🔒New Haven biotech Trevi Therapeutics builds billion-dollar valuation around lone late-stage cough drug

Trevi Therapeutics is one of the largest publicly traded bioscience firms in New Haven. Yet, unlike better-known Elm City life science companies such as Alexion Pharmaceuticals and Biohaven Ltd., Trevi has just one drug in its pipeline: Haduvio (oral nalbuphine ER), a treatment in development for chronic cough. One might assume having only one drug in the pipeline would be a turnoff to investors, but that was disproven last June, when Trevi announced it had raised $115 million via an underwritten public offering. The capital raise was “five times oversubscribed,” said Trevi co-founder and CEO Jennifer Good, “so it’s a lot of money out there in biotech, if you have good data.” Trevi is betting it does. Last June, the company reported positive Phase 2b results for Haduvio, with patients showing “statistically significant reductions in 24-hour cough frequency” across all dose levels tested after six weeks of treatment. Good, in a recent interview, said Haduvio “has worked on everything we’ve looked at.” That momentum helps explain why Trevi has raised more than $250 million since its 2011 founding and now has a market capitalization of about $1.34 billion. Trevi has also benefited from a competitive opening: It’s currently the only company developing a drug aimed at treating chronic cough. “Everything else in that space has failed,” Good said. “So we’re sort of sitting alone in this very big market.”

Treating IPF

The market for a drug to treat chronic cough is large, with millions of patients in the United States alone. But Trevi’s first commercial target is far narrower: roughly 150,000 patients with idiopathic pulmonary fibrosis (IPF), a rare disease that causes progressive lung scarring for reasons doctors still don’t fully understand. The scarring can trigger the brain to send a constant “cough signal” to the lungs, Good said — even though coughing can further damage already fragile tissue. And unlike a cold, there’s no mucus to clear. “You physically cough thousands of times,” she said. “People break ribs. They’re punching holes in their lungs.” IPF typically affects older men and is generally fatal due to the declining lung function it causes. Once someone is diagnosed with IPF, Good said, “it’s about a three- to five-year lifespan.” Other diseases can also scar the lungs, including bronchiectasis and rheumatoid arthritis. For Trevi, the underlying diagnosis matters less than the common symptoms. “If you have fibrotic lungs and coughing, you’re our patient,” she said. “We’re trying to treat that.”

Good said the broader group of lung-scarred patients totals about 228,000 nationwide, with most treated at roughly 80 specialized care centers — a dynamic that could let Trevi commercialize the drug with a lean sales force of about 50 representatives. Trevi — located on the 16th floor of 195 Church St., across from the New Haven Green — currently employs 35 people.

A $3B to $5B drug

Beyond that smaller group of lung-scarred patients, there are an estimated 2 million to 3 million people with refractory chronic cough — a persistent, unexplained cough that often begins after a viral infection but doesn’t respond to treatment. “They cough all the time, and if you’ve ever had a viral cough for a long time, you know how everything triggers it,” Good said. “You smell perfume, or you walk outside and you break into these big coughing fits.” One patient in Trevi’s drug trial last year coughed “3,500 times a day,” she said. “They don’t cough at night (while asleep), because it’s all neurological; they only cough during the day,” Good said. “They can’t go anywhere because it’s really disruptive.” Other drugmakers, including Boehringer Ingelheim, have tried to develop chronic cough treatments, but their efforts have failed in clinical trials, Good said. “So, by the time we got our data, everything else had failed and gone away,” she said. “We looked around and we were the only ones left.” With a large patient population and no existing effective therapy, Good said Haduvio “has the ability to be a $3 billion to $5 billion drug. It’s really a big opportunity with no competition.”

The founding

Trevi’s progress with Haduvio reflects the long-term vision of its co-founders, Good and Dr. Thomas Sciascia, the company’s chief science officer. Both previously worked at New York-based specialty drug development company Penwest Pharmaceuticals. Good, a Pacific Lutheran University business graduate, started her career in banking before holding senior finance roles at Penford Products, a Colorado-based chemical company. She later joined Penwest as chief financial officer and spent nearly 15 years there, including her final five as president and CEO. Penwest had a strategic partnership with Endo Pharmaceuticals, a generic drugmaker that ultimately acquired Penwest and its pain medication Opana ER in 2010 for about $168 million. At the time, Penwest was also developing what would later become Haduvio — a drug Good and Sciascia believed had far greater potential than Endo did. Good said Endo didn’t plan to pursue the drug’s development. “So (Sciascia) and I bought it out with personal money and started it literally at our kitchen tables,” she said, adding that Endo’s board also provided some angel investment funding. Good emphasized that while Haduvio falls within the opioid category, it’s a “mixed agonist” — a type of opioid drug that is not addictive in the way oxycodone is. “This drug we have was designed to basically get away from addiction,” she said. Good said she and Sciascia were drawn to the compound because it offered the possibility of opioid-like efficacy without the downside. “Tom and I were interested in this compound because we were hoping you’d get the efficacy of opioids without the baggage of addiction,” she said.

Phase 3

So far, Trevi’s clinical results have supported that early optimism. Just as importantly, Haduvio has been developed as a twice-daily oral drug, making it easier for patients to take than more complex therapies. Physicians who treat IPF patients say chronic cough remains one of the most difficult symptoms to manage. Philip Molyneaux, a professor of pulmonary medicine at Royal Brompton Hospital in London and an investigator in the Haduvio trials, said the condition is a persistent challenge in clinical care. “Chronic cough continues to represent a major unmet need in the care of my patients with IPF and imposes a significant burden on their day-to-day lives,” Molyneaux said. He said Haduvio’s trial results are encouraging because they show patients are coughing less and also feel better, supporting continued study of the drug. Trevi is preparing to launch a pivotal Phase 3 trial focused on IPF patients, which the company expects to begin in the first half of this year. As of the end of the third quarter, Trevi reported $194.9 million in cash, cash equivalents and marketable securities. Good said that gives the company ample resources to fund the Phase 3 program, though she expects Trevi will eventually need to raise additional capital and expand its workforce as it moves closer to commercialization. If the Phase 3 trials are successful, the next step would be seeking approval from federal regulators — a process that concerns Good amid ongoing leadership turnover at the U.S. Food and Drug Administration. She said the FDA has changed directors of its Center for Drug Evaluation and Research six times over the past year. “When you’re in a five- to 10-year (drug) development program, you can’t have six different leaders because they all have different views,” she said. “For companies like us, it’s really frustrating, because it’s really difficult to get solid advice that you’re confident is going to stick.” Good said she also worries about politics influencing regulatory decision-making. “I do have a lot of worries about it,” she said. “I think anytime politics creeps into scientific discussions, that’s probably not a good thing.” Ultimately, Good said her confidence rests with the drug itself and the relief it could bring to patients who currently have no effective treatment options. Helping people whose constant coughing is “ruining their day-to-day lives,” she said, “is really motivating.”