Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE) announced positive data from the GFORCE-1 Phase 1 study of MRT-8102, a molecular glue degrader targeting the NEK7 protein. The study evaluated the drug in 108 obese subjects with elevated cardiovascular disease (CVD) risk, who were randomized to receive once-daily doses of 5 mg, 20 mg, or 40 mg of MRT-8102 or placebo for four weeks, followed by a four-week safety follow-up period.
The company reported that MRT-8102 achieved robust and sustained degradation of NEK7, with a median reduction of approximately 80 to 90% across all three dose levels. The treatment resulted in substantial reductions in key pathogenic drivers of atherosclerotic cardiovascular disease (ASCVD). Local plaque inflammation drivers, including calprotectin, S100A12, and SAA, were reduced by 56%, 46%, and 51%, respectively. Additionally, the systemic inflammatory biomarkers IL-6 and high-sensitivity C-reactive protein (hsCRP) decreased by 54% and 85%, respectively. The thrombogenic factor fibrinogen was reduced by a median of 28%, and lipoprotein(a) was reduced by 24%, comparable to the effects of PCSK9 inhibitors. Notably, unlike IL-6 receptor blockade, MRT-8102 treatment did not increase LDL-C or triglyceride levels.
Safety data indicated that MRT-8102 was well tolerated over the eight-week study period. No serious adverse events were reported, and treatment-emergent adverse event rates were similar between the MRT-8102 and placebo groups (33% and 30%, respectively), with no evidence of increased infection risk.
Monte Rosa plans to initiate multiple Phase 2 studies of MRT-8102 in the coming year. These include GFORCE-2, a Phase 2b study in patients with stable coronary artery disease expected to begin in the first half of 2027; GEMINI-1, a Phase 2 study in gout expected to begin in Q4 2026 or Q1 2027; and GALAXY-1, a Phase 2 study in moderate to severe hidradenitis suppurativa expected to begin in the first half of 2027.
