Vistagen Therapeutics, Inc. · NASDAQ:VTGN
Vistagen Therapeutics — Investor Presentation (June 2025)
59 slides from Vistagen Therapeutics's investor presentation, Jun 2, 2025
Slide 1: Pioneering neuroscience with nose-to-brain neurocircuitry
Nasdaq: VTGN Pioneering neuroscience with nose-to-brain neurocircuitry Summer 2025
Slide 2: Forward-looking Statements
Forward-looking Statements 2 This presentation contains certain forward-looking statements that are within the meaning of 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
Slide 3: Highlights
3 Highlights - U.S. Registration-directed PALISADE Phase 3 program in Social Anxiety Disorder underway; positive PALISADE-2 Phase 3 trial reported in late 2023 - Multi-billion-dollar peak sales potential across several high prevalence indications - Partnering opportunities in multiple indications an
Slide 4: Pherines: Harnessing nose-to-brain neurocircuitry
Pherines Harnessing the power and potential of nose-to-brain neurocircuitry
Slide 5: Pherines: A new class of intranasal neuroscience product candidates
Pherines 5 A new class of intranasal neuroscience product candidates - Rapidly activate nose-to-brain neurocircuits affecting multiple high-prevalence indications - Non-systemic MOAs are distinguished from all FDA-approved drugs for target indications - No binding to neurons in the brain - Favorable
Slide 6: Clinical-stage Pherine Pipeline
Product Candidate Indication Preclinical Phase I Phase II Phase III Fasedienol Itruvone Acute Treatment of Social Anxiety Disorder Major Depressive Disorder (Monotherapy) • U.S. registration-directed Phase 3 program underway • First positive Phase 3 study reported in 2H 2023 • FDA Fast Track designa
Slide 7: Fasedienol: Acute Treatment of Social Anxiety Disorder
Acute Treatment of Social Anxiety Disorder Fasedienol
Slide 8: Social Anxiety Disorder (SAD)
Social Anxiety Disorder (SAD) 8 Presenting at work or school Eating/drinking in front of others Public speaking Making a phone call Emotional Symptoms • Overwhelming fear • Surges of anxiety • Extreme self-consciousness • Isolation leading to depression Source: ADAA Social Anxiety Brochure 2021 Chro
Slide 9: SAD Affects Over 10% of U.S. Adults
~31M SAD Prevalent Patients ~15M SAD Diagnosed Patients ~7M SAD Treated Patients Treatable Patients Patients suffering but unaware they may have SAD or not yet motivated to seek professional help 9 SAD Affects Over 10% of U.S. Adults Sources: Oracle Life Sciences. May 2024. U.S. National Health and
Slide 10: SAD Prevalence in the U.S. Continues to Grow
10 SAD Prevalence in the U.S. Continues to Grow Source: 1. NCS-R Survey, 2003; Kantar NHWS 2023, Internal Projections 15 31 2003 2005 2007 2009 2011 2013 2015 2017 2019 2021 2023 U.S. Adult SAD Prevalence (in Millions)1
Slide 11: There is no FDA-approved Acute Treatment of SAD
11 There is no FDA-approved Acute Treatment of SAD Off-label acute treatment options fall short of Physicians’ Preferred Product Profile Drug Fast-acting Non-systemic No Long-term Side Effects Non- sedating* No Cognitive Impairment No Withdrawal Syndrome No Abuse Potential Benzodiazepines1 Beta-bloc
Slide 12: Fasedienol Brings New Optimism for SAD Patients
Fasedienol Brings New Optimism for SAD Patients - Rapid-onset efficacy and differentiated safety - Potential to be the first FDA-approved acute treatment of SAD - Patient-tailored administration, as needed, up to several times a day - No observed systemic absorption or binding to neurons in the brai
Slide 13: High Intent to Prescribe a Product with Fasedienol's Profile
13 High Intent to Prescribe a Product with Fasedienol’s Profile Sources: Vistagen Proprietary Market Research, Online Survey, Jan 2022 (n=251) 51% 56% 0% 20% 40% 60% 80% 100% % of your SAD patients who would be appropriate candidates for Product X Psychiatrists (n=125) Primary Care Physicians (n=126
Slide 14: Fasedienol's Novel MOA
Sources: Monti L, and Liebowitz MR (2022). Neural circuits of anxiolytic and antidepressant pherine molecules. CNS Spectrums https://doi.org/10.1017/S109285292000190X Fasedienol’s Novel MOA A microgram-level dose of fasedienol is administered intranasally1 Activity Decreases 5 Stimulation of the lim
Slide 15: PALISADE-2 Phase 3 Trial for Acute Treatment of SAD
