- CEO Daphne Zohar
- Total raised $100 million
- Headquarters Boston, MA
On Thursday, members of Seaport Therapeutics’ founding team watched from afar as their old company, Karuna Therapeutics, got its schizophrenia drug approved by the FDA.
Now they plan to do it again.
Seaport, with $100 million to its name when it officially launched this spring, is working on major depressive disorder, generalized anxiety, mood disorders and other neuropsychiatric conditions. It’s a tall feat in one of the hardest therapeutic areas for drug development but, if successful, could impact tens of millions of people.
The new company spent the last five years inside PureTech Health, which runs a hub-and-spoke model, incubating startups and then spinning them out into separate entities.
“Investors actually often prefer to invest in a focused story that is more like a traditional biotech even though these hub-and-spoke models have been very successful from an R&D perspective,” said Daphne Zohar, the former PureTech CEO and now Seaport’s chief executive.
Karuna generated an approximately 59x return for PureTech when it was sold to Bristol Myers Squibb for $14 billion. With Seaport, PureTech still holds more than 50% of the company, with more backing from blue-chip biotech investors like ARCH, Sofinnova Investments and Third Rock Ventures.
Its Karuna alums include Zohar and Steve Paul, a neuroscience drug veteran whose career also includes stops as a co-founder of Sage Therapeutics and a longtime researcher at Eli Lilly. Several board members from Karuna are back as well, including Sofinnova Investments’ Jim Healy, former Johnson & Johnson executive Denice Torres, and ex-AstraZeneca SVP David Wheadon. They’re betting that Seaport can be the latest high-profile story in the neurology and psychiatry drug development resurgence.
It’s also a personal mission for Zohar, whose mother has anxiety and teenage daughter has depression. There’s a large unmet need — and market — for the drugs as well.
“If you actually look back across depression drugs that have been approved, it’s hard to find one that hasn’t been a commercial success,” Zohar said.
Combined, mood and anxiety disorders are “as large as obesity, certainly in the US,” said Paul, who serves as Seaport’s chairman.
Like Karuna, Seaport is working on turning older assets into novel treatments. And like Sage’s postpartum depression medicines Zulresso and Zurzuvae, it’s working on allopregnanolone, a neurosteroid made by the hormone progesterone. It’s working on creating prodrugs of two additional compounds that have already been tested in humans.
“That’s what makes me excited, that we have a relatively high probability of technical success and that the timelines will also play out in the near term,” Paul said. In “the next two, three, four years, we’ll know a lot about all three programs,” he said on the startup’s first drugs.
One key part of Seaport’s technology is what it calls its Glyph platform, which it has used in the first three programs. It “cloaks” a small molecule “as if it were a dietary fat,” co-founder and chief scientific officer Michael Chen said. “Once you do that, it’s absorbed through the lymphatic system of the gut, which is this very high capacity fat-absorbing machine.” The key is that the medicine avoids the liver, otherwise the liver could “chew up 99% of the drug and leave essentially nothing for the bloodstream and nothing for the brain to take advantage of.”
The startup is preparing for a potentially registration-enabling Phase 2b of the allopregnanolone prodrug, SPT-300, in major depressive disorder, Zohar said. Its second asset, a prodrug of agomelatine, is further behind and being studied for generalized anxiety disorder. The third pipeline project, for mood and neuropsychiatric disorders, goes after a “rapidly-acting antidepressant in much the same way that the psychedelic drugs are believed to work, like LSD and psilocybin, but without that trip,” Paul said.
Psychiatry trials can be full of risk, and unexpected placebo results have taken down other drugs. The Seaport team is doing what it can to mitigate that.
“What we want to do, obviously, is execute these trials in a way very much like we did at Karuna, where we control placebo response rates, keep them manageable, where we recruit people that really should be in the trials, not professional patients — people that don’t have inflated ratings at baseline, and then all of a sudden get better,” Paul said.
And it sees neuropsychiatric conditions as, potentially, just the start. Its Glyph platform is “broadly applicable” to oncology, metabolic diseases and other therapeutic areas, Chen said.
The first three assets are “sort of the tip of the iceberg we feel for a revolution in CNS,” Chen said.
Key backers: ARCH Venture Partners, Sofinnova Investments, Third Rock Ventures, PureTech Health
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