Even when melancholy medication handle identified and validated targets, their industrial potential might be constrained by dosing or security limitations. Seaport Therapeutics’ medication use a novel supply strategy to beat these limitations. The startup launched on Tuesday, backed by $100 million in financing.
Boston-based Seaport was fashioned by PureTech Well being, an organization that creates startups, sometimes round a platform expertise. One notable instance is neuropsychiatric medication developer Karuna Therapeutics, which grew and finally spun out of PureTech as a publicly traded firm with a lead drug taking a novel strategy to schizophrenia. Bristol Myers Squibb final yr struck a $14 billion deal to amass Karuna, whose schizophrenia drug is at the moment underneath FDA evaluation.
Former Karuna CEO Steven Paul is chair of Seaport’s board of administrators. The startup’s expertise platform, Glyph, leverages the lymphatic system for drug supply. The corporate says its medication are absorbed like dietary fat by the interior lymphatic system after which transported into circulation.
Glyph analysis was revealed in 2021 within the Journal of Managed Launch and in 2022 in Frontiers in Pharmacology. The expertise was initially developed at Monash College in Australia. In 2017, PureTech licensed the platform, which it continued to develop in a subsidiary named Glyph Biosciences. That firm was later merged with different PureTech subsidiaries, which collectively produced a pipeline that features Seaport’s two most superior drug candidates.
Seaport’s SPT-300 is a prodrug, a substance that’s pharmacologically inactive till changing into an lively therapeutic contained in the physique. SPT-300 is an oral prodrug of allopregnanolone, a neurosteroid discovered within the physique that regulates GABA-A receptors. Sage Therapeutics has already proven that these receptors might be efficiently drugged with Zulresso, the biotech’s FDA-approved post-partum melancholy drug. Whereas Zulresso is chemically similar allopregnanolone, it requires a burdensome 60-hour steady infusion.
Sage does have an oral different with Zurzuvae, a small molecule that additionally regulates GABA-A receptors. However FDA approval of Zurzuvae final yr coated solely post-partum melancholy, and never the a lot bigger main depressive dysfunction indication the corporate additionally sought. The regulator instructed Sage extra medical testing is required to display effectiveness on this indication.
Based on Seaport, SPT-300 (referred to as LYT-300 throughout its growth inside PureTech) retains the exercise and efficiency of endogenous allopregnanolone, however in an oral type that “has the potential to seize the breadth of the pure organic response.” The corporate added that this prodrug demonstrated proof-of-concept in a validated medical mannequin of tension in wholesome volunteers. The drug is at the moment in mid-stage growth for treating main melancholy with nervousness.
“We consider providing the confirmed mechanism of pure allopregnanolone by way of the modern orally administered strategy of LYT-300 represents an development that would have a very significant affect for sufferers,” PureTech CEO Daphne Zohar wrote in a letter to buyers included within the firm’s 2022 annual report. “LYT-300 can also unlock the category of medicines concentrating on GABA-A receptors, which has the potential to supply benefits over present requirements of care, reminiscent of speedy onset of motion, for a spread of circumstances together with melancholy, nervousness, and others.”
Seaport says Glyph permits it to develop oral medication with higher facet impact profiles. The expertise additionally circumvents excessive first-pass metabolism, during which metabolism of a drug at a selected location within the physique reduces the quantity of lively drug obtainable to succeed in circulation. That functionality is essential to the Seaport program SPT-320, a prodrug of agomelatine. Agomelatine medication have been authorized as antidepressants in Europe and Australia, however not the U.S. Agomelatine is related to a greater danger of liver damage because of excessive metabolism of the drug within the organ. Seaport says SPT-320 makes use of Glyph to bypass first-pass liver metabolism, which might in flip require decrease dosing and remove the necessity to monitor liver perform in sufferers. This Seaport program is in preclinical growth for generalized nervousness dysfunction.
A 3rd Seaport program, SPT-348, is a prodrug of a non-hallucinogenic neuroplastogen. This discovery-stage analysis might result in a brand new therapy for temper and different neuropsychiatric issues. SPT-348 leverages Glyph to enhance sure properties, reminiscent of how the drug interacts with the physique in addition to its tolerability. Different applications in discovery and preclinical growth handle targets that stay undisclosed.
“Given the traditionally low success charges inside neuropsychiatric drug growth, exactly fixing the earlier limitations of clinically validated mechanisms improves the chance of success and permits us to considerably speed up growth,” Paul, who was additionally a Sage co-founder, mentioned in a ready assertion.
Seaport’s Sequence A financing was co-led by Arch Enterprise Companions and Sofinnova Investments together with Third Rock Ventures and PureTech Well being. Together with the financing, Seaport introduced the appointment of Zohar as Seaport CEO and board member.
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