C4 Therapeutics (NASDAQ:CCCC) executives said the company’s lead multiple myeloma program, cemsidomide, remains the central focus of its development strategy as the field for IKZF1/3 degraders becomes more competitive following recent clinical data presentations.
Speaking at the Jefferies New York Conference, President and Chief Executive Officer Andrew Hirsch said C4 is positioning cemsidomide around two main opportunities: late-line multiple myeloma treatment and combinations with immune-directed agents that are moving into earlier lines of therapy.
Cemsidomide Data and Upcoming Readouts
He also emphasized the therapy’s safety profile, citing “very low rates of neutropenic complications” and low rates of discontinuations and dose reductions. Hirsch said that matters in multiple myeloma, where therapies are commonly used in combinations rather than as monotherapies.
C4 has started the Phase 2 MOMENTUM study of cemsidomide plus dexamethasone in fourth-line-plus multiple myeloma patients. Hirsch said the study is being conducted with registrational intent, with the goal of supporting a late-line submission if the data are supportive.
The company has guided to initial investigator-assessed data from MOMENTUM in the second half of 2027. Hirsch said the regulatory endpoint, based on an independent monitoring committee assessment along with durability data, is expected in mid-2028.
C4 has also begun a Phase 1b combination study of cemsidomide with elranatamab, Pfizer’s BCMA bispecific antibody. Hirsch said complete data from that study are expected in mid-2027, with updates planned during dose escalation.
Strategy Differs From Bristol Myers Squibb
The discussion also focused on recent Bristol Myers Squibb data for its CELMoD programs, including the SUCCESSOR-2 study. The moderator noted that SUCCESSOR-2 showed progression-free survival of 18 months versus 8.3 months, though the control arm was a doublet regimen.
Hirsch said C4 was not surprised that the trial showed a progression-free survival benefit, since it compared a triplet containing three active therapies against a doublet. He said the safety profile was also consistent with earlier mezigdomide data, including dose reductions and discontinuations. He noted that median relative dose intensity for mezigdomide in the study was 83%.
Hirsch said C4 does not plan to run head-to-head studies against approved IKZF1/3 degraders such as lenalidomide or pomalidomide because its strategy is not to replace those drugs. Instead, C4 is seeking a label in late-line disease with cemsidomide plus dexamethasone and is pursuing combinations with agents such as elranatamab.
He said Bristol Myers Squibb may need head-to-head data for reimbursement because it is seeking to replace lenalidomide and pomalidomide with iberdomide and mezigdomide.
Safety Profile Central to C4’s Positioning
Hirsch said C4 believes cemsidomide’s tolerability could support broad use in combinations. He pointed to a 6% rate of dose reductions due to tolerability in the company’s Phase 1 trial, as well as lower rates of G-CSF use compared with competing programs based on cross-trial comparisons.
He said investors should focus less on overall neutropenia rates and more on clinical consequences such as infections, treatment discontinuations and dose reductions. Hirsch said grade 4 neutropenia rates were consistent across C4’s dose cohorts, while grade 3 rates varied in part because the dose cohorts were not randomized and differed in patient characteristics.
For the elranatamab combination study, Hirsch said C4 does not intend to change the elranatamab dose. Patients will first complete the step-up dosing regimen currently used for elranatamab before cemsidomide is introduced. The study begins at 75 micrograms of cemsidomide, one dose below the company’s recommended Phase 2 dose, and is designed to explore 50-, 75- and 100-microgram dosing depending on emerging safety data.
Hirsch said C4’s goal is to establish cemsidomide as a preferred combination agent across multiple regimens in multiple myeloma. He also noted that C4 has announced plans to start a second Phase 1b study combining cemsidomide with an anti-CD38 antibody and a proteasome inhibitor.
Market Opportunity and Roche Collaboration
Chief Business Officer Scott Boyle said C4 estimates the fourth-line opportunity targeted by MOMENTUM at $1 billion to $1.5 billion in peak revenue potential. Including the company’s second-line combination strategy, Boyle said C4 sees a potential opportunity of about $4 billion for cemsidomide. He said additional combinations could expand that opportunity.
Boyle also discussed C4’s collaboration with Roche in degrader-antibody conjugates, or DACs. He described DACs as antibody-drug conjugates in which the cytotoxic payload is replaced by a degrader. The companies have announced work on two targets, though Boyle said the targets and timelines have not been disclosed.
Boyle said DACs could allow drug developers to pursue degrader targets that might not be tolerable with systemic delivery because the antibody component can direct the therapy to specific cell types.
Management Says Pipeline Remains Underappreciated
Asked what is most underappreciated about C4, Hirsch said the company’s preclinical pipeline is not yet fully recognized, partly because C4 has not shared data for competitive reasons. He also said cemsidomide remains underappreciated despite a recent increase in the company’s share price.
Hirsch described cemsidomide as a wholly owned, post-proof-of-concept asset with potential best-in-class characteristics in a large and growing market. He said the company’s development plan is focused on where the multiple myeloma market is moving, rather than where it has been.
About C4 Therapeutics (NASDAQ:CCCC)
C4 Therapeutics, Inc is a clinical-stage biopharmaceutical company focused on the discovery and development of targeted protein degraders. Utilizing its proprietary Controlled Inducible Degradation (CiD) platform, the company seeks to eliminate disease-causing proteins by harnessing the body’s natural protein disposal machinery. This approach aims to address a wide range of oncology and immuno-oncology indications by targeting proteins that have historically been difficult to inhibit with traditional small molecules or antibodies.
The company’s pipeline includes multiple small-molecule degrader candidates advancing through preclinical and clinical stages.
