Seaport Therapeutics said today it has closed on an oversubscribed $225 million Series B financing, with the proceeds set to be used toward enhancing its Glyph™ technology platform, which has shown clinical proof-of-concept, and advancing through clinical milestones with its pipeline of Glyph-based neuropsychiatric therapies.
The financing lifts the total capital raised by Seaport to $325 million since the company launched in April with an oversubscribed $100 million Series A financing.
Seaport isn’t saying how long of a financial runway it now has as a result of the Series B, while it finalizes financing details. “It’s definitely enough time to start and run a few important clinical studies,” Daphne Zohar, founder and CEO of Seaport Therapeutics, told GEN Edge.
Seaport’s most advanced therapeutic candidate is the PureTech-developed SPT-300 (formerly LYT-300), an oral prodrug of the endogenous neurosteroid allopregnanolone that is being developed to treat anxious depression. Allopregnanolone has shown therapeutic benefit in a range of neuropsychiatric conditions, but it is only approved as an intravenous infusion, which has limited the scope of its clinical use.
SPT-300 is one of three disclosed pipeline candidates of Seaport, all based on the Glyph platform. Glyph is designed to enable and enhance oral bioavailability, avoid first-pass metabolism, and reduce liver enzyme elevations or hepatotoxicity and other side effects, with the aim of advancing clinically active drugs that were previously hindered by those limitations.
“What Glyph does is essentially cloak a small molecule so that it looks to the body like a dietary fat and is now absorbed by the body as if it were a dietary fat. Glyph allows it to efficiently enter circulation and bypass first pass metabolism,” explained Michael Chen, PhD, Seaport’s co-founder and chief scientific officer.
“There are all these drugs, especially but not just in CNS, that are very potent, have clinical activity, but just have issues related to that first pass—either bioavailability, they can’t get in, they have poor PK [pharmacokinetic] properties. Sometimes they have adverse events, side effects, liver enzyme increases, or hepatotoxicity, all driven by their normal route of absorption,” Chen added. “Glyph allows us to shift that route.”
Enabling registration
Using the Glyph platform, Seaport said, SPT-300 has retained the activity and potency of endogenous allopregnanolone in an oral form and could potentially capture the breadth of the natural biological response. Seaport plans to advance SPT-300 into a Phase IIb clinical trial assessing the drug in patients with major depressive disorder with or without anxious distress.
The Phase IIb study is set to begin shortly though Seaport isn’t saying when. The trial would enroll approximately 300 patients and be designed to potentially serve as one of two registration-enabling studies, Seaport said. SPT-300 has shown proof-of-concept in a validated clinical model of anxiety in healthy volunteers during a Phase IIa trial.
Seaport’s pipeline also includes SPT-320 (formerly LYT-320), a novel prodrug of agomelatine being advanced into Phase I studies to treat Generalized Anxiety Disorder (GAD). SPT-320 uses the Glyph platform to bypass first-pass metabolism by the liver and thus has the potential to lower its effective dose, reduce liver exposure and eliminate the need for liver function monitoring that has held back agomelatine.
The reduction in dose could eliminate the need for liver function monitoring that has previously held back agomelatine’s development in GAD, according to Seaport, which adds that SPT-320 could become the first drug applying a new mechanism for treating GAD in decades.
“What we want to be able to show is that the Glyph platform helps address something that’s not really a huge issue, but it’s an issue that’s held back really the broad development of aglomelatine. And that is that aglomelatine is a little bit rough on the liver,” Zohar said.
Seaport aims to address that by delivering the same exposure to the drug with a dose that’s lower yet still effective, thus reducing side effects.
“It’s kind-of like a race between the liver and the brain,” Chen analogized. “And if you need a lot of drug to hit the liver in order to get a certain amount to hit the brain, then what Glyph does can give the brain a head start in that—so, less drug hitting the liver, more drug getting to the brain.”
Avoiding the “trip”
Another Seaport pipeline candidate, SPT-348, is a prodrug of a non-hallucinogenic neuroplastogen that is under development to treat mood and other neuropsychiatric disorders. SPT-348 leverages Glyph to create a potential first-in-class treatment with improved pharmacokinetics and tolerability compared to conventional psychedelics.
“The idea is to harness the activity and the pharmacology of psychedelics, which have shown some intriguing efficacy, but have some things holding them back, including the trip itself and all the baggage that comes along with that,” Zohar said. “We’ve identified a molecule that has much of the same pharmacology and activity. It causes neuroplasticity but does not cause a trip.”
