Alto Neuroscience announces results from replication study

Alto Neuroscience (ANRO) announced results from an independent, prospective replication study evaluating electroencephalography biomarkers in people with schizophrenia. The study successfully replicated previous findings, demonstrating that event-related theta-band responses, particularly theta-band inter-trial coherence, robustly differentiate people with schizophrenia from healthy individuals. The results provide strong validation for the use of this objective, brain-based measurement in identifying and evaluating patients. Alto is currently utilizing theta ITC as a key biomarker and primary outcome measure in its ongoing Phase 2 study of ALTO-101, an investigational novel PDE4 inhibitor for the treatment of CIAS. The analysis, which evaluated 155 individuals with schizophrenia and 272 healthy controls, was designed to replicate and extend prior findings from a large-scale study. The results showed that EEG measures of theta ITC and event-related spectral perturbation had the largest case-control differences, far exceeding traditional EEG and event-related potential measures in their ability to distinguish patients from healthy controls. Importantly, both theta ITC and ERSP were also significantly correlated with processing speed, a key domain of cognitive impairment in schizophrenia. Theta ITC and ERSP showed the largest differences between patients with schizophrenia and healthy controls, indicating a very strong separation between the groups. These novel theta-based measures outperformed more traditional biomarkers, including mismatch negativity and resting-state theta power. Neither of these traditional EEG measures demonstrated significant associations with processing speed. Both theta ITC and ERSP demonstrated a statistically significant correlation with processing speed, a core deficit in CIAS, reinforcing the biological relevance of this biomarker to the clinical impairment. These results strongly support Alto’s utilization of theta ITC as a biomarker for CIAS and as a primary outcome measure to evaluate the effects of ALTO-101 on cognitive impairment in the ongoing Phase 2 POC trial.