebo and improvements in area under the curve (AUC) of change from baseline for viral load at all timepoints. Qualitative improvement in time to undetectable viral load was observed at early timepoints, although median time to undetectable viral load was similar between groups. Overall, virology results were similar regardless of age or whether patients were enrolled from a hospitalized or outpatient setting. In a post hoc analysis of this Phase 2 study, zelicapavir demonstrated that treatment with zelicapavir resulted in a shorter time to complete resolution of RSV-related symptoms, as measured by ReSViNET, a parent/guardian clinical scoring system. Caregivers reported the severity of RSV-related symptoms daily from baseline through Day 14. A post hoc analysis of time to complete resolution of symptoms (defined as absent and discharged from hospital), showed an estimated Kaplan-Meier median of 6.99 days for zelicapavir versus 8.60 days for placebo. Similarly, an analysis of sustained resolution (defined as absent and remaining absent at all subsequent time points and discharged from hospital) resulted in 6.99 days for zelicapavir versus 10.68 days for placebo. EDP-323, Our RSV L-Protein Inhibitor: In addition to our N-protein inhibitor, zelicapavir, our second clinical candidate for RSV is EDP-323, a novel oral, direct-acting antiviral selectively targeting the RSV L-protein, a viral RNA-dependent RNA polymerase enzyme that contains multiple enzymatic activities required for RSV replication. EDP-323 has sub-nanomolar potency against RSV-A and RSV-B in vitro and has protected mice in a dose-dependent manner from RSV infection as demonstrated by both virological and pathological endpoints. EDP-323 is not expected to have cross-resistance to other classes of inhibitors and has the potential to be used alone, or in combination with other RSV mechanisms, to broaden the treatment window or addressable patient populations. Phase 2a Study of EDP-323 In September 2024, we announced positive top-line results for EDP-323 in a Phase 2a human challenge study. This study wasa randomized, double-blind, placebo-controlled, human challenge study of 142 healthy adult participants inoculated with RSV. Randomized participants (n=141) received either a once-daily (QD) 600 mg dose of EDP-323 for five days (high dose, n=47), a single 600 mg loading dose on day one followed by a 200 mg once-daily (QD) dose of EDP-323 for four days (low dose, n=47), or placebo for five days (n=47). The intent-to-treat-infected population (ITT-I) was defined as all randomized participants receiving challenge virus and at least one dose of study drug with confirmed RSV infection. EDP-323 demonstrated a rapid and sustained antiviral effect and reduced RSV symptoms. A highly statistically significant reduction (p<0.0001) was observed for the primary efficacy endpoint of area under the curve, or AUC, for viral load as measured by qRT-PCR in the ITT-I population for each of the EDP-323 dosing groups as compared with placebo. Specifically, EDP-323 lowered viral load AUC by 85% in the high dose arm and 87% in the low dose arm compared to placebo. There was no statistically significant difference between the two EDP-323 dosing groups. A highly statistically significant reduction (p<0.0001) was observed for the secondary efficacy endpoint of AUC for infectious viral load as measured by quantitative culture in the ITT-I population for each of the EDP-323 dosing groups, with a reduction in viral culture AUC by 98% in the high dose arm and 97% in the low dose arm compared to placebo. There was no statistically significant difference between the two EDP-323 dosing groups. For the secondary efficacy endpoint of AUC for total symptom score, a highly statistically significant reduction (p<0.0001) was observed in the ITT-I population for each of the EDP-323 dosing groups, with a symptom reduction of 66% in the high dose arm and 78% in the low dose arm compared to placebo. There was no statistically significant difference between the two EDP-323 dosing groups. ED P-323 demonstrated favorable PK, supportive of once-daily dosing. Mean trough plasma concentrations were maintained at 16-fold above the protein-adjusted EC 90 with the low dose, and 35-fold above the protein-adjusted EC 90 with the high dose, for both RSV-A and RSV-B strains. In addition, EDP-323 demonstrated a favorable safety profile overa 5-day dosing period and through 28 days of follow-up. Adverse events, or AEs, were similar between EDP-323 dosing groups and placebo. There were no serious AEs, no severe AEs, and no AEs leading to treatment discontinuation or study withdrawal. In addition, a post exposure prophylaxis, or PEP, analysis was performed in subjects who were not infected by Day 5 after RSV exposure. In this population, 68 RSV-exposed, susceptible subjects were randomized to receive EDP-323 (low dose n=24, high dose n=21) or placebo (n=23). Of these subjects, 26% (6/23) of those who received placebo became infected versus 0% (0/45) of EDP-323 recipients (p<0.001). Evaluated separately, the two EDP-323 dosing groups' PEP effects were statistically significant (low dose p=0.009, high dose p=0.022) versus placebo. Our Immunology