Receptor-interacting serine/threonine kinase 1 (RIPK1) regulates inflammatory signaling and induces apoptosis and necroptosis. Pharmacological inhibition of RIPK1 kinase activity has demonstrated efficacy in animal models of neurodegenerative, autoimmune and inflammatory diseases. SIR9900 is a potent and selective novel small molecule RIPK1 inhibitor. This first-in-human, phase I, randomized, double-blind, placebo-controlled study evaluated the safety, pharmacokinetics, and pharmacodynamics of single (3-200 mg) and multiple (3-60 mg daily for 10 days) ascending oral doses of SIR9900 in healthy adult (18-64 years, n = 80) and elderly participants (≥ 65 years, multiple doses 30 mg, n = 8). The study included a food effect component. Overall, SIR9900 was safe and well tolerated with no concerning dose-dependent trends in safety observed. SIR9900 was rapidly absorbed with a plasma maximum concentration time (T