C4 Therapeutics (CCCC) investor relations material

Strategic overview, positioning, and market opportunity

• Cimcitamide (also referred to as cemsidomide) is prioritized as a potentially best-in-class IKZF1/3 degrader for relapsed/refractory multiple myeloma, targeting rapid clinical advancement and differentiated label strategies.

• The development plan targets two key market segments: combination with BCMA-BITE in second line or later, and with dexamethasone in fourth line or later, projecting $2.5–$4 billion peak revenue.

• The RRMM market is projected to reach $46B by 2030, with significant share targeted through combinations with BCMA BITE and dexamethasone.

• Regulatory discussions have aligned on a fourth line-plus population for Phase II, with dose selection methodology agreed upon and a clear path to accelerated and full approval.

• Partnering strategies may expand indications, especially for maintenance settings, but current focus is on executing the outlined clinical plan.

Clinical trial results, patient population, and safety profile

• Phase I enrolled heavily pretreated, refractory multiple myeloma patients (median 7 prior therapies, 75% with prior BCMA therapy), representative of current multi-refractory MM.

• Achieved 40% ORR at 75 mcg and 50% ORR at 100 mcg, with median duration of response of 9.3 months (not reached at highest doses), and 67% of efficacy evaluable patients at the two highest dose levels remain on treatment.

• Cimcitamide plus dexamethasone showed a differentiated safety profile: neutropenia was manageable, with low rates of dose reductions (6%) and no discontinuations due to safety.

• Grade 3 neutropenia occurred in 24% and Grade 4 in 33% of patients, with low rates of febrile neutropenia, limited G-CSF use, and myelosuppression mostly limited to early cycles.

• Safety profile compares favorably to other IKZF1/3 degraders, with fewer treatment-disruptive adverse events.

Mechanism of action, pharmacodynamics, and efficacy

• Cimcitamide/cemsidomide degrades IKZF1/3, leading to myeloma cell death and T-cell activation, with deep and prolonged IKZF3 degradation and increased IL-2 cytokine expression observed at all dose levels.

• Dose-proportional pharmacokinetics and optimal IKZF1/3 degradation observed at 100 mcg dose level.

• Higher drug exposure correlated with greater reductions in serum-free light chains and more predictable responses.

• Efficacy was consistent regardless of prior BCMA, CAR-T, or T cell engager therapy.

• The 14 days on/14 days off dosing schedule supports neutrophil recovery and limits clinical consequences of neutropenia.