Novel Approach to Pre-Exposure Prophylaxis (PrEP) of COVID-19: Development of S-892216 Long-acting Injectable Suspension

S-892216 is a small-molecule compound developed by Shionogi & Co., Ltd. as a second-generation 3CLpro inhibitor against severe acute respiratory syndrome coronavirus 2. In this study, we evaluated the feasibility of developing a long-acting injectable suspension formulation of S-892216 towards future development of coronavirus disease 2019 pre-exposure prophylaxis medicine for immunocompromised patients. We found that the S-892216 drug substance had a low solubility suitable for long-acting injectable suspension development. The developed S-892216 injectable suspension showed prolonged plasma exposure in both rats and beagle dogs when formulated as a nanosuspension. Selecting polysorbate 20 as a stabilizer enabled manufacturing the nanosuspension with less wet-milling time than that of poloxamer P338. The developed injectable suspension was stable for 12 months at 5°C and 25°C/60% relative humidity after terminal sterilization by gamma irradiation. Thus, the developed injectable suspension shows potential for further development for human use.