Immuno-oncology, Venture

Atlas and OrbiMed back Boston’s Kyn in $49M round to pursue immunometabolism therapies

Boston biotech Kyn Therapeutics has raised $49 million in a Series A round to advance its immunometabolism therapies to treat cancer.

The money comes from Atlas Venture and OrbiMed — both repeat investors who first funded the company during its launch last March.

Mark Manfredi

Kyn is led by an Atlas entrepreneur-in-residence Mark Manfredi, who was previously chief scientific officer at Raze Therapeutics (also an Atlas-funded startup). Raze raised a $24 million Series A in 2014, but the company appears to have wound down pretty quickly. The website is no longer active, and Manfredi said Raze still has some assets and collaborations, but no longer employs anyone. Atlas’ Bruce Booth says the underlying cancer metabolism biology was too complicated to warrant further investment. Before Raze, Manfredi was VP of oncology biology at Takeda.

Now as CEO of Kyn, Manfredi is once again leading a company focused on immunometabolism to treat cancer, a growing area of immuno-oncology. The field leverages metabolic pathways and the broken-down molecules that result from metabolism (called metabolites). Kyn has an undisclosed number of preclinical programs designed to reverse the effects of metabolites promoted by cancer cells.

First, the company is targeting the IDO and TDO pathways. IDO and TDO are metabolic enzymes overexpressed in many cancers that convert tryptophan to kynurenine. Kynurenine accumulates in and around the tumor where it enters immune cells and binds the aryl hydrocarbon receptor. This triggers the broad suppression of the immune system, Manfredi said.

Kyn’s plan is to degrade kynurenine and/or antagonise the aryl hydrocarbon receptor.

The IDO pathway is already being eyed up by other companies, including Incyte, Bristol-Myers, and NewLink Genetics. But Manfredi tells me he thinks it’s important to target TDO, as well.

“The inhibitors out there only inhibit IDO,” Manfredi said. “Some tumors express IDO, but others express TDO as well, which also produces the suppressive metabolite kynurenine. We think if we go after that metabolite specifically, it will be more effective.”

Kyn plans to test their product candidates as single agents, as well as in combination studies with checkpoint inhibitors.

Of the company’s new $49 million, $28 million is going to fuel these programs. Manfredi said the company isn’t disclosing which cancers it’s tackling.

The rest of the cash is going to Kyn’s affiliate called Arrys Therapeutics, which has exclusively contracted Kyn to develop ARY-007. This program does not target IDO/TDO, but is still in the immunometabolism field. The product candidate blocks the EP4 receptor, which is involved in the prostaglandin E2 pathway. ARY-007 has already shown favorable therapeutic characteristics in human trials for osteoarthritic pain, Manfredi said.

The company is jumping into Phase Ib studies in 2018.

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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
Director of Operations
Atlas Venture Cambridge, MA

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