Tobevibart

SAN FRANCISCO--(BUSINESS WIRE)--Vir Biotechnology, Inc. (Nasdaq: VIR) today announced 24-week post-end of treatment data from Part B of the ongoing MARCH Phase 2 clinical study evaluating tobevibart and elebsiran without or with pegylated interferon alpha (PEG-IFNα) in participants with chronic hepatitis B (CHB). The study-defined primary endpoint, proportion of participants with undetectable hepatitis B surface antigen (HBsAg) at 24 weeks post-end of treatment, was achieved by 17% (3/18) and 21% (3/14) of participants with baseline HBsAg<1,000 IU/mL receiving tobevibart and elebsiran without or with PEG-IFNα, respectively. The detailed data were presented today at the European Association for the Study of the Liver (EASL) congress in Amsterdam (The Netherlands). CHB is a long-lasting, inflammatory liver disease caused by the hepatitis B virus (HBV).1 The World Health Organization estimates that 254 million people live with CHB, and an estimated 1.1 million yearly deaths are associated with the disease.2 Complications from CHB may include liver cirrhosis, liver failure and liver cancer.3 Although CHB can be treated, there is currently no cure.1 Participants in the trial received tobevibart and elebsiran without or with PEG-IFNα. Tobevibart was administered at 300 mg every 4 weeks; elebsiran, at 200 mg every 4 weeks; and PEG-IFNα, for patients receiving it, at 180 µg weekly. Participants with HBsAg loss (seroclearance) after 48 weeks of treatment who met eligibility criteria discontinued both NRTI (nucleos(t)ide reverse transcriptase inhibitor) as well as tobevibart and elebsiran without or with PEG-IFNα treatment. The current analysis includes data from participants in the trial who have reached Week 24 post-end of treatment: 51 participants receiving tobevibart and elebsiran without PEG-IFNα and 32 receiving tobevibart and elebsiran with PEG-IFNα. An additional 18 participants receiving tobevibart and elebsiran with PEG-IFNα are currently advancing through the trial. Study-defined primary efficacy endpoint – The study-defined primary efficacy endpoint is proportion of participants with HBsAg seroclearance (defined as undetectable HBsAg) at 24 weeks post-end of treatment. Tobevibart and elebsiran without or with PEG-IFNα resulted in HBsAg loss 24 weeks post-end of treatment in 17% (3/18) and 21% (3/14) of participants with baseline HBsAg<1,000 IU/mL, respectively. These proportions were 8% (4/51) and 16% (5/32) for tobevibart and elebsiran without or with PEG-IFNα, respectively, in all participants. Functional cure – Functional cure is defined as sustained undetectable HBsAg and HBV DNA below the lower limit of quantification (0.05 IU/mL) at 24 weeks post-end of treatment after discontinuing NRTIs. Tobevibart and elebsiran without or with PEG-IFNα resulted in functional cure in 11% (2/18) and 15% (2/13) of participants with HBsAg<1000 IU/mL, respectively. These proportions were 4% (2/51) and 10% (3/30) for the combinations without or with PEG-IFNα, respectively, in all participants. Modified functional cure (allowing viral blips) – An exploratory modified functional cure, allowing transient viremia (viral blips) defined as HBV RNA or HBsAg equal or above the lower limit of quantification for ≤35 days, was also evaluated. Tobevibart and elebsiran without or with PEG-IFNα resulted in 24 weeks post-end of treatment modified functional cure rates of 11% (2/18) and 23% (3/13) in participants with HBsAg<1000 IU/mL, respectively. These proportions were 6% (3/51) and 13% (4/30) for the combinations without or with