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Web Date: December 6, 2017

Obsidian launches with $49.5 million to fine tune cellular and gene therapies

Tunable technology was born in the labs of Stanford professor Thomas Wandless
Department: Business
Keywords: Start-ups, Obsidian, T-cells, Michael Gilman
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Gilman
Credit: Obsidian Therapeutics
A photo of Michael Gilman.
 
Gilman
Credit: Obsidian Therapeutics

Armed with $49.5 million in its first formal round of funding, Obsidian Therapeutics has launched to fine tune the activity of cellular and gene therapies. Led by serial entrepreneur Michael Gilman, the Boston-based biotech firm aims to make the treatments safer and more effective across a broader range of diseases.

Ever since early clinical trials suggested chimeric antigen receptor (CAR) T cells could quickly obliterate blood cancer in some patients, companies have been racing to figure out how to harness the technology, in which a patient’s own T cells are genetically engineered to include a protein receptor that helps them see and attack cancer cells.

The problem is that CAR T cells “are sort of on a therapeutic knife edge: They can either be profoundly effective or terribly toxic,” notes Gilman, who is also CEO of Arrakis Therapeutics and led Padlock Therapeutics until its acquisition by Bristol-Myers Squibb.

When CAR T cells home in on cancer cells, they can prompt a rapid—and potentially deadly—release of cytokines, proteins involved in immune system response. Although oncologists are getting better at managing that dangerous side effect, some patients have died.

Moreover, CAR T cells don’t produce lasting responses for every cancer patient, and it has been tough to get them to work in solid tumors, which feature a more complex tumor microenvironment.

Obsidian hopes its technology, which was discovered in the labs of its scientific founder, Stanford University chemical and systems biology professor Thomas Wandless, can address each of those limitations.

Wandless found a way to add a region on a protein, what he calls a “destabilizing domain,” that allows expression of the protein to be controlled based on exposure to a small molecule. Without the small molecule around, the protein is tagged for disposal in the cellular trash bin; when the small molecule—an already-approved drug—is given, the protein is stabilized and can do its job.

“The ground state is ‘off’,” Gilman explains. “If you don’t take the pill, nothing happens. Then you can fairly sensitively and precisely dial up the expression of the protein.”

By giving proteins something like a volume knob that can be tuned by small molecules, Obsidian expects to be able to control the speed at which CAR T-cells work their magic and avoid the sometimes-deadly cytokine storms. The company can also give cells “entirely new functionalities that help them cope with the solid tumor environment, which is a very unfriendly place for them,” Gilman adds.

Although most companies working on CAR T cells are primarily focused on oncology, Gilman says “we’re definitely looking beyond cancer.” In addition to autoimmune diseases, Obsidian is interested in applying its technology to hematopoietic stem cells used to fight blood cancers and other diseases.

Obsidian’s team, currently at 20 people, is set to double in size in the next year. With funding from backers including GV (the former Google Ventures), Atlas Venture, Takeda Ventures, Vertex Ventures, and Amgen Ventures, the firm is working towards getting its first treatment into the clinic in 2019.

 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society
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