What You Need to Know About C4 Therapeutics

What You Need to Know About C4 Therapeutics
January 9, 2017
By Mark Terry, BioSpace.com Breaking News Staff

C4 Therapeutics focuses on developing novel drugs based on what it refers to as the DEGRONIMID paradigm.

DEGRONIMID recruits the E3 ligase cereblon, which is part of the ubiquitin-proteasome system (UPS), to BRD4 by the proteasome. So, basically, C4 is working on a way of tagging harmful proteins so that they get taken out with the trash.

Andy Phillips, C4’s president and chief scientific officer, explained to BioSpace, “It’s similar to putting out trash, in many ways. Small towns and cities have pretty organized systems for getting rid of things. We put little Post-it notes on recycled materials or trash for the landfill, and cells have a similar system—a system called ubiquitin, to determine whether things are headed for general recycling or specifically headed for the trash. And there’s a system for putting the ubiquitin tags on as well.”

That system essentially allows the cell to recognize the protein that needs to be ubiquinated, i.e., tagged for destruction. It attaches the tag and ultimately assures the protein tagged for recycling or destruction is taken to the proteasome. The proteasome, Phillips said, “is very similar visually to what we see in a sink or InSinkErator (garbage disposal)—t’s a tube-shaped multi-protein complex that has an incredible array of shredding machinery on the inside. The protein gets recruited to the proteasome, fed into it and shredded into small pieces. Those small pieces being small amino acids, small building blocks of peptides, etc.”

C4 was founded on the work of Jay Bradner, currently president of the Novartis Institutes for BioMedical Research (NIBR), while he was a researcher at the Dana Farber Cancer Institute, and Nathanael Gray, professor of biological chemistry and molecular pharmacology at Harvard Medical School and an investigator at Dana Farber.

Phillips told BioSpace, “Mark Cohen really led putting the company together along with the investment group, and continues to play a very strong role in the company.”

Ken Anderson, the Kraft Family Professor of Medicine at Harvard Medical School, is also one of the scientific founders.

Company Leadership
Mark Cohenexecutive chairman. Cohen is also the co-founder and chief executive of Bublup, Neuro Tennis, and COBRO Ventures. He is also the co-founder and chairman of Acetylon Pharmaceuticals and OncoPep. He was also the co-founder and chief executive officer and chairman of OPNET Technologies.

Andy Phillipspresident and chief scientific officer. Before joining C4, Phillips was senior director at the Center for Development of Therapeutics at Broad Institute of MIT and Harvard. Prior to that, he was a professor of chemistry at Yale University and a professor of chemistry and biochemistry at the University of Colorado.

Andrea Armstrongchief administrative officer. Prior to joining CF, Armstrong was the chief human resources officer and vice president of administration at the New York Genome Center.

Isabel Chiusenior vice president, translational science and alliances. Before joining C4, Chiu was vice president of Translational Research at AVEO Oncology and at Enumeral Biomedical .

Stew Fishersenior vice president, discovery sciences. Previously, Fisher held senior leadership roles at the Broad Institute and before that, spent 15 years with
AstraZeneca .

Tim Heffernansenior vice president, biology. He was previously the co-director and head of drug development at the Institute for Applied Cancer Science at
MD Anderson Cancer Center.

Chris Nasveschukvice president, chemistry. Most recently Nasveschuk was with the Broad Institute.

Tom Needhamchief business officer. Before joining C4, Needham was a life science venture investor as a managing director at Synthesis Capital and a principal at Advent International.

Company Financing
Needham told BioSpace, “The company was launched in December 2015, and the financing was closed in early 2016, so the company really got launched in January. It’s a $75 million Series A financing, and that’s a brand new financing, the equity financing from investors.”

Cobro Ventures led the round and was joined by Cormorant Asset Management, The Kraft Group, EG Capital Group, Roche and Novartis . “Roche was obviously interested in the space and the Roche Venture Fund is an investor. Both of them are investors in the company, and really are strategic investors,” Needham said.

At this point, the company doesn’t exactly have pipeline products. “We have a number of things we’re very excited about. We’re in a privileged position in that we don’t have to pick a lead product at this time. Certainly our general portfolio is coming along very nicely, but we’re not ready to share with the world what our leading product or projects will be. Stay tuned. We’re very encouraged and there are a lot of things going well. I think the world will hearing from us soon,” Phillips said.

Market Competition
Proteasome inhibitors have made some headway in the market, with ’
Takeda Pharmaceuticals Velcade (bortezomib) and Amgen’s Kyprolis (carlfilzomib), as well as Celgene’s Revlimid (lenalidomide).

“There are some companies that are interested, broadly speaking, in protein homeostasis. What are the implications and how do we intervene? Our competitors, in quotations mark there, are companies like Forma Therapeutics,
Proteostasis Therapeutics , Myrexis, and Cleave Biosciences. They’re all generally interested in how we can leverage protein homeostasis in cells,” Phillips said.

Dollars and Deals
At the same time the company raised its $75 million Series A round, it announced that it had entered into a strategic collaboration deal with Roche (ROG) to develop novel drugs in the field of targeted protein degradation (TPD). “Publicly, there was a research relationship established on protein degradation in oncology and with targets of interest to the two parties. So the upfront payments and milestone payments could be valued up to $750 million,” Needham said.

C4 is also looking for more deals. “The partnerships are going to be an important part of validating the technology and accelerating molecules into the clinic. We are currently interested in looking at additional partnerships and we’ll both have a pipeline of in-house and pipeline of programs from partner programs that will be moving forward in partnership. We hope to announce additional partnerships as we move forward,” Needham said.

What to Look For
Aside from more partnerships, C4 expects to expand its internal efforts across various different fields, including chromatin biology, immuno-oncology and a handful of others.

“I believe strongly in collaboration as a mechanism to solve higher order problems and can often run much faster than any given one organization. So in two to three years, we really do want to see the early projects we’re working on with Roche progress to the point they’re developing candidates, perhaps into the clinic. And most importantly, for us as a company, is hitting a goal with our leading product into the clinic in 2018,” Phillips said.

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