C4 Therapeutics and Roche expanded their partnership to develop next-generation degrader-antibody conjugates, a novel oncology approach designed to improve the precision and therapeutic index of traditional antibody-drug conjugates.
C4 Therapeutics expanded its long-standing partnership with Roche through a new collaboration aimed at advancing an emerging oncology modality combining targeted protein degradation with antibody-drug conjugation (ADC).
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Over the last 15 years, ADCs have made important contributions in cancer therapy, yet their clinical utility has historically been challenged by a limited therapeutic margin. Degrader-based ADCs, or degrader-antibody conjugates (DACs), represent a potential step-change in this modality.1
Through the utilization of degrader payloads that target specific cellular dependencies, DACs offer a superior therapeutic index. These small-molecule degraders are characterized by a catalytic mechanism of action, a feature unique to this approach, rendering them exceptionally well suited for targeted antibody delivery.1
The agreement focuses on the development of degrader-antibody conjugates (DACs), a next-generation approach designed to integrate the specificity of antibody-drug conjugates with the catalytic activity of targeted protein degraders.1
The companies will initially collaborate on two programs directed at undisclosed oncology targets, with Roche leading preclinical, clinical and commercial development, while C4 Therapeutics contributes degrader payload design using its Torpedo platform.2
“For the past decade, C4T and Roche have worked together to drive research in targeted protein degradation and to establish this modality as a new way to treat cancer,” said Andrew Hirsch, president and chief executive officer of C4 Therapeutics. “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.”
Roche, which first partnered with C4 Therapeutics in 2016, framed the deal as a continuation of a broader strategy to invest in differentiated therapeutic platforms. “Our relationship with C4 Therapeutics is built on a decade of trust and shared scientific ambition,” said Boris Zaïtra, head of corporate business development at Roche. “We are pleased to enter into our third collaboration, expanding our long-standing partnership to pioneer the emerging modality of degrader-antibody conjugates.”
Financially, the agreement includes a $20 million upfront payment to C4 Therapeutics, with the potential for additional payments if Roche exercises an option on a third target.1 The company is also eligible for more than $1 billion in development, regulatory and commercial milestones, in addition to tiered royalties on future sales.
The collaboration reflects growing industry interest in improving upon traditional antibody-drug conjugates, which, despite commercial success, have faced limitations related to therapeutic index and off-target toxicity.
For Roche, the deal adds another layer to its antibody-based oncology strategy, while for C4 Therapeutics, it reinforces the commercial potential of targeted protein degradation beyond standalone small molecules.
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