C4 Therapeutics (NASDAQ:CCCC) outlined near-term clinical plans for its targeted protein degradation pipeline during a presentation at Barclays’ 28th Annual Global Healthcare Conference, highlighting progress in multiple myeloma and an upcoming decision point for its EGFR program in non-small cell lung cancer (NSCLC).
Company overview and key milestones
Chief Executive Officer Andrew Hirsch described C4 Therapeutics as a targeted protein degradation company focused on developing medicines in areas of high unmet need. The company currently has two clinical-stage programs.
- Cemsidomide, an IKZF1/3 degrader in development for multiple myeloma, is the company’s most advanced asset.
- CFT8919, an EGFR L858R degrader for NSCLC, is being evaluated in a Phase 1 study in China through partner Betta Pharmaceuticals.
Cemsidomide: Phase 1 results and rationale
Hirsch and Chief Medical Officer Leonard Reyno emphasized the foundational role of IKZF1/3 targeting in multiple myeloma, noting that earlier therapies in the IMiD class were not originally designed as optimized degraders. C4 argues cemsidomide is an optimized degrader with a profile supported by potency, selectivity, and pharmacokinetics.
Reyno summarized key elements from the first-in-human Phase 1 study, describing a heavily pretreated population with a median of seven prior lines of therapy. He said 75% of patients had been exposed to CAR-T therapies, T-cell engagers, or both, and that at the highest exposure level the study showed a 53% response rate. Reyno argued this response rate in such a pretreated setting supports the continued relevance of IKZF1/3 degradation even as immune-based strategies expand across earlier lines of care.
Reyno also highlighted dosing and pharmacokinetics as differentiators, stating cemsidomide is dosed in micrograms and has a 48-hour half-life. He said the half-life and potency enable anti-myeloma effects across a range of doses while allowing time for neutrophil recovery, supporting a manageable safety profile. He added that in the first-in-human dataset, there were “almost no discontinuations” due to safety-related events.
MOMENTUM Phase 2 design and timing
Reyno said the MOMENTUM trial is designed to mirror the Phase 1 approach with key changes intended to support global development and regulatory rigor. The study will enroll patients in the U.S. and Western Europe, and eligibility is fourth line plus. Reyno expects differences in treatment histories by geography, with U.S. patients likely having more prior lines and more progression after T-cell-directed therapies, while Western European patients may have fewer prior lines.
He said the trial is being run with “regulatory intent,” including independent review of safety and efficacy indices. While he noted the FDA is generally cautious about defining fixed thresholds for success in accelerated approval discussions, he said the company designed the study such that with 100 patients it can detect a 40% or greater response rate, and the company anticipates response duration of at least six months.
Management said they do not plan to provide interim updates, citing the study’s independent oversight and the company’s intent to avoid bias. Hirsch said an investigator-assessed response rate could be shared in the second half of 2027, while centrally assessed response and durability metrics are expected around mid-2028.
Combination strategy with elranatamab
Turning to the planned Phase 1b combination study with elranatamab, Reyno framed the rationale around addressing BiTE limitations such as T-cell exhaustion and suboptimal T-cell effect, which can contribute to relapse and limit depth of response. He said translational data from the Phase 1 cemsidomide study showed immune-related effects on T-cell populations and cytokines, even when administered with dexamethasone.
Reyno and Hirsch said they expect the combination’s opportunity to be measured not only by overall response rate, but by improvements in depth and quality of response, including more complete responses and potentially higher MRD-negative rates. Hirsch said the field may approach very high response rates with novel immune-directed regimens, making depth of response a key differentiator.
Reyno also said C4 benefits from learning generated in earlier elranatamab combination work, including supportive care and safety management practices relevant to BiTE administration. He noted that C4’s combination approach includes dexamethasone, which he said can augment anti-myeloma activity, help reduce cytokine release syndrome risk, and support neutrophil counts early in therapy.
For the Phase 1b, Reyno said the trial will be designed primarily around safety while also evaluating efficacy signals to inform Phase 3 planning. The study will start cemsidomide at 75 micrograms, which he said reflects confidence in the safety profile and allows flexibility to move to higher doses or expand at 75 micrograms, with the option to evaluate lower doses if needed.
CFT8919: data expected and decision point
Hirsch said C4 expects to receive data from the ongoing Phase 1 China study of CFT8919 this quarter, which will enable a decision on the path forward “this month.” He said the program was designed to address what the company viewed as a gap in outcomes between patients with EGFR DEL19 versus L858R mutations when treated with osimertinib, though he acknowledged advances have narrowed that gap. Hirsch said the company will assess the development path, noting the “bulk of the opportunity” appears to be in the frontline setting, and will determine whether C4 should pursue development itself or consider partnering, depending on the data.
Hirsch also cited the company’s year-end balance sheet of just under $300 million, which he said provides runway through the end of 2028 and supports execution across planned clinical milestones, including the MOMENTUM study readouts and combination trial development.
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.
