PureTech-founded Seaport Therapeutics has raised $225m in a Series B financing round to support the development of new prodrug treatments for psychiatric disorders. 

Seaport plans to use the new funds to push forward its pipeline of experimental drugs, including its most advanced candidate, SPT-300, which is being advanced into a Phase IIb trial for major depressive disorder.

SPT-300 is an oral prodrug of brexanolone, a neurosteroid compound with known anti-depressant effects. Topline results from Seaport’s SPT-300 Phase IIa proof-of-concept trial were reported in November 2023, where the study met its primary endpoint of salivary cortisol response.  

The financing was led by General Atlantic, with backing from several other major investors such as T Rowe Price, Foresite Capital, and Goldman Sachs. The latest funding comes after the company’s launch in April 2024, when it secured $100m in initial funding from founding investors ARCH Venture Partners, Sofinnova Investments, Third Rock Ventures, and co-founder Puretech Health.  

The funding will also support Seaport’s Glyph technology platform, which helps drugs be absorbed more efficiently by using the body’s lymphatic system. This platform could improve the delivery of drugs that have a low bioavailability, or have side effects such as liver enzyme elevations or hepatoxicity, says the company.  

The company has several other candidates in its pipeline, including SPT-320, an experimental prodrug of agomelatine being advanced into Phase I studies to treat generalised anxiety disorder (GAD). By leveraging Glyph, SPT-320 bypasses liver first-pass metabolism, allowing for lower dosing and reduced liver exposure. Seaport is also developing SPT-348 for mood and neuropsychiatric disorders and has several preclinical programmes under its belt. 

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Prodrugs are medications that start as inactive or less active, and once inside the body, are converted into the active form, usually through natural processes involving enzymes. Prodrugs can be used to enhance drug delivery, minimise side effects, and improve drug solubility and oral bioavailability.  

In the announcement accompanying the financing, Seaport’s founder Steve Paul said: “The development of important new neuropsychiatric medicines is often halted due to poor drug-like properties or unacceptable tolerability, challenges that our Glyph platform can now uniquely address.”  

The potential of prodrugs was recently in the spotlight in the case of xanomeline, which initially faced tolerability challenges, but once resolved, was approved Cobenfy (formerly KarXT) for schizophrenia. Xanomeline helps reduce symptoms of schizophrenia, but it can cause unpleasant side effects that include nausea and sweating. Trospium was added to the drug to block these side effects while still allowing xanomeline to work in the brain. Now, Cobenfy is expected to earn $2.99bn in revenues by 2030, as per GlobalData analysis.  

GlobalData is the parent company of Pharmaceutical Technology.

New York-based Terran Biosciences is taking it a step further by developing two prodrug versions of Cobenfy. Terran aims to curb issues surrounding medication adherence by optimising its dosing schedule to a more convenient once-daily oral regimen (TerXT), and a multi-month injectable (TerXT LAI).