Seaport Therapeutics Doses First Participant in Phase 1 Study of GlyphAgo for Generalized Anxiety Disorder

Seaport Therapeutics Doses First Participant in Phase 1 Study of GlyphAgo for Generalized Anxiety Disorder

By, Admin 15 September 2025

PureTech Health plc announced that its founded entity, Seaport Therapeutics, has dosed the first participant in a phase 1 study of GlyphAgo (SPT-320, Glyph Agomelatine). GlyphAgo is being developed to treat generalized anxiety disorder (GAD), one of the most common mental health conditions worldwide.

What is GlyphAgo?

  • A “Glyphed” oral prodrug of agomelatine
  • Uses Seaport’s proprietary Glyph platform to change how the drug is absorbed
  • Designed to:
    - Reduce liver exposure
    - Deliver therapeutic benefit at lower doses
    - Overcome dose-dependent liver risks that limit unmodified agomelatine

Agomelatine has shown clinical efficacy in four third-party randomized, placebo-controlled studies in GAD but has been restricted in use due to first-pass liver metabolism and related monitoring needs.

Why It Matters

  • Agomelatine’s proven efficacy: Effective as an anxiolytic and antidepressant; already approved for GAD in Australia and for depression in the EU and Australia.
  • Advantages over standard treatments: Lower risk of abuse potential, sexual dysfunction, and weight gain compared to SSRIs and benzodiazepines.
  • Problem: Over 90% lost to first-pass metabolism, requiring higher doses and causing liver enzyme elevations.
  • Solution with GlyphAgo: Redirects absorption to intestinal lymphatics, improving systemic exposure and reducing liver strain.

The Clinical Trial

  • Phase 1 proof-of-concept study will assess:
    - Safety
    - Tolerability
    - Pharmacokinetics
  • Goal: Show that therapeutic levels can be achieved at lower doses without liver enzyme increases.
  • Study design:
    - Multiple parts
    - Single- and multiple-ascending dose phases
    - Food-effect crossover portion
    - Combination of open-label and placebo-controlled arms

This is the second candidate from Seaport’s pipeline to advance into the clinic.

Expert View

“Anxiety disorders affect nearly 30% of adults in their lifetime, with GAD impacting ~100 million people worldwide. Yet in the U.S., no new drug class for GAD has been approved in decades. The key question is whether GlyphAgo can achieve effective exposure at lower doses, avoiding liver-related issues. If successful, it could redefine the treatment landscape for generalized anxiety disorder.”

  • Antony Loebel, Chief Medical Officer and President of Clinical Development at Seaport Therapeutics.

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