Pramipexole/Ondansetron

Looking to bounce back after its lead depression programme failed in a Phase II trial last year, Alto Neuroscience announced a small deal with Chase Therapeutics Tuesday through which it acquires a dopamine agonist combination product for treatment-resistant depression.ALTO-207, formerly CTC-501, combines pramipexole – a dopamine receptor agonist approved for Parkinson's disease – with the anti-nausea medication ondansetron in a fixed-dose formulation designed to enable higher dosing of pramipexole while mitigating its dose-limiting side effects. Pramipexole has shown antidepressant effects, but suffers from tolerability issues that require slow titration and often prevent patients from reaching therapeutic doses."With proprietary insights on dopamine biomarkers in depression that enable targeted neuropsychiatric drug development, we are uniquely positioned to advance ALTO-207, a differentiated, late-stage product candidate with robust clinical effects to date, which are supported with historical pramipexole data," said CEO Amit Etkin.According to Alto, the combination therapy demonstrated significant improvements over placebo in a completed 32-patient Phase IIa trial, with patients achieving a mean 8.2-point greater reduction on the Montgomery-Åsberg Depression Rating Scale (MADRS) at week eight. Additionally, 67% of patients reached the maximum allowable dose of 5 mg per day, suggesting the ondansetron component may have helped address tolerability concerns.The company plans to initiate a potentially pivotal Phase IIb trial with ALTO-207 in treatment resistant depression by mid-2026, with topline results due in 2027.Alto also acquired CTC-413, now known as ALTO-208, a combination of pramipexole and the anti-emetic NK-1 receptor antagonist aprepitant for Parkinson's disease.The deal includes $1.75 million upfront plus up to $71.5 million in milestones, adding a potential pivotal-stage readout to Alto's pipeline following last October's disappointing mid-stage results with ALTO-100, which targets brain-derived neurotrophic factor and missed its primary endpoint in biomarker-defined major depressive disorder.The company says its current cash is expected to fund planned operations into 2028, through at least five planned clinical study readouts.