Alto Neuroscience reported positive Phase II results for its precision depression therapy, ALTO-300, designed with the help of artificial intelligence (AI) as an add on treatment for people with depression who are not responsive to traditional antidepressants.
The investigators have identified an electroencephalogram (EEG) signature that characterizes people who are most likely to respond to the treatment, an approach which the trial results support.
The trial tested ALTO-300 both with initial biomarker selection and without. Those selected as likely responders by the EEG scan had a better response to the treatment than the group with no initial biomarker scan.
This is the third positive Phase II readout for the California-based company, which has a focus on developing precision psychiatric treatments for a range of conditions including depression and post traumatic stress disorder.
“Our conviction in the promise of precision medicine for the brain is bolstered by these results,” said Amit Etkin, founder, president, and CEO of Alto Neuroscience in a press statement. “Data from the ALTO-300 study showcase the potential of targeting patients’ underlying neurobiology to achieve clear clinical benefit and further validate our precision drug development approach.”
Although there are a number of effective existing treatments for depression, they do not work for everyone. Many patients do not respond to initial therapies and have to change medications, sometimes several times, or simply do not respond at all.
Alto Neuroscience founder and psychiatrist, Amit Etkin, founded the company to try and solve this problem in 2019 when he and his colleagues at Stanford first identified the EEG method for assessing whether a treatment for depression, or other related conditions, was likely to be effective with the help of machine learning.
The Phase II trial of ALTO-300 was completed in 8 weeks and included 239 patients between the ages of 18 and 74 years with major depressive disorder. The patients remained on a background antidepressant and ALTO was added to their treatment. Of this group, 110 individuals had an EEG test at baseline and the other half did not.
The results showed that patients shown as likely to be responsive by the biomarker EEG test had a better response to ALTO-300 than those without a biomarker test. Across the entire dataset, average improvements on the Montgomery–Åsberg Depression Rating Scale (MADRS) were 8.3 in the biomarker group versus 5.7 in the group with no biomarker test. In addition, significantly more patients shown as likely to be responsive by the biomarker test had a response to treatment at week 8 compared with no biomarker test at 62% vs 47%, respectively.
Safety and tolerability results were good overall and no unexpected adverse events were observed in the study group.
Alto is developing two other candidates for the treatment of depression and depression/PTSD, ALTO-202 and ALTO-100, respectively, both of which are at a similar stage of development to ALTO-300. ALTO-100 has also had recent positive Phase II results in a trial in patients with depression and in a second trial in patients with PTSD.
The company has backing from Eli-Lilly and other investors and raised a $45 million Series C funding round in November. It said it is planning more late-stage trials of its precision psychiatry therapies with the funding.
