The goal of this clinical trial is to learn about the action of Imdusiran (AB-729) in the liver of people with chronic hepatitis B. The main questions it aims to answer are:
* how well is it working in the liver
* how does Imdusiran affect the hepatitis B virus
Participants will receive injections of Imdusiran, one injection every 8 weeks, for a total of 4 doses. They will also undergo 2 liver biopsies: one with the first dose of Imdusiran, and the second 8 weeks after the last dose of Imdusiran.

开始日期2024-07-25

申办/合作机构

University of Maryland Baltimore

[+1]

NCT06277037

/ RecruitingN/A

A Long-Term Follow-up Study for Subjects With Chronic Hepatitis B Previously Treated With Imdusiran (AB-729)

This is a long term follow-up study for chronic hepatitis B (CHB) subjects who have received imdusiran treatment in a prior clinical trial, stopped NA therapy during that trial, and remain off therapy. Subjects may enroll after completing the end of study visit (baseline visit within 12 weeks ± 1 week from the end of study [EOS] visit) from their imdusiran clinical trial (the "parent study"). No interventions will be performed in this study other than blood sample collections, review of current medications, and reporting of any adverse events related to study procedures or NA therapy if restarted. Study participation will be for approximately 2 years (to complete a total of at least 3 years of follow-up while off NA therapy, inclusive of parent study participation).

开始日期2024-07-11

申办/合作机构

Arbutus Biopharma Corp.

NCT06245291

/ Withdrawn临床2期

A Phase 2a, Open-Label Multiple Dose Study Evaluating the Safety, Tolerability, and Pharmacodynamics of Imdusiran (AB-729) in Combination With Intermittent Dosing of Durvalumab, a PD-L1 Monoclonal Antibody, in Subjects With Chronic HBV Infection

This is a phase 2a, open-label, multicenter study investigating the safety, tolerability, and antiviral activity of durvalumab administered at targeted times during a 48-week treatment period of imdusiran in virologically-suppressed CHB subjects

开始日期2024-05-01

申办/合作机构

Arbutus Biopharma Corp.

100 项与 Arbutus Biopharma Corp. 相关的临床结果

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0 项与 Arbutus Biopharma Corp. 相关的专利（医药）

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101

项与 Arbutus Biopharma Corp. 相关的文献（医药）

2025-03-21·Organic Process Research & Development

Development of a Scalable Manufacturing Process for AB-343 Drug Substance: A Potential Candidate for the Treatment of Coronavirus Infections

作者: Singh, Rajeev K. ; Liu, Jia ; Pallerla, Mahesh ; Mason, Jeremy D. ; Vega, Marvin Marcus ; Wu, Zhenhua ; Sofia, Michael J. ; Pamulapati, Ganapati Reddy ; Pulipaka, Aravind B. ; Wang, Xu ; Spink, Jan M.

A scalable process for manufacturing of the anticoronavirus clin. candidate AB-343 has been developed.The lactam-containing subunit of the mol. was prepared using a novel synthetic route involving a nitro-Michael reaction and a rhodium-catalyzed nitro group hydrogenation followed by in situ translactamization sequence as a key transformation.The drug substance was assembled via sequential amide coupling and deprotection reactions, followed by a final dehydration of a primary amide to the corresponding nitrile using T3P.AB-343 drug substance was successfully manufactured on a multikilogram scale using this route, which was suitable for supporting IND-enabling studies and Phase I clin. development.

