Development of a dry powder inhalation product against Respiratory Syncytial Virus based on an endogenous anionic pulmonary surfactant lipid

基于内源性阴离子肺表面活性剂脂质的抗呼吸道合胞病毒干粉吸入产品的开发

• 批准号: 10697027
• 负责人: Ajay Gupta
• 金额: $ 29.01万
• 依托单位: CELESTIAL THERAPEUTICS INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-11 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10697027
• 关键词: Acute; Admission activity; Adult; Animals; Anti-Inflammatory Agents; Binding; Biomedical Engineering; Bronchoalveolar Lavage Fluid; California; Cardiotoxicity; Cells; Cessation of life; Chemistry; Child; Childhood; Chimeric Proteins; Clinical; Collaborations; Colorado; Communicable Diseases; Cotton Rats; Data; Development; Disease; Dose; Drug Industry; Drug Kinetics; Dryness; Elderly; Epithelial Receptor Cell; Epitopes; Failure; Formulation; Foundations; Generations; Genetic; Health; Hospitalization; Hospitals; Human; Immunology; In Vitro; Incidence; Infection; Inflammation; Inhalation; Inhalation Drug Administration; Injections; Intervention; Legal patent; Licensing; Lipids; Lower Respiratory Tract Infection; Marketing; Maximum Tolerated Dose; Metabolism; Methods; Modality; Monoclonal Antibodies; Outcome; Palivizumab; Particle Size; Persons; Pharmaceutical Preparations; Pharmacology and Toxicology; Phase; Phosphatidylglycerols; Phospholipids; Powder dose form; Preventive vaccine; Process; Prophylactic treatment; Pulmonary Surfactants; Qualifying; Quality Control; Rattus; Respiratory Syncytial Virus Infections; Respiratory syncytial virus; Safety; Sampling; Small Business Innovation Research Grant; Structure of parenchyma of lung; TLR2 gene; Testing; Therapeutic; Tissues; Toll-like receptors; Toxic effect; Toxicology; United States; Universities; Viral; Viral load measurement; Virus; Virus Replication; aged; antagonist; antimicrobial; clinical practice; curative treatments; drug distribution; experience; follower of religion Jewish; good laboratory practice; high risk; humanized monoclonal antibodies; improved; in vivo; inflammatory marker; large scale production; lung lesion; manufacture; mortality; nasal swab; novel; phase 1 study; pre-Investigational New Drug meeting; preclinical safety; preclinical study; prevent; prophylactic; safety study; surfactant; therapeutic vaccine; vaccine access; vaccine trial; validation studies; virology

PROJECT SUMMARY Human respiratory syncytial virus (hRSV) infection has an estimated global incidence of 33 million cases in children younger than 5 years, with up to 234,000 dying of the disease. Although often characterized as a pediatric disease, RSV infection in adults aged 65 years or older represent a substantial health burden. Recent failures of late-phase trials for vaccines and therapies based on monoclonal antibodies (mAb) prompt the development of novel interventions for RSV. To fill this urgent clinical need, Celestial Therapeutics is developing an endogenous anionic pulmonary surfactant lipid, palmitoyl-oleoyl-phosphatidylglycerol, to be administered via dry powder inhalation that acts as a dual-modal antiviral and anti-inflammatory agent. The mode of action of palmitoyl-oleoyl-phosphatidylglycerol has been extensively studied, however, to develop it into a stable and effective drug product, a dry powder formulation needs to be developed. Celestial therapeutics has already gathered preliminary data regarding the generation of a dry powder with the desired particle size. In this SBIR Fast-Track project, Celestial Therapeutics will complete the development of the dry powder inhalation (DPI) formulation suitable for inhalation. The Phase I study will 1) demonstrate the efficacy of DPI in vivo as a treatment and/or prophylactic agent against RSV when administered via inhalation; 2) confirm the safety profile of the DPI, and 3) show that the DPI has the desired pharmacokinetic profile in vivo. The successful outcomes of Phase I will open to a Phase II project where Celestial Therapeutics will optimize manufacturing and define quality controls (Aim II-1), followed by pivotal preclinical safety pharmacology and toxicology studies (Aim II-2). The DPI will improve the current clinical practice as it will be the first available dual-modal antiviral/anti-inflammatory prophylactic and interventional treatment against RSV. Serving both as treatment and prophylaxis, the DPI will be preferred over mAb injections. Upon completion of the Phase II project, a pre-IND meeting will be held with the FDA to discuss the data gathered.

项目概要 人类呼吸道合胞病毒 (hRSV) 感染的全球发病率估计为 3300 万例 5 岁以下儿童，多达 234,000 人死于该病。尽管经常被描述为 儿科疾病、65 岁或以上成年人的 RSV 感染构成了巨大的健康负担。最近的 基于单克隆抗体 (mAb) 的疫苗和疗法的后期试验失败促使 开发针对 RSV 的新干预措施。为了满足这一紧迫的临床需求，Celestial Therapeutics 正在开发 内源性阴离子肺表面活性剂脂质，棕榈酰-油酰-磷脂酰甘油，通过 干粉吸入剂，作为双模式抗病毒和抗炎剂。作用方式 然而，棕榈酰-油酰-磷脂酰甘油已被广泛研究，以将其发展成一种稳定且 为了获得有效的药物产品，需要开发干粉制剂。天体疗法已经 收集了有关生成具有所需粒度的干粉的初步数据。在本次SBIR中 Fast-Track项目，Celestial Therapeutics将完成干粉吸入剂（DPI）的开发 适合吸入的制剂。 I 期研究将 1) 证明 DPI 作为一种治疗方法的体内功效 和/或通过吸入施用时针对RSV的预防剂； 2) 确认DPI的安全性， 3) 显示 DPI 具有所需的体内药代动力学特征。第一阶段的成功成果 将启动二期项目，Celestial Therapeutics 将优化制造并定义质量 对照（目标 II-1），然后进行关键的临床前安全药理学和毒理学研究（目标 II-2）。新闻部 将改善当前的临床实践，因为它将是第一个可用的双模式抗病毒/抗炎药物 针对 RSV 的预防性和介入治疗。 DPI 既可作为治疗又可作为预防 优于单克隆抗体注射。第二阶段项目完成后，将召开预 IND 会议 FDA 讨论收集的数据。