Alto Neuroscience’s stock tumbled 60% on Wednesday morning, the day after the company said a mid-stage trial for its oral small molecule failed to improve symptoms of major depressive disorder.
In the Phase 2b trial, which the company described as a first-of-its-kind precision biomarker-based study in psychiatry, ALTO-100 didn’t show improvement over placebo in a change from baseline using the Montgomery-Åsberg Depression Rating Scale (MADRS) in 301 patients at the end of the six-week treatment period.
The trial also didn’t hit “key” secondary endpoints that included efficacy versus placebo in MDD as measured using the Clinician Global Impression Scale-severity — a tool used to measure the severity of illness — and remission rates based on MADRS. Alto said the safety and tolerability profile was “favorable” and consistent with previous data.
In a Phase 2a study last year, ALTO-100 hit the primary endpoint, with the treatment showing a greater improvement in both the monotherapy and adjunctive treatment groups.
Amit Etkin“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,” Alto CEO Amit Etkin said in a statement, adding that the company expects “our strong cash balance to support us through multiple near-term clinical milestones across our pipeline.”
Alto $ANRO went public earlier this year, bringing in $129 million in February, above its original plans to raise $89 million. In its latest financial filing in August, the Eli Lilly-backed startup said it expects its existing cash to provide runway into 2027.
ALTO-100 is still being investigated as an adjunctive treatment in a Phase 2b study in bipolar depression. Alto also has several upcoming data readouts for other assets that are expected next year. This includes ALTO-203, an H3 receptor inverse agonist, and ALTO-300 — both in major depressive disorder.
In a note on Wednesday, TD Cowen analysts said they were disappointed by the newest slate of data but still “optimistic” about the drug.
“We suspect the enrichment signal may have been seen in the adjunct MDD population,” TD Cowen’s Ritu Baral wrote. “Without additional detail on the Ph2b data, we hesitate to extend read-through to the rest of ANRO’s pipeline of agents paired with distinct biomarkers.”
Others on Wall Street were more concerned. Jefferies analysts told investors they think the “study’s failure is driven by a lack of drug effect rather than [management] execution error” and that Tuesday’s data “raises questions around ANRO’s overall biomarker approach to CNS/psychiatry.”