Kyn Therapeutics Banks $49M to Advance Cancer Immunometabolism Therapies

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Kyn Therapeutics launched with a $49 million Series A raise today. Investors were Atlas Venture and OrbiMed.

Kyn will focus on developing therapeutics based on immunometabolism. Each of the company’s pipeline products is meant to reverse the effects of a metabolite that causes the immune system to be suppressed. These metabolites are promoted by cancer cells.

Kyn has several programs already, but the most advanced is ARY-007, which is subcontracted from Arrys Therapeutics. ARY-007 blocks the EP4 receptor, which is part of the prostaglandin E2 pathway. It is strongly associated with immunosuppression in cancer. The compound has shown positive therapeutic effects in human clinical trials in non-cancer indications. The company plans to push the compound into a Phase Ib clinical trial in cancer. $21 million of the funds raised is allocated to Arrys for the ARY-007 program.

Other programs include a “Kynase” that breaks down kynurenine directly, which is involved in both the IDO and TDO immunosuppression pathways. Another program blocks immunosuppression regulated by the aryl hydrocarbon receptor (AHR). $28 million of the raise is allocated to these programs.

“We believe Kyn Therapeutics has differentiated its approach in a field that is rapidly substantiating its early promise,” said George Georgiou, founder of Kyn and professor of Engineering at the University of Texas, Austin, in a statement. “We are excited at the possibility of delivering our therapeutics to the many patients who stand to benefit from the cancer immunotherapy revolution underway.”

The company’s chief executive officer is Mark Manfredi. Manfredi was chief scientific officer of Raze Therapeutics, another Atlas Venture portfolio company, which recently closed its doors. Raze was also working in the immunometabolism arena, but found their approach to be too complex at this time to continue forward.

“The promise of immunometabolism lies in overcoming the barriers cancer creates against treatment, and we are very excited about the opportunities we’ve created by harnessing compelling research in this area,” Manfredi said in a statement. “Our preclinical research has delivered exciting results both in single agent studies and in combination with leading checkpoint inhibitors and other mechanisms. We are moving rapidly to launch a clinical oncology study in 2018.”

Corie Lok, writing for Xconomy, notes, “Other companies are also targeting the kynurenine pathway, but in a different way: by inhibiting an enzyme that makes kynurenine, called IDO. IDO inhibitors have generated a lot of interest from Big Pharma because they might help boost the effects of checkpoint inhibitors. While some have yielded disappointing results in clinical trials, others have produced encouraging data—and lots of hype. Incyte Pharmaceuticals of Wilmington, DE, has an IDO1 inhibitor, epacadostat, that is being tested in combination with multiple FDA-approved checkpoint inhibitors in a variety of early and late-stage clinical trials. A Phase III study testing epacadostat with Merck’s checkpoint inhibitor pembrolizumab (Keytruda) in patients with metastatic melanoma should produce data in 2018, and could be the first big validation for IDO inhibitors.”

Manfredi indicates that Kyn plans to evaluate its anti-kynurenine compound with checkpoint inhibitors, as well as a monotherapeutic. Cancer cells have multiple ways of suppressing the immune system, which is why checkpoint inhibitors don’t work in all patients, and why immunometabolic approaches may offer another pathway for immuno-oncology therapeutics.

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