VistaGen, Baylor Announce Successful Results of AV-101 for Suicidal Ideation in Vets

VistaGen Therapeutics and Baylor College of Medicine announced successful results from a first-step, Phase 1b clinical study with healthy U.S. military Veterans, which measured NMDAR (N-methyl-D-aspartate receptor) target engagement of VistaGen's investigational product candidate, AV-101, an oral NMDAR glycine site antagonist, for potential treatment of suicidal ideation in Veterans. The findings from the study were presented in a poster, titled "Evoked and Resting State Gamma Mechanics to Test NMDA Receptor Engagement of Kynurenine Pathway Modulator AV-101 in Healthy Veterans."

In the Phase 1b target engagement study, 10 healthy volunteer Veterans from Operation Enduring Freedom, Operation Iraqi Freedom or Operation New Dawn received single doses of AV-101 (720 mg and 1440 mg) and placebo, in a double-blind, randomized, cross-over controlled trial. The primary goal of the study was to identify and define a dose-response relationship between AV-101 and multiple electrophysiological (EEG) biomarkers related to NMDAR function, as well as blood biomarkers associated with suicidality. The findings suggest that, in healthy Veterans, the higher dose of AV-101 (1440 mg) was associated with dose-related increase in the 40 Hz Auditory Steady State Response (ASSR), a robust measure of the integrity of inhibitory interneuron synchronization.

Both doses of AV-101 were well-tolerated, and there were no dissociative adverse events or serious adverse events.

Dr. Marijn Lijffijt, assistant professor of psychiatry research at Baylor and the Michael E. DeBakey VA Medical Center (MEDVAMC) in Houston served as Principal Investigator of the study. VistaGen and the U.S. Department of Veterans Affairs (VA) entered into a Material Transfer Cooperative Research and Development Agreement (MT CRADA) regarding clinical trial material for this study, and VA funding was provided for all other study costs.

"According to the VA, over 20 veterans take their lives each day – a number that is alarming and unfortunate," said Mark A. Smith, M.D, Ph.D., VistaGen's Chief Medical Officer. "Nearly every day we hear stories in the news about how the suicide rate is increasing, and how it's even higher among U.S. Veterans than non-Veterans. Better therapies are needed for Veterans who are suffering from suicidal ideation. We interpret the findings of this biomarker study to mean that the high dose of AV-101 was sufficient to reduce NMDA function. Based on our recent preclinical studies demonstrating the ability of the transport inhibitor probenecid to markedly increase concentrations of AV-101 (approximately 7-fold) and its active metabolite 7-chloro-kynurenic acid (approximately 35-fold) in the rodent brain, it may be possible to increase and prolong NMDA antagonism even further when AV-101 and probenecid are combined. These human target engagement findings represent our first-step collaboration with Baylor and the VA, and they increase our confidence in AV-101's safety and its potential, especially with adjunctive probenecid, to treat this major health concern. We look forward to future discussions with Baylor and the VA regarding a second-step program involving Veterans who are battling suicidal ideation."

"Overall, this study is a promising start on the path to explore AV-101's potential to address the morbidity and mortality associated with suicidal depression," said Sanjay J. Mathew, M.D., vice chair for research and professor of psychiatry and behavioral sciences at Baylor, and a Staff Psychiatrist at MEDVAMC. "Substantially increased concentrations of 7-Cl-KYNA in VistaGen's recent preclinical studies of AV-101 with adjunctive probenecid are notable. Future clinical studies in military veterans could examine the effect of AV-101, at the 1440 mg dose combined with probenecid, in suicide risk. We look forward to further collaborations with VistaGen and the VA."

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