Peginterferon alfa-2a

Phase 2b Data Presented at EASL and Published in NEJM Show Potential for Bulevirtide 10 mg in Combination with Pegylated Interferon Alfa-2a as Finite Therapy for People with Chronic Hepatitis Delta Data Published in NEJM Demonstrate 46% of Patients Taking Bulevirtide 10 mg with PegIFN Achieved Post-Treatment Undetectable HDV RNA at Week 24 Data Presented at EASL Demonstrate Consistent Study Findings of Undetectable HDV RNA at Week 48 FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced data from the Phase 2b MYR204 open-label study assessing the efficacy and safety of the first-in-class entry inhibitor bulevirtide as monotherapy and in combination with pegylated interferon alfa-2a (PegIFN), in adults living with compensated chronic hepatitis delta virus (HDV) infection. Published in the New England Journal of Medicine (NEJM), the data demonstrate that the investigational combination of bulevirtide 10 mg with PegIFN was superior to investigational bulevirtide 10 mg monotherapy in achieving undetectable HDV RNA (lower limit of quantification (LLOQ), target not detected) at Week 24 after the end of treatment (EOT). The end of study data presented at the European Association for the Study of the Liver (EASL) Congress 2024, demonstrate that treatment with bulevirtide 10 mg in combination with PegIFN maintained a 46% rate of undetectable HDV RNA at Week 48 after EOT, confirming its potential as a finite therapy for adults living with chronic HDV. HDV affects an estimated 5% of people living with chronic hepatitis B (HBV), with a global prevalence of more than 12 million people. “HDV is the most severe form of viral hepatitis. For people living with HDV, bulevirtide 2 mg has been proven to be a successful long-term treatment approach, as highlighted in clinical trials and real-world data. These new data support the potential for bulevirtide as a finite treatment option, demonstrating that almost half of people treated with bulevirtide 10 mg in combination with PegIFN remained undetectable for HDV RNA one year after treatment cessation,” said Tarik Asselah, MD, PhD, Professor of Hepatology, Hôpital Beaujon APHP, Université Paris-Cité, Head of Viral Hepatitis, UMR1149 Inserm and principal investigator of the study. “These long-term data are the highest post-treatment response rates ever reported for HDV.” Bulevirtide 2 mg remains the only approved treatment for adults with chronic HDV and compensated liver disease in the European Economic Area (EEA), Great Britain and Switzerland and is not approved in the U.S. Bulevirtide 10 mg is an investigational product and is not approved anywhere. Data published in NEJM demonstrate that at Week 24 after EOT, undetectable HDV RNA was achieved by 32% and 46% of patients taking bulevirtide 2 mg in combination with PegIFN and bulevirtide 10 mg in combination with PegIFN, respectively. In the monotherapy groups, PegIFN monotherapy and bulevirtide 10 mg monotherapy, undetectable HDV RNA was achieved by 17% and 12%, respectively. The safety profiles of bulevirtide in combination with PegIFN were consistent with those of the individual components. The most frequent adverse events were leukopenia, neutropenia and thrombocytopenia, and most were mild to moderate. Data presented at EASL (GS-002) demonstrate that at Week 48 after EOT, undetectable HDV RNA was achieved by 26% and 46% of patients taking bulevirtide 2 mg in combination with PegIFN and bulevirtide 10 mg in combination with PegIFN, respectively. In the monotherapy groups, PegIFN monotherapy and bulevirtide 10 mg monotherapy, undetectable HDV RNA was achieved by 25% and 12%, respectively. “Chronic HDV can greatly impact those affected due to its rapid progression to liver failure, liver cancer and liver-related death. With these promising finite data for bulevirtide, we have the opportunity to support healthier futures for people living with HDV,” said Anu Osinusi, VP, Clinical Research for Hepatitis, Respiratory and Emerging Viruses, Gilead Sciences. “In addition to highlighting the curative potential of combination therapy for some people with chronic HDV, these final data support the safety pro bulevirtide. Ultimately, our focus remains on bringing treatment options to more people living with chronic HDV.” Also at EASL, late-breaking data (LB-309) on the pivotal Phase 3 MYR301 study evaluating bulevirtide as monotherapy for the treatment of adults