PRTC's SPTX Presents Phase 1 GlyphAgo Data at ECNP

PureTech Founded Entity Seaport Therapeutics Presents Additional Pharmacokinetic Data from Phase 1 Clinical Trial of GlyphAgo™ at the 39th European College of Neuropsychopharmacology (ECNP) Congress

PureTech Health plc (LSE: PRTC) ("PureTech" or the "Company"), a hub-and-spoke biotherapeutics company dedicated to giving life to science and transforming innovation into value, notes that its Founded Entity, Seaport Therapeutics, today announced the presentation of Phase 1 clinical data for GlyphAgo™ (SPT-320 or Glyph Agomelatine) at the 39th European College of Neuropsychopharmacology (ECNP) Congress, 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.

Seaport 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. Seaport also plans to initiate a Phase 2/3 clinical trial evaluating the efficacy and safety of GlyphAgo in patients with generalized anxiety disorder in the first half of 2027.

The full text of the announcement from Seaport is as follows:

Seaport Therapeutics Presents Additional Pharmacokinetic Data from Phase 1 Clinical Trial of GlyphAgo™ at the 39th European College of Neuropsychopharmacology (ECNP) Congress

First scientific presentation of detailed PK data demonstrates dose-dependent increases in agomelatine exposure, no food effect, and no accumulation of exposure over seven days of dosing

Detailed data reinforces previously reported topline results demonstrating that GlyphAgo achieved a statistically significant 6.8-fold increase in agomelatine bioavailability and substantially lower (10-fold) PK variability compared to unmodified agomelatine

Agomelatine levels comparable to those seen with efficacious doses of the unmodified drug were achieved at substantially lower doses, intended to reduce hepatic exposure and the potential for liver enzyme elevations

BOSTON--Oct. 9, 2026-- Seaport Therapeutics, Inc. (Nasdaq: SPTX) ("Seaport" or the "Company"), a clinical-stage therapeutics company developing novel neuropsychiatric medicines, today announced the presentation of Phase 1 clinical data for GlyphAgo™ (SPT-320 or Glyph Agomelatine) at the 39th European College of Neuropsychopharmacology (ECNP) Congress, 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 exposure
• Poster Number: PS02-2029
• Presenter: Daniel Bonner, Ph.D., Co-Founder and Senior Vice President, Platform, at Seaport Therapeutics
• Date and Time: Sunday, October 11th at 12:35 PM CEST

Seaport 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.

About GlyphAgoTM (SPT-320 or Glyph Agomelatine)

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 GlyphTM 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 within the range observed to be effective in third-party placebo-controlled studies in GAD but at a lower dose that is designed to reduce liver exposure. Based on the data generated to date, Seaport believes GlyphAgo has the potential to become a leading treatment for GAD.

About Seaport Therapeutics

Seaport Therapeutics (Nasdaq: SPTX) is a clinical-stage therapeutics company focused on inventing and developing new medicines for patients with depression, anxiety, and other debilitating neuropsychiatric disorders. Through its differentiated approach, the Company identifies clinically validated mechanisms with established efficacy and safety which had historically been limited by high first-pass metabolism, low bioavailability, and/or side effects. Seaport applies its proprietary GlyphTM platform to overcome those limitations and invent innovative oral therapies. With an experienced team of industry leaders, Seaport has a proven track record in neuropsychiatry drug discovery and development and delivering successful business outcomes. Seaport aims to develop novel, leading treatment options that will make a significant impact for patients and their families. For more information, please visit www.seaporttx.com.