Core B - MappBiopharmaceutical, Inc.

核心 B - MappBiopharmaceutical, Inc.

基本信息

批准号：
10362728
负责人：
Larry Zeitlin
金额：
$ 80.23万
依托单位：
HENRY M. JACKSON FDN FOR THE ADV MIL/MED
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-20 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10362728
关键词：
Antibodies Antiviral Agents Biological Assay Cell Line Cell physiology Clinical Communicable Diseases Data Development Dose Drug Kinetics Ebola Effectiveness Etiology European Family Fatality rate Formulation Generations Goals Hamsters Hand Hendra Virus Henipavirus Human Individual Infection Investigational Drugs Lead Marburgvirus Medicine Modeling Monoclonal Antibodies Nipah Virus Paramyxovirus Point Mutation Prevention Public Health RNA RNA Viruses Reagent Research Project Grants Research Support Respiratory Disease Safety Specificity Testing Therapeutic Therapeutic Monoclonal Antibodies Toxicology United States Food and Drug Administration Vaccines Variant Virulent Virus Work Zoonoses clinical development drug development efficacy study glycosylation in vivo in vivo evaluation infectious disease treatment lead candidate meetings nervous system disorder nonhuman primate pathogenic virus research clinical testing response

项目摘要

Abstract Over the past 40 years, the majority of the major etiological agents of newly emerged or identified infectious diseases in humans have been viruses, and most have been zoonoses caused by RNA viruses. The emergence or reemergence of pathogenic viruses are continuous threats to public health. Two recently emergent, zoonotic RNA viral pathogens come from the henipavirus genus within the paramyxovirus family: Hendra virus (HeV) and Nipah virus (NiV). HeV and NiV can cause a systemic and often fatal respiratory and/or neurological disease in at least 11 mammalian species including humans, with fatality rates ranging from 40-100%. There are no vaccines or therapeutics licensed for these viruses, highlighting an important unmet public health need. Due to their high potency and specificity, as well as their excellent clinical safety and efficacy record, monoclonal antibodies (mAbs) are an appealing platform for anti-viral therapeutics. With over 50 mAbs approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA), many of the manufacturing, formulation, and regulatory challenges of mAb drug development are well understood. The utility of antibodies, both naturally occurring and passively applied, has been evident for prevention and post- exposure treatment of infectious diseases for over a century. Three highly potent lead candidate therapeutic mAbs with anti-henipaviral activity are currently in hand, allowing development activities to begin immediately at the initiation of the CETR effort. Core B will focus on optimizing these candidates, down-selecting to the lead product format (a single mAb vs. a cocktail), and advancing the product towards clinical evaluation and development. To achieve these goals, we propose the following Specific Aims: 1. Optimize the individual in vivo potency of the 3 lead mAbs; 2. Evaluate the optimized mAbs in combinations to identify a lead product candidate; 3. Perform Investigational New Drug (IND)-enabling work. The 5 year effort will culminate with a final milestone of conducting a pre-IND meeting with the FDA.

抽象的过去 40 年来，新出现或确定的传染病的大多数主要病原体人类疾病都是由病毒引起的，而且大多数是由RNA病毒引起的人畜共患疾病。这致病病毒的出现或再次出现对公众健康构成持续威胁。最近两个新出现的人畜共患 RNA 病毒病原体来自副粘病毒科的亨尼帕病毒属：亨德拉病毒（HeV）和尼帕病毒（NiV）。 HeV 和 NiV 可导致全身性且往往致命的呼吸道疾病和/或包括人类在内的至少 11 种哺乳动物物种的神经系统疾病，死亡率范围从 40-100%。目前还没有针对这些病毒的疫苗或治疗药物获得许可，这凸显了一个重要的问题未满足的公共卫生需求。由于其高效力和特异性，以及出色的临床安全性和有效性记录，单克隆抗体（mAb）是抗病毒治疗的一个有吸引力的平台。拥有超过 50 个单克隆抗体经美国食品药品监督管理局 (FDA) 和欧洲药品管理局 (EMA) 批准，许多单克隆抗体药物开发的制造、配方和监管挑战众所周知。这抗体的效用，无论是自然产生的还是被动应用的，对于预防和治疗后的作用都是显而易见的。暴露治疗传染病已有一个多世纪的历史。目前拥有三种具有抗亨帕病毒活性的高效主要候选治疗性单克隆抗体，允许开发活动在 CETR 工作启动时立即开始。核心B将重点关注优化这些候选药物，向下选择主导产品形式（单一 mAb 与鸡尾酒），以及推动产品走向临床评估和开发。为了实现这些目标，我们建议具体目标如下： 1. 优化 3 个先导单克隆抗体的个体体内效力； 2. 评估优化单克隆抗体组合以确定主导候选产品； 3. 进行新药研究（IND）支持工作。 5年的努力将以召开 IND 前会议作为最后的里程碑与 FDA 合作。