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]

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.

ACTRN12622000317796 / Active, not recruiting临床2期

A Phase 2a, Randomized, Blinded, Multicenter Study Investigating a Combination of AB-729 and VTP-300 to evaluate their safety and reactogenicity in Virologically-Suppressed Chronic Hepatitis B Participants.

开始日期2022-06-02

申办/合作机构

Arbutus Biopharma Corp.

[+1]

100 项与 Imdusiran 相关的临床结果

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100 项与 Imdusiran 相关的转化医学

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100 项与 Imdusiran 相关的专利（医药）

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项与 Imdusiran 相关的文献（医药）

2024-10-11·ACS Infectious Diseases

Control of Hepatitis B Virus with Imdusiran, a Small Interfering RNA Therapeutic

Article

作者: Cuconati, Andrea ; Paratala, Bhavna ; Thi, Emily P. ; Graves, Ingrid E. ; Ye, Xin ; Rijnbrand, Rene ; McClintock, Kevin ; Micolochick Steuer, Holly M. ; Espiritu, Christine ; Sofia, Michael J. ; Lee, Amy C. H. ; Harasym, Troy ; Jarosz, Agnes ; Snead, Nicholas M. ; Teng, Xiaowei ; Abbott, Cory ; Ardzinski, Andrzej ; Lam, Angela M.

Chronic hepatitis B is a global health concern with a high risk of end-stage liver disease. Current standard-of-care agents have low cure rates, and new therapies are needed. Small interfering RNAs (siRNAs) that target viral RNAs fulfill a gap not addressed by standard-of-care agents and may contribute to a functional cure. Here, we describe the preclinical characterization of imdusiran (AB-729), a novel, pan-genotypic siRNA therapeutic that effectively reduces HBsAg, viral antigens, and viral replication in chronic hepatitis B patients and is currently in Phase 2 clinical studies. In hepatitis B virus (HBV) cell-based systems, imdusiran possessed pan-genotypic nanomolar potency and retained activity against HBV target site polymorphisms. Imdusiran was active against nucleos(t)ide analogue- and capsid assembly modulator-resistant HBV isolates, and combination with standard-of-care agents was additive. In an HBV adeno-associated virus mouse model, HBsAg was reduced up to 3.7 log₁₀ after a single imdusiran dose, with sustained suppression for 10 weeks. Imdusiran did not intrinsically stimulate cytokine release in healthy donor human whole blood, supportive of its mechanism of action as a direct acting RNA interference antiviral. Taken together, these data support imdusiran in combination treatment approaches toward chronic hepatitis B functional cure.

AIDS reviews4区 · 医学

Hepatitis B Gene Therapy Coming to Age.

