CFT1946

C4T has advanced preclinical and clinical research to explore how targeted protein degradation may offer improvement over approved therapies that inhibit mutant BRAF V600. C4T advanced CFT1946, an investigational, orally bioavailable brain penetrant small molecule degrader of BRAF V600 mutations in solid tumors into 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. In May 2025, C4T announced the decision to not advance its BRAF program beyond the current Phase 1 trial of CFT1946 and seek partnership opportunities to maximize its potential given the high unmet need and strong degrader rationale for treating BRAF V600 mutant solid tumors.

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.

Scientific Presentations and Publications

Preliminary Results from a Phase 1 Study of CFT1946, a Novel BiDAC™ Degrader in Mutant BRAF V600 Solid Tumors

Phase 1/2 Study of CFT1946, a Novel BiDAC™ Degrader Targeting Mutant BRAF V600X Solid Tumors Including Metastatic Colorectal Cancer (CRC) in Combination with Cetuximab

CFT1946, a potent, selective BRAF V600X mutant-specific degrader demonstrates superior activity as a single agent to clinically approved BRAF inhibitors and standard of care combinations in preclinical models of BRAF V600X melanoma, CRC, NSCLC, and brain metastasis

The Discovery and Characterization of CFT1946: A Potent, Selective, and Orally Bioavailable Degrader of Mutant BRAF for the Treatment of BRAF-driven Cancers

A Phase 1/2 Study Of CFT1946, A Novel Bifunctional Degradation Activating Compound, or BiDAC™Degrader, of Mutant BRAF V600 as Monotherapy and in Combination with Trametinib, in Mutant BRAF V600 Solid Tumors

Preclinical Evaluation of CFT1946 as a Selective Degrader of Mutant BRAF for the Treatment of BRAF Driven Cancers