Small Molecule · Apimostinel

Apimostinel (GATE-202)

Phase 2Syndeio Biosciences, Inc.

Second-generation intravenous NMDA-receptor modulator for the acute treatment of major depressive disorder. An amidated tetrapeptide (Thr-Pro-(2R)-2-benzyl-Pro-Thr-amide) derived from the Naurex GLYX-13/rapastinel chemotype; a benzyl substituent improves metabolic stability and potency (~1000-fold more potent in vitro than rapastinel). Acts as a positive modulator at a novel site on the NMDA receptor, independent of the glycine co-agonist site, enhancing activity-dependent synaptic plasticity (mechanism contrasts ketamine's channel block). Originated at Naurex → Allergan/AbbVie (AGN-241660) → Gate Neurosciences (GATE-202), now operating as Syndeio Biosciences. Coded as small_molecule per project convention despite peptidic structure.

Also known as: Apimostinel, GATE-202, NRX-1074, AGN-241660, 1421866-48-9

Data current as of

Modality
Small molecule
Chemical class
Tetrapeptide, peptide
Chemistry
Single enantiomer
Mechanism
GluN2B PAM
Highest phase
Phase 2
Lead indication
Major depressive disorder
Developer
Syndeio Biosciences, Inc.
Trials
2 tracked · 1 recruiting · 13 sites
Next catalyst
2029 — Topline data (Major depressive disorder)

Mechanism of action

Positive modulator of the NMDA receptor acting at a novel binding site independent of the glycine co-agonist site; enhances NMDAR-mediated, activity-dependent synaptic plasticity rather than blocking the channel. Same allosteric-site family as the sibling oral compound zelquistinel (GATE-251). The original 2014 Naurex Phase 2 registered it as an 'NMDA receptor functional partial agonist'; the current company characterization is a positive allosteric modulator (PAM).

TargetActionAffinity
GluN2BprimaryGRIN2BPAM—ⓘ

Formulations

FormulationRouteRegimenPharmacokinetics
Apimostinel oralOral——
Apimostinel intravenous injection
Single IV injection; doses of 1 mg, 5 mg, or 10 mg evaluated in Phase 2 MDD trial (NCT02067793)
IntravenousSingle dose—

Development timeline

Phase 2Feb 2015 – Mar 2029
  1. UpcomingPhase 2 apimostinel +/- ASAT in MDD: primary completion anticipated 2029
  2. Investigator-led Phase 2 study NCT06400121 (apimostinel 10 mg IV +/- ASAT digital training; U. Pittsburgh / Syndeio) started.
  3. Naurex/Allergan Phase 2 dose-ranging IV study (NCT02067793, 1/5/10 mg, n=151) completed.
  4. pendingNaurex Phase 2 (NCT02067793): single-dose IV apimostinel reported rapid 24-hour antidepressant effect↗

Apimostinel (GATE-202) for Major depressive disorder

Phase 2RecruitingMajor depressive disorder indication →

Apimostinel (GATE-202), single intravenous-dose NMDAR modulator for acute MDD. Currently in an investigator-led Phase 2 study (NCT06400121, University of Pittsburgh / Dr. Rebecca Price, with Syndeio Biosciences as collaborator) testing apimostinel 10 mg IV with or without subsequent Automated Self-Association Training (ASAT) digital neurocognitive training to extend the duration of single-dose antidepressant effect. A prior Naurex/Allergan Phase 2 dose-ranging study (NCT02067793, 1/5/10 mg IV, n=151) completed Feb 2015.

Readouts

  • 2029AnticipatedTopline dataNCT06400121

    Phase 2 apimostinel +/- ASAT in MDD: primary completion anticipated 2029

  • 2015-02-01ReportedTopline datapendingNCT02067793

    Naurex Phase 2 (NCT02067793): single-dose IV apimostinel reported rapid 24-hour antidepressant effect ↗

Clinical trials

NCT06400121Phase 2Recruitingn=150

Phase 2, Randomized, Double-Blind, Placebo-Controlled, Single Intravenous Dose, Parallel Efficacy Study of Apimostinel With or Without Subsequent Automated Self-Association Training in Subjects With Major Depressive Disorder

Started Oct 2024· Primary completion Mar 2029· 📍 1 site across 1 country (United States)

NCT02067793Phase 2Completedn=151

Study of Intravenous NRX-1074 in Patients With Major Depressive Disorder

Started Mar 2014· Primary completion Feb 2015· 📍 12 sites across 1 country (United States)

Related compounds

Other GluN2B compounds

More from Syndeio Biosciences, Inc.

Identifiers

Sources

  1. Apimostinel — Wikipedia
  2. Apimostinel + Automated Neurocognitive Training for Depression (NCT06400121) — ClinicalTrials.gov
  3. Gate Neurosciences and University of Pittsburgh Collaborate to Initiate Phase 2 Trial Combining Apimostinel with Digital Therapeutic for Depression — Syndeio Biosciences / Gate Neurosciences
  4. Study of Intravenous NRX-1074 in Patients With Major Depressive Disorder — ClinicalTrials.gov