Programs In immunology, we are designing and developing highly potent and selective, oral small molecule inhibitors for the treatment of type 2 inflammatory disease by targeting key mechanisms of immune response. Type 2 immune responses are characterized by the overproduction of interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13), and immunoglobulin E (IgE), through the activation of T helper 2 (Th2) cells, CD4+ T cells,B cells, and innate cellular response consisting of mast cells, ILC2s, eosinophils, basophils, and IL-4 and/or IL-13-activated macrophages. This immune response is a crucial part of the body's defense mechanism; however, an overactive response is the primary driver of a number of inflammatory diseases, including AD, urticarias, asthma, eosinophilic esophagitis (EoE), allergic rhinoconjunctivitis, prurigo nodularis (PN), chronic rhinosinusitis with nasal polyps (CRSwNP), as well as some forms of COPD and other conditions. Our initial targets include the receptor tyrosine kinase, known as KIT, which is critical for regulating mast cell activity. KIT inhibitors may have potential in the treatment of CSU and other mast-cell-driven diseases. We are also targeting STAT6, a transcription factor responsible for IL-4/IL-13 signaling, which drivesa Th2 dominant phenotype. STAT6 inhibitors may have potential in the treatment of AD and other type 2 immune driven phenotypes. Background and Overview of CSU CSU is a severely debilitating, chronic inflammatory skin disease with no identified triggers. Clinical manifestations include hives, angioedema, or both. Hives are variable in size and shape and are characterized by swelling, itchiness, and/or a burning sensation. Angioedema is characterized by pronounced deep tissue swelling along with tingling, burning, tightness and sometimes pain. Patients with CSU also experience symptoms beyond skin manifestations, including sleep disturbances, fatigue, irritability, anxiety and depression and can affect performance at work or school. CSU is typically a self-limiting disorder, persisting for 2-5 years although some reports estimate that more than half of patients suffer for more than 5 years. CSU may also recur after months or years of full remission. CSU impacts twice as many women as men, with an estimated global prevalence between 0.5% - 1% of the population, which means that at any given time in the U.S. alone approximately 1.75-3.5 million people are experiencing this condition. The peak age of diagnosis is during the core years of working age, 20-40 years old. Standard of care treatment for CSU is antihistamines, however in approximately half the patients, symptom alleviation is not adequate. Only a minority of these uncontrolled cases, approximately 10%, are treated with the biologic approved overa decade ago, which does not fully relieve symptoms for most patients, likely in part due to impacting only IgE-dependent activation pathways. While there are two agents newly approved for CSU, an IL-4 and IL-13 monoclonal antibody (DUPIXENT ® ) and BTK inhibitor (RHAPSIDO ® ), there still remains substantial unmet need for an oral agent which offers efficacy against hives and itch for all patients irrespective of prior treatments and/or drugs taken concomitantly, with an acceptable safety profile. Scientific Background Our approach to treating CSU is to directly target mast cells which are the root cause of pathology in CSU, and multiple other diseases. Mast cells are tissue-resident immune cells (e.g., skin, lung or GI) that can be activated through various cell surface receptors, resulting in a signaling cascade that leads to degranulation and release of tryptase, histamine and other inflammatory mediators. This release of inflammatory mediators from mast cells and subsequent propagation of a type 2 inflammatory response has been implicated in multiple inflammatory diseases, including chronic urticaria, prurigo nodularis, eosinophilic esophagitis, asthma, and AD. Current therapies modulate only a small subset of either mast cell stimulants or the downstream mediators of inflammation that mast cells produce (e.g., antihistamines), but do not address the underlying cause of disease, as they do not directly affect mast cells themselves. We are targeting mast cells by inhibiting KIT, a central regulator of mast cell development and activation. KIT provides pro-survival signals critical to mast cell survival and, therefore, the inhibition of KIT signaling leads to rapid mast cell inactivation and depletion through apoptosis, thereby directly reducing the quantity of mast cells available to drive pathology. Clinical proof of concept for this approach has been demonstrated with positive phase 2 data for anti-KIT monoclonal antibodies in CSU, suggesting best-in-disease efficacy and a reasonable safety profile. Competitive Landscape There are a number of different mechanisms being explored for the treatment of CSU, including inhibitors of IL-4R, IgE, Bruton's tyrosine kinase, or BTK, and MRGPRX2. Specifically for KIT inhibitors, there are companies with antibodies in development, including Celldex (barzolvolimab- Phase 3) and Jasper (briquilimab- Phase 1b/2a), as well as companies with oral, small