Neuroactive Steroid · SPT-300

GlyphAllo (SPT-300)

Phase 2Seaport Therapeutics, Inc. (SPTX)

Oral prodrug of allopregnanolone built on Seaport Therapeutics' Glyph platform (triglyceride-mimetic, absorbed via intestinal lymphatics, bypassing first-pass metabolism). The released active moiety allopregnanolone is an endogenous neuroactive steroid and GABA-A receptor positive allosteric modulator. In development for major depressive disorder, with or without anxious distress.

Also known as: SPT-300, GlyphAllo

Data current as of

Key facts

Modality
Neuroactive Steroid
Chemical class
neuroactive steroid, pregnane steroid
Chemistry
Single enantiomer · Prodrug
Mechanism
GABA-A receptor PAM
Highest phase
Phase 2
Lead indication
Major depressive disorder
Developer
Seaport Therapeutics, Inc. (SPTX)
Trials
1 tracked · 1 recruiting · 59 sites

Mechanism of action#

Oral prodrug releasing allopregnanolone, an endogenous neuroactive steroid and positive allosteric modulator of GABA-A receptors; the Glyph triglyceride-mimetic enables lymphatic absorption and bypasses first-pass hepatic metabolism.

TargetActionAffinity
GABA-A receptorprimaryPAM—ⓘ

Formulations#

FormulationRouteRegimenPharmacokinetics
SPT-300 oral (GlyphAllo)Glyph triglyceride-mimetic prodrug (intestinal lymphatic transport, bypasses first-pass hepatic metabolism)
Oral once-daily prodrug of allopregnanolone. Phase 1 single/multiple ascending doses 70-1000 mg; Phase 2a single 375 mg dose; Phase 2b BUOY-1 dosed once-daily over a six-week treatment period. Approximately nine-fold greater allopregnanolone exposure than previously reported for oral allopregnanolone.
OralOnce daily—

Development timeline#

Jul 24Oct 24Jan 25Apr 25Jul 25Phase 217 Jul 2025 — phase change — First patient dosed in Phase 2b BUOY-1 (GlyphAllo/SPT-300) in MDD with/without anxious distress.19 Jun 2025 — phase change — Phase 2b BUOY-1 study (NCT07065240) initiated.9 Apr 2024 — Licensing deal — PureTech transfers Glyph IP and the SPT-300 (formerly LYT-300) program to founded entity Seaport
Phase change Readout Event UpcomingHover a marker for details.
Phase 2Apr 2024 – Jul 2025
  1. First patient dosed in Phase 2b BUOY-1 (GlyphAllo/SPT-300) in MDD with/without anxious distress.↗
  2. Phase 2b BUOY-1 study (NCT07065240) initiated.
  3. Licensing dealPureTech transfers Glyph IP and the SPT-300 (formerly LYT-300) program to founded entity Seaport↗

GlyphAllo (SPT-300) for Major depressive disorder#

Phase 2RecruitingMajor depressive disorder indication →

SPT-300 (GlyphAllo) for MDD, with or without anxious distress. After positive Phase 1 PK/PD and a Phase 2a proof-of-concept (Trier Social Stress Test), advanced to the Phase 2b BUOY-1 study (NCT07065240, n=360); first patient dosed 17 Jul 2025.

Clinical trials#

NCT07065240BUOY-1Phase 2Recruitingn=360

Monotherapy Study of SPT-300 in Adults With Major Depressive Disorder, With or Without Anxious Distress (BUOY-1)

Started Jun 2025· Primary completion Mar 2027· 59 sites across 7 countries

United StatesPolandCzechiaGermany

Conference coverage#

SPT-300 appears in 3 CNS Pulse conference abstracts:

Sources#

  1. BUOY-1 (NCT07065240) — ClinicalTrials.gov
  2. Seaport Therapeutics (Founded Entity) — PureTech Health
  3. Seaport Therapeutics Announces First Patient Dosed in Phase 2b BUOY-1 Study of GlyphAllo (SPT-300) in MDD — Seaport Therapeutics