本帖最后由 sir 于 2020-8-27 20:31 编辑
Arbutus之前做过RNAi+NA+干扰素联合的方案，效果不太好停止了，看来Arbutus认为联合ABI-H0731会比干扰素的方案更好？
Assembly Biosciences and Arbutus Biopharma Announce Clinical Collaboration Agreement to Evaluate the Combination of Core Inhibitor ABI-H0731 with RNAi Therapeutic AB-729 in Patients with Chronic Hepatitis B Virus Infection
August 27, 2020 at 8:00 AM EDT
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SOUTH SAN FRANCISCO, Calif. and WARMINSTER, Pa., Aug. 27, 2020 (GLOBE NEWSWIRE) -- Assembly Biosciences, Inc. (Nasdaq: ASMB) and Arbutus Biopharma Corporation (Nasdaq: ABUS), today announced that the companies have entered into a clinical collaboration agreement to evaluate Assembly’s lead hepatitis B virus (HBV) core inhibitor candidate ABI-H0731 in combination with Arbutus’ proprietary GalNAc delivered RNAi therapeutic AB-729 and standard-of-care nucleos(t)ide reverse transcriptase inhibitor (NrtI) therapy for the treatment of patients with chronic HBV infection. A randomized, multi-center, open-label Phase 2 clinical trial will explore the safety, pharmacokinetics, and antiviral activity of the triple combination of HBV core inhibitor ABI-H0731, RNAi therapeutic AB-729 and an NrtI compared to the double combinations of ABI-H0731 with an NrtI and AB-729 with an NrtI. This clinical trial is projected to initiate in the first half of 2021 and enroll approximately 60 virologically-suppressed patients with HBeAg negative or positive chronic HBV infection. Patients will be dosed for 48 weeks, with a 24 week follow-up period. As part of the collaboration, the companies may add cohorts in the future, to evaluate other patient populations and/or combinations. “Our team at Assembly is committed to driving the field of HBV research toward the ultimate goals of finite therapy and cure,” said John McHutchison, AO, MD, Chief Executive Officer and President of Assembly Biosciences. “One of our key priorities for this year has been to execute a clinical collaboration to initiate a new combination therapy trial, as we believe that multi-drug combinations with non-overlapping mechanisms may result in higher response rates and potentially shorten the duration of treatment. We are excited to combine what we view as the most advanced core inhibitor with a promising RNAi therapeutic in this new trial as we continue to work to advance novel treatment options for patients living with this chronic disease.” William Collier, President and Chief Executive Officer of Arbutus, stated, “Arbutus is focused on discovering and developing a cure for chronic hepatitis B. We maintain this can best be accomplished through a combination of agents with different mechanisms of action that target distinct parts of the virus lifecycle. To this end, we are advancing a proprietary portfolio of compounds at various stages of clinical and preclinical