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Development of highly potent human monoclonal for RSV immuno-prophylaxis

开发用于 RSV 免疫预防的高效人单克隆抗体

基本信息

批准号：
10080251
负责人：
Larry Zeitlin
金额：
$ 99.88万
依托单位：
MAPP BIOPHARMACEUTICAL, INC.
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-01-15 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10080251
关键词：
2 year old Adult Age-Years Antibodies Asthma Biological Products Bioreactors Caring Cell Line Child Childhood Chinese Hamster Ovary Cell Chronic Clinical Complex Congestive Heart Failure Cost Effectiveness Analysis Cotton Rats Country Data Developing Countries Development Disease Dose Drug Kinetics Elderly Formulation Future Generations Goals Half-Life Health Benefit Hospitalization Hospitals Human Immune response In Vitro Industry Standard Infant Influenza A virus Lead Lebanon Life Lower respiratory tract structure Lung diseases Medical Medicine Monoclonal Antibodies Nursing Homes Palivizumab Pharmaceutical Preparations Phase Population Price Production Public Health Rehabilitation therapy Research Respiratory Syncytial Virus Vaccines Respiratory Tract Diseases Respiratory syncytial virus Respiratory syncytial virus RSV F glycoprotein Savings Seasons Serum Structure Technology Testing Texas Tissues Toxicology Universities Vaccination Wheezing austin base burden of illness cell bank clinical development college cost cross reactivity high risk high risk infant human monoclonal antibodies humanized mouse immunoprophylaxis improved in vivo in vivo evaluation lead candidate murine antibody neonate prevent prophylactic response success

项目摘要

PROJECT SUMMARY Respiratory syncytial virus (RSV) is a leading cause of infant hospitalizations in the U.S., and the disease burden among the elderly is similar to non-pandemic influenza A. Traditional strategies have failed to generate an effective RSV vaccine, and in some instances vaccination resulted in enhanced disease, underscoring the complexity of the human immune response to RSV. Although a prophylactic antibody is available (palivizumab, a humanized mouse mAb marketed by MedImmune as Synagis®), its high cost and modest efficacy have restricted its use to high-risk infants. Moreover, due to this high cost, palivizumab is inaccessible to children in developing nations and is unavailable in 4 of the 5 most populous countries – more than half the world’s population does not have access to this type of treatment. The public health benefit and the worldwide accessibility would undoubtedly be improved by lowering the cost of RSV immunoprophylaxis. In this Phase 2 proposal, the University of Texas at Austin, Adimab (Lebanon, NH), Einstein College of Medicine (The Bronx, NY) and Mapp Biopharmaceutical, Inc. (San Diego, CA), teamed to develop a fully human, highly potent mAb that can be administered in a single dose per RSV season. With a more potent mAb (i.e. lower dose) that can be dosed less frequently (due to extended serum half-life), the team’s objective is to dramatically lower the price and increase the availability of RSV immunoprophylaxis. In addition, competition in the marketplace may also help to reduce costs and increase accessibility globally, especially since palivizumab currently has a monopoly on the RSV market. Our Phase 1 effort identified 3 lead candidates (from a panel of 445 mAbs), all of which are dramatically more potent in vitro and in vivo than palivizumab. Further, these mAbs have similar neutralization activity to AstraZeneca’s second generation RSV mAb MEDI8897 (currently in late stage clinical development) against the 5 RSV strains tested to date. After the success of these Phase 1 efforts, we propose the following Specific Aims for Phase 2: 1) Select a lead candidate based on breadth and potency of neutralization activity against a panel of clinical isolates; 2) Generate a CHO cell line appropriate for GMP manufacture; 3) Manufacture for IND-enabling studies; 4) Conduct IND-enabling studies.

项目总结