with chronic HDV infection were also presented and reinforced bulevirtide as an efficacious and generally well-tolerated long-term treatment option. Patients had similar rates of combined response (virologic response and ALT normalization) at Week 144 compared to Week 96, with 57% and 54%, respectively, among those receiving bulevirtide 2 mg or 10 mg. This is consistent with and builds on the data shared at EASL 2023. Bulevirtide continued to be generally well-tolerated through Week 144, and the safety pro similar between the bulevirtide 2 mg and 10 mg treatment arms, with the study investigators attributing no serious adverse events to bulevirtide treatment. Through 144 weeks of treatment, dose-dependent increases in bile acids remained asymptomatic, were not associated with any clinical sequelae and did not result in any discontinuations or treatment interruption. In July 2023, the European Commission (EC) granted full Marketing Authorization (MA) for Hepcludex® (bulevirtide) 2 mg for the treatment of adults with chronic HDV and compensated liver disease. Bulevirtide was initially granted conditional MA from the EC in July 2020 to provide people living with HDV urgent access to treatment. Bulevirtide’s conditional MA license in Great Britain was converted to a full MA in August 2023, and a full MA was granted in Switzerland in February 2024. In regions where it is not approved, including the U.S., bulevirtide 2 mg is an investigational product. In these regions, health authorities have not established the safety and efficacy of bulevirtide. About MYR204 The MYR204 study was a randomized, open-label, controlled, parallel-group, multicenter, Phase 2b trial, in which a total of 174 patients were randomized and received PegIFN alone for 48 weeks; bulevirtide 2 mg with PegIFN for 48 weeks, followed by bulevirtide 2 mg alone for 48 weeks; bulevirtide 10 mg with PegIFN for 48 weeks, followed by bulevirtide 10 mg alone for 48 weeks; or bulevirtide 10 mg alone for 96 weeks. All patients were followed for an additional 48 weeks after EOT. The primary endpoint of MYR204 was undetectable HDV RNA at 24 weeks after EOT. Secondary efficacy endpoints included undetectable HDV RNA at Week 48 (all groups) during treatment, undetectable HDV RNA at Week 96 (all bulevirtide groups) during treatment, and undetectable HDV RNA at Week 48 after EOT (all groups). About MYR301 MYR301 is an ongoing, Phase 3 clinical trial evaluating the long-term efficacy and safety of bulevirtide in 150 people living with chronic HDV randomly allocated to treatment with bulevirtide 2 mg once daily (n=49), 10 mg once daily (n=50) or no antiviral treatment (delayed treatment, n=51). Primary efficacy and safety data were assessed at Week 48. After Week 48, patients in the delayed treatment group of the study were switched to bulevirtide 10 mg once daily for an additional 96 weeks. The total duration of treatment across all groups in the study is 144 weeks. The primary endpoint, combined response, is defined as an undetectable HDV RNA or ≥ 2log10 IU/ml decline from baseline and ALT normalization at Week 48. Secondary endpoints at Week 48 include undetectable HDV RNA (key secondary endpoint), ALT normalization, and a change from baseline in liver stiffness measured by transient elastography. About HDV HDV is considered the most aggressive or severe form of viral hepatitis, associated with more rapid progression towards liver-related death and liver cancer in people with HBV. On average, HDV progresses to cirrhosis within five years and to liver cancer within 10 years. Nearly 5% of people who have a chronic infection with HBV are estimated to have HDV, equating to 12-15 million people worldwide. The prevalence of HDV infection is largely underestimated due to lack of universal testing of HBV positive individuals for HDV. About Gilead Sciences in Liver Disease For decades, Gilead has pioneered the way forward to improve the lives of people living with liver disease around the world. We have helped to transform hepatitis C from a chronic condition into one that can be cured for millions of people. For people living with hepatitis B or D, our focus on advancing our medicines drives hope that today’s research will turn into tomorrow’s cures. Beyond viral hepatitis, we’re working to deliver advanced treatments for people living with primary biliary cirrhosis (PBC). But our commitment doesn’t stop there. Through