Neuroactive Steroid · SPT-300
GlyphAllo (SPT-300)
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
- 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.
| Target | Action | Affinity |
|---|---|---|
| GABA-A receptorprimary | PAM | —ⓘ |
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| 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. | Oral | Once daily | — |
Development timeline
- First patient dosed in Phase 2b BUOY-1 (GlyphAllo/SPT-300) in MDD with/without anxious distress.↗
- Phase 2b BUOY-1 study (NCT07065240) initiated.
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)
Conference coverage
SPT-300 appears in 3 CNS Pulse conference abstracts:
- Unlocking medicines for neuropsychiatry by enhancing oral absorption using a lymphatic-targeting prodrug technology
- Unlocking medicines for neuropsychiatry by enhancing oral absorption using a lymphatic-targeting prodrug technology
- Prediction of human pharmacokinetic profiles of Glyph platform prodrugs using animal and human data via a semi-mechanistic pharmacokinetic model
Identifiers
Sources
- BUOY-1 (NCT07065240) — ClinicalTrials.gov
- Seaport Therapeutics Announces First Patient Dosed in Phase 2b BUOY-1 Study of GlyphAllo (SPT-300) in MDD — Seaport Therapeutics