ALTO NEUROSCIENCE, INC.

Bristol Myers Squibb's Cobenfy, approved by the FDA in September, marked a significant breakthrough in schizophrenia treatment, while AbbVie's muscarinic candidate emraclidine failed mid-stage trials, positioning BMS as the clear winner. Cobenfy's efficacy in three registrational trials contrasts with emraclidine's failure to show significant symptom improvement in Phase II trials, leading to a 12% drop in AbbVie's stock. BMS's acquisition of Karuna Therapeutics for $14 billion in December 2023 further solidified its lead in the schizophrenia market.

Innovation in neuropsychiatry is reviving after 40 years of dormancy, with recent approvals like Bristol Myers Squibb’s Cobenfy and Sage Therapeutics’ Zurzuave. Large Phase III studies on psychedelics aim to shift from anecdotal to evidence-based treatments. Challenges include high costs of Phase III trials and lack of effective animal models for CNS disorders. Investment in neuroscience is cyclical, with a need for better patient selection and biomarkers. Infrastructure and less intrusive diagnosis methods, like blood-based biomarkers, are crucial for tackling neurodegenerative diseases. AI and analytics advancements could improve diagnostic efficiency and patient targeting, despite regulatory hurdles and mixed public perception in neuropsychiatry.

Sangamo Therapeutics' shares surged 69% after FDA alignment on an Accelerated Approval pathway for its Fabry disease gene therapy, isaralgagene civaparvovec (ST-920), using data from its Phase I/II STAAR trial. The company plans to submit a BLA in the second half of 2025, three years ahead of previous estimates.

Alto Neuroscience's ALTO-100, designed to treat low BDNF levels, failed to meet primary and secondary endpoints in a phase 2b trial for major depressive disorder. Despite positive phase 2a results, the placebo-controlled phase 2b trial showed no significant improvement in MADRS scores. ALTO-100 is still being tested for bipolar depression and PTSD, and the company has other potential treatments in clinical testing.

Alto Neuroscience's ALTO-100 drug showed no significant improvement over placebo in a major depressive disorder trial, causing a sharp drop in share value. The company plans to analyze data to determine future steps for the drug, which is also being tested for PTSD and bipolar depression. Despite the setback, analysts believe Alto's biomarker-based approach remains promising.

Alto Neuroscience's Phase 2b trial of ALTO-100 for depression failed to show significant improvement over placebo, raising doubts about its precision medicine approach. Despite this, the company remains confident in its biomarker stratification strategy and is continuing a Phase 2b trial for ALTO-300, expected to report data in 2025.

Alto Neuroscience's Phase IIb trial of ALTO-100 for major depressive disorder (MDD) failed to meet its primary endpoint, showing no significant improvement in symptoms compared to placebo. Despite the setback, ALTO-100 maintained a favorable safety profile and Alto remains committed to advancing precision medicine in psychiatry.

Alto Neuroscience's Phase 2b trial of ALTO-100 for major depressive disorder (MDD) did not meet its primary endpoint, showing no significant improvement in depressive symptoms compared to placebo, despite maintaining a favorable safety profile. The company plans to analyze the full data set to determine future steps for ALTO-100 in MDD.