4区 · 医学

Review

作者: Soriano, Vicente

The major pandemics caused by chronic viral infections is produced by HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV), with estimates of 38, 70, and 250 million people worldwide, respectively (Fig. 1). During the last couple of years, the advent of direct oral antivirals has allowed pursuing global HCV eradication. In an unprecedented manner, these drugs cure more than 95% of hepatitis C patients when given for only 2-3 months. The enthusiasm on HCV has renewed the interest for curative strategies for both HIV and HBV. However, important biological differences between all three viruses may preclude envisioning a similar rapid success for either HIV or HBV than for HCV infection. As shown in figure 1, once infection of targeted cells has occurred, the viral genetic material only replicates in the cytosol for HCV whereas it enters the nucleus and integrates into the chromosomes as provirus for HIV or is converted in a circular covalently closed form (cccDNA) for HBV (Fig. 1). Blocking viral nucleic acid replication for a minimum lag of time allows definitive clearance of HCV infection, with degradation of residual cytoplasmic HCV-RNA strands. In contrast, blocking viral replication has only a transient effect on HIV or HBV, as mRNA expression resumes following treatment discontinuation, given the stability of the HIV provirus or the HBV cccDNA, respectively. The European Liver meeting took held in Paris on April 2018. A relatively large number of presentations addressed distinct new hepatitis B therapeutic strategies. Table 1 summarizes some of the molecules that have been investigated so far with more promising results, grouping them into distinct drug classes (Soriano et al. Exp Op Inv Drugs 2017;26:843-51), based on their distinct mechanism of action and targeted steps in the HBV life cycle (Fig. 2). Considering the pros and cons of novel HBV therapeutic candidates, it has become apparent new HBV gene therapies among the most attractive. Several advances have contributed to position gene therapy in front within the experimental HBV armamentarium. First, progresses in delivery systems, including the use of polymers and nanoformulations have allowed developing easier forms of administration that now are becoming subcutaneous and monthly. Second, the synthetic production of oligonucleotide formulations has reduced costs. Third, the specificity against HBV is higher than for other experimental agents, as immune modulators that enhance innate immunity, such as TLR agonists (i.e., GS-9620) or checkpoint inhibitors (i.e., nivolumab). Fourth, significant declines in serum hepatitis B surface antigen (HBsAg) are demonstrated during gene therapy, which have never been seen using the most potent polymerase inhibitors (i.e., tenofovir or entecavir). Finally, unanticipated significant reductions in cccDNA are seen with HBV gene therapy, most likely as prove of an indirect benefit of waning the immunosuppressive effect of large over amounts of HBsAg released by infected hepatocytes that contributes to T-cell exhaustion. In a pioneering study, Roche was the first to publish the potent effect of an oral small molecule that blocked HBV gene expression (Mueller et al. J Hepatol 2018;68:412-20). The drug belonged to the dihydroquinolizinone class, and directly or indirectly modified viral RNAs, promoting their degradation. This posttranscriptional silencing was accompanied by rapid drops in HBV-DNA and more importantly in serum HBsAg in the humanized mice. However, Roche decided to discontinue any further clinical development of the drug. Nowadays, two major groups of agents are being developed as HBV gene therapies. At this time, interference RNA (iRNA) molecules and nucleic acid polymers (NAPs) are the most promising. Overall, iRNA is double-stranded RNA molecules, 20 nucleotides long. One strand matches a segment of specific HBV mRNA and induces its degradation. Several iRNA molecules have entered into Phase II clinical trials (Flisiak et al. Exp Op Biol Ther, in press), including ARB-1467 and AB-729 (Arbutus), ARO-HBV (Arrowhead), ALN-HBV (Alnylam), and IONIS-HBVRx (Ionis). In most cases, they are tested as part of combination therapy with nucleos(t)ide analogs and/or peginterferon. NAPs are phosphorothioate 40 length oligonucleotides that no map any HBV sequence. However, they interact with a liver host target protein (apolipoprotein-like) and result in specific inhibition of HBV mRNAs. This is followed by rapid suppression of HBsAg release (Roehl et al. Mol Ther Nuc Acids 2017;8:1-12). In a pilot study with intravenous REP-2139, investigators from Replicor demonstrated strong reductions in HBV-DNA along with significant drops in HBsAg and seroconversion in some patients. More interestingly was the recognition of significant reductions in hepatic cccDNA, most likely a result of an indirect effect following the removal of large amounts of HBsAg from the bloodstream that contributes to impaired T-cell responses in chronic hepatitis B patients (Bazinet et al. EASL, Paris 2018; abstract FRI-343). An improved NAP, named REP-2165 and subcutaneous administration are currently being tested.

