Amidst a “renaissance” of interest in neuropsychiatry, Seaport’s executive team is taking nothing for granted.
Seaport Therapeutics’ leadership knows a thing or two about the ups and downs of developing drugs for neuropsychiatry. So when it came time to develop a new company after their exit from Karuna Therapeutics, they stuck to what they knew: a proven mechanism and impeccable clinical trial design.
“At Seaport, there’s a lot of experience. A lot of scar tissue around the table from these studies,” CEO Daphne Zohar told BioSpace in an interview. She’s also joined at Seaport by former Karuna CEO Steven Paul, who serves as board chair.
Zohar said there’s maybe never been a better time to launch a new neuroscience company given what she called a “renaissance” of interest in the space. Karuna’s drug KarXT was approved last year to treat schizophrenia after the biotech’s acquisition by Bristol Myers Squibb tand will be marketed as Cobenfy.
But that major success was also sandwiched between two huge loses for neuropsychiatry last year: the failure of a rival drug from Cerevel, purchased by AbbVie for nearly $9 billion the same week BMS scooped up Karuna, and Sage Therapeutics’ unsuccessful attempt at getting a drug approved for major depressive disorder when it got the greenlight for postpartum depression.
The Seaport mission is personal for Zohar. She left her executive role at PureTech Health, an entity she founded that launched Karuna and Seaport, to become CEO of the new venture in part because she has family members with depression and anxiety.
“We felt like this platform and these programs really would benefit from a focused, dedicated effort. I’m personally also motivated to do something in the space,” Zohar said of the transition. Seaport brought along the Glyph platform, which uses the lymphatic system to bypass the liver, thereby reducing the dose needed and limiting potential liver toxicity while boosting oral bioavailability, according to the company.
The experienced team helped pull in Karuna’s early investors, so Seaport—a member of BioSpace’s NextGen Class of 2025—was able to raise funds twice in 2024: an initial $100 million at launch in April, then $225 million in series B cash in October. Zohar said the initial round was kept small as she remained at PureTech. Once Seaport was launched, the phone began ringing off the hook.
“The process . . . was really exciting, because it showed that investors really appreciate the potential in neuropsychiatric disorders,” Zohar said. “These are among the most widely prescribed drugs of all time.”
20/20 Vision
Despite widespread availability of options for depression and anxiety, there’s a massive unmet need, Seaport Chief Scientific Officer Michael Chen told BioSpace. These drugs can take a long time to work or come with debilitating side effects. Sometimes they just don’t work for every person.
“There are a lot of drugs . . . that work okay, and that leaves room for some of the mechanisms that we’re working on, which we feel could really improve on standard of care,” Chen said. “It’s interesting that even the drugs that don’t work great actually do well commercially,” which reflects the massive population in need of these types of drugs, he added.
Zohar said that translatability in the neuropsychiatry space has been tough, so Karuna’s team used a mechanism that had already been tested. Seaport is doing something similar and also taking lessons from the clinical trial design of KarXT to build out its clinical program.
“We have the benefit of looking back at other clinical studies that were done and I think that helps—a little bit of 20/20 hindsight in developing our studies going forward,” Zohar said. “If you’re starting fresh, you don’t have that benefit.”
Seaport’s lead asset is a prodrug of allopregnanolone dubbed SPT-300. The drug, without the Glyph modification, is a naturally occuring neurosteroid that has been used in the past to treat post-partum depression (PPD). You may know it by its other name, brexanolone, which was developed by Sage for the disorder. Sage has since withdrawn it from the U.S. market as of January 1. The problem with brexanolone was that it had to be infused over 60 hours, so it was only used in severe circumstances. With the Glyph platform, Seaport hopes to offer an oral version of the drug.
Besides the connection to brexanolone, that peer company has also helped teach Seaport ? some lessons about clinical execution in neuropsychiatry. Sage’s oral Zurzuvae has now been approved to treat PPD. The drug is fast acting, but Sage was unable to get an approval in MDD, which would have been a larger population. Partner Biogen has now offered to buy out the struggling company, whose shares have dropped by more than 90% over the past two years.
From Sage’s experience with Zurzuvae, Seaport has learned to be vigilant of a high placebo effect in clinical trials given the promise of early action, Chen explained. “There are tradeoffs in clinical trial design that go along with things like trying to capture the rapidly acting antidepressant effect,” he said. You would think monitoring early and often in this case would be helpful, but Chen said it’s actually important to back off and check in fewer times in the first weeks to ensure you’re not stoking a placebo effect.
SPT-300 will move into a Phase IIb study soon, Zohar said. Seaport is taking its time developing the trial to ensure it’s done right. Even with the success of Karuna, Zohar said she and her colleagues are not assuming everything will go as planned.
“We’re definitely not riding on the coattails of a positive,” she said. “If anything, if you have people counting on you, it makes you even more diligent and worried that you want to make sure you do everything well. So you have to really focus on all the details and not take anything for granted.”