2024-12-01·Antiviral Research

Biological characterization of AB-343, a novel and potent SARS-CoV-2 Mpro inhibitor with pan-coronavirus activity

Article

作者: Chen, Chia-yi ; Ardzinski, Andrzej ; Fan, Kristi Y ; Konz Makino, Debora L ; Blaesse, Michael ; Wasserman, Adam ; Prasad, Archna ; Sheraz, Muhammad ; Bergmann, Andreas ; Mani, Nagraj ; Kultgen, Steven G ; Sofia, Michael J. ; Micolochick Steuer, Holly M. ; Chen, Chia-Yi ; McGovern-Gooch, Kayleigh R. ; Vega, Marvin ; Lam, Angela M ; von König, Konstanze ; Lam, Angela M. ; McGovern-Gooch, Kayleigh R ; Gotchev, Dimitar ; Nguyen, Duyan ; Cuconati, Andrea ; Cole, Andrew G. ; Lindstrom, Aaron ; Cole, Andrew G ; Weiss, Susan R ; Konz Makino, Debora L. ; Weiss, Susan R. ; Kultgen, Steven G. ; Wang, Xiaohe ; Fan, Kristi Y. ; Kowalski, Rose ; Wang, Xu ; Sofia, Michael J ; Bracci, Nicole ; Maskos, Klaus ; Micolochick Steuer, Holly M ; Tercero, Breanna

Since the SARS-CoV-2 outbreak, there have been ongoing efforts to identify antiviral molecules with broad coronavirus activity to combat COVID-19. SARS-CoV-2's main protease (M^pro) is responsible for processing the viral polypeptide into non-structural proteins essential for replication. Here, we present the biological characterization of AB-343, a covalent small-molecule inhibitor of SARS-CoV-2 M^pro with potent activity in both cell-based (EC₅₀ = 0.018 μM) and enzymatic (K_i = 0.0028 μM) assays. AB-343 also demonstrated excellent inhibition of M^pro of other human coronaviruses, including those from the alpha (229E and NL63) and beta (SARS-CoV, MERS, OC43, and HKU1) families, suggesting the compound could be active against future coronaviruses. No change in AB-343 potency was observed against M^pro of SARS-CoV-2 variants of concern, including Omicron, suggesting that AB-343 could be developed as a treatment against currently circulating coronaviruses. AB-343 also remained active against several M^pro variants which confer significant resistance to nirmatrelvir and ensitrelvir, which are presently the only M^pro inhibitors authorized for the treatment of COVID-19, further supporting the evaluation of AB-343 as a novel and potent therapeutic for COVID-19 and other coronaviruses.

2024-11-14·Journal of Medicinal Chemistry

Rational Design of Macrocyclic Noncovalent Inhibitors of SARS-CoV-2 M^pro from a DNA-Encoded Chemical Library Screening Hit That Demonstrate Potent Inhibition against Pan-Coronavirus Homologues and Nirmatrelvir-Resistant Variants

Article

作者: Sofia, Michael J. ; Cuconati, Andrea ; Preuss, Franziska ; Zhang, Ying ; Mani, Nagraj ; Prasad, Archna ; Wang, Xu ; Wang, Xiaohe ; Maskos, Klaus ; Liu, Jenny ; von König, Konstanze ; Lam, Angela M. ; Keefe, Anthony D. ; McGovern-Gooch, Kayleigh ; Carpino, Philip ; Vega, Marvin M. ; Schmitt, Andreas ; Turcotte, Stéphane ; Clark, Matthew A. ; Johnstone, Shawn ; Cole, Andrew G. ; Gotchev, Dimitar ; Guilinger, John P. ; Chen, Chia-yi ; Tercero, Breanna ; Konz Makino, Debora L. ; Centrella, Paolo A. ; Fan, Kristi Yi

The recent global COVID-19 pandemic has highlighted treatments for coronavirus infection as an unmet medical need. The main protease (M^pro) has been an important target for the development of SARS-CoV-2 direct-acting antivirals. Nirmatrelvir as a covalent M^pro inhibitor was the first such approved therapy. Although M^pro inhibitors of various chemical classes have been reported, they are generally less active against nirmatrelvir-resistant variants and have limited pan-coronavirus potential, presenting a significant human health risk upon future outbreaks. We here present a novel approach and utilized DNA-encoded chemical library screening to identify the noncovalent M^pro inhibitor 5, which demonstrated a distinct binding mode to nirmatrelvir. A macrocyclization strategy designed to lock the active conformation resulted in lactone 12 with significantly improved antiviral activity. Further optimization led to the potent lactam 26, which demonstrated exceptional potency against nirmatrelvir-resistant variants as well as against a panel of viral main proteases from other coronaviruses.

