US, Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial of Fasedienol Nasal Spray for the Acute Treatment of Anxiety Induced by a Public Speaking Challenge in Adult Subjects With Social Anxiety Disorder, With an Open-Label Extension (PALISADE-4)

This U.S. Phase 3 clinical trial is designed to evaluate the efficacy, safety, and tolerability of the acute intranasal (i.n.) administration of Fasedienol Nasal Spray (fasedienol) (3.2 µg) to relieve symptoms of acute anxiety in adult subjects ages 18 through 65 with Social Anxiety Disorder induced by a public speaking challenge (PSC) in a clinical setting. In addition, safety and tolerability of i.n. administration of 3.2 µg of fasedienol, as-needed, up to 6 times per day for up to 12 months, will be assessed in those subjects who complete PALISADE-4 and choose to enter the distinct open-label extension phase of the study.

Start Date16 Sep 2024

Sponsor / Collaborator

VistaGen Therapeutics, Inc.

NCT06358651 / RecruitingPhase 3

This U.S. Phase 3 clinical trial is designed to evaluate the efficacy, safety, and tolerability of the acute intranasal (i.n.) administration of Fasedienol Nasal Spray (fasedienol) (3.2 µg) to relieve symptoms of acute anxiety in adult subjects ages 18 through 65 with Social Anxiety Disorder induced by a public speaking challenge (PSC) in a clinical setting. In addition, safety and tolerability of i.n. administration of 3.2 µg of fasedienol, as-needed, up to 6 times per day for up to 12 months, will be assessed in those subjects who complete PALISADE-3 and choose to enter the distinct open-label extension phase of the study.

Start Date28 Mar 2024

Sponsor / Collaborator

VistaGen Therapeutics, Inc.

NCT04404192 / CompletedPhase 2

A Phase 2a Double-blind, Placebo-controlled, Parallel Study of PH94B Nasal Spray in the Treatment of Adjustment Disorder With Anxiety

This placebo-controlled clinical study is designed to evaluate the efficacy, safety and tolerability of administration of PH94B nasal spray four times per day as a treatment of Adjustment Disorder with Anxiety symptoms in adults. Subject participation in the Study will last a total of 6 to 10 weeks, depending on the duration of the screening period and whether they need a washout of concomitant anxiolytics. Upon signing an investigation review board approved informed consent, all subjects will complete Visit 1 (Screening) and enter a screening period lasting 7 to 35 days that could include taper of concomitant anxiolytics, if necessary. Screening visit will consist of safety assessments (medical history, physical examination, laboratory samples, electrocardiogram, urine drug screen, and urine pregnancy test [if appropriate]) and psychiatric assessments to determine eligibility. Subjects will then return to complete Visit 2 (Baseline). If the subject continues to meet inclusion and exclusion criteria, the subject will be randomized 1:1 to PH94B or placebo. Subjects will then commence 4 weeks of double-blind treatment with randomized investigational product (PH94B or placebo) four times per day.
Subjects will return for weekly site visits (Visits 3, 4, 5, and 6), in which the subject will return the vial dispensed at the previous visit and receive a new vial, except at Visit 6 in which no new vial will be dispensed. Changes in AEs and concomitant medications will be collected. During these visits, psychiatric scales will be completed. When the subject returns for Visit 6, besides the assessments completed at Visits 3 through 5, the subjects will complete a brief physical examination, electrocardiogram, laboratory tests (chemistry and blood), and urinalysis. Any remaining IP vials will be collected. The subject will then come back after a one week washout period for Follow-up visit (Visit 7).

Start Date12 Oct 2021

Sponsor / Collaborator

VistaGen Therapeutics, Inc.

100 Clinical Results associated with Aloradine

100 Translational Medicine associated with Aloradine

100 Patents (Medical) associated with Aloradine

Literatures (Medical) associated with Aloradine

01 Mar 2024·Human psychopharmacology

Effect of fasedienol (PH94B) pherine nasal spray and steroidal hormones on electrogram responses and autonomic nervous system activity in healthy adult volunteers

Article

Author: Monti, Louis ; Lappalainen, Jaakko ; Hanover, Rita ; Salmán, Ester ; Baker, Ross A. ; Smith, Mark

Abstract:

Objective:

Fasedienol (PH94B) is a pherine compound formulated as a nasal spray that is hypothesized to regulate olfactory‐amygdala circuits of fear and anxiety. Fasedienol's effect on the local electrogram of nasal chemosensory neurons (EGNR) and autonomic nervous system (ANS) responses versus steroidal hormones and controls in healthy adults is reported.

Methods:

Eight males and 8 females randomly received aerosolized control (propylene glycol) and study drugs (fasedienol, 17β‐estradiol, progesterone, cortisol, and testosterone, 0.4 μg each in propylene glycol) onto the nasal septum mucosal lining at 30‐min intervals over 2 sessions. EGNR was continuously monitored; autonomic parameters were recorded before and after administration.