molecules in early clinical development (Sanofi/Blueprint). Based on industry reports, by 2032 the market for urticaria is projected to be approximately $7 billion, the market for AD is projected be approximately $33 billion and the projected combined market for asthma, COPD, allergic rhinoconjunctivitis, CRSwNP, and PN is projected to be approximately $40 billion. Our KIT program We have a preclinical stage program to develop oral KIT inhibitors for the treatment of CSU and potentially other indications by depleting mast cells, thereby addressing a primary driver of these diseases. We have selected EDP-978 as our clinical candidate. EDP-978 demonstrates potent nanomolar activity in both binding (Kd = 0.3nM) and cellular function assays (EC 50 = 1.6-3.4nM), sub-nanomolar activity in vivo (EC 50 = 0.25nM), and high selectivity for KIT versus other kinases. EDP-978 also demonstrates strong in vitro and in vivo absorption, distribution, metabolism and excretion (ADME) properties. We are finalizing the IND-enabling activities for EDP-978 in the fourth quarter of 2025 and expect to file an IND in the first quarter of 2026. Background and Overview of AD AD is a chronic dermatological disease characterized by dry, red, inflamed, irritated and itchy skin, and has significant quality of life impacts such as leadinga limited lifestyle, avoidance of social interactions and impacted activities. The disease affects an estimated 7.3% of the U.S, adult population and approximately 40% of those have moderate to severe disease. The majority (>90%) of moderate to severe patients are treated with an IL-4 and IL-13 monoclonal antibody (e.g., DUPIXENT® (dupilumab)) despite modest efficacy, while a minority (<10%) are treated with an oral janus kinase, or JAK inhibitor (e.g., RINVOQ ® (upadacitinib)) due to safety concerns (black box warning for serious infections, mortality, malignancy, major adverse cardiovascular events, or MACE, and thrombosis). Thus, there is a significant need for an efficacious and safe oral agent. Scientific Background Dysregulation of the Th2 immune response drives many allergic and autoimmune diseases, including AD and asthma, which is characterized by an overproduction of IL-4 and IL-13. STAT6 is a transcription factor predominantly expressed in immune and epithelial cells that is responsible for IL-4/IL-13 signaling, which results in a Th2 dominant phenotype. Evidence for STAT6 as a key driver of AD and asthma is the presence of STAT6 gain-of-function variants resulting in severe AD and STAT6 loss-of-function variants protect against type 2 high asthma. Furthermore, clinical validation of this pathway exists in a number of immunology indications from anti-IL-4 and 13 monoclonal antibodies and JAK inhibitors, which block the IL-4/IL-13 signaling pathway. Our STAT6 inhibitor program offers the potential for an "oral Dupixent", as it directly blocks IL-4/IL-13 signaling, reduces inflammation in Th2 driven preclinical models and no oral therapies selectively targeting this pathway are currently available. Competitive Landscape The moderate-to-severe AD treatment landscape is dominated by biologics targeting the IL-4 and/or IL-13 pathway (e.g., DUPIXENT ® (dupilumab), ADBRY ® (tralokinumab-ldrm), and EBGLYSS™ (lebrikizumab-lbkz)), with JAK inhibitors (e.g., RINVOQ ® (upadacitinib) and CIBINQO ® (abrocitinib)) as the only oral option. Multiple oral mechanisms are in development, including modulators of MRGPRX2, IRAK4, ITK, STAT6, RASP and PKM2. The latest stage oral assets being evaluated in moderate-to-severe AD patients are in Phase 2b (Evommune - MRGPRX2) and Phase 1 (Corvus- ITK; Kymera - STAT6). For STAT6 inhibitors specifically, companies with oral assets in preclinical development include Sanofi/Recludix, J&J/Kaken, Gilead/LEO, DeepCure, and JW Pharma. Our STAT6 program We have a discovery stage program to develop an oral STAT6 inhibitor for the treatment of type 2 immune driven diseases, initially focusing on AD and potentially other indications by blocking the IL-4/IL-13 signaling pathway, thereby addressing a primary driver of these diseases. We have selected EPS-3903 as our lead development candidate. EPS-3903 demonstrates nanomolar potency in both binding (Kd=0.4nM) and cellular assays, including inhibition of IL-4 induced STAT6 phosphorylation in human peripheral blood mononuclear cells, or hPBMCs (EC 50 = 4nM), STAT6-mediated cellular proliferation (EC 50 = 8nM) and prevention of STAT6-driven biomarkers of type 2 inflammation (including TARC EC 50 = 16nM and periostin EC 50 = 3nM). Further, EPS-3903 is highly selective, with no inhibition of other STATs in hPBMCs and more than 1000-fold biochemical selectivity over other STATs, demonstrating significantly more selectivity than JAK inhibitors. EPS-3903 also demonstrates a rapid, continuous and complete (>90%) inhibition of phosphorylated STAT6 after oral dosing in mice. Importantly, EPS-3903 shows in vivo efficacy comparable to dupilumab, or an anti-mouse IL-4 and IL-13 antibody, in multiple disease models of asthma (ovalbumin, house dust mite) and AD (MC903). In the house dust mite challenge asthma model, EPS-3903 results in complete (>90%) inhibition of lung pSTAT6 and