PEG-IFNα, respectively, in all participants. The safety and tolerability profile of tobevibart and elebsiran is consistent with prior studies. The data show that the combination is well tolerated, with no new safety concerns and generally only mild or moderate treatment emergent adverse events being reported throughout the study. "The MARCH data demonstrate that combinations of tobevibart and elebsiran can achieve and maintain HBsAg loss in a subset of participants with low baseline HBsAg levels,” said Mark Eisner, M.D., MPH, Chief Medical Officer, Vir Biotechnology. “These findings provide important insights into the challenges of achieving functional cure in chronic hepatitis B and will inform future development efforts in the field.” As previously communicated, Phase 3 development of combinations of tobevibart and elebsiran in CHB will not move forward without a global development and commercialization partner, which has not been secured. The Company plans to streamline the final stages of the MARCH Phase 2 program to ensure continued participant benefit and safety, while applying continued financial stewardship. Cash runway guidance into mid-2027 remains unchanged, based on the current operating plan. Vir Biotechnology is fully committed to the continued development of tobevibart and elebsiran in chronic hepatitis delta, based on the transformational potential of the first-of-its-kind investigational combination to achieve complete suppression of the hepatitis delta virus, as shown by compelling positive efficacy and safety data from the Phase 2 SOLSTICE clinical trial. About Tobevibart and Elebsiran Tobevibart is an investigational broadly neutralizing monoclonal antibody targeting the hepatitis B surface antigen (HBsAg). It is designed to inhibit the entry of hepatitis B and hepatitis delta viruses into hepatocytes and to reduce the level of circulating viral and subviral particles in the blood. Tobevibart was identified using Vir Biotechnology’s proprietary monoclonal antibody discovery platform. The Fc domain has been engineered to increase immune engagement and clearance of HBsAg immune complexes and incorporates Xencor’s Xtend™ technology to extend half-life. Tobevibart is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis delta. Elebsiran is an investigational hepatitis B virus-targeting small interfering ribonucleic acid (siRNA) discovered by Alnylam Pharmaceuticals, Inc. It is designed to degrade hepatitis B virus RNA transcripts and limit the production of hepatitis B surface antigen. Current data indicates that it has the potential to have direct antiviral activity against hepatitis B virus and hepatitis delta virus. Elebsiran is administered subcutaneously, and it is currently in clinical development for the treatment of patients with chronic hepatitis delta. About Vir Biotechnology, Inc. Vir Biotechnology, Inc., is a clinical-stage biopharmaceutical company focused on powering the immune system to transform lives by discovering and developing medicines for serious infectious diseases and cancer. Its clinical-stage portfolio includes programs for chronic hepatitis delta and multiple dual-masked T-cell engagers across validated targets in solid tumor indications. Vir Biotechnology also has a preclinical portfolio of programs across a range of infectious diseases and oncologic malignancies. Vir Biotechnology routinely posts information that may be important to investors on its website. References: 1 CDC Hepatitis B Basics | Hepatitis B | CDC, accessed April 2025. 