Another of Alto Neurosciences’ machine learning-derived, biomarker-based depression therapies has improved symptoms, boosting the case for the biotech’s precision psychiatry approach.
ALTO-300 was tested as an adjunctive treatment in an eight-week phase 2a study of patients with major depressive disorder who had an inadequate response to antidepressants. The study enrolled 239 patients between 18 and 74 years of age who remained on a background antidepressant and had ALTO-300 added to their treatment regimen.
Alto used an electroencephalogram (EEG) biomarker, a test that measures electrical activity in the brain, to determine which patients might benefit from treatment over others. Of the 239 patients, 110 underwent an EEG procedure at the start of the study.
Investigators found that patients with the EEG biomarker demonstrated clinical improvement on a scale that measures depression severity called the Montgomery–Åsberg Depression Rating Scale (MADRS).
Specifically, 55 patients with the biomarker experienced an 8.3-point mean improvement, compared to 5.7 in the group of 48 patients without it. The differences started to show at week 1 and improved through week eight, Alto said.
More of the biomarker-identified patients demonstrated a clinical response of a 50% or more reduction in depression symptoms, Alto said. At week 4, the rate was 47% vs 27% for the non-biomarker group and at week 6 the rate was 58% compared to 34%.
ALTO-300 was safe and tolerable with no unexpected adverse events, Alto said, but the company did not provide detailed data.
The company has already started a phase 2b study for ALTO-300 in 200 patients that's expected to read out in the first half of 2025.
The ALTO-300 results build on a phase 2a readout for ALTO-100, issued in January, which similarly showed improvements in depression severity at six weeks. In that study, 59 patients that Alto identified as having a relevant brain biomarker experienced a mean 15.5-point reduction in their severity score while the 64 patients without the biomarker saw a more modest 10.6-point decrease.
Alto’s precision psychiatry approach is backed by Eli Lilly and other investors, who pitched into a $45 million series C in November. At the time, the company said the cash would support four phase 2 trials that have readouts expected by early 2025.
Alto also expects to advance its next two candidates, ALTO-101 and ALTO-203, into phase 2 proof-of-concept trials, with readouts in late 2024 and through the first half of 2025.
Editor's note: This story was updated to correct the second mention of ALTO-300.