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局 (BARDA)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 因为它和H5N1病毒的死亡率分别为~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，使其成为有记录以来最致命的病毒(1918年流感的死亡率约为2.5%)。的确有 目前还没有批准用于严重流感感染的治疗方法，在H7N9病例中， 感染后会发展成严重感染，需要住院治疗。这个项目试图提供一些希望 通过开发最有效的广谱人类抗体疗法来预防此类疫情的爆发 目前可用的CM-IAV1。CM-IAV1是一种广泛中和的人类单抗，与 第1组和第2组禽流感。CM-IAV1已经被证明可以保护小鼠免受致死性(非致死性) 实验室菌株)H7N9和H5N1在感染后72小时单剂给药。要充分利用这一点 出色的临床前数据，我们组建了一支世界级的团队，专注于推进CM-IAV1 送进诊所。本申请中提出的实验将采用一种很有前途的临床前药物， 再加上我们持续和平行的投资，创造了一项具有巨大潜力的临床资产 最相关的疾控中心优先大流行的相关流感感染的发病率和死亡率 菌株。我们相信，开发这种抗体，在这个时候，并由这个团队代表着最大的希望 针对全球甲型流感爆发的可怕可能性，提供有意义的救生保护。 这个项目的首要目标是开发一种新的广谱的、拯救生命的大流行疗法。 通过研究新药(IND)使有希望的临床前候选人感染甲型流感 从研究到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.