C4 Therapeutics, Roche expand partnership on degrader-antibody conjugates in USD 1b+ deal

C4 Therapeutics, Inc. (Nasdaq: CCCC), a Watertown, Massachusetts-based clinical-stage biopharmaceutical company, has entered into a new collaboration agreement with Roche (SIX: RO, ROP; OTCQX: RHHBY) to discover and develop degrader-antibody conjugates (DACs) for oncology. The deal is the third collaboration between the two companies since their initial partnership in 2016.

Under the terms, C4 Therapeutics will receive a USD 20 million upfront payment and is eligible for over USD 1 billion in discovery, regulatory, and commercial milestone payments, plus tiered royalties on future net sales. The collaboration combines C4 Therapeutics’ proprietary TORPEDO platform for targeted protein degradation with Roche’s antibody design and conjugation capabilities. The joint research plan covers two undisclosed oncology targets, with Roche holding an option to extend the collaboration to a third target upon an additional payment of undisclosed value.

The DAC Modality

DACs represent a hybrid of two established but distinct oncology modalities: antibody-drug conjugates (ADCs) and targeted protein degradation (TPD). Where conventional ADCs deliver cytotoxic payloads to antigen-expressing tumor cells, DACs substitute a small-molecule protein degrader as the payload. Once internalized by the tumor cell via the antibody vehicle, the degrader recruits an E3 ubiquitin ligase to tag a specific intracellular protein for proteasomal destruction. A key mechanistic feature of degraders is their catalytic mode of action: a single degrader molecule can sequentially degrade multiple copies of the target protein before being released, distinguishing them from occupancy-dependent inhibitors that require continuous target engagement.

The TORPEDO platform integrates DNA-encoded library technology, a Cereblon toolkit, AI-assisted ternary complex modeling, and proteomics to design degraders with properties suited to conjugation, including controlled molecular weight, solubility, and linker attachment compatibility. These engineering requirements distinguish DAC payload design from standard PROTAC chemistry, where molecular weight and hydrophobicity have historically limited drug-like properties.

The specific oncology targets covered by the collaboration were not disclosed.

Deal background and context

The C4 Therapeutics Roche partnership dates to 2016, when Roche became one of the earliest large-pharma investors in the targeted protein degradation field through an initial collaboration with C4 Therapeutics. C4 Therapeutics has maintained an active partnering strategy alongside its internal pipeline, signing other major collaborations including with Merck KGaA, Biogen, and Betta Pharmaceuticals.

The DAC modality is an area of increasing industry activity, sitting at the intersection of two fields that have each attracted substantial investment. The ADC market has seen more than USD 100 billion in deal value over the past several years, driven by approvals and late-stage data across HER2, TROP2, and other targets. Payload innovation has become a primary axis of differentiation as the number of ADC programs in development has expanded, with cytotoxin payloads including topoisomerase I inhibitors and tubulin inhibitors now widely deployed.

Organizations pursuing degrader payloads as a next-generation ADC approach include Arvinas, which disclosed work on DAC constructs leveraging its PROTAC technology. Nurix Therapeutics has explored degrader-based conjugate strategies in its pipeline. At the 2025 American Association for Cancer Research annual meeting, China’s DaCure Therapeutics presented preclinical data for DAC-1522, a Trop2-targeting DAC. And Accutar Biotechnology presented preclinical data for a KIF11-targeting DAC at the 2025 American Society of Clinical Oncology annual meeting.