DS-2319b (nafamostat mesilate)

DS-2319b is an inhaled powder formulation of nafamostat mesilate, a synthetic serine protease inhibitor, developed by Daiichi Sankyo for the treatment of COVID-19 (SARS-CoV-2 infection). Nafamostat mesilate has been used clinically in Japan for decades (under the brand name Futhan) for the treatment of acute pancreatitis and disseminated intravascular coagulation (DIC). In the context of COVID-19, DS-2319b was designed to deliver the drug directly to the lungs to inhibit the host cell surface protease TMPRSS2 (Transmembrane Protease, Serine 2). TMPRSS2 is a critical factor for viral entry, as it cleaves the SARS-CoV-2 spike protein to facilitate membrane fusion between the virus and the host cell. By blocking this step, DS-2319b aimed to prevent viral replication and disease progression. Despite demonstrating potent inhibition of SARS-CoV-2 entry in vitro, Daiichi Sankyo announced the discontinuation of DS-2319b development in June 2021 following a Phase 1 clinical trial in healthy volunteers, citing the overall development landscape and results from non-clinical and early clinical studies.

Other names

nafamostat mesylate