— In the proof-of-concept study, ALTO-101 did not achieve statistical significance on primary endpoint; signals observed across EEG measures including near-significant improvement in theta-ITC (p=0.052) —

— Alto has developed a modified-release, once-daily oral formulation of ALTO-101; the Company plans to explore partnering opportunities for this formulation —

— Development of ALTO-207 remains the top priority for the Company; Phase 2b on track to initiate in 1H 2026 —

Alto Neuroscience, Inc. (NYSE:ANRO), a clinical-stage biopharmaceutical company focused on precision medicines for neuropsychiatric disorders, today announced topline data from its Phase 2 proof-of-concept (POC) clinical trial evaluating ALTO-101 for the treatment of cognitive impairment associated with schizophrenia (CIAS), and provided an update on the Company's pipeline and prioritization.

ALTO-101 did not achieve statistical significance on primary electroencephalography (EEG) or cognitive endpoints versus placebo; however, the study demonstrated directional improvements across certain EEG measures, including a near-significant effect on theta-ITC (n=83, d=0.34, p=0.052) – a measure correlated with cognitive performance across datasets. In a pre-specified analysis in a more cognitively impaired subgroup (n=59), ALTO-101 exhibited nominally significant effects on theta-ITC compared to placebo (d=0.44, p=0.03). Further, certain EEG measures, including theta-ITC, showed improvements from day 5 to day 10 in the trial, suggesting a longer treatment period may elucidate greater effects. ALTO-101 demonstrated a favorable tolerability profile, with rates of nausea and vomiting — hallmark side effects associated with the PDE4 inhibitor class — in line with placebo rates. This finding suggests the pharmacokinetic profile of ALTO-101 may overcome a key tolerability barrier that has historically limited PDE4 inhibitor adoption. High rates of application site skin reactions were observed across both active and placebo arms.

Separately, the Company has developed a modified-release oral formulation of ALTO-101 that has demonstrated an improved pharmacokinetic and tolerability profile relative to the immediate-release formulation. Alto believes this formulation may offer potential benefits across multiple therapeutic areas and intends to explore partnering opportunities. The formulation is covered by a pending patent application.

Based on these results, the Company does not plan to independently advance ALTO-101 in CIAS and will instead prioritize resources toward its lead program, ALTO-207, while exploring strategic partnering opportunities for ALTO-101. The Company expects to present more data from this study at a future medical conference.