ALTO-101 · program
ALTO-101 for Schizophrenia
- Fda Fast Track
DISCONTINUED in CIAS. The Phase 2 double-blind, placebo-controlled, dose-escalating crossover proof-of-concept study (NCT06502964; transdermal ALTO-101T) did NOT achieve statistical significance on its primary EEG or cognitive endpoints versus placebo. The overall effect on theta-ITC (theta inter-trial coherence, a measure correlated with cognitive performance) was a near-miss (d=0.34, p=0.052, n=83); a pre-specified, more cognitively impaired subgroup showed a nominally significant theta-ITC effect (d=0.44, p=0.03, n=59). ALTO-101 was generally well tolerated with substantially lower class-related (nausea/vomiting) adverse events via transdermal delivery. On Apr 1, 2026 Alto announced it does NOT plan to independently advance ALTO-101 in CIAS, will explore strategic partnering, and is prioritizing resources toward its lead program ALTO-207. FDA had granted Fast Track designation for ALTO-101 in CIAS (Oct 3, 2025).
Development timeline
- Upcoming↗
- FDA granted Fast Track designation to ALTO-101 for cognitive impairment associated with schizophrenia (CIAS).↗
- Phase 2 double-blind, placebo-controlled, dose-escalating crossover study of transdermal ALTO-101 in CIAS initiated (NCT06502964); primary endpoint = EEG theta band activity; ~70 adults (ages 21-55).↗
- Positive Phase 1 results reported for ALTO-101, a novel PDE4 inhibitor; transdermal delivery showed substantially lower class-related (emetic) adverse events.↗
Readouts
- 2026-04-01AnticipatedTopline dataNCT06502964
Clinical trials in Schizophrenia
NCT06502964ALTO-101-201Phase 2Completedn=82
Double-Blind, Placebo-Controlled Study of ALTO-101 in Patients With Schizophrenia and Cognitive Impairment
missedprimaryEEG theta band activity (and cognition) after 5 and 10 days of dosing vs placebo — theta-ITC d=0.34 (overall, n=83); d=0.44 in cognitively impaired subgroup (n=59) (0.052)
Primary EEG and cognitive endpoints NOT met vs placebo. Overall theta-ITC near-miss (d=0.34, p=0.052, n=83); pre-specified more cognitively impaired subgroup nominally significant (d=0.44, p=0.03, n=59). Generally well tolerated, with substantially lower class-related (nausea/vomiting) AEs via transdermal delivery. Trial ran to completion (not stopped early); outcome=missed.
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| ALTO-101 oral 1 mg single oral dose (Phase 1 comparator arm to the transdermal patch) | Oral | Single dose | — |
| ALTO-101 transdermal patchMEDRx proprietary transdermal delivery system (TDS) patch 18 mg per dose delivered via a once-daily 24-hour patch; steady-state plasma concentrations maintained over 24 h (Day 2 Cmax ~27.9 ng/mL) | Transdermal | Once daily | — |
Mechanism of action
Phosphodiesterase-4 (PDE4) inhibitor. By inhibiting PDE4-mediated breakdown of cyclic AMP (cAMP), ALTO-101 increases neuronal cAMP signaling implicated in synaptic plasticity, learning and memory — the rationale for targeting cognitive impairment in schizophrenia. Transdermal delivery is intended to reduce the dose-limiting emetic side effects of the PDE4 class.
| Target | Action | Affinity |
|---|---|---|
| Phosphodiesterase 4primaryPDE4 | Inhibitor | —ⓘ |
← Full ALTO-101 compound page (identity, identifiers, all indications)
Sources
- Alto Neuroscience Announces Positive Phase 1 Results for ALTO-101, a Novel PDE4 Inhibitor in Development for Schizophrenia — Alto Neuroscience
- Alto Neuroscience Initiates Phase 2 Study of ALTO-101 in CIAS — Alto Neuroscience
- Alto Neuroscience Receives FDA Fast Track Designation for ALTO-101 for CIAS — Alto Neuroscience
- Alto Neuroscience Reports Topline Data from Phase 2 Proof-of-Concept Study of ALTO-101 and Highlights Pipeline Advancements — Alto Neuroscience
- Double-Blind, Placebo-Controlled Study of ALTO-101 in Patients With Schizophrenia and Cognitive Impairment (NCT06502964) — ClinicalTrials.gov