First patient dosed in BUOY-1 study targeting MDD with or without anxious distress

Seaport Therapeutics has dosed the first patient in its phase 2b BUOY-1 trial of GlyphAllo, a novel oral prodrug of allopregnanolone, for major depressive disorder (MDD) with or without anxious distress.

GlyphAllo is designed to overcome limitations of allopregnanolone, a molecule known for its rapid antidepressant and anxiolytic effects.

The BUOY-1 study builds on successful phase 1 and phase 2a data and will assess the efficacy, safety and tolerability of GlyphAllo in up to 360 adults over six weeks. Patients will be randomised to receive either GlyphAllo or placebo once daily.

Eligible participants may enter an open-label extension phase, receiving GlyphAllo for an additional six weeks. The primary endpoint is change from baseline in the HAM-D-17 depression rating scale.

Daphne Zohar, CEO of Seaport Therapeutics, said: “The initiation of BUOY-1 marks a significant milestone for Seaport’s pipeline, bringing us closer to a potential new treatment for major depression, which impacts around 280 million people globally – nearly 60 percent of whom also experience anxious distress.”

Antony Loebel, Chief Medical Officer, added: “CNS clinical trials are inherently complex, and we are applying our team’s extensive expertise to implement a high-quality study.”

Phase 1 data showed GlyphAllo achieved nine times greater exposure than oral allopregnanolone and matched levels seen with IV dosing. EEG and eye movement tests confirmed dose-dependent brain activity.

In phase 2a, GlyphAllo significantly reduced salivary cortisol in a validated stress model, meeting its primary endpoint with a p-value of 0.0001. The treatment was well-tolerated, with mostly mild and transient side effects.

The trial aims to validate GlyphAllo as a first-in-class treatment for MDD, offering a new option for patients with depression and anxiety.