301

项与 Arbutus Biopharma Corp. 相关的新闻（医药）

2025-04-23

·investor.arbutusbio.com

Arbutus to Present Imdusiran and AB-101 Data at EASL Congress 2025

Five abstracts accepted for poster presentations WARMINSTER, Pa., April 23, 2025 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (Nasdaq: ABUS) (“Arbutus” or the “Company”), a clinical-stage biopharmaceutical company focused on infectious disease, today announced that five abstracts, including one late-breaker, have been accepted for presentation at the European Association for the Study of the Liver (EASL) Congress 2025 taking place May 7 - 10, 2025 in Amsterdam, Netherlands. The following abstracts will be presented as posters in the Viral Hepatitis B and D: New Therapies, Unapproved Therapies or Strategies session on May 8, 2025, from 8:30 am – 5:00 pm CET. Abstract Number: 1768 Title: IM-PROVE I: characterization of chronic hepatitis B (CHB) subjects with functional cure or HBV DNA suppression after completion of imdusiran plus short courses of pegylated interferon alfa-2a (IFN) and discontinuation of nucleos(t)ide analogue (NA) therapy Presenter: Prof. Man-Fung Yuen Presentation Date: May 8, 2025 Key Findings: Within this small group of subjects who achieved functional cure or HBV DNA

