Monte Rosa Therapeutics Conference Call Summary Company Overview - **Company**: Monte Rosa Therapeutics (NasdaqGS:GLUE) - **Focus**: Development of MRT-8102, a NEK7-directed molecular glue degrader for treating atherosclerotic cardiovascular disease (ASCVD) and other inflammatory conditions Key Industry Insights - **Clinical Study**: Ongoing phase I study of MRT-8102 in healthy volunteers and subjects at elevated cardiovascular disease risk - **Market Opportunity**: Significant unmet medical need in ASCVD, with nearly 40% of patients achieving LDL-C targets still experiencing life-threatening cardiovascular events [doc id='17'][doc id='34'] Core Findings from Interim Results - **Efficacy**: - MRT-8102 demonstrated a **78% reduction** in high sensitivity CRP (hsCRP) after a single dose and an **85% sustained reduction** after four weeks in high-risk subjects [doc id='5'][doc id='29] - **94% of subjects** achieved hsCRP levels below 2 mg/L after four weeks, indicating lower cardiovascular risk [doc id='29] - **31% reduction** in fibrinogen levels, an independent atherosclerotic risk factor, observed during treatment [doc id='29] - **Safety Profile**: - No serious adverse events reported across 112 subjects in the study [doc id='30] - Treatment-emergent adverse events were mild to moderate, with no evidence of increased infection risk [doc id='30] Mechanism of Action - **NEK7 Targeting**: MRT-8102 selectively degrades NEK7, leading to sustained inhibition of NLRP3 inflammasome activity and cytokine release, which is believed to be more effective than downstream targeting of IL-6 [doc id='9'][doc id='10] - **Comparison with Other Treatments**: MRT-8102's efficacy in reducing hsCRP is comparable to high doses of IL-6 targeting antibodies, but with a more favorable safety profile [doc id='7'][doc id='12] Future Development Plans - **Expanded Study**: The phase I study, now named G-Force One, will include additional dose levels and is expected to provide data in the second half of 2026 [doc id='34] - **Phase II Study**: Plans to initiate a phase II study named G-Force Two in 2026 for ASCVD [doc id='34] - **Exploration of Additional Indications**: Potential expansion into other inflammatory conditions such as recurrent pericarditis, gout, and asthma [doc id='32] Important Metrics and Data - **Dosing Information**: - Single ascending dose (SAD) and multiple ascending dose (MAD) cohorts completed with doses ranging from 5 mg to 400 mg [doc id='5'][doc id='19] - Optimal NEK7 degradation achieved at doses as low as 5 mg [doc id='46] - **Biomarker Analysis**: - Significant reductions in IL-6 levels, a key stimulator of CRP production, observed [doc id='24] - Near-perfect correlation between NEK7 degradation and IL-1 beta levels, indicating effective suppression of the inflammatory pathway [doc id='25] Conclusion - Monte Rosa Therapeutics is positioned to make significant advancements in the treatment of ASCVD and other inflammatory diseases through the development of MRT-8102, with promising interim results indicating both efficacy and safety. The company plans to expand its clinical studies and explore additional therapeutic indications, leveraging its innovative approach to targeting NEK7.