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

针对大流行性流感的重要广谱抗体的临床前开发

• 批准号: 10778847
• 负责人: Colleen Doyle Cooper
• 金额: $ 99.96万
• 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 2025-05-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10778847
• 关键词: Amantadine; Animal Model; Antibodies; Authorization documentation; Avian Influenza; B-Lymphocytes; COVID-19 pandemic; Cell Line; Centers for Disease Control and Prevention (U.S.); Cessation of life; China; Clinic; Clinical; Clinical Paths; Data; Development; Disease Outbreaks; Domestic Fowls; Dose; Drug Kinetics; Economics; Event; Fatality rate; Ferrets; Frequencies; Goals; Health; Health Priorities; Hospitalization; Hour; Human; Infection; Influenza; Influenza A Virus, H5N1 Subtype; Influenza A Virus, H7N9 Subtype; Influenza A virus; International; Intervention; Investigational Drugs; Investments; Laboratories; Letters; Life; Medical; Modeling; Modernization; Morbidity - disease rate; Mus; Mutation; Neuraminidase; Oryctolagus cuniculus; Oseltamivir; Pathogenicity; Persons; Pharmaceutical Preparations; Phase; Population; Readiness; Recording of previous events; Rimantadine; Security; Services; Suspension Culture; Symptoms; Technology; Temperature; Therapeutic; Therapeutic antibodies; Time; Toxic effect; Toxicology; Travel; Virus; Work; World Health Organization; authority; cell bank; cost; economic impact; experimental study; flu; foot; global health; high throughput screening; human monoclonal antibodies; influenza infection; influenza outbreak; inhibitor; innovation; manufacture; mortality; novel; novel therapeutics; pandemic disease; pandemic influenza; pandemic potential; pandemic preparedness; pre-clinical; preclinical development; preclinical study; programs; prophylactic; public health relevance; research and development; respiratory virus; social; therapeutic candidate; therapeutically effective; transmission process; virtual; wild bird

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.

卫生与公共服务（HHS）和生物医学高级研发局（Barda）表明，严重的大流行性流感疫情是目前对国家和全球安全的最大威胁。疾病控制中心H7N9是流感病毒最威胁性的，其与H5N1的死亡率分别为约40％和约60％。模型已经预测，H7N9大流行可能导致世界三分之一的人口感染，约40％被感染的人死亡，这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％）。目前尚无针对严重流感感染的批准治疗，就H7N9〜98％的感染而言，受感染的患者会出现严重的感染并需要住院。该项目旨在通过推进目前可用的最有效的广谱人类抗体治疗方法，即CM-IAV1，以提供这种爆发的希望。 CM-IAV1具有巨大的希望，因为它已经被证明可以保护小鼠免受致命（非实验性菌株）H7N9和H5N1的侵害，而在感染后单剂量72小时时给予。我们已经组建了一个拥有出色的临床前数据的世界一流团队，现在专注于将CM-IAV1推进到诊所。本应用程序中提出的实验将采用有希望的实验室产品，并与我们持续和平行的投资一起创造了一种临床资产，具有巨大潜力，从而从最相关的CDC优先级别的大流行病中降低发病率和死亡率相关的流感感染。我们认为，目前，这种抗体的开发是该团队的最大希望，即提供有意义的救生保护，以防止全球流感的可怕可能性成为爆发。该项目的总体目标是推进一种新颖的广谱，为大流行性流感的救生治疗，从有希望的临床前候选者通过研究新药（IND）增强了IND提交的研究。