Alto Neuroscience, Inc. (“Alto”) (NYSE: ANRO), a clinical stage biopharmaceutical company focused on the development of novel precision medicines for neuropsychiatric disorders, today announced that the Phase 2b study of ALTO-100 in patients with major depressive disorder (MDD) did not meet its primary endpoint, assessed by a change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS), compared to placebo. The favorable safety and tolerability profile of ALTO-100 was consistent with previously reported studies.

“We are disheartened by the results from this study as the unmet need in this patient population is immense,” said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. “While the results are surprising and disappointing, I am proud of our team for conducting a first-of-its-kind precision biomarker-based study in psychiatry. We will move quickly to evaluate the full data set to better understand these findings and incorporate learnings from this large data set across our platform. We remain committed to our mission of helping patients get better faster by bringing precision medicine to psychiatry, and we expect our strong cash balance to support us through multiple near-term clinical milestones across our pipeline.”

Topline results from the Phase 2b study

The randomized, double-blind, placebo-controlled Phase 2b study was designed to evaluate ALTO-100 in adults with MDD, defined by an objective, memory based cognitive biomarker assessed prior to randomization. The primary endpoint was the change from baseline to the end of the 6-week double-blind treatment period on the MADRS, which is the standard regulatory endpoint in depression. The study was conducted across 34 sites in the U.S. and enrolled 301 adults with MDD.

• The biomarker-defined MDD patient group treated with ALTO-100 did not demonstrate a statistically significant improvement in depressive symptoms compared to placebo.
• ALTO-100 did not demonstrate benefit over placebo on the pre-specified key secondary analyses.
• ALTO-100 continued to demonstrate a favorable safety and tolerability profile, with no new safety signals observed in this study as compared to the previously completed clinical trials of ALTO-100.
  • The most common adverse events from the trial related to treatment with ALTO-100 were headache, nausea, and abnormal dreams – all of which were experienced at similar rates to placebo.
• The Company expects to complete analysis of the full data set to determine the most appropriate next steps, if any, to further evaluate ALTO-100 in MDD.

Adam Savitz, M.D., Ph.D., chief medical officer of Alto Neuroscience added, “While the Phase 2b results did not replicate the clinical results observed in the Phase 2a trial, we believe our approach to collecting and stratifying based on biomarkers represents an innovative approach to developing neuropsychiatric drugs. We are deeply grateful to the patients, physicians, trial site staff, and advocacy partners for their support.”

ALTO-100 is also being evaluated as an adjunctive treatment in a Phase 2b study in bipolar depression.

The Company expects its current cash position to fund planned operations into 2027 and through multiple upcoming clinical readouts, including two additional readouts in MDD with ALTO-203 and ALTO-300 expected in the first half of 2025.