C4 Therapeutics (CCCC) Status Update summary

Portfolio and Pipeline Progress

• Achieved significant milestones in targeted protein degradation, advancing multiple clinical programs and collaborations, with the TORPEDO platform validated by internal pipeline expansion and partnerships with Biogen, Merck, and Betta Pharmaceuticals.

• Cemsidomide advanced rapidly as a best-in-class IKZF1/3 degrader, showing compelling activity in multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL), with ongoing clinical programs.

• Initial clinical data for CFT1946 (BRAF V600X degrader) and CFT8919 (EGFR L858R degrader) demonstrated proof of mechanism and activity, with further readouts planned for 2025.

• C4T aims to become a fully integrated biotech company focused on orally bioavailable degraders in oncology and non-oncology indications.

Clinical Progress and Trial Updates

• Cemsidomide showed strong anti-tumor and immunomodulatory activity in heavily pre-treated MM and NHL, including patients with prior CAR-T, BCMA, and T-cell engager therapies.

• In MM, cemsidomide plus dexamethasone achieved a 36% overall response rate at 75 μg and 26% across all doses, with durable responses and a wide therapeutic index.

• In NHL, cemsidomide monotherapy achieved a 38% overall response rate, with 44% in PTCL and 100% in AITL subtype, and a 25% complete metabolic response rate in PTCL.

• Responses were observed across all dose levels, with deepening and durable responses up to 18 months.

• Ongoing dose escalation and combination studies are planned in MM and NHL.

Safety and Tolerability

• Cemsidomide was well-tolerated in both MM and NHL, with manageable neutropenia and low rates of infections and febrile neutropenia.

• Most neutropenia events occurred in the first two cycles, with limited G-CSF use (26%) and no dose reductions due to adverse events in MM.

• In NHL, 48% experienced grade ≥3 neutropenia, but cases were manageable and did not lead to discontinuation.

• Safety profile compares favorably to mezigdomide, with fewer neutropenic events, lower G-CSF use, and lower rates of grade ≥3 infections.

• Only one dose-limiting toxicity was observed, and the maximum tolerated dose has not been exceeded.