our ground-breaking science and collaborative partnerships, we strive to create healthier futures for everyone living with liver disease. We are committed to a future without liver disease. About Gilead Sciences Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, cancer and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials or studies within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical trials or studies, including those involving Hepcludex (bulevirtide); uncertainties relating to regulatory applications and related filing and approval timelines, including the risk that the FDA and other regulatory authorities may not approve bulevirtide for the treatment of HDV, and the risk that any such approvals, if granted, may be subject to significant limitations on use; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements. Hepcludex, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies. For more information about Gilead, please visit the company’s website at , follow Gilead on X (@Gilead Sciences), or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000. View source version on businesswire.com: Contacts Meaghan Smith, Media public_affairs@gilead.com Jacquie Ross, Investors investor_relations@gilead.com Source: Gilead Sciences, Inc. View this news release online at:

At the end of treatment, 33.3% of patients receiving imdusiran for 48 weeks, interferon (IFN) for 24 weeks and ongoing nucleoside analogue (NA) therapy achieved undetectable levels of HBsAg that were maintained in 100% of these patients 24 weeks after completing imdusiran and IFN treatment Of the patients who have stopped all therapy, six still have undetectable levels of HBsAg and HBV DNA, with two of these patients reaching 12 weeks off all therapy All six patients have seroconverted and have high titers of anti-HBsAg antibodies These new Phase 2a data were presented at the European Association for the Study of the Liver (EASL) Congress 2024 WARMINSTER, Pa., June 05, 2024 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (Nasdaq: ABUS) (“Arbutus” or the “Company”), a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to develop a functional cure for people with chronic hepatitis B virus (cHBV) infection, today announced new data from its Phase 2a clinical trial IM-PROVE I (AB-729-201) showing that imdusiran, the Company’s RNAi therapeutic, and 24 weeks of pegylated interferon alfa-2α (IFN), a standard-of-care immunomodulator, added to ongoing nucleos(t)ide analogue (NA) therapy, reduced HBsAg levels and led to sustained HBsAg loss in some patients with cHBV during and after treatment. These data were presented today in the Viral Hepatitis B and D: New therapies, unapproved therapies or strategies poster session, and will be featured during a poster tour on Thursday, June 6, 2024, at the European Association for the Study of the Liver (EASL) Congress. Select key data from this Phase 2a clinical trial include: Some patients who received either 48 or 24 weeks of imdusiran and 24 weeks of IFN with their ongoing NA therapy achieved undetectable HBsAg at the end-of-treatment (EOT) (33.3%, n=4/12; and 23.1%, n=3/13, respectively) that was sustained 24 weeks after completing imdusiran and IFN treatment (33.3%, n=4/12 and 15.4%, n=2/13, respectively). All six patients with sustained HBsAg loss have seroconverted with high anti-HBsAg antibody levels (43.8 to >1,000 mIU/mL suggestive of immune control) and are being followed for maintenance of both undetectable levels of HBsAg and HBV DNA for 24 weeks while off all therapy to assess for a functional cure. Two of the six patients have reached 12 weeks off all therapy while maintaining both undetectable levels of HBsAg and HBV DNA. The remaining four patients are at various timepoints less than 12 weeks off therapy with undetectable levels of HBsAg and HBV DNA. A total of 21 patients from across the four treatment cohorts have discontinued all therapy and are in the follow-up period. One patient that received 12 weeks of IFN treatment with imdusiran and NA therapy has maintained undetectable levels of HBsAg and HBV DNA while off all therapy for six months, thereby achieving a functional cure. “These data are impressive with robust HBsAg response rates that are sustained after end-of-treatment in patients receiving imdusiran and IFN,” commented Professor Man-Fung Yuen, D.Sc., M.D., Ph.D., Chief of the Division of Gastroenterology