15 15 PALISADE-2 Phase 3 Trial for Acute Treatment of SAD : A VISIONARY APPROACH TO MENTAL HEALTH CARE U.S. randomized, double-blind, placebo-controlled, single-dose administration Phase 3 trial to evaluate the efficacy, safety, and tolerability of fasedienol for the acute treatment of SAD induced b
Slide 16: Summary of PALISADE-2 Phase 3 Top-line Efficacy Results
LS Mean SUDs change from baseline vs. placebo Met Patient-reported Primary Efficacy Endpoint Met Clinician-reported Secondary Efficacy Endpoint Met Patient-reported Exploratory Efficacy Endpoint Summary of PALISADE-2 Phase 3 Top-line Efficacy Results CGI-I proportion of responders vs. placebo PGI-
Slide 17: PALISADE-2 Primary Efficacy Endpoint: Change in SUDS
13.8 8.0 0 5 10 15 20 (p=0.015) Absolute Change in Least-squares Mean SUDS (V2-V3) Fasedienol Placebo PALISADE-2 Primary Efficacy Endpoint (Patient-reported): Change in Least-squares Mean SUDS Scores Met primary efficacy endpoint with a change from Baseline of 5.8 points better than placebo 17 N=70
Slide 18: PALISADE-2 Secondary Endpoint: CGI-I Responders
CGI-I Score 1 = Very Much Less Anxious 2 = Much Less Anxious 3 = A Little Less Anxious 4 = No Change 5 = A Little More Anxious 6 = Much More Anxious 7 = Very Much More Anxious 37.7% 21.4% 0% 5% 10% 15% 20% 25% 30% 35% 40% (p=0.033) CGI-I % Responders* (Rating of 1 or 2) Fasedienol Placebo PALISADE-2
Slide 19: PALISADE-2 Exploratory Endpoint: PGI-C Responders
PGI-C Score 1 = Very Much Less Anxious 2 = Much Less Anxious 3 = A Little Less Anxious 4 = No Change 5 = A Little More Anxious 6 = Much More Anxious 7 = Very Much More Anxious 40.6% 18.6% 0% 5% 10% 15% 20% 25% 30% 35% 40% 45% (p=0.003) PGI-C % Responders* (Rating of 1 or 2) Fasedienol Placebo PALISA
Slide 20: PALISADE-2 Tolerability Profile
No severe or serious adverse events were reported No discontinuations due to adverse events following the single dose of fasedienol Adverse events were infrequent and mild or moderate in severity There were no treatment-emergent adverse events reported above a 2% occurrence, except pyrexia in the pl
Slide 21: PALISADE Open Label Safety Study
Long-term self-administration of 3.2 μg of fasedienol as needed, up to 4 times per day prior to anxiety-provoking social and performance stressors in daily life, with a mean study duration of 4 months, and a maximum study duration of over 10 months Design Results • 56.8% of subjects reported at leas
Slide 22: PALISADE-3 and PALISADE-4 Phase 3 SAD Trials with OLE
22 PALISADE-3 and PALISADE-4 Phase 3 SAD Trials with OLE* U.S. randomized, double-blind, placebo-controlled, single-dose administration Phase 3 trials to evaluate the efficacy, safety, and tolerability of fasedienol for acute treatment of anxiety in adult subjects with SAD induced by a public speaki
Slide 23: Fasedienol U.S. Registration-directed Phase 3 Program
23 Fasedienol U.S. Registration-directed Phase 3 Program To complement the positive PALISADE-2 Phase 3 trial, Vistagen is conducting two ongoing PALISADE Phase 3 studies as part of its U.S. registration-directed fasedienol Phase 3 program for the acute treatment of SAD PALISADE-3 and PALISADE-4 Phas
Slide 24: PALISADE-3 and PALISADE-4 Study Enhancements
- No mask-wearing during the public speaking challenges - Recurring in-person training of clinical site personnel - Expanded subject eligibility review at screening - Direct surveillance by Vistagen clinical site-facing staff, reduced reliance on CRO - Treatment administration by clinical site healt
Slide 25: Itruvone: Major Depressive Disorder
Major Depressive Disorder Itruvone
Slide 26: MDD is a Highly Prevalent and Unsatisfied Market
MDD is a Highly Prevalent and Unsatisfied Market Sources: 1. National Institute of Mental Health, https://www.nimh.nih.gov/health/statistics/major-depression.shtml; 2. World Health Organization, https://www.who.int/news-room/fact-sheets/detail/depression; 3. Rush AJ, et al. Am J. Psychiatry. 2006, 1
Slide 27: Itruvone has Potential to Transform Treatment of MDD
Itruvone has Potential to Transform Treatment of MDD - Novel non-systemic, neurocircuitry-focused MOA is differentiated from all FDA-approved depression therapies - Positive exploratory Phase 2A trial - Designed for rapid-onset antidepressant effects - Observed to be non-sedating, non-addictive - We
Slide 28: Itruvone's Novel MOA
Sources: Monti L, and Liebowitz MR (2022). Neural circuits of anxiolytic and antidepressant pherine molecules. CNS Spectrums https://doi.org/10.1017/S109285292000190X Itruvone’s Novel MOA Microgram-level intranasal dose of itruvone is administered intranasally 1 Ac tiv ity In cr ea se s 5 The stimul
