ALTO-101 Receives FDA Fast Track Designation for Treatment of Cognitive Impairment Related to Schizophrenia

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Alto Neuroscience announced US Food and Drug Administration (FDA) Fast Track designation for ALTO-101, a transdermally administered treatment for cognitive impairment associated with schizophrenia.¹ There are currently no FDA approved treatments for cognitive impairment in schizophrenia.

The FDA based the Fast Track designation on data from a phase 1 trial of the drug which found greater exposure and fewer adverse events with novel transdermal administration of ALTO-101 vs an oral PDE4 inhibitor.² Alto Neuroscience reported significant and clinically relevant effects of ALTO-101 as measured by both electroencephalogram (EEG) and cognitive performance in healthy participants. Current research on the drug is with a phase 2 trial (NCT06502964), comparing ALTO-101 with placebo on EEG markers related to cognitive processing markers and measures of cognition in adults with cognitive impairment associated with schizophrenia. The primary endpoint for the study looks at effect on theta band activity measured by EEG at the end of each drug dose period.³

“Receiving Fast Track designation from the FDA underscores the critical need for new, effective treatments for patients suffering from cognitive impairment associated with schizophrenia,” said Amit Etkin, MD, PhD, chief executive officer of Alto Neuroscience, in a press release. “This designation is a significant milestone for the ALTO-101 program and we believe it is a testament to its potential as a novel treatment approach. Our Phase 1 data, which demonstrated significant and clinically relevant effects of ALTO-101 on both EEG measures and cognitive performance in healthy subjects, provides strong validation for its mechanism. We are committed to advancing this program expeditiously for the millions of patients who currently have no approved treatment options to address these debilitating cognitive deficits.”¹

ALTO-101 is a novel small molecule phosphodiesterase-4 (PDE4) inhibitor. PDE4 is an enzyme which breaks down cyclic adenosine monophosphate (cAMP), which is used in neural signaling and synaptic plasticity. Signaling and plasticity are essential for learning and memory; by inhibiting the PDE4 enzyme, ALTO-101 can increase cAMP, which may assist neural circuits and improve cognitive functioning. With deficits in cognitive function related to schizophrenia¾like impaired attention, memory, processing speed, and executive function¾ALTO-101 potentially can address this aspect of the disorder.

With Fast Track designation, the drug may be eligible for more frequent FDA meetings, as well as being eligible for accelerated approval and priority review. Enrollment is ongoing for a phase 2 proof-of-concept study of ALTO-101 for individuals with cognitive impairment associated with schizophrenia.⁴

References

1. Alto Neuroscience receives FDA fast track designation for ALTO-101 for the treatment of cognitive impairment associated with schizophrenia. Press release. October 3, 2025. Accessed October 3, 2025. https://www.businesswire.com/news/home/20251003096029/en/Alto-Neuroscience-Receives-FDA-Fast-Track-Designation-for-ALTO-101-for-the-Treatment-of-Cognitive-Impairment-Associated-with-Schizophrenia

2. Alto Neuroscience announces positive phase 1 results for ALTO-101, a novel PDE4 inhibitor in development for schizophrenia. Press release. April 23, 2024. Accessed October 3, 2025. https://investors.altoneuroscience.com/news/news-details/2024/Alto-Neuroscience-Announces-Positive-Phase-1-Results-for-ALTO-101-a-Novel-PDE4-Inhibitor-in-Development-for-Schizophrenia/default.aspx#xd_co_f=ZDUwNWMyNTktOTU0ZS00NzdiLTg5OGItZDNkNzE4NTZhZGRj~

3. Double-blind, placebo-controlled study of ALTO-101 in patients with schizophrenia and cognitive impairment. ClinicalTrials.gov. July 24, 2025. Accessed October 3, 2025. https://clinicaltrials.gov/study/NCT06502964#xd_co_f=ZDUwNWMyNTktOTU0ZS00NzdiLTg5OGItZDNkNzE4NTZhZGRj~

4. Kuntz L. Phase 2 study initiated: ALTO-101 for cognitive impairment with schizophrenia. Psychiatric Times. June 20, 2024. https://www.psychiatrictimes.com/view/phase-2-study-initiated-alto-101-for-cognitive-impairment-with-schizophrenia