Alto Neuroscience at TD Cowen summit: pramipexole combo takes center stage

On September 23, 2026, Alto Neuroscience presented ALTO-207, a pramipexole and ondansetron combination, at the TD Cowen 6th Annual Novel Mechanisms in Neuropsychiatry Summit. The drug aims to address the issue of treatment-resistant depression, a condition where patients struggle to reach effective doses of pramipexole due to nausea and vomiting. Pramipexole, a dopamine D3/D2 agonist, has shown strong efficacy in depression when used alone, but its tolerability issues prevent clinicians from titrating to higher doses.

ALTO-207's unique selling point is its ability to reduce nausea and vomiting, allowing for faster and more effective dosing of pramipexole. The Phase IIb trial, which will enroll 178 patients, is designed to be conservative while still providing enough data to demonstrate the drug's effect. The trial's primary endpoint is a Cohen's d of 0.45, with statistical significance beginning at around 0.3 Cohen's d.

The company anticipates that over half of the patients will reach the target dose of 3.2 milligrams of pramipexole plus 15 milligrams of ondansetron daily. This dose is higher than historical averages of 1.5 to 2.3 milligrams. The trial will compare ALTO-207 to a placebo, with patients continuing on their current antidepressants during the two-week titration period and the six-week maintenance period.

Alto Neuroscience argues that the commercial case for ALTO-207 is supported by real-world prescribing patterns. Approximately 75% of clinicians titrate pramipexole at least 1.5 times slower than FDA labeling, with an average time to reach 1 milligram exceeding 18 months. Some clinicians even avoid the drug due to tolerability concerns.

By offering a better-tolerated version of pramipexole, Alto Neuroscience aims to meet the growing need among patients with two to five treatment failures, who may require a more accessible and effective treatment option.