Daphne Zohar, Seaport Therapeutics founder and CEO, and a member of its board

Seaport Therapeutics, the eighth and latest of the “founded entities” companies to be created by PureTech Health, formally launched today with an oversubscribed $100 million Series A financing and a focus on developing neuropsychiatric therapies based on its Glyphtech platform.

Seaport said the financing will support rapid advancement of its clinical-stage pipeline, as well as further development of the Glyph platform, which has demonstrated clinical proof-of-concept.

Based on pioneering research by the research group of Christopher Porter, PhD, director of the Monash Institute of Pharmaceutical Sciences at Monash University, Glyph applies the lymphatic system’s natural lipid absorption and transport process to create new therapies by bypassing the liver—a process designed to enhance oral bioavailability, reduce the dose of new drugs, reduce first-pass hepatotoxicity, and provide novel composition intellectual property.

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.

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. In a Phase IIa clinical trial, SPT-300 showed proof-of-concept in a validated clinical model of anxiety in healthy volunteers.

Christopher Porter, PhD, director of the Monash Institute of Pharmaceutical Sciences at Monash University

Seaport’s pipeline also includes SPT-320 (formerly LYT-320), a novel prodrug of agomelatine being advanced to treat Generalized Anxiety Disorder. 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.

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.

SPT-348 is a newly disclosed program, Jefferies equity analyst Peter Welford, CFA, reported in a research note today.

Seaport added that it has additional “multiple” discovery and preclinical programs in development.

“We are dedicated to bringing first and best-in-class medicines to those that are suffering from depression, anxiety and other neuropsychiatric disorders,” said Daphne Zohar, Seaport’s founder and CEO, and a member of its board. “I’m excited to deliver on this mission along with a stellar team of senior leaders and investors.”

Leadership transition

Zohar is transitioning from her longtime role as founding CEO of PureTech and has agreed to step down from its board immediately—but will still serve PureTech as a senior advisor and observer to its board.

Succeeding Zohar as PureTech CEO as of today will be a PureTech senior executive, Bharatt Chowrira, PhD, who will continue to serve as a director on the company’s board. In addition to his board role, Chowrira has been PureTech’s president and chief business, finance, and operating officer, having served on PureTech’s senior management team since March 2017.

Before joining PureTech, he held leadership roles including CEO, COO, and general counsel in multiple biotech companies, including Auspex Pharmaceuticals, which was acquired in 2015 for $3.5 billion by Teva Pharmaceuticals, and Sirna Therapeutics, which was acquired in 2006 for $1.1 billion by Merck & Co., where Chowrira served as a vice president.

Eric Elenko, PhD, a PureTech co-founder and current chief innovation officer, has been promoted to president of PureTech, succeeding Chowrira in that role.

Under Zohar’s leadership, PureTech’s R&D effort created 28 therapies, of which two have received U.S. FDA clearance and European marketing authorization—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 authorized by the agency.

Under FDA review

A third PureTech-created therapy, KarXT (xanomeline-trospium), is under FDA review. KarXT is an antipsychotic, M1 / M4 muscarinic receptor agonist that would be a first-in-class treatment for adult schizophrenia. The FDA has set a September 26, 2024, target action date under the Prescription Drug User Fee Act (PDUFA) for the drug’s new drug application (NDA).

KarXT had been developed by Karuna Therapeutics, a neuro drug developer and PureTech-founded entity that has been acquired for $14 billion by Bristol Myers Squibb, in a deal completed March 18. Karuna’s CEO and chairman, Steven M. Paul, MD, is a founder of Seaport who has been named chair of its board.

Before Karuna, Paul served as president of research and development at Eli Lilly, where he oversaw the development of CNS drugs such as Zyprexa® (olanzapine) and Cymbalta® (duloxetine), as well as xanomeline, which during his tenure showed initial anti-psychotic and pre-cognitive properties.

Seaport’s Series A round was co-led by ARCH Venture Partners and Sofinnova Investments along with Third Rock Ventures and PureTech Health. PureTech—which disclosed it invested $32 million into Seaport—created Karuna in 2009, while ARCH, Sofinnova and Third Rock were among investors in that company.

Following the Series A financing, PureTech will hold a 61.5% equity ownership stake on a diluted basis, following the issuing of new shares.

Investors showed little response to the Seaport news, as shares of PureTech on the London Stock Exchange dipped 0.23%, from 215.50 pence to 215 pence.

“Seaport has the potential to meaningfully change the lives of patients with neuropsychiatric disorders,” said James Healy, MD, PhD, managing partner at Sofinnova Investments. “We’ve had the pleasure of knowing Steve and Daphne for a number of years, as one of the investors in Karuna, and we believe this team has the unique expertise to help solve the challenges of treating serious mental health conditions. I am eager to support Seaport as an investor and board member as the team continues to advance its clinical-stage pipeline of novel therapeutics.”

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