“Our belief is that with potent pharmacology, with neuroplasticity, you don’t need the experience of the trip itself,” Zohar added. “That’s the hypothesis we’re going to be testing in [SPT-348], even though it’s been in people and has been shown not to have that trip.”
Beyond the three candidates, Seaport said, is a pipeline with an undisclosed “multiple” discovery and preclinical programs underway—including an oral CBD program that Seaport has previously disclosed, which Zohar said has “pretty far advanced preclinically.”
Seaport reasons that its Glyph-based candidates can help it establish a beachhead in the neuropsychiatric drug space, which has revived after years of scant activity following large-scale acquisitions like that of the PureTech-founded Karuna Therapeutics, acquired for $14 billion by Bristol Myers Squibb in a deal completed in March; and AbbVie’s $8.7 billion purchase of Cerevel Therapeutics, completed in August.
“A lot of pharma companies are looking for the next obesity-like opportunity, and neuropsychiatry has those characteristics. That includes depression, but GAD is just as large in terms of the unmet need, the number of patients. And importantly, existing drugs have drawbacks that we might be able to address.”
Those drawbacks range from taking weeks to work, to showing only modest efficacy and, for many patients, tolerability issues such as sexual dysfunction and weight gain.
“There’s a very big opportunity,” Zohar said. “What’s also interesting about Glyph is that it’s not limited just to CNS. We can help other pharmaceutical companies solve issues like the ones that we’re addressing internally, such as oral bioavailability, high first pass metabolism, certain tolerability-related issues.”
While Seaport is focused on advancing its neuropsychiatry programs itself, Zohar said, it could partner with other companies on Glyph-based candidates in other therapeutic areas. By the time the neuropsychiatric candidates are ready to reach the market, Seaport reckons, it will either have grown large enough to launch them itself, or work with a pharma giant to do so.
Needing additional financing
Zohar said the Series A financing was needed to spin out Seaport and become independent. “But in order to run major late-stage studies in depression, it was clear that we would need additional financing,” she recalled. “It wasn’t that we needed [the Series B] right away. It wasn’t like we spent a lot of the $100 million. But the idea of having that additional funding in place to be able to complete these studies is one that we were very open to.”
Fortunately for Seaport, the Series A sparked enough interest in the company among potential investors that it could be selective about which of them could join the Series B.
That financing was assembled by a syndicate of investors led by General Atlantic, a growth equity investment firm with $83 billion in assets under management.
“We are impressed with the team’s outstanding CNS clinical track record, as well as Seaport’s Glyph platform and innovative pipeline,” stated Brett Zbar, MD, managing director and global head of life sciences at General Atlantic. “The approach to clinical development and trial design demonstrates the deep neuropsychiatric expertise around the table, which we believe offers unique advantages that will contribute to Seaport’s success. We look forward to supporting the Company’s next phase of development.”
Participating with General Atlantic in the financing were funds and accounts advised by T. Rowe Price Associates, Foresite Capital, Invus, Goldman Sachs Alternatives, CPP Investments, and other new investors. Founding investors ARCH Venture Partners, Sofinnova Investments, Third Rock Ventures, and co-founder PureTech Health also participated in the round.
As the initial public offering (IPO) market improves, Seaport envisions a future in which it goes public.
“It definitely makes sense that the public markets would be the place for this company to grow,” Zohar said. “When and where and how we do that is not something we’ve finalized yet. But over time, that’s something that we definitely see on the horizon.”
Seaport is the eighth and latest of the “founded entities” companies to be created by PureTech Health. Zohar previously led PureTech, whose R&D effort created 28 therapies, of which three have received U.S. FDA clearance and European marketing authorization.
The most recent is Cobenfy™ (formerly KarXT®, xanomeline-trospium), a Karuna-developed antipsychotic, M1 / M4 muscarinic receptor agonist that received FDA approval on September 26 as a first-in-class treatment for adult schizophrenia.
The other two PureTech-developed therapies are Plenity®, a weight management aid to adults with excess weight or obesity; and EndeavorRx®, the first and only video game treatment for attention deficit hyperactivity disorder (ADHD) authorized by the agency.
Boston-based Seaport has a workforce of just over 20 employees: “Definitely one of the areas we’re building out is our clinical team, as we’re gearing up to conduct our studies,” Zohar said.
