[Updated 2/15/17, 8:10 pm ET. See below.] Liver disease is challenging for doctors because it can develop without symptoms, making diagnosis difficult without removing cells for examination. For these reasons, fatty liver disease is often called a “silent disease,” says Ariel Feldstein, a gastroenterologist at the University of California San Diego.
Feldstein has been studying the liver for nearly 20 years, and his research now forms the basis of a newly launched company called Jecure Therapeutics. Backed by $20 million in Series A funding from Versant Ventures, San Diego-based Jecure aims to develop a new class of drugs to treat an advanced form of fatty liver disease called nonalcoholic steatohepatitis, or NASH.
While the liver normally contains some fat, the buildup of too much can lead to fatty liver disease. One version is associated with alcoholism. The nonalcoholic version tends to develop in people who are overweight or have diabetes and affects as many as 25 percent of people in the United States, according to the American Liver Foundation. NASH occurs when fatty buildup leads to inflammation and scarring of the liver. There are currently no FDA-approved NASH drugs. Patients facing liver failure require a liver transplant.
Jecure has no drug candidates yet, but its technology—based on Feldstein’s research and licensed from UCSD—aims to find them. Jeffrey Stafford, CEO of Jecure, says Versant’s backing will fund three or four programs up to Phase 1 clinical trials. The company is also developing a blood-based diagnostic for NASH that could take the place of the biopsy now used to diagnose the disease. If all goes well, the company could begin trials in 2019. But by then, one or more NASH drugs developed by other companies could be on the market.
Intercept Pharmaceuticals (NASDAQ: ICPT), a New York-based company, is angling to be the first. Last year, the FDA approved Intercept’s obeticholic acid (Ocaliva) as a treatment for the rare liver disease primary biliary cirrhosis, which causes the immune system to attack the liver. Intercept is now in late-stage clinical studies evaluating that drug as a potential NASH treatment.
Large drug firms have entered the NASH race by acquisition. Gilead Sciences (NASDAQ: GILD) last April shelled out $400 million up front for the rights to a subsidiary of Nimbus Therapeutics that was pursuing a NASH therapeutic. The Nimbus drug NDI-010976 targets an enzyme called Acetyl CoA Carboxylase, or ACC. That enzyme regulates the creation of fatty acids and has a role in some metabolic functions, such as fat buildup—a contributing factor in NASH.
Last September, Allergan (NYSE: AGN) paid $600 million up front for South San Francisco-based Tobira Therapeutics even though Tobira reported underwhelming NASH data in a Phase 2 trial of its drug cenicrivoroc. Tobira pointed out that patients showed enough improvement in fibrosis, or liver scarring, to warrant a Phase 3 clinical trial.
Stafford acknowledges Jecure is behind but says the more advanced drugs are repurposed from other applications, or they focus on the metabolism or regulation of fat. He says Jecure’s focus on the inflammasome, a complex of proteins that plays a role in the inflammation and liver cell death that occur with NASH, sets it apart.
[The following two paragraphs were added to include American Liver Foundation comment.] Inflammasomes play a role in both alcoholic and nonalcoholic fatty liver disease, says Rohit Loomba, chair of the American Liver Foundation’s medical advisory committee and a professor of medicine at UCSD. (Loomba’s research is separate from that of Feldstein and he has no connection to Jecure.) So far, most of the research on the inflammasome is from animal studies but it’s a valid target for intervention, he says. Inflammation is a hallmark trigger for the liver damage from NASH.
Still, there is much about NASH that remains unknown. For example, even after diagnosing the condition, clinicians can’t tell which patients will worsen. Identifying those patients will be important for targeting patients with any treatment. A diagnostic that can find proteins in the blood indicative of fibrosis could offer a way to identify those patients. “A biopsy only tells you what has already happened,” Loomba says. “What is dynamically happening is not known.”
It’s the second time around for Stafford at a Versant-backed company. He and James Veal, now Jecure’s chief scientific officer, were part of the team at Quanticel Pharmaceuticals, a San Diego-based cancer company acquired by Celgene (NASDAQ: CELG) in 2015 for $100 million up front with the potential for as much as $385 million in milestone payments. Brad Bolzon, managing director at Versant, says Stafford approached him with the proposal of a new company pursuing NASH drugs.
Stafford welcomes the work behind the current NASH clinical studies, which he says have helped advance understanding that different facets of the disease could lend themselves to different treatment approaches. That means a Jecure drug could become part of a combination therapy with another company’s drug that addresses the metabolism of fat. He adds that the company’s work with the inflammasome could also have applications in addressing lung and kidney fibrosis.