Alto Neuroscience presents key data, study findings on ALTO-300

Alto Neuroscience presented key findings at the 63rd annual meeting of the American College of Neuropsychopharmacology, showcasing ongoing clinical-stage programs.
Amit Etkin, MD, PhD, spoke with Psychiatric Times about the three programs coming out of Alto Neuroscience about precision psychiatry. The study for ALTO-300, an oral antidepressant being studied as an adjunct treatment for major depressive disorder (MDD), is in phase 2b and is selecting patients based on an electroencephalographic (EEG) signature.¹ The trial is testing for the efficacy of the drug against placebo, however Etkin said patients without the EEG signature are being included in the trial to understand the difference between those with and without the biomarker. ALTO-300 is a 5-HT2C serotonin receptor antagonist, increasing dopamine release and enhancing neural signaling stability.¹ Etkin said the drug is one of the most advanced for Alto Neuroscience.
Also discussed was an earlier stage program named ALTO-101, which aims at cognitive impairment associated with schizophrenia, according to Etkin. There are no current treatments for cognitive impairment in schizophrenia, Etkin says, and it is the determinate of a long term course. Alto is developing a drug that blocks the break down of cyclic adenosine monophosphate (cAMP), allowing for increased neuroplasticity. ALTO-101 is currently in a phase 2 proof of concept trial and is on track to read out in the second half of 2025.
Etkin said Alto Neuroscience is looking to change the way treatments are selected. Etkin said, "the expectation is that the use of the EEG biomarker would be in the drug label, which would mean that psychiatrists would be assessing this measure in their patients."
In a press release from Alto Neuroscience, they discussed a second presentation on ALTO-203, a novel histamine inverse agonist for MDD. ALTO-203 is currently in a phase 2 proof of concept trial and is specifically targeting patients with ahedonia. The histamine H3 receptor acts as an inhibitory autoreceptor that regulates the release of histamine and other neurotransmitters like dopamine, norepinepherine, and serotonin.¹

Dr Etkin is cofounder and CEO of Alto Neuroscience, and a professor of psychiatry and behavioral sciences at Stanford University.

References

1. Alto Neuroscience Announces Data Presented at the 63rd Annual Meeting of the American College of Neuropsychopharmacology. News release. Alto Neuroscience. December 11, 2024. Accessed December 23, 2024. https://investors.altoneuroscience.com/news/news-details/2024/Alto-Neuroscience-Announces-Data-Presented-at-the-63rd-Annual-Meeting-of-the-American-College-of-Neuropsychopharmacology/default.aspx