Merck KGaA bolsters protein degradation pipeline with $756M C4 pact

04 Mar 2024
firstwordpharma.com
Phase 1PROTACsLicense out/in
C4 Therapeutics has inked a potentially lucrative deal with Merck KGaA to discover two targeted protein degraders against undisclosed oncogenic proteins. The collaboration adds to Merck's growing portfolio of protein degradation projects as it expands its presence in the space.
Under the agreement, C4 will receive an upfront payment of $16 million from Merck, which will help cover the costs of discovery research efforts for the two programmes. In turn, Merck will be responsible for developing and commercialising any drug candidates emerging from the partnership.
C4 is eligible to receive up to approximately $740 million in combined discovery, development, and commercial milestones across the two programmes. It will also be able to pocket mid-single to low-double digit tiered royalties on potential future sales of any approved products.
Merck's protein powerplay
The deal marks Merck's fourth collaboration in the protein degradation space, following agreements inked in 2022 with Amphista potentially worth over €932 million ($1 billion), Proxygen for up to €495 million ($537 million), and Celeris Tx. The German pharma giant has been actively pursuing partnerships to bolster its pipeline of targeted protein degraders, a modality that has drawn interest from a number of other major players, including Novo Nordisk (for more, see – Spotlight On: Targeted protein degradation grows up).
For the collaboration, C4T will leverage its proprietary TORPEDO platform. According to the company, the platform allows it to create both molecular glue degraders, or so-called MonoDACs, and heterobifunctional degraders, referred to as BiDACs, providing the capability to target "almost any disease-causing protein."
CEO Andrew Hirsch said the deal "highlights [our] differentiated approach to targeted protein degradation science and our strong track record of designing novel targeted protein degrader medicines with desirable drug-like properties."
C4 is also partnered with Merck & Co. to develop degrader-antibody conjugates in a deal potentially worth $600 million.
However, Monday’s alliance comes on the heels of a corporate restructuring at C4, which recently cut 30% of its workforce, or about 45 positions, to extend its cash runway into 2027. The layoffs followed the company's decision to discontinue development of its BRD9-targeted degrader, CFT8634, due to insufficient efficacy in a Phase I trial.
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