Alto’s biomarker-based depression study provides positive data

Etkin_Alto Neuroscience

Alto CEO Amit Etkin, MD, Ph.D./Courtesy of Alto Neuroscience

lucky number seven bioroom‘s NextGen Bio 2023 listing, Alto Neuroscience, kicked off 2023 — and JP Morgan week — hot with positive data from a unique major depressive disorder study.

ALTO-100 was developed using the company’s AI-enabled biomarker platform, which evaluates brain function measurements such as EEG and computational behavioral testing to identify patients most likely to respond to the company’s therapies.

In the phase IIa study, Alto wanted to determine whether these measures would be able to distinguish who is responding to therapy and who is not.

ALTO-100 aims to restore plasticity in the brain. In conversation with bioroom, Founder and CEO of Alto Amit Etkin, MD, Ph.D. explained that plasticity allows the brain to be flexible and adapt to new information.

Not all MDD patients have cognition problems, but ALTO-100 is aimed at those who do.

Top-line data showed that 61% of biomarker-defined patients achieved a clinical response to Alto’s candidate, characterized by a 50% reduction in depression symptoms. This was compared to 33% of patients who did not have this biomarker.

After six weeks of treatment, the biomarker-defined patient group achieved a 15.5% greater reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) scores compared to a 10.6% reduction in the biomarker-negative cohort.

Alto reported a positive tolerability profile for the experimental treatment, which has been tested in more than 395 patients to date. Based on these results, the company wasted no time in starting the Phase IIb study, with the first patient enrolled on Tuesday.

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If these results are replicated, they will guide Alto in developing treatment for this subset of responders. Importantly, it would also identify subgroups for which therapy would not be effective, Etkin said.

Alto will be presenting highlights of this data at JPM on Wednesday afternoon.

A paradigm shift

A paradigm shift is taking place in precision neuropsychiatry. The field is no longer content with the trial and error approach to treating depression, post-traumatic stress disorder, anxiety disorders, and other neuropsychiatric disorders.

“We seem to have 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 big biomarkers come in.”

In 2020, nearly one in 10 Americans reported having a depressive episode, according to a study conducted at Columbia University.

“There’s just no way that a single disorder that’s so common could have a single biology or cause, and yet we completely ignore that fact,” Etkin said.

This is why drugs fail in clinical development, “not because they aren’t effective, but because we haven’t yet identified the patients in which they are 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 work best for each individual patient.

Talia Cohen Solal_Genetika+
Talia Cohen Solal, Ph.D.

Genetika+ combines a patient’s genetic background with their environmental background using clinical data and the patient’s history.

The genetic information “says [the patient] whether a drug makes it to the brain via the liver,” said Talia Cohen Solal, Ph.D., CEO and co-founder, in an interview with bioroom.

Cohen Solal described the process of creating a “brain in a bowl” for each patient using their blood cells.

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“Using stem cell technology, we create a brain model, almost like a biopsy of the brain for that person,” she said. Using high-throughput, high-content screening, “we can then expose that to all the different antidepressants and see which ones [one] will have the strongest effect in ameliorating the actual effect of the disease on the brain.”

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