139

项与 Imdusiran 相关的新闻（医药）

2024-12-12

·艾美达医药咨询

大佬一键清仓一个赛道

MNC罗氏拿出了一把“大砍刀”。在罗氏2024Q2的PPT展示中，抗感染管线梯队中有5款管线，其中4款分别为Ruzotolimod（TLR7激动剂）、Xalnesiran（小干扰RNA）、PDL1 LNA和HBsAg单抗，均处于一、二期临床。待到2024Q3的展示时风云变幻，罗氏将上述目标适应症为乙肝的4条管线一次性砍掉，公司并没有给出“清仓”的具体原因，市场上最多的猜测是临床管线数据“不尽人意+罗氏精简管线将精力和投入聚集在核心领域”。不过对于罗氏而言，抗感染板块一直以来算是公司比较边缘的模块，公司在2024Q2介绍2025年以后关键驱动中，抗感染（乙肝）板块的分子并未位列其中，但之前的边缘板块心血管代谢领域却合作开发出了口服GLP-1和新一代降压药Zilebesiran两大潜在重磅产品。另外，一键清仓自家乙肝管线的MNC，还不止罗氏一家。 01 强生也曾一键清仓过无独有偶，强生曾经一次性放弃了公司的乙肝管线梯队。 2023年7月，强生在进行2023Q2业绩展示时管线显示，JNJ-3989（HBV siRNA）、JNJ-3283（PD-1单抗）、JNJ-0440（衣壳组装调节剂CAM）、JNJ-4964（口服TLR7激动剂）等乙肝管线从公司研发管线展示中被剔除，而另一条备受市场关注的管线JNJ-6379因有效性不佳早在2022年被强生放弃。同样，抗感染板块在强生也属于一个比较尴尬的位置，强生的强项在肿瘤、自免和神经科学板块，而精简乙肝管线也可以视为聚焦在更有收效比的领域。实质上强生和罗氏在乙肝开发的方向其实较为相近，可以看到两者均探索了小核酸疗法、TLR7激动剂和PD-1层面的开发。但值得注意的是，强生的部分乙肝管线在被放弃后迎来了另一个MNC接盘方。JNJ-3989是一款可以靶向所有乙肝病毒（HBV）RNA的 siRNA分子，2018年强生从Arrowhead公司获得授权许可，2023年10月强生与GSK就JNJ-3989签订了全球开发和转让协议，未来由全权负责所有未来的开发和商业化活动，并承担未来需要向Arrowhead支付的预付款和里程碑付款。从JNJ-3989已有的临床二期数据显示，使用单药治疗虽然能使得患者乙肝表面抗原（HBsAg)水平有明显的下降，患者停药后仍存在持续的HBsAg应答，但达到HBsAg清除的患者比例较少；在寻求联用的过程中，联用JNJ-6379（衣壳抑制剂）、Nivolumab（PD-1）均未能提升疗效，而JNJ-3989联用长效干扰素则做出了较为明显的效果，JNJ-3989先诱导患者HBsAg初始下降后，加用长效干扰素进一步增大HBsAg降幅，19%的患者出现至少一次的HBsAg清除。罗氏这次清仓的管线中也有一款小核酸药物Xalnesiran（RG6346），Xalnesiran是一款靶向HBV基因组HBsAg编码区的siRNA药物。在已公布的临床数据显示，Xalnesiran联用长效干扰素治疗48周的HBsAg清除率分别为6.7%、17.6%和30.0%，Xalnesiran未来能否顺利获得买家接盘，只能说难度较大。 02 荆棘满地的乙肝赛道尽管治愈乙肝的临床需求巨大，但目前研发上主要要达到的目标是功能性治愈而非完全治愈。抗乙肝病毒治疗在临床上有三个治疗里程碑：部分治愈、功能性治愈、彻底治愈（区别如下），部分治愈目前尚能达到。功能性治愈和完全彻底治愈区别在于，功能性治愈未能清除肝内共价闭合环状的DNA和整合基因组的HBV DNA，功能性治愈是经过一段时间的治疗后患者的免疫系统足以压制乙肝病毒，也能安全停药，肝损伤恢复，肝癌风险降到最低。但由于乙肝病毒仍然存在，随着患者免疫力下降，仍有复发的可能。目前，乙肝的一线用药主要分为干扰素和核苷（酸）类似物两大类，这两大类药物虽然有一定疗效，但需要接受终身治疗，并且无法在短期内清除乙肝病毒，并且治愈率较低。乙肝之所以难治，核心在于HBV病毒会通过肝细胞膜上NTCP作为受体进入并感染肝细胞，在其中建立其基因组，即具有染色体特征的共价闭合环状DNA（cccDNA），同时HBV病毒还可能将编码表面抗原的部分基因片段至宿主肝细胞基因组中，这两个部分很难被靶向和清除。