Vir Biotechnology启动VIR-3434的慢性乙型肝炎病毒感染的1期临床试

StephenW

Vir Biotechnology Initiates Phase 1 Clinical Trial of VIR-3434 for Chronic Hepatitis B Virus Infection
Novel investigational HBV-neutralizing monoclonal antibody with therapeutic vaccine-like properties
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May 27, 2020 08:00 ET | Source: Vir Biotechnology, Inc.

SAN FRANCISCO, May 27, 2020 (GLOBE NEWSWIRE) -- Vir Biotechnology, Inc. (Nasdaq: VIR) today announced the initiation of a Phase 1 clinical trial of VIR-3434, an investigational monoclonal antibody that neutralizes hepatitis B virus (HBV) and has been engineered to potentially also act as a therapeutic vaccine. The commencement of first-in-human dosing marks the start of Vir’s second clinical program aimed at a functional cure for HBV.

“We firmly believe that a functional cure will require a cocktail of drugs that has both antiviral and immune stimulatory activity. We have selected our drug candidates with this in mind,” said Phillip Pang, M.D., Ph.D., Chief Medical Officer of Vir. “In the case of VIR-3434, it is remarkable to have a drug candidate that by itself has the potential to be both an antiviral and a therapeutic vaccine. When combined with our siRNA candidate, VIR-2218, we believe that this cocktail could achieve very high rates of functional cure.”

VIR-3434 is an HBV-neutralizing monoclonal antibody designed to block entry of all 10 genotypes of HBV into hepatocytes, and also to reduce the level of virions and subviral particles in the blood. It has also been Fc engineered to include the XX2 “vaccinal mutation,” for which Vir has licensed exclusive rights for all infectious diseases. VIR-2218, an investigational small interfering ribonucleic acid (siRNA) that mediates RNA interference, is currently being investigated in a Phase 2 trial for the treatment of chronic HBV infection.

“The vaccinal mutations incorporated into the Fc domain of VIR-3434 act in concert to potentially trigger the correct FcGamma receptors on dendritic cells, resulting in their maturation,” said Jeffrey V. Ravetch, M.D., Ph.D., Theresa and Eugene M. Lang Professor and Head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology at The Rockefeller University, who discovered these mutations and their role. “If they work in humans the way they do in mice, after this antibody has captured an HBV virion or subviral particle, we believe the antibody will deliver this payload to immature dendritic cells, stimulating them to mature and subsequently result in HBV specific T cells.”

The Phase 1 clinical trial of VIR-3434 is a randomized, placebo-controlled trial designed to assess the safety, tolerability, pharmacokinetics, antiviral and immunomodulatory activity of VIR-3434 in healthy volunteers and patients with chronic HBV infection. The company plans to enroll patients at multiple trial sites in several countries in the Asia Pacific and European regions. The trial is designed to progress from healthy volunteers to chronic HBV patients in a staggered, parallel fashion with the goal of rapidly generating early proof-of-concept data in patients. Data are expected to be available in 2021.

“The initiation of this clinical trial is welcome news as we pursue new agents that can, either individually or in combination, stop viral replication and reignite the body’s immune response to restore control,” said Edward J. Gane, M.D., Professor of Medicine at the University of Auckland, New Zealand and Chief Hepatologist, Transplant Physician and Deputy Director of the New Zealand Liver Transplant Unit at Auckland City Hospital and a lead investigator of the trial.

StephenW

Vir Biotechnology启动VIR-3434的慢性乙型肝炎病毒感染的1期临床试验
具有治疗性疫苗样特性的新型研究性HBV中和单克隆抗体
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东部时间2020年5月27日08:00 |资料来源：Vir Biotechnology，Inc.。

旧金山，2020年5月27日（全球新闻）-Vir Biotechnology，Inc.（纳斯达克股票代码：VIR）今天宣布启动VIR-3434的1期临床试验，该试验性单克隆抗体可中和乙型肝炎病毒（HBV）并已被设计为还可以用作治疗性疫苗。首次人类剂量给药的开始标志着Vir的第二项临床计划的开始，该计划旨在有效治愈HBV。

“我们坚信，功能性治愈将需要一系列具有抗病毒和免疫刺激活性的药物。我们考虑到这一点选择了候选药物，” Vir首席医学官Phillip Pang博士说。 “就VIR-3434而言，拥有候选药物本身具有潜在的抗病毒和治疗疫苗作用是非常了不起的。当与我们的候选siRNA VIR-2218结合使用时，我们相信这种混合物可以实现很高的功能治愈率。”

VIR-3434是中和HBV的单克隆抗体，旨在阻止HBV的所有10个基因型进入肝细胞，并降低血液中病毒体和亚病毒颗粒的水平。它也经过Fc工程改造，以包含XX2“疫苗突变”，Vir为此获得了所有传染病的专有权。 VIR-2218是一种介导RNA干扰的研究性小干扰核糖核酸（siRNA），目前正在治疗慢性HBV的2期试验中进行研究。

“掺入VIR-3434 Fc结构域的疫苗突变可协同作用，潜在触发树突状细胞上正确的FcGamma受体，从而使其成熟，”医学博士Theresa和Eugene M的Jeffrey V. Ravetch说道。 Lang洛克菲勒大学教授兼分子遗传学和免疫学伦纳德·瓦格纳实验室负责人，他发现了这些突变及其作用。 “如果它们像在小鼠中一样在人类中起作用，则在该抗体捕获了HBV病毒粒子或亚病毒颗粒后，我们相信该抗体会将有效载荷传递给未成熟的树突状细胞，刺激它们成熟并随后产生HBV特异性T细胞。”

VIR-3434的1期临床试验是一项随机，安慰剂对照的试验，旨在评估VIR-3434在健康志愿者和慢性HBV感染患者中的安全性，耐受性，药代动力学，抗病毒和免疫调节活性。该公司计划在亚太地区和欧洲地区的多个国家/地区的多个试验地点招募患者。该试验旨在以交错，平行的方式从健康志愿者向慢性HBV患者发展，目的是快速生成患者的早期概念验证数据。预计将于2021年获得数据。

“这项临床试验的启动是令人欢迎的消息，因为我们寻求可以单独或组合使用的新型药物，这些药物可以停止病毒复制并重新激活人体的免疫反应以恢复控制，”医学博士Edward J. Gane说道。新西兰奥克兰大学兼首席肝病学家，移植医师，奥克兰市医院新西兰肝脏移植科副主任，以及该试验的首席研究员。