Alto Neuroscience (ANRO) investor relations material

ALTO-207 program overview

• ALTO-207 combines pramipexole and ondansetron to address tolerability issues, enabling higher and faster dosing for treatment-resistant depression (TRD).

• Real-world use of pramipexole is limited by slow titration due to nausea, but efficacy is strong, especially for anhedonia.

• The phase II-B trial uses a custom titration pack to reach a 3.2 mg pramipexole target, with most patients expected to tolerate this dose.

• The trial is powered conservatively, aiming for a Cohen's d of 0.45, with dropout rates expected to align with industry standards.

• Safety monitoring focuses on nausea, impulse control disorders, and QTc prolongation, with measures in place to minimize risks.

Clinical development and timelines

• Enrollment for the phase II-B ALTO-207 trial is on track, with top-line data expected in the second half of next year.

• Plans are in place to initiate phase III trials for both adjunctive and monotherapy use before phase II-B readout, pending FDA alignment.

• Flexibility exists to adjust phase III design based on phase II-B results, particularly regarding sample size.

• The program aims to provide a differentiated, take-home treatment option for a broad range of TRD patients.

• Efforts are underway to validate anhedonia scales for potential inclusion in labeling and publications.

Broader pipeline updates

• ALTO-300 (agomelatine) is in phase II-B for adjunctive MDD treatment, with a biomarker-enriched design and top-line data expected in the first half of next year.

• ALTO-100 targets bipolar depression with a pro-neuroplasticity mechanism, focusing on patients with learning and memory impairments; readout is anticipated mid-2027.

• Both programs have implemented rigorous patient eligibility and compliance checks to ensure high-quality data.

• Advancement to phase III for these programs depends on achieving statistical significance on MADRS change and demonstrating good tolerability.