Alto Neuroscience Announces Initiation of Phase 2 Study of ALTO-203 in Patients with Major Depressive Disorder

Alto Neuroscience, Inc. (“Alto”) (NYSE: ANRO) today 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.

“This is the fifth Phase 2 study we have initiated across our pipeline, a milestone that marks significant progress in our efforts to redefine mental healthcare through our Precision Psychiatry Platform,” said Jessica Powell, chief development officer of Alto Neuroscience. “In a Phase 1 study, ALTO-203 demonstrated an acute increase in positive emotion relative to placebo and across several dosage levels. We look forward to completing this proof-of-concept study in patients as we believe this response may be an important attribute of an antidepressant to benefit patients with MDD and higher levels of anhedonia specifically.”

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.