MRT-8102 Phase 1 Study Shows 85% hsCRP Drop, 94% Achieve <2 mg/L
Monte Rosa’s interim Phase 1 study of MRT-8102 showed 85% median CRP reduction and 94% of subjects achieved <2 mg/L after four weeks. NEK7 degradation was deep and sustained across 5–400 mg doses with mild‐to‐moderate adverse events, and Monte Rosa expects a Phase 2 ASCVD trial launch and H2 2026 readout.
1. Interim Phase 1 Data for MRT-8102 Demonstrate Deep Inflammation Suppression
In the ongoing GFORCE-1 Phase 1 study of MRT-8102, a NEK7-directed molecular glue degrader, 24 subjects with elevated cardiovascular disease risk completed four weeks of dosing. Across single ascending dose (5–400 mg) and multiple ascending dose cohorts, peripheral blood T cells exhibited 80–90% NEK7 degradation within 24 hours of dosing. After four weeks, median high-sensitivity C-reactive protein (hsCRP) levels fell by 85% from a baseline median of 6.3 mg/L, and 94% of participants achieved hsCRP below 2 mg/L—a threshold linked to reduced cardiovascular events. Reductions in IL-1β and IL-6 mirrored NEK7 degradation, with median IL-6 dropping 55% in high-CRP subjects. Safety was favorable, with only mild to moderate adverse events reported and no signs of increased infection risk.
2. Platform Validation and Competitive Positioning of MRT-8102
These results validate Monte Rosa’s molecular glue degrader platform, marking the first time an oral degrader targeting NEK7 achieved CRP reductions comparable to IL-1/IL-6 biologics. Consistent NEK7 degradation at low (5 mg) through high (400 mg) doses suggests a broad therapeutic window and potential for dose optimization. The company plans to initiate a Phase 2 GFORCE-2 study in atherosclerotic cardiovascular disease in 2026, with additional proof-of-concept trials in metabolic dysfunction-associated steatohepatitis, gout and recurrent pericarditis also under evaluation. A readout from the expanded GFORCE-1 study is anticipated in the second half of 2026.
3. Inconclusive MRT-2359 Data in Heavily Pretreated Prostate Cancer Patients
Interim data from the MODeFIRe-1 Phase 1/2 study of MRT-2359, a molecular glue degrader directed at CDK2/cyclin E1, in heavily pretreated metastatic castration-resistant prostate cancer patients were inconclusive. Limited target engagement and variable pharmacodynamic responses were observed across the initial six patients, with no consistent reductions in circulating tumor biomarkers. Safety appeared manageable, but efficacy signals did not meet prespecified thresholds. Monte Rosa plans to refine dosing strategies and present updated data at the ASCO Genitourinary Cancers Symposium in February 2026.