BOSTON — September 9, 2026
Seaport Therapeutics, Inc. announced positive topline results from a Phase 1 driving simulation trial of GlyphAllo™ (SPT-300) in healthy volunteers, supporting the continued clinical development of the company’s investigational oral therapy for major depressive disorder (MDD). The study met its primary endpoint, demonstrating that an evening dose of 375 mg GlyphAllo did not impair next-morning driving performance compared with placebo on Day 5 following multiple-day dosing. A key secondary endpoint was also met, with a single 250 mg evening dose showing no impairment in next-morning driving performance on Day 2. GlyphAllo was well tolerated across evaluated doses, with most adverse events mild and transient and no serious adverse events reported. The results provide an additional safety and differentiation milestone as Seaport advances GlyphAllo through its potentially registration-enabling Phase 2b BUOY-1 study.
GlyphAllo Shows No Next-Morning Driving Impairment
The Phase 1 trial was specifically designed to assess whether evening administration of GlyphAllo could affect driving performance the following morning, an important consideration for a potential neuropsychiatric therapy intended for daily use. The randomized, double-blind, placebo- and active-controlled crossover study enrolled 33 healthy volunteers, who received bedtime doses followed by simulated driving assessments approximately nine hours later. Driving performance was evaluated using the validated Cognitive Research Corporation Driving Simulator-MiniSim, with Standard Deviation of Lateral Position (SDLP) serving as the primary measure of lane-weaving and driving impairment. The study evaluated a single 250 mg dose on Day 2 and multiple-day dosing at 375 mg on Day 5. The active control, 7.5 mg zopiclone, produced statistically significant impairment compared with both GlyphAllo and placebo, confirming that the trial was sensitive enough to detect driving-related effects.
Safety Data Support Ongoing BUOY-1 Development
The favorable driving-performance findings add to the safety and tolerability profile supporting GlyphAllo’s ongoing clinical development in MDD. GlyphAllo is a novel Glyphed oral prodrug of allopregnanolone, designed to overcome the bioavailability limitations of allopregnanolone while potentially delivering rapid and durable antidepressant effects. Seaport previously reported therapeutically relevant exposures following oral administration in Phase 1 and initial proof-of-concept findings in a Phase 2a study. The latest trial evaluated the 375 mg dose currently being investigated in BUOY-1, making the absence of next-morning driving impairment particularly relevant to the company’s development strategy. Seaport plans to submit the driving simulation results to the U.S. Food and Drug Administration as part of the ongoing GlyphAllo development program and intends to present additional analyses at future scientific meetings.
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Seaport Advances Potential First-in-Class Oral Therapy
Seaport is actively enrolling patients in BUOY-1, a global, randomized, double-blind, placebo-controlled Phase 2b study evaluating GlyphAllo in patients with MDD with or without anxious distress. The potentially registration-enabling trial is designed to further establish the safety and efficacy profile of the oral therapy and represents the next major clinical milestone for the program. Seaport expects to report BUOY-1 topline results in the first half of 2027. The company is positioning GlyphAllo as a potential first-in-class treatment that could combine the clinically validated neuropsychiatric activity of allopregnanolone with the convenience of oral administration and an evening dosing regimen. With positive driving simulation results at both 250 mg and 375 mg, no serious adverse events and Phase 2b enrollment underway, Seaport Therapeutics is strengthening the clinical profile of GlyphAllo as it advances toward pivotal development in major depressive disorder..
Source:Seaport Therapeutics, press release
