VistaGen Therapeutics is a clinical-stage biopharmaceutical company committed to developing novel medicine to treat depression and other diseases and disorders associated with the central nervous system (CNS).


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 clinical studies conducted by 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 lead drug candidate, 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 SSRIs and 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 1 clinical studies funded by the U.S. National Institutes of Health (NIH), AV-101 was safe and well-tolerated, without any serious adverse events.

In 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 NIMH-funded Phase 2 clinical efficacy and safety study of AV-101 in subjects with treatment-resistant MDD. Dr. Zarate, Chief of the NIMH’s Experimental Therapeutics & Pathophysiology Branch and an internationally recognized expert in the field of depression, was among the first clinical researchers in the world to discover the therapeutic potential of ketamine in treatment-resistant MDD.

Stem Cell Technology-based Drug Rescue and Regenerative Medicine

VistaGen is among the first generation of companies using pluripotent stem cell technology for potential commercial applications focused on producing proprietary new chemical entities (NCEs) through drug rescue and regenerative therapies. VistaGen’s CardioSafe 3D is a customized human cellular bioassay system using VistaGen’s mature, functional human heart cells to predict heart toxicity of potential drug rescue NCEs in vitro, long before they are ever tested in animal or human studies. VistaGen intends to explore collaborative arrangements to apply its pluripotent stem cell-derived cells for regenerative medicine purposes involving cancer and diseases and conditions related to blood, cartilage, heart and liver cells.