Boston — Seaport Therapeutics, Inc. has dosed the first patient in a Phase 2a clinical trial evaluating GlyphAgo, or SPT-320, in adults with generalized anxiety disorder and sleep disturbance.
The six-week study, being conducted in Australia, is designed to assess the effects of GlyphAgo on sleep and anxiety symptoms and establish proof of pharmacology.
GlyphAgo is an oral prodrug of agomelatine developed using Seaport’s Glyph platform. Agomelatine acts on melatonin MT1 and MT2 receptors and the serotonin 5-HT2C receptor and has previously been studied in generalized anxiety disorder.
“Anxiety disorders affect more than 300 million people globally, and place a substantial burden on patients, families, and healthcare systems,” said Daphne Zohar, co-founder and chief executive officer of Seaport Therapeutics. “Patients with generalized anxiety disorder experience persistent anxiety symptoms that can make it difficult to carry out normal activities, and sleep disturbances are among the most frequently reported debilitating symptoms.”
Patients in the Phase 2a trial are being randomized in a double-blind design to receive one of two GlyphAgo doses: 16 mg per day, containing approximately 5 mg of agomelatine, or 32 mg per day, containing approximately 10 mg.
The study will evaluate sleep using patient-reported measures, including the Insomnia Severity Index, as well as EEG-based measurements of sleep architecture.
Additional endpoints include anxiety severity measured by the Hamilton Anxiety Scale, overall illness severity, safety, tolerability and pharmacokinetics.
Seaport expects topline data from the Phase 2a trial in early 2028.
“Agomelatine has been shown to improve sleep quality and sleep architecture without the daytime sleepiness seen with other therapies, making it a compelling candidate for patients with GAD and sleep disturbance,” said Daniel Bonner, Ph.D., co-founder and senior vice president of platform at Seaport Therapeutics.
“We designed GlyphAgo with our Glyph platform to bypass first-pass liver metabolism and address the bioavailability and hepatic limitations of unmodified agomelatine. We believe that GlyphAgo represents a potentially important treatment advance for people with GAD.”
In a Phase 1 trial in healthy volunteers, GlyphAgo demonstrated a statistically significant 6.8-fold increase in bioavailability compared with unmodified agomelatine.
After seven days of once-daily dosing, the 16 mg and 32 mg GlyphAgo doses produced therapeutically relevant agomelatine exposure and were generally well tolerated. The company reported no serious or severe adverse events, no liver-related adverse events and no clinically significant changes in ALT, AST or bilirubin.
GlyphAgo is designed to be absorbed through the intestinal lymphatic system, potentially allowing it to bypass first-pass liver metabolism and achieve therapeutic exposure at lower doses than unmodified agomelatine.
Seaport said the approach could potentially reduce liver exposure and the risk of liver enzyme elevations associated with agomelatine.
The company also plans to begin a global randomized, double-blind, placebo-controlled Phase 2/3 trial of GlyphAgo in generalized anxiety disorder in the first half of 2027. Topline data from that study are expected by the end of 2028.
