Small Molecule · ALTO-300

ALTO-300 (agomelatine)

Phase 2Alto Neuroscience, Inc. (ANRO)

Biomarker-guided oral agomelatine (melatonin MT1/MT2 agonist + 5-HT2C antagonist) in Phase 2b by Alto Neuroscience as adjunctive treatment for MDD, with patients selected by an EEG biomarker. Dosed 25 mg.

Also known as: ALTO-300, agomelatine

Data current as of

Key facts

Modality
Small molecule
Chemical class
Naphthalene, acetamide
Chemistry
Achiral
Mechanism
MT1 agonist
Highest phase
Phase 2
Lead indication
Major depressive disorder
Developer
Alto Neuroscience, Inc. (ANRO)
Trials
1 tracked · 1 recruiting · 45 sites

Mechanism of action#

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.

0.1 nM1 nM10 nM100 nM1 µMMT1MT1 — agonist — Ki 0.1 nMKi 0.1 nMMT2MT2 — agonist — Ki 0.12 nMKi 0.12 nM5-HT2C5-HT2C — antagonist — Ki 631 nMKi 631 nM
Binding affinity on a log scale — further left is more potent. Values from the sourced literature (see table).
TargetActionAffinity
MT1primaryMTNR1AAgonistKi 0.1 nMⓘ
5-HT2CHTR2CAntagonistKi 631 nMⓘ
MT2MTNR1BAgonistKi 0.12 nMⓘ

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%

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.↗

ALTO-300 (agomelatine) for Major depressive disorder#

Phase 2ActiveMajor depressive disorder indication →

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.

Clinical trials#

NCT05922878Phase 2Recruitingn=200

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

· 45 sites across 1 country

United States

Sources#

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