CFT1946 is an orally bioavailable BiDAC™ degrader (or bifunctional degradation activating compound) currently in a Phase 1/2 clinical trial for the treatment of BRAF V600 mutant solid tumors, including non-small cell lung cancer, colorectal cancer and melanoma. BRAF V600 is an abnormal version of the protein BRAF, which can lead to cancerous uncontrolled cell growth. We designed CFT1946 to be potent and selective against BRAF V600 mutant targets. Our preclinical research shows that CFT1946 is active in models with BRAF V600E-driven cancers and in models resistant to BRAF inhibitors.
Opportunity for Targeted Protein Degradation
Targeted protein degradation (TPD) could offer improvement over approved therapies that inhibit abnormal BRAF V600. Resistance is a common limitation of approved BRAF inhibitor therapies against this abnormal protein and often results from alterations in BRAF or BRAF-interacting proteins upstream in the signaling pathway that render inhibitors ineffective. Approved inhibitors also exhibit a phenomenon known as “paradoxical activation” which can lead to certain toxicities. Complete removal of the abnormal BRAF protein through degradation has the potential to overcome these limitations of currently approved inhibitors.