Boston — Seaport Therapeutics, Inc. said repeat dosing of GlyphAgo showed favorable safety, tolerability and pharmacokinetics in the multiple-ascending dose portion of a Phase 1 proof-of-concept trial in healthy volunteers.
Seaport, a clinical-stage therapeutics company developing neuropsychiatric medicines, said the data support planned advancement of GlyphAgo into two parallel Phase 2 trials in patients with generalized anxiety disorder.
GlyphAgo, also known as SPT-320, is a Glyphed oral prodrug of agomelatine. The company said seven-day dosing achieved therapeutic exposures of agomelatine at doses projected to avoid liver enzyme elevations and reduce or eliminate the need for liver function testing, which has limited agomelatine’s clinical use.
The company said GlyphAgo AUC0-24 and Cmax increased dose-dependently over the range of doses studied. Agomelatine exposures following GlyphAgo administration in the multiple-ascending dose portion were consistent with data from the single-ascending dose and crossover portions of the trial. There was no unmodified agomelatine arm in the multiple-ascending dose portion.
Across all dose levels evaluated, GlyphAgo was well tolerated, with no serious or severe adverse events, no liver-related adverse events and no clinically significant changes in liver-related laboratory parameters, Seaport said.
“We are enthusiastic about the data from our Phase 1 program for GlyphAgo, where we’ve now observed consistent safety, tolerability, and PK across all cohorts,” said Daphne Zohar, Co-Founder and Chief Executive Officer of Seaport Therapeutics. “We believe these results substantially derisk our future clinical development approach and strengthen the differentiated profile of GlyphAgo. The complete Phase 1 data package further validates our Glyph platform and supports the advancement of GlyphAgo into two parallel Phase 2 trials as we work to bring a new treatment option to patients with generalized anxiety disorder who have not had a new medicine approved in almost 20 years.”
The Phase 1 proof-of-concept trial included 174 participants and evaluated the safety, tolerability and pharmacokinetics of GlyphAgo, as well as its pharmacokinetics compared with agomelatine alone. The trial included single-ascending dose and multiple-ascending dose cohorts, along with a crossover portion that included food-effect and within-participant comparisons between GlyphAgo and agomelatine.
In previously reported crossover results, GlyphAgo showed a 6.8-fold increase in agomelatine bioavailability compared with orally administered unmodified agomelatine. The company said GlyphAgo also showed significantly lower pharmacokinetic variability compared with unmodified agomelatine.
Seaport said the crossover portion included participants taking estrogen-containing oral contraceptives, which are known to increase agomelatine exposure because of liver drug-drug interaction. GlyphAgo exposure was unaffected by oral contraceptives, further supporting its ability to bypass first-pass liver metabolism, the company said.
In a separate single-ascending dose portion of the trial, in which no participants were taking oral contraceptives, GlyphAgo showed a 9.6- to 14.5-fold increase in dose-normalized exposure compared with agomelatine.
Seaport expects to initiate a Phase 2a proof-of-pharmacology trial in the second half of 2026. The randomized, double-blind trial will evaluate two dose levels of GlyphAgo and assess its potential effects on sleep, including objective measures of sleep architecture, in patients with generalized anxiety disorder and sleep disturbance. Topline data are expected in early 2028.
The company also expects to begin a Phase 2b trial of GlyphAgo in the first half of 2027. The randomized, double-blind, placebo-controlled, potentially registration-enabling trial will evaluate the efficacy and safety of GlyphAgo in patients with generalized anxiety disorder, with topline data expected by the end of 2028.
Seaport said GlyphAgo is designed to enhance lymphatic absorption and avoid first-pass liver metabolism, increasing oral bioavailability while reducing liver exposure. The company said the approach could enable agomelatine exposure levels considered effective in generalized anxiety disorder at a lower dose.
