DXTX-1464 / Differentiated Therapeutics - LARVOL DELTA

Discovery of DXTX-1464: A first-in-class, highly potent and selective degrader of CCNE1/CCNE2 and CDK2 for cancer therapy (AACR 2025) - "Targeted degradation of CCNE1, CCNE2, and CDK2 represents a novel therapeutic approach for cancers characterized by Cyclin E dependencies or CDK2 hyperactivation. By eliminating CCNE1/CCNE2-CDK2 complexes, we propose this strategy will circumvent resistance to CDK4/6 inhibitors in HR+/HER2− breast cancers and will address oncogenic signaling in Cyclin E-amplified or overexpressed solid tumors. These findings support the further development of CCNE1/CCNE2 degraders and provide a rationale for their clinical application in patients with Cyclin E-driven malignancies."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CCNE1 • CCNE2 • CDK2 • CDKN1A • CRBN