Alto Neuroscience, a biopharmaceutical company focused on developing precision medicines for neuropsychiatric disorders, announced that its Phase 2b clinical trial of ALTO-100 for major depressive disorder (MDD) did not meet its primary endpoint. The study, which assessed the change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) compared to placebo, failed to demonstrate a statistically significant improvement in depressive symptoms in patients treated with ALTO-100.
The randomized, double-blind, placebo-controlled trial enrolled 301 adults with MDD across 34 sites in the U.S. Participants were defined by an objective, memory-based cognitive biomarker assessed prior to randomization. While the drug maintained a favorable safety and tolerability profile, it did not show benefit over placebo in pre-specified key secondary analyses.
Impact on Alto Neuroscience and Future Plans
Following the announcement, Alto Neuroscience's stock price experienced a significant drop. Amit Etkin, M.D., Ph.D., founder and CEO of Alto Neuroscience, expressed disappointment but reaffirmed the company's commitment to precision medicine 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," Etkin stated.
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."
ALTO-100 and Precision Psychiatry Platform
ALTO-100, a novel small molecule acquired from Palisade Bio, is also being evaluated as an adjunctive treatment in a Phase 2b study for bipolar depression. Alto Neuroscience's Precision Psychiatry Platform aims to leverage brain biomarkers to predict treatment response, using EEG activity, neurocognitive assessments, and wearable data.
The company's pipeline includes other drug candidates in development for MDD, such as ALTO-203 and ALTO-300, with data expected in the first half of 2025. Alto Neuroscience anticipates its current cash position will fund operations into 2027, supporting multiple upcoming clinical readouts.
Analyst Perspectives
Despite the trial failure, some analysts remain optimistic about Alto Neuroscience's approach. William Blair analyst Myles Minter noted that placebo-controlled MDD studies are historically high-risk and that the company remains confident in its biomarker stratification approach. Stifel analyst Paul Matties added that the failure of ALTO-100 should not undermine the company's overall concept and that other assets should not be written off.
