Peginterferon alfa-2a

2024年初，腾盛博药宣布将优化资源配置，集中投入乙肝项目，一年后，公司交出了一份扎实的成绩单。上周发布的财务业绩，让我们看到了公司在资金使用上的精准和克制，而在昨天闭幕的2025年亚肝会（APASL）上，公布的包括ENSURE研究队列4数据在内的最新临床进展，又让我们看到了公司临床研发的大胆和高效。这个乙肝创新药赛道低调的领跑者，正在毫不动摇地在实现乙肝功能性治愈的道路上前行。01现金充沛，专注核心，回购股票彰显信心在生物医药行业融资环境趋紧的背景下，至2024年底，公司手握超过人民币24亿现金储备，足以支撑运营至2028年，充裕的资金不仅为腾盛博药目前在研的乙肝治愈联合疗法临床试验的持续推进提供了坚实的保障，也为未来的战略行动预留了充足的资源。这样的现金储备，来自于极为克制的资金使用，行政开支同比减少了22%，主要来源于组织结构的优化，研发开支同比减少38%，完全聚焦乙肝项目。对于管线中的非乙肝项目，像非常有潜力的的针对多重耐药/广泛耐药菌的新型抗生素BRII-693、长效HIV药物BRII-732与BRII-753，公司表示将寻求合作伙伴，利用外部资源来推进。对于资源有限的小公司，聚焦于最有希望的核心产品是明智之举，如果因为觉得多个产品都非常有潜力，都想靠自己推进，反而容易导致资源分散，每个项目都得不到足够的支持，从而影响整体研发效率。腾盛博药的管理层在这方面非常果断，我们也希望能很快听到这些非乙肝项目合作的好消息。在该省的地方非常省，但在该花的地方公司花得很坚决。2024年12月，公司以1,800万美元完成了对BRII-179知识产权的全资收购。此举不仅彻底摆脱了未来潜在的分成负担，更将这款可能具有重大战略价值的乙肝免疫疗法的临床供应与商业化主导权牢牢掌握在了手中。而在今年乙肝功能性治愈关键数据发布前，公司还启动了总额6,000万港元（占已发行股份10%）的股票回购计划，截至3月已累计耗资约530万港元回购443.3万股。公司以自有资金逆势增持，不仅释放“股价显著低估”的信号，更凸显管理层对临床研究结果的乐观预期，这一举措无疑为投资者注入了强心剂。02中期数据亮眼：患者富集策略有望改写乙肝治愈格局在2025年亚太肝病学会年会（APASL）上，腾盛博药公布了ENSURE研究新增的队列4的最新数据，管理层在电话会上把队列4定位为对患者富集策略的概念验证性试验。腾盛博药创造性地提出的这一患者富集策略，设想可以通过BRII-179诱导的免疫应答反应来识别具有较强内在免疫的患者，从而识别出最有希望对治愈疗法产生效果的优势患者。此前公布的ENSURE研究队列1-3的数据证明了elebsiran联合长效干扰素对比干扰素单药的优效性。而研究队列4，通过召回之前在BRII-179和elebsiran联合疗法研究中接受过BRII-179给药的患者，重新加入ENSURE研究，以此评估BRII-179免疫识别的潜力。队列4的参与者基于他们之前由BRII-179诱导的乙肝表面抗体应答水平进行分组，其中抗体滴度峰值大于等于10IU/L的被定义为BRII-179应答者，抗体滴度峰值小于10IU/L的定义为BRII-179无应答者。本次公布的数据显示，24周治疗后，BRIl-179应答者实现了56%的乙肝表面抗原清除率，显著高于BRII-179无应答者中的10%。在治疗半程的时候，这两组参与者的清除率差异已经很显著，这样的中期数据非常令人鼓舞，腾盛博药已在去年启动了一项前瞻性的2b期临床ENRICH研究进一步验证这一患者富集策略，ENRICH研究已于去年11月完成入组。我们不得不感叹腾盛博药管理层把钱用在刀刃上的能力，在创造性地提出用BRII-179筛选优势患者的策略后，没有贸然地马上开展大规模的新试验，而是想到利用正在进行中的ENSURE试验，创造性地加入队列4，做一个小范围的快速的概念验证，这让后续的ENRICH试验开展得更有底气。如果这个筛选优势患者策略最终成功，对于慢乙肝治愈创新疗法的格局可能产生颠覆性的影响，因为腾盛博药设计的这一富集策略主要依赖于对患者的内在免疫应答能力的识别，而业界已逐渐达成共识，内在免疫正是患者实现乙肝功能性治愈的关键。因此BRII-179完全可以成为任何乙肝治愈性疗法的前置步骤，提高功能性治愈可能性的同时减少不必要的治疗干预。腾盛博药还启动了另一项2b期临床ENHANCE研究来评估BRII-179，elebsiran和长效干扰素三联给药和长效干扰素单药对照的效果。此前的数据显示，与长效干扰素单药相比，在长效干扰素基础上联用elebsiran或BRII-179都可以增加乙肝表面抗原清除率。这项研究主要是为了确认这种疗效是否可以互相叠加，从而最大限度地提高功能性治愈率。ENHANCE研究已于今年1月完成入组。03静水流深：乙肝治愈仍是创新药的下一片蓝海2023年，强生砍掉了所有乙肝新药研发管线，而罗氏继2022年将长效干扰素派罗欣退出中国市场后，2024年终止了所有临床阶段的乙肝研发管线，前后仅一年多时间就见证了两家全球制药巨头退出乙肝新药研发领域，乙肝治愈的难度让很多人望而却步。但这个难以攻克的难题又是有着巨大吸引力的超级蓝海，乙肝依然是重大公共卫生问题之一，中国有超过7,000万乙肝病毒携带者，其中慢乙肝患者有大约2000万到3000万。近年来，随着治疗指南的更新和患者教育的深入，越来越多的慢乙肝患者更早地开始进行规范的抗病毒治疗。而“功能性治愈”理念的提出与推广，将进一步推动基层医疗观念和大众认知的更新。相信未来乙肝治疗格局将被重塑，以功能性治愈为目标，将显著降低肝硬化、肝细胞癌等疾病进展风险（如下图所示），改善患者生活质量，摆脱终身用药。Reference: Yip TCF, et al. J Hepat. 2019;70(3):361-370中国慢乙肝患者对于治愈的渴望和执念可以直观地从长效干扰素市场的规模管中窥豹。在欧美，长效干扰素由于耐受性问题，在慢乙肝治疗上的使用率极低，甚至现在很少有医生有处理长效干扰素用药不良反应的经验。罗氏的派罗欣，在退出中国市场前，在中国以外的市场销售额已不足销售峰值的10%。但在中国，国产的派格宾，作为唯一的长效干扰素上市药物，这两年销售额一直在快速增长，23年全年销售接近18亿，24年预计还有30%-50%的增长，根据派格宾的价格和用量推测，可能有接近10万的慢乙肝患者在尝试长效干扰素治疗。众所周知，目前长效干扰素只适合慢乙肝中非常小部分的优势人群，即使在优势人群中，功能性治愈率也并不理想，且存在较多不良反应。设想一下，如果有创新的治愈疗法，可以应用于更广泛的患者、实现更高的治愈率、有更可控的不良反应，愿意尝试的患者的数量级非常有可能达到百万级别，这将是个年销售额可达数百亿的市场。换个角度看，现有的存量慢乙肝患者中，如果有50%尝试治愈性疗法，就有1000多万的患者规模，几千亿的市场规模。更重要的是，这是一种治愈性疗法，意味着对医疗支出不会形成长期的负担。这几年我国每年新发肝硬化超过50万例，肝癌超过30多万例，其中80%-90%与乙肝病毒感染相关。而乙肝的功能性治愈能显著降低肝硬化、肝细胞癌等疾病的发病率，实际会避免未来花费更多医疗资源，在卫生经济学方面具有成本效益，相信相关创新疗法的研发和上市也将获得有力的政策支持。结语：有钱有研，铸就企业抗周期韧性在生物科技板块估值承压、资本趋于谨慎的当下，腾盛博药以24亿现金的护城河和核心资产的精准布局作为双重防线，展现出穿越周期的独特韧性。管理层通过股票回购与战略收购释放的强烈信心，叠加近期乙肝管线积极的数据，为其股价构筑了坚实的安全边际。尽管新药研发天然伴随长周期、高风险的挑战，但公司专注核心乙肝管线的战略定力已初显成效，如果未来1-2年间 ENRICH、ENHANCE试验的关键数据能持续验证疗效，腾盛博药有望以科研创新为矛、现金流为盾在众多瞄准乙肝功能性治愈的创新药企中杀出重围。识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

