Roche has entered a new collaboration with C4 Therapeutics (C4T), agreeing to pay $20 million upfront and commit more than $1 billion in potential milestone payments to jointly develop degrader-antibody conjugates (DACs) for oncology. The agreement provides Roche access to two DAC programs, with an option to expand the collaboration to include a third target.
DACs combine features of antibody-drug conjugates (ADCs) and targeted protein degraders (TPDs). Similar to ADCs, these therapies use antibodies linked to payloads to direct treatment toward cells expressing specific receptors. However, instead of delivering cytotoxic chemotherapy agents, DACs carry protein degraders designed to break down disease-associated proteins, including those that are difficult to address with traditional drug approaches. This distinction allows DACs to act through targeted protein degradation rather than broad cell-killing mechanisms.
Under the collaboration, Roche will identify and engineer antibodies against two undisclosed cancer targets. C4T will apply its Torpedo platform to create degrader payloads. Roche will then link these payloads to its antibodies and advance the resulting candidates through preclinical and clinical development, while also managing regulatory and commercialization responsibilities. The agreement includes the possibility of adding a third target, which would trigger an additional payment to C4T, although the amount has not been disclosed. In addition to milestone payments, C4T is eligible to receive tiered royalties on any products that reach the market.
The companies have not disclosed the specific cancer targets involved in the partnership. C4T CEO Andrew Hirsch discussed the types of targets that may benefit from this approach, noting that DACs can be useful in situations where safety considerations are important, as the antibody component enables more selective delivery of the degrader. He also explained that, in some cases, the antibody may contribute additional activity by engaging with the receptor while simultaneously delivering the payload to the intended cells.
While DACs offer a different mechanism of action, their development introduces additional complexity. ADCs are effective partly because their payloads are highly potent, requiring only a limited number of molecules to be attached to each antibody. In contrast, protein degraders, although potent, may require a higher number of molecules per antibody. This difference can affect the overall structure and behavior of the conjugate, making development and optimization more challenging.
Roche addressed these challenges while emphasizing the importance of advancing more complex therapeutic designs. “We believe that more complex modalities have to be mastered,” said Barbara Lueckel, Ph.D., Roche’s global head of research technologies partnering. She noted that although some research efforts may ultimately lead to more conventional formats, there is an increasing need to work with sophisticated approaches that involve linking larger small molecules to antibodies.
This agreement builds on a long-standing relationship between Roche and C4T that began in 2016, when Roche partnered with the company shortly after its launch. At that time, the collaboration was based on early experimental data and focused on targeted protein degraders. Over the years, the partnership has evolved, including changes such as the discontinuation of an EGFR-related program, but the companies have continued to collaborate in the targeted protein degradation field.
Roche Invests Heavily in Next-Generation Therapeutics
In this landmark deal, Roche is committing $20 million upfront with the potential for over $1 billion in milestone payments. This significant investment reflects Roche’s confidence in C4 Therapeutics’ DAC platform, which is designed to selectively degrade disease-causing proteins.
By backing this technology, Roche aims to expand its pipeline in oncology and other serious diseases where traditional therapies fall short.
Strategic Importance of Roche’s DAC Collaboration
The Roche collaboration with C4 Therapeutics centers on leveraging advanced protein degradation science. Unlike conventional inhibitors, DACs eliminate harmful proteins entirely, offering a more effective therapeutic approach.
This Roche deal strengthens its position in the rapidly growing field of targeted protein degradation, a space attracting significant interest across the biopharmaceutical industry.
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