Seaport reports 6.8-fold GlyphAgo bioavailability increase

• Seaport Therapeutics (NASDAQ:SPTX) reported Phase 1 data showing GlyphAgo increased agomelatine bioavailability 6.8-fold versus unmodified agomelatine.
• The company also reported roughly 10-fold lower pharmacokinetic variability and therapeutically relevant exposure at lower doses.
• Seaport said the results support further development of GlyphAgo as a potential treatment for generalized anxiety disorder.

Seaport Therapeutics (NASDAQ:SPTX) presented Phase 1 GlyphAgo data showing a statistically significant 6.8-fold increase in agomelatine bioavailability compared with unmodified agomelatine.

The completed proof-of-concept study enrolled 174 healthy volunteers and evaluated safety, tolerability and pharmacokinetics across multiple trial components.

“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 Seaport Therapeutics Senior Vice President Daniel Bonner.

GlyphAgo also showed about 10-fold lower pharmacokinetic variability, with dose-dependent exposure increases, no accumulation over seven days and no apparent food effect.

Seaport said the prodrug achieved therapeutically relevant agomelatine exposure at lower doses and may reduce liver exposure, although potential reductions in liver enzyme elevations or monitoring requirements remain to be established in later studies.

In the single-ascending-dose portion, GlyphAgo variability ranged from 12.9% to 26.6% for AUC₀-₂₄ and 17.1% to 50.5% for Cmax, versus 200% and 217%, respectively, for unmodified agomelatine.

Seaport also reported no effect from estrogen-containing oral contraceptives on agomelatine exposure after GlyphAgo dosing, which the company said further supports its approach of bypassing first-pass liver metabolism.