Alto Neuroscience (ANRO) Stifel 2024 Healthcare Conference summary

Clinical trial updates and timelines

• Four phase 2 trials are ongoing, each targeting different psychiatric disorders and subpopulations, with 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 of 2025; ALTO-100 in bipolar depression in 2026.

• Trial designs have shifted to focus on adjunctive studies and compliance monitoring after learnings from ALTO-100.

• Compliance is now confirmed via PK checks or in-clinic dosing, especially for monotherapy studies.

• No large-scale monotherapy efficacy studies are planned due to compliance risks.

Key learnings from ALTO-100 trial

• Negative top-line data was reported when combining monotherapy and adjunctive groups.

• Adjunctive group showed expected drug-placebo difference, attributed to higher compliance.

• Monotherapy group had low compliance, impacting results; compliant patients showed consistent drug and biomarker effects.

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

• Biomarker approach was validated in compliant patients, supporting the overall strategy.

ALTO-300 and biomarker strategy

• ALTO-300 (agomelatine) is being developed as an adjunctive treatment, leveraging a validated EEG biomarker to predict response.

• Biomarker is specific to the drug, does not predict placebo or standard antidepressant outcomes, and is derived from a single electrode for scalability.

• Phase 2b prospectively selects biomarker-positive patients, with a small biomarker-negative group for comparison.

• Study is blinded and randomized, with data expected in the first half of next year.

• Commercial scalability of the EEG-based diagnostic is being considered for both home and clinical use, with potential for procedure code reimbursement.