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.

卫生与公众服务部（HHS）和生物医学高级研究与发展管理局（巴尔达）表示，严重的大流行性流感爆发是目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，因为它与H5 N1一起沿着的致死率分别为~40%和~ 60%。模型预测，H7N9大流行可能导致世界人口的三分之一感染，约40%的感染者死亡，使其成为有史以来最致命的病毒（1918年流感的死亡率约为2.5%）。目前没有批准的治疗严重流感感染的方法，在H7N9的情况下，约98%的感染者发展为严重感染并需要住院治疗。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CM-IAV 1，为这种疫情提供一些保护的希望。CM-IAV 1有很大的希望，因为它已经被证明可以保护小鼠免受致命的（非实验室菌株）H7N9和H5 N1感染后72小时单剂量给药。我们已经组建了一支拥有出色临床前数据的世界级团队，现在正专注于将CM-IAV 1推进临床。本申请中提出的实验将采用一种有前景的实验室产品，并与我们的持续和平行投资一起，创造一种具有巨大潜力的临床资产，以减少与最相关的CDC优先流行毒株相关的流感感染的发病率和死亡率。我们相信，在这个时候，由这个团队开发这种抗体代表了提供有意义的救生保护以应对全球甲型流感爆发的可怕可能性的最佳希望。该项目的总体目标是推进一种新的广谱，拯救生命的治疗大流行性流感A感染从有前途的临床前候选药物，通过研究性新药（IND）使能研究，以IND申请。