Preliminary data from Cohort 4 of the ENSURE study supports a novel enrichment strategy to utilize BRII-179 to identify patients who are immune responders and have the potential to achieve higher HBsAg loss at EOT 48-week EOT data from Cohort 1-3 of the ENSURE study clearly suggests the added benefits of elebsiran towards achieving a higher rate of HBsAg loss in combination with PEG-IFNα DURHAM, N.C. and BEIJING, China, March 30, 2025 /PRNewswire/ -- Brii Biosciences Limited ("Brii Bio," or the "Company", stock code: 2137.HK), a biotechnology company developing therapies to improve patient health and choice across diseases with high unmet medical needs, announced new data from its ongoing Phase 2 ENSURE study as a late-breaking oral presentation at the 34th Annual Meeting of Asian Pacific Association for the Study of the Liver (APASL 2025) in Beijing, China. ENSURE (NCT05970289) is a multicenter, open-label Phase 2 study. Cohorts 1-3 were designed to evaluate the contribution of elebsiran, an investigational small interfering ribonucleic acid (siRNA), in combination with pegylated interferon alpha (PEG-IFNα) in participants with chronic HBV infection with baseline hepatitis B surface antigen (HBsAg) of 100-3,000 IU/mL. Participants who completed 9 doses of BRII-179, a recombinant protein-based therapeutic vaccine, in combination with elebsiran (BRII-835) in a previous APAC study BRII-179-835-001 (NCT04749368) were enrolled to Cohort 4 of this study and received elebsiran and PEG-IFNα combination treatment. The design of Cohort 4 as part of this study was based on insight from previous studies that a significant proportion of the chronic HBV patients fail to generate a sufficient immune response after receiving multiple doses of BRII-179, and therefore unlikely to have the immune support to achieve sustainable functional cure. Emerging data from Cohort 4 showed that participants who previously had BRII-179 induced anti-HBs response achieved a substantially higher rate of HBsAg seroclearance than those who did not. At Week 24, more than half of the BRII-179 responders (55.6% [10/18]) achieved HBsAg seroclearance, compared to only 10.0% (1/10) in non-responders. These latest data suggest that BRII-179 can serve as a predictive tool for enriching patients more likely to respond to curative therapies. Additional data from Cohorts 1-3 of the ENSURE study showed that higher end of treatment (EOT) HBsAg loss and seroconversion rates in participants receiving elebsiran in combination with PEG-IFNα than those receiving PEG-IFNα alone. "The positive Cohort 4 data from the ENSURE study opens new doors for HBV functional cure," said Dr. Grace Lai-Hung Wong, Professor of Gastroenterology and Hepatology at CUHK Medical Data Analytics Centre (MDAC) and Department of Medicine and Therapeutics in Hong Kong SAR, China. "Previous studies have suggested that BRII-179 may offer a unique opportunity to identify CHB patients who are able to elicit the necessary HBsAg antibody response. I believe these new findings provide clear evidence supporting such value proposition and further substantiate the role of BRII-179 in shaping future combination therapies." "We are encouraged