ALTO-207 · program
ALTO-207 for Treatment-resistant depression
ALTO-207 (pramipexole + ondansetron fixed-dose, modified-release combination) for treatment-resistant depression. Registration-enabling Phase 2b trial (NCT07553637) initiated April 2026 and recruiting: ~178 adults with TRD (2-5 prior treatment failures, on stable background antidepressant), randomized 1:1 to ALTO-207 vs placebo over 8 weeks, titrated to 3.2 mg pramipexole + 15 mg ondansetron/day; primary endpoint change from baseline in MADRS. Topline data expected 2H 2027. Design intended to replicate the positive PAX-D pramipexole signal (Cohen's d 0.87, Lancet Psychiatry 2025) and the positive ALTO-207 Phase 2a MDD result (MADRS Cohen's d 1.1), supporting a streamlined path to registration.
Development timeline
- Registration-enabling Phase 2b trial (NCT07553637) of ALTO-207 in TRD initiated; ~178 patients, 1:1 vs placebo, 8 weeks, MADRS primary endpoint; topline 2H 2027.↗
- Alto Neuroscience acquired ALTO-207 (formerly CTC-501) from Chase Therapeutics; the completed Phase 2a study (NCT03642964) in MDD met primary and secondary endpoints (MADRS LSM diff vs placebo -8.2 at Week 8, p=0.025, Cohen's d=1.1).↗
Readouts
- 2H 2027AnticipatedTopline dataNCT07553637
ALTO-207 Phase 2b TRD topline (MADRS) ↗
Clinical trials in Treatment-resistant depression
NCT07553637Phase 2Recruitingn=178
A Randomized, Double-blind, Placebo-controlled Trial of ALTO-207 in Adults With Treatment-resistant Depression
NCT03642964CTC-501Phase 2Completedn=24
A Phase 2a Study to Evaluate the Safety, Tolerability and Initial Efficacy of Pramipexole IR, Given With Ondansetron in Patients With Major Depressive Disorder
metprimaryMADRS total score change from baseline at Week 8 — LSM difference vs placebo -8.2; Cohen's d=1.1 (0.025)
CTC-501 (now ALTO-207) met its primary and secondary endpoints: significantly greater improvement on MADRS vs placebo at Week 8 (LSM diff -8.2, p=0.025, Cohen's d=1.1); CGI-S Cohen's d=1.0. Well tolerated. Results presented at SOBP 2026.
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| ALTO-207 modified-release oral fixed-dose combinationmodified-release fixed-dose combination (pramipexole + ondansetron) Fixed-dose combination of pramipexole and ondansetron; titrated up to a target dose of 3.2 mg pramipexole and 15 mg ondansetron per day in the Phase 2b TRD trial | Oral | Once daily | — |
Mechanism of action
Combination of pramipexole, a dopamine D3-preferring D3/D2 receptor full agonist with established antidepressant activity, and ondansetron, a selective 5-HT3 receptor antagonist included to suppress pramipexole-associated nausea/emesis and thereby enable faster titration to higher (more efficacious) pramipexole doses. Antidepressant effect is driven by the pramipexole dopaminergic component; ondansetron is a tolerability enabler.
| Target | Action | Affinity |
|---|---|---|
| D3primaryDRD3 | Agonist | pKi 8.5ⓘ |
| 5-HT3 receptorHTR3A | Antagonist | —ⓘ |
| D2DRD2 | Agonist | —ⓘ |
← Full ALTO-207 compound page (identity, identifiers, all indications)
Sources
- A Randomized, Double-blind, Placebo-controlled Trial of ALTO-207 in Adults With Treatment-resistant Depression (NCT07553637) — ClinicalTrials.gov
- Alto Neuroscience Announces Acquisition of Novel Dopamine Agonist Combination Product Candidate (ALTO-207/CTC-501) — Alto Neuroscience IR
- Alto Neuroscience Initiates Phase 2b Trial of ALTO-207 in Treatment-Resistant Depression — Alto Neuroscience / Business Wire
- Alto Neuroscience Initiates Phase 2b Trial of ALTO-207 in Treatment-Resistant Depression — Alto Neuroscience / BioSpace
- Ondansetron: A Selective 5-HT3 Receptor Antagonist and Its Applications in CNS-Related Disorders — PMC
- Phase 2a Study of Pramipexole IR With Ondansetron in MDD (NCT03642964) — ClinicalTrials.gov
- Pramipexole (ligand 953) - dopamine receptor binding data — IUPHAR/BPS Guide to Pharmacology