Alto Neuroscience (ANRO) Investor presentation summary

Pipeline and milestones

• Five late-stage data readouts expected in the next three years; portfolio opportunity spans 25M+ patients, with >900 patients dosed across studies.

• ALTO-207 PACE-1 Phase 2b is enrolling, with topline data expected 2H 2027; Phase 3 PACE-2 and PACE-3 initiation planned for early 2027 and 2H 2027, respectively.

• ALTO-300 Phase 2b topline data expected 1H 2027; ALTO-100 bipolar depression Phase 2b data expected mid-2027.

• Additional candidates include ALTO-101 and ALTO-203 with Phase 2 proof-of-concept completed, and ALTO-202 and ALTO-208 described as Phase 2-ready.

ALTO-207 for treatment-resistant depression

• Combines pramipexole, a D3/D2 agonist, with ondansetron, a 5-HT3 antagonist, in a modified-release formulation designed to reduce nausea and vomiting and enable faster titration.

• In a Phase 2a MDD trial (N=32), ALTO-207 reached a mean 4.1 mg/day pramipexole dose in 8 days; week-8 MADRS difference vs. placebo was 8.2 points, with d=1.1 and p=0.025.

• Phase 2a safety findings: nausea and vomiting were the most common adverse events and were mild to moderate; no sleepiness was reported in the treatment arm.

• PACE-1 is an 8-week, placebo-controlled Phase 2b adjunctive TRD study (N=178), with MADRS change from baseline as the primary outcome; topline data expected 2H 2027.

• PAX-D reported pramipexole effect size d=0.87 in TRD; a pooled analysis of eight studies found Hedges’ g=0.64 (p<0.001), with larger effects at higher doses (p=0.027).

ALTO-300 and ALTO-100

• ALTO-300 (agomelatine) is in biomarker-guided Phase 2b development as adjunctive MDD treatment; its primary endpoint is week-6 MADRS change in EEG biomarker-positive patients.

• The ALTO-300 Phase 2b design targets ~200 biomarker-positive patients for final analysis; interim results will inform final sample size.

• ALTO-100 is being evaluated adjunctively in bipolar depression in a 200-patient, biomarker-guided Phase 2b trial; primary endpoint is week-6 MADRS change in the cognitive biomarker-positive population.

• The ALTO-100 trial reported 96% PK positivity in blinded analysis of its first cohort and is supported by an $11.7M Wellcome Trust award.