Alto Neuroscience, Inc. announced the initiation of its Phase 2 double-blind, single- and multiple-dose study to determine the pharmacodynamic effects of ALTO-203 in MDD patients as well as assess its safety, tolerability, and pharmacokinetics. To date, ALTO-203 has demonstrated positive emotional and cognitive effects in healthy participants after a single dose. The present study will evaluate these effects in patients with MDD to determine the potential of ALTO-203 as an antidepressant.

ALTO-203 is a novel small molecule histamine H3 receptor inverse agonist being developed for the treatment of patients with MDD and elevated anhedonia, or the lack of motivation or pleasure. This Phase 2 study consists of two sequential double-blind, placebo-controlled treatment periods and examines two doses of ALTO-203 and placebo given as monotherapy in patients with MDD. The first period uses a randomized single-dose treatment design to evaluate patient pharmacodynamic responses to ALTO-203 compared to placebo.

The powered primary outcome is measured by an acute change in positive emotion assessed by the alertness and mood components of the Bond-Lader Visual Analog Scale (BL-VAS), an established scale of subjective feelings also used in a prior Phase 1 study of ALTO-203. The second period uses a 28-day, multi-dose exposure design to assess the safety of ALTO-203 in patients with MDD. Exploratory, non-powered objectives for the multi-dose period will evaluate changes in measures of depression, anhedonia, and other clinical symptoms, along with cognition, EEG, and wearables.

Alto expects to enroll approximately 60 adult participants with MDD and evidence of anhedonia, and report topline data from this study in the first half of 2025.