Even if a depression treatment addresses a known and validated target, its commercial potential may be limited by dosage and safety limitations. Seaport Therapeutics’ medicines use new delivery approaches to overcome these limitations. The startup launched on Tuesday with $100 million in funding.
Boston-based Seaport was founded by PureTech Health, a company that typically creates startups around platform technologies. One notable example is Karuna Therapeutics, a neuropsychiatric drug developer. The company grew into a publicly traded company developing lead drugs with new approaches to schizophrenia, which he eventually spun out of PureTech. Last year, Bristol-Myers Squibb signed a $14 billion deal to acquire Karna, whose schizophrenia drug is currently under FDA review.
Steven Paul, former CEO of Karuna, chairs Seaport’s board of directors. The startup’s technology platform, his Glyph, leverages the lymphatic system for drug delivery. The company says its drug is absorbed through the body’s lymphatic system and transported into circulation, similar to dietary fat.
Glyph’s research was published in the Journal of Controlled Release in 2021 and Frontiers in Pharmacology in 2022. The technology was originally developed at Monash University in Australia. In 2017, PureTech licensed the platform and continued development in a subsidiary called Glyph Biosciences. This company later merged with his other PureTech subsidiaries, and together he produced a pipeline that included Seaport’s two most advanced drug candidates.
Seaport’s SPT-300 is a prodrug, a substance that is pharmacologically inactive until it is converted into an active therapeutic agent in the body. SPT-300 is an oral prodrug of allopregnanolone, a neurosteroid that modulates GABA-A receptors in the body. Sage Therapeutics has already shown that these receptors can be successfully targeted with Zurresso, its FDA-approved postpartum depression drug. Although Zurresso is chemically identical to allopregnanolone, it requires a continuous infusion that lasts for 60 hours.
Sage has an oral alternative with sage, a small molecule that similarly modulates GABA-A receptors. However, the FDA approved Zurzuvae last year only for postpartum depression, not the larger indication the company had sought for major depressive disorder. Regulators told Sage that further clinical trials were needed to prove efficacy in this indication.
According to Seaport, SPT-300 (called LYT-300 during development within PureTech) retains the activity and potency of endogenous allopregnanolone, but in an oral dosage form; “It has the potential to capture a wide range of natural biological responses.” The company added that the prodrug has demonstrated proof of concept in a validated clinical model of anxiety in healthy volunteers. This drug is currently in mid-stage development as a treatment for major depression accompanied by anxiety.
“We believe that delivering a proven mechanism of natural allopregnanolone through LYT-300’s innovative oral administration approach is an advancement that has the potential to have a truly meaningful impact for patients. ” PureTech CEO Daphne Zohar said in a letter to investors included in the company’s 2022 annual report. report. “LYT-300 also has the potential to unlock a class of drugs that target GABA-A receptors, providing a rapid onset of action for a variety of conditions including depression, anxiety, and other conditions that currently remain the standard of care. may offer more benefits than others.”
Seaport says Glyph will enable the development of oral medications with better side effect profiles. This technology also avoids high first-pass metabolism, where metabolism of the drug at specific locations in the body reduces the amount of active drug available to reach the circulation. This ability is key to the Seaport program SPT-320, a prodrug of agomelatine. The drug agomelatine is approved as an antidepressant in Europe and Australia, but not in the United States. Agomelatine is associated with a high risk of liver damage due to the high metabolism of the drug within the organ. Seaport said SPT-320 uses Glyph to avoid first-pass metabolism in the liver, which may result in lower doses needed and the need to monitor patients’ liver function. . The Seaport program is in preclinical development for generalized anxiety disorder.
The third Seaport program, SPT-348, is a non-hallucinogenic neuroplastogen prodrug. This discovery-stage research could lead to new treatments for mood and other neuropsychiatric disorders. SPT-348 utilizes Glyph to improve certain properties of the drug, such as how it interacts with the body and its tolerability. Other programs in discovery and preclinical development are addressing goals that remain undisclosed.
“Given the historically low success rate in neuropsychiatric drug development, precisely resolving the previous limitations of clinically validated mechanisms will improve the probability of success and significantly accelerate development.” Paul, who is also a co-founder of Sage, said in a prepared statement. statement.
Seaport’s Series A funding was co-led by Arch Venture Partners and Sofinnova Investments, along with Third Rock Ventures and PureTech Health. In conjunction with the financing, Seaport announced the appointment of Mr. Zohar as Seaport’s CEO and director.
Image: Alexei Morozov, Getty Images
