When physician-scientist Jay Bradner left the Dana-Farber Cancer Institute last year, he left behind some key scientific work that had already intrigued a group of investors. Bradner is now president of the Novartis Institutes for Biomedical Research, but his Dana-Farber research continued in the hands of others. It’s now the basis of a new startup called C4 Therapeutics that debuts today with a hefty financing round.
C4 has raised a whopping $73 million Series A from an interesting mix of backers: a group of angel investors, pharmaceutical companies, and even the owner of the New England Patriots. Cobro Ventures, an investment firm formed by tech entrepreneur Marc Cohen and his brother Alain, is leading the round, and is joined by The Kraft Group (the holding company formed by Patriots owner Robert Kraft), Cormorant Asset Management, some unnamed angel investors, New York private equity firm EG Capital, and pharmaceutical giants Roche and Novartis.
The goal is to become a large-scale developer of drugs that harness the ubiquitin-proteasome system (UPS), a sort of garbage disposal system cells use to identify and rid themselves of unwanted proteins.
Other drug developers aim to tweak this system as well, among them San Francisco-based Nurix and two Boston area companies, Forma Therapeutics and Proteostasis Therapeutics. But Cohen believes C4 has put together the most “comprehensive approach” to date, based on a new type of drug called “degronimids” that the company says can target any number of problematic proteins—including some that other drugs can’t reach.
Cohen says degronimids could impact a wide range of diseases including cancer, though those claims won’t be put to the test for another few years. (He wouldn’t specify which disease the company will target first.) C4’s two most advanced drug prospects are about 18 to 24 months away from its first trial, according to Cohen.
Still, C4 already has the support of Roche, which has formed an alliance with the startup that could be worth $750 million if everything breaks right.
“This is one of those companies that we’re not building to sell right away,” Cohen says. “We’re looking at this as a company that’s going to be around for 20 years or so and make 20 drugs.”
Not only would that be unprecedented in the history of the pharmaceutical industry, it would make for a very different result than Cohen and Kraft got the last time they teamed up to form a biotech. Both are members of the Dana-Farber board of trustees and teamed up seven years ago with Bradner and multiple myeloma expert Kenneth Anderson to form Acetylon Pharmaceuticals, a cancer drug developer that has a deal in place to be acquired by Celgene (NASDAQ: CELG).
They reunited with Anderson and Bradner to co-found C4, along with Harvard Medical School biochemist Nathanael Gray. (It’s Gray’s second launch this week after Petra Pharma).
“We were quite familiar with each other and comfortable in terms of how we work together,” Cohen says.
Bradner is listed as a founder but is no longer involved with C4 because of a potential conflict of interest with his new gig at Novartis. Cohen wouldn’t say whether Bradner owns equity in C4, and Novartis didn’t respond to a request for comment.
But Bradner did, in effect, lay the groundwork for C4 to continue on in his absence. “He’s done an amazing job in putting a package of intellectual property, knowhow, and in particular training people beneath him to continue this moving forward,” Cohen says.
So what exactly are degronimids? Cohen says they’re small molecules—chemical compounds—that enter a cell and “trick” the UPS system into tagging an undesirable protein as trash and discarding it.
The UPS system has two parts: ubiquitin, which tags proteins for removal; and the proteasome, which disposes of them. A degronimid has two binding molecules, or ligands, on it. Think of them as two hands. One grabs a tagging molecule, and the other a protein C4 wants to mark for destruction. A degronimid brings the two together, so the bad protein is flagged and the protein is hauled off to the proteasome and destroyed. C4 can customize them to latch on to a variety of different proteins. (The approach was featured in a May 2015 paper in Science.)
“We’re really letting the body do the heavy lifting here,” Cohen says. “All we’re doing is the matchmaking.”
By actively flagging unwanted proteins, C4 hopes to destroy ones that other drugs haven’t been able to. The company also believes tumors hit with this approach won’t be able to build up resistance to the drugs, a common problem with cancer. Cohen says the key is to destroy the proteins, not just block their functions and let them live to see another day—which is valuable time to mutate and figure out a new way to do their job.
“We’re taking that disease causing protein and we’re blowing it out of the water,” he says. Hence the name C4, a type of plastic explosive. “And it happens quickly so we believe that the likelihood of mutation-based resistance is going to be significantly diminished.”
Jason Fisherman, a veteran biotech investor most recently at Synthesis Capital, has been named C4’s CEO in conjunction with the financing. The company will soon move its work out of Dana-Farber and into Mass Innovation Labs in Kendall Square, which opened last year in one of the buildings that used to be home to Vertex Pharmaceuticals (NASDAQ: VRTX).