Monte Rosa Therapeutics Begins First-in-Human Trial Of NEK7 Degrader MRT-8102 For Inflammatory Conditions

Monte Rosa Therapeutics has officially commenced dosing in a Phase 1 clinical trial of MRT-8102, a NEK7-targeted molecular glue degrader (MGD) being developed to treat inflammation-related diseases. These conditions are associated with overactivation of the NLRP3 inflammasome and elevated levels of inflammatory cytokines IL-1β and IL-6. Initial data from the study is anticipated in the first half of 2026.

“The initiation of the MRT-8102 Phase 1 study represents another exciting step forward for our immunology and inflammation pipeline. MRT-8102 is the only clinical-stage MGD that selectively targets NEK7, a protein central to NLRP3 inflammasome activation and the downstream dysregulation of IL-1β and IL-6 that underlie multiple inflammatory diseases. We believe MRT-8102 could offer a differentiated approach to treating these diseases based on the exciting potency, selectivity, and durable pharmacodynamics seen in our preclinical studies. Importantly, one cohort of the ongoing Phase 1 study will evaluate changes in C-reactive protein (CRP) and other key inflammatory markers in subjects with high CVD risk. We believe this cohort could provide early proof of concept for cardio-immunology indications such as pericarditis and atherosclerotic cardiovascular disease and help guide future development activities,” said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. 

The trial, conducted in healthy volunteers, is a randomised, double-blind, placebo-controlled study featuring both single ascending dose (SAD) and multiple ascending dose (MAD) arms. It aims to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of MRT-8102, with a focus on NEK7 protein degradation and response to inflammasome activation.

In addition to the SAD and MAD phases, a third part of the study will enroll individuals with high cardiovascular disease risk due to obesity and elevated C-reactive protein (CRP) levels. This arm will assess changes in CRP, other inflammation markers, and drug pharmacokinetics, while continuing to monitor safety and tolerability.