Summary of Alto Neuroscience Conference Call Company Overview - **Company**: Alto Neuroscience (NYSE:ANRO) - **Focus**: Development of psychiatric drugs targeting disorders such as depression, treatment-resistant depression (TRD), bipolar depression, and schizophrenia, utilizing a biomarker-driven precision medicine approach [5][6][7] Key Programs and Milestones - **Current Pipeline**: Four drugs in phase 2 programs, with readouts expected in the next 12 to 24 months [5] - **Alto 101**: Focused on cognitive impairment in schizophrenia, with readout expected in Q1 2026 [6] - **Alto 207**: Targeting TRD, expected to enter phase 2B in 2026, with a promising mechanism involving dopamine agonism [6][12] - **Alto 300**: Adjunctive treatment in depression, targeting a biomarker derived from EEG signals, expected to read out in mid-2026 [7] - **Alto 100**: Targeting bipolar depression, also in phase 2B, with readout in the second half of 2026 [7] Strategic Acquisitions - **Acquisition of Alto 207**: Acquired from Chase Pharmaceuticals for a small upfront cost, motivated by a strong scientific rationale and clinical efficacy signals from previous studies [8][11][12] FDA Interactions and Regulatory Strategy - **FDA Meetings**: Discussed phase 2B design and requirements for phase 3, including a TOX study and dose-ranging study on ondansetron [14][15] - **Accelerated Timeline**: Phase 2B expected to launch in the first half of 2026, with potential for phase 3 to start by early 2027 [15][16] Efficacy and Study Design - **Phase 2B Design**: One-to-one randomization, targeting a higher dose than previous studies, with an eight-week duration [21][22] - **Efficacy Thresholds**: Aiming for a Cohen's d effect size greater than 0.5, with a target of at least a two-point delta in TRD population [26][28] Biomarker Approach - **Biomarker Strategy**: Utilizing EEG-derived biomarkers to identify patient populations likely to respond to treatments, with a focus on hypodopaminergic states in TRD [34][36] - **Alto 101**: Employing a theta response biomarker to assess cognitive improvement in schizophrenia [40][41] Future Outlook - **Upcoming Readouts**: Anticipated data for Alto 101 in early 2026 and Alto 300 in mid-2026, with a focus on expanding the pipeline and potential new business development opportunities [49][50] - **Market Potential**: Emphasis on addressing high unmet needs in psychiatric disorders with differentiated treatment profiles [6][7][49] Additional Insights - **Execution Rigor**: Implementation of enhanced trial execution standards and AI tools to improve patient selection and data integrity [52][53] - **Market Positioning**: Alto Neuroscience aims to leverage its unique biomarker-driven approach to differentiate itself in the competitive landscape of psychiatric drug development [38][39]

Summary of Alto Neuroscience Conference Call Company Overview - Alto Neuroscience is a psychiatric drug developer focusing on treatment-resistant depression, bipolar depression, cognitive impairment, and schizophrenia [2][3] - The company employs a biology-forward precision approach to understand disease mechanisms and develop targeted drugs for specific patient subgroups [2][3] Key Programs and Developments Alto 300 (Agomelatine) - Agomelatine is an antidepressant approved in Europe and Australia, functioning as a melatonin agonist and 5-HT2C antagonist [4] - The drug is being developed as an adjunctive treatment for depression in the U.S. market, aiming to replace less tolerated antipsychotics [4][5] - A phase 2B trial is set to read out in mid-2026, involving 200 patients with a biomarker [6][40] - A biomarker based on EEG has been identified to predict better responses to treatment, enhancing patient targeting [5][6] Alto 207 (Pramipexole and Ondansetron Combination) - This fixed-dose combination targets treatment-resistant depression by stimulating dopamine receptors while mitigating nausea through ondansetron [21][25] - Historical data shows significant efficacy, with a Cohen's D effect size of 0.9 in a recent trial [23][25] - The phase 2B trial is expected to launch in the first half of 2026, with a phase 3 trial anticipated by early 2027 [25][33] Alto 101 (PDE4 Inhibitor) - Focused on cognitive impairment in schizophrenia, this program utilizes EEG biomarkers to measure outcomes [35][36] - A proof of concept trial is underway, with results expected in Q1 2026 [39][40] Alto 100 (Neuroplasticity Enhancer) - A phase 2B study is being conducted for bipolar depression, targeting patients with neuroplasticity deficits [39] - The readout for this program is scheduled for the second half of 2026 [40] Financial Outlook - The company has a cash runway extending into 2028, supporting multiple upcoming trials and readouts [40][41] - Recent funding of $50 million from a PIPE led by Perceptive has facilitated the acceleration of the Alto 207 program [40][41] Additional Insights - The company emphasizes the importance of rigorous patient compliance and documentation in clinical trials to mitigate risks observed in previous studies [8][9][10] - The FDA's feedback on the Alto 100 program has influenced the design and expectations for future trials, particularly regarding enrichment strategies [14][15] - The potential for agomelatine to replace antipsychotics is highlighted as a significant clinical opportunity due to its better tolerability profile [4][13] This summary encapsulates the key points discussed during the conference call, focusing on the company's strategic direction, ongoing clinical trials, and financial health.