Monte Rosa Therapeutics (NASDAQ:GLUE) reported interim clinical results from its ongoing phase 1 study of MRT-8102, an oral NEK7-directed molecular glue degrader being evaluated in healthy volunteers and subjects at elevated cardiovascular disease (CVD) risk. Executives said the interim dataset showed rapid and sustained reductions in inflammatory biomarkers, with no safety concerns identified to date.
Interim phase 1 results highlight reductions in hsCRP and fibrinogen
Chief Executive Officer Marcus Warmuth said MRT-8102 produced “rapid and compelling” reductions in high-sensitivity C-reactive protein (hsCRP) across all doses tested in both healthy volunteers and high-CVD-risk subjects, totaling 112 participants as of the December 23, 2025 data cutoff.
In part three of the study, which includes participants at elevated CVD risk, the interim analysis covered 24 subjects who completed four weeks of dosing at 40 mg once daily (randomized 3:1 active drug to placebo, with approximately 36 subjects planned for this portion). Chief Medical Officer Philip Janku said MRT-8102 drove a median hsCRP decline of 80% after one week and 85% after four weeks, with 94% of subjects reaching hsCRP levels below 2 mg/L after four weeks. The company also reported a 31% reduction in fibrinogen after four weeks of dosing.
Mechanistic readouts: NEK7 degradation and downstream cytokines
Janku detailed pharmacodynamic data showing rapid and sustained NEK7 degradation in peripheral blood T cells. He said approximately 80% to 90% degradation was observed six hours after a single dose, and that similar levels were maintained after repeated dosing ranging from seven days (MAD) to up to four weeks (part three). The company also stated that even 5 mg achieved roughly 80% NEK7 degradation after seven daily doses, consistent with the drug’s catalytic mechanism of action.
In biomarker analyses:
- SAD: Across subjects treated with a single dose (40 mg to 400 mg), the company reported a 52% reduction in CRP at 96 hours post-dose, with larger median reductions (72% and 78%) in subsets with baseline CRP ≥1 mg/L and ≥2 mg/L, respectively.
- MAD: Across seven-day dosing (5 mg to 200 mg), the company reported a 61% reduction in CRP in all treated subjects and reductions approaching ~80% in subsets with higher baseline CRP. Janku said 7 of 9 subjects (78%) with baseline CRP ≥2 mg/L achieved hsCRP below 2 mg/L after seven days.
- IL-6: MRT-8102 reduced IL-6 by 55% in 14 MAD subjects with baseline CRP ≥1 mg/L, and Janku said IL-6 levels fell below 1.65 pg/mL, a threshold referenced from the CANTOS trial as being associated with reduced cardiovascular risk.
- IL-1β (ex vivo): The company reported close to 80% inhibition of IL-1β secretion in whole-blood stimulation assays and described a near-perfect correlation between NEK7 degradation and IL-1β suppression.
CSF findings suggest CNS exposure at one dose level
Monte Rosa also described cerebrospinal fluid (CSF) sampling conducted at a single dose level (100 mg) in the MAD portion. Janku said MRT-8102 CSF levels were consistent with concentrations needed to be active against NEK7. In two subjects with elevated IL-6 in CSF at baseline, IL-6 levels in CSF decreased following treatment, while baseline plasma IL-6 levels were low—an observation the company said was consistent with a CNS/CSF-driven effect in those individuals.
Safety update: 112 subjects dosed, no serious adverse events reported
Monte Rosa presented blinded safety data across SAD, MAD, and part three, noting that 112 subjects had completed dosing by the data cutoff. The company said MRT-8102 was well tolerated with no serious adverse events, treatment-emergent adverse events that were mild to moderate, no evidence of increased infection risk, and no dose dependency of adverse events.
Management noted one participant in part three was diagnosed with asymptomatic acute infectious hepatitis A during the study, with a transient grade 3 ALT elevation that improved while the participant continued treatment for a couple of days. Because the safety dataset remains blinded, the company said it does not yet know whether the participant received MRT-8102 or placebo.
Development plans: expanded “G-Force One” and a phase 2 “G-Force Two” in 2026
Based on the interim results, Monte Rosa said it is expanding the phase 1 CRP proof-of-concept study in elevated CVD risk subjects. The expanded study is now named G-Force One and will explore additional dose levels, while continuing the 40 mg cohort. The company said it plans to enroll three dose cohorts, randomized 3:1 active drug to placebo, for a total of approximately 108 subjects. Additional dose levels will be disclosed later. Data from the expanded G-Force One study are expected in the second half of 2026.
The company also said it plans to initiate a phase 2 study in atherosclerotic cardiovascular disease (ASCVD), named G-Force Two, in 2026. During the Q&A, Warmuth said trial size in CV outcomes studies is driven by effect size and suggested the biomarker modulation observed could influence future study design, while noting it remains early.
Management also discussed potential future opportunities for the NEK7 program beyond ASCVD, citing areas with acute or recurrent inflammatory flares and additional cardiometabolic and inflammatory indications, including MASH, recurrent pericarditis, gout, osteoarthritis, and asthma.
Separately, the company highlighted broader pipeline progress, including its RAF1-directed program MRT-6160 (licensed to Novartis) moving toward initiation of multiple phase 2 studies in immune-mediated diseases, and plans to present updated data for MRT-2359 in metastatic castration-resistant prostate cancer at ASCO GU in late February, with a phase 2 study (Modifier One) planned this year. Monte Rosa also said it expects an IND submission for its CDK2 program by year-end.
About Monte Rosa Therapeutics (NASDAQ:GLUE)
Monte Rosa Therapeutics is a biotechnology company focused on accelerating drug discovery through the integration of single-cell genomics and artificial intelligence. Founded in 2020 and headquartered in Cambridge, Massachusetts, the company has built a proprietary platform designed to identify novel therapeutic targets and optimize lead candidates for areas of high unmet medical need. By combining cutting-edge computational methods with comprehensive cellular profiling, Monte Rosa aims to streamline the preclinical development process and uncover insights into disease biology that might otherwise remain hidden.
The company’s main business activities center on using its AI-driven discovery engine to pursue programs in immuno-oncology and neuroscience.