decreased inflammation comparable to dupilumab, including clinically relevant biomarkers of eosinophils and thymus and activation-regulated chemokine, or TARC, in the lung and serum IgE. In the MC903 atopic dermatitis model, EPS-3903 demonstrates complete (>90%) inhibition of pSTAT6 in the skin and spleen, comparable to dupilumab, as well as a robust decrease in serum IgE. EPS-3903 displays favorable in vitro and in vivo ADME properties, supportive of once-daily dosing potential. We have initiated IND-enabling activities with the goal of filing an IND in the second half of 2026. Our Out-Licensed HCV Protease Inhibitor Products Background and Overview of HCV Market HCV is a virus that is a common cause of viral hepatitis, an inflammation of the liver. HCV is typically contracted by contact with the blood or other body fluids of another individual infected with HCV. HCV is a leading cause of chronic liver disease, including cirrhosis, liver failure and cancer, and the leading cause of death from liver disease in the United States. HCV disease progression occurs overa period of 20 to 30 years, with the majority of HCV-infected individuals generally exhibiting no major symptoms in the early stages of the disease. Therefore, until a major symptom is diagnosed, many individuals are unaware they are infected and live undiagnosed without seeking treatment. For that reason, combined with the new availability of effective treatments for HCV, the United States Centers for Disease Control and Prevention, or CDC, issued new guidelines in 2013 recommending screening for all Americans born between the years 1945 and 1965 so that HCV-infected individuals will be aware of their condition and can consider treatment options. Approximately 290,000 people die every year from HCV-related liver diseases. According to the CDC, there are an estimated 5,000 new cases of acute HCV infections in 2023, the most recent year for which the CDC has published data, with an estimated total of 69,000 acute HCV infections. In 2023, there were over 100,000 cases of newly reported chronic HCV, in addition to over 11,000 deaths in the United States due to HCV. We believe that both the acute and chronically infected populations remain significantly untreated, even with the introduction of several new treatment regimens beginning in 2013. The approved treatments for HCV have provided significant benefit to HCV patients. To date, these treatments have cure rates approaching 100% in several subpopulations. Medical practice defines a "cure" as the point at which there is no quantifiable virus in a patient's blood fora sustained period of time after cessation of therapy, which is often referred to as a sustained virologic response, or SVR. For AbbVie's MAVYRET/MAVIRET regimen, the majority of chronic HCV patients only require 8 weeks of treatment compared to 12 weeks with other HCV regimens, including Gilead's EPCLUSA ® and HARVONI ® in almost all HCV genotypes. Since the introduction of Gilead's Harvoni ® and AbbVie's VIEKIRA PAK ® in late 2014, the reported worldwide sales of the leading HCV therapies have declined from $23 billion in 2015 to $2.9 billion in 2024. Through the first nine months of calendar 2025, reported worldwide net sales were $2.0 billion. HCV sales have declined since their peak in 2015 due to payers obtaining additional discounts, competitive market dynamics and a decline in the number of patients treated annually after the initial wave of diagnosed chronic HCV patients who had urgency for treatment. Despite the high numbers of HCV patients that have been successfully treated, there remains a large population of chronic HCV-infected patients who have yet to be treated with one of the newer "high cure" regimens. In addition, and as noted above, new HCV infections (principally in association with IV drug use) are an ongoing target population for treatment. Our Out-Licensed Products in AbbVie's Marketed Therapies Glecaprevir - Our protease inhibitor, glecaprevir, which is part of the latest HCV regimen from AbbVie, was developed by AbbVie in combination with pibrentasvir, AbbVie's second NS5A inhibitor. This co-formulated combination, marketed under the tradenames MAVYRET ® (U.S.) and MAVIRET ® (ex-U.S.), contains two novel DAAs that target and inhibit proteins essential for the replication of HCV. MAVYRET/MAVIRET is approved in the U.S., EU, Japan and numerous other countries globally as an 8-week, pan-genotypic, fixed-dose combination treatment, dosed once-daily as three oral tablets, taken with food, for acute or chronic HCV patients without cirrhosis and new to treatment. MAVYRET/MAVIRET is also approved as a treatment for patients with specific treatment challenges, including those GT-1 patients not cured by prior treatment experience with either a protease inhibitor or an NS5A inhibitor (but not both), and in patients with limited treatment options, such as those with severe chronic kidney disease, or CKD, or those with genotype 3 chronic HCV. MAVYRET/MAVIRET is approved for use in patients across all stages of CKD with any of the major HCV genotypes (GT1-6). The approvals of MAVYRET/MAVIRET for the treatment of CKD are supported by data from nine registrational studies in AbbVie's clinical development program, which evaluated more than 2,300 patients in 27 countries across all major HCV genotypes (GT1-6) and special populations: 8 weeks for treatment-naïve, non-cirrhotic patients: In November 2016, results from several Phase 3 studies of this combination demonstrated 97.5% of chronic HCV infected patients without cirrhosis and new to treatment across all major genotypes (GT1-6) achieved sustained virologic response at 12 weeks post-treatment, referred to as SVR 12 , with just 8 weeks of MAVYRET/MAVIRET treatment. 