Monte Rosa公布MRT-8102 GFORCE-1 I期积极结果

In obese subjects at elevated cardiovascular disease (CVD) risk, MRT-8102, a NEK7-directed molecular glue degrader in development for the treatment of NLRP3/IL-1-driven inflammatory diseases, normalized multiple atherosclerotic cardiovascular disease (ASCVD) pathogenic drivers of local plaque inflammation, thrombosis, and systemic inflammation

Robust and sustained NEK7 degradation observed across 5 mg, 20 mg, and 40 mg once-daily dose levels, with similar biomarker reductions at all three doses

HMGB1, calprotectin, S100A12, and SAA, damage-associated molecular patterns (DAMPs) linked to atherosclerotic plaque progression and instability, and IL-1β, all established key pathogenic drivers of ASCVD, were reduced to levels comparable to normal physiological levels seen in the healthy volunteer population of Phase 1 study

MRT-8102 was safe and well tolerated over four weeks of dosing and four weeks of follow-up, with no serious adverse events, treatment-emergent adverse event rates comparable to placebo, and no evidence of increased infection risk

Phase 2 trials planned across coronary artery disease (GFORCE-2), gout (GEMINI-1), and moderate to severe hidradenitis suppurativa (GALAXY-1)

Company to host conference call and webcast today, Oct. 1, at 8:00 a.m. ET

BOSTON, Oct. 01, 2026 (GLOBE NEWSWIRE) -- Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, today announced positive data from GFORCE-1, a Phase 1 study evaluating MRT-8102, a NEK7-directed MGD being developed for the treatment of inflammatory conditions driven by the NEK7/NLRP3 pathway.

“The GFORCE-1 data are highly encouraging and show that MRT-8102 does precisely what we designed it to do: potently and selectively degrade NEK7 and reduce levels of upstream and downstream drivers of residual plaque inflammation and thrombotic risk, and it does so with a differentiated and favorable safety profile,” said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. “We are particularly excited about our translational approach, including our unique and broad analysis of the NEK7/NLRP3 upstream pathway, that has allowed us to gain unprecedented insights into how inhibition of the pathway through NEK7 degradation leads to normalization of many of the most important drivers of atherosclerotic plaque formation, progression, and rupture. To that end, we observed compelling reductions of HMGB1, calprotectin, S100A12, SAA, and IL-1β. These DAMPs and cytokines are linked to pathogenic biology within atherosclerotic plaques and vessel walls, and they have been identified as independent risk factors of much greater significance than some of the systemic inflammatory markers evaluated in other studies. We have also seen intriguing correlation of these markers with NLRP3 risk alleles, opening up opportunities for a precision medicine approach. The GFORCE-1 study results, alongside a body of genetic, biological, and clinical data, reinforce our rationale for degrading NEK7 to simultaneously dampen multiple key ASCVD disease drivers that can lead to atherosclerosis, plaque progression, and thrombogenesis. We believe targeting NEK7 at the top of the NLRP3 signaling cascade has the potential to provide a degree of clinical impact across NEK7/NLRP3-driven diseases not achievable by targeting individual downstream cytokines.”

Filip Janku, M.D., Ph.D., Chief Medical Officer of Monte Rosa Therapeutics, commented, “We believe our results represent the most comprehensive translational data set reported to date for the NEK7/NLRP3 pathway. GFORCE-1 was designed to provide a broad view of the pharmacodynamic activity and safety of MRT-8102, and the profile we observed further bolsters our enthusiasm for continued development in cardiovascular disease and other indications. With dose selection now informed by these data, we plan to initiate GFORCE-2, a focused Phase 2b study in patients with coronary artery disease, in the first half of 2027. In GFORCE-2, our goal is to connect imaging-based coronary artery plaque assessment, such as fat attenuation index (FAI), with NLRP3 genetics and molecular drivers of local disease pathogenesis and systemic inflammation to inform the design of an innovative and efficient Phase 3 study focused on the most disease-modifiable patient population. We also expect to initiate GEMINI-1, a Phase 2 study in gout, in Q4 2026 or Q1 2027, and GALAXY-1, a Phase 2 study in moderate to severe hidradenitis suppurativa, in the first half of 2027, representing additional substantial opportunities associated with this pathway.”

