Phase 2 Study Initiated: ALTO-101 for Cognitive Impairment With Schizophrenia

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Alto Neuroscience has announced the initiation of a phase 2 double-blind, placebo-controlled study of the transdermal formulation of ALTO-101, a novel PDE4 inhibitor being studied for the treatment of cognitive impairment associated with schizophrenia (CIAS). Data from this phase 2 study is expected in the second half of 2025.¹

“We are excited to initiate our sixth phase 2 study as a company, across our pipeline programs, as we continue to redefine mental healthcare with Alto’s Precision Psychiatry Platform,” said Amit Etkin, MD, PhD, founder and CEO of Alto Neuroscience. “Cognitive impairment is disabling in many psychiatric disorders including schizophrenia, depression, and neurodegenerative diseases. ALTO-101 has the potential to address the cognitive aspects of these diseases with a known pro-cognitive mechanism, while also overcoming the side effects typically associated with PDE4 inhibitors. We look forward to completing this proof-of-concept study, as we believe ALTO-101 may benefit patients with CIAS and potentially become an important therapeutic option for a broad range of indications.”

The cross-over double-blind, placebo-controlled phase 2 study is expected to enroll approximately 70 adult participants aged 21 to 55 years old with schizophrenia and a demonstrable level of cognitive impairment. Alto will then evaluate the effects of ALTO-101 on electroencephalography (EEG) markers relevant to cognitive function and explore its effects on cognitive performance. The primary outcome in the study is the effect of ALTO-101 on theta band activity as measured using EEG at the end of each dose period.

The initiation of this phase 2 study comes at the heels of a recently completed phase 1 study of ALTO-101 in healthy adults, which demonstrated positive effects on cognition and EEG measures relevant to cognitive function. Alto’s novel transdermal formulation of ALTO-101 exhibited greater systemic drug exposure than orally administered ALTO-101 while also demonstrating a reduction in typical class-related adverse events.

At the Society of Biological Psychiatry Annual Meeting, Alto presented data that demonstratd theta band activity has both the greatest correlation with cognitive function in patients with schizophrenia among a comprehensive set of EEG measures as well as greatest case-control sensitivity. The findings support the suitability of the primary outcome measure being evaluated in the present study to demonstrate robust proof-of-concept of ALTO-101 as a potential treatment for CIAS.

Additionally, at the 2024 American Society of Clinical Psychopharmacology Annual Meeting, researchers shared the results from a recent phase 1 study of ALTO-101 for the treatment of cognitive impairment in central nervous system disorders, such as schizophrenia, in a poster presentation.² ALTO-101 increases cyclic adenosine monophosphate levels in critical brain regions, suggesting that it could be a novel treatment for cognitive deficits.

“These findings demonstrate strong pharmacodynamic effects of ALTO-101 in driving key brain processes important for cognition as measured by EEG, along with behavioral evidence of cognitive improvement,” the investigators stated.² “Since these measures index schizophrenia-related deficits in cognition and cognitive processing, these data support further development of ALTO-101 for the treatment of cognitive impairment associated with schizophrenia.”

References

1. Alto Neuroscience initiates phase 2 study of ALTO-101, a novel PDE4 inhibitor, in cognitive impairment associated with schizophrenia. News release. June 20, 2024. https://investors.altoneuroscience.com/news/news-details/2024/Alto-Neuroscience-Initiates-Phase-2-Study-of-ALTO-101-a-Novel-PDE4-Inhibitor-in-Cognitive-Impairment-Associated-with-Schizophrenia/default.aspx

2. Phase 1 study findings support efficacy of ALTO-101 for the treatment of cognitive impairment in schizophrenia. Psychiatric Times. June 6, 2024. https://www.psychiatrictimes.com/view/phase-1-study-findings-support-efficacy-of-alto-101-for-the-treatment-of-cognitive-impairment-in-schizophrenia