8 weeks for GT-3: Data from AbbVie's ENDURANCE-3 study were presented at the 2017 ILC, demonstrating that 95% of patients with challenging-to-treat, genotype 3, or GT3, chronic HCV infection, without cirrhosis and new to treatment, achieved SVR 12 after8 weeks of treatment with MAVYRET/MAVIRET. 8 weeks for compensated cirrhosis: Based on data from AbbVie's EXPEDITION-8 study, which demonstrated that with 8 weeks of MAVYRET treatment, 100 percent (n=273/273) of genotype 1, 2, 4, 5 and 6 patients achieveda sustained virologic response 8 weeks after treatment (SVR 8 ) per protocol analysis. Based on this data and a second cohort of the study in GT3 chronic HCV-infected patients, MAVYRET is now approved for all genotypes with compensated cirrhosis in the U.S. 12 weeks with chronic kidney disease: Results were also presented from AbbVie's EXPEDITION-4 study in chronic HCV patients with chronic kidney disease, or CKD, in which 98% of patients (n=102/104) across all major genotypes (GT1-6) achieved SVR 12 with 12 weeks of treatment with MAVYRET/MAVIRET. In June 2025, the FDA approveda label expansion for MAVYRET as the first and only treatment for acute HCV. The label expansion was supported by data from a Phase 3, multicenter, single-arm prospective study evaluating the safety and efficacy of MAVYRET eight-week treatment in adults with acute HCV infection. The study results showed MAVYRET to be a highly efficacious treatment for people with acute HCV. The majority of the adverse events reported were mild or moderate in severity. The most common adverse events were fatigue, asthenia, headache, and diarrhea. Paritaprevir - The first protease inhibitor developed through our collaboration with AbbVie, paritaprevir, is part of AbbVie's 3-DAA regimen approved for the treatment of genotype 1 and 4 HCV patients. This 3-DAA combination was sold as VIEKIRA PAK ® (paritaprevir/ritonavir/ombitasvir/dasabuvir) in the U.S. from December 2014 to December 2018, and as VIEKIRAX ® +EXVIERA ® in most other jurisdictions, for non-cirrhotic patients and those with early stage, or compensated, cirrhosis. These regimens have been almost entirely replaced by MAVYRET/MAVIRET. Collaboration and License Agreement with AbbVie We entered intoa Collaborative Development and License Agreement with Abbott Laboratories in November 2006 to develop and commercialize HCV NS3 and NS3/4A protease inhibitors. The agreement, which was amended in January and December 2009, was then assigned to AbbVie Inc. on January 1, 2013 in connection with Abbott's transfer of its research-based pharmaceuticals business to AbbVie. Under the agreement, we have granted AbbVie an exclusive, worldwide, royalty-bearing license, including a right to grant sublicenses, to specified intellectual property, including several issued U.S. patents, relating to protease inhibitors. We also granted AbbVie access to our drug discovery capabilities in the HCV NS3 and NS3/4A protease inhibitor field. AbbVie granted us a co-exclusive (together with AbbVie), royalty-free, fully paid license, without the right to grant sublicenses, to certain of AbbVie's intellectual property, AbbVie's interest in joint intellectual property and improvements discovered by AbbVie, for the purpose of allowing us to conduct certain development and commercialization activities in the United States relating to protease inhibitors. AbbVie is responsible for and has funded all costs associated with the development, manufacturing and commercialization of paritaprevir, glecaprevir and any other compounds under this agreement. Under the agreement, we are eligible to receive milestone payments and royalties with respect to these compounds. So long as a product candidate is being developed or commercialized under the agreement, we undertake not to conduct any activity, or grant licenses to a third party, relating to protease inhibitors. A joint steering committee was established under the agreement with review and oversight responsibilities for all research, development and commercialization activities. The joint steering committee is comprised of three of our senior personnel and three senior personnel from AbbVie; however, AbbVie has final authority to make all decisions regarding development and commercialization activities. The research program and the evaluation period, which was performed by both parties, ended in June 2011. The first commercialized compound was paritaprevir with the second commercialized compound, glecaprevir, approved in 2017 and marketed under the tradenames MAVYRET ® (U.S.) or MAVIRET™ (ex-U.S.). Under this collaboration we have received $396 million in payments from AbbVie