Benzinga | Mar 22, 2021 08:39AM EDT

VistaGen Therapeutics Says Co's Poster Presentation At Anxiety And Depression Association Of America 2021 Conference 'Differentiates PH94B's Mechanism Of Action From Highly-Addictive Benzodiazepines'

VistaGen Therapeutics, Inc. (NASDAQ:VTGN), a biopharmaceutical company committed to developing a new generation of medicines with the potential to go beyond the current standard of care for anxiety, depression and other central nervous system (CNS) disorders, announced today that data highlighting the proposed mechanism of action (MOA) of its Phase 3 investigational drug candidate, PH94B nasal spray, were recently presented in a poster session at the Anxiety and Depression Association of America's 2021 Virtual Annual Conference. PH94B is designed with potential to provide rapid-onset acute treatment of anxiety for millions of individuals suffering from social anxiety disorder (SAD) without directly activating gamma-amino butyric acid (GABA-A) receptors. PH94B's MOA is, therefore, fundamentally differentiated from the MOA of benzodiazepines such as alprazolam, diazepam and lorazepam, which are direct GABA-A receptor positive modulators. Among VistaGen's core goals is for PH94B to displace these and other widely-used but highly-addictive benzodiazepines in the acute treatment paradigm for SAD and other anxiety disorders and phobias.



PH94B is an investigational odorless pherine nasal spray entering Phase 3 clinical development in the U.S. for the acute treatment of anxiety in adults with SAD, the third most common mental health disorder among Americans, affecting approximately 20 million individuals. PH94B also has therapeutic potential in a wide range of additional anxiety disorders and phobias. Self-administered in microgram-level doses, in Phase 2 clinical studies, PH94B produced rapid-onset anti-anxiety effects within approximately 15 minutes, without the troubling side effects associated with benzodiazepines.

To help differentiate PH94B's mechanism of action from that of benzodiazepines, VistaGen studied whether PH94B had positive modulatory effects on GABA receptors.

Key results in the recent ADAA poster presentation include the following:

* PH94B had no significant effect on GABA potentiation at doses up to 10 micromolar, compared to the 300 percent potentiation induced by diazepam, a commonly-prescribed benzodiazepine.

* The concentration of PH94B that gives the half-maximal response (EC50) could not be calculated for PH94B, whereas diazepam's half-maximal response (EC50) was 72 nanomolar.

* PH94B had no agonist or antagonist effects on GABA receptors compared to the effect of GABA (EC50= 4.7 micromolar) and bicuculline (EC50= 1.6 micromolar), respectively.

"The results are in agreement with PH94B's lack of benzodiazepine-like side effects and safety concerns reported in PH94B clinical studies -- for example, lack of sedation, cognitive impairment or abuse liability potential," said Louis Monti, M.D., Ph.D., Vice President, Translational Medicine of VistaGen. "This study demonstrated that PH94B's mechanism of action is through neural regulation of forward inhibitory GABAergic neurons in the limbic amygdala and is differentiated from benzodiazepines' mechanism of action, which is through a direct local potentiating effect on GABA receptors. These data are key in understanding PH94B's overall potential effectiveness and safety for individuals suffering from SAD and many other anxiety disorders."

"Given the FDA's recent Drug Safety Communication that outlined and highlighted the safety risks associated with benzodiazepine use, the implications resulting from this study are significant," added Mark Smith, M.D., Ph.D., Chief Medical Officer of VistaGen. "PH94B may have the potential to displace benzodiazepines altogether and become the safer alternative to help the millions of Americans suffering from anxiety with limited options for safe, effective treatment options. These existing treatments can actually hurt instead of help. We look forward to launching our Phase 3 clinical development program for PH94B next quarter and continuing to push forward in our mission to get it into the hands of those in need as soon as possible."