Alto Neuroscience (ANRO) Investor Day 2024 summary

Strategic vision and future plans

• Aims to redefine psychiatric drug development by matching patients to targeted therapies using precision biomarkers, focusing on major depressive disorder (MDD) with poor memory/cognition.

• Focused on developing novel, precision medicines for neuropsychiatric disorders, leveraging biomarkers to identify responsive subpopulations and reduce development risk.

• Commercial strategy centers on scalable, objective biomarker tests and IP protection into the early 2040s.

• Plans to expand beyond depression to schizophrenia, bipolar depression, and PTSD, aiming for broad impact across psychiatry.

• 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.

• Extensive quality control, real-time data review, and external raters ensure high-quality data and balanced study populations.

• Statistical plan focuses on the poor memory population, with secondary analyses in monotherapy and more impaired subgroups.