and Hepatology, the University of Hong Kong, who presented the data at the Congress. “Unlike other RNAi candidates in development that have been evaluated in combination with IFN, in this trial, imdusiran was administered less frequently, at a lower dose, and when combined with a shorter 24-week course of IFN, achieved undetectable HBsAg that is sustained after end of treatment and into early off-treatment follow-up. This trial evaluated small groups of patients, yet there is reason to believe that the combination of imdusiran and IFN could potentially lead to a functional cure in those patients that remain off all therapy. These data are extremely important for the HBV community, and I look forward to continuing to follow the patients who have discontinued all treatment.” To confirm undetectable HBsAg measured by the trial assay (lower limit of quantitation of 0.05 IU/mL), the Abbott HBsAg Next Qualitative assay, an ultrasensitive, research use only assay with a detection limit of 0.005 IU/mL, was utilized. The Next Assay confirmed HBsAg loss in six of the seven patients at EOT, and those six maintained HBsAg loss for 24 weeks after completing imdusiran and IFN treatment. These data from the IM-PROVE I trial suggest that the combination of imdusiran and 24 weeks of IFN was generally safe and well-tolerated. There were no serious adverse events (SAEs) related to imdusiran or IFN, and no adverse events (AEs) leading to discontinuation. The most common imdusiran-related treatment emergent adverse events (TEAEs) were transient ALT elevations and injection site bruising. The IFN-related TEAEs were consistent with the known safety pro IFN. “There is a significant need for a functional cure for the more than 250 million patients chronically infected with HBV worldwide,” commented Dr. Karen Sims, Chief Medical Officer of Arbutus Biopharma. “These data further support our belief that lowering surface antigen with imdusiran and incorporating an immunomodulator in the treatment regimen has the potential to provide a functional cure for patients with cHBV. We look forward to following the progress of these patients as well as those in our other Phase 2a trials evaluating imdusiran with other immunomodulators.” The poster that was presented at EASL Congress 2024 can be accessed through the Arbutus website under Publications. IM-PROVE I Trial Details The IM-PROVE I Phase 2a clinical trial (AB-729-201; NCT04980482) enrolled 43 HBeAg-negative, NA-suppressed patients with cHBV infection. After a 24-week lead-in with imdusiran (60 mg every 8 weeks) added to ongoing NA therapy, patients were randomized into one of the following four cohorts: A1: Imdusiran + NA + IFN weekly for 24 weeks (n=12) A2: NA + IFN weekly for 24 weeks (n=13) B1: Imdusiran + NA + IFN weekly for 12 weeks (n=8) B2: NA + IFN weekly for 12 weeks (n=10) After completion of the IFN treatment period (Week 52 for cohorts A1 and A2 and Week 40 for cohorts B1 and B2), patients underwent a 24-week follow-up period on NA therapy alone and were then assessed for discontinuation of NA therapy. Patients with ALT levels less than two times the upper limit of normal, undetectable HBV DNA, and HBsAg <100 IU/mL at two consecutive visits at least 24 weeks after the last dose of imdusiran, qualified to discontinue all therapy and will be followed for at least 48 weeks. Safety, antiviral and immunologic assessments were obtained throughout the treatment and follow-up periods. HBsAg was assessed via Roche Cobas Elecsys HBsAg II assay (lower limit of quantitation [LLOQ] = 0.05 IU/mL) and results <LLOQ were analyzed by Abbott HBsAg Next Qualitative assay (detection limit = 0.005 IU/mL). About Imdusiran (AB-729) Imdusiran is an RNA interference (RNAi) therapeutic specifically designed to reduce all HBV viral proteins and antigens including hepatitis B surface antigen, which is thought to be a key prerequisite to enable reawakening of a patient’s immune system to respond to the virus. Imdusiran targets hepatocytes using Arbutus’ novel covalently conjugated N-Acetylgalactosamine (GalNAc) delivery technology enabling subcutaneous delivery. Clinical data generated thus far has shown single and multiple doses of imdusiran to be generally safe and well-tolerated, while also providing meaningful reductions in hepatitis B surface antigen and hepatitis B DNA. Imdusiran is currently in multiple Phase 2a clinical trials. About