Alto Neuroscience Announces Robust Replication of EEG Biomarker to Objectively Identify Patients with Cognitive Impairment in Schizophrenia

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MOUNTAIN VIEW, Calif.--(BUSINESS WIRE)--Sep 9, 2025--

Alto Neuroscience, Inc. (“Alto”) (NYSE: ANRO) a clinical-stage biopharmaceutical company focused on the development of novel precision medicines for neuropsychiatric disorders, today announced positive results from an independent, prospective replication study evaluating electroencephalography (EEG) biomarkers in people with schizophrenia. The study successfully replicated previous findings, demonstrating that event-related theta-band responses, particularly theta-band inter-trial coherence (ITC), robustly differentiate people with schizophrenia from healthy individuals.

The results provide strong validation for the use of this objective, brain-based measurement in identifying and evaluating patients. Alto is currently utilizing theta ITC as a key biomarker and primary outcome measure in its ongoing Phase 2 study of ALTO-101, an investigational novel PDE4 inhibitor for the treatment of CIAS.

“This successful replication marks an important and significant step forward for Alto and the field as we aim to bring objectivity and precision to complex conditions like schizophrenia,” said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. “For too long, drug development in this area has been hampered by subjective measures and biological heterogeneity. These data provide further compelling evidence that we have a reliable, non-invasive approach to identify specific patient populations and measure the effects of targeted therapies. Previously in a Phase 1 trial, ALTO-101 demonstrated significant effects on theta ITC and cognition after a single dose in healthy subjects. These outcomes taken together enhance our confidence in the relevance of theta ITC as a primary outcome in our ongoing Phase 2 trial of ALTO-101, as we work to deliver a much-needed new treatment option for patients.”

The analysis, which evaluated 155 individuals with schizophrenia and 272 healthy controls, was designed to replicate and extend prior findings from a large-scale study. The results showed that EEG measures of theta ITC and event-related spectral perturbation (ERSP) had the largest case-control differences, far exceeding traditional EEG and event-related potential measures in their ability to distinguish patients from healthy controls. Importantly, both theta ITC and ERSP were also significantly correlated with processing speed, a key domain of cognitive impairment in schizophrenia.

“The search for reliable biomarkers in psychiatry has been a long and challenging endeavor. The clear and replicable differentiation between patients with schizophrenia and healthy controls shown by these theta-band responses represents a clear advancement,” commented L. Elliot Hong, M.D., Professor of Psychiatry at the University of Texas Health Science Center at Houston. “These findings may provide the field with a validated, scalable biomarker that is likely to enhance the rigor of clinical trials and holds the potential to guide clinical practice and personalize patient care in the future. This is the kind of robust scientific validation needed to move the needle in developing new treatments for severe mental illness.”

Summary of Key Findings:

In this independent replication cohort, key findings demonstrated the strength of theta-band responses as biomarkers for CIAS:

• Strong differentiation: Theta ITC and ERSP showed the largest differences between patients with schizophrenia and healthy controls (Cohen’s d = 0.64 and 0.78, respectively; p < 0.001), indicating a very strong separation between the groups.
• Superior performance compared to traditional EEG markers: These novel theta-based measures outperformed more traditional biomarkers, including mismatch negativity (MMN) (Cohen’s d = 0.41) and resting-state theta power (Cohen’s d = 0.40). Neither of these traditional EEG measures demonstrated significant associations with processing speed.
• Consistent correlation with cognition: Both theta ITC and ERSP demonstrated a statistically significant correlation with processing speed, a core deficit in CIAS (p < 0.05 and p < 0.01, respectively), reinforcing the biological relevance of this biomarker to the clinical impairment.

These results strongly support Alto’s utilization of theta ITC as a biomarker for CIAS and as a primary outcome measure to evaluate the effects of ALTO-101 on cognitive impairment in the ongoing Phase 2 POC trial.

Alto expects to publish full details of this analysis through upcoming medical conferences or peer-reviewed publications.

About Cognitive Impairment Associated with Schizophrenia (CIAS)

Cognitive impairment is a core and disabling feature of schizophrenia, affecting areas such as memory, attention, processing speed, and executive function. These deficits are a primary determinant of poor functional outcomes for patients, impacting their ability to work, maintain social relationships, and live independently. Currently, there are no approved treatments for CIAS, representing a significant unmet medical need for the millions of people living with schizophrenia worldwide.

About Alto Neuroscience

Alto Neuroscience is a clinical-stage biopharmaceutical company with a mission to redefine psychiatry by leveraging neurobiology to develop personalized and highly effective treatment options. Alto’s Precision Psychiatry Platform™ measures brain biomarkers by analyzing EEG activity, neurocognitive assessments, wearable data, and other factors to better identify which patients are more likely to respond to Alto product candidates. Alto’s clinical-stage pipeline includes novel drug candidates in bipolar depression, major depressive disorder, treatment resistant depression (TRD), and schizophrenia, and other mental health conditions. For more information, visit www.altoneuroscience.com or follow Alto on X.

Forward-Looking Statements

This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “expects,” “plans,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding Alto’s expectations about the potential benefits, activity, effectiveness and safety of its product candidates and Precision Psychiatry Platform (“Platform”); statements regarding Alto’s expectations for the design, progress and results of its ongoing Phase 2 POC trial of ALTO-101 in CIAS; expectations regarding the timing of future publications,and Alto’s expectations with regard to the design and results of its clinical trials. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including uncertainties inherent in the initiation, progress and completion of clinical trials, including the Phase 2 POC trial of ALTO-101, and other important factors, any of which could cause Alto’s actual results to differ from those contained in the forward-looking statements, which are described in greater detail in the section titled “Risk Factors” in each of Alto’s Annual Report on Form 10-K for the fiscal year ended December 31, 2024 and Alto’s Quarterly Report on Form 10-Q for the fiscal quarter ended June 30, 2025 filed with the Securities and Exchange Commission (“SEC”) as well as in other filings Alto may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Alto expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as required by law.

Availability of Information on Alto’s Website

Alto routinely uses its investor relations website to post presentations to investors and other important information, including information that may be material. Accordingly, Alto encourages investors and others interested in Alto to review the information it makes public on its investor relations website.

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CONTACT: Investor and Media Contact:

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KEYWORD: UNITED STATES NORTH AMERICA CALIFORNIA

INDUSTRY KEYWORD: MENTAL HEALTH HEALTH NEUROLOGY CLINICAL TRIALS PHARMACEUTICAL BIOTECHNOLOGY

SOURCE: Alto Neuroscience, Inc.

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PUB: 09/09/2025 07:09 AM/DISC: 09/09/2025 07:09 AM

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