Alto Neuroscience, a California-based biotech company, is making strides in depression therapy using artificial intelligence (AI) to match patients with drugs based on brain biomarkers. In a phase 2a clinical trial, their approach has shown promise in improving the treatment outcomes for patients with major depressive disorder (MDD) who do not respond well to their current therapies.
AI-powered Patient Selection
The eight-week study focused on testing a drug known as ALTO-300, an oral medication administered once daily. Alto has not disclosed the drug’s mechanism of action. The trial involved 239 patients diagnosed with major depressive disorder who had not shown significant improvement with their current treatments.
A subgroup of 110 patients was selected for inclusion based on an AI-powered assessment of their electroencephalogram (EEG) at the beginning of the study. This EEG assessment identified specific “brain biomarkers” that indicated these patients were more likely to respond positively to treatment with ALTO-300.
The selected patients continued their standard treatments, and ALTO-300 was added to their regimen. After four weeks of treatment, a significantly higher percentage of patients with the identified EEG biomarker achieved a clinical response compared to those without the biomarker.
Positive Clinical Outcomes
A clinical response was defined as a 50% or greater improvement in depression symptoms based on the widely used Montgomery-Åsberg Depression Rating Scale (MADRS). The results were compelling:
– At week four, 47% of patients with the EEG biomarker achieved a clinical response, compared to 27% of the control group.
– Similar trends were observed at six weeks (57% vs. 34%) and eight weeks (62% vs. 47%).
Amit Etkin, CEO of Alto Neuroscience, highlighted that these findings demonstrate the potential of targeting patients’ underlying neurobiology to achieve significant clinical benefits. He also praised Alto’s machine learning-driven data science approach, which is instrumental in delivering personalized treatment to patients with MDD.
Phase 2b Study and Future Directions
Building on the success of their phase 2a trial, Alto has initiated a placebo-controlled phase 2b study for ALTO-300. This study includes 200 patients with moderate to severe MDD, and the drug will once again be added to their existing background therapy. The study is expected to provide results in the first half of 2025, with the primary endpoint being MADRS scores compared to the placebo group at six weeks.
Alto’s precision psychiatry approach, which leverages EEG biomarkers and other factors like neurocognitive task performance and wearable data, depending on the specific drug candidate, has previously shown promise with ALTO-100. ALTO-100 targets brain-derived neurotrophic factor (BDNF) and has demonstrated encouraging results in trials involving patients with post-traumatic stress disorder and MDD.
Advancing precision medicine for mental health
Amit Etkin emphasized Alto’s commitment to precision medicine for the brain, citing these recent results as a testament to the potential of their approach. Alto Neuroscience’s strategy involves utilizing various biomarkers and patient data to tailor treatments to individual needs.
The company, which recently secured $45 million in third-round financing and $60 million in a Series B funding round, plans to allocate these resources to advance its drug candidates into phase 3 clinical testing. Additionally, Alto is actively working on therapies for other neuropsychiatric and neurodegenerative conditions, including schizophrenia.
Alto Neuroscience’s AI-driven approach to depression therapy, centred around identifying brain biomarkers and delivering personalized treatments, has shown promising results in a phase 2a trial. This innovative precision psychiatry approach holds the potential to significantly improve the lives of patients with major depressive disorder, offering hope for more effective and tailored treatments in the future.