Alto Neuroscience (ANRO) Corporate presentation summary

Mission and strategic approach

• Aims to redefine psychiatry by developing personalized, neurobiology-driven medicines for mental health disorders, focusing on faster and more effective patient outcomes.

• Utilizes a precision medicine strategy, leveraging pharmacodynamic biomarkers to identify responsive patient populations and reduce development risk.

• Portfolio targets major unmet needs in mental health, including depression, schizophrenia, and cognitive disorders.

Pipeline and clinical programs

• Pipeline includes multiple late-stage programs: ALTO-207 for treatment-resistant depression (TRD), ALTO-300 for major depressive disorder (MDD), ALTO-100 for bipolar depression, and ALTO-101 for cognitive impairment associated with schizophrenia (CIAS).

• ALTO-207 combines a D3/D2 agonist with a 5-HT3 antagonist, showing robust antidepressant effects and improved tolerability, with Phase 2b topline data expected in 2H 2027 and Phase 3 initiation planned for early 2027.

• ALTO-300 (agomelatine) is positioned as an adjunctive MDD treatment, with a biomarker-guided Phase 2b trial underway and topline data expected in 1H 2027.

• ALTO-100 targets hippocampal neuroplasticity for bipolar depression, with a biomarker-guided Phase 2b trial supported by Wellcome Trust funding.

• ALTO-101, a novel PDE4 inhibitor, is in development for CIAS, demonstrating pro-cognitive effects and improved tolerability with innovative formulations.

Clinical data and differentiation

• ALTO-207 enables higher, faster pramipexole dosing with improved tolerability, achieving significant antidepressant effects and addressing dose-limiting side effects seen with pramipexole alone.

• Pramipexole demonstrates leading efficacy for anhedonia and overall depressive symptoms in TRD, with consistent results across multiple studies.

• ALTO-300 (agomelatine) offers efficacy comparable to other adjunctive treatments but with superior tolerability and minimal liver function test (LFT) concerns at the 25mg dose.

• Biomarker-guided trials for ALTO-300 and ALTO-100 are designed to enrich for likely responders, following FDA enrichment guidelines.