VistaGen Therapeutics is a clinical-stage biopharmaceutical company committed to developing novel medicine to treat depression, cancer and diseases and disorders involving the central nervous system.


AV-101 for Depression

Depression is a global public health concern. The World Health Organization estimates that “depression is the leading cause of disability worldwide, and is a major contributor to the global burden of disease,” affecting 350 million people globally. According to the U.S. Centers for Disease Control and Prevention (CDC), “one in 10 Americans aged 12 and over takes antidepressant medication.”

Today, millions of depression patients are poorly-served by currently available antidepressants, most of which involve the neurotransmitters serotonin and serotonin/norepinephrine (SSRIs and SNRIs) and require several weeks to months before any therapeutic benefit can be achieved.

Ketamine, a classic NMDA receptor (NMDAR) antagonist, has been shown in revolutionary clinical trials conducted by Dr. Carlos Zarate of the U.S. National Institute of Mental Health (NIMH) and others to act rapidly to alleviate symptoms of depression in treatment-resistant patients suffering with Major Depressive Disorder (MDD). Although the potential for widespread therapeutic use of ketamine has been severely limited by its side effects, high risk for abuse and behavioral impairment, and inconvenient i.v. administration in a clinical setting, these studies inspired development of a new generation of antidepressants with potential to deliver the fast-acting antidepressant effects of ketamine without its serious side effects.

VistaGen’s AV-101 (L-4-chlorokynurenine) is an orally-available NMDAR glycine-binding site antagonist. Its mechanism of action is fundamentally different from all commonly-prescribed antidepressants, including all selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), which take weeks to months to achieve any therapeutic benefit. In preclinical studies, AV-101 demonstrated the robust, fast-acting, antidepressant-like effects of ketamine, without ketamine’s undesirable side effects. Additionally, in two randomized, double-blind, placebo-controlled Phase I clinical studies funded by the U.S. National Institutes of Health (NIH), AV-101 was safe and well-tolerated, without any serious adverse events. There were no signs of sedation, hallucinations or the schizophrenia-like side effects often associated with ketamine and other classic NMDAR channel blockers.

In early-2015, VistaGen entered a Cooperative Research and Development Agreement (CRADA) with the NIMH. Under the CRADA, VistaGen, and the NIMH, led by Dr. Carlos Zarate as Principal Investigator, are collaborating on an NIH-funded Phase 2 clinical efficacy and safety study of AV-101 in subjects with treatment resistant Major Depressive Disorder. The study is expected to begin during the second half of 2015.

Stem Cell Technology-based Drug Rescue

With the mature, functional human heart cells and liver cells produced using its pluripotent stem cell technology, VistaGen has developed two novel, customized human cellular bioassay systems, CardioSafe 3D and LiverSafe 3D, for predicting heart toxicity and liver toxicity of new drug candidates in vitro, long before they are ever tested in animal or human studies. We use CardioSafe 3D and LiverSafe 3D to advance our internal drug rescue programs, which are focused on producing new chemical entities (NCEs) for our internal development pipeline. These drug rescue NCEs are intended to be novel, safer variants of drug candidates previously optimized and tested for efficacy by pharmaceutical companies and others but terminated before FDA approval due to heart or liver toxicity concerns. Our initial drug rescue programs are focused on NCEs for treatment of cancer.