Monte Rosa Therapeutics presents preclinical data at AACR on MRT-51443

Monte Rosa Therapeutics (GLUE) announced the company will present preclinical data on the potential of its highly selective cyclin-dependent kinase 2-directed molecular glue degrader, MRT-51443, to treat HR-positive/HER2-negative breast cancer at the American Association for Cancer Research, AACR, Annual Meeting 2025, being held April 25-30 in Chicago, IL. Summary of findings: MRT-51443 exhibited potency, selectivity, and favorable drug-like properties. MRT-51443 demonstrated superior selectivity as compared to several clinical-stage small molecule CDK2 inhibitors. In cellular assays, MT-51443 induced deep CDK2 degradation, resulting in CDK2-dependent cancer cell growth inhibition. Degradation of CDK2 with MRT-51443 delayed resistance to CDK4/6 inhibition in vitro and exhibited strong anti-tumor activity in combination with CDK4/6 inhibitors in vivo. MRT-51443 in combination with CDK4/6 inhibition and anti-estrogen therapy drove deep tumor regressions and achieved superior tumor regression compared to standard of care CDK4/6 inhibition and anti-estrogen therapy in HR+/HER2- breast cancer models. Specifically, in the MCF7 model, the combination of MRT-51443 + ribociclib + fulvestrant demonstrated median tumor growth of -77% versus -3% for ribociclib + fulvestrant. In the T47D model, MRT-51443 + ribociclib + fulvestrant demonstrated median tumor growth of -61% versus -10% for ribociclib + fulvestrant. The combination of MRT-51443 + ribociclib also resulted in robust tumor regression in both models.