针对cccDNA的清除成为全球乙肝药物研发者的主要研发方向，可以分为直接靶向cccDNA和间接靶向cccDNA两大类。不过，直接靶向cccDNA一直以来是乙肝药物开发的巨大挑战，目前在研药物更多的是间接靶向cccDNA，通过影响cccDNA的生命周期来实现对cccDNA的清除，主要包括进入抑制剂、衣壳抑制剂、小核酸疗法和HBsAg抑制剂等。进入抑制剂方面，吉利德的Bulevirtide走在最前面，其原理是与HBV竞争性结合肝细胞表面受体NTCP，阻断HBV进入感染肝细胞。在过往二期临床数据中，Bulevirtide单药治疗效果并不理想，其与干扰素联用48周取得了比较好的效果使用，20%患者实现HBsAg清除，市场正在等待其三期数据的出炉。病毒核衣壳组装抑制剂（CpAM）的研发则进展不畅，简而言之，CpAM是通过干扰HBV病毒核衣壳的组装和功能，从而影响HBV DNA的复制且严重削弱子代病毒的毒性和再次侵染能力。这个方向过去也不乏海外公司探索，如先驱Assembly开发了一系列的管线梯队，最终分别以疗效不足、肝毒性和主动终止等原因结束研发。另外罗氏、强生的CpAM后续也被自家主动放弃或终止。目前来看，siRNA、ASO疗法路线势头较好，其大致原理为阻止HBV转录物并诱导其降解。除了上述提到的JNJ-3989、Xalnesiran之外，GSK的3228836、Vir公司的VIR-2218在二期临床中均展现了有25%以上患者实现乙肝表面抗原清除，不过更加考验药物实际疗效的是HBV DNA复阳率和药效的持续性。另外，HBsAg抑制剂和ASO方向也有非常积极的进展，Replicor公司的HBsAg抑制剂REP2139/REP2165在一项联合干扰素、富马酸替诺福韦酯的三联治疗二期临床中，48周有高达60%的患者实现乙肝表面抗原的清除，及60%的患者实现表面抗体阳转。 03 国内进展据数据统计，中国乙肝病毒感染者约8600万人，而表面抗原携带者人数是全球最多，乙肝药物研发企业并不在少数。从开发方向看，siRNA疗法和核衣壳抑制剂为国内药企参与最多的路线。 sirna疗法方面，恒瑞医药的HRS-5635目前在众多国内自主研发的管线里率先进入临床二期，但具体数据尚未披露，反而正大天晴TQA3038披露了部分一期数据，其最高剂量爬到800mg，且安全性良好（不良事件均为轻微，并在研究结束前得到缓解）。另外，合作开发管线中腾盛博药引进的VIR-2218和齐鲁药业引进的AB-729海外开发进度较快，处于临床二期。核衣壳抑制剂方面，比较亮眼的是广生堂的GST-HG141，不仅顺利完成国内临床二期，同时取得了较为惊艳的数据，GST-HG141治疗90例患者的慢性乙型肝炎低病毒血症二期临床数据显示：GST-HG141联合核苷类似物连续治疗24周，高低剂量组HBV DNA低于检测下限的比例达到81.5%和84.0%，远超核苷类似物单药治疗（32.1%），且患者HBV DNA和pgRNA下降幅度均超过1 log10，进一步验证了GST-HG141阻断HBV病毒复制和耗竭cccDNA的作用。另外，广生堂还布局了HBsAg抑制剂GST-HG121和表面抗原抑制剂GST-HG131，整体布局较为全面。当然，国内还有一大堆新的研发者正在涌现，包括舶望制药、浩博医药、新通药物等一级公司，他们正在用自己独特的开发路线来解决乙肝难以治愈或达到功能性治愈的问题。结语：罗氏、强生等MNC清仓乙肝管线，并不意味着这个领域的开发失去希望，更可能像部分MNC退货中国资产的案例一样，只是自身资源再配置做出的战略调整。在新药研发成功率创新低和药物研发成本不断增加的背景下，做出这样的选择无可厚非，投资者需要理性看待。本文转载自瞪羚社/Kris. ------------------------------ 「长按」二维码添加小达「进群」与更多行业伙伴共探市场前沿资讯艾美达医药咨询艾美达（北京）医药信息咨询有限公司，成立于2014年4月，是一家专业的医药行业咨询服务提供商。公司致力于将产业政策研究与真实世界的数据挖掘深度结合，洞悉行业政策对市场的影响，通过专业的研究提供前瞻性的市场分析，为企业产品上市后的市场准入提供整体解决方案。

