Seaport Therapeutics To Present Phase 1 Clinical Data For GlyphAgo At The European College Of Neuropsychopharmacology Congress, October 10-13

Congress is taking place October 10-13, 2026, in Munich, Germany. The poster represents the first scientific presentation of data from the GlyphAgo Phase 1 program and provides detailed pharmacokinetic (PK) analyses supporting previously reported topline results and reinforcing GlyphAgo's differentiated profile.GlyphAgo is a novel, "Glyphed" oral prodrug of agomelatine designed to enhance lymphatic absorption and bypass first-pass liver metabolism. In the Phase 1 program, GlyphAgo demonstrated a statistically significant 6.8-fold increase in bioavailability of agomelatine compared to unmodified agomelatine and showed significantly lower (10-fold) PK variability. GlyphAgo achieved therapeutically relevant exposure of agomelatine at substantially lower doses that are designed to reduce liver exposure. Seaport believes this approach has the potential to reduce the risk of liver enzyme elevations and reduce the need for routine liver function monitoring that has historically limited agomelatine’s clinical use."The data presented at ECNP provide important clinical validation that our Glyph™ platform can meaningfully improve the pharmacokinetic profile of medicines historically limited by high first-pass liver metabolism," said Daniel Bonner, Ph.D., Co-Founder and Senior Vice President, Platform, at Seaport Therapeutics. "The increased exposure and markedly reduced inter-individual variability observed in the Phase 1 program are particularly compelling. More predictable drug exposure may translate into more consistent clinical outcomes for patients, further supporting the development of GlyphAgo as a potential treatment for generalized anxiety disorder."The completed multi-part Phase 1 proof-of-concept trial evaluated the safety, tolerability and pharmacokinetics of GlyphAgo in 174 healthy volunteers. The newly presented results include data from the multiple-ascending dose (MAD) portion and analyses supporting the absence of a food effect with GlyphAgo. The single- and multiple-ascending dose portions of the trial demonstrated dose-dependent increases in agomelatine exposure and showed no accumulation of exposure over seven days of dosing, supporting a consistent profile with repeat dosing. Additional analyses presented in the poster further characterize the substantially reduced PK variability observed with GlyphAgo, with variability in both AUC₀-₂₄ and Cmax substantially lower than with unmodified agomelatine. Specifically, in the SAD portion, PK variability (geometric CV%) observed in participants dosed with GlyphAgo ranged from 12.9% to 26.6% for AUC₀-₂₄ and from 17.1% to 50.5% for Cmax, compared with 200% and 217%, respectively, for unmodified agomelatine. In the crossover portion, PK variability in participants dosed with GlyphAgo ranged from 22.6% to 29.7% for AUC₀-₂₄ and from 26.5% to 44.0% for Cmax, compared with ranges of 234.6% to 350.1% and 303.7% to 500.9%, respectively, for unmodified agomelatine. As previously noted, the data showed no effect of estrogen-containing oral contraceptives on agomelatine exposure following GlyphAgo dosing, further supporting the ability of GlyphAgo to bypass first-pass hepatic metabolism and avoid drug-drug interactions that occur in the liver.Details of the presentation are as follows:Title: GlyphAgo demonstrated 6.8-fold increased bioavailability and 10-fold reduced variability versus unmodified agomelatine in healthy volunteers at doses projected to mitigate liver exposurePoster Number: PS02-2029Presenter: Daniel Bonner, Ph.D., Co-Founder and Senior Vice President, Platform, at Seaport TherapeuticsDate and Time: Sunday, October 11th at 12:35 PM CESTSeaport has initiated a Phase 2a clinical trial evaluating GlyphAgo in adults with generalized anxiety disorder and sleep disturbance, with topline results expected in early 2028. The Company also plans to initiate a Phase 2/3 clinical trial evaluating the efficacy and safety of GlyphAgo in patients with GAD in the first half of 2027.