selonsertib + simtuzumab

Selonsertib + simtuzumab is an investigational combination therapy evaluated for the treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis. Selonsertib is a selective small molecule inhibitor of apoptosis signal-regulating kinase 1 (ASK1), a serine/threonine kinase involved in promoting inflammation, apoptosis, and fibrosis under conditions of oxidative stress. Simtuzumab is a monoclonal antibody targeting lysyl oxidase-like-2 (LOXL2), an enzyme implicated in fibrogenesis. The combination was studied to assess whether dual inhibition could provide additive or synergistic anti-fibrotic effects in NASH patients with stage 2 or 3 fibrosis. Clinical trials found that while selonsertib showed some reduction in liver fibrosis, the addition of simtuzumab did not enhance efficacy and simtuzumab alone was ineffective for this indication[1][4][7].