siRNA引进/卖出临床2期临床1期临床申请

2024-11-26

·GlobeNewswire-Health Care

Arbutus to Participate in H.C Wainwright @ Home Virtual Fireside Chat

WARMINSTER, Pa., Nov. 26, 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 that the Company will participate in the virtual H.C Wainwright @ Home fireside chat series taking place on Tuesday, December 3, 2024 at 11:00 am ET. To access the live webcast of the fireside chat, please visit: https://investor.arbutusbio.com/events-presentations. An archived replay of the webcast will be available on the Arbutus website for a limited time after the event. About Arbutus Arbutus Biopharma Corporation (Nasdaq: ABUS) is a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to develop novel therapeutics with distinct mechanisms of action, which can potentially be combined to provide a functional cure for patients with chronic hepatitis B virus (cHBV). Arbutus believes the key to success in developing a functional cure involves suppressing HBV DNA, reducing surface antigen, and boosting HBV-specific immune responses. Arbutus’ pipeline of internally developed, proprietary compounds includes an RNAi therapeutic, imdusiran (AB-729), and an oral PD-L1 inhibitor, AB-101. Imdusiran has achieved meaningful functional cure rates in patients with cHBV when administered as combination therapy. Plans are underway to advance imdusiran into a Phase 2b clinical trial. AB-101 is currently being evaluated in a Phase 1a/1b clinical trial. For more information, visit www.arbutusbio.com. Contact Information Investors and Media Lisa M. CaperelliVice President, Investor RelationsPhone: 215-206-1822Email: lcaperelli@arbutusbio.com

临床2期临床结果

2024-11-15

·GlobeNewswire-Health Care

Arbutus’ Imdusiran Achieves Functional Cure in cHBV Patients when Combined with a Short Course of Interferon

