With $43M, Nimbus Sheds “Discovery” Tag, Heads to First Clinical Test

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several metabolic disorders like diabetes and obesity. But attempts to target ACC with a drug haven’t worked so far. Most recently, for instance, Pfizer dropped an ACC inhibiting drug for diabetes, Nicholson says.

According to Nicholson, it’s tough to design a drug that tightly binds to ACC. Nimbus believes it can succeed where others haven’t because it has designed what’s known as an “allosteric” inhibitor for ACC. This means rather than focusing on the area where ACC directly interacts with other molecules—the “active” site—to start a chemical reaction, Nimbus’s drug is targeting a different region—the “allosteric” site—which Nicholson likens to a “volume control” for the enzyme. By binding to this part of the enzyme, a drug can theoretically shut down ACC and the fat buildup it can cause in the liver.

Nimbus is using this approach to go after NASH, a leading cause of cirrhosis and liver failure. NASH occurs when fat builds up in the liver, typically due to sugary and fatty diets, leading to inflammation, scarring, and potentially liver transplants if unchecked. About 16 million folks in the U.S. have the disease, the worldwide market is expected to grow to $1.6 billion by 2020, according to a report from Allied Market Research, and there are no approved treatments for it.

No surprise, then, that a number of biotechs and large pharmaceutical companies have barreled into NASH research, among them New York-based Intercept Pharmaceuticals (NASDAQ: ICPT), Foster City, CA-based Gilead Sciences (NASDAQ: GILD), and France’s GenFit.

Indeed, the NASH market has become closely watched on Wall Street. When a Phase 2b study for Intercept’s drug, obeticholic acid, was stopped early last year because of unexpectedly good results, shares skyrocketed more than 200 percent. Intercept has since become one of the most volatile biotech stocks on Wall Street and it leads the NASH chase, awaiting regulatory guidance on the structure of a Phase 3 trial.

Nimbus thinks it can compete based on its drug’s mechanism, says Nicholson. Unlike other mechanisms being used, blocking ACC solves the “underpinnings” of NASH, stops the fat from building up in the liver, and may do so with fewer side effects, he says. That’s the Nimbus hypothesis—“all to be determined,” he cautions. (Intercept’s drug has been tied to some elevation of “bad” cholesterol levels, for instance, although those effects so far appear manageable.)

Nicholson also thinks the large size of the NASH market will leave “a lot of room for different therapeutic approaches.”

“There’s an awful lot of proof that needs to come out of clinical studies before the community really knows what is going to be the best mechanism overall,” he says. “Of course we’re backing our horse, but we’re backing it with what we think is an intelligent approach for treating the disease.”

Pfizer Venture Investments and Lightstone Ventures led the $43 million round, which was oversubscribed and included participation from all of Nimbus’s Series A backers—including Atlas, SR One, Lilly Ventures, and Gates. Nimbus has now raised some $67 million in venture cash since its inception. It’s also got three other preclinical programs in development for certain cancers and inflammatory diseases.

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