Results:

Fasedienol significantly increased EGNR amplitude (males: 5.0 vs. 0.6 mV, p < 0.001; females:5.7 vs. 0.6 mV, p < 0.001), and rapidly reduced respiratory rate (p < 0.05), heart rate (p < 0.01), and electrodermal activity (p < 0.05) versus control. EGNR and ANS responses after steroidal hormone administration were similar to control. 81% reported feeling less tense/more relaxed after receiving fasedienol, but not after receiving either control or steroidal hormones.

Conclusions:

Intranasal fasedienol, but not control or steroidal hormones, activated EGNR and rapidly reduced ANS responses, consistent with sympatholytic effects. Combined with subjective reports, results suggest fasedienol may provide acute relief in anxiety conditions.

01 Feb 2024·Drugs

A Neuroanatomic and Pathophysiologic Framework for Novel Pharmacological Approaches to the Treatment of Post-traumatic Stress Disorder

Review

Author: Norred, Michael A ; Hamner, Mark B ; Zuschlag, Zachary D

Post-traumatic stress disorder (PTSD) is a debilitating disorder inflicting high degrees of symptomatic and socioeconomic burdens. The development of PTSD results from a cascade of events with contributions from multiple processes and the underlying pathophysiology is complex, involving neurotransmitters, neurocircuitry, and neuroanatomical pathways. Presently, only two medications are US FDA-approved for the treatment of PTSD, both selective serotonin reuptake inhibitors (SSRIs). However, the complex underlying pathophysiology suggests a number of alternative pathways and mechanisms that may be targets for potential drug development. Indeed, investigations and drug development are proceeding in a number of these alternative, non-serotonergic pathways in an effort to improve the management of PTSD. In this manuscript, the authors introduce novel and emerging treatments for PTSD, including drugs in various stages of development and clinical testing (BI 1358894, BNC-210, PRAX-114, JZP-150, LU AG06466, NYV-783, PH-94B, SRX246, TNX-102), established agents and known compounds being investigated for their utility in PTSD (brexpiprazole, cannabidiol, doxasoin, ganaxolone, intranasal neuropeptide Y, intranasal oxytocin, tianeptine oxalate, verucerfont), and emerging psychedelic interventions (ketamine, MDMA-assisted psychotherapy, psilocybin-assisted psychotherapy), with an aim to examine and integrate these agents into the underlying pathophysiological frameworks of trauma-related disorders.

01 May 2022·Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy AssociationQ1 · MEDICINE

Medial Patellofemoral Ligament Reconstruction Using Adductor-Transfer and Adductor-Sling at Nonanatomic Femoral Attachment Sites Leads to Unfavorable Graft-Length Change Patterns: A Descriptive Biomechanical Study

Q1 · MEDICINE

Article

Author: Dong, Shikui ; Chen, Jiebo ; Xu, Junjie ; Zhao, Jinzhong ; Qiao, Yi ; Han, Kang ; Ye, Zipeng ; Xu, Caiqi

PURPOSE:

To compare the graft length change patterns in nonanatomic adductor-transfer (AT) and adductor-sling (AS) medial patellofemoral ligament (MPFL) reconstruction with those in anatomic MPFL reconstruction (MPFLR) and to investigate the favorable isometric ranges (FIRs) of knee flexion.

METHODS:

Eight small fresh-frozen cadaveric knees were mounted in a knee-customized jig with tensioned muscles to measure graft length changes from two patellar points to four femoral attachments using a linear variable displacement transducer. Femoral attachments were at the MPFL footprint center (MPFL-C) in anatomic MPFLR, adductor magnus (AM) footprint center (AM-C) in AT, and at 5-mm (AM-5) or 10-mm (AM-10) points proximal to AM-C in AS. The FIRs of these femoral attachments were determined after zeroing the graft length changes at different initial fixation angles.

RESULTS:

Anatomic MPFL-C resulted in almost isometric graft length changes from 0° to 90°. At AM-C, the graft length changes displayed an increase from 0° to 45° and significantly greater length changes than those at MPFL-C from 60° to 90°. The graft length changes at both AM-5 and at AM-10 continuously increased with knee flexion angles and presented significantly larger graft length changes than those at MPFL-C and at AM-C from 30° to 90° and 60° to 90°, respectively. After zeroing graft length changes at different fixation angles, the FIRs of the MPFL-C covered all knee flexion angles, regardless of the patellar attachments and initial fixation angles. Moreover, with the smaller FIRs of AM-C observed at any fixation angle when compared with MPFL-C, fixing the graft at 0° to 30° in AT allowed the FIRs to cover the whole functional flexion range. However, the significantly larger graft length changes of both AM-5 and AM-10 resulted in extremely limited FIRs at any fixation angle.

CONCLUSION:

Anatomic MPFL-C resulted in a favorable graft length change range (less than 2 mm) at 0° to 90° of knee flexion, which was close to the isometric graft behavior. However, nonanatomic attachments of AM-C in AT, and both AM-5 and AM-10 in AS caused significant anisometric graft length change patterns and limited FIRs. Moreover, AT had a smaller range of graft length change but wider FIRs compared to AS, indicating superior graft behavior for MPFLR.

CLINICAL RELEVANCE:

Anatomic MPFLR is preferable for the treatment of in skeletally immature patients, followed in preference by nonanatomic AT. Nonanatomic AS should be performed cautiously.