that the Cohort 4 from the ENSURE study continue to support our enrichment strategy in developing a functional cure for chronic HBV in target populations," said David Margolis, MD, Chief Medical Officer of Brii Bio. "The results underscore the potential of BRII-179 in identifying patients who are more likely to respond to regimens aimed at functional cure, thereby enhancing functional cure rates in the target population while reducing exposure to costly therapies for those with a lower probability of cure. We are committed to advancing BRII-179 in combination with various modalities through our ongoing studies and collaborations with strategic partners, aiming to deliver higher functional cure rates to 254 million patients worldwide living with chronic HBV infection." Abstract Number: OP0335 Presentation Title: Responders to Prior BRII-179 Treatment Achieved Faster and Higher Rate of HBsAg Seroclearance Following Treatment of Elebsiran and PEG-IFNα in Participants with Chronic Hepatitis B Virus Infection: Preliminary Data from ENSURE Study Presenter: Grace Lai-Hung Wong, MBChB (CUHK), MD (CUHK), FRCP (Lond, Edin), FHKCP, FHKAM (Medicine), Professor of Gastroenterology and Hepatology at CUHK Medical Data Analytics Centre (MDAC) and Department of Medicine and Therapeutics in Hong Kong SAR, China Among the 28 of the 31 participants enrolled in Cohort 4 with baseline HBsAg ≥ 100 IU/mL being analyzed, 18 participants with peak anti-HBs ≥ 10 IU/L induced by prior BRII-179 treatment were defined as BRII-179 responders and 10 participants with peak anti-HBs < 10 IU/L were defined as non-responders. At Week 24 of treatment with elebsiran + PEG-IFNα, 39.3% (11/28) of the Cohort 4 participants achieved HBsAg seroclearance. The rate of HBsAg seroclearance at Week 24 in the BRII-179 responders was 55.6% (10/18), notably higher compared to the non-responders at 10% (1/10). Responders to prior BRII-179 treatment appeared to achieve a faster HBsAg seroclearance compared to BRII-179 naïve participants receiving elebsiran + PEG-IFNα as previously reported. Elebsiran and PEG-IFNα combination therapy was generally safe and well tolerated in participants with virally suppressed chronic HBV infection. Treatment with elebsiran + PEG-IFNα is ongoing for 48 weeks. Abstract Number: LB0009 Presentation Title: Higher end of treatment (EOT) HBsAg loss and seroconversion rates in participants with chronic HBV infection receiving elebsiran (BRII-835) and pegylated interferon alfa-2a (PEG-IFNα) compared to PEG-IFNα alone: Week 48 results from ongoing ENSURE study Presenter: Jidong Jia, M.D., Ph.D., Professor of Medicine at the Liver Research Centre, Beijing Friendship Hospital, Capital Medical University in Beijing, China The rates of HBsAg seroclearance at EOT in elebsiran 200 mg + PEG-IFNα and elebsiran 100 mg + PEG-IFNα cohorts were 26.3% (5/19) and 33.3% (6/18), respectively, notably higher compared to PEG-IFNα alone cohort (5.6%) in participants with baseline HBsAg levels 100-3,000 IU/mL. Greater HBsAg reductions at EOT were observed in elebsiran + PEG-IFNα combination cohorts (mean [SE]: -2.47 [0.28] or -3.01 [0.28] log10 IU/mL in elebsiran 200 mg or 100 mg, respectively) than in PEG-IFNα cohort (-1.02 [0.30] log10 IU/mL). Elebsiran in combination with PEG-IFNα