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Tempest Therapeutics launch shows IDO inhibitors are still hot

The start-up unveils with $70 million in series B funding to develop cancer immunotherapy compounds, including an IDO1 inhibitor

by Ryan Cross
March 30, 2018 | A version of this story appeared in Volume 96, Issue 14


A model of epacadostat binding to a heme cofactor in the IDO1 enzyme.
Credit: ACS Med. Chem. Lett.
Incyte's IDO1 inhibitor, epacadostat (top), binds the heme group (bottom) in IDO1. The IDO1 inhibitor from BMS and Tempest binds the apo form of IDO1 without a heme group.

San Francisco-based Tempest Therapeutics emerged from stealth mode this morning and announced raising $70 million in series B funding for four cancer immunotherapy drug programs. The start-up’s lead candidate inhibits an enzyme called indoleamine 2,3-dioxygenase 1, or IDO1.

IDO1 inhibitors have been the target of several big pharma partnerships over the past few years. Although Pfizer announced in January that it was ending its IDO1 inhibitor partnership with iTeos Therapeutics, Tempest’s large fundraising suggests the industry is still excited about targeting the enzyme.

IDO1 metabolizes the amino acid tryptophan into kynurenine, which suppresses the immune system. Tumors with high IDO1 activity are thus shielded from the immune system’s cancer-killing abilities.

Interestingly, inhibiting IDO1 alone doesn’t do much to stop cancer. But early data suggest that first eliminating a tumor’s protective environment with IDO inhibitors and then subjecting the tumor to checkpoint inhibitors, a class of drugs that release the brakes of immune cells, can form a powerful therapy.

The field’s front-runner is Incyte’s IDO1 inhibitor epacadostat, currently in a Phase III clinical trial in combination with Merck & Co.’s checkpoint inhibitor Keytruda. Positive results from that trial would be “a tremendous validation for targeting the IDO1 pathway,” says Tempest CEO Tom Dubensky.

Some of Tempest’s compounds were developed in 2013 by Inception Sciences, a small-molecule drug discovery incubator cofounded by Versant Ventures in 2011. Last year, Tempest quietly spun off from Inception with about $22 million in series A funding. Impressed with the drug candidates, Dubensky, formerly chief scientific officer of Aduro Biotech, joined Tempest in September.

Even with multiple IDO1 inhibitors in clinical trials, Dubensky sees room for more and says Tempest’s compound, set to enter the clinic in 12 months, could be the best.

One reason lies in how the inhibitors bind IDO1. The enzyme contains a heme cofactor, which epacadostat binds. An IDO1 inhibitor from Bristol-Myers Squibb works by binding the apo form of the enzyme that lacks the heme cofactor, inhibiting it longer. Tempest’s compound works like the BMS inhibitor and is also less toxic to liver cells, according to Dubensky.

Tempest’s latest funding was led by Versant. About a third of the money came from Chinese investors, which Tempest hopes will help expand use of its immunotherapy compounds in China.

“This is still early days for developing IDO inhibitors,” Dubensky says. “There are so many companies with effective checkpoint inhibitors without IDO inhibitors. We think there will be a very strong demand.”


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