Core B - MappBiopharmaceutical, Inc.

核心 B - MappBiopharmaceutical, Inc.

• 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
• 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

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 在过去的40年中，大多数新出现或确定的传染性的主要病因 人类的疾病一直是病毒，大多数是由RNA病毒引起的人畜共患病。这 病毒病毒的出现或重新出现是对公共卫生的持续威胁。最近两个 新兴的人畜共患病毒病毒病原体来自Paramyxovirus家族中的Henipavirus属： Hendra病毒（HEV）和Nipah病毒（NIV）。 HEV和NIV会引起系统性且经常致命的呼吸道 至少包括人类在内的至少11种哺乳动物的神经疾病，死亡率范围为 从40-100％开始。这些病毒没有许可的疫苗或治疗剂，突出了一个重要的 未满足的公共卫生需求。 由于它们的高效力和特异性以及其出色的临床安全和功效记录， 单克隆抗体（mAB）是抗病毒治疗剂的吸引人的平台。超过50 mabs 获得食品和药物管理局（FDA）和欧洲药品局（EMA）的批准，许多 众所周知，MAB药物开发的制造，配方和调节性挑战。这 抗体的效用是自然发生和被动应用的，在预防和后 传染病的暴露治疗已有一个多世纪。 目前，三个具有抗墨西哥病毒活性的高度有效的铅候选治疗单元格， 允许开发活动立即开始进行CORTH工作。核心B将关注 优化这些候选人，向下选择铅产品格式（单个mab vs.鸡尾酒），然后 将产品推向临床评估和开发。为了实现这些目标，我们建议 以下特定目的：1。优化3个铅mab的个体体内效力； 2。评估 优化组合中的mAb以识别铅产品候选者； 3。执行调查新药 （IND） - 实现工作。 5年的努力将以举行预先会议的最后一个里程碑达到最终形象 与FDA。