Small Molecule · GM-1020

Blixeprodil (GM-1020)

Phase 2Gilgamesh Pharmaceuticals, Inc.

Blixeprodil (GM-1020), the (R)-enantiomer of 4-fluorodeschloroketamine, is an orally bioavailable non-competitive NMDA-receptor (channel/PCP-site) antagonist in the arylcyclohexylamine class, designed for ketamine-like rapid antidepressant efficacy with oral dosing and improved tolerability. Lead indication major depressive disorder.

Also known as: GM-1020, Blixeprodil, (R)-4-fluorodeschloroketamine

Data current as of

Modality
Small molecule
Chemical class
arylcyclohexylamine
Chemistry
Single enantiomer
Mechanism
NMDA receptor antagonist
Highest phase
Phase 2
Lead indication
Major depressive disorder
Developer
Gilgamesh Pharmaceuticals, Inc.
Trials
1 tracked · 1 sites

Mechanism of action

Non-competitive NMDA-receptor antagonist binding the PCP/channel site (voltage-dependent block), non-subunit-selective across GluN2A/GluN2B. Low-micromolar affinities.

TargetActionAffinity
NMDA receptorprimaryGRIN1AntagonistKi 3.25 µMⓘ

Formulations

FormulationRouteRegimenPharmacokinetics
Blixeprodil oral
140 mg and 210 mg oral doses studied (Phase 2a: 140 mg single dose in Part A; 140 mg or 210 mg twice weekly for 2 weeks in Part B)
OralTwice weeklyt½ 4.3 h · Tmax 1.5 h · F 60%

Development timeline

Phase 2May 2024 – Jan 2026
  1. Positive Phase 2a topline; -6.3 MADRS vs placebo at 24h (p=0.006); 53% Day-42 remission. Late-stage studies planned for 2026.↗
  2. Phase 2a MDD trial initiated; first subject dosed.↗

Blixeprodil (GM-1020) for Major depressive disorder

Phase 2CompletedMajor depressive disorder indication →

Blixeprodil (GM-1020) for MDD. Phase 2a (NCT06309277) completed; positive topline announced 6 Jan 2026: single oral dose gave -6.3 MADRS vs placebo at 24h (p=0.006); 53% remission at Day 42 (multiple-dose arm), sustained through 28-day follow-up. Company intends late-stage studies in 2026.

Clinical trials

NCT06309277Phase 2Completedn=46

Two-Part Study of Single and Multiple Oral Doses of GM-1020 in Major Depressive Disorder

Started Feb 2024· Primary completion Mar 2025· 📍 1 site across 1 country (United Kingdom)

metprimaryMADRS change vs placebo, 24h after single 140mg oral dose — -6.3 points (effect size 0.85) (0.006)

Day 8 -5.1 (p=0.076); 53% remission at Day 42 in the multiple-dose arm, sustained through 28-day follow-up.

Related compounds

Other NMDA receptor compounds

More from Gilgamesh Pharmaceuticals, Inc.

Identifiers

Sources

  1. Blixeprodil — Wikipedia
  2. Gilgamesh Pharma Announces Positive Topline Phase 2a Results for Blixeprodil (GM-1020) in Major Depressive Disorder — Gilgamesh / PR Newswire
  3. GM-1020 Phase 2a MDD (NCT06309277) — ClinicalTrials.gov
  4. GM-1020: oral NMDA antagonist with antidepressant-like effects — Molecular Psychiatry (PMC)
  5. prnewswire.com — Reference