BOSTON, June 8, 2026
PureTech Health and its Founded Entity Seaport Therapeutics announced positive results from the multiple-ascending dose (MAD) portion of a Phase 1 proof-of-concept clinical trial evaluating GlyphAgo™ (SPT-320), a novel oral prodrug of agomelatine developed using Seaport’s proprietary Glyph™ platform. The study demonstrated favorable safety, tolerability, and pharmacokinetic profiles following repeat dosing in healthy volunteers, supporting the advancement of GlyphAgo into two planned Phase 2 clinical trials for generalized anxiety disorder (GAD). The results further validate PureTech’s strategy of identifying clinically proven therapies and enhancing their performance through innovative drug delivery technologies.
PureTech-Originated Glyph Platform Demonstrates Strong Clinical Potential
The GlyphAgo program and the underlying Glyph™ platform were originally developed within PureTech Health before being advanced by Seaport Therapeutics. The technology is designed to improve oral drug delivery by enabling absorption through the intestinal lymphatic system, helping medicines bypass first-pass liver metabolism. This approach aims to increase systemic drug exposure while reducing liver-related safety concerns. In the Phase 1 study, seven-day repeat dosing of GlyphAgo achieved therapeutic agomelatine exposure levels while maintaining a favorable safety profile. No serious adverse events, severe adverse events, liver-related adverse events, or clinically significant liver laboratory abnormalities were reported across the evaluated dose levels.
Phase 1 Data Support Improved Bioavailability and Reduced Liver Exposure
The comprehensive Phase 1 program enrolled 174 healthy volunteers and included single-ascending dose, multiple-ascending dose, crossover, and food-effect evaluations. Previously reported crossover data demonstrated that GlyphAgo delivered approximately 6.8-fold greater bioavailability than conventional oral agomelatine while reducing pharmacokinetic variability by nearly 10-fold. Additional analyses showed that GlyphAgo exposure remained unaffected by estrogen-containing oral contraceptives, highlighting the platform’s ability to avoid liver-mediated drug interactions. Researchers believe these characteristics could allow therapeutic agomelatine exposure at lower doses, potentially reducing or eliminating the need for routine liver function monitoring that has historically limited the broader use of agomelatine.
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Two Parallel Phase 2 Trials Planned in Generalized Anxiety Disorder
Building on the positive Phase 1 findings, Seaport Therapeutics plans to initiate a randomized, double-blind Phase 2a proof-of-pharmacology study during the second half of 2026. The trial will evaluate two dose levels of GlyphAgo in patients with generalized anxiety disorder and sleep disturbance, examining sleep architecture and other objective sleep-related outcomes. Topline data are expected in early 2028. The company also plans to launch a Phase 2b placebo-controlled trial during the first half of 2027 to assess the efficacy and safety of GlyphAgo in a broader GAD patient population. This potentially registration-enabling study is expected to generate topline results by the end of 2028.
Novel Anxiety Treatment Addresses Longstanding Unmet Need
Generalized anxiety disorder affects millions of people worldwide and remains an area with limited therapeutic innovation. Agomelatine has demonstrated anti-anxiety and antidepressant activity in several international markets but has faced challenges related to liver metabolism and monitoring requirements. By combining clinically validated pharmacology with the innovative Glyph™ delivery platform, PureTech Health and Seaport Therapeutics aim to create a next-generation treatment that improves exposure, safety, and patient convenience. The successful Phase 1 results strengthen confidence in GlyphAgo’s development path and reinforce the broader potential of the Glyph™ platform to transform neuropsychiatric drug development through enhanced delivery and pharmacokinetic performance.
Source: PureTech Health press release
