First positive U.S. Phase 3 study of an investigational therapy for social anxiety disorder in over 15 years

Statistically significant rapid-onset reduction in patient-reported Subjective Units of Distress Scale (SUDS) score compared to placebo in a public speaking challenge (primary endpoint, p=0.015)

Trial also met the secondary endpoint, demonstrating a statistically significant difference in proportion of responders compared to placebo as measured by the Clinical Global Impressions Improvement (CGI-I) scale (secondary endpoint, p=0.033)

Fasedienol was well-tolerated and demonstrated a favorable safety profile consistent with all prior trials of fasedienol in social anxiety disorder

Over 25 million Americans are living with social anxiety disorder and 188 million worldwide, including at least 11.3 million in China.^1,2,3

Shanghai - August 10, 2023 -- AffaMed Therapeutics (“AffaMed”) announced today that its partner Vistagen Therapeutics (‘Vistagen’ - NASDAQ: VTGN), a clinical-stage biopharmaceutical company aiming to transform the treatment landscape for individuals living with anxiety, depression and other central nervous system (CNS) disorders, reported positive top-line results from its Phase 3 PALISADE-2 trial evaluating the efficacy, safety, and tolerability of fasedienol (PH94B) nasal spray in adults diagnosed with social anxiety disorder (SAD). The trial met its primary endpoint, with fasedienol demonstrating a statistically significant difference in average SUDS score during a public speaking challenge compared to placebo (p=0.015). The trial also met its secondary endpoint, demonstrating a statistically significant difference in the proportion of clinician-assessed responders between fasedienol and placebo as measured by the CGI-I scale (p=0.033). Fasedienol was well-tolerated and demonstrated a favorable safety profile consistent with all prior trials.

In June 2020, VistaGen entered into a strategic licensing and collaboration agreement with AffaMed Therapeutics for the clinical development and commercialization of PH94B in China, South Korea, and Southeast Asia.

“We are thrilled that these compelling top-line results from the Phase 3 PALISADE-2 trial confirm what was seen in the Phase 2 studies in social anxiety disorder and highlight the potential for fasedienol, with its novel and unique proposed mechanism of action, to transform what is possible for more than 25 million people living with social anxiety in the U.S. and millions more affected worldwide,” stated Shawn Singh, Chief Executive Officer of Vistagen. “As a new class of medicines, our pherine nasal spray pipeline holds the potential to transform the treatment landscape across numerous therapeutic areas. At the head of that class, fasedienol’s potential, as demonstrated in this Phase 3 trial, sets the stage for the first fundamentally new class of medicine for individuals living with SAD in more than 20 years.”

Dr. Dayao Zhao, Chief Executive Officer of AffaMed commented “We are extremely pleased to see the results from the PALISADE-2 trial demonstrating the potential for fasedienol in the treatment of social anxiety, and we look forward to working together with Vistagen to bring forward this new treatment option for the rapidly growing number of individuals living with SAD in China, South Korea, and Southeast Asia”.

Primary Efficacy Endpoint

The PALISADE-2 trial (n=141) met its primary efficacy endpoint, the difference in mean SUDS score during the public speaking challenge at baseline (Visit 2) and treatment (Visit 3) for patients who received fasedienol (n=70) compared to placebo (n=71) at Visit 3. Fasedienol-treated patients demonstrated a statistically significant greater change in mean SUDS score (least-squares (LS) mean = -13.8) compared to placebo (LS mean = -8.0), for a difference between groups of -5.8 (p=0.015).

Secondary Efficacy Endpoint

The trial met its secondary endpoint, demonstrating a statistically significant difference in the proportion of clinician-assessed responders between fasedienol and placebo as measured by the CGI-I scale. Responders were identified as those who were rated ‘very much less anxious’ or ‘much less anxious’ with 37.7% (n=70) of fasedienol-treated patients rated as responders, as compared to 21.4% (n=71) of those treated with placebo (p=0.033).

Exploratory Efficacy Endpoints

The trial met an important exploratory endpoint of the difference in the proportion of patient-assessed responders between fasedienol and placebo as measured by the Patient’s Global Impression of Change (PGI-C) scale. Responders were identified as those who self-rated ‘very much less anxious’ or ‘much less anxious’ with 40.6% (n=70) of fasedienol-treated patients rated as responders, as compared to 18.6% (n=71) of those treated with placebo (p=0.003).

