Small Molecule · ALTO-101

ALTO-101

DiscontinuedAlto Neuroscience, Inc. (ANRO)
  • Fda Fast Track

Novel small-molecule phosphodiesterase-4 (PDE4) inhibitor from Alto Neuroscience, developed for cognitive impairment associated with schizophrenia (CIAS) and delivered via a proprietary transdermal patch (ALTO-101T) intended to provide steady-state exposure and mitigate the nausea/vomiting hallmark of the PDE4 class. PDE4 inhibition raises intracellular cAMP, a second messenger central to neuronal signaling and synaptic plasticity relevant to learning and memory.

Also known as: ALTO-101, ALTO-101T

Data current as of

Modality
Small molecule
Chemical class
PDE4 inhibitor
Mechanism
Phosphodiesterase 4 inhibitor
Highest phase
Discontinued
Lead indication
Schizophrenia
Developer
Alto Neuroscience, Inc. (ANRO)
Designations
Fda Fast Track
Trials
1 tracked · 14 sites
Next catalyst
2026-04-01 — Topline data (Schizophrenia)

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.

TargetActionAffinity
Phosphodiesterase 4primaryPDE4Inhibitor—ⓘ

Formulations

FormulationRouteRegimenPharmacokinetics
ALTO-101 oral
1 mg single oral dose (Phase 1 comparator arm to the transdermal patch)
OralSingle 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)
TransdermalOnce daily—

Development timeline

DiscontinuedApr 2026
  1. Upcoming↗
Phase 2Jun 2024 – Oct 2025
  1. FDA granted Fast Track designation to ALTO-101 for cognitive impairment associated with schizophrenia (CIAS).↗
  2. 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).↗
Phase 1Jan 2024
  1. Positive Phase 1 results reported for ALTO-101, a novel PDE4 inhibitor; transdermal delivery showed substantially lower class-related (emetic) adverse events.↗

ALTO-101 for Schizophrenia

DiscontinuedDiscontinuedSchizophrenia indication →

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).

Readouts

  • 2026-04-01AnticipatedTopline dataNCT06502964

Clinical trials

NCT06502964ALTO-101-201Phase 2Completedn=82

Double-Blind, Placebo-Controlled Study of ALTO-101 in Patients With Schizophrenia and Cognitive Impairment

Started Jun 2024· Primary completion Feb 2026· 📍 14 sites across 1 country (United States)

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.

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Identifiers

    Sources

    1. Alto Neuroscience Announces Positive Phase 1 Results for ALTO-101, a Novel PDE4 Inhibitor in Development for Schizophrenia — Alto Neuroscience
    2. Alto Neuroscience Initiates Phase 2 Study of ALTO-101 in CIAS — Alto Neuroscience
    3. Alto Neuroscience Receives FDA Fast Track Designation for ALTO-101 for CIAS — Alto Neuroscience
    4. Alto Neuroscience Reports Topline Data from Phase 2 Proof-of-Concept Study of ALTO-101 and Highlights Pipeline Advancements — Alto Neuroscience
    5. Double-Blind, Placebo-Controlled Study of ALTO-101 in Patients With Schizophrenia and Cognitive Impairment (NCT06502964) — ClinicalTrials.gov