Alto Neuroscience (ANRO) investor relations material

Pipeline overview and clinical strategy

• Advancing a Precision Psychiatry Platform using biomarkers to match treatments for neuropsychiatric disorders.

• Lead program ALTO-207 is in a three-trial PACE program for treatment-resistant depression, with phase II-B data expected in H2 2027 and phase III trials initiating in 2027.

• ALTO-300 (MDD) and ALTO-100 (bipolar depression) are in phase II-B, with top-line data expected in 2027.

• ALTO-207, ALTO-300, and ALTO-100 each target different mechanisms: dopamine agonism, melatonergic/serotonergic, and neuroplasticity, respectively.

• ALTO-101, a PDE4 inhibitor, is being developed with improved tolerability and is a candidate for partnering.

ALTO-207 program and clinical rationale

• ALTO-207 combines pramipexole and ondansetron to enhance efficacy and tolerability in treatment-resistant depression.

• Ondansetron mitigates pramipexole-induced nausea, enabling higher and faster dosing.

• Modified release formulation and titration pack are designed for clinical ease and higher target dosing.

• PACE program includes adjunctive and monotherapy trials to address diverse prescriber needs.

• Phase II-B is powered for 80% at Cohen's d of 0.45, with phase III to include dose response and open-label arms.

Supporting clinical evidence and trial design

• PAX-D and PRIME-PRAXOL studies showed robust efficacy for pramipexole in depression and anhedonia.

• ALTO-207 aims to differentiate from antipsychotics by offering better efficacy and fewer side effects.

• Phase II-B and III trials are designed to support registration, with ongoing FDA discussions for alignment.

• Not waiting for phase II-B readout to initiate phase III, leveraging existing efficacy and safety data.