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

项目总结 年，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岁以下的儿童，多达234,000人死于这种疾病。尽管经常被描述为 在儿科疾病中，65岁或65岁以上成年人的呼吸道合胞病毒感染是一个巨大的健康负担。近期 基于单抗的疫苗和治疗的后期试验失败促使 开发针对呼吸道合胞病毒的新型干预措施。为了满足这一迫切的临床需求，天文治疗公司正在开发 一种内源性阴离子肺表面活性物质脂质，棕榈酰油酰磷脂酰甘油，通过 作为双模抗病毒和消炎剂的干粉吸入剂。的行动模式 棕榈酰油酰磷脂酰甘油已被广泛研究，但要将其开发成稳定的和 有效的药物产品，需要开发干粉制剂。天道疗法已经 收集了关于产生具有所需颗粒尺寸的干粉的初步数据。在此SBIR中 快车道项目，天庭治疗公司将完成干粉吸入剂(DPI)的开发 适合吸入的配方。第一阶段研究将1)证明DPI作为一种治疗方法在体内的疗效 和/或通过吸入给药时预防RSV的药物；2)确认DPI的安全概况， 3)表明DPI在体内具有理想的药动学特征。第一阶段的成功成果 将开启一个第二阶段项目，在该项目中，Skestial Treateutics将优化制造并定义质量 对照(AIM II-1)，然后是关键的临床前安全性药理学和毒理学研究(AIM II-2)。DPI 将改进目前的临床实践，因为它将是第一个可用的双模抗病毒/抗炎药物 RSV的预防和介入治疗。DPI既是治疗又是预防，它将 比注射单抗更可取。在第二阶段项目完成后，将与以下人员举行IND前会议 FDA将讨论收集到的数据。

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.