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

开发用于治疗高危大流行性流感的 CM-IAV1

• 批准号: 10480298
• 负责人: Colleen Doyle Cooper
• 金额: $ 30万
• 依托单位: CELDARA MEDICAL, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-25 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10480298
• 关键词: Academia; Advanced Development; Aerosols; Antibodies; Avian Influenza; Avian Influenza A Virus; B-Lymphocytes; Cell Line; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chinese Hamster Ovary Cell; Clinic; Clinical; Clinical Paths; Data; Development; Disease Outbreaks; Domestic Fowls; Dose; Drug Kinetics; Fatality rate; Future; Goals; Government; Health; Hemagglutinin; Hospitalization; Hour; Human; Industry; Infection; Influenza; Influenza A Virus, H5N1 Subtype; Influenza A Virus, H7N9 Subtype; Influenza A virus; Investigational Drugs; Investments; Lead; Letters; Life; Medical; Modeling; Monoclonal Antibodies; Morbidity - disease rate; Mus; Mutation; Oryctolagus cuniculus; Persons; Pharmaceutical Preparations; Phase; Population; Property; Readiness; Recording of previous events; Reporting; Security; Services; Societies; Sudan Ebola virus; Technology; Temperature; Therapeutic; Therapeutic antibodies; Time; Tissues; Toxic effect; Toxicology; Viral; Virus; Work; anti-influenza; authority; cell bank; coronavirus disease; cross reactivity; effective therapy; experimental study; flu; high risk; high throughput screening; human monoclonal antibodies; human mortality; in vivo; influenza infection; influenza outbreak; innovation; mortality; novel; pandemic disease; pandemic influenza; pandemic preparedness; pre-clinical; preclinical development; predictive modeling; programs; prophylactic; research and development; respiratory virus; transmission process; virtual; wild bird

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.

项目概要 卫生与公众服务部 (HHS) 以及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当前对国家和地区的最大威胁。 全球安全。疾病控制中心将 H7N9 列为最具威胁的甲型流感病毒 因为它与 H5N1 的死亡率分别约为 40% 和 60%。模型预测， H7N9 大流行可能导致世界三分之一人口感染，其中约 40% 死亡 感染，使其成为历史上最致命的病毒（1918 年流感的死亡率约为 2.5%）。有 目前尚无批准治疗严重流感感染的治疗方法，而就 H7N9 而言，约 98% 感染者发展为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来在此类疫情中提供保护 目前可用，CM-IAV1。 CM-IAV1 是一种广泛中和的人单克隆抗体，具有交叉反应性 第 1 组和第 2 组禽流感。 CM-IAV1 已被证明可以保护小鼠免受致命（非 实验室菌株）H7N9 和 H5N1（感染后 72 小时内单剂量给药）。为了利用这一点 出色的临床前数据，我们组建了一支世界一流的团队，专注于推进 CM-IAV1 进入诊所。本申请中提出的实验将采用一种有前途的临床前药物，并且， 与我们持续和平行的投资一起，创建具有巨大潜力的临床资产，以减少 与疾病预防控制中心最相关的大流行病相关的流感感染的发病率和死亡率 菌株。我们相信，此时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，防止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型广谱救生疗法来治疗大流行病 通过研究性新药 (IND) 启用，有希望的临床前候选药物感染甲型流感 研究到 IND 备案。