Business Concentrates PETROCHEMICALS
Interest in IDO inhibitors remains high Tempest Therapeutics fundraising shows continued interest in the cancer immunotherapy target San Francisco-based Tempest Therapeutics emerged from stealth mode last week 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.
Incyte’s IDO1 inhibitor, epacadostat (top), binds the heme group (bottom) in IDO1. The inhibitor from BMS and Tempest binds the apo form of IDO1 without a heme group. 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 fundraising suggests the industry is still excited about 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. Inhibiting IDO1 alone doesn’t stop cancer. But early data suggest that first inhibiting IDO1 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 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 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. 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. Inhibitors like epacadostat bind a heme cofactor inside IDO1. Tempest’s compound and an IDO1 inhibitor from Bristol-Myers Squibb work differently. They bind the apo form of the enzyme, which lacks the heme cofactor, and inhibit it longer.—RYAN
CROSS
ENERGY
Growth of renewables soared in 2017 Renewables
Coal
Natural gas
12.8%
2.5%
7.7%
The energy mix in the U.S. shifted in 2017 compared with 2016, according to the U.S. Energy Information Administration. Power from natural gas declined for the first time since 2013, due primarily to lower overall demand for electricity. Coal power continued its inexorable decline. But renewable sources of energy, primarily wind and solar photovoltaics, grew significantly during the year.
12
C&EN | CEN.ACS.ORG | APRIL 2, 2018
Nova plans ethylene exports Canadian chemical maker Nova Chemicals is working with the oil and gas infrastructure firm Energy Transfer Partners to develop an ethylene export terminal on the U.S. Gulf Coast. The terminal would have the capacity to export 800,000 metric tons of ethylene per year and start up mid-2020. The partners haven’t set a location for the facility, but it would connect with a natural gas liquid storage facility in Mont Belvieu, Texas, where Nova runs an ethylene trading hub. Nova hopes the project would provide a way to ship low-cost U.S. ethylene to overseas plants making derivatives such as polyethylene. The company says the project is contingent on customer interest. Nova isn’t the first company to seize on the idea. Energy services company Enterprise Products Partners and maritime gas carrier Navigator Holdings are also planning an ethylene terminal on the U.S. Gulf Coast. And Odfjell Terminals is considering an export facility for its Houston Ship Channel location. Nova has been aggressively expanding into the U.S. This year, the company formed a joint venture with its sister company, Borealis, and oil giant Total to build an ethylene cracker and polyethylene plant in Texas. And last year, Nova bought Williams Companies’ cracker in Geismar, La. That purchase, for $2.1 billion, also gave the company the trading hub in Mont Belvieu. The Geismar plant is a merchant seller of ethylene and makes no derivatives of its own. However, at the IHS Markit World Petrochemical Conference in March, Naushad Jamani, Nova’s senior vice president for olefins and feedstock, said the site, on the Mississippi River, has 200 hectares of unused land. “That provides us with ideas and opportunities that we are studying at the moment,” he said.—ALEX TULLO
C R E D I T: ACS M E D. CH EM . L ET T.
ONCOLOGY
