Business & Tech

Casma aims to open new drug frontier

They met the first day of their PhD program at the Massachusetts Institute of Technology in 1983, two young men who became great pals. One introduced the other to a Wellesley College student, who liked the new guy so much she married him. Both men graduated from MIT, then worked together at a couple of biotechnology companies.

Thirty-five years after that first encounter in the chemical engineering building at MIT — Building 66 — Keith Dionne and Frank Gentile, are leading a new Cambridge biotech, Casma Therapeutics Inc. It was formally launched Thursday by Third Rock Ventures with more than $58 million in venture capital.

“I was a kid from a farm in Idaho, and he was a kid from New York City,” Dionne, Casma’s chief executive, said of Gentile, the interim chief operating officer. “We formed a fast friendship.”

CEO Keith Dionne and COO Frank Gentile in the 80s.
CEO Keith Dionne and COO Frank Gentile in the 80s.

Fast indeed. Both men bonded over their mutual love of long-distance running along the Charles and ran the Boston Marathon together in 1986.

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“We’ve been in three marathons together,” said Gentile, a native of Brooklyn’s Bay Ridge neighborhood whose father was a construction worker.

Now they have embarked on a decidedly more cerebral exercise. They want Casma to develop new medicines based on Nobel prize-winning discoveries about how cells detoxify and repair themselves.

That process is called autophagy, and if you’ve never heard of it, you’re in good company. Dionne, a 59-year-old veteran of Constellation Pharmaceuticals Inc., Millennium Pharmaceuticals Inc., and Cyto Therapeutics, said he didn’t know anything about it either until January of last year, when he joined Third Rock as an “entrepreneur-in-residence.”

At the time, Gentile, 56, also a veteran of Millennium and CytoTherapeutics as well as other companies, was working as a venture partner at Third Rock. There was growing buzz about autophagy, a natural house-cleaning process in which cells grind up debris and excess proteins and recycle them.


Dr. Beth Levine, an investigator at the University of Texas Southwestern Medical Center, had discovered the first gene in mammals that makes autophagy possible.

And the 2016 Nobel Prize in medicine has been awarded to Yoshinori Ohsumi, a Japanese cell biologist, for his discoveries about how yeast cells break down and recycle their own components during autophagy.

Folks at Third Rock had spent much of 2016 wrestling with a question: Could drugs be developed to induce autophagy and help cells rid themselves of debris associated with diseases?

After Dionne drilled into the subject, he concluded that it was possible.

“Data suggested that if we can induce autophagy and spike it up, we can clear out a lot of the gunk in these cells and clear out the manifestations of the disease,” he said.


Those diseases, he said, could range from fairly common neurodegenerative disorders like Alzheimer’s and Parkinson’s diseases to rare genetic diseases.

Third Rock decided to form a company dedicated to the effort. It was named Casma, after a river in Peru, because the founders felt that autophagy is like a flowing river that cleans and rejuvenates.

The startup, located on Sydney Street, has about 10 full-time employees but could have about two dozen by the end of the year, Dionne said.

Among the scientific founders are Levine, the autophagy expert who discovered the mammalian gene.

Gentile expects to serve as interim chief operating officer for a year or two and then return to Third Rock. (He’s married to the former Erin Fox, the Wellesley student Dionne introduced him to over 30 years ago.)

Dionne said he plans to be there “until we get some good drugs out and make a difference.”

Jonathan Saltzman can be reached at