Gilead and Roche Bet on Protein Degraders for Their Cancer Drug Pipelines Leave a comment

Many cancer drugs work by blocking proteins associated with tumor progression, but there’s growing industry interest in drugs that eliminate such proteins altogether. Gilead Sciences and Roche have both dipped their toes into this pool of protein degrader research through partnerships. Now they’re diving in, bringing assets from the class to their respective pipelines.

Gilead has exercised its option to license Kymera Therapeutics drug candidate KT-200, Kymera announced Thursday. This degrader drug is designed to target CDK2, a protein that drives breast cancers and other solid tumors. Small molecules designed to block CDK2 are in development in the hands of several companies, but Kymera contends that these CDK2 inhibitors also affect proteins closely related to the target, leading to side effects. KT-200 is a so-called molecular glue designed to selectively address CDK2, sparing other proteins in the CDK family.

In 2025, Gilead paid $40 million up front to begin a collaboration with Kymera in a deal that gave the drugmaker an exclusive option to license the CDK2 program. Exercising that option now triggers a $45 million payment to Kymera. Kymera said Gilead plans to advance this drug to the preclinical research that could support an investigational new drug application with a goal of submitting that filing in 2027. Gilead could pay out up to $665 million more if the drug achieves milestones; Kymera would also receive royalties from Gilead’s sales of a commercialized product.

Developers of CDK2-blocking small molecules include BeOne Medicines (formerly BeiGene) as well as clinical-stage startups such as Iambic and Avenzo Therapeutics. Oncology was the initial focus of Kymera’s protein degrader research. In recent years, it has turned its focus to applications of this modality in immunology. Sanofi is an immunology partner, having exercised rights to Kymera IRAK4 degrader on track to enter clinical testing this year in a range of inflammatory conditions. In a research note, Leerink Partners analyst Thomas Smith said Gilead’s licensing of Kymera’s CDK2 degrader further validates the biotech’s early-stage development capabilities, supporting its leadership position among oral degraders.

Kymera’s CDK2 degrader could find a fit with Tubulis, Gilead’s latest acquisition. Tubulis uses its proprietary platform technologies to develop antibody drug conjugates (ADCs) for cancer. Speaking during a Tuesday conference call to discuss this acquisition and the broader pipeline, Gilead Chief Medical Officer Dietmar Berger said the Tubulis technologies enable development of ADCs with better stability and greater capacity to carry a variety of drug payloads. Those payloads could include protein degraders, he said. Such drugs have the potential to go beyond oncology.

“Ovarian cancer and then other areas in oncology are the first direction, but there is real opportunity to build out and move into inflammation and into virology,” Berger said of the Tubulis assets.

Pairing degraders with ADCs is the focus of a new Roche collaboration with C4 Therapeutics. The two companies have been protein degrader R&D partners since 2016. On Thursday, the companies announced a new collaboration focused specifically on developing degrader-antibody drug conjugates (DACs). An ADC leverages the targeting ability of an antibody, which is linked to a toxic drug payload. In a DAC, a protein degrader is the drug payload.

According to the deal terms, C4 and Roche will collaborate on two DAC programs for cancer targets that remain confidential and are exclusive to this collaboration. C4 will use its proprietary technology to design degrader drug payloads. Roche will select and design the antibody. The pharmaceutical company will also conjugate the antibody to the degrader payload. The deal terms make Roche responsible for advancing DAC candidates through preclinical and clinical development as well as commercialization of any approved products.

Roche is paying C4 $20 million up front to join the field of DAC developers, which includes companies such as Pfizer and Bristol Myers Squibb as well as startups like Fortitude Bio. If Roche exercises its option for a third target, C4 would receive an additional payment, though those financial details were not disclosed. Across the entire collaboration, C4 could receive more than $1 billion in milestone payments, plus royalties from Roche’s sales of any commercialized DACs from the alliance.

“Our new collaboration leverages C4T’s ability to design highly catalytic and selective degraders, as well as degrader payloads for DACs, alongside Roche’s extensive experience developing ADCs with specific binding,” C4 President and CEO Andrew Hirsch said in a prepared statement. “Together, these capabilities build a powerful new modality that can offer transformative medicines for patients.”

Public domain image by the National Cancer Institute