Alto reported positive data from a first-of-its-kind Phase IIb trial of major depressive disorder candidate ALTO-100.
Alto CEO Amit Etkin, M.D., Ph.D./Courtesy of Alto Neuroscience
Lucky number seven on BioSpace’s NextGen Bio 2023 list, Alto Neuroscience came into 2023 – and JP Morgan week – hot, with positive data from a first-of-its-kind study in major depressive disorder.
ALTO-100 was developed with the company’s AI-enabled biomarker platform, which evaluates brain function measures like EEG and computerized behavioral tests to identify patients most likely to respond to the company’s therapies.
In the Phase IIa study, Alto sought to determine if, using these measures, it was possible to distinguish who would respond to the therapy from those who would not.
ALTO-100 aims to restore plasticity in the brain. In an interview with BioSpace, Alto Founder and CEO Amit Etkin, M.D., Ph.D. explained that plasticity enables the brain to be flexible and adapt to new information.
Not all MDD patients have issues with cognition, but ALTO-100 is targeted toward those who do.
Topline data revealed that 61% of biomarker-defined patients achieved a clinical response to Alto’s candidate, characterized as a 50% reduction in depression symptoms. This was compared to 33% of patients who did not possess this biomarker.
After six weeks of treatment, the biomarker-defined patient group achieved a 15.5-point mean reduction in Montgomery–Åsberg Depression Rating Scale (MADRS) scores compared to a 10.6-point reduction in the biomarker-negative cohort.
Alto reported a positive tolerability profile for the experimental treatment, which has so far been tested in more than 395 patients. Based on these results, the company wasted no time in launching the Phase IIb study, with the first patient enrolled Tuesday.
If these results are replicated, they will guide Alto to develop the treatment for this subgroup of responders. Importantly, it would also identify subgroups for whom the therapy would not be effective, Etkin said.
Alto will present highlights from this data at JPM Wednesday afternoon.
A Paradigm Shift
There is a paradigm shift building in precision neuropsychiatry. The field is no longer satisfied with the trial-and-error approach to treating depression, post-traumatic stress disorder, anxiety disorder and other neuropsychiatric illnesses.
“We have what seems like a lot of drugs, but actually, it’s a very limited repertoire of drug mechanisms,” Etkin said. “We have biological treatments but no biology to characterize the patient receiving the treatment, and that’s where biomarkers writ large come in.”
In 2020, nearly one in 10 Americans reported having a depressive episode, according to research conducted at Columbia University.
“There’s just no way any single disorder that’s that common has one single biology or cause, and yet we totally ignore that fact,” Etkin said.
This is why drugs fail in clinical development, “not because they’re not effective, but because we haven’t actually identified the patients for whom they’re effective,” he said.
Alto is not alone in this revolution. Tel Aviv-based biotech Genetika+ is developing a blood test to determine which currently marketed drugs will work best for each individual patient.
Genetika+ combines a patient’s genetic background with their environmental background using clinical data and patient history.
The genetic information “tells [the patient] whether a drug is going to make it past the liver to the brain,” said Talia Cohen Solal, Ph.D., CEO and co-founder, in an interview with BioSpace.
Cohen Solal described the process, which involves generating a “brain in a dish” for every patient using their blood cells.
“Using stem cell technology, we generate a brain model, almost like a biopsy of the brain for that individual,” she said. Using high throughput and high content screening, “We can then expose that to all the different antidepressants and see which [one] is going to have the strongest impact in improving the actual effect of the illness on the brain.”