临床结果临床2期siRNA

2025-04-09

·生物制品圈

2025年，mRNA会迎来自己的第二春吗？

新冠时代，mRNA疫苗如同“救火队长”，用编码刺突蛋白的简单指令扑灭疫情之火。如今，褪去紧急使用的光环，它必须回答一个更深刻的命题：如何从“战时状态”的应急工具，蜕变为改写人类疾病治疗史的“生命编程语言”？行业的阵痛与新生在此刻交织。当曾经支撑起千亿美元市场的mRNA疫苗管线逐渐降温，Moderna、BioNTech等巨头不得不直面“后新冠悬崖”的财报压力，但低谷中孕育的新生力量同样澎湃——将mRNA技术用于更常见广阔疾病市场的尝试，先后迎来里程碑。站在2025年的春天回望，mRNA技术早已超越“疫苗”的狭义定义，它既是肿瘤微环境中激活T细胞的“免疫开关”，也是罕见病患者体内替代缺陷蛋白的“分子补丁”，更是基因治疗中比CRISPR更温和的“临时指令”。当新冠红利成为历史注脚，这场属于mRNA的“二次革命”，或许才是真正属于它的春天——一个无需疫情催熟、只需静待技术开花的季节。1走出国门当我们仍在仰视海外“mRNA三巨头”的精彩履历时，海的那边早已察觉到来自东方的创新力量。今年1月，法国专利研究公司KnowMade发布一篇研究报道，主要阐述了世界范围内mRNA领域专利竞争格局。KnowMade曾在半导体知识产权研究方面具有深厚的专业积累和广泛的市场影响力，因此该医药方面的报道也吸引人关注。数据显示，在全球范围内，mRNA产业专利申请活动在2024年略有增加，共公布了735个新专利家族，而2023年为639个。这一上升趋势反映了各行业和各地区对创新的日益重视。最显著的差异出现在第三季度——2024年公布了200个专利家族，而2023年同期仅为120个。激增的第三季度，开花的mRNA。除了“三巨头”的日常“霸榜”，同写意发现了一抹中国红——艾博生物凭借19个新专利家族在2024年位列至第四位，正式入驻全球前五。从艾博生物的发展历程来看，这一成绩似乎有迹可循。自2019年成立以来，新冠的火热带动资本的浪潮，其自是其中的宠儿。6年已经过去，这一排名的含金量究竟如何？根据公开资料查阅了艾博生物的主要技术专利情况，同写意此前曾在一篇报道进行盘点。资料显示，决定mRNA“命运”的技术，艾博生物均有涉及，涵盖mRNA设计、LNP递送技术、创新制剂开发、大规模生产的各环节，贯穿mRNA管线全流程。mRNA药物要想真正发挥作用，高效的递送系统不可或缺。而LNP正是实现这一目标的“核心载体”。其中，阳离子脂质的开发是推动LNP技术进步的关键。而艾博生物是全国唯一一家拥有全流程专利的公司。在各种行业会议中，目前只有艾博生物展示过其独有的修饰技术，可以完全突破Moderna的修饰专利，在蛋白表达和抗体的滴度方面不输100% M1ψ修饰。这类专利保护不仅是在mRNA修饰上，在递送系统的竞争也同样激烈。只有少数企业如Moderna、Acuitas、Arbutus和艾博生物等，研发的阳离子脂质经过大规模临床验证，其他不少企业或者直接使用Moderna开发的SM-102作为递送系统的核心成分，或者自有的阳离子脂质与递送系统及相关产品依然还处于临床相对早期阶段，递送平台的效果还有待更多数据来验证。同时，近年来，查阅以往的资料亦能发觉，艾博生物的主要发力点覆盖了环状RNA及CMC工艺技术等。我们很早就知道，RNA技术有一个关键的缺陷——RNA通常以线性形式存在，而这种形式的mRNA的寿命很短。在几小时内，细胞内的核酸酶就会把它们降解掉。RNA这种转瞬即逝的性质对用作疫苗来说并不是个大问题，因为它只需要很短的时间来编码出蛋白质，就能引发免疫反应。但是，对于大多数治疗应用来说，最好是能让RNA留存的时间更长。而这是环状RNA（circRNA）的一个优势——其共价闭合环形结构可以保护自身免受核酸酶的降解，从而具有更好的稳定性和更长的寿命。理论上，即使在低剂量水平下，环状RNA也能增强治疗潜力。艾博生物构建了基于I型内含子的circRNA新环化系统。相较于常规的PIE（Permuted Intron-Exon）构建方法，该系统通过对前体RNA各元件的重新设计，实现了无需引入额外序列的“无痕”环化。据称，环化效率更高。而在工艺技术专利方面，同写意发现，该公司设计了一步合成环状RNA的方法，通过对反应条件的摸索设计，整合体外转录（IVT）与核酶自剪接反应，实现模板DNA转录与前体RNA环化在相同反应体系中的无缝衔接。在提高环化效率的同时，省略了前体RNA的纯化步骤。除了mRNA修饰、递送系统、制剂及稳定性、大规模生产能力等硬件实力，AI辅助抗原设计和序列优化对疫苗的蛋白表达量、细胞免疫、体液免疫水平，疫苗的有效性、稳定性、成药性、专利保护性，临床数据，以及真实世界保护效力和安全性，也起到至关重要的作用。