Medical Innovation Exchange

Merck offers up to $610M for one of C4’s protein degraders

Merck & Co. was the talk of the town in Madrid after signing a multi-billion dollar antibody drug conjugate (ADC) deal with Daiichi Sankyo to open this year’s European Society for Medical Oncology annual meeting.

Now the Keytruda maker is back to the dealmaking table, and looking at antibody conjugates from a different lens. The pharma is paying $10 million upfront to C4 Therapeutics to develop an exclusive degrader-antibody conjugate (DAC), a play on words that summarizes C4’s protein degrader offering.

C4 also stands to make $600 million in biobucks on the single asset, according to Tuesday’s announcement. Merck has the option to license three additional DACs from the biotech that, if pursued, would push the total value of the deal to $2.5 billion. 

C4 is one of a growing number of targeted protein degradation biotechs that have entered the fold in recent years, including the likes of Nurix, Amphista, PeptiDream and Proxygen. C4’s platform differentiates itself by developing two types of degraders: one that binds directly to the E3 ligase (known as a molecular glue) creating a new landing for that disease-causing protein; and another that binds to both the protein and ligase independently. The hope is that this will vastly expand the scope of problematic proteins that targeted degradation could deal with. 

Merck is C4’s fourth collaboration, including prior pacts with Biogen and Roche. The deal with Biogen aims C4’s Torpedo platform at neurological diseases, namely Parkinson’s and Alzheimer’s. The deal with Roche is broader, with the partners not specifying disease areas of interest, and was expanded in 2019. What is known is that the Swiss pharma handed back an epidermal growth factor receptor (EGFR) target back in 2020. 

C4 launched in 2015 out of the lab of Jay Bradner, M.D., back when he was a physician-scientist at the Dana-Farber Cancer Institute. Shortly after the biotech’s founding, Bradner, who is credited as one of C4’s scientific co-founders, was hired as president of the Novartis Institutes for BioMedical Research. 

Beyond its business development ventures, C4 is growing an internal pipeline that includes two clinical-stage meds. The lead asset is a molecular glue targeting IKZF1 and IKZF3 for patients with multiple myeloma and non-Hodgkin’s lymphomas. C4 previously decided not to advance a third clinical-stage candidate, CFT8634, due to “insufficient single agent efficacy.”

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