Monte Rosa Therapeutics Announces First Subjects Dosed in Phase 1 Study of a NEK7-Directed Molecular Glue Degrader for the Treatment of Multiple Inflammatory Diseases

Monte Rosa Therapeutics, Inc. recently announced the first subjects have been dosed in a Phase 1 study evaluating MRT-8102, a NEK7-directed MGD being developed for the treatment of inflammatory conditions driven by the NLRP3 inflammasome, IL-1β, and IL-6. Initial results from the Phase 1 study are expected in H1 2026.

“The initiation of the MRT-8102 Phase 1 study represents another exciting step forward for our immunology and inflammation pipeline,” said Markus Warmuth, MD, Chief Executive Officer of Monte Rosa Therapeutics. “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.”

The MRT-8102 Phase 1 study is a randomized, double-blind, placebo-controlled trial in healthy volunteers that includes both single ascending dose (SAD) and multiple ascending dose (MAD) cohorts. The study is designed to evaluate safety and tolerability, pharmacokinetics (PK), and pharmacodynamics (PD), including NEK7 degradation and ex vivo responses to inflammasome stimulation. Part 3 of the Phase 1 study is a randomized, placebo-controlled trial that will enroll subjects with increased CVD risk due to obesity and elevated CRP, designed to evaluate safety and tolerability, change in CRP levels, pharmacokinetics, and changes in other inflammatory markers.

MRT-8102 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that targets NEK7 for the treatment of inflammatory diseases linked to NLRP3, IL-1β, and IL-6 dysregulation. NEK7 has been shown to be required for NLRP3 inflammasome assembly, activation and IL-1β release both in vitro and in vivo. Aberrant NLRP3 inflammasome activation and the subsequent release of active IL-1β and interleukin-18 (IL-18) has been implicated in multiple inflammatory disorders, including cardiovascular disease, gout, osteoarthritis, neurologic disorders including Parkinson’s disease and Alzheimer’s disease, and metabolic disorders. In a non-human primate model, MRT-8102 was shown to potently, selectively, and durably degrade NEK7, and resulted in near-complete reductions of IL-1β and caspase-1 following ex vivo stimulation of whole blood. MRT-8102 has demonstrated a considerable safety margin (>200-fold exposure margin over projected human efficacious dose) in GLP toxicology studies.

Monte Rosa Therapeutics is a clinical-stage biotechnology company developing highly selective molecular glue degrader (MGD) medicines for patients living with serious diseases in the areas of oncology, autoimmune and inflammatory diseases, and more. MGDs are small molecule protein degraders that have the potential to treat many diseases that other modalities, including other degraders, cannot. Monte Rosa’s QuEEN (Quantitative and Engineered Elimination of Neosubstrates) discovery engine combines AI-guided chemistry, diverse chemical libraries, structural biology, and proteomics to rationally design MGDs with unprecedented selectivity. Monte Rosa has developed the industry’s leading pipeline of MGDs, which spans autoimmune and inflammatory diseases, oncology, and beyond. Monte Rosa has a global license agreement with Novartis to advance VAV1-directed molecular glue degraders and a strategic collaboration with Roche to discover and develop MGDs against targets in cancer and neurological diseases previously considered impossible to drug. For more information, visit www.monterosatx.com.