C4 Therapeutics (NASDAQ:CCCC) executives said the company’s upcoming European Hematology Association presentation on cemsidomide will provide longer follow-up from previously disclosed patients, while its broader development strategy remains focused on late-line multiple myeloma and combinations with T-cell engagers.
Speaking at TD Cowen’s 7th Oncology Summit, Chief Medical Officer Len Reyno said the EHA update will build on data previously presented at the International Myeloma Society meeting last fall and a subsequent company press release. He said the data set showed cemsidomide activity in a heavily pretreated population with a median of seven prior lines of therapy, including 75% of patients who had received CAR-T therapy, a T-cell engager BiTE, or both.
EHA Update to Focus on Follow-Up, Not New Patients
Reyno said investors should not expect a new patient cohort at EHA. Instead, the presentation will include the same patients previously described, with a more recent data cutoff and longer follow-up.
“What you can expect to see at EHA, in particular, is an updated experience from the 19 patients who were enrolled at 100, more evidence and more characteristics of long-term safety, and as well as the response characteristics over time,” Reyno said.
He added that because the patient population has already been defined, the company does not expect a change in the overall response rate already disclosed after IMS. However, he said the update will include more detail on durability and safety over time.
On safety, Reyno emphasized neutropenia as a key issue for the drug class. He said cemsidomide’s 14-days-on, 14-days-off dosing schedule, supported by what he described as a unique 48-hour half-life, has shown what C4 views as a differentiated profile. Across dose levels, he cited about a 33% incidence of Grade 4 neutropenia, 47% of patients receiving any G-CSF, and no patients discontinuing the study for safety-related reasons. He also said only 6% of patients required a dose reduction by cycle two.
Regulatory-Intent MOMENTUM Study Remains on Track
Reyno said the ongoing MOMENTUM study is being conducted with regulatory intent, limiting how much the company can disclose while the trial is underway. He said enrollment remains on track with the company’s previously stated goal of completing enrollment in the first quarter of 2027.
“We’ve had good acceptability of the trial,” Reyno said, adding that C4 has been able to find new sites in the U.S. and internationally as it works toward enrolling 100 patients.
Chief Executive Officer Andrew Hirsch said C4 estimates the fourth-line-plus multiple myeloma setting represents about a $1.5 billion market opportunity. He said the company expects that opportunity to grow as CAR-T therapies and BiTEs move into earlier treatment lines, allowing more patients to live longer but ultimately relapse and need additional options.
C4 Sees Differentiation Versus Other CELMoDs
Reyno compared cemsidomide with Bristol Myers Squibb’s mezigdomide and iberdomide, saying C4 believes cemsidomide has shown a response rate comparable to mezigdomide at a similar stage of development, while its safety profile looks more like iberdomide.
He said Bristol’s more advanced programs will provide useful context for the class. Regarding Bristol’s SUCCESSOR-2 trial of mezigdomide plus carfilzomib and dexamethasone, Reyno said C4 was not surprised the study was positive, because it added IKZF1/3 degradation to a doublet that did not include that mechanism.
Reyno said he will be watching the size of the treatment benefit, mezigdomide dose intensity, dose reductions, supportive care use and infection-related complications. Hirsch said C4’s development plans had already assumed SUCCESSOR-2 would be positive and that the result does not change the company’s strategy.
On Bristol’s SUCCESSOR-1 study, which compares mezigdomide against pomalidomide, Hirsch said the trial will be important because it tests a next-generation degrader head-to-head against an earlier-generation drug. Reyno said the data could help C4 as it designs future phase 3 studies, even though the trial does not directly compete with C4’s clinical development plan.
Combination Strategy Centers on BiTEs
C4’s pivotal strategy centers on combining cemsidomide with a BiTE, executives said. Reyno said a phase 1 study combining cemsidomide with Pfizer’s elranatamab is open and recruiting, with cemsidomide starting at 75 micrograms. If that dose is declared safe, the company may explore 100 micrograms and expand the 75-microgram cohort, he said.
Reyno said the initial goal is to show cemsidomide can be combined with elranatamab without compromising delivery of the BiTE. He added that C4 expects the regimen to be highly active and will look for early complete responses, including MRD-negative complete responses. The company expects to share more robust results in 2027.
C4 also recently announced plans to begin additional combination studies in the first half of next year with CD38- and proteasome inhibitor-based triplets. Reyno said those studies are intended to establish cemsidomide’s combinability profile rather than serve as pivotal trials.
At ASCO, Hirsch said C4 will also watch data for iberdomide in a frontline quadruplet regimen and golcadomide in newly diagnosed aggressive B-cell lymphoma, saying both could provide broader context for next-generation degraders.
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.