News (Medical) associated with Aloradine

07 Nov 2024

·www.businesswire.com

Vistagen Reports Fiscal Year 2025 Second Quarter Financial Results and Corporate Update

SOUTH SAN FRANCISCO, Calif.--( BUSINESS WIRE )-- Vistagen (Nasdaq: VTGN), a late clinical-stage company dedicated to pioneering neuroscience based on nose-to-brain neurocircuitry, today reported financial results for its fiscal year 2025 second quarter ended September 30, 2024, and provided a corporate update. “We initiated our PALISADE-4 Phase 3 trial during our second quarter, achieving yet another significant milestone in our fasedienol U.S. registration-directed Phase 3 Program for the acute treatment of social anxiety disorder,” said Shawn Singh, Chief Executive Officer of Vistagen. “We are actively recruiting for both our PALISADE-3 and PALISADE-4 Phase 3 trials and remain primarily focused on execution. Our broad and diverse neuroscience pipeline is based on our novel, non-systemic, neurocircuitry-focused approaches to treating multiple challenging disorders in high-prevalence markets with inadequate current treatment options. As we head into 2025, we expect data from multiple Phase 3 clinical trials in social anxiety disorder and further advancement of our non-systemic pherine product candidates in Phase 2 programs for treatment of major depressive disorder and hormone-free treatment of menopausal hot flashes, each with potential to set a new standard of care.” Neuroscience Pipeline Highlights Leveraging its pioneering neuroscience and deep understanding of nose-to-brain neurocircuitry, Vistagen is advancing a broad and diverse pipeline of innovative non-systemic intranasal pherine product candidates. Fasedienol for the Acute Treatment of Social Anxiety Disorder (SAD) During the second quarter, Vistagen announced initiation of its PALISADE-4 Phase 3 trial of fasedienol for the acute treatment of SAD. Vistagen’s PALISADE-3 and PALISADE-4 Phase 3 trials remain on track to produce top-line results in 2025. Itruvone for Major Depressive Disorder (MDD) Vistagen continues preparations and planning for Phase 2B development of itruvone as a novel, non-systemic, stand-alone treatment for MDD without the weight gain, sexual side effects, and safety concerns associated with currently available depression therapies. PH80 for Vasomotor Symptoms (Hot Flashes) due to Menopause Vistagen’s ongoing U.S. Investigational New Drug Application (IND)-enabling program for PH80 is designed to support its planned submission of a U.S. IND to facilitate further Phase 2 clinical development of PH80 in the U.S. as a novel non-systemic, hormone-free treatment option for millions of women affected by vasomotor symptoms (hot flashes) due to menopause. Corporate Highlight Raising Awareness at Nasdaq on World Mental Health Day Vistagen partnered with The Goldie Hawn Foundation’s MindUP to raise awareness of global mental health challenges and the power of partnership and shared commitment to advance neuroscience-based innovation in a Nasdaq Closing Bell ceremony in New York City on World Mental Health Day. Financial Results for Fiscal Year 2025 Second Quarter Ended September 30, 2024 Research and development (R&D) expense R&D expense was $10.2 million for the three months ended September 30, 2024, as compared to $3.9 million for the three months ended September 30, 2023. The increase in R&D expense was primarily due to an increase in research, development, and contract manufacturing expenses related to our PALISADE Phase 3 Program for fasedienol in SAD, an increase in headcount, and an increase in consulting and professional service fees. General and administrative (G&A) expense G&A expense was $4.2 million for the three months ended September 30, 2024, as compared to $3.2 million for the three months ended September 30, 2023. The increase in G&A expense was primarily due to an increase in headcount and professional service fees. Net loss Net loss was $13.0 million for the three months ended September 30, 2024, as compared to $6.6 million for the three months ended September 30, 2023. Other financial highlights Cash, cash equivalents, and marketable securities were $97.6 million as of September 30, 2024. Conference Call: Vistagen will host a conference call and live audio webcast this afternoon at 5:00 p.m. Eastern Time to provide a corporate update. U.S. Dial-in (Toll-Free): 1-800-717-1738 International Dial-in Number (Toll): 1-646-307-1865 Conference ID: 1196845 Webcast: https://viavid.webcasts.com/starthere.jsp?ei=1692083&tp_key=a59cae127b A live audio conference call webcast will also be available via the above link. Participants should access this webcast site 10 minutes before the start of the call. In addition, a telephone playback of the call will be available after approximately 8:00 p.m. Eastern Time on Thursday, November 7, 2024. To listen to the replay, call toll-free 1-844-512-2921 within the United States or 1-412-317-6671 when calling internationally (toll). Please use the replay