50% of patients who had baseline HBsAg levels less than 1000 IU/mL achieved functional cure in Cohort A1 of the IM-PROVE I Phase 2a clinical trial Overall, in Cohort A1, 25% of patients achieved functional cure Data to be presented in late-breaker poster session at AASLD – The Liver Meeting® on Monday, November 18, 2024 WARMINSTER, Pa., Nov. 15, 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 IM-PROVE I Phase 2a clinical trial (AB-729-201) showing that six doses of imdusiran, the Company’s RNAi therapeutic candidate, and 24 weeks of pegylated interferon alfa-2α (IFN), a standard-of-care immunomodulator, added to ongoing nucleos(t)ide analogue (NA) therapy, led to a functional cure rate of 50% (3/6) in HBeAg-negative patients with baseline HBsAg levels less than 1000 IU/mL, and an overall functional cure rate of 25% (3/12). Patients with HBsAg levels less than 1000 IU/mL represent a significant portion of the cHBV population. These data will be presented as a late-breaker poster presentation on November 18, 2024 at The American Association for the Study of Liver Diseases (AASLD) – The Liver Meeting® 2024. “For the first time, we are seeing a meaningful percentage of HBV patients functionally cured with an RNAi therapeutic and interferon,” commented Professor Man-Fung Yuen, D.Sc., M.D., Ph.D., Chief of the Division of Gastroenterology and Hepatology, the University of Hong Kong and Principal Investigator of the IM-PROVE I clinical trial, who will present the data at AASLD. “While 48 weeks of interferon can be used as a standard of care treatment for HBV patients, historically less than 10% of patients experience a functional cure. Here, with the combination of imdusiran and 24 weeks of interferon, we see a 50% functional cure rate in HBV patients with HBsAg less than 1000 IU/mL at baseline and a 25% functional cure rate overall. In addition, I was pleased to see that this regimen with a short course of interferon was generally safe and well-tolerated. These data are extremely impressive and provide hope for the millions of HBV patients worldwide and the medical community that a finite curative treatment is possible with imdusiran and interferon.” Key data from patients in Cohort A1 that received 6 doses of imdusiran plus 24 weeks of IFN in addition to ongoing NA therapy include: 50% of patients (3/6) with baseline HBsAg <1000 IU/mL achieved a functional cure (defined as sustained HBsAg loss and HBV DNA less than the lower limit of quantification (LLOQ) 24 weeks off all treatment (including NAs), with or without hepatitis B surface antibodies (anti-HBs)).Overall, 25% of patients (3/12) achieved a functional cure.Those patients that achieved a functional cure also seroconverted with anti-HBs levels increasing as patients lost HBsAg.The combination of imdusiran and 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 late-breaker poster, titled, “IM-PROVE I: Imdusiran in Combination with Short Courses of Pegylated Interferon Alfa-2a in Virally Suppressed, HBeAg Negative Subjects with Chronic HBV (cHBV) Infection Leads to Functional Cure”, is available on the Company’s website and provides the complete data set for all four cohorts of patients dosed in this clinical trial. Additional immune activation data in those patients in Cohort A1 that achieved a functional cure will be presented by Dr. Emily Thi, Senior Director, Immunobiology and Biomarkers Research at Arbutus Biopharma in a poster titled, “Soluble Immune Biomarker Profiling of Chronic Hepatitis B Subjects Treated with Imdusiran in Combination with Pegylated Interferon Alfa Reveals Phases of Immune Activation.” The data in this poster show that patients in Cohort A1 had greater increases in favorable immune biomarkers than those in other cohorts. Functionally cured patients and those with baseline HBsAg <1000 IU/mL had elevations of key immune biomarkers during the imdusiran lead-in, IFN treatment and follow-up periods, suggesting immune activation induced by imdusiran plus IFN treatment. “We are extremely excited to have functionally cured these patients with the imdusiran and interferon treatment regimen. 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. “Excess production of surface antigen is believed to contribute to host immune exhaustion, resulting in inadequate immune response and failure to suppress the virus. These data support our belief that lowering surface antigen with imdusiran and incorporating an immunomodulator in the treatment regimen provides a functional cure in some patients with cHBV. We thank all the patients and investigators who participated in this clinical trial.” All of the above posters that will be presented at AASLD – The Liver Meeting can be accessed through the Arbutus website under Publications. IM-PROVE I CLINICAL 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, 4 doses) added to ongoing NA therapy, patients were randomized into one of the following four cohorts: Cohort A1: imdusiran (2 doses) + NA + IFN weekly for 24 weeks (n=12), Cohort A2: NA + IFN weekly for 24 weeks (n=13), Cohort B1: Imdusiran (1 dose) + NA + IFN weekly for 12 weeks (n=8) and Cohort 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. 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. In a Phase 2a clinical trial, imdusiran achieved meaningful functional cure rates in patients with cHBV when combined with pegylated interferon alfa-2α and nucleos(t)ide analogue therapy. Additional clinical data generated thus far has shown imdusiran to be generally safe and well-tolerated, while also providing meaningful reductions in hepatitis B surface antigen and hepatitis B DNA. Plans are underway to advance imdusiran into a Phase 2b clinical trial. 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 million people in the United States suffer from chronic HBV infection. Approximately 1.1 million 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 develop novel therapeutics with distinct mechanisms of action, which can potentially be combined to provide a functional cure for patients with chronic hepatitis B virus (cHBV). Arbutus believes the key to success in developing a functional cure involves suppressing HBV DNA, reducing surface antigen, and boosting HBV-specific immune responses. Arbutus’ pipeline of internally developed, proprietary compounds includes an RNAi therapeutic, imdusiran (AB-729), and an oral PD-L1 inhibitor, AB-101. Imdusiran has achieved meaningful functional cure rates in patients with cHBV when administered as combination therapy. Plans are underway to advance imdusiran into a Phase 2b clinical trial. AB-101 is currently being evaluated in a Phase 1a/1b clinical trial. For more information, visit www.arbutusbio.com. 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 IM-PROVE I Phase 2a clinical trial data; the potential for finite curative treatment to be possible with imdusiran, interferon and NA therapy; the IM-PROVE I Phase 2a clinical trial data supporting Arbutus’ belief that lowering surface antigen with imdusiran and incorporating an immunomodulator in the treatment regimen combined with ongoing NA therapy provides a functional cure in some patients with cHBV; the potential to lead to a functional cure for HBV; Arbutus’ future development plans for its product candidates; the expected results of Arbutus’ clinical development plans and clinical trials with respect to its product candidates; Arbutus’ expectations with respect to the release of data from its clinical trials and the expected timing thereof; and the potential for Arbutus’ 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 www.sedar.com and at www.sec.gov. 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

