Seaport Therapeutics (SPTX) investor relations material

Pipeline and strategy

• Three programs span clinical and preclinical development: GlyphAllo in a Phase IIb potentially registration-enabling MDD study, GlyphAgo in Phase IIa GAD development, and preclinical Glyph2BLSD exploring psychedelic benefits without the trip.

• Glyph is a lymphatic-targeting prodrug platform designed to address oral bioavailability, liver-related adverse events and other limitations; each modified molecule generates new composition-of-matter IP.

• The platform uses dietary fat to alter absorption and bypass first-pass liver metabolism; GlyphAllo achieved exposures comparable to IV allopregnanolone with once-daily oral dosing in trials.

GlyphAllo and BUOY-1

• BUOY-1 is a global, placebo-controlled MDD study of up to 360 patients; primary analysis covers all participants, with top-line results expected in H1 2027.

• Treatment runs for six weeks, followed by a six-week open-label extension; the primary endpoint is HAMD-17 at week six, addressing concerns about two-week treatment and durability in prior zuranolone studies.

• The trial uses one active and one placebo arm with 1:1 randomization, flexible dosing across three dose levels, and fewer clinician-administered assessments to limit expectancy and placebo effects.

• Anxious distress is a prespecified, stratified subgroup; depending on results and FDA discussion, it could inform future development. The subgroup occurs in 60%-70% of MDD patients, depending on the study.

• Top-line driving-study data showed no next-day impairment after single or repeated GlyphAllo dosing; blood levels fall to 15% or less of Cmax by 6-8 hours post-dose.

GlyphAgo development

• Agomelatine has demonstrated efficacy in MDD and GAD, but liver enzyme elevations and required liver monitoring have limited its clinical and commercial potential; GlyphAgo aims to reduce liver exposure while retaining efficacious exposure.

• Phase I top-line results showed 6.8-fold higher bioavailability versus agomelatine, ~10-fold lower PK variability, and no observed interaction with the cited drug-interaction mechanisms occurring in the liver.

• A Phase IIa proof-of-pharmacology study in GAD with sleep disturbance has started; it will assess sleep-focused endpoints and multiple doses. A separate Phase II/III potentially registration-enabling GAD study is planned.

• GlyphAgo Phase IIa results are expected in early 2028, followed by the potentially registration-enabling Phase II/III trial at the end of 2028.