for license payments, proceeds from a sale of preferred stock, research funding payments and milestone payments. We also receive annually tiered, double-digit royalties per protease inhibitor product developed under the agreement, which range from ten percent up to twenty percent, or on a blended basis from the low double digits up to the high teens. However, if a product is determined to be a combination product, as is the case for both glecaprevir and paritaprevir, the net sales of the combination product are adjusted on a country-by-country and product-by-product basis to reflect a good faith determination of the relative value of each pharmaceutically active ingredient, based on the estimated fair market value. This means thata portion of AbbVie's worldwide annual net sales of a combination product or regimen is first allocated to one of our protease inhibitors and then that royalty-bearing portion is multiplied by the annually tiered royalty rates to determine our actual royalty for the protease product in that regimen in a given period. Under the terms of our agreement, as amended in October 2014, 50% of AbbVie's net sales of MAVYRET/MAVIRET are allocated to glecaprevir. Beginning with each January 1, the cumulative net sales of a given royalty-bearing protease inhibitor product start at zero for purposes of calculating the tiered royalties on a product-by-product basis. Under this collaboration, we have received royalty payments from AbbVie totaling $954 million through September 30, 2025. Further details of these tiered royalties are set forth in Note 7 in Notes to Consolidated Financial Statements included in this report, which are incorporated herein by this reference. Royalties owed to us under the agreement can be reduced by AbbVie in certain circumstances, including (i) if AbbVie exercises its right to license or otherwise acquire rights to intellectual property controlled by a third party where a product could not be legally developed or commercialized in a country without the third-party intellectual property right, (ii) where a product developed under the collaboration agreement is sold in a country and not covered by a valid patent claim in such country, or (iii) where sales of a generic product are equal to at leasta specified percentage of AbbVie's market share of a product in a country. AbbVie's obligation to pay royalties on products developed under the agreement expires on a country-by-country and product-by-product basis upon the later of (i) the date of expiration of the last of the licensed patents with a valid claim covering the product in the applicable country, and (ii) ten years after the first commercial sale of the product in the applicable country. Our intellectual property existing as of the effective date of the agreement remains our property. Any intellectual property jointly developed is jointly owned. We will have the unilateral right to enforce our patent rights on any covered product following the first commercial sale of such product, as will AbbVie. In the event of infringement related to any of our patents, we will have the first right and option to initiate legal proceedings or take other actions. In the event of infringement related to any AbbVie patents, AbbVie will have the first right and option to initiate legal proceedings or take other actions. In the event of infringement of a joint patent right, we will discuss with AbbVie whether to initiate legal proceedings or take other actions. AbbVie will have the obligation to defend at its sole expense any actions brought against either party alleging infringement of third-party rights by reason of the activities conducted under the agreement and we will have the right to obtain separate counsel at our own expense. Additionally, AbbVie, at its sole expense, will be responsible for all trademark prosecution. Subject to the exceptions described above,a party's rights and obligations under the agreement continue until: (i) such time as AbbVie is no longer developing a product candidate or (ii) if, as of the time AbbVie is no longer developing any product candidates, AbbVie is commercializing any other protease inhibitor product, such time as all royalty terms for all covered products and all co-development terms for all co-developed products have ended. Accordingly, the final expiration date of the agreement is currently indeterminable. Either party may terminate the agreement for cause in the event of a material breach, subject to prior notice and the opportunity to cure, or in the event of the other party's bankruptcy. Additionally, AbbVie may terminate the agreement for any reason upon specified prior notice. If we terminate the agreement for cause or AbbVie terminates without cause, any licenses and other rights granted to AbbVie will terminate and AbbVie will be deemed to have granted us (i) a non-exclusive, perpetual, fully paid, worldwide, royalty-free license, with the right to sublicense, under AbbVie's intellectual property used in any product candidate and (ii) an exclusive (even as to AbbVie), perpetual, fully paid, worldwide, royalty-free license, with the right to sublicense, under AbbVie's interest in joint intellectual property rights