Alto Neuroscience (ANRO) Leerink Global Healthcare Conference 2025 summary

Strategic overview and pipeline status

• Focus on precision psychiatry, integrating drug development with biomarker-driven patient selection across depression, bipolar disorder, and schizophrenia, with four Phase 2 readouts expected by end of 2026 and cash runway into 2028.

• Biomarkers are used both for understanding drug mechanisms and for selecting patients most likely to respond, with prospective replication built into trial design.

• Decentralized clinical trial infrastructure established, enabling scalable biomarker studies and rigorous patient selection.

• ALTO-100 and ALTO-300 are lead assets in Phase 2b, targeting bipolar and major depression, respectively, with distinct biomarkers and mechanisms.

• ALTO-203 and ALTO-101 are earlier-stage assets, with all programs expected to have readouts by 2026.

ALTO-300 program insights

• ALTO-300, an approved antidepressant in Europe and Australia, uses a unique biomarker based on neural variability from EEG data to identify responders.

• Machine learning identified sample entropy as a key biomarker, prospectively replicated in independent patient groups.

• Phase 2b trial design includes blinded biomarker-based patient selection, with primary efficacy population being biomarker positive.

• Interim analysis led to trial continuation and sample size increase from 150 to 200 biomarker positive patients, with enhanced site-level controls and compliance measures.

• Readout expected mid-2026, with intensified oversight and diversified patient recruitment to mitigate site-level risks.

ALTO-100 program learnings

• ALTO-100 targets hippocampal neuroplasticity, with a biomarker based on verbal memory impairment guiding patient selection.

• Phase 2b trial top-line was negative, but adjunctive treatment group showed a near-significant signal, attributed to site-level non-compliance in the monotherapy group.

• Compliance issues were clustered at certain sites, leading to strengthened compliance monitoring and site oversight in ongoing and future trials.

• Continued development in bipolar depression is supported by external funding and unmet need, with a 2026 readout planned.