CFT1946 is an investigational, orally bioavailable small molecule degrader of BRAF V600 mutations in solid tumors currently being evaluated in a Phase 1/2 global clinical trial in patients refractory to BRAF inhibitors. CFT1946 is designed to be potent and selective against the BRAF V600 mutant form. Initial clinical data from the Phase 1 trial demonstrate that CFT1946 has a well-tolerated safety profile, demonstrates dose-dependent bioavailability and degradation of BRAF V600E protein, and demonstrates evidence of monotherapy anti-tumor activity. CFT1946 is the only degrader of BRAF V600 mutant solid tumors in clinical trials.
CFT1946
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.
