Small Molecule · ALTO-207

ALTO-207

Phase 2Alto Neuroscience, Inc. (ANRO)

A fixed-dose combination of pramipexole (a dopamine D3-preferring D3/D2 full agonist) and ondansetron (a selective 5-HT3 receptor antagonist) in a novel modified-release formulation. The ondansetron component mitigates pramipexole-associated nausea/vomiting, enabling more rapid titration to higher, potentially more antidepressant pramipexole doses (Phase 2b target 3.2 mg pramipexole + 15 mg ondansetron/day). Formerly CTC-501; in development for treatment-resistant depression.

Also known as: ALTO-207, CTC-501, pramipexole/ondansetron, pramipexole, ondansetron

Data current as of

Modality
Small molecule
Chemical class
aminobenzothiazole, carbazole
DEA schedule
Unscheduled
Mechanism
D3 agonist
Highest phase
Phase 2
Lead indication
Treatment-resistant depression
Developer
Alto Neuroscience, Inc. (ANRO)
Trials
2 tracked · 1 recruiting · 49 sites
Next catalyst
2H 2027 — Topline data (Treatment-resistant depression)

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.

TargetActionAffinity
D3primaryDRD3AgonistpKi 8.5ⓘ
5-HT3 receptorHTR3AAntagonist—ⓘ
D2DRD2Agonist—ⓘ

Formulations

FormulationRouteRegimenPharmacokinetics
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
OralOnce daily—

Development timeline

Phase 2Jun 2025 – Dec 2027
  1. UpcomingALTO-207 Phase 2b TRD topline (MADRS)↗
  2. 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.↗
  3. 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).↗

ALTO-207 for Treatment-resistant depression

Phase 2RecruitingTreatment-resistant depression indication →

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.

Readouts

  • 2H 2027AnticipatedTopline dataNCT07553637

    ALTO-207 Phase 2b TRD topline (MADRS) ↗

Clinical trials

NCT07553637Phase 2Recruitingn=178

A Randomized, Double-blind, Placebo-controlled Trial of ALTO-207 in Adults With Treatment-resistant Depression

Started May 2026· Primary completion Nov 2027· 📍 48 sites across 2 countries (United States, United Kingdom)

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

Started Sept 2018· Primary completion Dec 2025· 📍 1 site across 1 country (United States)

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.

Conference coverage

ALTO-207 appears in 2 CNS Pulse conference abstracts:

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Identifiers

    Sources

    1. A Randomized, Double-blind, Placebo-controlled Trial of ALTO-207 in Adults With Treatment-resistant Depression (NCT07553637) — ClinicalTrials.gov
    2. Alto Neuroscience Announces Acquisition of Novel Dopamine Agonist Combination Product Candidate (ALTO-207/CTC-501) — Alto Neuroscience IR
    3. Alto Neuroscience Initiates Phase 2b Trial of ALTO-207 in Treatment-Resistant Depression — Alto Neuroscience / Business Wire
    4. Alto Neuroscience Initiates Phase 2b Trial of ALTO-207 in Treatment-Resistant Depression — Alto Neuroscience / BioSpace
    5. Ondansetron: A Selective 5-HT3 Receptor Antagonist and Its Applications in CNS-Related Disorders — PMC
    6. Phase 2a Study of Pramipexole IR With Ondansetron in MDD (NCT03642964) — ClinicalTrials.gov
    7. Pramipexole (ligand 953) - dopamine receptor binding data — IUPHAR/BPS Guide to Pharmacology