at both 200 mg and 100 mg doses achieved similar HBsAg reductions and seroclearance rates. Elebsiran and PEG-IFNα combination therapy was generally safe and well tolerated in participants with virally suppressed chronic HBV infection. Post-treatment follow-up is ongoing and will continue for 24 weeks after discontinuation of treatment. As part of Brii Bio's unique approach to developing a functional cure for HBV, the Company and its partners are actively progressing multiple combination studies with our differentiated portfolio, including BRII-179, a recombinant protein-based HBV immunotherapeutic being evaluated in multiple combination studies with elebsiran led by Brii Bio; elebsiran being evaluated in combination with PEG-IFNα in studies led by Brii Bio and tobevibart, an investigational broadly neutralizing monoclonal antibody targeting HBV, being evaluated in multiple Phase 2 and 3 tobevibart and elebsiran combination studies led by Vir Biotechnology. Key data readouts will be shared in the coming months at the scientific conferences throughout 2025. About Hepatitis B Hepatitis B virus (HBV) infection is one of the world's most significant infectious disease threats with more than 254 million people infected globally.[1] Chronic HBV infection is the leading cause of liver disease and an estimated 820,000 people die of complications from chronic HBV infection each year.[1] HBV is of exceptional concern in China, where 87 million people are chronically infected.[2] About BRII-179 BRII-179 is a novel recombinant protein-based HBV immunotherapeutic candidate that expresses the Pre-S1, Pre-S2, and S HBV surface antigens, and is designed to induce enhanced and broad B-cell and T-cell immunity. In November 2023, the Center for Drug Evaluation (the "CDE") of the National Medical Products Administration (the "NMPA") granted BRII-179 Breakthrough Therapy Designation. About Elebsiran (BRII-835, VIR-2218) Elebsiran is an investigational subcutaneously administered HBV-targeting siRNA designed to degrade hepatitis B virus RNA transcripts and limit the production of hepatitis B surface antigen. It has the potential to have direct antiviral activity against HBV and HDV. It is the first siRNA in the clinic to include Enhanced Stabilization Chemistry Plus technology to enhance stability and minimize off-target activity, which potentially can result in an increased therapeutic index. Brii Bio licensed exclusive rights to develop and commercialize elebsiran for the Greater China territory from Vir Biotechnology, Inc. in 2020. About Brii Bio Brii Biosciences Limited ("Brii Bio", stock code: 2137.HK) is a biotechnology company developing therapies to address major public health challenges where patients experience high unmet medical needs, limited choice and significant social stigmas. With a focus on infectious diseases, the Company is advancing a broad pipeline of unique therapeutic candidates with lead programs against hepatitis B virus (HBV) infection. The Company is led by a visionary and experienced leadership team and has operations in key biotech hubs, including Raleigh-Durham, the San Francisco Bay Area, Beijing and Shanghai. For more information, visit . SOURCE Brii Biosciences Limited WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED