Arbutus 将在 EASL International Liver Congress™ 2022 上展示七幅科学

StephenW

Arbutus 将在 EASL International Liver Congress™ 2022 上展示七幅科学海报

    Arbutus Biopharma Corporation (GLOBE NEWSWIRE) 22 小时前

   
电话会议和网络广播，讨论计划于美国东部时间 2022 年 6 月 27 日上午 8:00 在 EASL ILC 2022 上展示的新数据

WARMINSTER, Pa., June 07, 2022 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (Nasdaq: ABUS) 是一家临床阶段的生物制药公司，利用其广泛的病毒学专业知识开发针对特定病毒性疾病的新疗法，今天宣布了七篇摘要已被接受在 2022 年 6 月 22 日至 26 日在英国伦敦举行的欧洲肝脏研究协会 (EASL) 国际肝脏大会™ 2022 (ILC 2022) 上进行海报展示。这些海报将于 2022 年 6 月 25 日星期六上午 9:00 至下午 6:00（美国东部时间上午 4:00 至下午 1:00）在 BST 病毒性肝炎治疗会议上展示，并将包括更新的数据在可用的地方。

Arbutus 将于 2022 年 6 月 27 日星期一美国东部时间上午 8:00 召开电话会议，讨论在 EASL ILC 上展示的新数据。

接受的海报展示摘要如下：

摘要编号：3393 标题：在接受 AB-729 治疗 48 周后，在乙型肝炎表面抗原水平低的慢性乙型肝炎患者中停止核苷（酸）类似物治疗后观察到的病毒标志物持续抑制 演讲者：Man-Fung 教授Yuen 主要发现：参与试验 AB-729-001 的患者每 4、8 或 12 周接受 60mg 或 90mg AB-729，持续 48 周，在最后一剂 AB 后至少 24 周评估是否有资格停止 NA 治疗-729。摘要报告了同意停止所有治疗的 7 名患者中的 5 名的数据。所有 5 名患者都完成了 4 至 16 周的 NA 治疗随访，没有患者符合临床或病毒复发标准。数据显示，在 AB-729 诱导的 HBsAg 抑制至 <100 IU/mL 后停止 NA 治疗似乎具有良好的耐受性，并导致 HBV DNA 和 HBsAg 的持续抑制，而没有早期临床或病毒复发的证据。将显示更新的数据。

摘要编号：1509 标题：第三代衣壳抑制剂 AB-836 在健康受试者 (HS) 和慢性乙型肝炎 (CHB) 受试者中的安全性、耐受性、药代动力学 (PK) 和抗病毒活性演讲者： Edward J. Gane 教授主要发现： AB-836-001 是一项正在进行的临床试验，评估单剂量和多剂量 AB-836 在健康受试者和 CHB 患者中的安全性、PK 和抗病毒活性。数据表明，在健康受试者中单次和多次剂量的 AB-836 以及在 CHB 患者中每天一次最多 100mg 持续 28 天通常是安全且耐受性良好的。此外，在治疗的第 28 天观察到强大的抗病毒活性。将显示更新的数据。

摘要编号：3414 标题：停止 AB-729 治疗后维持长期抑制，并在 HBeAg+ 受试者中观察到类似的治疗反应 演讲者：Man-Fung Yuen 教授 主要发现：来自专门 HBeAg+ 队列的新数据和其他后续-报告了参与正在进行的 AB-729-001 临床试验的其他患者队列的最新数据。数据显示，AB-729 重复给药总体上仍然是安全的且耐受性良好，并且 HBsAg 的强劲和持续下降在不同治疗方案中具有可比性。此外，基线时的 HBeAg 状态和 DNA+ 似乎都不会影响反应。将显示更新的数据。

摘要编号：1530 标题：AB-729 短干扰 RNA 抑制持久 HBsAg 的药效学与肝脏内 RNA 诱导的沉默复合物 (RISC) 负载的药代动力学相关 演讲者：Emily P. Thi 博士 主要发现：数据表明 HBsAg 的药效学在 AAV-HBV 小鼠模型中由 AB-729 介导的减少与 AB-729 siRNA 加载到 RNA 诱导的沉默复合物 (RISC) 上的药代动力学一致，RISC 是负责 RNA 干扰活性的复合物。

摘要编号：1537 标题：通过 RNA 干扰治疗剂 AB-729 抑制乙型肝炎表面抗原与 HBV DNA+ 慢性乙型肝炎患者的细胞因子特征增加相关 演讲者：Sharie C. Ganchua 博士 主要发现：在 AB-729 给药后，a与 HBV DNA- 患者相比，在 HBV DNA+ 患者中观察到具有 T 细胞激活特征的更大范围的细胞因子和可溶性免疫生物标志物反应。这些结果表明，在 AB-729 给药后，HBV DNA+ 患者的免疫反应性更强。
摘要编号：1543 标题：在慢性乙型肝炎患者中，RNA 干扰治疗剂 AB-729 介导的乙型肝炎表面抗原减少与 T 细胞活化和耗尽的 CD8 T 细胞减少有关 演讲者：Emily P. Thi 博士 主要发现：每 4 或 8 周重复给药 60mg AB-729 伴随着 HBV 特异性 T 细胞活化和增殖，伴有轻度至中度 ALT 升高。治疗结束时和随访 8-12 周时耗尽的 CD8 T 细胞减少表明 AB-729 介导的 HBsAg 降低后 HBV 特异性 T 细胞免疫恢复（重新唤醒）可能是持久的。

摘要编号：1508 标题：能够重振慢性乙型肝炎患者 T 细胞反应的小分子口服 PD-L1 检查点抑制剂的临床前活性 演讲者：Emily P. Thi 博士 主要发现：数据显示 AB-101 和我们的其他新产品口服小分子 PD-L1 抑制剂化合物能够介导来自慢性乙型肝炎患者的 HBV 特异性 T 细胞的活化和恢复活力。此外，每天口服一次 AB-101 显示出与抗 PD-L1 抗体相当的体内抗肿瘤功效，并且具有进一步开发的有利临床前特征。

EASL ILC 2022 会议与会者可在会议网站 https://easl.eu/event/international-liver-congress-2022 上获取摘要。这些海报预计将在 2022 年 6 月 22 日会议开始时提供给与会者。这些海报随后将在 Arbutus 的网站 www.arbutusbio.com 上提供。

关于 AB-729

AB-729 是一种 RNA 干扰 (RNAi) 治疗剂，专门设计用于减少所有 HBV 病毒蛋白和抗原，包括乙型肝炎表面抗原，这被认为是重新唤醒患者免疫系统以对病毒作出反应的关键先决条件。 AB-729 使用 Arbutus 的新型共价结合 N-乙酰半乳糖胺 (GalNAc) 递送技术靶向肝细胞，该技术可实现皮下递送。迄今为止产生的临床数据表明，单剂量和多剂量的 AB-729 通常是安全且耐受性良好的，同时可显着降低乙型肝炎表面抗原和乙型肝炎 DNA。 AB-729目前正在进行多项2a期临床试验。

关于 AB-836

AB-836 是下一代口服乙型肝炎病毒 (HBV) 衣壳抑制剂，可与 HBV 核心蛋白相互作用，而后者又是病毒复制所必需的。目前针对 HBV 的标准护理疗法主要是核苷（酸）类似物，它们抑制病毒聚合酶并显着减少但不消除病毒复制。 AB-836 与核苷（酸）类似物的组合旨在通过阻止功能性病毒衣壳的组装来完全消除感染细胞中的病毒复制。此外，AB-836 已被证明可抑制共价闭合环状 DNA (cccDNA) 的补充，这是病毒自我复制所需的病毒遗传库。正在进行的 1a/1b 期临床试验的初步数据表明，AB-836 通常是安全的、耐受性良好的，并提供强大的抗病毒活性。

