Monte Rosa Reports Positive Phase 1 Interim Data For NEK7 Degrader MRT-8102 In Inflammatory Diseases

Monte Rosa Therapeutics, Inc, a clinical-stage biotechnology company focused on the development of molecular glue degrader (MGD)-based therapeutics, announced positive interim data from its ongoing Phase 1 clinical trial evaluating MRT-8102, a NEK7-directed molecular glue degrader being developed for inflammatory diseases driven by the NLRP3 inflammasome, IL-1, and IL-6 signaling.

The Phase 1 study includes single ascending dose (SAD), multiple ascending dose (MAD), and Part 3 cohorts. To date, 48 subjects have been enrolled in SAD cohorts, 40 subjects in MAD cohorts, and 24 subjects in Part 3 have completed four weeks of dosing.

“Today we showcased the potential of MRT-8102, an orally bioavailable molecular glue degrader of NEK7, to transform the treatment of ASCVD and other cardiovascular and cardiometabolic diseases. In this interim data readout, after 4 weeks of dosing MRT-8102 decreased median high-sensitivity CRP (hsCRP) levels by 85% and resulted in suppression of hsCRP to <2 mg/L in 94% of subjects, despite a significantly higher median baseline level of 6.3 mg/L as compared to benchmark clinical trials. These remarkable interim data from our ongoing Phase 1 study of MRT-8102 demonstrate for the first time that treatment with an oral molecular glue degrader of NEK7 led to levels of CRP reduction comparable to those previously reported with biologic therapies,” said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. “During both the SAD and MAD portions of the study, with doses ranging from 5 to 400 mg daily, we observed substantial and approximately equivalent degradation of NEK7 across all dose levels, as well as corresponding reductions in IL-1β and IL-6, along with a favorable safety profile. Importantly, we saw substantial decreases in CRP levels across all dose levels that were nearly equivalent to those achieved in Part 3 of the trial, suggesting maximum activity from the lowest dose level and pointing to a broad safe dosing range available for further development. We believe our data support the potential of MRT-8102 to be an oral best-in-class therapeutic among agents targeting the NLRP3/IL-1/IL-6 pathway and establish the significant potential opportunity for MRT-8102 in multiple chronic inflammatory diseases, including ASCVD.”

Across all cohorts and dose levels, MRT-8102 demonstrated rapid, deep, and sustained degradation of NEK7, achieving approximately 80–90% target degradation in peripheral blood T cells. Pharmacodynamic assessments demonstrated robust anti-inflammatory activity, characterized by significant reductions in high-sensitivity C-reactive protein (hsCRP) following both single-dose and multiple-dose administration over seven days.

In MAD cohorts, MRT-8102 resulted in marked suppression of IL-1β secretion in subjects with elevated baseline CRP levels. Among high-CRP subjects across all dose levels, endogenous IL-6 levels were significantly reduced, with median IL-6 declining by 55%, reaching levels below established cardiovascular risk thresholds.

Filip Janku, M.D., Ph.D., Chief Medical Officer of Monte Rosa Therapeutics, commented, “Based on the highly encouraging data for MRT-8102 we have observed so far, we are expanding our proof-of-concept GFORCE-1 study in subjects with elevated CVD risk, in order to accelerate the anticipated Phase 2 (GFORCE-2) study of MRT-8102 in ASCVD. We expect results from the GFORCE-1 study in H2 2026. Moreover, we are evaluating additional Phase 2 proof-of-concept studies in metabolic dysfunction-associated steatohepatitis (MASH), gout, and recurrent pericarditis, conditions strongly linked to NLRP3 pathway activation.”

Notably, in two subjects with elevated baseline cerebrospinal fluid (CSF) IL-6, MRT-8102 treatment led to a 75% reduction in CSF IL-6, while plasma IL-6 levels in these individuals were low at baseline. This finding may suggest central nervous system or CSF-specific activity of MRT-8102.

In Part 3 of the study, which enrolled subjects with elevated cardiovascular disease (CVD) risk, MRT-8102 demonstrated a clinically meaningful reduction in systemic inflammation. Among the 24 subjects dosed for four weeks as of the December 23, 2025 data cutoff, hsCRP levels decreased by 85%, compared with no significant change in the placebo group. Additionally, 94% of treated subjects achieved hsCRP levels below 2 mg/L after four weeks of dosing, compared with a median baseline hsCRP of 6.3 mg/L.

MRT-8102 was well tolerated across all study parts. Based on blinded safety data, adverse events were infrequent, mild to moderate in severity, self-limiting, and showed no dose-dependent relationship. Importantly, there was no evidence of increased infection risk, supporting the continued clinical development of MRT-8102.