Lead program: Phase II

Seaport Therapeutics

Data updated June 27, 2026

3 Drug Candidates

Seaport Therapeutics is a Boston-based biopharmaceutical company developing neuropsychiatric medicines using its proprietary Glyph™ lymphatic delivery platform. The Glyph technology bypasses first-pass hepatic metabolism by routing drugs through the lymphatic system, improving oral bioavailability. Its lead candidate SPT-348 (Glyph2BLSD™) is a prodrug of BOL-148 (2-bromo-LSD), a non-hallucinogenic neuroplastogen targeting headache disorders and TRD. The company raised $325M across a $100M Series A (2024) and $225M Series B (2024–2025), backed by PureTech Health, ARCH Venture Partners, Third Rock Ventures, and General Atlantic.

Pipeline Intelligence

Developer Momentum

Programme tracker

Active candidates: 3
Active programmes: 3
Lead stage: Phase II
Forecast coverage: 3 of 3

Latest sourced update

Seaport Therapeutics Pipeline - Glyph2BLSD

Jun 27, 2026 - company-website - Seaport Therapeutics - Glyph2BLSD (SPT-348)

Next known catalyst

Phase II topline

Timing not specified - GlyphAllo (SPT-300) / GlyphAllo BUOY-1 Phase 2b Programme (MDD) - Confidence: 55%

12 sources0 pipeline-linked trials0 pipeline-linked papers1 Phase II1 Phase I1 Preclinical

Development Programmes

GlyphAllo (SPT-300)

Phase II

Major Depressive Disorder (MDD)

Major depressive disorder

Programme Tracker

Major Depressive Disorder (MDD)

Primary: US (FDA)

Phase IIActive

Forecast

Phase II topline

BUOY-1 Phase 2b enrolling (NCT07065240); ~360 participants; 6-week HAMD-17 primary endpoint

Milestones

Pre-clinical completed

Completed

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)

Seaport Announces Science Translational Medicine Publication for GlyphAllo(Publication)[Verified]

Phase II started

Completed

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.

Seaport Announces First Patient Dosed in Phase 2b BUOY-1 Study of SPT-300(Press release)[Verified]ClinicalTrials.gov NCT07065240 - BUOY-1 SPT-300 in MDD(Registry update)[Verified]

Recorded Events

Mar 25, 2026: Pre-clinical completed

Jul 1, 2025: Phase II started

Evidence Links

Seaport Announces First Patient Dosed in Phase 2b BUOY-1 Study of SPT-300

Press release - Seaport Therapeutics - Jul 17, 2025 - Verified

Seaport announced first patient dosing in the Phase 2b BUOY-1 study of GlyphAllo/SPT-300 for MDD with or without anxious distress.

ClinicalTrials.gov NCT07065240 - BUOY-1 SPT-300 in MDD

Registry update - ClinicalTrials.gov - May 19, 2026 - Verified

Registry lists BUOY-1 as a recruiting Phase 2 SPT-300 study in 360 participants with major depressive disorder.

Seaport Announces Science Translational Medicine Publication for GlyphAllo

Publication - Seaport Therapeutics - Mar 25, 2026 - Verified

Publication announcement says preclinical and first-in-human data supported the ongoing Phase 2b BUOY-1 trial.

Seaport Reports Q1 2026 Results and BUOY-1 Enrollment Progress

Press release - BioSpace / Seaport Therapeutics - Jun 12, 2026 - Verified

Recent update says BUOY-1 enrollment is on track and topline data are expected in the first half of 2027.

GlyphAgo (SPT-320)

Phase I

Anxiety Disorders Major Depressive Disorder (MDD)

Generalised anxiety disorder / MDD

Programme Tracker

Anxiety Disorders

Primary: US (FDA)

Phase IActive

Forecast

Phase II started

Phase 1 GlyphAgo/SPT-320 trial has positive SAD, crossover, and MAD data reported through June 2026. Seaport plans a Phase 2a GAD trial in H2 2026 and a Phase 2b GAD trial in H1 2027.

Milestones

Phase I started

Completed

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.

Seaport Doses First Participant in Phase 1 GlyphAgo Study(Press release)[Verified]ANZCTR 389549 - Phase 1 Single and Multiple Ascending Dose Trial of SPT-320(clinical-trial-registry)[Verified]

Phase I topline

Completed

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

Seaport Announces Positive Phase 1 Proof-of-Concept Topline Results for GlyphAgo(Press release)[Verified]Seaport Reports Positive Multiple-Ascending Dose Data for GlyphAgo(Press release)[Verified](Press release)[Verified]

Recorded Events

Apr 2, 2026: Phase I topline

Sep 1, 2025: Phase I started

Evidence Links

ANZCTR 389549 - Phase 1 Single and Multiple Ascending Dose Trial of SPT-320

clinical-trial-registry - ANZCTR - Jun 26, 2026 - Verified

Trial registry for the Phase 1 single- and multiple-ascending-dose study of SPT-320/GlyphAgo in healthy participants.

Seaport Doses First Participant in Phase 1 GlyphAgo Study

Press release - Seaport Therapeutics - Sep 11, 2025 - Verified

Company announced first participant dosed in Phase 1 proof-of-concept study of GlyphAgo/SPT-320 for generalized anxiety disorder.

Seaport Announces Positive Phase 1 Proof-of-Concept Topline Results for GlyphAgo

Press release - Seaport Therapeutics - Apr 2, 2026 - Verified

Positive SAD and crossover Phase 1 data supported moving GlyphAgo toward Phase 2 trials in GAD.

Seaport Reports Positive Multiple-Ascending Dose Data for GlyphAgo

Press release - BioSpace / Seaport Therapeutics - Jun 8, 2026 - Verified

Repeat-dose Phase 1 data reported favorable safety, tolerability, and pharmacokinetics, with no liver-related adverse events observed.

Glyph2BLSD (SPT-348)

LSD

Preclinical

Headache Disorders (Cluster & Migraine)Treatment-Resistant Depression (TRD)

Cluster headache / treatment-resistant depression

Programme Tracker

Headache Disorders (Cluster & Migraine)

Primary: US (FDA)

Pre-clinicalActive

SPT-348/Glyph2BLSD remains preclinical; Seaport's June 2026 SEC update says first-in-human-enabling studies are expected by year-end 2027.

Milestones

Pre-clinical completed

In progress

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