C4 Therapeutics (NASDAQ:CCCC) executives outlined plans to advance their lead multiple myeloma program and expand the company’s broader targeted protein degradation (TPD) platform during a fireside chat at the Guggenheim Conference.
Company focus and pipeline overview
Management described C4 Therapeutics as a TPD-focused company with a clinical pipeline led by cemsidomide, an IKZF1/3 degrader in the same broad class as IMiDs and CELMoDs. The company is preparing to move cemsidomide into later-stage clinical development, while continuing to build out a discovery pipeline and collaborations.
- An EGFR degrader in clinical development in China run by partner Betta Pharmaceuticals, with C4 planning to review data and determine whether to initiate U.S. clinical development depending on results and the “evolving landscape.”
- A wholly owned discovery pipeline focused on inflammation, neuroinflammation, and neurodegenerative conditions, with additional details expected over time, though management said it has not shared much yet for competitive reasons.
- Collaborations including prior work with Biogen, which is now advancing two C4 degraders for IRAK4 and BTK in phase I development, as well as ongoing collaborations with Roche (two targets) and Merck KGaA.
How MRD guidance could influence myeloma development
Chief Medical Officer Len Reyno said the FDA’s draft guidance on measurable residual disease (MRD) negativity as a potential surrogate endpoint in multiple myeloma “helps,” primarily because it may enable earlier assessment of efficacy in trials where time-to-event endpoints can take a long time to mature. He noted, however, that MRD remains guidance and that implementation and expectations may vary “asset by asset.”
Reyno also flagged an open question: how MRD negativity rates will map to time-to-event outcomes such as progression-free survival (PFS), particularly because some historical MRD data came from older trials where MRD was not prospectively measured or used different assays. He pointed to Bristol Myers Squibb’s disclosure that a phase III trial with iberdomide met an MRD-negative endpoint, while emphasizing that details and how it maps to PFS have not been reported.
For C4, Reyno said MRD gives the company another way to characterize efficacy early as it advances cemsidomide in two key clinical efforts: a single-arm phase II trial in later-line myeloma and a combination study with a T-cell engager, where MRD testing is planned for patients achieving complete responses (CRs).
Cemsidomide: phase II MOMENTUM trial in fourth-line-plus
CFO Kendra Adams said C4 will start its phase II study, called MOMENTUM, “this quarter.” The trial will evaluate cemsidomide in the fourth-line-plus setting in combination with dexamethasone.
Reyno said the company’s execution plan targets enrolling patients over 12 months, with sites opening and first patient dosing expected “imminently.” He added that after enrollment, the company will be assessing response rate, durability of response (including PFS), and safety.
Regarding what would support accelerated approval in a single-arm setting, Reyno described an approach built around a threshold response rate: in this late-line population, he said the company assumed “off the shelf” regimens could deliver at least a 20% response rate and designed the 100-patient trial to be able to show a higher level, targeting at least a 40% response rate. He also emphasized the importance of a “clean” safety profile, including avoiding discontinuations that could complicate evaluation.
On timing for data, Reyno said C4 has previously disclosed it would provide an early investigator-assessed read of response rate roughly within about a year of closing the study, while “full regulatory endpoints” will require longer follow-up into 2028.
BCMA bispecific combination study with Pfizer-supplied elranatamab
In addition to MOMENTUM, management described a planned phase IB study combining cemsidomide with elranatamab (a BCMA-targeted bispecific T-cell engager), supported by a supply agreement with Pfizer. Adams said the combination study is expected to start in the second quarter.
Reyno said the study is designed to enroll patients with two to four prior lines of therapy. The dosing plan begins at 75 (for cemsidomide), with three potential dose levels considered: 50, 75, and 100. The goal, he said, is to move quickly and identify a dose suitable for a phase III trial within about 18 months of opening the study.
Reyno described a sequencing approach where elranatamab step-up dosing is administered first, noting that some patients may not tolerate step-up dosing. Cemsidomide is then introduced after step-up dosing is completed. He added that supportive care restrictions used in earlier cemsidomide testing would not apply in this setting; for example, patients could receive G-CSF if needed. One key operational consideration, he said, is monitoring overlapping risk such as persistent neutropenia, with an aim to avoid cemsidomide dosing that would trigger elranatamab hold requirements.
On disclosure, Reyno said the company plans to provide “reasonable top-line updates” as the study progresses, including after completion and adequate safety follow-up of the first cohort, likely via press release or alongside quarterly reporting. Timing for initial previews was described as dependent on enrollment and site activation, though the company expects to announce first patient dosing (with cemsidomide, after step-up dosing) and completion of the first cohort when reached.
Financing and runway
Adams said C4 completed financing in the fall of last year, extending cash runway to the end of 2028, which she characterized as “about three years of runway,” enabling execution of the studies discussed. She also noted a potential additional funding component of over $200 million tied to two classes of warrants, which she said could support moving quickly from phase IB and phase II into phase III planning and potentially phase III execution.
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.
