Alto Neuroscience (ANRO) TD Cowen 45th Annual Healthcare Conference summary

Pipeline overview and strategy

• Focus on precision psychiatry using scalable biomarkers like EEG and behavioral measures for patient selection and dosing in clinical trials.

• Four novel agents in the clinic: Alto 100 and Alto 300 in phase II-B, Alto 101 and Alto 203 in earlier stages, with multiple readouts expected through 2026.

• Cash runway extends into 2028, supporting ongoing and future trials.

• Biomarker-driven approach aims to improve clinical outcomes and de-risk later-stage trials.

• Active patient selection and large-scale trials are ongoing across multiple indications.

Alto 300 program

• Alto 300 (agomelatine) is used as adjunctive treatment in depression, leveraging EEG and machine learning to identify responsive patients.

• Biomarker (EEG neural variability/entropy) predicts better drug response and is prospectively validated.

• Interim analysis led to removal of 52 patients due to site/data issues, with trial upsized to 200 biomarker-positive patients.

• Readout expected mid-2026, with improved trial conduct based on learnings from Alto 100.

• EEG biomarker is scalable, requiring only an 8-minute recording and minimal setup, suitable for clinical and home use.

Alto 100 program

• Alto 100 targets neuroplasticity in the hippocampus, with a biomarker identifying patients with memory impairment who respond better.

• Phase II-B in MDD failed to meet significance, but adjunctive subgroup showed a near-significant effect (Cohen's d 0.47, p=0.09).

• Non-compliance and site-level issues identified as main drivers of null results, not drug tolerability.

• Bipolar phase II-B is ongoing, all adjunctive, with enhanced compliance monitoring and centralized eligibility review.

• Mechanistic rationale for bipolar depression is similar to MDD, with shared neuroplasticity deficits.