Alto Neuroscience (ANRO) Stifel 2024 Healthcare Conference summary

Clinical trial updates and timelines

• Four phase 2 trials are ongoing, targeting different psychiatric disorders with mechanistically independent drugs, with key readouts expected in 2025 and 2026.

• ALTO-300 and ALTO-203 MDD readouts are expected in the first half of next year, ALTO-101 for cognition in schizophrenia in the second half, and ALTO-100 in bipolar depression in 2026.

• Trial designs have been adjusted to focus on patient compliance, especially favoring adjunctive studies over monotherapy due to compliance issues observed in ALTO-100.

• Compliance is now confirmed through PK checks or in-clinic dosing, and large-scale monotherapy efficacy studies are being avoided.

Key learnings from ALTO-100 trial

• Negative top-line data was reported when combining adjunctive and monotherapy groups, with the monotherapy group showing poor compliance.

• Adjunctive group showed expected drug-placebo difference, attributed to higher compliance, confirmed by blood PK checks.

• Consistent drug and biomarker effects were observed in compliant patients across both groups.

• Future studies are designed to ensure compliance and target more clearly defined patient populations.

Biomarker-driven approach and validation

• EEG-based biomarkers, derived via machine learning, are used to prospectively select patients likely to respond to specific drugs.

• Biomarker for ALTO-300 is specific to the drug, does not predict placebo or standard antidepressant response, and is validated across multiple datasets.

• Phase 2b design for ALTO-300 includes biomarker-positive and a small biomarker-negative comparison group, with blinded randomization.

• The biomarker can be measured with a single electrode, enabling potential scalability for home or clinic use.