Monte Rosa Therapeutics Presents Preclinical Data at American Association for Cancer Research (AACR) Annual Meeting 2025 on the Potential of its CDK2-directed Molecular Glue Degrader to Treat HR-positive/HER2-negative Breast Cancer

Core Insights - Monte Rosa Therapeutics, Inc. announced preclinical data indicating that its CDK2-directed molecular glue degrader, MRT-51443, in combination with CDK4/6 inhibition and anti-estrogen therapy, achieved superior tumor regression in HR-positive/HER2-negative breast cancer models compared to standard care therapies [1][2][4] Group 1: Preclinical Findings - The combination of MRT-51443 with CDK4/6 inhibitors and anti-estrogen therapy resulted in deeper tumor responses than the standard of care [2][5] - In the MCF7 model, the combination of MRT-51443, ribociclib, and fulvestrant demonstrated a median tumor growth reduction of -77% compared to -3% for ribociclib and fulvestrant alone [5] - In the T47D model, the same combination showed a median tumor growth reduction of -61% versus -10% for ribociclib and fulvestrant [5] Group 2: Mechanism and Selectivity - MRT-51443 exhibited highly selective degradation of CDK2 with no detectable off-target activity, leading to robust downstream CDK2 pathway suppression [4][5] - The degradation of CDK2 with MRT-51443 delayed resistance to CDK4/6 inhibition in vitro, addressing a common issue where tumors become reliant on the CDK2 pathway [2][5] Group 3: Future Developments - Monte Rosa anticipates submitting an Investigational New Drug (IND) application for its cell cycle program in 2026 [2] - The company is focused on developing highly selective molecular glue degrader medicines for various serious diseases, including oncology [7]