Vistagen Therapeutics, Inc. released of positive Phase 3 Trial Results. Positive Phase 3 PALISADE-2 study of fasedienol yields statistically significant top-line results for the acute treatment of anxiety in adults with SAD. The Company?s Phase 3 PALISADE-2 trial (n=141) met its primary efficacy endpoint, the difference in mean Subjective Units of Distress Scale (SUDS) score during the public speaking challenge at baseline (Visit 2) and treatment (Visit 3) for patients who received fasedienol (n=70) versus 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).

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 Clinical Global Impressions Improvement (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). Additionally, the trial met the 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). Finally, 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). Fasedienol was observed to be well-tolerated with no severe or serious adverse events (AEs) reported. All treatment-emergent AEs reported for the overall study were mild or moderate.

There were no AEs reported in the fasedienol treatment arm above 2% occurrence. Fasedienol is a rapid-onset investigational neuroactive nasal spray with a proposed rapid-onset, non-systemic mechanism of action that sets it apart from all currently approved anti-anxiety medications. Phase 3 PALISADE-3 study of fasedienol for the acute treatment of anxiety in adults with SAD.

Based on the positive top-line results of the Phase 3 PALISADE-2 study, currently preparing for Phase 3 PALISADE-3 trial, with potential to initiate the trial during the first half of calendar 2024. Like PALISADE-2, PALISADE-3 will be designed as a U.S. multi-center, randomized, double-blind, placebo-controlled, Phase 3 clinical study 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 as the primary efficacy endpoint. Preparations for Phase 3 FEARLESS Program in SAD underway after positive U.S. Food and Drug Administration (FDA) feedback on use of Liebowitz Social Anxiety Scale (LSAS) as a primary efficacy endpoint in a Phase 3 real-world study.

To complement PALISADE Phase 3 Program for fasedienol in SAD, the Company is currently preparing for its Phase 3 FEARLESS trial, with potential to initiate the trial in the second half of calendar 2024 with a study design similar to the registration trials for the three drugs currently approved for the treatment of SAD using the LSAS as the primary efficacy endpoint. Accordingly, FEARLESS will be designed as a randomized, double-blind, placebo-controlled Phase 3 trial of fasedienol in adults with SAD to evaluate the efficacy, safety and tolerability of multiple administrations of fasedienol, on a patient-tailored as-needed basis, up to six times per day in their daily lives, in a real-world setting over a multiple week period. To complement the positive results of PALISADE-2, believe the Phase 3 FEARLESS study design also will align with the way SAD patients will use fasedienol in their daily lives, should it be approved, because planned fasedienol treatment model includes both repeated experiences of acute reduction of anxiety during performance and social events, evidenced by decreased SUDS scores as in PALISADE-2, as well as longer-term overall reduction in severity of SAD evidenced by reductions in LSAS scores, as will be assessed in FEARLESS.