C4 Therapeutics (CCCC) 3rd Annual Guggenheim Healthcare Innovation Conference summary

Cemsidomide profile

• Cereblon-modulating degrader targets IKZF1 and IKZF3; intended to inhibit myeloma plasma-cell proliferation and support immune-cell expansion and activation.

• Longer half-life and lower protein binding enable lower-dose scheduling; management sees potential for a differentiated safety and efficacy profile.

Clinical evidence and dose selection

• In the 72-patient first-in-human cemsidomide-plus-dexamethasone study, ORR was 53% at the 100 mcg RP2D, 40% at the next dose and 36% across dose levels.

• 75% of first-in-human patients had prior CAR-T, BiTE therapy or both; the 14-days-on/14-days-off schedule was associated with low Grade 4 neutropenia and G-CSF use, per management.

• Management selected 100 mcg for late-line refractory disease, citing higher exposure and anti-myeloma control with only a modest modeled increase in neutropenia risk.

• In the elranatamab combination, 75 mcg cleared safety review and expansion is underway; escalation has reached 100 mcg. Combination-study data are guided for mid-2027.

MOMENTUM and potential registration path

• MOMENTUM enrollment is guided to finish in Q1 2027 across up to 60 U.S., U.K. and Western European sites; eligibility includes third-line-plus patients, including those with and without prior BiTE or CAR-T exposure.

• Initial investigator-assessed data are expected in H2 2027 as an early read; management expects investigator and independent response assessments to broadly track, while noting regulators will consider independent response, safety and duration.

• Management is targeting at least 40% ORR for accelerated-approval consideration, alongside duration and safety; it expects the efficacy bar to reflect contemporaneous treatment options when data are presented, likely in 2028 or later.

• A planned phase III strategy would use protocol-defined MRD-negative CR for potential accelerated approval and time-to-event data for full approval; if MOMENTUM supports accelerated approval, management expects the phase III trial could also convert it to full approval.