Core B - MappBiopharmaceutical, Inc.

摘要 在过去的40年里，大多数新出现或确定的传染性疾病的主要病原体 人类的疾病都是病毒引起的，大多数是由RNA病毒引起的人畜共患病。的 致病性病毒的出现或重新出现是对公共卫生的持续威胁。两名最近 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可引起全身性且通常致命的呼吸道感染。 包括人类在内的至少11种哺乳动物的死亡率 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，这突出了一个重要的问题。 未满足的公共卫生需求。 由于其高效力和特异性，以及其出色的临床安全性和有效性记录， 单克隆抗体（mAbs）是抗病毒治疗的一个有吸引力的平台。超过50个mAb 经美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）批准， mAb药物开发的制造、配制和监管挑战是众所周知的。的 抗体的效用，无论是天然存在的还是被动应用的，对于预防和治疗后， 暴露治疗传染病已经有超过世纪的历史了。 目前已有三种具有抗亨尼帕病毒活性的高效先导候选治疗mAb， 允许开发活动在CETR工作启动时立即开始。核心B将侧重于 优化这些候选物，向下选择主导产品形式（单一mAb与混合物），以及 推进产品的临床评价和开发。为了实现这些目标，我们建议 具体目标：1。优化3种先导mAb的个体体内效力; 2.评价 优化的mAb组合以鉴定先导产物候选物; 3.进行新药试验 （IND）-使能工作。5年的努力将以进行IND前会议的最后一个里程碑而告终 和食品药物管理局

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.