to develop product candidates resulting from covered compounds and to commercialize any products derived from such compounds. Upon our request, AbbVie will also transfer to us all rights, title and interest in any related product trademarks, regulatory filings and clinical trials. If AbbVie terminates the agreement for our uncured breach, the royalty payments payable by AbbVie may be reduced, the licenses granted to AbbVie will remain in place, we will be deemed to have granted AbbVie an exclusive license under our interest in joint intellectual property, AbbVie will continue to have the right to commercialize any covered products, and all rights and licenses granted to us by AbbVie will terminate. Royalty Sale Agreement In April 2023, we entered intoa royalty sale agreement with an affiliate of OMERS, a Canadian public employee pension fund, pursuant to which we were paid a $200.0 million cash purchase price in exchange for 54.5% of our future quarterly royalty payments on net sales of MAVYRET/MAVIRET, after June 30, 2023, through June 30, 2032, subject to a cap on aggregate payments to OMERS equal to 1.42 times the purchase price. For accounting purposes, we will continue to record 100% of HCV royalties earned under the AbbVie agreement as royalty revenue in our consolidated statements of operation. The $200.0 million received in April 2023 was recognized on our consolidated balance sheets as a liability which will be reduced by the payments made to OMERS over the term of the Agreement. We will recognize imputed interest expense over the life of the royalty sale agreement based on our estimated future MAVYRET/MAVIRET royalties. Other Programs for Out-Licensing in Virology Our SARS-CoV-2 Program Background and Overview of SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, is the virus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the COVID-19 pandemic. SARS-CoV-2 is the seventh known coronavirus to infect people, after 229E, NL63, OC43, HKU1, MERS-CoV, and the original SARS-CoV. Patients at higher risk for developing severe complications from COVID-19 include the elderly and those with underlying medical conditions like cardiovascular disease, diabetes, chronic respiratory disease, or cancer. As of October 2025, the World Health Organization estimated over7 million deaths have been caused by COVID-19. There are also many patients who experience continuing effects of COVID-19, often referred to as "long COVID". While vaccines that reduce the severity of COVID-19 are available, uptake has not been optimal. In addition, breakthrough infection occurs in many cases because the vaccines are not completely effective or their effect diminishes over time, especially against emerging variants. Thus, there remains an urgent need for effective, safe and well-tolerated, conveniently-dosed, once-daily oral antiviral treatments. Scientific Background All coronaviruses havea single-stranded, positive-sense RNA (+ssRNA) genome, which is the largest known genome for an RNA virus. The overall structure of the SARS-CoV-2 genome is shared with other betacoronaviruses, namely MERS-CoV and SARS-CoV. The 3C-like protease, or 3CL protease (also known as 3CLpro or the main protease, or Mpro), is essential for viral replication, and is a highly attractive target for the development of direct-acting antiviral agents. Competitive Landscape In the United States, there are two oral antiviral treatments for non-hospitalized, high-risk patients with SARS-CoV-2 infection: PAXLOVID™, a 3CL protease inhibitor (nirmatrelvir) boosted with ritonavir (full approval), and LAGEVRIO™ (molnupiravir), a polymerase inhibitor (Emergency Use Authorization). The most advanced oral, direct acting antiviral (DAA) for the treatment of high-risk patients with SARS-CoV-2 is in Phase 3 studies (Pfizer/ibuzatrelvir). EDP-235, Our Lead, Oral, 3CL Protease Inhibitor We leveraged our expertise in developing protease inhibitors to discover compounds specifically designed to target the SARS-CoV-2 virus and potentially other coronaviruses. We selected EDP-235, an oral inhibitor of the coronavirus 3CL protease, for clinical development. In addition to nanomolar activity against all SARS-CoV-2 variants tested to date, EDP-235 has potent antiviral activity against other human coronaviruses, enabling the potential for a pan-coronavirus treatment, including possibly coronaviruses that may infect human populations in the future. Furthermore, EDP-235 has good tissue distribution, and is projected to have four times higher drug levels in lung tissue compared to plasma. In May 2023, we reported topline results from a Phase 2 clinical trial of EDP-235 in non-hospitalized, symptomatic patients with mild to moderate COVID-19 who were not at increased risk for developing severe disease. EDP-235 met the primary endpoint of the trial and was generally safe and well-tolerated. A dose-dependent improvement in total symptom score was observed with EDP-235 treatment compared to placebo, which achieved statistical significance (p<0.05) in the 400 mg treatment group at multiple time points, starting as early as one day after the first dose. An analysis of a subset of six symptoms showed a two-day shorter time (5 