A number of companies are trying to improve cancer immunotherapy by disrupting the ways that tumors evade the immune system. Tempest Therapeutics is now joining that group with $70 million in financing to advance its drug pipeline.
Tempest is a spinoff from a drug discovery unit supported by Versant Ventures, which co-led the Series B financing round. Tom Dubensky, CEO of the San Francisco startup, acknowledges that other companies, big and small, are further ahead in the race to develop drugs with similar mechanisms. But he says Tempest’s small-molecule drug candidates could stand out, because they have the potential for reduced side effects and better efficacy. Tempest will still have to show those benefits in clinical trials, of course. The first one is expected to start next year.
Tempest’s lead drug, TPST-8844, blocks IDO, an enzyme produced by tumors that helps cancers evade the immune system by suppressing immune cells. IDO has become a hot target for drug companies. Flexus Biosciences had not yet started clinical testing of its IDO inhibitor when it was acquired in 2015 by Bristol-Myers Squibb for $800 million up front. Other companies that have advanced IDO inhibitors into the clinic include NewLink Genetics (NASDAQ: NLNK) of Ames, IA, and Incyte Pharmaceuticals (NASDAQ: INCY), based in Wilmington, DE.
Those companies are currently testing their drugs in combination with a different type of cancer immunotherapy called a “checkpoint inhibitor.” These drugs release the brakes on the immune system’s cancer-killing T cells. But checkpoint inhibitors don’t work well on everyone, so some drug companies are trying to broaden the cancer types they can treat and the patients they can reach by combining these treatments with other drugs, such as IDO inhibitors.
Bristol has reported encouraging results from early-stage studies testing its IDO inhibitor combined with its checkpoint inhibitor nivolumab (Opdivo). NewLink is testing its drug, indoximod, with AstraZeneca’s (NYSE: AZN) durvalumab (Imfinzi) in a Phase 2 study enrolling pancreatic cancer patients.
The most advanced of these combination studies is a Phase 3 clinical trial testing Incyte’s epacadostat with Merck (NYSE: MRK) checkpoint drug pembrolizumab (Keytruda). That study is expected to report results in coming months.
Dubensky calls the Bristol and Incyte drugs “the lead horses.” Positive data from their studies will help validate all IDO drug developers. But he adds that Tempest could catch up, and even surpass other IDO-blocking drugs. In preclinical testing, he says, the Tempest drug has not damaged liver cells. Dubensky also says preclinical tests showed that the drug was limited in its binding to blood proteins, which means that there was more of the drug available to block IDO. Those characteristics could set the Tempest drug apart in this new class of drugs, Dubensky contends.
Besides its lead drug targeting IDO, Tempest’s pipeline includes two other pre-clinical compounds developed to disrupt other ways that cancers evade the immune system. The company also has a fourth compound whose details Tempest has not disclosed. With the financing, Tempest aims to start testing its lead drug in humans within 12 months. After that drug starts clinical testing, Tempest aims to bring two more drug programs into the clinic soon afterward. Dubensky says the financing should support the company through mid-2020.
Tempest’s drugs were developed within Inception Sciences, the drug discovery incubator of venture capital firm Versant Ventures. Last summer, Versant infused $22 million into a unit of Inception Sciences that would become Tempest, providing the startup’s Series A financing, Dubensky says. Soon after, Dubensky left cancer immunotherapy developer Aduro Biotech (NASDAQ: ADRO), where he was chief scientific officer, to take the helm at Tempest.
Versant is known for backing companies in a “build-to-buy” model, which involves providing a startup with capital to advance its science far enough to become an attractive acquisition for a larger company. That’s not the plan with Tempest, which Dubensky says will operate as a traditional biotech company developing its own drugs.
But Tempest will be looking for partners as the company starts to produce clinical data. Dubensky is betting that companies developing new checkpoint inhibitors will seek cancer immunotherapy combinations that could expand the reach of their drugs.
“If [checkpoint inhibition] becomes one of the immunotherapy backbones, there are going to be folks that want an effective IDO inhibitor,” he says.
The Series B financing round was led by Versant, F-Prime Capital Partners, and Quan Capital. Other investors participating in the round include Lilly Asia Ventures, Foresite Capital, and Eight Roads Ventures. Dubensky notes that three of the investors in Tempest’s Series B round are based in China. As checkpoint inhibitors take off in that country, IDO blocking drugs could follow, he says.
Metastatic melanoma cells image by the National Cancer Institute.