ALTO-203 · program
ALTO-203 for Major depressive disorder
Phase 2 exploratory POC (NCT06391593) in MDD with elevated anhedonia. The single-dose primary efficacy endpoint (Bond-Lader VAS) was NOT met (high placebo response), but positive pharmacodynamics were reported: EEG theta/beta ratio identified as a patient-selection biomarker (p<0.05 at 25 µg), plus improvements in sustained attention and objective sleep. Next steps TBD.
Development timeline
Clinical trials in Major depressive disorder
NCT06391593Phase 2Completedn=69
Phase 2 PD/PK/Safety Study of ALTO-203 in Major Depressive Disorder
missedprimaryBond-Lader VAS (positive emotion) — single dose
Primary efficacy endpoint not met (high placebo response). PD-positive: EEG theta/beta ratio reduced (p<0.05 at 25 µg); sustained-attention and objective-sleep improvements; ~2-pt MADRS improvement at Week 3 (25 µg).
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| ALTO-203 oral 25 mcg or 75 mcg once daily (QD); evaluated in a single-dose crossover period plus a 28-day multi-dose once-daily period in the Phase 2 MDD proof-of-concept trial (NCT06391593) | Oral | Once daily | — |
Mechanism of action
Histamine H3 receptor inverse agonist; H3 (auto/heteroreceptor) blockade increases dopamine in reward circuitry and enhances arousal/attention/mood — the rationale for targeting anhedonia in MDD.
| Target | Action | Affinity |
|---|---|---|
| H3 receptorprimaryHRH3 | Inverse agonist | —ⓘ |
← Full ALTO-203 compound page (identity, identifiers, all indications)
Sources
- Alto Neuroscience Identifies Biomarker and Reports Positive Pharmacodynamic Results from Exploratory Phase 2 Proof-of-Concept Trial of ALTO-203 — Alto Neuroscience
- investors.altoneuroscience.com — Reference
- PD, PK, and Safety of ALTO-203 in Patients With MDD — ClinicalTrials.gov