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 had established a relationship with the corresponding researchers right before and learned that this new discovery was underway to become the nucleus for a new biotech:
C4T’s technology represents a new class of heterobifunctional small molecules – TPD therapeutics called “Degronimids” – where one part of the molecule targets the disease-causing protein-, and the other part binds cereblon, thereby leading to the degradation of the target via the cell’s natural ‘trash can’ machinery (the ubiquitin/proteasome system (UPS)). TPD promises to make a broader range of otherwise difficult-to-inhibit target proteins addressable. In addition, the potential for drug resistance could be reduced, or specific target selectivity could be built-in.
When Barbara Lueckel, Head of Research Technologies, Roche Pharma Partnering, 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 said. However, Roche scientists were eager to work on this new approach. “We were excited about the science and really wanted to be the first pharma partner of this promising new biotech,” she recalls. Given C4T had to build its team and platform, the collaboration was set up in a way where the research plan was jointly executed by scientists at Roche and C4T, based on a constant flow of new compounds and exchange of experimental results.
“We really developed the C4T platform together,” says Stewart Fisher, Chief Scientific Officer, C4 Therapeutics. Despite the vast differences in the sizes of the companies, the partners considered themselves as equals and put all their focus on advancing the science. “Right from the beginning it has really been a collaborative partnership that allowed us to grow as a company. Having such strong partners with Roche really made us who we are today,” says Fisher.
After two years,
“As C4T grew as a company over the years, it became essential that we stayed flexible and adapted the way we were collaborating. The time came where it made perfect sense to place the operational responsibility for drug candidate identification entirely in C4T’s hands, with Roche scientists still staying very engaged in the project discussions. This led to a re-shaped 2nd agreement between Roche and C4T building a new foundation for this next phase of our partnership. This customized approach to partnering is the essence of how we want to collaborate with our partners at Roche,” says Lueckel.
“Roche took that leap of faith back in 2015,” says Fisher. “The science and Roche as our first and very committed partner have exceeded our expectations many fold over.”
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