VistaGen Therapeutics and AffaMed Therapeutics Submit IND Application in China for PH94B Nasal Spray, a Potential First-in-Class Rapid-Onset Treatment for Social Anxiety Disorder

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Today (November 8), a public disclosure from the Center for Drug Evaluation (CDE) of China's National Medical Products Administration indicates that a clinical trial application for a PH94B nasal spray, jointly filed by VistaGen Therapeutics and Shanghai Aimai Medical Technology Co., Ltd. (hereinafter referred to as Aimai Medical), has been submitted and accepted in China. Public information shows that PH94B is a potential "first-in-class," fast-acting neurosteroid candidate drug under development by VistaGen, which has globally advanced to Phase 3 clinical trials for the treatment of social anxiety disorder (SAD). Incubated by Vivo Capital, Aimai Medical holds the development and commercialization rights for PH94B in Greater China, South Korea, and Southeast Asia. What, then, are the distinctive features of this investigational drug?

Screenshot source: CDE official website

According to publicly available information, PH94B is a potential "first-in-class," odorless, fast-acting (within approximately 15 minutes) synthetic neurosteroid nasal spray with the potential to treat various anxiety-related disorders. In December 2019, the U.S. FDA granted PH94B Fast Track designation for the as-needed treatment of social anxiety disorder. According to a press release from VistaGen at the time, this was the first Fast Track designation granted by the FDA for a social anxiety disorder (SAD) candidate drug.

It is reported that PH94B is designed for intranasal administration at microgram doses, fundamentally distinguishing it from all current anti-anxiety medications, including benzodiazepines. Its uniqueness lies in activating peripheral nasal chemosensory neurons to trigger neural circuits in the brain that inhibit fear and anxiety, rather than binding to neuronal receptors in the central nervous system (CNS), thereby limiting the molecule's transport into the systemic circulation and minimizing potential systemic exposure. Consequently, PH94B exhibits a rapid-onset pharmacological profile and a favorable safety profile, producing rapid anxiolytic effects without requiring systemic absorption and distribution.

Previously, PH94B demonstrated positive results in Phase 2 clinical studies. During both the public speaking challenge (p=0.002) and the social interaction challenge (p=0.009), the investigational drug rapidly reduced (within 15 minutes) anxiety symptoms in subjects. Subsequently, VistaGen initiated the Phase 3 trials PALISADE-1 and PALISADE-2 for the acute treatment of anxiety in adults.

In June 2020, EverInsight, a company incubated by CBiopharma, entered into a strategic partnership with VistaGen to develop and commercialize PH94B, a drug candidate for the treatment of anxiety disorders, in Greater China, South Korea, and Southeast Asia. Under the terms of the agreement, EverInsight will be responsible for the clinical development, regulatory submissions, and commercialization of the PH94B nasal spray in the designated collaboration regions for the acute treatment of social anxiety disorder (SAD) and other potential anxiety-related indications. Pursuant to the agreement, EverInsight will pay an upfront payment of $5 million, plus up to $172 million in additional development and commercial milestone payments.

In October 2020, AffaMed Therapeutics, another company also incubated by C-Bridge Capital, entered into a definitive merger agreement with EverInsight. The post-merger entity retained the name AffaMed Therapeutics (i.e., Aima Medical), with Dr. Dayao Zhao serving as Chief Executive Officer. Subsequently, PH94B became one of the pipeline products under development at AffaMed Therapeutics. According to the public notice issued by the Center for Drug Evaluation (CDE), the clinical trial application for the PH94B nasal spray submitted in China was filed by VistaGen Therapeutics and AffaMed Therapeutics.

Social anxiety disorder is a health issue of widespread concern. According to data from the National Institutes of Health (NIH), it is the third most common psychiatric disorder, following depression and substance abuse. Individuals with SAD experience intense and persistent anxiety or fear in certain social situations, such as meeting new people, going on dates, attending job interviews, answering questions in class, or interacting with cashiers at stores.

Currently, SAD is typically managed with long-term treatment using certain regulatory-approved antidepressants, which are characterized by a slow onset of action (taking several weeks) and limited therapeutic efficacy. Furthermore, both antidepressants and off-label benzodiazepines are associated with known adverse effects and safety concerns. Consequently, there is a significant unmet clinical need for novel, safe, and effective therapies. We hope that the PH94B nasal spray progresses smoothly through its clinical development, bringing a new treatment option to patients at the earliest opportunity.

References:

[1] Center for Drug Evaluation, National Medical Products Administration. Retrieved Nov. 8, 2021, from https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d

[2] AffaMed Therapeutics Announces Definitive Merger Agreement with EverInsight Therapeutics and Appointment of Dr. Dayao Zhao as CEO. Retrieved Oct 14, 2020, from https://world.einnews.com/pr_news/528352300/affamed-therapeutics-everinsight-therapeutics-ceo

[3]VistaGen Therapeutics and EverInsight Therapeutics Enter Strategic Collaboration to Develop and Commercialize PH94B for Anxiety Disorders in Greater China, South Korea and Southeast Asia. Retrieved Jun. 25，2020, from https://www.vistagen.com/news-media/press-releases/detail/141/vistagen-therapeutics-and-everinsight-therapeutics-enter

[4]U.S. FDA Grants VistaGen Therapeutics Fast Track Designation for PH94B for Treatment of Social Anxiety Disorder. Retrieved Dec. 10, 2019, from https://www.vistagen.com/news-media/press-releases/detail/131/u-s-fda-grants-vistagen-therapeutics-fast-track