GFORCE-1 (clinicaltrials.gov identifier NCT07119125) enrolled 108 obese subjects with elevated CVD risk, randomized to MRT-8102 at once-daily doses of 5 mg, 20 mg, or 40 mg, or to placebo. The GFORCE-1 study followed best-in-class data from the single ascending dose (SAD) and multiple ascending dose (MAD) cohorts in healthy volunteers, and those data were previously reported. The GFORCE-1 study evaluated safety and tolerability, along with multiple pharmacodynamic markers, over a four-week treatment regimen, followed by four weeks of safety follow-up. Multiple dose levels were explored to support dose selection for further development across various NLRP3-driven diseases, including ASCVD, gout, and hidradenitis suppurativa.

Summary of GFORCE-1 Results

• GFORCE-1 enrolled 108 obese subjects with elevated CVD risk, randomized to MRT-8102 at 5 mg, 20 mg, or 40 mg once daily, or to placebo, for 4 weeks of dosing and 4 weeks of follow-up safety evaluation.
• MRT-8102 achieved robust and sustained NEK7 degradation, with a median reduction of approximately 80 to 90% observed across all three dose levels.
• Both local drivers of plaque growth and progression and systemic inflammatory biomarkers were substantially reduced following MRT-8102 administration at all three dose levels to levels comparable with baseline values from Phase 1 healthy volunteers.
• Median values of calprotectin, S100A12, and SAA, which are critical drivers of ASCVD progression, were lowered by 56%, 46%, and 51%, respectively.
• Median values of HMGB1 and IL-1β were elevated at baseline and decreased toward healthy volunteer levels following treatment among subjects with elevated levels. Median reductions were 40% and 37%, respectively, in subjects with levels in the top quartile.
• The thrombogenic factor fibrinogen was reduced by a median of 28% to levels consistent with those in healthy volunteers.
• IL-6 and hsCRP, biomarkers of systemic inflammation, were reduced by a median of 54% and 85%, respectively. All three doses of MRT-8102 resulted in rapid and sustained reductions in hsCRP to levels comparable to baseline in healthy volunteers from the healthy volunteer cohorts.
• MRT-8102 administration reduced median lipoprotein(a) by 24%, comparable to PCSK9 inhibitors. Unlike IL-6(R) blockade, MRT-8102 treatment did not increase LDL-C or triglyceride levels.
• Significant increases in baseline biomarker levels were identified in carriers of NLRP3 risk alleles (approximately 30% of the GFORCE-1 population), particularly for DAMPs and IL-1β, suggesting a higher-risk, genetically enrichable population for potential future development.
• MRT-8102 was well tolerated over four weeks of dosing and four weeks of follow-up. No serious adverse events (SAEs) were reported. Rates of treatment-emergent adverse events (TEAEs) were similar between MRT-8102 and placebo, occurring in 33% of MRT-8102 participants and 30% of placebo participants, with no evidence of increased infection risk.

Phase 2 Program for MRT-8102

Monte Rosa expects to initiate multiple Phase 2 studies of MRT-8102 in indications with high unmet need and strong biologic rationale for targeting the NEK7/NLRP3 pathway:

• GFORCE-2, a focused Phase 2b study of MRT-8102 in patients with stable coronary artery disease and residual inflammation, is expected to initiate in H1 2027. The study design, pending regulatory feedback, will evaluate changes in local pathogenic drivers of ASCVD, systemic biomarkers, and cardiovascular imaging over a six-month dosing period to specifically observe modulation of plaque biology, as well as changes in inflammatory, thrombogenic, and lipid mediators of disease. The Company is working to complete long-term preclinical toxicology studies to support this 6-month study.
• GEMINI-1, a Phase 2 study of MRT-8102 in patients with gout, is expected to initiate in Q4 2026 or Q1 2027. The study will investigate prevention of flare recurrence following management of acute flares with MRT-8102. Initial data are expected in H2 2027.
• GALAXY-1, a Phase 2 study of MRT-8102 in patients with moderate to severe hidradenitis suppurativa, is expected to initiate in H1 2027.

Investor Conference Call

Monte Rosa will host a conference call and webcast presentation today, October 1, 2026, at 8:00 a.m. ET. A webcast of the presentation will be accessible via the “Events & Presentations” section of Monte Rosa’s website at ir.monterosatx.com. Registration for the conference call is available at the following link. An archived version of the webcast will be made available for 30 days following the presentation.