Roche is jumping into degrader-antibody conjugates, a modality that in recent years has attracted investments from Merck KGaA and Bristol Myers Squibb.
Roche is fronting $20 million to ink another deal with long-time partner C4 Therapeutics and join its fellow Big Pharma players in advancing a novel type of targeted protein degradation therapy.
Under the terms of the new agreement, announced Thursday morning, the pharma’s upfront payment will provide access to two degrader-antibody conjugate (DAC) programs, as well as the opportunity to add a third target. If Roche exercises this option, C4 Therapeutics (C4T) will be entitled to an additional payment, though the specific amount was not disclosed.
On top of the upfront commitments, Roche has also put more than $1 billion on the line in discovery, regulatory and commercial milestones. C4T will also be eligible for tiered royalties on future sales, if any products from the partnership reach the market.
The partners did not disclose what specific indications they will go after, revealing only that their DACs will be designed against “undisclosed oncology targets.”
C4T will design the degrader payload while Roche will be in charge of creating the antibody. The pharma will also assume responsibility for taking the resulting construct through preclinical and clinical development, as well as handling regulatory and commercialization activities.
Roche first became a C4T partner in January 2016, when the biotech launched with $73 million in series A funds. Aside from supporting the financing round, the pharma at the time signed a deal with C4T to develop targeted protein degraders, with a potential contract value over $750 million.
Structurally, DACs resemble antibody-drug conjugates (ADCs), also using antibodies to seek out certain proteins found on target malignant cells. Unlike ADCs, which carry cancer-killing chemicals, DACs instead carry molecular glue degraders, which are compounds that force the interaction between two typically unrelated molecules, ultimately leading to the destruction of a disease-causing protein.
Such an approach presents “a new way to treat cancer,” according to the companies’ news release on Thursday, “that leverages both the specificity and catalytic efficiency of degraders with the delivery capabilities of ADCs.”
Several pharma companies have bought into the promise of DACs—a couple of them through partnerships with C4T. Merck in December 2023, for instance, paid the biotech $10 million, though the pharma axed the agreement last November. In March 2024, Merck KGaA—a similarly named but completely separate entity headquartered in Germany—also linked up with C4, putting out $16 million upfront and promising up to $740 million in milestones.
Meanwhile, Bristol Myers Squibb in November 2025 acquired Orum Therapeutics’ ORM-6151 for acute myeloid leukemia or high-risk myelodysplastic syndromes. The pharma paid $100 million for the DAC and promised up to $180 million in milestones.
