C4 Therapeutics (CCCC) 2024 Wells Fargo Healthcare Conference summary

Program updates and clinical progress

• Two main clinical programs, cemsidomide and CFT-1946 (BRAF V600X degrader), are in phase 1 dose escalation with significant progress and upcoming data readouts at ESMO and in Q4.

• CFT-1946 targets resistance mechanisms in BRAF-mutant cancers by degrading the mutant protein, aiming for improved durability and safety over inhibitors.

• Dose escalation for CFT-1946 has reached 640 mg, declared safe, with expansion into PK/PD cohorts and ongoing exploration of higher doses if warranted.

• Cemsidomide has shown promising activity and safety at multiple dose levels in multiple myeloma, with expansion cohorts ongoing and robust data expected.

• NHL data for cemsidomide will be more complex due to various subtypes, with analysis focusing on PK/PD and exposure-response relationships.

Trial design and patient population

• CFT-1946 phase 1 uses a Bayesian logistic regression model, enrolling at least 30 patients across four dose levels, with global recruitment in the US and Europe.

• Patients must have had prior BRAF inhibitor therapy, often heavily pre-treated with standard of care regimens.

• Expansion cohorts include pharmacodynamic assessments with pre- and post-exposure biopsies to link drug exposure to target degradation.

• Additional cohorts are planned for combinations with EGFR and MEK inhibitors in relevant tumor types.

• Dose escalation decisions are data-driven, balancing safety, exposure, and value for the program.

Clinical development strategy and competitive landscape

• CFT-1946 is intended for internal development through proof of concept, with potential for registrational studies in melanoma and CRC based on data.

• Cemsidomide development is more complex, likely requiring a partner for broader advancement due to treatment paradigm complexity.

• The therapeutic index for cemsidomide is considered wide, with neutropenia managed in practice and multiple safe dose levels established.

• Competitive landscape includes new therapies like bispecifics and CAR-Ts; cemsidomide is positioned for combination strategies with emerging agents.

• The Q4 cemsidomide data set is expected to be sufficient for partnership discussions.