access ID number 1196845. About Fasedienol Nasal Spray for Acute Treatment of Social Anxiety Disorder Fasedienol is a potential first-in-class, investigational neuroactive pherine nasal spray designed to have rapid onset with a novel mechanism of action (MOA) that is differentiated from all currently approved anxiety medications. Fasedienol is designed to regulate the olfactory-amygdala neural circuits of fear and anxiety and attenuate the tone of the sympathetic autonomic nervous system, without systemic absorption, potentiation of GABA-A receptors, or binding to neurons in the brain. Vistagen’s U.S. registration-directed PALISADE Phase 3 program for fasedienol is focused on the acute treatment of SAD. Fasedienol has not demonstrated any signals of abuse potential or suggested any potential for psychological and physical dependence in any clinical trial conducted to date. There is no U.S. FDA-approved acute treatment for SAD. The U.S. FDA has granted Fast Track designation for the development of fasedienol for the acute treatment of SAD. About Itruvone Nasal Spray for Major Depressive Disorder Itruvone is an investigational pherine nasal spray designed to have rapid onset, with a novel proposed neurocircuitry-focused mechanism of action (MOA) that is fundamentally differentiated from the MOA of all currently approved treatments for depression disorders. Itruvone is administered intranasally at microgram-level doses and is designed to regulate olfactory-to-amygdala neural circuitry believed to increase the activity of the limbic-hypothalamic sympathetic nervous system and increase the release of catecholamines to produce antidepressant effects, without systemic absorption or brain penetration and without many of the side effects and safety concerns potentially associated with currently approved antidepressants. Vistagen is developing itruvone as a potential new non-systemic, stand-alone treatment for major depressive disorder, and the FDA has granted Fast Track designation for the development of itruvone for that indication. About PH80 Nasal Spray for Vasomotor Symptoms (Hot Flashes) Due to Menopause PH80 is a hormone-free investigational neuroactive pherine nasal spray with a novel neurocircuitry-focused mechanism of action (MOA) that is fundamentally differentiated from all currently approved treatment options for women’s health indications. PH80’s proposed MOA does not require systemic absorption or binding to neurons in the brain. Vistagen is developing PH80 as a potential new non-systemic, hormone-free treatment for the management of vasomotor symptoms (hot flashes) due to menopause. About Vistagen Headquartered in South San Francisco, CA, Vistagen (Nasdaq: VTGN) is a late clinical-stage company leveraging its pioneering neuroscience and deep understanding of nose-to-brain neurocircuitry to develop and commercialize a broad and diverse pipeline of intranasal product candidates called pherines. Each pherine product candidate in Vistagen’s neuroscience pipeline is designed to rapidly activate olfactory system and brain neurocircuitry to achieve desired therapeutic benefits and differentiated safety without requiring systemic absorption or binding to neurons in the brain. Vistagen’s neuroscience pipeline also includes an oral prodrug, AV-101, with potential to impact certain neurological conditions involving the NMDA receptor. Vistagen is passionate about developing transformative treatment options to improve the lives of individuals underserved by the current standard of care for multiple highly prevalent disorders, including social anxiety disorder, major depressive disorder, and vasomotor symptoms (hot flashes) associated with menopause. Connect at www.Vistagen.com . Forward-looking Statements This press release contains certain forward-looking statements within the meaning of the federal securities laws. These forward-looking statements involve known and unknown risks that are difficult to predict and include all matters that are not historical facts. In some cases, you can identify forward-looking statements by the use of words such as “may,” “could,” “expect,” “project,” “outlook,” “strategy,” “intend,” “plan,” “seek,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “strive,” “goal,” “continue,” “likely,” “will,” “would” and variations of these terms and similar expressions, or the negative of these terms or similar expressions. Such forward-looking statements are necessarily based upon estimates and assumptions that, while considered reasonable by Vistagen and its management, are inherently uncertain. As with all pharmaceutical products, there are substantial risks and uncertainties in the process of development and commercialization and actual results or developments may differ materially from those projected or implied in these forward-looking statements. Among other things, there can be no guarantee that any of Vistagen’s product candidates will successfully complete ongoing or future clinical trials, receive regulatory