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

项目摘要 人类呼吸道合胞病毒（hRSV）感染在全球的发病率估计为3300万例， 5岁以下儿童，多达23.4万人死于这种疾病。虽然经常被描述为 在儿科疾病中，RSV感染在65岁或以上的成年人中代表了相当大的健康负担。最近 基于单克隆抗体（mAb）的疫苗和疗法的后期试验失败， 开发针对RSV的新型干预措施。为了满足这一迫切的临床需求，天体治疗正在开发 内源性阴离子肺表面活性剂脂质，棕榈酰-油酰-磷脂酰甘油， 干粉吸入剂，作为双模式抗病毒和抗炎剂。的作用模式 然而，棕榈酰-油酰-磷脂酰甘油已被广泛研究，以将其开发成稳定且 为了开发有效的药物产品，需要开发干粉制剂。天体疗法已经 收集了关于产生具有所需粒度的干粉的初步数据。在此SBIR中 快速通道项目，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作为治疗药物的体内疗效 和/或通过吸入给药时针对RSV的预防剂; 2）确认DPI的安全性特征， 和3）显示DPI在体内具有所需的药代动力学特征。第一阶段的成功成果 将开放第二阶段项目，其中天体治疗将优化制造和定义质量 对照组（目的II-1），然后是关键临床前安全性药理学和毒理学研究（目的II-2）。新闻部 将改善目前的临床实践，因为它将是第一个可用的双模式抗病毒/抗炎 针对RSV的预防性和干预性治疗。作为治疗和预防，DPI将 优于mAb注射。II期项目完成后，将举行IND前会议， FDA讨论收集的数据。

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.