Preclinical development of an important, broad-spectrum antibody for pandemic influenza

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疫情是当前对国家和全球安全的最大威胁。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，约40%的感染者死亡，使其成为有记录以来最致命的病毒(1918年的流感死亡率约为2.5%)。目前还没有批准的治疗严重流感感染的方法，在H7N9病例中，98%的感染者发生严重感染，需要住院治疗。该项目寻求通过发展目前可用的最有效的广谱人类抗体疗法CM-IAV1，在这种暴发中提供一些保护的希望。CM-IAV1有很大的前景，因为已经证明，当感染72小时后单次给药时，它可以保护小鼠免受致命的(非实验室毒株)H7N9和H5N1的感染。我们已经组建了一支拥有出色临床前数据的世界级团队，现在正专注于推动CM-IAV1进入临床。本申请中介绍的实验将采用一种前景看好的实验室产品，并与我们持续和平行的投资一起，创造出具有巨大潜力的临床资产，以减少与最相关的疾控中心优先大流行毒株的流感感染相关的发病率和死亡率。我们相信，目前和这个团队开发这种抗体代表着最大的希望，即提供有意义的挽救生命的保护，以抵御全球甲型流感爆发的可怕可能性。该项目的总体目标是推进一种新的广谱、拯救生命的甲型流感大流行感染治疗方法，从有前途的临床前候选药物到使能研究新药(IND)，再到IND申请。

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 has great promise since it 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. We have assembled a world-class team with outstanding preclinical data and are now focused on advancing CM-IAV1 into the clinic. The experiments presented in this application will take a promising laboratory product 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.