approval or be commercially successful, or that Vistagen will be able to successfully replicate the result of past studies of its product candidates, including fasedienol, itruvone, PH80 or its other product candidates. Other factors that may cause such a difference include, without limitation, risks and uncertainties relating to conducting and/or completing ongoing clinical trials, including PALISADE-3 and/or PALISADE-4; completing IND-enabling programs for applicable product candidates, including PH80; launching planned clinical trials for any of our product candidates, including fasedienol; Vistagen’s submission of a new drug application (NDA) to the U.S. FDA for any product candidate, including fasedienol; the ability of any clinical trial information submitted by the Company to the U.S. FDA to support a NDA; the scope and enforceability of Vistagen’s patents, including patents related to Vistagen’s pherine product candidates and AV-101; fluctuating costs of materials and other resources and services required to conduct Vistagen’s ongoing and/or planned clinical and non-clinical trials; market conditions; the impact of general economic, industry or political conditions in the United States or internationally; and other technical and unexpected hurdles in the development, manufacture and commercialization of Vistagen’s product candidates. These risks are more fully discussed in the section entitled “Risk Factors” in Vistagen’s Annual Report on Form 10-K for the fiscal year ended March 31, 2024, and Quarterly Report on Form 10-Q for the period ended September 30, 2024, as well as discussions of potential risks, uncertainties, and other important factors in our other filings with the U.S. Securities and Exchange Commission (SEC). Vistagen’s SEC filings are available on the SEC’s website at www.sec.gov . You should not place undue reliance on these forward-looking statements, which apply only as of the date of this press release and should not be relied upon as representing Vistagen’s views as of any subsequent date. Vistagen explicitly disclaims any obligation to update any forward-looking statements other than as may be required by law. If Vistagen does update one or more forward-looking statements, no inference should be made that Vistagen will make additional updates with respect to those or other forward-looking statements. VISTAGEN THERAPEUTICS, INC. CONDENSED CONSOLIDATED BALANCE SHEETS September 30, 2024 March 31, 2024 (Unaudited) ASSETS Current assets: Cash and cash equivalents $ 84,246 $ 119,166 Marketable securities 13,332 - Prepaid expenses and other current assets 2,370 1,506 Total current assets 99,948 120,672 Property and equipment, net 467 435 Right-of-use asset - operating lease 1,583 1,820 Other assets 498 726 Total assets $ 102,496 $ 123,653 LIABILITIES AND STOCKHOLDERS ’ EQUITY Current liabilities: Accounts payable $ 715 $ 1,547 Accrued expenses 3,815 2,235 Deferred revenue - current portion 2,468 791 Operating lease obligation - current portion 525 550 Total current liabilities 7,523 5,123 Deferred revenue - non-current portion 730 2,674 Operating lease obligation - non-current portion 1,269 1,570 Total liabilities 9,522 9,367 Commitments and contingencies Stockholders’ equity: Preferred stock, $0.001 par value; 10,000,000 shares authorized at September 30, 2024 and March 31, 2024; no shares outstanding at September 30, 2024 and March 31, 2024 - - Common stock, $0.001 par value; 325,000,000 shares authorized at September 30, 2024 and March 31, 2024; 27,059,629 and 27,029,731 shares issued at September 30, 2024 and March 31, 2024, respectively 27 27 Additional paid-in capital 476,801 474,441 Treasury stock, at cost, 4,522 shares of common stock held at September 30, 2024 and March 31, 2024 (3,968 ) (3,968 ) Accumulated other comprehensive income 22 - Accumulated deficit (379,908 ) (356,214 ) Total stockholders’ equity 92,974 114,286 Total liabilities and stockholders’ equity $ 102,496 $ 123,653 VISTAGEN THERAPEUTICS CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (unaudited) Three Months Ended September 30, Six Months Ended September 30, 2024 2023 2024 2023 Revenues: Sublicense and other revenue $ 183 $ 278 $ 267 $ 455 Total revenues 183 278 267 $ 455 Operating expenses: Research and development 10,215 3,851 17,863 $ 8,048 General and administrative 4,195 3,207 8,762 $ 6,185 Total operating expenses 14,410 7,058 26,625 $ 14,233 Loss from operations (14,227 ) (6,780 ) (26,358 ) $ (13,778 ) Other income, net: Interest income, net 1,273 192 2,671 $ 290 Loss before income taxes (12,954 ) (6,588 ) (23,687 ) $ (13,488 ) Income taxes (7 ) — (7 ) $ (3 ) Net loss $ (12,961 ) $ (6,588 ) $ (23,694 ) $ (13,491 ) Unrealized gain on marketable securities 20 — 22 — Comprehensive loss $ (12,941 ) $ (6,588 ) $ (23,672 ) $ (13,491 ) Basic and diluted net loss per common share $ (0.42 ) $ (0.66 ) $ (0.77 ) $ (1.55 ) Weighted average common shares outstanding, basic and diluted 30,632,347 10,042,530 30,617,970 8,717,050

