Development of CM-IAV1 for Treatment of High-risk Pandemic Influenzas

项目摘要 卫生与公众服务部（HHS）和生物医学高级研究与发展管理局（Biomedical Advanced Research and Development Authority） （巴尔达）表示，严重的大流行性流感爆发是目前对国家和 全球安全。疾病控制中心将H7N9列为最具威胁性的甲型流感病毒 因为它与H5 N1沿着的致死率分别为~40%和~ 60%。模型预测， H7N9大流行可能导致世界三分之一的人口感染，其中约40%的人死亡 感染，使其成为有史以来最致命的病毒（1918年流感的死亡率为2.5%）。有 目前还没有批准的治疗严重流感感染的药物，在H7N9的情况下， 感染者发展成严重感染并需要住院治疗。该项目旨在提供一些希望， 通过推进最有效的广谱人类抗体治疗， 目前可用的CM-IAV 1。CM-IAV 1是一种广泛中和的人单克隆抗体，与 第一组及第二组禽流感。CM-IAV 1已经被证明可以保护小鼠免受致命的（非致命的）感染。 实验室菌株）H7N9和H5 N1，在感染后72小时单次给药。利用这一 出色的临床前数据，我们已经组建了一个世界级的团队，专注于推进CM-IAV 1 进了诊所本申请中提出的实验将采用一种有前途的临床前药物， 再加上我们持续和平行的投资，创造了一个具有巨大潜力的临床资产， 疾病预防控制中心（CDC）优先考虑的最相关流行病中与流感感染相关的发病率和死亡率 菌株我们相信，在这个时候，由这个团队开发这种抗体代表了最好的希望， 提供有意义的救生保护，以应对全球甲型流感爆发的可怕可能性。 该项目的总体目标是开发一种新的广谱，拯救生命的治疗大流行病的药物。 从有希望的临床前候选药物到研究性新药（IND）-使 研究到IND备案。

Project Summary Health and human services (HHS) and the Biomedical Advanced Research and Development Authority (BARDA) have suggested a severe pandemic influenza outbreak is the greatest current threat to national and global security. The Center for Disease Control rates H7N9 as the most threatening of the Influenza A viruses as it, along with H5N1, have fatality rates of ~40% and ~60%, respectively. Models have predicted that an H7N9 pandemic could result in infection of one third of the world population and death of ~40% of those infected, making it the deadliest virus in recorded history (the 1918 flu had a fatality rate of ~2.5%). There is currently no approved therapeutic for severe influenza infection, and in the case of H7N9 ~98% of those infected develop severe infection and require hospitalization. This project seeks to provide some hope of protection in such an outbreak by advancing the most effective broad-spectrum human antibody therapeutic currently available, CM-IAV1. CM-IAV1 is a broadly neutralizing human monoclonal that is cross-reactive for group 1 and group 2 avian influenza. CM-IAV1 has already been shown to protect mice against lethal (non- laboratory strain) H7N9 and H5N1 when given in a single dose 72 hours post-infection. To leverage this outstanding preclinical data, we have assembled a world-class team that is focused on advancing CM-IAV1 into the clinic. The experiments presented in this application will take a promising preclinical agent and, together with our continued and parallel investments, create a clinical asset with enormous potential to reduce morbidity and mortality associated influenza infection from the most relevant CDC- prioritized pandemic strains. We believe that development of this antibody, at this time, and by this team represents the best hope of offering meaningful lifesaving protection against the terrifying possibility of a global Influenza A outbreak. The overarching goal of this project is to advance a novel broad-spectrum, lifesaving therapeutic for pandemic influenza A infection from promising preclinical candidate through investigational new drug (IND)-enabling studies to IND filing.