Core B - MappBiopharmaceutical, Inc.

摘要 在过去的40年里，大多数新出现或已确定的传染性疾病的主要病原体 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。这个 致病病毒的出现或重新出现是对公共健康的持续威胁。最近的两个 新出现的人畜共患核糖核酸病毒病原体来自副粘病毒家族中的海尼帕病毒属： 亨德拉病毒(HEV)和尼帕病毒(NIV)。戊型肝炎病毒和新城疫病毒可以引起全身性的，通常是致命的呼吸道疾病。 和/或包括人类在内的至少11种哺乳动物的神经系统疾病，死亡率不等 从40%到100%。目前还没有针对这些病毒的疫苗或疗法许可，这突显了一个重要的 未得到满足的公共卫生需求。 由于它们的高效性和特异性，以及良好的临床安全性和有效性记录， 单抗是抗病毒治疗的一个有吸引力的平台。有超过50个单抗 由食品和药物管理局(FDA)和欧洲药品管理局(EMA)批准，许多 对单抗药物开发的制造、配方和监管方面的挑战已有充分的了解。这个 抗体的效用，无论是自然产生的还是被动应用的，在预防和预防后都是显而易见的。 暴露治疗传染病已有一个多世纪的历史。 三种具有抗流感病毒活性的高度有效的候选治疗性单抗目前正在研制中， 使发展活动能够在《消除对妇女一切形式歧视公约》工作开始时立即开始。核心B将专注于 优化这些候选者，向下选择主要产品形式(单一单抗与鸡尾酒)，以及 将该产品推向临床评估和开发。为达致这些目标，我们建议 具体目标如下：1.优化3个前导单抗的体内效价；2.评价 优化组合中的单抗以确定主要候选产品；3.进行研究新药 (IND)-使工作成为可能。5年的努力将以举行IND前会议的最后里程碑而告终 与食品药品管理局合作。

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.