Alto Neuroscience Begins Phase 2 Trial of ALTO-101 for Schizophrenia-Related Cognitive Impairment

LOS ALTOS, Calif.-- Alto Neuroscience, Inc. has announced the beginning of a Phase 2 double-blind, placebo-controlled clinical trial for the transdermal formulation of ALTO-101, a PDE4 inhibitor being developed to treat cognitive impairment in schizophrenia patients. The results from this study are expected to be available in the latter half of 2025.

Amit Etkin, M.D., Ph.D., the founder and CEO of Alto Neuroscience, expressed enthusiasm about the company's sixth Phase 2 study. He emphasized the significance of cognitive impairment in psychiatric disorders such as schizophrenia, depression, and neurodegenerative diseases. ALTO-101 aims to address these cognitive issues with a known pro-cognitive mechanism, while also mitigating the side effects commonly associated with PDE4 inhibitors. Etkin is optimistic about the potential of ALTO-101 to become a vital treatment option for various indications beyond cognitive impairment associated with schizophrenia.

Previously, Alto completed a Phase 1 trial of ALTO-101 in healthy adults, which showed positive effects on cognition and EEG measures related to cognitive function. The new transdermal formulation of ALTO-101 demonstrated greater systemic drug exposure compared to the oral formulation and had fewer associated adverse events.

The new Phase 2 study will involve a cross-over, double-blind, placebo-controlled, and dose-escalating approach. It will enroll approximately 70 adults aged 21-55 years with schizophrenia and notable cognitive impairment. The study will assess the effects of ALTO-101 on EEG markers significant to cognitive function and explore its impact on cognitive performance. The primary outcome will be the effect on theta band activity, as measured by EEG, at the end of each dosage period.

During a recent Society of Biological Psychiatry (SOBP) Annual Meeting, Alto presented data demonstrating that theta band activity has the highest correlation with cognitive function in schizophrenia patients compared to other EEG measures. This finding, which was prospectively replicated, supports the use of theta band activity as a primary outcome measure for the current study, providing robust proof-of-concept for ALTO-101 as a potential treatment for cognitive impairment associated with schizophrenia.

ALTO-101 is a small molecule PDE4 inhibitor designed to address cognitive impairment in schizophrenia, a condition marked by negative and cognitive symptoms, with no targeted treatments currently available. The transdermal delivery system for ALTO-101, developed in collaboration with MEDRx, aims to achieve steady state drug concentrations to enhance safety, tolerability, and pharmacokinetics. In earlier Phase 1 clinical trials, ALTO-101 showed brain penetration, significant CNS-relevant pharmacodynamic effects, and was well-tolerated across therapeutic doses.

Schizophrenia is a severe, chronic mental illness affecting approximately 24 million individuals worldwide, including 2.8 million in the United States. It features a complex set of symptoms, including hallucinations, delusions, difficulty enjoying life, social withdrawal, and cognitive deficits such as impaired memory, concentration, and decision-making. Many individuals with schizophrenia struggle to live independently and often need lifelong caregiver support. About 70% of people with schizophrenia experience cognitive impairment, and there are no approved treatments specifically targeting these cognitive and negative symptoms.

Alto Neuroscience is a biopharmaceutical company focused on transforming psychiatry through neurobiology, aiming to develop personalized treatments. Their Precision Psychiatry Platform™ uses brain biomarkers from EEG activity, neurocognitive assessments, and wearable data to identify patients likely to respond to their treatments. Alto's clinical pipeline includes drug candidates targeting depression, PTSD, schizophrenia, and other mental health conditions.