ALTO-300 · program

ALTO-300 (agomelatine) for Major depressive disorder

Phase 2ActiveAlto Neuroscience, Inc. (ANRO)

ALTO-300 (agomelatine 25 mg) Phase 2b adjunctive for MDD, EEG-biomarker-selected (NCT05922878). Favorable interim analysis (Feb 2025) recommended continuing with ~50 more biomarker-positive patients (final ~200); topline expected mid-2026. Phase 2a (Dec 2023) showed greater MADRS improvement in biomarker-positive patients.

Data current as of

Development timeline

Phase 2Dec 2023 – Feb 2025
  1. Favorable Phase 2b interim analysis; study continues (final sample ~200); topline expected mid-2026.↗
  2. Positive MDD Phase 2a in EEG-biomarker-positive patients.↗

Clinical trials in Major depressive disorder

NCT05157945Phase 2Completedn=148

ALTO-300 in Depression (ALTO-300-004)

Started Feb 2022· Primary completion Apr 2023· 📍 4 sites across 1 country (United States)

NCT05118750Phase 2Completedn=91

ALTO-300 in Depression

Started Dec 2021· Primary completion May 2023· 📍 11 sites across 1 country (United States)

NCT05922878Phase 2Recruitingn=200

Phase 2b Study of ALTO-300 (Agomelatine) in Major Depressive Disorder

· 📍 45 sites across 1 country (United States)

Formulations

FormulationRouteRegimenPharmacokinetics
ALTO-300 oral tablet
25 mg once daily; agomelatine's approved (Valdoxan) label specifies 25 mg once daily taken orally at bedtime. Alto is developing ALTO-300 at 25 mg as an adjunctive treatment for MDD.
OralOnce nightlyt½ 2 h · Tmax 1.5 h · F 1%

Mechanism of action (compound-wide)

Melatonin MT1/MT2 receptor agonist and 5-HT2C antagonist; the melatonergic agonism (primary) plus 5-HT2C antagonism underlies antidepressant activity. ALTO-300 pairs this with an EEG biomarker for patient selection.

TargetActionAffinity
MT1primaryMTNR1AAgonistKi 0.1 nMⓘ
5-HT2CHTR2CAntagonistKi 631 nMⓘ
MT2MTNR1BAgonistKi 0.12 nMⓘ

← Full ALTO-300 compound page (identity, identifiers, all indications)

Sources

  1. Agomelatine — Wikipedia
  2. ALTO-300 Phase 2b favorable interim — Alto Neuroscience
  3. ALTO-300 Phase 2b MDD (NCT05922878) — ClinicalTrials.gov
  4. clinicaltrials.gov — clinicaltrials.gov
  5. clinicaltrials.gov — clinicaltrials.gov
  6. businesswire.com — Reference
  7. Valdoxan 25 mg film-coated tablets - Summary of Product Characteristics — electronic medicines compendium (emc)