Seaport Therapeutics

Actual: Mar 25, 2026

Science Translational Medicine peer-reviewed publication: lymphatic transport mechanism validated in animals and humans

Why it matters: StM publication validates the Glyph technology platform mechanism for GlyphAllo and the broader pipeline. Academic validation of lymphatic prodrug delivery is critical for the regulatory submission.

Watch next: BUOY-1 primary endpoint results (HAM-D-17 at 6 weeks)

Actual: Jul 1, 2025

BUOY-1 Phase 2b first patient dosed; NCT07065240

Why it matters: GlyphAllo is an oral prodrug of allopregnanolone (a GABA-A positive allosteric modulator) that uses Seaport's Glyph technology to bypass hepatic first-pass metabolism via lymphatic absorption, achieving ~9× greater allopregnanolone exposure than unmodified oral allopregnanolone. Brexanolone (Zulresso) IV showed the same mechanism is clinically active; GlyphAllo offers an oral, outpatient-deliverable form.

Actual: Sep 1, 2025

Phase 1 first participant dosed

Why it matters: GlyphAgo is an oral Glyph prodrug of agomelatine (MT1/MT2 agonist + 5-HT2C antagonist). Agomelatine is approved in Europe for MDD but has limited US uptake due to poor oral bioavailability and hepatotoxicity concerns from high doses. GlyphAgo's lymphatic route avoids first-pass liver exposure, potentially resolving both issues.

Actual: Apr 2, 2026

Phase 1 proof-of-concept positive topline: 6.8× bioavailability vs unmodified agomelatine; 9.6–14.5× dose-normalised exposure; 10× reduction in PK variability; no SAEs or liver-related AEs

Why it matters: 6.8× bioavailability improvement with 10× PK variability reduction validates the Glyph platform for agomelatine. Critically, no hepatotoxicity signals — addressing the main safety concern that limited unmodified agomelatine's uptake. Two parallel Phase 2 trials now planned.

Watch next: Phase 2a (sleep/GAD proof-of-pharmacology) and Phase 2b (registration-enabling RCT) initiation

Why it matters: SPT-348 applies Seaport's Glyph lymphatic absorption technology to 2-bromo-LSD (BOL-148) — a non-hallucinogenic LSD analog. The Glyph linker could improve BOL-148 bioavailability and reduce dosing variability, potentially addressing the same limitations that affect unmodified BOL-148 (low oral bioavailability). This is a next-generation formulation approach to the same compound Ceruvia is developing as NYPRG-101.

Watch next: IND-enabling study initiation and Phase 1 timeline announcement