Phase 2Phase 3Financial StatementFast Track

05 Nov 2024

·www.businesswire.com

Vistagen to Present at the 2024 Neuroscience Education Institute Congress

SOUTH SAN FRANCISCO, Calif.--( BUSINESS WIRE )-- Vistagen (Nasdaq: VTGN), a late clinical-stage company dedicated to pioneering neuroscience based on nose-to-brain neurocircuitry, today announced that it will present posters highlighting new prevalence data for social anxiety disorder (SAD), an indication for which fasedienol, its lead intranasal pherine product candidate, is in U.S. registration-directed Phase 3 development for the acute treatment of the disorder, and two additional non-systemic intranasal pherine product candidates in its neuroscience pipeline, itruvone in Phase 2 development for major depressive disorder and hormone-free PH80 in Phase 2 development for the management of vasomotor symptoms (hot flashes) due to menopause, at the 2024 Neuroscience Education Institute (NEI) Congress in Colorado Springs, Colorado from November 7 to 10, 2024. Poster Presentation Date: Friday, November 8, 2024, 3:35 p.m. Mountain Time Title: Prevalence Trends and Demographic Profiles of Social Anxiety Disorder: A Cross-sectional Study Using U.S. National Health and Wellness Survey Authors: Ross A. Baker, PhD; Josh Prince; Soohyun Hwang, PhD, MPH; Nikoletta Sternbach Poster Number: 95 Poster Presentation Date: Friday, November 8, 2024, 3:35 p.m. Mountain Time Title: Itruvone Nasal Spray Depolarizes Electrogram of Nasal Receptors and Increases Gamma Bandwidth of the Olfactory Bulb Electrogram in Healthy Subjects Authors: Louis Monti, MD, PhD; Danajane Katz, BS; Ester Salmán, MPH; Weiping Zhang, PhD; Ross A. Baker, PhD; Rita Hanover, PhD Poster Number: 66 Poster Presentation Date: Friday, November 8, 2024, 3:35 p.m. Mountain Time Title: Pain Symptom Cluster Analysis from the Daily Symptom Report in a Phase 2a Study of PH80 for the Treatment of Premenstrual Dysphoric Disorder (PMDD) Authors: Louis Monti, MD, PhD; Ross A. Baker, PhD; Rita Hanover, PhD Poster Number: 94 The posters will be available on the Publications page of Vistagen’s website on Monday, November 11, 2024. About Fasedienol Nasal Spray for Acute Treatment of Social Anxiety Disorder Fasedienol is a potential first-in-class, investigational neuroactive pherine nasal spray designed to have rapid onset with a novel mechanism of action (MOA) that is differentiated from all currently approved anxiety medications. Fasedienol is designed to regulate the olfactory-amygdala neural circuits of fear and anxiety and attenuate the tone of the sympathetic autonomic nervous system, without systemic absorption, potentiation of GABA-A receptors, or direct activity on neurons in the brain. Vistagen’s U.S. registration-directed PALISADE Phase 3 program for fasedienol is focused on the acute treatment of SAD. Fasedienol has not demonstrated any signals of abuse potential or suggested any potential for psychological and physical dependence in any clinical trial conducted to date. There is no U.S. FDA-approved acute treatment for SAD. The U.S. FDA has granted Fast Track designation for the investigation of fasedienol for the acute treatment of SAD. About Itruvone Nasal Spray for Major Depressive Disorder Itruvone is an investigational pherine nasal spray designed to have rapid onset, with a novel proposed neurocircuitry-focused mechanism of action (MOA) that is fundamentally differentiated from the MOA of all currently approved treatments for depression disorders. Itruvone is administered intranasally at microgram-level doses and is designed to regulate olfactory-to-amygdala neural circuitry believed to increase the activity of the limbic-hypothalamic sympathetic nervous system and increase the release of catecholamines to produce antidepressant effects, without systemic absorption or brain penetration and without many of the side effects and safety concerns potentially associated with currently approved antidepressants. The FDA has granted Fast Track designation for the development of itruvone as a potential treatment for major depressive disorder. About PH80 Nasal Spray for Vasomotor Symptoms (Hot Flashes) Due to Menopause PH80 is a hormone-free investigational neuroactive pherine nasal spray with a novel neurocircuitry-focused mechanism of action (MOA) that is fundamentally differentiated from all currently approved treatment options for women’s health indications. PH80’s proposed MOA does not require systemic absorption or direct activity on neurons in the brain. Vistagen is developing PH80 as a potential new non-systemic, hormone-free treatment for the management of vasomotor symptoms (hot flashes) due to menopause. About Vistagen Headquartered in South San Francisco, CA, Vistagen (Nasdaq: VTGN) is a late clinical-stage company leveraging a deep understanding of nose-to-brain neurocircuitry to develop and commercialize a broad and diverse pipeline of intranasal product candidates called pherines. Each pherine product candidate in Vistagen’s neuroscience pipeline is designed to rapidly activate olfactory system and brain neurocircuitry to achieve desired therapeutic benefits and differentiated safety without requiring systemic absorption or direct activity on neurons in the brain. Vistagen’s neuroscience pipeline also includes an oral prodrug, AV-101, with potential to impact certain neurological conditions involving the NMDA receptor. Vistagen is passionate about developing transformative treatment options to improve the lives of individuals underserved by the current standard of care for multiple highly prevalent disorders, including social anxiety disorder, major depressive disorder, and vasomotor symptoms (hot flashes) associated with menopause. Connect at www.Vistagen.com . Forward-looking Statements This press release contains certain forward-looking statements within the meaning of the federal securities laws. These forward-looking statements involve known and unknown risks that are difficult to predict and include all matters that are not historical facts. In some cases, you can identify forward-looking statements by the use of words such as “may,” “could,” “expect,” “project,” “outlook,” “strategy,” “intend,” “plan,” “seek,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “strive,” “goal,” “continue,” “likely,” “will,” “would” and variations of these terms and similar expressions, or the negative of these terms or similar expressions. Such forward-looking statements are necessarily based upon estimates and assumptions that, while considered reasonable by Vistagen (the Company) and its management, are inherently uncertain. As with all pharmaceutical products, there are substantial risks and uncertainties in the process of development and commercialization and actual results or developments may differ materially from those projected or implied in these forward-looking statements. Among other things, there can be no guarantee that fasedienol, itruvone, PH80, or any of the Company’s other product candidates will successfully complete ongoing or future clinical trials, receive regulatory approval or be commercially successful. These risks and others are more fully discussed in the section entitled “Risk Factors” in the Company’s Annual Report on Form 10-K for the fiscal year ended March 31, 2024, and in the Company’s Quarterly Report on Form 10-Q for the period ended June 30, 2024, as well as discussions of potential risks, uncertainties, and other important factors in our other filings with the U.S. Securities and Exchange Commission (SEC). The Company’s SEC filings are available on the SEC’s website at www.sec.gov . You should not place undue reliance on these forward-looking statements, which apply only as of the date of this press release and should not be relied upon as representing the Company’s views as of any subsequent date. The Company explicitly disclaims any obligation to update any forward-looking statements other than as may be required by law. If the Company does update one or more forward-looking statements, no inference should be made that the Company will make additional updates with respect to those or other forward-looking statements.