days to 3 days) to improvement in patients receiving EDP-235 400 mg who were enrolled within three days of symptom onset (p<0.01). No effect on virologic endpoints as measured in the nose was detected due to the rapid viral decline in the placebo arm of this highly immunologically-experienced, standard risk population. However, in the subset of patients who were nucleocapsid seronegative (indicating no recent natural infection with SARS-CoV-2), a viral load decline was observed at day five in the 400 mg group of 0.8 log overall and1 log in the patients with symptom onset within three days before treatment with EDP-235. We will continue to focus on potential collaborations to progress EDP-235, as we will not advance this candidate into Phase 3 studies on our own. Our HBV Program Background and Overview of HBV Hepatitis B virus, or HBV, is a potentially life-threatening liver infection. It is estimated that close to 300 million people worldwide are chronically infected, and 15-40% of patients with chronic HBV infection develop chronic liver disease, including cirrhosis, liver cancer, or liver decompensation. HBV is a leading cause of chronic liver disease and liver transplantation. Current approaches to treatment include interferon therapy and/or inhibitors of HBV nucleoside reverse transcriptase, which suppress the virus but require lifelong therapy and rarely result in full eradication of the virus from the liver. Treatment with interferon offers modest cure rates, and is accompanied by serious side effects, including flu-like symptoms, fatigue, headache and nausea. New treatments that can provide functional cures to chronically-infected patients are urgently needed. Scientific Background HBV is a partially double-stranded DNA virus with a complex life cycle. There are multiple mechanisms associated with HBV replication that could potentially be targeted with new drugs. Mechanisms under study for HBV include entry inhibitors, core inhibitors or capsid assembly modulators (CAMs), siRNA/ASO targeting the HBVS antigen, and immune modulators (e.g., TLRs, PD-L1s, therapeutic vaccines, etc.). These new HBV mechanisms are being studied with nucleoside inhibitors and in combination with each other, with the goal of achieving a functional cure for a significant number of HBV patients. We believe that HBV, like HIV and HCV, will be optimally treated with multiple agents that have different mechanisms, and therefore seek to develop a combination regimen. We initially focused on inhibitors of the HBV core protein, as it playsa critical role in viral replication, intracellular trafficking, and maintenance of chronic infections. Core inhibitors are replication inhibitors that have been shown to act at multiple steps in the HBV lifecycle; preventing proper uncoating, nuclear import, assembly, and recycling as well as potentially impacting other viral processes. This approach is supported by clinical validation, demonstrating reduction of viral RNA and DNA in chronic HBV patients in Phase 2 clinical studies. Competitive Landscape While there are antiviral medications prescribed for HBV that can suppress HBV DNA, they generally have low cure rates, resulting in the need for lifelong treatment. Many companies are seeking to develop new HBV drugs that alone or in combination with other mechanisms could lead to a functional cure for HBV. Vir, GSK, Arbutus, and Roche have multiple combination regimens under investigation in later stage clinical studies. In addition, a number of companies have Phase 1 or earlier stage HBV programs. EDP-514 Our lead clinical candidate for the treatment of chronic infection with HBV is EDP-514, a core inhibitor that displays potent anti-HBV activity in vitro at multiple points in the HBV lifecycle. Two Phase 1b studies of EDP-514 demonstrate the compound is safe with strong antiviral activity in two different chronic HBV patient populations - those who have a high viral load and those who are on a treatment with a nucleoside reverse transcriptase inhibitor. Our goal has been to developa combination therapy approach, including existing approved treatments such as a nucleoside reverse transcriptase inhibitor, or NUC, with EDP-514 and one or more other mechanisms, which could lead to a functional cure for patients with chronic HBV infection. Advancement of this program is dependent upon our accessing another compound that could be developed with EDP-514 for such a treatment regimen. Drug Discovery We have internally discovered all of the compounds in our research and development programs. Our scientists have expertise in the areas of medicinal chemistry, molecular virology, pharmacology, and toxicology with highly developed sets of skills in compound generation, target selection, screening and pharmacology, preclinical development and lead optimization. We are utilizing these skills and capabilities in our discovery and development of small molecule drugs with an emphasis on virology and immunology indications. We focus on virology and immunology indications representing large and growing market opportunities with significant unmet medical needs. Our selection ...

View stock analysis, news, and events for Enanta Pharmaceuticals, Inc.