Boston — Seaport Therapeutics, a clinical-stage biopharmaceutical company focused on developing innovative neuropsychiatric medicines, presented new preclinical data on its lead candidate, SPT-320, at the Society of Biological Psychiatry (SOBP) Annual Meeting held April 24-26 in Toronto. SPT-320 is an oral prodrug of agomelatine currently in development as a novel treatment for generalized anxiety disorder (GAD).
The new data show that SPT-320 significantly enhances the delivery of agomelatine by improving its absorption and reducing its impact on the liver—a key limitation that has hindered broader use of agomelatine in treating GAD. The preclinical findings demonstrated that SPT-320 increased lymphatic transport of agomelatine to over 50 percent, compared to less than one percent for agomelatine administered alone. This shift in absorption from the liver to the lymphatic system substantially raised plasma levels of agomelatine, with more than a tenfold increase in systemic exposure observed in preclinical models.
Agomelatine, a melatonin receptor agonist and serotonin 2C receptor antagonist, is already approved for the treatment of generalized anxiety disorder in Australia and for major depressive disorder in both Australia and the European Union. Despite its proven efficacy, agomelatine’s clinical use has been limited by the drug’s rapid breakdown in the liver, where more than 90 percent of the unmodified compound is lost to first-pass metabolism. This metabolic process can lead to dose-dependent liver enzyme elevations, necessitating frequent liver monitoring for patients.
Seaport Therapeutics’ proprietary Glyph™ platform, which underpins the design of SPT-320, addresses this challenge by redirecting drug absorption toward the intestinal lymphatic system, bypassing the liver and mitigating risks associated with liver toxicity.
“We demonstrate, for the first time, that SPT-320 has the potential to deliver therapeutically relevant levels of agomelatine with a substantially lower dose, which could significantly reduce the impact on the liver while preserving the validated efficacy of agomelatine,” said Daniel Bonner, Ph.D., Co-Founder and Senior Vice President of Platform at Seaport Therapeutics. “These positive results further validate our Glyph prodrug platform and support initiating clinical development of SPT-320.”
The encouraging preclinical data provide the foundation for advancing SPT-320 into Phase 1 clinical trials, where Seaport will assess the safety, tolerability, and pharmacokinetics of the drug in humans. If successful, SPT-320 could offer a safer and more effective treatment option for patients with generalized anxiety disorder, potentially overcoming a longstanding hurdle in agomelatine’s clinical use.
