Alto Reports Positive Phase II PTSD Data After Mid-Stage MDD Win

PTSD_iStock, designer491

Pictured: Cracked figure of a head symbolizing distress/iStock, designer491

Alto Neuroscience on Tuesday announced that its investigational drug ALTO-100 showed a favorable efficacy and safety profile in a Phase IIa trial in patients with post-traumatic stress disorder.

The study also demonstrated that Alto’s precision psychiatry approach could lead to better outcomes for post-traumatic stress disorder (PTSD) patients. In a subgroup of patients defined by a certain cognitive profile, treatment with ALTO-100 reduced scores in the clinician-administered PTSD scale for DSM-5 (CAPS-5) by 17.5 points. In contrast, the candidate improved CAPS-5 scores by only 12.9 points in patients without this cognitive profile.

The difference was statistically significant, indicating that the company’s approach could identify potential drug responders by looking at patients’ neurobiological profiles, according to Alto’s announcement.

In addition, in the biomarker-defined patients, ALTO-100 elicited a clinical response rate of 46% compared to only 26% in those without the specific cognitive profile.

This difference fell short of statistical significance. However, Alto noted that the Phase IIa study was designed to evaluate the “effect size on enrichment” and was not powered to detect significance.

Tuesday’s data further validates Alto’s AI-enabled Precision Psychiatry Platform, CEO Amit Etkin said in a statement, adding that the company’s approach also has the potential to “meaningfully de-risk future development” in other indications and therapeutic areas.

“These data move us closer to transforming neuropsychiatric treatment through a robust understanding of biological drivers of treatment response at the level of individual patients,” Etkin said.

Alto’s Phase IIa trial was an open-label holdout dataset-controlled study that enrolled 90 patients with primary PTSD and 133 with major depressive disorder (MDD). The study lasted for eight weeks and its primary endpoint was the change in CAPS-5 score at week four.

In January 2023, Alto posted data from the study’s MDD population, similarly highlighting the potential of its precision platform. In patients that satisfied specific cognitive criteria, ALT-100 achieved a clinical response rate of 61%. Meanwhile, in those that were not selected by Alto’s AI-enabled platform, clinical response rate was only 33%.

At the time, Etkin told BioSpace that ALT-100 works by restoring plasticity in the brain, which then allows for better flexibility and adaptability to new information.

In both the PTSD and MDD populations, ALT-100 demonstrated a favorable safety and tolerability profile, with no concerning signals detected. Alto has also kicked off a Phase IIb study of the candidate.

Last month, ALT-100 made BioSpace’s list of the 10 neuropsychiatric drugs to watch as they near regulatory review.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at or

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