Alto Neuroscience halted its skin-delivered PDE4 inhibitor ALTO-101 after a Phase 2 trial failed to meet the primary cognition endpoint in schizophrenia-related cognitive impairment. The trial of 83 patients did not show statistically significant improvement versus placebo on an EEG-based measure. The company noted some directional improvements across EEG measures and identified nominal effects in a predefined subgroup, but concluded the evidence base was insufficient to advance ALTO-101 further, including for an oral reformulation unless partnered. Instead, Alto said it will prioritize ALTO-207, a combination expected to enter a Phase 2b study for treatment-resistant depression. For the sector, the result is a reminder that CNS trial endpoints remain difficult to hit and that even biologically plausible targets can struggle without clear translational biomarkers.