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

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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.