BOSTON — October 7, 2026
Seaport Therapeutics announced that the first patient has been dosed in a Phase 2a clinical trial evaluating GlyphAgo (SPT-320) in adults with generalized anxiety disorder (GAD) and co-morbid sleep disturbance. The six-week trial, being conducted in Australia, is designed to establish proof-of-pharmacology by assessing the effects of GlyphAgo on sleep and anxiety symptoms. The study represents an important clinical development milestone for Seaport as it advances the oral prodrug toward potential treatment of GAD. GlyphAgo is being developed using the company’s proprietary Glyph platform, which is designed to improve the delivery and exposure of agomelatine while reducing first-pass liver metabolism. Seaport expects to report topline Phase 2a data in early 2028 and plans to initiate a global Phase 2/3 study in GAD during the first half of 2027.
GlyphAgo Targets Sleep and Anxiety Symptoms
The Phase 2a study will enroll patients with GAD and sleep disturbance and randomly assign participants in a double-blind design to one of two daily GlyphAgo dose levels: 16 mg/day, equivalent to approximately 5 mg of agomelatine, or 32 mg/day, equivalent to approximately 10 mg. The primary focus is to evaluate pharmacologic effects on sleep using patient-reported measures including the Insomnia Severity Index (ISI) and EEG-based assessments of sleep architecture. Additional assessments will examine anxiety severity using the Hamilton Anxiety Scale (HAM-A), overall illness severity through the Clinical Global Impression-Severity scale, as well as safety, tolerability and pharmacokinetics. The trial is intended to generate clinical evidence on whether GlyphAgo can produce relevant agomelatine exposure and affect sleep and anxiety-related measures in patients with GAD.
Phase 1 Data Support GlyphAgo Development
Seaport’s decision to advance GlyphAgo into Phase 2a is supported by Phase 1 data in healthy volunteers, in which the candidate demonstrated a statistically significant 6.8-fold increase in bioavailability compared with unmodified agomelatine. The result exceeded the program’s prespecified two-fold target. After seven days of once-daily dosing, the 16 mg and 32 mg GlyphAgo doses achieved therapeutically relevant agomelatine exposures while using substantially lower amounts of the active drug than the approved 25 mg dose of unmodified agomelatine. Seaport also reported substantially lower inter-subject variability, with geometric coefficient of variation for agomelatine exposure approximately 10-fold lower than that observed with 25 mg agomelatine. In the Phase 1 study, GlyphAgo was well tolerated, with no serious or severe adverse events, liver-related adverse events, or clinically significant changes in liver-related laboratory parameters reported.
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Glyph Platform Designed to Reduce Liver Exposure
GlyphAgo is an oral prodrug of agomelatine designed to use the intestinal lymphatic system for absorption and bypass first-pass hepatic metabolism. Seaport believes this approach can improve oral bioavailability while achieving therapeutically relevant systemic exposure at lower doses and reducing liver exposure. Agomelatine is a clinically validated MT1/MT2 melatonin receptor agonist and 5-HT2C receptor antagonist that is approved for GAD in Australia and for major depressive disorder in Australia and the European Union. The company is developing GlyphAgo to potentially address limitations associated with unmodified agomelatine, including low bioavailability and hepatic considerations. Beyond the ongoing Phase 2a study, Seaport plans to begin a global randomized, double-blind, placebo-controlled Phase 2/3 trial in GAD during the first half of 2027, with topline results expected by the end of 2028. The company’s clinical strategy positions GlyphAgo as a potential next-generation oral treatment for patients with anxiety and associated sleep disturbance.
Source::Seaport Therapeutics,, press release