Phase 2Phase 3Fast Track

23 Sep 2024

·www.businesswire.com

Vistagen Initiates PALISADE-4 Phase 3 Study of Fasedienol for the Acute Treatment of Social Anxiety Disorder

SOUTH SAN FRANCISCO, Calif.--( BUSINESS WIRE )-- Vistagen (Nasdaq: VTGN) a late clinical-stage neuroscience-focused biopharmaceutical company dedicated to the development and commercialization of groundbreaking therapies for psychiatric and neurological disorders based on nose-to-brain neurocircuitry, today announced enrollment of the first subject in its PALISADE-4 Phase 3 trial of fasedienol, an investigational neuroactive pherine nasal spray in U.S. registration-directed Phase 3 development for the acute treatment of social anxiety disorder (SAD). “With the initiation of PALISADE-4 as planned, we have achieved another important milestone in our registration-directed PALISADE Phase 3 program for fasedienol, which has potential to deliver a transformative acute treatment option to over 30 million Americans suffering from the debilitating effects of SAD, including increased risk for depression, alcohol abuse, and suicide attempts,” said Shawn Singh, Chief Executive Officer of Vistagen. “Current pharmacological therapies approved by the U.S. FDA do not include an acute treatment option. With pioneering neuroscience, we are breaking new ground in the development of a treatment for SAD with our novel product candidate designed for non-systemic, rapid activation of nose-to-brain neural circuits to reduce fear and anxiety associated with SAD.” About Vistagen’s PALISADE Phase 3 Program for Fasedienol for the Acute Treatment of SAD Vistagen's U.S. registration-directed PALISADE Phase 3 development program for fasedienol for the acute treatment of SAD includes the ongoing PALISADE-3 and PALISADE-4 Phase 3 trials, each a randomized, double-blind, placebo-controlled Phase 3 trial designed to evaluate the efficacy, safety, and tolerability of the acute administration of fasedienol to relieve anxiety symptoms in subjects with SAD induced by a public speaking challenge conducted in a clinical setting. PALISADE-3 and PALISADE-4 are designed similarly to Vistagen’s PALISADE-2 Phase 3 trial of fasedienol, from which positive data was reported last year. The primary outcome measure in each of the PALISADE Phase 3 trials is a subject’s self-rated Subjective Units of Distress Scale (SUDS). Similar to PALISADE-3 initiated earlier this year, the PALISADE-4 Phase 3 U.S. multi-center trial is planned to randomize approximately 236 adults aged 18 through 65. Subjects will be randomized in a 1:1 ratio to fasedienol or placebo. PALISADE-3 and PALISADE-4 also include open-label extension phases to evaluate the safety and tolerability of ongoing use of fasedienol in a real-world setting over a period of up to 12 months. Vistagen believes either PALISADE-3 or PALISADE-4, if successful, together with PALISADE-2, may establish substantial evidence of the effectiveness of fasedienol in support of a potential fasedienol New Drug Application (NDA) submission to the FDA for the acute treatment of SAD. About Fasedienol Nasal Spray Fasedienol is a potential first-in-class, investigational neuroactive pherine nasal spray designed to have rapid onset with a novel proposed mechanism of action (MOA) that is differentiated from all currently approved anxiety medications. Fasedienol is designed to regulate the olfactory-amygdala neural circuits of fear and anxiety and attenuate the tone of the sympathetic autonomic nervous system, without systemic absorption, potentiation of GABA-A receptors, or direct activity on neurons in the brain. Vistagen’s U.S. registration-directed PALISADE Phase 3 program for fasedienol is focused on the acute treatment of SAD. Fasedienol has not demonstrated any signals of abuse potential or suggested any potential for psychological and physical dependence in any clinical trial conducted to date. There is no U.S. FDA-approved acute treatment for SAD. The U.S. FDA has granted Fast Track designation for the investigation of fasedienol for the acute treatment of SAD. About Social Anxiety Disorder Social anxiety disorder (SAD) affects over 30 million Americans. A person with SAD feels intense, persistent, and sometimes disabling 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 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. There is no U.S. FDA-approved acute treatment for SAD. About Vistagen Headquartered in South San Francisco, CA, Vistagen (Nasdaq: VTGN) is a late clinical-stage neuroscience-focused biopharmaceutical company dedicated to the development and commercialization of groundbreaking therapies for psychiatric and neurological disorders based on its pioneering approach and deep understanding of nose-to-brain neurocircuitry. Vistagen’s diversified pipeline of pherine product candidates is designed exclusively as nasal sprays administered at microgram level doses to rapidly activate chemosensory neurons in the nasal cavity with novel non-systemic proposed mechanisms of action designed to impact the olfactory system and brain neurocircuitry to achieve diverse therapeutic effects. Favorable safety data have been generated in all clinical studies of Vistagen’s pherine product candidates completed to date. Vistagen’s neuroscience pipeline also includes an oral prodrug with the potential to modulate NMDA receptor activity in certain neurological conditions, such as levodopa-induced dyskinesia associated with Parkinson’s disease therapy and neuropathic pain. At Vistagen, we are passionate about creating novel and differentiated treatments that set new standards of care for millions of people living with anxiety, depression, and other neurological disorders. Connect at www.Vistagen.com . Forward-looking Statements This press release contains certain forward-looking statements within the meaning of the federal securities laws. These forward-looking statements involve known and unknown risks that are difficult to predict and include all matters that are not historical facts. In some cases, you can identify forward-looking statements by the use of words such as “may,” “could,” “expect,” “project,” “outlook,” “strategy,” “intend,” “plan,” “seek,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “strive,” “goal,” “continue,” “likely,” “will,” “would” and variations of these terms and similar expressions, or the negative of these terms or similar expressions. Such forward-looking statements are necessarily based upon estimates and assumptions that, while considered reasonable by Vistagen and its management, are inherently uncertain. As with all pharmaceutical products, there are substantial risks and uncertainties in the process of development and commercialization and actual results or developments may differ materially from those projected or implied in these forward-looking statements. Among other things, there can be no guarantee that any of Vistagen’s drug candidates will successfully complete ongoing or future clinical trials, receive regulatory approval or be commercially successful, or that Vistagen will be able to successfully replicate the result of past studies of its product candidates, including fasedienol, itruvone, PH80 or its other drug candidates. Other factors that may cause such a difference include, without limitation, risks and uncertainties relating to conducting and/or completing ongoing clinical trials, including PALISADE-3 and/or PALISADE-4; launching planned clinical trials for any of our product candidates, including fasedienol; Vistagen’s submission of a new drug application (NDA) to the U.S. FDA for any product candidate, including fasedienol; the ability of any clinical trial information submitted by the Company to the U.S. FDA to support a NDA; the scope and enforceability of Vistagen’s patents, including patents related to Vistagen’s pherine drug candidates and AV-101; fluctuating costs of materials and other resources and services required to conduct Vistagen’s ongoing and/or planned clinical and non-clinical trials; market conditions; the impact of general economic, industry or political conditions in the United States or internationally; and other technical and unexpected hurdles in the development, manufacture and commercialization of Vistagen’s product candidates. These risks are more fully discussed in the section entitled “Risk Factors” in Vistagen’s most recent Annual Report on Form 10-K for the fiscal year ended March 31, 2024, and Quarterly Report on Form 10-Q for the period ended June 30, 2024, as well as discussions of potential risks, uncertainties, and other important factors in our other filings with the U.S. Securities and Exchange Commission (SEC). Vistagen’s SEC filings are available on the SEC’s website at www.sec.gov . You should not place undue reliance on these forward-looking statements, which apply only as of the date of this press release and should not be relied upon as representing Vistagen’s views as of any subsequent date. Vistagen explicitly disclaims any obligation to update any forward-looking statements other than as may be required by law. If Vistagen does update one or more forward-looking statements, no inference should be made that Vistagen will make additional updates with respect to those or other forward-looking statements.

