Company Announcements

– Convergent clinical and preclinical evidence supports the mechanistic link between ALTO-300 and the biomarker, a measure of greater EEG irregularity, being used for patient selection –

– Completed Phase 2a and ongoing Phase 2b trial of ALTO-300 in MDD underscore favorable tolerability profile for 25mg dose –

MOUNTAIN VIEW, Calif.--(BUSINESS WIRE)--May 29, 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 a presentation at the American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, in Scottsdale, Arizona, held May 27-30, 2025.

ALTO-300, also known as agomelatine, is an oral, small molecule designed to act as a melatonin agonist and 5-HT2C antagonist being developed at 25mg as an adjunctive treatment in the United States for patients with MDD, characterized by an EEG biomarker. Agomelatine is an approved antidepressant medication at both 25mg and 50mg in Europe and Australia but has not been approved in the United States. In clinical studies, the 50mg dose of agomelatine was associated with low levels of reversible liver enzyme elevations, which were not associated with liver failure. In comparison to the 50mg dose of agomelatine, the 25mg dose has been shown to have similar antidepressant activity while avoiding the rates of liver function test (LFT) elevations associated with the 50mg dose.

“Our ASCP presentation continues to support the unique biomarker opportunity for patient stratification and reinforces the well-established safety and tolerability profile for ALTO-300,” said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. “Agomelatine has been studied in thousands of patients globally and evidence from meta-analyses and real-world clinical care demonstrates the 25mg dose achieves an optimal balance of antidepressant activity without the concern of LFT elevation. These data are consistent with the positive results from our completed Phase 2a trial, and we are encouraged by the safety and tolerability profile of ALTO-300 in our ongoing Phase 2b trial in patients with major depressive disorder. Taken together, we believe the selected 25mg dose of ALTO-300 is well positioned to demonstrate clinical effects while avoiding the low LFT elevation rates associated with the 50mg dose, which typically occur early, are non-cumulative, resolve quickly, and are not associated with liver failure.”

Summary of Data Presented

ALTO-300 Safety and Tolerability Profile

The most common adverse event observed in the completed Phase 2a trial of ALTO-300 was headache. Additionally, the Phase 2a and Phase 2b trials have involved monitoring for elevated liver enzymes (≥ 3 times the upper limit of normal), with the Phase 2b trial including a stopping rule for elevated liver enzymes. No LFT elevations ≥ 3 times the upper limit of normal were observed in the Company’s 239-patient completed Phase 2a trial, and no patients have been stopped in the ongoing Phase 2b trial due to liver enzyme elevation, which remains blinded.

ALTO-300 EEG Biomarker

The ALTO-300 biomarker signal likely reflects increased neural noise due to elevated 5-HT2C tone and reduced dopaminergic activity. Increasing 5-HT2C activity in a preclinical rodent model or directly depleting dopamine in a healthy human volunteer study—both the oppositive mechanistic effect of ALTO-300—resulted in greater EEG irregularity, consistent with a biomarker positive profile. These data reinforce the direct link between ALTO-300 and the EEG biomarker used to identify MDD patients who are more likely to be responders to treatment.

The following poster presented at ASCP 2025 is available under “Publications” in the platform section of Alto’s website:

• ALTO-300 as Adjunctive Treatment for Major Depressive Disorder Supported by Mechanistic Validation of Patient Selection Biomarker and Well-Established Safety and Tolerability Profile
  • Poster First Author: Michael Avissar, Ph.D.

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, 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, and effectiveness of its product candidates, biomarkers, and Precision Psychiatry Platform (“Platform”); 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 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 Alto’s Annual Report on Form 10-K for the fiscal year ended December 31, 2024 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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20250529090308/en/

Investor Contact:
Nick Smith
investors@altoneuroscience.com

Media Contact:
Mari Purpura
media@altoneuroscience.com

Source: Alto Neuroscience, Inc.