根据企查查数据库，目前国内mRNA企业中，只有艾博生物和蓝鹊生物拥有计算机软件著作权。考虑到专利一直是mRNA产业的卡脖子因素——决定着中国mRNA产业是否需要假手于人，看海外公司的脸色行事——因此强调一万遍其重要性也不为过。毫不过分地说，技术专利将决定一家企业的发展上限，更在一定程度上决定着中国mRNA产业的国际地位。如今，艾博生物的成绩或将成为中国的一剂强心剂。但未来的答卷，值得诸君审阅吗？2“钱”为万法主即便上述情况令人雀跃，但审视mRNA产业的未来，离不开商业化能力。目前，中国mRNA企业可分为三大梯队：• 第一梯队：艾博生物、石药集团等，具备全链条技术能力；• 第二梯队：蓝鹊生物、瑞吉生物等，专注细分技术或适应症；• 第三梯队：复星医药、康希诺等传统药企通过合作或授权切入赛道。审视上述企业的花期长短，需要一双向“钱”看的眼睛。同写意根据公开资料查询，全球mRNA市场预计2030年达230亿美元，中国占比有望超20%。除传染病疫苗外，三大领域将成增长引擎——肿瘤治疗、预防性疫苗、蛋白替代疗法。而全球mRNA领域融资中，中国企业占比近半，但技术成熟度参差不齐。mRNA赛道退潮之下，昔日该赛道中的明星公司中不乏陨落，濒临破产。业内需要看到实打实的产品进展，而不是华丽的融资数字。根据截至2025年3月的最新信息，同写意发现，中国多家企业在mRNA技术领域的管线进展显著，尤其在RSV（呼吸道合胞病毒）疫苗和肿瘤疫苗领域竞争激烈。在这场摩拳擦掌的军备竞赛中，同样是几家欢喜几家愁。我们需要看到，除了新冠以外更多的想象空间。传染病和肿瘤疫苗成为了兵家必争之地。根据Precedence Research预测，到2034年，全球mRNA治疗市场规模将飙升至426.4亿美元。目前，全球超50个mRNA肿瘤疫苗进入临床，中国企业的关键是如何在靶点选择上差异化。从官方管线信息来看，各大公司呈现出多元发展的态势，其中艾博生物将更多精力放在肿瘤、蛋白替代和传染病领域，以寻求“后新冠时代”的发展方向，目前，行业已经公开了三个mRNA肿瘤疫苗的III期临床，都来自Moderna。基于公开的数据，我们没办法预测它们到底能不能成功，但至少从III期的规模看，Moderna仍有一定底气。然而，3月初云顶新耀传来mRNA治疗性肿瘤疫苗首次给药的消息，2024年9月艾博生物也发布临床结果，上述公司也是目前我们能挖掘的主要声量——留给中国公司的时间不多了。而在传染病疫苗领域，艾博生物的进展所属头部，公开资料显示，其自主研发的RSV疫苗和VZV疫苗已获批临床，均采用其独创的碱基修饰技术和自有的LNP，该系统的核心组分为国内唯一经大规模III期临床验证且拥有自主知识产权的可电离脂质，展现出良好的安全性和有效性，已获得中美澳及欧洲多个主要国家的专利授权。尽管进展频频，但仍不可松懈。面对三巨头的环伺，中国企业需要发出更响亮的声音。若中国企业能持续攻克核心专利、拓展适应症、深化国际合作，mRNA技术或将成为中国生物医药“弯道超车”的标志性领域。正如诺奖得主魏斯曼所言：“若美国停滞不前，中国可能成为mRNA领导者。” 这一预言能否成真，取决于技术、产业与政策的协同进化。技术需要用之于人，企业需要有能力变现，mRNA产业才能迎来良性的长足发展，谁能最快跑出来，谁就能拥有话语权。3写在最后人们习惯用阶段性的词汇形容一个产业，例如，2024年，是公认的“ADC年”。2025年已走过三个月，我们尚不知今年的词眼会落在谁的身上。对于mRNA而言，2025年似乎是开了个好头，无论是海外机构对艾博生物的肯定，还是首次mRNA肿瘤疫苗传来的进展，这个因为新冠结束渐渐失去热度的行业，正在用自己的技术和专利能力温暖自身。回头望去，中国mRNA企业的征途才刚刚启航。这片星辰大海中，既有肿瘤疫苗治愈生命的璀璨星辰，也有未知病毒突袭的暗礁险滩。当艾博生物的专利排名跻身全球前五时，这不只是榜单上的一个亮眼数字，更是一束照亮中国生物医药创新之路的璀璨星光。它们都昭示着一个事实——中国mRNA产业，正以科学与人文的双翼，飞越技术的崇山峻岭，叩响生命奥秘的下一道门扉。春天似乎真的来了。参考资料：https://www.knowmade.com/technology-news/life-sciences-news/healthcare-technology-news/patenting-activity-in-2024-an-insightful-analysis/https://mp.weixin.qq.com/s/Sfbjb03lwXGYXr3o7ukSfA识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明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不本站。

