Alto Neuroscience (ANRO) Investor Day 2024 summary

Strategic vision and future plans

• Focused on precision medicine for neuropsychiatric disorders, leveraging proprietary biomarkers to identify responsive subpopulations and reduce development risk, with a particular focus on MDD patients with poor memory/cognition.

• Five ongoing Phase 2 trials across four novel assets, with over 800 patients dosed and a cash runway into 2027, supporting operations through key milestones.

• Commercial strategy centers on scalable, objective cognitive and EEG-based assessments, with both at-home and in-clinic testing, and a biomarker-driven approach.

• IP protection extends into the early 2040s, with a focus on patient selection and scalable testing.

• Platform approach aims to systemically reduce development risk and expand precision psychiatry to other neuropsychiatric conditions.

Clinical development and scientific rationale

• ALTO-100 targets MDD and bipolar depression patients with poor memory, enhancing hippocampal neuroplasticity via BDNF signaling.

• The memory biomarker is a validated, self-administered cognitive test adapted from established neuropsychological assessments.

• Poor memory/cognition is prevalent in 30-50% of MDD patients, predicts treatment resistance, and is linked to greater disability and lower response to standard antidepressants.

• ALTO-100 has shown robust efficacy in biomarker-positive patients across two prospective and two retrospective studies, with no increased placebo response in this subgroup.

• Phase 2a and pilot decentralized studies confirm feasibility of at-home biomarker collection and consistent patient stratification.

Phase 2b trial design and regulatory engagement

• Phase 2b trial in MDD completed enrollment (N=301), with topline data expected October 2024; primary outcome is MADRS change in biomarker-positive patients at week 6.

• Study design follows FDA enrichment guidelines, with randomization stratified by biomarker and treatment type (monotherapy/adjunctive).

• Early FDA feedback led to increased powering for monotherapy subgroup; Phase 2b data will inform Phase 3 design, likely including the full MDD population.

• Step-down statistical testing built into analysis plan, with advancement to Phase 3 based on effect size of 0.3 or higher.

• Ongoing dialogue with FDA on biomarker registration as a software device, integrated with the drug development program.