A decade of trust looking into the future of new modalities

Building on a decade of trust and shared scientific ambition, Roche and C4 Therapeutics (C4T) have now entered their third collaboration, taking a step into the rapidly emerging field of degrader-antibody conjugates (DACs).

ADCs have made important contributions to cancer therapy, but their clinical utility has historically been challenged by a limited therapeutic margin. Degrader-based ADCs (DACs) represent a potential step-change in this modality approach. By utilising degrader payloads that target specific cancer cellular dependencies, DACs offer a superior therapeutic index. Degraders are characterised by a catalytic mechanism of action—a feature unique to this payload class— rendering them exceptionally well-suited for targeted antibody delivery.

In this collaboration, C4T will leverage its TORPEDO® platform to develop the highly potent, conjugation-ready degrader payloads. Roche will then take over to generate, optimise, and conjugate the antibodies, ultimately delivering molecules for the clinic.

 “We are honored to work alongside Roche to rapidly progress this new modality by relying on our commitment to learning from one another and advocating for new, exciting ways to advance scientific discovery. We’re hopeful this shared mindset will help us develop yet another new modality that could offer transformative medicines for patients.”

The original partnership expanded as C4T developed into a clinical-stage company, which included establishing its proprietary TORPEDO® platform and strengthening its pipeline.

The operational responsibility for drug candidate identification was placed entirely in C4T's hands, with Roche scientists staying heavily engaged in project discussions. 

This led to expanded agreements between Roche and C4T focused on creating orally bioavailable heterobifunctional degraders.

In late 2015, a publication in Science magazine showed for the first time in a successful preclinical in-vivo experiment that binders to an E3 ligase named cereblon could be exploited for targeted protein degradation (TPD). Roche established a relationship with the corresponding researchers just prior to this publication and learned that this new discovery was underway to become the nucleus for a new biotech: C4 Therapeutics (C4T).

When Barbara Lueckel, now Head of Research Technologies at Roche Corporate Business Development, visited the then-empty C4T labs back in 2015, there wasn't much to see. “It was all hope and aspiration at the beginning,” she recalls. However, Roche scientists were eager to work on this new approach, making Roche the very first pharma partner of this promising new biotech.

Given C4T had to build its team and platform, the collaboration was set up so that the research plan was jointly executed by scientists at Roche and C4T. “We really developed the C4T platform together,” noted Stew Fisher, former Chief Scientific Officer at C4T.