临床结果临床2期

100 项与 Imdusiran 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
慢性乙型肝炎	临床2期	澳大利亚	Assembly Biosciences, Inc.	2021-05-07
慢性乙型肝炎	临床2期	保加利亚	Assembly Biosciences, Inc.	2021-05-07
慢性乙型肝炎	临床2期	加拿大	Assembly Biosciences, Inc.	2021-05-07
慢性乙型肝炎	临床2期	新西兰	Assembly Biosciences, Inc.	2021-05-07
乙型肝炎	临床申请	中国	齐鲁制药有限公司	2022-05-10
乙型肝炎	临床申请	中国	Arbutus Biopharma Corp.	2022-05-10

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ACTRN12622000317796 (IM-PROVE II \| AB-729-202, GlobeNewswire) 人工标引	临床2期	慢性乙型肝炎	22	Imdusiran, VTP-300, low-dose nivolumab	構簾觸積顧鹽觸艱夢醖(衊網鬱蓋襯膚鏇淵範餘) = 窪夢遞壓醖網選簾選襯網繭鹽鬱簾憲顧鏇衊夢 (襯製鏇獵鏇選齋餘壓積 )	积极	2024-11-15
NCT04980482 (AB-729-201, EASL2024) 人工标引	临床2期	慢性乙型肝炎	43	imdusiran (A1: 24 wks IFN + 2 imdusiran doses + NA)	鏇簾憲淵鹹構鹹膚餘憲(憲壓網廠壓糧顧齋遞遞) = 蓋鏇鑰醖鹽醖鑰獵繭鹹繭壓壓繭繭築齋鹹襯鏇 (蓋襯齋夢鹹簾艱膚艱艱 ) 更多	积极	2024-06-01
				imdusiran (A2: 24 wks IFN + NA)	鏇簾憲淵鹹構鹹膚餘憲(憲壓網廠壓糧顧齋遞遞) = 選襯廠餘鹹廠壓鹽襯構繭壓壓繭繭築齋鹹襯鏇 (蓋襯齋夢鹹簾艱膚艱艱 ) 更多
AB-729-202 (GlobeNewswire) 人工标引	临床2期	乙型肝炎	40	imdusilan+VTP-300	獵鬱鬱製鏇夢遞艱獵廠(網齋選網簾獵築獵膚鬱) = There were no serious adverse events, Grade 3 or 4 adverse events or treatment discontinuations. 繭簾壓選製餘網蓋鏇壓 (製觸膚蓋構網糧憲範構 ) 更多	积极	2023-11-09
				imdusilan+placebo
Phase 2a (EASL2022)	临床2期	HBV RNA transcripts \| HBV DNA \| hepatitis B surface antigen (HBsAg)	-	AB-729 siRNA	醖齋淵構衊鹹鑰積壓鏇(鬱簾憲鹹醖顧窪積簾廠) = 觸艱淵構選鏇鬱積鏇壓憲繭艱繭餘窪齋醖願積 (餘繭簾獵製憲構觸糧鹹 )	积极	2022-06-25
				Control GalNAc siRNA	醖齋淵構衊鹹鑰積壓鏇(鬱簾憲鹹醖顧窪積簾廠) = 鑰餘築壓製鬱齋鬱衊顧憲繭艱繭餘窪齋醖願積 (餘繭簾獵製憲構觸糧鹹 )
NCT04820686 (AB-729-001, EASL2022) 人工标引	临床2期	慢性乙型肝炎	27	AB-729	鏇繭網選繭齋壓齋齋製(糧艱廠遞壓蓋築糧鑰醖) = 範齋艱鬱醖淵夢窪膚遞鬱鬱衊衊構顧繭構遞製 (鑰鹹衊膚顧願憲糧積廠 )	积极	2022-06-22
EASL2021	N/A	慢性乙型肝炎 HBsAg	-	AB-729	窪蓋鏇獵製衊鏇膚衊簾(範鏇鹹蓋齋遞製襯壓繭) = 憲鏇製醖壓製鹽製衊襯範觸顧顧鹹衊窪選鏇築 (糧鹽簾鏇齋製築壓糧簾 ) 更多	-	2021-06-23