development that have the potential to lead to a functional cure with a finite treatment duration.” Mr. Collier added, “This clinical collaboration in which both companies share expertise and costs has the potential to provide proof of concept data regarding the safety and efficacy of combining some of the most promising drug candidates and expedite efforts to advance a much needed HBV treatment regimen.” About ABI-H0731, Assembly’s Lead HBV Core Inhibitor
Assembly’s HBV portfolio includes three clinical-stage small molecule candidates, all of which are HBV core inhibitors that target multiple steps of the HBV lifecycle. In Phase 2 clinical trials, first-generation core inhibitor ABI-H0731 administered with nucleos(t)ide analogue reverse transcriptase inhibitor (NrtI) therapy has been well-tolerated, has shown statistically superior antiviral activity in HBV DNA suppression compared to NrtI therapy alone, and has demonstrated significant declines in HBV pgRNA that may indicate decreased cccDNA levels. In the ongoing Phase 2 open-label extension trial, Assembly has begun transitioning patients off combination therapy, to then monitor for sustained virologic response (SVR). 核心抑制剂ABI-H0731与RNAi治疗性AB-729联合治疗慢性乙型肝炎病毒感染的疗效评价
2020年8月27日美国东部时间上午8:00
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加利福尼亚州南旧金山和宾夕法尼亚州沃明斯特，2020年8月27日（环球新闻专线）--Assembly Biosciences，Inc.（纳斯达克：ASMB）和杨梅生物制药公司（纳斯达克：ABUS），今天宣布，两家公司已签订临床合作协议，以评估Assembly领先的乙型肝炎病毒（HBV）核心抑制剂候选人ABI-H0731，并结合杨梅的专利GalNAc提供的RNAi治疗AB-729和护理标准（t）ide逆转录酶抑制剂（NrtI）治疗慢性乙型肝炎病毒感染的治疗。
一项随机、多中心、开放标签的第2期临床试验将探讨HBV核心抑制剂ABI-H0731、RNAi治疗AB-729和NrtI三重组合的安全性、药代动力学和抗病毒活性，并与ABI-H0731和NrtI和AB-729和NrtI的双重组合进行比较。这项临床试验预计于2021年上半年开始，并纳入约60名HBeAg阴性或阳性慢性HBV感染的病毒学抑制患者。给药48周，随访24周。作为合作的一部分，公司未来可能会增加队列，以评估其他患者群体和/或组合。
“我们在Assembly的团队致力于推动HBV研究领域朝着有限治疗和治愈的最终目标前进，”Assembly Biosciences首席执行官兼总裁、医学博士John McHutchison说。“我们今年的重点工作之一是开展临床合作，启动新的联合治疗试验，因为我们相信，具有非重叠机制的多药联合治疗可能会导致更高的疗效，并可能缩短治疗时间。我们很高兴在这项新的试验中结合我们认为最先进的核心抑制剂和有前途的RNAi治疗方法，因为我们继续努力为患有这种慢性病的患者提供新的治疗选择。”
杨梅公司总裁兼首席执行官威廉科利尔（William Collier）表示：“杨梅致力于发现和开发一种治疗慢性乙型肝炎的药物。我们认为，这一目标最好是通过结合具有不同作用机制的药物，针对病毒生命周期的不同部分。为此，我们正在推进临床和临床前发展的各个阶段的专利化合物组合，这些化合物有可能在有限的治疗时间内实现功能性治疗。”
Collier先生补充道：“这两家公司共享专业知识和成本的临床合作，有可能提供关于联合一些最有希望的候选药物的安全性和有效性的概念证明数据，并加快推进急需的乙肝治疗方案的努力。”
关于ABI-H0731，Assembly的领先HBV核心抑制剂
Assembly的HBV产品组合包括三个临床阶段的小分子候选，所有这些都是针对HBV生命周期的多个步骤的HBV核心抑制剂。在第二阶段临床试验中，第一代核心抑制剂ABI-H0731与核仁（t）类似物逆转录酶抑制剂（NrtI）联合应用具有良好的耐受性，与单独使用NrtI治疗相比，在抑制HBV DNA方面显示出更高的抗病毒活性，并且已证明HBV pgRNA的显著下降可能表明cccDNA水平降低。在正在进行的第2阶段开放标签扩展试验中，Assembly已经开始将患者从联合治疗过渡到监测持续的病毒学反应（SVR）。
关于杨梅AB-729（Gal Nac RNAi）
AB-729是一种针对肝细胞的RNA干扰（RNAi）治疗方法，使用杨梅的新型共价结合N-乙酰半乳糖胺（GalNAc）给药技术，使皮下注射成为可能。AB-729抑制病毒复制，降低所有HBV抗原，包括临床前模型中的乙型肝炎表面抗原。减少乙型肝炎表面抗原被认为是使病人的免疫系统重新唤醒对病毒作出反应的关键先决条件。在一项正在进行的单剂量和多剂量1a/1b期临床试验中，AB-729显示了积极的初步安全性和耐受性数据，并显著降低了乙型肝炎表面抗原。
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发表于 2020-8-27 20:30
