The body’s cellular cleanup crew takes on all sorts of jobs, from eliminating misfolded proteins in brain cells to helping repair damaged cells. It makes sense, then, that the so-called ubiquitin-proteasome system is attracting greater interest for therapeutic applications — and the field of companies racing to exploit those just got a bit more crowded.
C4 Therapeutics, based in Cambridge, Mass., launched Thursday with $73 million in initial funding. The company is spinning out research from the Dana-Farber Cancer Institute, but its sights reach further than cancer to include cardiovascular, gastrointestinal, and central nervous system diseases.
C4 thinks it has a way to assassinate disease-causing proteins that drugs cannot reach or that grow resistant to drugs. Its approach rests on molecules the company has created and dubbed “degronimids” that can label specific proteins to be wiped out by the ubiquitin-proteasome system and cleared from the cell. It’s a method known as targeted protein degradation therapeutics.
“They basically put a sticky note on a new protein that says, ‘Come and degrade me,’” said Nathanael Gray, a principal investigator at Dana-Farber and a C4 cofounder. “Many proteins that are considered undruggable … can be induced to be degraded by this approach.”
Other cofounders include Dr. Ken Anderson from Dana-Farber and Dr. James “Jay” Bradner, whose lab at Dana-Farber developed the technology underlying C4’s therapy. (Bradner recently left Dana-Farber and will become president of the Novartis Institutes for Biomedical Research in March, so he will no longer be involved with C4.)
C4 also announced Thursday it had struck a deal with Roche to apply the degronimid technology to a number of undisclosed proteins. The company did not say how much it received from Roche upfront, but said the deal could eventually be worth $750 million with possible milestone payments and royalties.
As scientists have been able to tease apart the mechanisms behind the ubiquitin-proteasome system, the field has garnered more interest for its potential therapeutic value. A conference on the issue sprang up three years ago, attracting researchers from institutions and companies from around the world. Some are exploring how to save helpful proteins from destruction, while others are like C4, using the system to take out certain proteins.
“It’s a large area that’s completely unexplored,” said Alexander Statsyuk, an assistant chemistry professor at Northwestern University who studies the system. “It’s like a gold mine.”
But plenty of challenges remain at this early stage, Statsyuk said. One example: it can still be hard to reach certain proteins with therapies.
C4 hopes to start its first human trials within the next two years, but wouldn’t say for which diseases.
The company brought on Dr. Jason Fisherman, most recently a venture capitalist at Synthesis Capital, as chief executive. It’s moving to space at the Mass Innovation Labs, a facility in Cambridge’s Kendall Square, later this month.
As for the company’s name, it references a fourth chemical step in the protein degradation process when the degronimid technology comes in. But yes, it also alludes to the explosive.
“That is part of the name because that’s what we do, shock and awe,” said Marc Cohen, a C4 cofounder and founder of the lead investor Cobro Ventures. “We degrade proteins quickly. It’s just like destroying them with explosives.”
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