C4 Therapeutics (NASDAQ:CCCC) used a presentation at TD Cowen’s 46th Annual Healthcare Conference to outline its near- and mid-term clinical plans, emphasizing its lead multiple myeloma program cemsidomide and a development strategy aimed at potential accelerated approval pathways.
Focus on targeted protein degradation and a lead myeloma program
Chief Executive Officer Andrew Hirsch described C4 as a targeted protein degradation company seeking to build a “sustainable pipeline” and ultimately become fully integrated. He said the company’s clinical oncology portfolio is anchored by cemsidomide, an IKZF1/3 degrader, with additional clinical assets including an EGFR L858R degrader, CFT8919. Hirsch also said the company has begun discussing a discovery strategy aimed at inflammation, neuroinflammation, and neurodegeneration.
Cemsidomide: rationale, Phase I results, and differentiation claims
Hirsch argued that IKZF1/3 degradation remains central to multiple myeloma biology despite advances in immune-directed agents. He described two mechanisms he said are important for the class: effects on hematopoietic stem cell differentiation (impacting plasma cell formation) and T-cell activation through increased IL-2 production. He positioned the immune activation feature as potentially relevant to addressing T-cell exhaustion seen with some immune-directed therapies, particularly in combinations.
Discussing prior data, Hirsch said cross-trial comparisons suggest cemsidomide has a competitive efficacy profile versus other IKZF1/3 degraders in development, including Bristol Myers Squibb’s CELMoD portfolio. He highlighted that C4’s Phase I study enrolled what he described as a contemporary, heavily pretreated population: 100% triple-class exposed, 100% previously treated with anti-CD38 therapy, and 75% previously treated with BCMA-directed therapies or CAR-T.
Chief Medical Officer Len Reyno provided additional detail on Phase I learnings. He said the overall response rate across all studied doses was 36%, and that response rates increased at higher doses, with a 53% response rate at 100 micrograms. Reyno said cemsidomide showed a safety profile consistent with class effects, including transient neutropenia, but he emphasized what he described as relatively low rates of neutropenia versus other CELMoDs and low use of G-CSF. He also said the study saw very few dose reductions and “almost zero” discontinuations due to drug-related side effects.
Reyno said the company views a 14-days-on/14-days-off schedule as an additional differentiator, citing patient preference for time off treatment and neutrophil recovery during the off period, as well as ease of combining with existing myeloma regimens.
MOMENTUM Phase II and an accelerated approval goal
Hirsch said the company has initiated the MOMENTUM Phase II single-arm study in approximately 100 patients, in a similar population to the Phase I trial, and that enrollment has started and patients have been dosed. Reyno said the company is still early in execution and is expanding beyond the U.S.-only footprint of the Phase I study by activating sites in Europe and other regions.
Management said it is targeting a roughly 12-month enrollment period and anticipates finishing enrollment in the first quarter of 2027. Hirsch and Reyno described the regulatory framework for a potential accelerated approval package as centered on data quality and rigor, including independent efficacy assessments and sponsor blinding to emerging data to avoid bias.
Reyno said the company is looking for a response rate at least in line with its Phase I experience, and he emphasized durability (citing at least six months) and predictable safety as key components of the overall evidence package. Hirsch added that the FDA’s evaluation would be made in the context of available therapies at the time of any submission.
Combination plans: elranatamab study and MRD-negative CR considerations
C4 expects to start a Phase Ib combination study next quarter with elranatamab, Pfizer’s BCMA bispecific T-cell engager (BiTE). Hirsch said the combination study is intended to serve as a foundation for a Phase III pivotal trial that could function as a confirmatory study for the MOMENTUM accelerated approval approach. Management also described a second potential accelerated approval opportunity for the combination program, depending on early response metrics and MRD-negative complete response (CR) rates.
In Q&A, Hirsch clarified that a chart shown comparing outcomes of BiTE combinations versus CAR-T referenced competitor data using a less potent IKZF1/3 degrader. He said those results improved overall response rates but did not meaningfully improve deeper responses, and he argued cemsidomide’s potency could lead to higher CR rates.
Reyno discussed the FDA’s draft guidance on measurable residual disease (MRD) negativity and said C4 designed studies expecting MRD-negative CR to be considered in approval packages, including accelerated approval. He said MRD-negative CR is not central to the single-agent Phase II study, though the company will assess MRD status for CR patients. He said MRD-negative CR could be more influential in Phase III trial design, with a predefined analysis comparing MRD-negative CR rates between arms.
Reyno also said the company views Bristol Myers Squibb’s plan to evaluate iberdomide in a second-line trial using MRD-negative CR as informative for how regulators may assess such endpoints and for designing a cost-effective, faster Phase III program.
When asked what success looks like in the elranatamab combination study, Reyno said key goals include identifying at least one dose that is safe over multiple cycles and observing a high CR rate and MRD-negative CRs, while noting that a Phase I study is not powered to definitively establish those rates. He added that C4 does not plan large expansion cohorts in Phase Ib and instead intends to use the data to design the Phase III study.
On additional combination work, Reyno said C4 plans to generate combination safety data with established backbone agents such as carfilzomib and anti-CD38 therapies, while monitoring emerging therapies for potential future combination opportunities, including possible sequencing approaches with CAR-T.
Collaborations and early-stage discovery strategy
Beyond internal programs, Hirsch said C4 has active discovery collaborations with Roche and with Merck KGaA focused on the KRAS family. He also said Biogen has taken a second degrader delivered by C4 into the clinic, describing the two Biogen programs as an “RAC4 degrader and a BTK degrader for autoimmune diseases.” Hirsch added that C4 expects to deliver another development candidate to a collaboration partner this year.
Hirsch briefly outlined the company’s newer discovery approach in inflammation, neuroinflammation, and neurodegeneration, citing platform learnings including blood-brain barrier penetration, high catalytic activity, and the ability to fine-tune degradation kinetics (including partial degradation). He said C4 has identified three validated pathways and five novel, “undruggable” targets, but is not disclosing targets for competitive reasons. He also said the company is considering “sentinel indications” that could de-risk larger opportunities such as Alzheimer’s disease.
In closing remarks, Hirsch said he believes cemsidomide remains underappreciated by investors as a wholly owned asset with potential to be foundational in myeloma care. Reyno added that, despite advances, there remains demand for well-tolerated late-line therapies and that immune-directed strategies still have room for improvement, arguing that cemsidomide’s safety profile could support broader combination use.
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.