HBV Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). HBV can cause chronic infection which leads to a higher risk of death from cirrhosis and liver cancer. Chronic HBV infection represents a significant unmet medical need. The World Health Organization estimates that over 250 million people worldwide suffer from chronic HBV infection, while other estimates indicate that approximately 2.4 million people in the United States suffer from chronic HBV infection. Approximately 820,000 people die every year from complications related to chronic HBV infection despite the availability of effective vaccines and current treatment options. About Arbutus Arbutus Biopharma Corporation (Nasdaq: ABUS) is a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to identify and develop novel therapeutics with distinct mechanisms of action, which can be combined to provide a functional cure for patients with chronic hepatitis B virus (cHBV). We believe the key to success in developing a functional cure involves suppressing HBV DNA, reducing surface antigen, and boosting HBV-specific immune responses. Our pipeline of internally developed, proprietary compounds includes an RNAi therapeutic, imdusiran (AB-729), and an oral PD-L1 inhibitor, AB-101. Imdusiran has generated meaningful clinical data demonstrating an impact on both surface antigen reduction and reawakening of the HBV-specific immune response. Imdusiran is currently in three Phase 2a combination clinical trials. AB-101 is currently being evaluated in a Phase 1a/1b clinical trial. For more information, visit . Forward-Looking Statements and Information This press release contains forward-looking statements within the meaning of the Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, and forward-looking information within the meaning of Canadian securities laws (collectively, forward-looking statements). Forward-looking statements in this press release include statements about the potential to lead to a functional cure for HBV, our future development plans for our product candidates; the expected results of our clinical development plans and clinical trials with respect to our product candidates; our expectations with respect to the release of data from our clinical trials and the expected timing thereof; and the potential for our product candidates to achieve success in clinical trials. With respect to the forward-looking statements contained in this press release, Arbutus has made numerous assumptions regarding, among other things: the effectiveness and timeliness of preclinical studies and clinical trials, and the usefulness of the data; the timeliness of regulatory approvals; the continued demand for Arbutus’ assets; and the stability of economic and market conditions. While Arbutus considers these assumptions to be reasonable, these assumptions are inherently subject to significant business, economic, competitive, market and social uncertainties and contingencies. Additionally, there are known and unknown risk factors which could cause Arbutus’ actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements contained herein. Known risk factors include, among others: anticipated pre-clinical studies and clinical trials may be more costly or take longer to complete than anticipated, and may never be initiated or completed, or may not generate results that warrant future development of the tested product candidate; Arbutus may elect to change its strategy regarding its product candidates and clinical development activities; Arbutus may not receive the necessary regulatory approvals for the clinical development of Arbutus’ products; economic and market conditions may worsen; market shifts may require a change in strategic focus. A more complete discussion of the risks and uncertainties facing Arbutus appears in Arbutus’ Annual Report on Form 10-K, Arbutus’ Quarterly Reports on Form 10-Q and Arbutus’ continuous and periodic disclosure filings, which are available at and at . All forward-looking statements herein are qualified in their entirety by this cautionary statement, and Arbutus disclaims any obligation to revise or update any such forward-looking statements or to publicly announce the result of any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments, except as required by law. Contact Information Investors and Media Lisa M. Caperelli Vice President, Investor Relations Phone: 215-206-1822 Email: lcaperelli@arbutusbio.com