Psychedelic · GM-2505

Bretisilocin (GM-2505)

Phase 2Gilgamesh Pharmaceuticals, Inc.

Bretisilocin (GM-2505) is 5-fluoro-N-methyl-N-ethyltryptamine (5F-MET), a DMT analogue and rapid/short-acting serotonergic psychedelic given by IV infusion for moderate-to-severe MDD, designed for a ~60-90 min experience. Not a 5-MeO-DMT compound. AbbVie agreed to acquire the asset from Gilgamesh (Aug 2025, up to $1.2B).

Also known as: GM-2505, Bretisilocin, 5F-MET, 5-fluoro-N-methyl-N-ethyltryptamine

Data current as of

Key facts

Modality
Psychedelic
Chemical class
tryptamine
DEA schedule
Unscheduled
Chemistry
Achiral
Mechanism
5-HT2A agonist
Highest phase
Phase 2
Lead indication
Major depressive disorder
Developer
Gilgamesh Pharmaceuticals, Inc.
Trials
1 tracked · 1 recruiting · 1 sites

Mechanism of action#

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.

1 nM10 nM100 nMSERTSERT — releaser — EC50 8.4 nMEC50 8.4 nM5-HT2C5-HT2C — agonist — EC50 9.5 nMEC50 9.5 nM5-HT2A5-HT2A — agonist — EC50 15 nMEC50 15 nM
Binding affinity on a log scale — further left is more potent. Values from the sourced literature (see table).
TargetActionAffinity
5-HT2AprimaryHTR2AAgonistEC50 15 nMⓘ
5-HT2CHTR2CAgonistEC50 9.5 nMⓘ
SERTSLC6A4ReleaserEC50 8.4 nMⓘ

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

Development timeline#

Jan 24Jul 24Jan 25Jul 25Jan 26Jul 26TodayPhase 113 May 2024 — Partnership — AbbVie–Gilgamesh collaboration and option-to-license agreement30 Nov 2023 — phase change — Phase 1 SAD completed; single IV doses produced 60-90 min psychedelic effects, well tolerated.Phase 225 Aug 2025 — phase change — AbbVie announced agreement to acquire bretisilocin (GM-2505), up to $1.2B.25 Aug 2025 — Acquisition — AbbVie to acquire Gilgamesh's bretisilocin (GM-2505) program27 May 2025 — phase change — Positive Phase 2a topline in MDD: 94% MADRS remission at Day 29.
Phase change Readout Event UpcomingHover a marker for details.
Phase 2May 2025 – Aug 2025
  1. AbbVie announced agreement to acquire bretisilocin (GM-2505), up to $1.2B.↗
  2. AcquisitionAbbVie to acquire Gilgamesh's bretisilocin (GM-2505) program↗
  3. Positive Phase 2a topline in MDD: 94% MADRS remission at Day 29.↗
Phase 1Nov 2023 – May 2024
  1. PartnershipAbbVie–Gilgamesh collaboration and option-to-license agreement↗
  2. Phase 1 SAD completed; single IV doses produced 60-90 min psychedelic effects, well tolerated.↗

Bretisilocin (GM-2505) for Major depressive disorder#

Phase 2RecruitingMajor depressive disorder indication →

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.

Clinical trials#

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.

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 and Gilgamesh Pharmaceuticals Announce Collaboration and Option-to-License Agreement to Develop Next-Generation Therapies for Psychiatric Disorders — AbbVie
  3. AbbVie to Acquire Gilgamesh Pharmaceuticals' Bretisilocin — AbbVie
  4. GM-2505 Phase 2a MDD (NCT06236880) — ClinicalTrials.gov
  5. GM-2505 positive Phase 2a topline in MDD — Gilgamesh / PR Newswire
  6. prnewswire.com — Reference