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.