信使RNA疫苗财报

2025-03-20

·investors.barinthusbio.com

Barinthus Bio Reports Full Year 2024 Financial Results and Updates on Corporate Developments

Strategic transformation ongoing, positioning the Company as a focused leader in immunology and inflammatory diseases Highly differentiated, potentially curative immunotherapy for celiac disease (VTP-1000) in the clinic, with first data expected in third quarter of 2025 Proprietary SNAP-TI platform promoting antigen-specific immune tolerance is anticipated to drive multiple future pipeline and partnership opportunities Strategic prioritization of resources expected to provide a cash runway into 2027 OXFORD, United Kingdom and GERMANTOWN, Md., March 20, 2025 (GLOBE NEWSWIRE) -- Barinthus Biotherapeutics plc (NASDAQ: BRNS) (“Barinthus Bio,” or the “Company”), an immunology and inflammation (I&I) company focused on developing therapies that promote immune tolerance with curative potential, today announced its financial results for the year ended December 31, 2024 and provided an overview of the Company’s business updates. “We’ve entered 2025 with a refreshed strategic focus on immunological and inflammatory diseases. Following our restructuring, we are strongly positioned to advance our highly differentiated lead asset,VTP-1000, (and the underlying SNAP-TI platform) in patients with celiac disease. Through design innovations enabling greater targeting of disease antigens, intramuscular administration and potentially improved tolerability, VTP-1000 has promise to be a leading therapy for the approximate 80 million people worldwide with celiac disease. We look forward to reporting single-ascending dose Phase 1 data for this program in the third quarter of this year.” said Bill Enright, Chief Executive Officer of Barinthus Bio. “VTP-1000 is based on our innovative SNAP-TI platform, which is differentiated based on its capacity to promote antigen-specific immune tolerance that specifically guides a patient's T cells to suppress unwanted inflammation and restore the natural state of immune non-responsiveness to healthy tissue without affecting immunity against cancer or infections. Given this mild and potentially curative approach to restoring balance to the immune system, we believe SNAP-TI is poised to drive multiple future pipeline and partnership opportunities for the company particularly for autoimmune diseases where broadly immunosuppressive drugs are not optimal." “Turning to our development candidates designated for partnering, we reported highly encouraging results from two Phase 2 trials in our chronic hepatitis B (“CHB”) program demonstrating that VTP-300 contributed to the achievement of undetectable HBsAg levels in eight participants, with two participants meeting functional cure criteria. Further Phase 2 data are anticipated in the second quarter of 2025, which are expected to strengthen VTP-300’s market positioning as a component of a functional cure for CHB.” 2024 Corporate MilestonesClinical developments Celiac Disease (VTP-1000) In April 2024, Barinthus Bio received clearance from the U.S. Food and Drug Administration and Australian regulatory authorities on an Investigational New Drug application to progress VTP-1000 in a first in human clinical trial in celiac disease. In September 2024, Barinthus Bio initiated the first-in-human, Phase 1 AVALON trial for VTP-1000 in celiac disease. The AVALON trial aims to enroll 42 participants with celiac disease and will be conducted in two parts: the first part, a randomized double-blind placebo controlled single ascending dose, followed by the second part, a randomized double-blind placebo-controlled multiple ascending dose and incorporating a controlled gluten challenge to assess the impact of VTP-1000 administration on patients’ exposure to gluten. Chronic Hepatitis B (VTP-300) In June 2024, Barinthus Bio presented interim data from the two Phase 2 trials of VTP-300, which achieved 19% undetectable HBsAg levels across both studies, indicating potential rates of functional cure. The majority of patients who were assessed reached very low levels of HBsAg and eligibility for nucleos(t)ide discontinuation. In October 2024, the Company completed enrollment of the Phase 2b HBV003 clinical trial for VTP-300 in CHB. In November 2024 Barinthus Bio reported positive updated interim data from the Phase 2b HBV003 clinical trial for VTP-300 showing that as of the data cut off, eight participants achieved complete HBsAg loss (defined as HBsAg levels below the lower limit of quantitation [

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