关于 PD-L1

PD-1/PD-L1 等免疫检查点在免疫耐受的诱导和维持以及 T 细胞活化中发挥重要作用。我们已经确定了一类小分子口服 PD-L1 抑制剂，我们相信它们将允许控制检查点阻断，实现口服给药，并减轻检查点抗体疗法常见的系统安全性问题。我们的主要口服 PD-L1 抑制剂候选药物 AB-101 目前正在进行 IND 研究。我们相信 AB-101 有可能与其他批准和研究的药物联合使用，以实现我们对 HBV 慢性感染患者实现功能性治愈的使命。我们还在探索我们内部 PD-L1 产品组合的肿瘤学应用。

StephenW

Arbutus to Present Seven Scientific Posters at EASL International Liver Congress™ 2022

    Arbutus Biopharma Corporation (GLOBE NEWSWIRE) 22 hrs ago

   
Conference Call & Webcast to discuss new data being presented at EASL ILC 2022 scheduled for June 27, 2022 at 8:00 am ET

WARMINSTER, Pa., June 07, 2022 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (Nasdaq: ABUS), a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to develop novel therapeutics that target specific viral diseases, today announced that seven abstracts have been accepted for poster presentations at the European Association for the Study of the Liver (EASL) International Liver Congress™ 2022 (ILC 2022) taking place June 22 - 26, 2022 in London, UK. The posters will be presented in the Viral hepatitis B/D therapy session on Saturday, June 25, 2022 between 9:00 am – 6:00 pm BST (4:00 am – 1:00 pm ET), and will include updated data where available.

Arbutus will hold a conference call at 8:00 am ET on Monday, June 27, 2022, to discuss the new data being presented at EASL ILC.

The accepted abstracts for poster presentations are as follows:

Abstract Number: 3393 Title: Continued suppression of viral markers observed following discontinuation of nucleos(t)ide analogue therapy in chronic hepatitis B subjects with low hepatitis B surface antigen levels after 48 weeks of treatment with AB-729 Presenter: Prof. Man-Fung Yuen Key Findings: Patients participating in trial AB-729-001 who received 60mg or 90mg of AB-729 every 4, 8 or 12 weeks for 48 weeks were assessed for eligibility to stop NA therapy at least 24 weeks after their last dose of AB-729. The abstract reports data on 5 of the 7 patients that consented to stop all therapy. All 5 patients completed between 4 and 16 weeks of follow-up off NA therapy, and no patients met clinical or viral relapse criteria. The data showed that discontinuation of NA therapy after AB-729-induced suppression of HBsAg to <100 IU/mL appears to be well-tolerated and leads to continued suppression of HBV DNA and HBsAg without evidence of early clinical or viral relapse. Updated data will be presented.

Abstract Number: 1509 Title: Safety, tolerability, pharmacokinetics (PK), and antiviral activity of the 3rd generation capsid inhibitor AB-836 in healthy subjects (HS) and subjects with chronic hepatitis B (CHB) Presenter: Prof. Edward J. Gane Key Findings: AB-836-001 is an ongoing clinical trial evaluating safety, PK and antiviral activity of single and multi-doses of AB-836 in healthy subjects and CHB patients. Data has shown that single and multiple doses of AB-836 in healthy subjects and up to 100mg once daily for 28 days in CHB patients has been generally safe and well-tolerated. In addition, robust antiviral activity was observed at Day 28 of treatment. Updated data will be presented.

Abstract Number: 3414 Title: Long-term suppression maintained after cessation of AB-729 treatment and comparable on-treatment response observed in HBeAg+ subjects Presenter: Prof. Man-Fung Yuen Key Findings: New data from a dedicated HBeAg+ cohort and additional follow-up data from other cohorts of patients participating in the on-going AB-729-001 clinical trial were reported. The data showed that AB-729 repeat dosing continues to be generally safe and well tolerated with robust and sustained declines in HBsAg that are comparable across treatment regimens. In addition, neither HBeAg status nor DNA+ at baseline appear to affect response. Updated data will be presented.

Abstract Number: 1530 Title: Pharmacodynamics of durable HBsAg suppression by AB-729 short interfering RNA correlates with pharmacokinetics of RNA-induced silencing complex (RISC) loading within liver Presenter: Dr. Emily P. Thi Key Findings: Data suggest that pharmacodynamics of HBsAg reduction mediated by AB-729 in an AAV-HBV mouse model coincides with the pharmacokinetics of AB-729 siRNA loading onto the RNA-induced silencing complex (RISC), the complex responsible for RNA interference activity.

