BPL-003 · program

BPL-003 (intranasal 5-MeO-DMT benzoate) for Treatment-resistant depression

Phase 2ActiveAtai Beckley N.V. (AtaiBeckley) (ATAI)
  • Breakthrough Therapy

Indications for BPL-003: Treatment-resistant depression · Phase 2 Alcohol use disorder · Phase 2

BPL-003 (intranasal mebufotenin) for treatment-resistant depression. Phase 2b (NCT05870540, n=196) met its primary endpoint with rapid, durable single-dose MADRS reductions (8 mg -12.1, 12 mg ~-10.8 to -11.1 vs 0.3 mg -5.8 at Day 29). FDA Breakthrough Therapy granted Oct 2025; pivotal Phase 3 planned ~Q2 2026. Also in development for alcohol use disorder.

Data current as of

Development timeline

Phase 2Jul 2025 – Oct 2025
  1. FDA granted Breakthrough Therapy Designation for BPL-003 in TRD; Phase 3 planned ~Q2 2026.↗
  2. Positive Phase 2b topline: single 8 mg / 12 mg dose produced rapid significant MADRS reductions vs 0.3 mg comparator at Day 29, largely maintained to Day 57.↗

Clinical trials in Treatment-resistant depression

NCT05870540Phase 2Completedn=196

Dose-Finding Study of Intranasal BPL-003 in Treatment-Resistant Depression (with OLE)

Started Sept 2023· Primary completion Mar 2025· 📍 42 sites across 6 countries (United States, Spain, Poland, Germany)

metprimaryMADRS change at Day 29 — 8 mg -12.1; 12 mg ~-10.8 to -11.1; vs 0.3 mg -5.8

Single dose; 8 mg and 12 mg statistically significant vs comparator, effects largely maintained to Day 57 (company PR / press coverage).

NCT05660642Phase 1/2Recruitingn=64

Open-Label Phase 2a Study of BPL-003 in Treatment Resistant Depression

Started Feb 2023· Primary completion Nov 2026· 📍 3 sites across 1 country (United Kingdom)

Formulations

FormulationRouteRegimenPharmacokinetics
BPL-003 intranasal dry powderAptar Unidose dry-powder intranasal spray device
Single intranasal dose; doses of 8 mg and 12 mg studied in Phase 2b TRD (8 mg selected for Phase 3); 1-12 mg range in Phase 1 SAD.
IntranasalSingle doset½ 0.33 h · Tmax 0.15 h

Mechanism of action (compound-wide)

Delivers 5-MeO-DMT, a non-selective serotonergic agonist with highest affinity at 5-HT1A and additional 5-HT2A activation; 5-HT2A agonism mediates classic psychedelic effects while potent 5-HT1A agonism shapes its short-acting profile.

TargetActionAffinity
5-HT1AprimaryHTR1AAgonistKi 1.9 nMⓘ
5-HT2AHTR2AAgonist—ⓘ

← Full BPL-003 compound page (identity, identifiers, all indications)

Sources

  1. BPL-003 Phase 2b (NCT05870540) — ClinicalTrials.gov
  2. BPL-003 Phase 2b results — Psychedelic Alpha
  3. FDA Breakthrough Therapy for BPL-003 — atai / Beckley Psytech
  4. clinicaltrials.gov — ClinicalTrials.gov
  5. en.wikipedia.org — Reference
  6. Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-MeO-DMT benzoate) in healthy participants — Journal of Psychopharmacology (PMC)