Alto Neuroscience Reports Positive Phase 2a Results for Oral Candidate ALTO-100 in PTSD, Validating Precision Psychiatry Approach

▎Edited by the WuXi AppTec content team

Recently, Alto Neuroscience, Inc. announced the results of the PTSD cohort from the Phase 2a clinical trial of its oral candidate therapy ALTO-100, demonstrating the efficacy and favorable safety profile of ALTO-100 in patients with PTSD.Reported in January 2023Major Depressive Disorder (MDD) CohortBased on the results of the PTSD cohort, ALTO-100 continues to demonstrate significant therapeutic potential for patients with comorbid mood and affective disorders as well as plasticity deficits.

PTSD is a mental disorder that can be triggered by responses to traumatic events (interpersonal violence, combat, life-threatening accidents, or natural disasters). The core features of PTSD include a variety of symptoms: such as re-experiencing phenomena (i.e., flashbacks and nightmares), avoidance behaviors, emotional numbing (i.e., amnesia, anhedonia, withdrawal, negative emotions), and heightened arousal (i.e., insomnia, irritability, poor concentration, hypervigilance). Psychiatric comorbidities are also common; individuals with PTSD may abuse substances, experience mood and other anxiety-related affective disorders, engage in impulsive and risky behaviors, and self-harm. The prevalence of PTSD varies across populations and countries, ranging from 0.2% to 4%.

ALTO-100 is an orally administered drug developed by Alto Neuroscience using its artificial intelligence biomarker platform. It targets brain-derived neurotrophic factor (BDNF) and can restore patients' neural plasticity, enabling the brain to flexibly adapt to new information. Notably,Alto Neuroscience's precision psychiatry platform detects brain biomarkers by analyzing EEG activity, behavioral performance, wearable device data, genetics, and other factors to match the right medication for each patient.

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The results announced this time come from an 8-week open-label study designed to evaluate the efficacy and safety of ALTO-100 in patients with MDD or PTSD. The study included 133 patients with primary MDD (moderate to severe) and 90 patients with primary PTSD. The primary endpoint was the change in CAPS-5 scores from baseline at week 4. CAPS-5 scoring is the gold standard for PTSD assessment, consisting of a 20-item structured interview used for diagnosing and evaluating PTSD symptoms.

In this study, according to the CAPS-5 score results,Compared to patients without specific biomarkers, PTSD symptoms improved more significantly in the subgroup of patients screened with specific biomarkers.At week 4, the biomarker-defined PTSD patient group (44 individuals) showed an average reduction of 17.5 points in CAPS-5 scores, while the non-biomarker patient group (40 individuals) exhibited a reduction of 12.9 points (p=0.04, d=0.37).46% of patients defined by biomarkers achieved clinical remission (defined as a 50% or greater reduction in CAPS-5 PTSD symptoms from baseline), compared to only 26% of patients without biomarker characteristics achieving clinical remission (p=0.065).

Currently, ALTO-100 has been studied in 395 subjects and has shown good tolerability.

This research found no new safety signals, consistent with the report from January this year.