The trial also met the exploratory endpoint of the difference in the proportion of patients in each treatment group with a 20-point improvement in patient-assessed SUDS score from baseline (Visit 2) to treatment (Visit 3). Of the fasedienol-treated patients, 35.7% (n=70) demonstrated this statistically significant and clinically meaningful improvement in SUDS score, as compared to 18.6% (n=71) in the placebo-treated group (p=0.020).

Safety

Fasedienol was observed to be well-tolerated in the study with no severe or serious adverse events (AEs) reported. All treatment-emergent adverse events reported for the overall study were mild or moderate. There were no AEs reported in the fasedienol treatment arm above 2% occurrence.

About the Phase 3 PALISADE-2 Trial

PALISADE-2 was a multi-center, randomized, double-blind, placebo-controlled, Phase 3 clinical study in adults diagnosed with SAD. The study was designed to evaluate the efficacy, safety, and tolerability of the acute administration of fasedienol to relieve anxiety symptoms in adult patients with SAD during a simulated anxiety-provoking public speaking challenge, as measured using the patient-reported SUDS score.

Enrolled patients had a diagnosis of SAD and demonstrated marked social anxiety at enrollment, as evidenced by a baseline score on the Liebowitz Social Anxiety Scale (LSAS) of at least 70. A total of 141 patients were enrolled in the U.S. multi-center trial. The total enrollment reflects the pause in enrollment after receiving top-line results from PALISADE-1 to allow for independent third-party biostatisticians to conduct an interim analysis of the 141 patients randomized in the trial up to the date of the pause. Although the results of the independent interim analysis indicated that continuation of PALISADE-2 would not be futile, Vistagen determined the best course of action was to close the PALISADE-2 study given the expense, time and methodological complexities involved in resuming PALISADE-2.

Additional analysis of data from the Phase 3 PALISADE-2 trial is ongoing, with plans to present these results at future scientific meetings.

About Fasedienol Nasal Spray

Vistagen’s fasedienol (PH94B) is a first-in-class, rapid-onset investigational pherine nasal spray with a novel proposed mechanism of action (MOA) that regulates the olfactory-amygdala neural circuits of fear and anxiety and attenuates the tone of the sympathetic autonomic nervous system, without systemic distribution, potentiation of GABA-A receptors or direct activity on neurons in the brain. Vistagen is developing fasedienol in a Phase 3 program for the treatment of social anxiety disorder. Designed for intranasal administration in low microgram doses, the proposed novel MOA of fasedienol is fundamentally differentiated from all currently approved anti-anxiety medications, including all SSRIs and SNRIs as well as benzodiazepines prescribed off-label.

About Social Anxiety Disorder

Social anxiety disorder (SAD) affects over 25 million Americans and 188 million worldwide, including at least 11.3 million in China ^1,2,3. A person with SAD feels intense, persistent symptoms of anxiety or fear in certain social situations, such as meeting new people, making comments in a business meeting, dating, being on a job interview, answering a question in class, or talking to a cashier in a store. Doing common, everyday things in front of people causes profound anxiety or fear of being embarrassed, evaluated, humiliated, judged, or rejected. SAD can get in the way of going to work, attending school, or doing a wide variety of things in a situation that is likely to involve interpersonal interaction. It can lead to avoidance and opportunity costs that can significantly impact a person's employment and social activities and can be very disruptive to their overall quality of life. SAD is commonly treated long-term with certain FDA-approved antidepressants, which have a slow onset of effect (several weeks) and provide limited therapeutic benefits, and with benzodiazepines, which are not FDA-approved for treating SAD. Both antidepressants and benzodiazepines have known side effects and significant safety concerns that may make them unattractive to individuals affected by SAD.

About AffaMed Therapeutics

 AffaMed Therapeutics is a clinical stage biopharmaceutical company focused on developing and commercializing transformative pharmaceutical, digital and surgical products that address critical unmet medical needs in ophthalmological, neurological and psychiatric disorders for patients in Greater China and around the world. The leadership team at AffaMed Therapeutics has gained deep industry expertise and an extensive track record in high-quality discovery, clinical development, regulatory affairs, business development, manufacturing, and commercial operations at leading multi-national biopharmaceutical companies in China and globally.

References

1. National Health and Wellness Survey (NHWS), 2021.

2. Stein, D.J., Lim, C.C.W., Roest, A.M. et al. The cross-national epidemiology of social anxiety disorder: Data from the World Mental Health Survey Initiative. BMC Med 15, 143 (2017).

3. Frost & Sullivan. January 2022. Global Market Study of CNS and Opthalmic Treatment Market, 2022. Shanghai, China.