BOSTON — September 9, 2026
Seaport Therapeutics, Inc. reported positive topline results from a Phase 1 driving simulation trial evaluating GlyphAllo™ (SPT-300 or Glyph Allopregnanolone), a novel Glyphed oral prodrug of allopregnanolone being developed for major depressive disorder (MDD). The trial met its primary endpoint, showing that an evening dose of 375 mg GlyphAllo did not impair next-morning simulated driving performance compared with placebo on Day 5 following multiple-day dosing. The 375 mg dose represents the highest dose currently being evaluated in the company’s potentially registration-enabling Phase 2b BUOY-1 trial. The study also met its key secondary endpoint, demonstrating that a single 250 mg evening dose did not impair next-morning driving performance on Day 2. For Seaport, the findings provide an important clinical development milestone as the company evaluates whether GlyphAllo can combine the therapeutic potential of allopregnanolone with a differentiated tolerability and next-morning functioning profile.
GlyphAllo Shows No Next-Morning Driving Impairment
The Phase 1 trial enrolled 33 healthy volunteers in a randomized, double-blind, placebo- and active-controlled, three-way crossover design. Participants received GlyphAllo at bedtime and completed simulated driving assessments approximately nine hours later using the Cognitive Research Corporation Driving Simulator-MiniSim, a validated tool used in clinical development. The primary measure was Standard Deviation of Lateral Position (SDLP), a widely used assessment 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, with a 7.5 mg dose of zopiclone included as an active control. Zopiclone produced statistically significant driving impairment compared with both GlyphAllo and placebo on Days 2 and 5, confirming that the study design was sensitive enough to detect impaired driving performance. GlyphAllo was well tolerated at all evaluated doses, with most adverse events described as mild and transient and no serious adverse events reported. The results add another differentiating data point to the clinical profile Seaport is building around its oral neuropsychiatric medicine.
Safety Data Support Ongoing BUOY-1 Development
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 expects to present additional analyses at future scientific meetings. The company is actively enrolling patients in BUOY-1, a global, randomized, double-blind, placebo-controlled Phase 2b study designed to evaluate the safety and efficacy of GlyphAllo in people with MDD, including patients with or without anxious distress. The trial is intended to provide potentially registration-enabling evidence for the program, with topline results expected in the first half of 2027. GlyphAllo is designed to overcome the bioavailability limitations associated with oral allopregnanolone while maintaining its clinically validated mechanism and potential rapid antidepressant, anxiolytic and sleep-promoting effects. Previous Phase 1 work demonstrated therapeutically relevant exposures with oral dosing, while a Phase 2a study generated initial proof-of-concept using an objective stress biomarker and showed a favorable tolerability profile. The latest driving findings strengthen the safety and usability package being assembled for regulatory discussions.
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Seaport Advances Potential First-in-Class Oral Therapy
GlyphAllo represents a central component of Seaport Therapeutics’ strategy to develop differentiated oral medicines for neuropsychiatric disorders by applying its proprietary Glyph™ platform to clinically validated mechanisms that have historically faced limitations involving first-pass metabolism, bioavailability or side effects. Allopregnanolone has already demonstrated antidepressant activity in third-party clinical development for postpartum depression, a form of MDD, providing a mechanistic foundation for Seaport’s approach. With BUOY-1 progressing in MDD and the 375 mg dose now supported by driving-performance data, Seaport is positioning GlyphAllo for a potentially important late-stage development milestone. Successful BUOY-1 results could provide the next major catalyst for the program, while the company’s planned FDA submission and additional scientific presentations are expected to further define its regulatory and clinical strategy. Seaport’s broader pipeline targets depression, anxiety and other debilitating neuropsychiatric disorders, with GlyphAllo serving as a leading example of its effort to translate established biology into differentiated oral therapies.
Source: Seaport Therapeutics, press release
