Alto Neuroscience has announced that it has completed patient enrollment in its Phase 2 proof-of-concept trial of ALTO-101, a novel transdermal PDE4 inhibitor aimed at treating cognitive impairment associated with schizophrenia (CIAS). 

 

Topline data are expected after dosing and analysis, which will guide the drug’s next development steps.

 

Cognitive impairment is a persistent, core feature of schizophrenia affecting nearly all patients and remains a major driver of long-term disability, with no currently approved pharmacologic treatments.

 

Alto met its enrollment goal with 83 patients across 13 US clinical sites. The randomized, double-blind, placebo-controlled crossover study evaluates ALTO-101’s effects on electroencephalography (EEG) measures linked to cognitive dysfunction. Participants receive 10 days of ALTO-101 or placebo, followed by a washout, then 10 days of the alternate treatment—allowing sensitive within-subject comparisons of EEG and cognitive outcomes.

 

“This milestone brings us closer to potentially delivering a first-of-its-kind treatment for the millions of patients suffering from the debilitating cognitive effects of schizophrenia," said Amit Etkin, founder and CEO of Alto Neuroscience. 

 

"Our baseline results have already replicated findings from three independent datasets, reinforcing our confidence in ALTO-101’s mechanism and our biomarker-driven approach. We look forward to reporting data from this study around the end of the first quarter.”

 

The study’s primary endpoint is theta-band inter-trial coherence (ITC), an EEG measure closely correlated with cognitive performance. Secondary endpoints include resting-state theta power, mismatch negativity, and auditory steady-state response, while cognitive performance is measured using select domains of the MATRICS Consensus Cognitive Battery (MCCB) and a computerized processing speed test.

 

Baseline analyses confirmed a significant link between reduced theta ITC and slower processing speed, replicating prior schizophrenia datasets and validating theta ITC as a biomarker for cognitive impairment. Alto’s patient selection strategy further enriched the study population for these deficits, strengthening the scientific rationale for ALTO-101.

 

Administered via a proprietary transdermal delivery system developed with MEDRx, ALTO-101 aims to reduce gastrointestinal side effects commonly associated with oral PDE4 inhibitors while maintaining central nervous system engagement.