Dana-Farber spinout C4 tackles protein degradation with $73M round, $750M Roche deal in hand

Jay Bradner

While Jay Bradner is transitioning to head up the Novartis Institutes for BioMedical Research, some of the most important work he did at the prestigious Dana-Farber Cancer Institute is now advancing toward the clinic at a nearby startup that's launching today with a hefty $73 million round and a $750 million partnership with Roche ($RHHBY).

The startup is called C4, which is joining a very exclusive club of biotechs tackling protein degradation, with designs on moving far past protein inhibition. The biotech is being helmed by Jason Fisherman, a venture veteran and former researcher at the National Cancer Institute. And while Bradner's new role at NIBR leaves him outside the circle of founding scientists who will continue to help guide the company, the scientific pedigree of the scientists who are still involved is equally impressive. Ken Anderson and Nathanael Gray, both at Harvard Medical and Dana-Farber, are listed as co-founders.

They'll be working with a big bankroll from a round led by Cobro Ventures, an angel group that seeded the company last year, with Roche and Bradner's new company Novartis taking stakes along with Cormorant Asset Management, The Kraft Group (a conglomerate run by Patriots owner Robert Kraft, a longtime friend of Anderson's) and EG Capital Group.

So with Novartis coming in early as an investor, maybe Bradner won't always be watching C4's progress from the sidelines.

The biotech has plans to head to the clinic 18 to 24 months from now with small molecule binders--dubbed degronimids--that can target, destroy and clear proteins through the ubiquitin/proteasome system. That should provide an array of targets, some of which may be partnered with other top players like Roche, says Marc Cohen, the executive chairman of C4 and Cobro (for Cohen brothers) co-founder. Cobro also backed 2013 Fierce 15 company Acetylon, another Dana-Farber licensee.

"Drug discovery research around the ubiquitin/proteasome system is an exciting and growing field, and the discovery of degronimids represents the first all-chemical solution to ligand-mediated protein degradation," said Gray in a statement.

Back in May, Bradner published his work on degronimids, illustrating how enzymes that attach ubiquitin to them could tag target proteins and then drag them to a proteasome for disposal and recycling. The approach was successfully used on cancer cells, pointing to the possibility of developing conjugates that could defeat drug resistance.

And they're not alone in this space. Just a few months ago Celgene ($CELG) bought into Nurix's work on the ubiquitin/proteasome system. And Cohen isn't in the least bit surprised that 2015 Fierce 15 company Arvinas, a Yale spinout, is already at work on protein degradation as well. 

"This is a paradigm shift, a big opportunity with multiple companies in the space coming in," he notes, adding that Bradner made some of the key lab breakthroughs 5 years ago. 

Cohen also underscored his long-term interest in the company, looking to foster a biotech that can create 20 to 40 new drugs over the next 20 years.

There's a lot that Cohen isn't talking about right now. Staff? No numbers for now, but hiring fast. Initial targets? Not disclosing at this point. There's also no word on the upfront from Roche, though in most preclinical deals like this the upfront tends to be small with the payoff coming down the road.

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