Alto Neuroscience (ANRO) investor relations material

Portfolio and 2027 milestones

• Late-stage psychiatry pipeline includes ALTO-207 for treatment-resistant depression (TRD), ALTO-300 as adjunctive depression treatment, and ALTO-100 for bipolar depression, with biomarker-based patient selection across programs.

• Expected 2027 Phase IIb readouts: ALTO-300 in H1, ALTO-100 mid-year, and ALTO-207 in H2; $320 million in cash is expected to fund operations through 2030.

• ALTO-207 Phase III could start in early 2027, subject to FDA alignment, before the Phase IIb readout; a second Phase III for indication expansion is planned for H2 2027.

ALTO-207 efficacy and trial design

• ALTO-207 combines pramipexole and ondansetron; the latter is intended to improve tolerability and enable faster, higher pramipexole dosing.

• PAX-D enrolled 150 well-characterized, highly treatment-resistant patients across nine UK sites; results showed a Cohen’s d near 0.9 at 12 weeks and persistent benefit through 48 weeks.

• The Phase IIb trial randomizes 178 patients 1:1 to 3.2 mg pramipexole plus 15 mg ondansetron or placebo; it is powered at 80% for a Cohen’s d of 0.45, with two-week titration and eight weeks of treatment.

• Proposed Phase III doses are 1.6 mg and 3.2 mg pramipexole, each with 15 mg ondansetron; the Phase IIb evaluates the higher dose, while FDA feedback will cover the design and timing for Phase III.

• FDA feedback is expected in late Q4 2026 or early 2027; the submission includes Phase I PK data and blinded Phase IIb tolerability data, including titration success and adverse-event discontinuations.

ALTO-300 and ALTO-100

• ALTO-300 is agomelatine, approved in Europe as a monotherapy antidepressant and being developed as a well-tolerated adjunctive option; an EEG biomarker may further enrich response beyond all-comer efficacy.

• The ALTO-300 EEG marker was replicated prospectively and linked to the drug’s mechanism; it uses a single electrode, with a potential Cohen’s d improvement of 0.1 between biomarker-enriched and all-comer populations described as compelling.

• ALTO-100 targets bipolar depression with a learning-and-memory test to identify patients with neuroplasticity impairment; the next readout could support progression to Phase III if positive.

• In the ALTO-100 MDD study, the pre-specified adjunctive population showed Cohen’s d of 0.47, nearly significant but not powered for significance; noncompliance affected the broader results.