2 World Health Organization. Global Hepatitis Report 2024: Action for Access in Low- and Middle-income Countries. World Health Organization; 2024. 3 NIH National Institute of Diabetes and Digestive and Kidney Diseases Hepatitis B - NIDDK (nih.gov), accessed April 2025. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “should,” “could,” “may,” “might,” “will,” “plan,” “potential,” “aim,” “expect,” “anticipate,” “promising” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements regarding: the therapeutic potential of the combination of tobevibart and elebsiran to treat chronic hepatitis B and chronic hepatitis delta; Vir Biotechnology’s commitment to the continued development of the combination of tobevibart and elebsiran in chronic hepatitis delta and the transformational potential of the combination to achieve complete hepatitis delta viral suppression in a majority of patients; Vir Biotechnology’s anticipated cash runway; Vir Biotechnology’s strategy and plans; and any assumptions underlying any of the foregoing. Many factors may cause differences between current expectations and actual results, including, without limitation: unexpected safety or efficacy data or results observed during clinical studies or in data readouts, including the occurrence of adverse safety events; risks of unexpected costs, delays or other unexpected hurdles; challenges in accessing manufacturing capacity; clinical site activation rates or clinical enrollment rates that are lower than expected; the timing and outcome of Vir Biotechnology’s planned interactions with regulatory authorities, as well as general difficulties in obtaining any necessary regulatory approvals; successful development and/or commercialization of alternative product candidates by Vir Biotechnology’s competitors, as well as changes in expected or existing competition; geopolitical changes or other external factors; and unexpected litigation or other disputes. In light of these risks and uncertainties, the events or circumstances referred to in the forward-looking statements may not occur. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical studies may not be indicative of full results or results from later stage or larger scale clinical studies and do not ensure regulatory approval. The actual results may vary from the anticipated results, and the variations may be material. You are cautioned not to place undue reliance on any scientific data presented or these forward-looking statements, which are based on Vir Biotechnology’s available information, expectations and assumptions as of the date of this press release. Other factors that may cause Vir Biotechnology’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Vir Biotechnology’s filings with the U.S. Securities and Exchange Commission, including the section titled “Risk Factors” contained therein. Except as required by law, Vir Biotechnology assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

ENSURE 研究队列 4 的治疗结束（ EOT ）数据表明，对既往 BRII-179 治疗有应答的患者在接受治愈性治疗后相较 BRII-179 未经治患者实现了更快、更高的表面抗原清除率，强调了利用 BRII-179 识别和免疫激活患者，以提高功能性治愈结果的新型富集策略 ENSURE 研究队列 1-3 的 24 周随访结果表明，与 PEG-IFNα 单药相比， elebsiran + PEG-IFNα 联合治疗具有持续的非治疗性获益 北京和北卡罗来纳州达勒姆 2025年5月8日 /美通社/ -- 腾盛博药生物科技有限公司 （"腾盛博药"或"公司"，股票代码：2137.HK），一家致力于针对患者需求未被满足的疾病开发治疗方案，以改善患者健康状况和治疗选择的生物技术公司，今日宣布，在荷兰阿姆斯特丹举行的2025年欧洲肝病研究协会（EASL）会议上以最新突破壁报的形式公布其正在进行的ENSURE 2期研究数据。 ENSURE（NCT05970289）是一项多中心、开放性2期研究。队列1-3旨在评估elebsiran（一种研究性小干扰核糖核酸（siRNA））在与聚乙二醇干扰素α（PEG-IFNα）联合治疗慢性乙型肝炎病毒（HBV）感染者（基线乙肝表面抗原（HBsAg）水平为100-3,000 IU/mL）中的作用。 队列4入组了在先前的亚太地区研究BRII-179-835-001（NCT04749368）中接受过9剂BRII-179（一种基于重组蛋白的治疗性疫苗）联合elebsiran给药的参与者，接受elebsiran与PEG-IFNα联合治疗。