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.

项目摘要 健康与公共服务（HHS）和生物医学高级研发局 （Barda）表明，严重的大流行性流感爆发是目前对国家和国家的最大威胁 全球安全。疾病控制中心H7N9是流感病毒的最威胁 因此，与H5N1一起，死亡率分别为〜40％和约60％。模型预测了 H7N9大流行可能导致世界三分之一的人口感染，其中约40％ 被感染，使其成为记录史上最致命的病毒（1918年流感的死亡率约为2.5％）。有 目前尚未批准严重流感感染的治疗方法，在H7N9〜98％的情况下 感染会发展出严重的感染并需要住院。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，在这种爆发中的保护 目前可用的CM-IAV1。 cm-iav1是一种广泛中和的人类单克隆，具有交叉反应的 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性（非 - 实验室应变）H7N9和H5N1在感染后72小时以单剂量给药时。利用这一点 出色的临床前数据，我们组建了一个世界一流的团队，该团队专注于推进CM-IAV1 进入诊所。本应用程序中提出的实验将采用有希望的临床前代理，并且 加上我们持续和平行的投资，创建具有巨大潜力减少的临床资产 来自最相关的CDC优先大流行病的发病率和死亡率相关的流感感染 菌株。我们认为，目前，该抗体的开发是最大的希望 提供有意义的救生保护，以防止全球流感的恐怖可能性爆发。 该项目的总体目标是推动新颖的广谱，救生的大流行治疗 流感的感染来自有希望的临床前候选者，通过研究新药（IND）增强 研究提交的研究。