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Indication	Highest Phase	Country/Location	Organization	Date
Phobic Disorders	Phase 3	CN	Affamed Therapeutics (Us), Inc.	30 Jan 2022
Phobic Disorders	Phase 3	-	VistaGen Therapeutics, Inc.	30 Jan 2022
Anxiety Disorders	Phase 3	US	VistaGen Therapeutics, Inc.	24 May 2021
Phobia, Social	Phase 3	US	VistaGen Therapeutics, Inc.	24 May 2021
Adjustment disorders	Phase 2	US	VistaGen Therapeutics, Inc.	12 Oct 2021
Mood Disorders	Phase 2	US	VistaGen Therapeutics, Inc.	12 Oct 2021
Premenstrual Dysphoric Disorder	Phase 2	US	VistaGen Therapeutics, Inc.	12 Oct 2021

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05011396 (PALISADE-2, Corporate Publications) Manual	Phase 3	Phobia, Social	141	PH94B	ltestjpccq(qcywpaqefw) = selahqwtbr npqjgprkwx (altrcxujsl ) Met View more	Positive	07 Aug 2023
				Placebo	ltestjpccq(qcywpaqefw) = atxctmwovy npqjgprkwx (altrcxujsl ) Met View more
NCT05030350 (Corporate Publications) Manual	Phase 3	Phobia, Social	481	PH94B	kthdfhlitr(tldnohhdir) = zlslsgdhrn bodkbbukdz (znnluewcam ) View more	Positive	22 Mar 2023
NCT04754802 (PALISADE-1, Corporate Publications) Manual	Phase 3	Phobia, Social	-	PH94B	oqmjqdbtza(khzmzilzlj) = the trial did not meet its primary endpoint ulgglkotok (fxnwlledzk ) View more	Negative	22 Jul 2022
				Placebo

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