这些参与者根据他们之前接受 BRII-179 治疗后产生的抗HBs应答进行分组：抗HBs滴度峰值 ≥ 10 IU/L的参与者被定义为抗HBs应答者，抗HBs滴度峰值 < 10 IU/L 的参与者被定义为无应答者。本研究队列 4 的设计基于BRII-179可以区分免疫应答者和无应答者的一种见解，从而为预测未来的治疗应答提供了可能。 队列4的中期数据显示，抗HBs应答者的HBsAg血清清除率显著高于无应答者。EOT（第48周）时，61%（11/18）的抗HBs应答者达到HBsAg血清清除，而无应答者为10%（1/10）。在11名实现HBsAg清除的抗HBs应答者中，91%（10/11）在EOT时的抗HBs滴度≥100 IU/L。 值得注意的是， 队列4中的BRII-179经治参与者比队列2和队列3中BRII-179未经治参与者更快实现HBsAg清除，第24周时在BRII-179经治参与者中已有83%（10/12）的参与者实现HBsAg清除，而BRII-179未经治参与者为55% （6/11）。这些发现表明，快速的HBsAg血清清除率和较高的抗HBs滴度可转化为持久的HBsAg清除，以及评估缩短PEG-IFNα疗程的可能性。 ENSURE研究队列1-3的其他数据表明，与PEG-IFNα单药治疗相比，100或200 毫克elebsiran与PEG-IFNα联合治疗在EOT24周后均可实现更高的HBsAg清除率，支持siRNA的额外获益。 腾盛博药首席医学官David Margolis博士表示："ENSURE研究队列4的数据令人鼓舞。我们在目标人群中发现，经过BRII-179预治疗产生免疫应答的患者在实现较高的HBsAg血清清除率方面表现出显著优势。借助BRII-179，我们可以识别内在免疫受损程度较低的患者，并进一步增强其免疫应答。这种方法可使 HBsAg 清除更持久，并有可能缩短 PEG-IFNα的治疗时间。我们正在全速推进临床工作，以期为慢性乙型肝炎患者提供有意义的可选方案。" 摘要编号： LB25123/ LBP-018 标题： 对既往BRII-179治疗产生应答的慢性乙型肝炎病毒感染参与者在接受elebsiran 和 PEG-IFNα 治疗后可获得更快更高的乙型肝炎表面抗原清除率：来自ENSURE研究的治疗结束时数据 主讲人： 黄丽虹教授，MBChB（CUHK），MD（CUHK），FRCP（Lond, Edin），FHKCP，FHKAM（Medicine），香港中文大学医学数据分析中心（MDAC）及香港中文大学内科及药物治疗学系肠胃及肝病科专科教授，中国香港特别行政区 共分析了28例基线HBsAg > 100和≤ 3000 IU/mL的参与者。在既往研究中，BRII-179诱导的18例参与者的抗HBs滴度峰值≥ 10 IU/L（定义为抗HBs应答者）和10例参与者< 10 IU/L（定义为无应答者）。 在开始elebsiran + PEG-IFNα治疗时，抗HBs应答者（539.4 [106.7-2165.0] IU/mL）的HBsAg中位数（范围）在数值上高于无应答者（219.3 [106.7-671.5] IU/mL）。EOT（第48周）时，61%（11/18）的抗HBs应答者达到HBsAg血清清除，而无应答者为10%（1/10）。 在HBsAg转阴的抗HBs应答者中，91%（10/11）在EOT时的抗HBs滴度≥100 IU/L。 BRII-179经治参与者比BRII-179未经治参与者更快实现HBsAg清除，第24周时已有83%（10/12）的参与者实现HBsAg清除（BRII-179未经治参与者为55% （6/11））。 Elebsiran + PEG-IFNα联合治疗在BRII-179经治的参与者中总体安全且可耐受。 摘要编号： LB25115/ LBP-016 标题： Elebsiran 和 PEG-IFNα联合治疗与PEG-IFNα治疗慢性乙型肝炎病毒感染参与者的有效性和安全性：正在进行的2期、随机、开放性ENSURE研究的随访结果 主讲人： David Margolis，M.D.，MPH，腾盛博药首席医学官 第72周（EOT后24周）时，与PEG-IFNα单药治疗相比，在接受elebsiran 200 mg或100 mg与PEG-IFNα联合治疗的参与者中观察到更高的HBsAg转阴率（21.1% [4/19]或33.3% [6/18] vs 5.6% [1/18]），所有11例实现HBsAg清除的参与者基线HBsAg < 1500IU/mL。 联合治疗队列和PEG-IFNα单药治疗队列之间治疗中出现的不良事件（TEAE）的发生率相当。大多数TEAE与PEG-IFNα的已知副作用一致。 作为腾盛博药开发HBV功能性治愈的独特方法的一部分，公司及其合作伙伴正在积极推进我们差异化产品组合的多项联合研究，包括BRII-179（正在腾盛博药领导的多项elebsiran联合 疗法 中进行 评估 ）；elebsiran（正在腾盛博药领导的PEG-IFNα联合 疗法 中进行 评估 ）；以及tobevibart（一种靶向HBV的研究性广泛中和单克隆抗体，正在Vir Biotechnology领导的在多项2期和3期tobevibart和elebsiran联合 疗法 中进行 评估 ）。数月后，我们将在2025年的科学会议上分享关键数据。 关于乙型肝炎 乙型肝炎病毒（HBV）感染是世界上最重大的感染性疾病威胁之一，全球感染人数超过2.54亿。 [1] 慢性HBV感染是肝脏疾病的主要原因，每年约有82万人死于慢性HBV感染的并发症。 [1] 中国慢性HBV感染人数达8,700万，非常值得关注。 [2] 关于 BRII-179 BRII-179是一种基于重组蛋白质的新型HBV 免疫治疗候选药物，可表达HBV的Pre-S1、Pre-S2和S表面抗原，旨在诱导增强和广泛的B细胞和T细胞免疫应答。腾盛博药于2018年12月从VBI Vaccines, Inc.（"VBI"）引进了BRII-179，还自2023年7月起，将BRII-179的独家许可扩展至全球市场。2023年11月，中国国家药品监督管理局（NMPA）药品审评中心（CDE）授予BRII-179突破性治疗认定。 关于 Elebsiran （曾用名 BRII-835 ， VIR-2218 ） Elebsiran是一种经皮下注射给药的靶向乙型肝炎病毒（HBV）的小干扰核糖核酸（siRNA）研究性药物，旨在降解HBV RNA转录本及限制乙型肝炎表面抗原的产生，其具有针对HBV及丁型肝炎病毒（HDV）的直接抗病毒活性。其是首个进入临床的采用增强稳定化学增强技术的siRNA，以增强稳定性并最大程度地减少脱靶活性，从而有可能提高治疗指数。腾盛博药于2020年从Vir Biotechnology, Inc. 获得了在大中华地区开发和商业化elebsiran的独家权益。 关于腾盛博药 腾盛博药（股票代码：2137.HK）是一家生物技术公司，致力于针对存在巨大未被满足的患者需求、治疗手段有限，以及给患者带来严重社会歧视的重大公共卫生挑战开发创新疗法。公司专注于感染性疾病，正在推进一条涵盖多种独特候选药物的产品管线，重点包括针对乙型肝炎病毒（HBV）感染的领先项目。在富有远见卓识和经验丰富的领导团队带领下，公司在位于罗利-达勒姆、旧金山湾区、北京和上海的主要生物技术中心开展业务。欲了解更多信息，请访问 www.briibio.com。 [1] World Health Organization. (April 2024). Global hepatitis report 2024: action for access in low- and middle-income countries. World Health Organization. Retrieved from https://www.who.int/publications/i/item/9789240091672 [2] World Health Organization. Hepatitis. World Health Organization. Retrieved from https://www.who.int/china/health-topics/hepatitis#:~:text=There%20are%2087%20million%20people,living%20with%20chronic%20hepatitis%20C.