C-4 – the plastic explosive, that is – is designed to produce "shock and awe" in military use. Although there's a biological tie-in as the fourth chemical step in producing enzymatic reactions, it was more the blast metaphor that led to the naming of C4 Therapeutics, which hopes to blow a hole in conventional thinking about the development of targeted drugs.

"We have a 'shock and awe' kinetic effect on proteins which works very quickly," said Marc Cohen, the software and biotech entrepreneur who is C4's lead investor and co-founder.

The Cambridge, Mass.-based company certainly made an auspicious debut, launching with a $73 million series A largely backed by a syndicate of angel investors and a deal in hand with Roche AG said to be worth more than $750 million.

The company's platform is based on a 2010 discovery in the lab of James "Jay" Bradner, the prolific physician-scientist-entrepreneur of the Dana-Farber Cancer Institute and Harvard Medical School, who is prepping to become president of the Novartis Institutes for Biomedical Research and a member of the pharma's executive committee, effective March 1.

In what was hailed as a more potent form of targeted treatments, Bradner and colleagues devised an all-chemical solution to harness the protein degradation process that occurs naturally in the body. The technology targets disease-causing proteins and facilitates their rapid destruction and clearance from the cell.

The platform has obvious implications in cancer because it doesn't just disable malicious proteins in tumor cells, as current agents do, but destroys them entirely. But just as the texture of the C-4 explosive can be molded into any shape, the C4 Therapeutics team said their platform can be targeted "to any disease-causing protein of our choice," Cohen said.

The work by the Dana-Farber team was published last year in Science.

C4 calls its active agents degronimids – chemical adapters conjugated with selective small molecules that are designed to recruit a cell's ubiquitin/proteasome system to "naturally" degrade targeted proteins. Degronimids offer the potential to remove previously undruggable proteins, including those known to develop resistance to inhibitors.

Even before the discovery was published, the technology was moving "at lightning speed" in the Bradner lab, Cohen said.

"In order to get to escape velocity and make a play toward the clinic – which is what everyone wants to see happen – it needed significantly more resources," he explained.

C4 executed a license agreement with Dana-Farber providing global exclusivity for all applications of the degronimid technology. Company execs said development of a new class of targeted, selective, small drug-like molecules will offer significant advantages across a range of disease mechanisms – especially those involving targets traditionaly viewed as undruggable.

"There are a lot of shots on goal," Cohen said.

'WE THINK THIS IS A WIDE OPEN SPACE'

Other C4 co-founders include Bradner, who will not play an active role; Ken Anderson, director of the Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics at Dana-Farber; and Nathanael Gray, professor of biological chemistry and molecular pharmacology at Harvard Medical School and a principal investigator at Dana-Farber.

The founders have serious Street cred. In addition to Bradner and Cohen – an investor in Acetylon Pharmaceuticals Inc. and Oncopep Inc., both of Boston and wielding Dana-Farber technology – Gray was named co-founder of New York-based Petra Pharma Corp. the day before the C4 launch. Petra is the first life science start-up for the 1-year-old New York arm of Accelerator Corp. Gray's also a co-founder of Syros Pharmaceuticals Inc., of Cambridge, Mass. (See BioWorld Today, Jan. 6, 2016.)

"We've done this before," Cohen told BioWorld Today.

Cohen's Cobro Ventures led the A round, which included investments from Cormorant Asset Management, Kraft Group, EG Capital Group and undisclosed angel investors, as well as Roche and Novartis AG, both based in Basel, Switzerland.

Jason Fisherman, long-time venture investor at Synthesis Capital and Advent International, was named CEO in conjunction with the round.

The size of the financing – "not your typical series A," Cohen admitted – is designed to advance two existing candidates into the clinic. Cohen expects that to occur in 18 to 24 months. The company also will build out rapidly, adding chemists, biologists and biochemists with the goal of identifying and validating additional candidates in short order.

The alliance with Roche, whom Cohen called C4's "flagship partner," was facilitated by Dana-Farber's longstanding relationships with big pharma. The deal calls for C4 to develop therapeutics using the degronimid technology aimed at a specific set of target proteins. Based on successful completion of a defined preclinical development phase, Roche has the option to pursue additional preclinical and clinical development as well as commercialization.

C4 is set to receive an undisclosed up-front payment and development, regulatory and commercial milestone payments for each target, as well as sales milestone payments and potential tiered product royalties. The parties declined to disclose additional details on the terms and targets, but said the potential value exceeded $750 million.

Roche was "very quick to the table and appreciated the potential behind the science and the technology," Cohen said. "We're both very excited about the opportunity to make some game-changing drugs."

The collaboration, which will begin immediately, "has no boundaries," he added. "We think this is a wide open space. Even though we come from Dana-Farber, this is beyond oncology."

Central nervous system, gastrointestinal and cardiovascular indications are among the potential targets that C4 will explore, Cohen said.

And Roche won't be the company's last collaborator, he promised. "We're going to partner with the best of the best. We launched C4 not to be your typical company that makes a compound or two and then sells. We're building this company to be around in 20 years and to make 20 to 40 drugs."

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