Alto Neuroscience (ANRO) investor relations material

Strategic focus and pipeline overview

• Aims to develop highly effective psychiatric treatments using biomarkers to match patients with targeted drug mechanisms.

• Pipeline includes ALTO-207 (pramipexole/ondansetron), ALTO-100 (neuroplasticity enhancer), and ALTO-300 (agomelatine adjunctive therapy).

• Targets broad psychiatric indications: depression, treatment-resistant depression, substance abuse, bipolar depression, and schizophrenia.

ALTO-207 clinical development and efficacy

• ALTO-207 combines pramipexole and ondansetron to address dopamine deficiency in treatment-resistant depression.

• Pramipexole’s efficacy is limited by dose-dependent nausea/vomiting, mitigated by ondansetron co-formulation.

• PAX-D study (150 patients, 48 weeks) showed sustained, large effect size (Cohen’s d 0.87, 7.4 MADRS points) but high dropout due to adverse events.

• Phase IIa proof-of-concept (32 patients) with the combination showed even greater efficacy (Cohen’s d 1.1, 8.2 MADRS points) and improved tolerability.

Ongoing and future clinical trials

• Phase II-B trial for ALTO-207 launched in Q2, reading out in H2 next year, with 178 patients and improved dosing formulation.

• Trial is powered to detect smaller effect sizes and aims to support a phase III launch by early 2027.

• Current cash runway funds all phase II-B and phase III trials through 2029.