A First-in-Human (FIH) Study to Assess the Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses, and Alternative Formulations of R941552 (R552): A selective Receptor Interacting Protein 1 (RIP1) Kinase Inhibitor

IPK1 (receptor-interacting serine/threonine kinase 1) mediates cell survival through NF-kB, or cell death through apoptosis or necroptosis downstream of TNF receptor activation. R552 is a potent and selective RIPK1 inhibitor that has been shown to block inflammatory cell death (necroptosis). R552 is being developed for the treatment of autoimmune and inflammatory disorders. Preclinical data suggested that solubility may limit exposure; alternative formulations were also assessed in this first-in-human (FIH) study.