Seaport Therapeutics announced positive Phase 1 data for GlyphAgo (SPT-320), a novel oral prodrug of agomelatine for generalized anxiety disorder (GAD), with results showing consistent safety and tolerability across all trial cohorts. The multiple-ascending dose portion confirmed that 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—a major limitation of the unmodified medication.
The Phase 1 program, which included 174 participants, demonstrated remarkable improvements in the drug’s bioavailability profile. In head-to-head crossover studies, GlyphAgo showed a 6.8-fold increase in bioavailability of agomelatine compared with orally administered unmodified agomelatine, and achieved 9.6 to 14.5-fold higher dose-normalized exposure in a separate trial arm. The drug also showed significantly lower (10-fold) PK variability compared to unmodified agomelatine.
A particularly compelling finding emerged regarding drug interactions: while estrogen-containing oral contraceptives significantly increase agomelatine exposure through liver drug-drug interaction, GlyphAgo exposure was unaffected by oral contraceptives, further supporting its ability to bypass first-pass liver metabolism. Across all dose levels, 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 expects to initiate a Phase 2a proof-of-pharmacology trial in the second half of 2026, designed to characterize benefits on sleep in patients with GAD and sleep disturbance, with topline data expected in early 2028. A Phase 2b registration-enabling trial is expected to begin in the first half of 2027, with efficacy and safety results expected by the end of 2028.
This article is an AI-assisted summary. All facts and figures are drawn from the original report: https://www.biospace.com/press-releases/puretech-founded-entity-seaport-therapeutics-reports-positive-multiple-ascending-dose-data-from-phase-1-proof-of-concept-trial-of-glyphago-in-healthy-volunteers