Monte Rosa Therapeutics presents preclinical data on MRT-8102

Monte Rosa Therapeutics (GLUE) announced the company will present preclinical data on the potential of MRT-8102 at the American Heart Association’s, AHA, Scientific Sessions 2025, held November 7-10 in New Orleans, LA. Summary of key findings: MRT-8102 is a selective, potent, and durable NEK7 degrader. Activation of the NLRP3 inflammasome critically depends on NEK7. Administration of MRT-8102 led to inhibition of NLRP3 inflammasome in vitro and in vivo and subsequently inhibited production of multiple inflammatory cytokines. In in vitro assays, MRT-8102 inhibited pyroptotic membrane permeabilization in stimulated human monocyte-derived macrophages, unlike anti-IL-1 and anti-IL-6 therapies. In vitro, NEK7 degradation inhibited cholesterol crystal-induced NLRP3 inflammasome activation, a key driver of atherosclerotic plaque pathogenesis, more potently than selnoflast, an NLRP3 inhibitor currently in development. MRT-8102 demonstrated near-complete suppression of IL-1beta and Caspase-1 activity in ex vivo-stimulated whole blood from orally dosed cynomolgus monkeys. Degrading NEK7 to modulate the inflammasome represents a novel and differentiated approach with potential therapeutic application in multiple cardiovascular and cardiometabolic diseases, including pericarditis and atherosclerosis.