GM-2505 · program

Bretisilocin (GM-2505) for Major depressive disorder

Phase 2RecruitingGilgamesh Pharmaceuticals, Inc.

GM-2505 (bretisilocin) for moderate-to-severe MDD — Gilgamesh's lead program. Phase 2a (NCT06236880) reported positive topline 27 May 2025: single 10 mg IV gave -18.5 MADRS at 24h, deepening to -28.0 (94% remission) at Day 29 and sustained -25.1 at Day 74. AbbVie agreed to acquire the asset (Aug 2025) to advance late-stage development. MDD is the only named clinical indication.

Data current as of

Development timeline

Phase 2May 2025 – Aug 2025
  1. AbbVie announced agreement to acquire bretisilocin (GM-2505), up to $1.2B.↗
  2. Positive Phase 2a topline in MDD: 94% MADRS remission at Day 29.↗
Phase 1Nov 2023
  1. Phase 1 SAD completed; single IV doses produced 60-90 min psychedelic effects, well tolerated.↗

Clinical trials in Major depressive disorder

NCT06236880Phase 2Recruitingn=124

Phase 2a Study of Two Repeated Doses of GM-2505 in Major Depressive Disorder

Started Jan 2024· Primary completion Oct 2026· 📍 1 site across 1 country (United Kingdom)

metprimaryMADRS change at Day 29 (10 mg) — -28.0 points (94% remission)

Initial-cohort topline (n=40) reported 27 May 2025: -18.5 at 24h, -21.6 at Day 14 (70% remission), -28.0 at Day 29 (94% remission), -25.1 sustained at Day 74. Registry has no posted results.

Formulations

FormulationRouteRegimenPharmacokinetics
GM-2505 IV infusion
Single ascending IV doses up to 20 mg studied in Phase 1 (threshold effects at 1-3.3 mg; optimal psychedelic range ~10-15 mg IV; intense effects at 20 mg IV)
IntravenousSingle doset½ 0.75 h · Tmax 0.25 h

Mechanism of action (compound-wide)

A well-balanced 5-HT2A and 5-HT2C agonist that also releases serotonin; 5-HT2B partial agonist/antagonist with weak 5-HT1A activity. 5-HT2A agonism drives the psychedelic and rapid antidepressant effects.

TargetActionAffinity
5-HT2AprimaryHTR2AAgonistEC50 15 nMⓘ
5-HT2CHTR2CAgonistEC50 9.5 nMⓘ
SERTSLC6A4ReleaserEC50 8.4 nMⓘ

← Full GM-2505 compound page (identity, identifiers, all indications)

Sources

  1. A novel psychedelic 5-HT2A receptor agonist GM-2505: The pharmacokinetic, safety, and pharmacodynamic profile from a randomized trial healthy volunteer — J Psychopharmacology (2025)
  2. AbbVie to Acquire Gilgamesh Pharmaceuticals' Bretisilocin — AbbVie
  3. GM-2505 Phase 2a MDD (NCT06236880) — ClinicalTrials.gov
  4. GM-2505 positive Phase 2a topline in MDD — Gilgamesh / PR Newswire
  5. prnewswire.com — Reference