Seaport Therapeutics Advances GlyphAgo™ (SPT-320) to Phase 1 with First Healthy Volunteer Dosed

09/11/2025 – 07:05 AM

GlyphAgo is an oral prodrug of agomelatine, a medicine with established clinical efficacy in generalized anxiety disorder (GAD)

GlyphAgo is designed to overcome a key limitation of agomelatine by shifting absorption toward the intestinal lymphatics, avoiding first-pass liver metabolism, and increasing systemic exposure of the drug

Phase 1 proof-of-concept study will evaluate the safety, tolerability, and pharmacokinetics of GlyphAgo and is designed to demonstrate therapeutic levels of agomelatine at lower doses that reduce liver exposure

BOSTON – Seaport Therapeutics, a biopharmaceutical firm focusing on neuropsychiatric medicines, announced the first participant dosed in its Phase 1 study of GlyphAgo™ (SPT-320), an oral prodrug targeting Generalized Anxiety Disorder (GAD). PureTech Health plc (Nasdaq: PRTC, LSE: PRTC), a biotherapeutics company with a stake in Seaport Therapeutics, noted the development.

GlyphAgo utilizes Seaport’s proprietary Glyph™ technology to enhance the oral bioavailability of agomelatine, a drug already demonstrating efficacy in GAD treatment. Agomelatine’s clinical use has been somewhat hampered by its first-pass liver metabolism, which can lead to liver-related side effects. GlyphAgo aims to circumvent this issue by promoting absorption through the intestinal lymphatics, thereby reducing the drug’s exposure to the liver.

This study’s initiation signals Seaport Therapeutics’ forward momentum, marking their second therapeutic candidate to enter clinical trials.

Seaport Therapeutics Advances Second Therapeutic Candidate into Clinical Development with Dosing of First Participant in Phase 1 Study of GlyphAgo™ (SPT-320) in Healthy Volunteers

GlyphAgo is an oral prodrug of agomelatine, a medicine with established clinical efficacy in four out of four previous third-party randomized, placebo-controlled studies in generalized anxiety disorder (GAD)

Building on agomelatine’s proven clinical efficacy, GlyphAgo is designed to overcome a key limitation of agomelatine by shifting absorption toward the intestinal lymphatics, avoiding first-pass liver metabolism, and increasing systemic exposure of the drug

Phase 1 proof-of-concept study will evaluate the safety, tolerability, and pharmacokinetics of GlyphAgo and is designed to demonstrate therapeutic levels of agomelatine at lower doses that reduce liver exposure

BOSTON – September 11, 2025 – Seaport Therapeutics, a clinical-stage biopharmaceutical company advancing novel neuropsychiatric medicines with a proven strategy and team, today announced that the first participant has been dosed in the Phase 1 study of GlyphAgo™ (SPT-320 or Glyph Agomelatine), a “Glyphed” oral prodrug of agomelatine in development for the treatment of generalized anxiety disorder (GAD). The study will evaluate the safety, tolerability, and pharmacokinetics of GlyphAgo in healthy adult volunteers. This marks the second therapeutic candidate in Seaport’s pipeline in clinical development.

Agomelatine, a clinically validated melatonin receptor agonist and serotonin 2C receptor antagonist, is an effective anxiolytic and antidepressant approved for the treatment of GAD in Australia and major depressive disorder (MDD) in Australia and the European Union (EU). In GAD, agomelatine has demonstrated statistically significant separation from placebo in four out of four third-party placebo-controlled studies and has better efficacy and tolerability – including reduced risk of abuse potential, sexual dysfunction, and weight gain – than standard of care drugs, like selective serotonin reuptake inhibitors (SSRIs) or benzodiazepines. However, over 90 percent of unmodified agomelatine is lost to first-pass liver metabolism and its use has been limited by dose-dependent liver enzyme elevations and the need for frequent liver monitoring.

Using Seaport’s proprietary Glyph™ platform, GlyphAgo is designed to overcome this limitation by shifting absorption toward the intestinal lymphatics, avoiding first-pass liver metabolism, and increasing systemic exposure of agomelatine. As a result, GlyphAgo has the potential to achieve exposure levels that have demonstrated efficacy in GAD at a lower dose that does not cause an increase in liver enzymes and reduces or eliminates the need for liver function testing.

“Anxiety disorders are increasingly prevalent, with GAD affecting a significant portion of the global adult population. The development of GlyphAgo represents a potentially significant advancement, particularly given the limited innovation in GAD treatments of late,” commented Antony Loebel, M.D., Chief Medical Officer, President of Clinical Development at Seaport Therapeutics. “The Phase 1 study’s main objective is to ascertain whether GlyphAgo can deliver effective exposure levels of agomelatine at a lower dose, mitigating the liver-related concerns associated with higher doses.”

The Phase 1 trial will encompass multiple phases to evaluate GlyphAgo’s safety and pharmacokinetics against standard agomelatine treatments. The study incorporates both single- and multiple-ascending dose phases, alongside food-effect crossover analysis using both open-label and placebo-controlled study designs.

Preclinical studies have indicated GlyphAgo’s role in bolstering lymphatic absorption, increasing systemic exposure to agomelatine. Data presented at the Society of Biological Psychiatry (SOBP) Annual Meeting 2025 supported the increased plasma exposure of agomelatine following oral dosing of GlyphAgo. These results highlight the technology’s ability to specifically target drug delivery via the lymphatic system.

CNBC Analysis:
The progress of Seaport Therapeutics’ GlyphAgo into Phase 1 trials marks a crucial step in addressing GAD, a condition affecting a substantial number of individuals worldwide. The innovative Glyph™ platform holds promise in overcoming the limitations of current agomelatine treatments by enhanced lymphatic absorption. This directed approach not only seeks to amplify drug exposure but also to considerably lower the possibility of liver toxicity.

From a commercial perspective, the successful development of GlyphAgo could capture a sizeable share of the GAD treatment market. However, significant milestones lie ahead, notably confirming the promising preclinical findings in human trials and evidencing the drug’s safety to regulators. Pharmaceutical companies such as Seaport continues to focus increasingly not only on efficacy but also on targeted biodistribution, GlyphAgo might set a precedent for the future of neuropsychiatric medicine. The investment community will closely observe the drug’s progress, as a positive outcome might increase interest in Seaport and attract more capital.