New Investigational Social Anxiety Disorder Drug Differentiates Mechanism of Action

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VistaGen Therapeutics announced new mechanism of action data from a study in laboratory rats that demonstrated a single intranasal dose of PH94B was largely confined to the nasal passages and minimal or undetectable in most other tissues, including the central nervous system (CNS). This supports the proposed mechanism of action of PH94B: binding to receptors of peripheral neurons in the nasal passages, not to neuronal receptors in the CNS, and limiting molecule movement to the circulatory system.

“In this study, the absence of radiolabeled PH94B in the rodent brain is an encouraging sign that PH94B may have limited circulatory systemic exposure when administered intranasally,” stated Mark Smith, MD, PhD, Chief Medical Officer of VistaGen. “Furthermore, the tissue distribution of radiolabeled carbon-14 PH94B was minimal in the tested lab animals, with the highest concentration primarily in the nasal turbinates. These findings strongly support a local disposition of PH94B in the olfactory receptor neurons and an absence of binding of PH94B in the central nervous system. We believe that this is another positive indication supporting the clinical development of PH94B.”

PH94B is an investigational, odorless, CNS pherine nasal spray with a rapid onset of approximately 15 minutes. The investigation agent is intended for the treatment of social anxiety disorder (SAD), with therapeutic potential in multiple additional anxiety disorders. The investigation agent is intended for the treatment of social anxiety disorder (SAD), with therapeutic potential in multiple additional anxiety disorders. PH94B is administered intranasally in microgram doses, and it activates peripheral nasal chemosensory neurons that trigger neural circuits in the brain to suppress fear and anxiety.

“We are very excited about these new study results, which further highlight how the mechanism of action of PH94B is fundamentally differentiated from all current anti-anxiety therapies,” said Shawn K. Singh, Chief Executive Officer of VistaGen. “When combined with previously announced preclinical electrophysiology data demonstrating that the mechanism of action of PH94B does not involve direct activation of GABA-A receptors, which is in distinct contrast to the mechanism of action of benzodiazepines, we see a growing body of evidence suggesting that PH94B has potential to achieve anti-anxiety effects without requiring systemic uptake or causing benzodiazepine-like side effects and safety concerns.”

VistaGen has initiated 2 ongoing phase 3 clinical trials of PH94B—PALISADE-1 and PALISADE-2—for potential acute treatment of anxiety in adults with SAD; the US Food and Drug Administration has granted it fast track designation.

“At a time when the current drug treatment paradigm for social anxiety disorder, or SAD, is falling far short of delivering necessary relief without worrisome potential consequences, an innovative treatment alternative is imperative. If successfully developed in our ongoing PALISADE Phase 3 Program, PH94B has the potential to fill that void as the first fast-acting, on demand acute treatment of anxiety for more than 23 million Americans who suffer from SAD,” Singh said further.

Reference

1. VistaGen Therapeutics. VistaGen Therapeutics reports new preclinical mechanism of action data supporting PH94B’s potential anti-anxiety activity via peripheral nasal neurons without entry into the brain. October 5, 2021. https://www.globenewswire.com/news-release/2021/10/05/2308651/0/en/VistaGen-Therapeutics-Reports-New-Preclinical-Mechanism-of-Action-Data-Supporting-PH94B-s-Potential-Anti-Anxiety-Activity-via-Peripheral-Nasal-Neurons-without-Entry-into-the-Brain.html