お知らせ • Jun 09
Seaport Therapeutics Reports Positive Multiple-Ascending Dose Data from Phase 1 Proof-Of-Concept Trial of Glyphago
Seaport Therapeutics announced positive data from the multiple-ascending dose (MAD) portion of its Phase 1 proof-of-concept clinical trial evaluating repeat dosing of GlyphAgo (SPT-320), a novel, Glyphed oral prodrug of agomelatine, in healthy volunteers. Repeat dosing of GlyphAgo demonstrated a safety, tolerability, and pharmacokinetic (PK) profile consistent with previously reported single-ascending dose (SAD) and crossover data, supporting its planned advancement of GlyphAgo into two parallel Phase 2 trials in patients with generalized anxiety disorder (GAD). Seaport expects to initiate a Phase 2a proof-of pharmacology trial in the second half of 2026. This randomized, double-blind trial of two dose levels of GlyphAgo is designed to demonstrate proof-of-pharmacology by characterizing the potential benefits of GlyphAgo on sleep, including objective measures of sleep architecture, in patients with GAD and sleep disturbance. Topline data from this trial are expected in early 2028. Seaport also expects to initiate a Phase 2b trial of GlyphAgo in the first half of 2027. This randomized, double-blind, placebo-controlled, potentially registration-enabling trial is designed to evaluate the efficacy and safety of GlyphAgo in patients with GAD. Topline data from this trial are expected by the end of 2028. The GlyphAgo program and the underlying Glyph platform were initially advanced at PureTech, applying the Company's strategy of identifying clinically validated pharmacology and overcoming key limitations through targeted innovation. The Glyph platform and related programs are now being advanced by PureTech's Founded Entity, Seaport Therapeutics. Repeat dosing of GlyphAgo confirms favorable safety, tolerability, and pharmacokinetics observed across the Phase 1 program, with no liver-related adverse events observed. New data demonstrate seven-day dosing of GlyphAgo achieved therapeutic exposures of agomelatine at doses projected to avoid liver enzyme elevations and reduce or eliminate the need for liver function testing. Results support dose selection and planned advancement into two parallel Phase 2 trials in patients with generalized anxiety disorder. The MAD data showed that seven-day dosing of GlyphAgo achieved therapeutic exposures of agomelatine at doses that reduce liver exposure and are projected to avoid liver enzyme elevations and reduce or eliminate the need for liver function testing that has previously limited agomelatine's clinical use. GlyphAgo AUC0-24 and Cmax increased dose-dependently over the range of doses studied, and agomelatine exposures following GlyphAgo administration in the MAD portion were consistent with data from the SAD and crossover portions of the trial. There was no unmodified agomelatine arm in the MAD 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 observed, further supporting observations from the SAD and crossover cohorts. The Phase 1 proof-of-concept trial, which included 174 participants, was conducted in multiple parts to evaluate the safety, tolerability, and PK of GlyphAgo and to compare the PK of GlyphAgo to agomelatine alone. The trial included SAD and MAD cohorts, as well as a crossover portion (including both food-effect and within-participant comparison between GlyphAgo and agomelatine), using both open-label and placebo-controlled designs. In the previously reported results from the head-to-head crossover portion of the trial, GlyphAgo demonstrated a 6.8-fold increase in bioavailability of agomelatine compared with orally administered unmodified agomelatine. GlyphAgo also showed significantly lower (10-fold) PK variability compared to unmodified agomelatine. The crossover portion included participants who were taking estrogen-containing oral contraceptives that are known to increase agomelatine exposure due to liver drug-drug interaction. In contrast, GlyphAgo exposure was unaffected by oral contraceptives, further supporting the ability of GlyphAgo to bypass first-pass liver metabolism. GlyphAgo demonstrated a 9.6 to 14.5-fold increase in dose-normalized exposure compared to agomelatine in a separate SAD portion of the trial in which no participants were on oral contraceptives. Seaport expects to initiate a Phase 2a proof-of pharmacology trial in the second half of 2026. This randomized, double-blind trial of two dose levels of GlyphAgo is designed to demonstrate proof-of-pharmacology by characterizing the potential benefits of GlyphAgo on sleep, including objective measures of sleep architecture, in patients with GAD and sleep disturbance. Topline data from this trial are expected in early 2028. Seaport also expects to initiate a Phase 2b trial of GlyphAgo in the first half of 2027. This randomized, double-blind, placebo-controlled, potentially registration-enabling trial is designed to evaluate the efficacy and safety of GlyphAgo in patients with GAD. Topline data from this trial are expected by the end of 2028. Seaport plans to present additional analyses from the Phase 1 trial at future upcoming scientific meetings. GlyphAgo is a novel, "Glyphed" oral prodrug of agomelatine, a clinically validated anti-anxiety and antidepressant that is approved for the treatment of GAD in Australia and Major Depressive Disorder in Australia and the European Union. Using Seaport's proprietary Glyph platform, GlyphAgo is designed to enhance lymphatic absorption and avoid first-pass liver metabolism, thereby enhancing oral bioavailability and reducing side effects. By leveraging an alternative absorption pathway via the intestinal lymphatic system used by dietary fats, GlyphAgo is designed to increase systemic exposure of agomelatine, enabling exposure levels of agomelatine that are effective in GAD but at a lower dose that reduces liver exposure and reduces or eliminates the need for liver function testing. Based on the data generated to date, Seaport believes GlyphAgo has the potential to become a leading treatment for GAD.