Abstract Number: 1537 Title: Inhibition of hepatitis B surface antigen by RNA interference therapeutic AB-729 is associated with increased cytokine signatures in HBV DNA+ chronic hepatitis B patients Presenter: Dr. Sharie C. Ganchua Key Findings: Following AB-729 dosing, a greater breadth of cytokine and soluble immune biomarker responses with T cell activation signatures were observed in HBV DNA+ patients compared to HBV DNA- patients. These results suggest that HBV DNA+ patients are more immunologically responsive following AB-729 dosing.
Abstract Number: 1543 Title: Reduction of hepatitis B surface antigen mediated by RNA interference therapeutic AB-729 in chronic hepatitis B patients is associated with T cell activation and a decline in exhausted CD8 T cells Presenter: Dr. Emily P. Thi Key Findings: Repeat dosing of 60mg of AB-729 every 4 or 8 weeks is accompanied by HBV-specific T-cell activation and proliferation with mild to moderate ALT elevations. A decline in exhausted CD8 T-cells at the end of treatment and at 8-12 weeks of follow-up suggest that HBV-specific T-cell immune restoration (reawakening) following AB-729-mediated HBsAg reduction may be durable.

Abstract Number: 1508 Title: Preclinical activity of small-molecule oral PD-L1 checkpoint inhibitors capable of reinvigorating T cell responses from chronic hepatitis B patients Presenter: Dr. Emily P. Thi Key Findings: Data showed that AB-101 and our other novel oral small molecule PD-L1 inhibitor compounds are able to mediate activation and reinvigoration of HBV-specific T-cells from CHB patients. In addition, once daily oral administration of AB-101 displays in vivo anti-tumor efficacy comparable to anti-PD-L1 antibody and possesses a favorable preclinical profile for further development.

Abstracts are available to EASL ILC 2022 conference attendees on the conference website at https://easl.eu/event/international-liver-congress-2022. The posters are expected to be made available to conference attendees at the start of the meeting on June 22, 2022. The posters will be available subsequently on Arbutus’ website at www.arbutusbio.com.

About AB-729

AB-729 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. AB-729 targets hepatocytes using Arbutus’ novel covalently conjugated N -Acetylgalactosamine (GalNAc) delivery technology that enables subcutaneous delivery. Clinical data generated thus far has shown single- and multi-doses of AB-729 to be generally safe and well-tolerated while providing meaningful reductions in hepatitis B surface antigen and hepatitis B DNA. AB-729 is currently in multiple Phase 2a clinical trials.

About AB-836

AB-836 is a next generation oral hepatitis B virus (HBV) capsid inhibitor that interacts with HBV core protein, which in turn is required for viral replication. The current standard-of-care therapy for HBV is primarily nucleos(t)ide analogues that inhibit the viral polymerase and significantly reduce, but do not eliminate viral replication. AB-836 in combination with nucleos(t)ide analogues is designed to completely eliminate viral replication in infected cells by preventing the assembly of functional viral capsids. In addition, AB-836 has been shown to inhibit the replenishment of covalently closed circular DNA (cccDNA), the viral genetic reservoir which the virus needs to replicate itself. Preliminary data from an on-going Phase 1a/1b clinical trial has shown that AB-836 is generally safe and well-tolerated and provides robust antiviral activity.

About PD-L1

Immune checkpoints such as PD-1/PD-L1 play an important role in the induction and maintenance of immune tolerance and in T-cell activation. We have identified a class of small molecule oral PD-L1 inhibitors that we believe will allow for controlled checkpoint blockade, enable oral dosing, and mitigate systemic safety issues typically seen with checkpoint antibody therapies. Our lead oral PD-L1 inhibitor candidate, AB-101, is currently in IND-enabling studies. We believe AB-101 has the potential to be used in combination with other approved and investigational agents for our mission to achieve a functional cure for HBV chronically infected patients. We are also exploring oncology applications for our internal PD-L1 portfolio.