Slide 29: Rapid-onset antidepressant effects observed with itruvone
Rapid-onset antidepressant effects with itruvone observed in MDD study participants with minimal side effects Design: Phase 2A randomized, double-blind, placebo-controlled, parallel design exploratory clinical study (n=30) Dosing: 3.2 µg or 6.4 µg of itruvone or placebo i.n., 2 times per day for 8 w
Slide 30: Itruvone Phase 2A Study in MDD
30 Itruvone Phase 2A Study in MDD Sources: Monti, L., Nicolini, H., Liebowitz, M., & Hanover, R. (2019). “A Placebo Controlled Trial of PH10: Test of a New Rapidly Acting Intranasally Administered Antidepressant.” Br J Phar Med Res 4(6): 2157-2168. Hamilton Depression (HAMD-17) Score Reduction From
Slide 31: Itruvone Phase 2B Clinical Plan
31 Itruvone Phase 2B Clinical Plan* Planning for Phase 2B development of itruvone as a non-systemic monotherapy for MDD is underway - Potential Design: U.S. randomized, double-blind, placebo-controlled, parallel study in male and female subjects (18 to 65 years old) with a confirmed diagnosis of mod
Slide 32: PH80: Vasomotor Symptoms (Hot Flashes) due to Menopause
Vasomotor Symptoms (Hot Flashes) due to Menopause PH80
Slide 33: Menopausal Hot Flashes: Highly Prevalent, Disrupts Daily Life
Menopausal Hot Flashes: Highly Prevalent, Disrupts Daily Life 33 • Hallmark symptoms include sudden sensations of heat, night sweats, flushed skin, anxiety, and chills lasting for several minutes • On average, symptoms persist for more than 7 years, however, they may last for over a decade • Frequen
Slide 34: Menopausal Hot Flashes: Current Treatments
Menopausal Hot Flashes: Highly Prevalent, Disrupts Daily Life 34 Current Treatments • First line treatment is Hormonal Therapy • Estrogen • Progesterone • Combination of both • SSRI/SNRIs are used as alternatives to Hormone Therapy • Brisdelle (paroxetine) • Off label therapies such as venlafaxine,
Slide 35: PH80's potential to transform treatment of Menopausal Hot Flashes
PH80’s potential to transform treatment of Menopausal Hot Flashes 35 PH80 Nasal Spray - Novel neurocircuitry-focused MOA differentiated from all approved treatments - Non-hormonal and non-systemic - Rapid-onset potential to be taken as-needed to provide relief in the moment - Potential for different
Slide 36: PH80's Novel MOA
PH80’s Novel MOA Microgram-level intranasal dose of PH80 is administered1 Activity Decreases The stimulation of neurons in the limbic amygdala and the hypothalamus decreases the activity of the autonomic nervous system and decreases activation of the trigeminal-vascular neural circuits Downstream ef
Slide 37: PH80 Phase 2A Study in Menopausal Hot Flashes
PH80 Phase 2A Study in Menopausal Hot Flashes 37 Objective: Proof-of-principle evaluation of PH80 efficacy and tolerability for the management of vasomotor symptoms (hot flashes) due to menopause Study Details: Randomized, double-blind, placebo-controlled, Phase 2A study. Participants self- administ
Slide 38: PH80 Phase 2A: Met Primary Efficacy Endpoint
PH80 Phase 2A Study in Hot Flashes: Met Primary Efficacy Endpoint Statistically and clinically significant improvement vs. placebo in the number of hot flashes at 1 week and maintained through 4 weeks of treatment (p<0.001) 0 1 2 3 4 5 6 7 8 9 Baseline Week 1 Week 2 Week 3 Week 4 Follow-up Daily Mea
Slide 39: PH80 Phase 2A: Met Secondary Efficacy Endpoint
PH80 Phase 2A Study in Hot Flashes: Met Secondary Efficacy Endpoint Ho t F la sh es - Bo th er Ho t F la sh es - Sw ea t Ho t F la sh es - Se ve rit y 0 0.5 1 1.5 2 2.5 Baseline Week 1 Week 2 Week 3 Week 4 Follow Up PH80 Placebo 0 0.5 1 1.5 2 2.5 Baseline Week 1 Week 2 Week 3 Week 4 Follow Up PH80 P
Slide 40: Additional Clinical-stage Neuroscience Product Candidates
Additional Clinical-stage Neuroscience Product Candidates
Slide 41: Premenstrual Dysphoric Disorder: PH80
Premenstrual Dysphoric Disorder PH80
Slide 42: PH80 Phase 2A Study in PMDD
PH80 Phase 2A Study in Premenstrual Dysphoric Disorder (PMDD) 42 Study Details: Randomized, double-blind, placebo-controlled, exploratory Phase 2A study. Subjects who did not respond to placebo at a screening visit returned after the onset of symptoms during the next menstrual cycle. At the second s
Slide 43: PH80 Phase 2A Study in PMDD: Met Primary Efficacy Endpoint
PH80 Phase 2A Study in PMDD: Met Primary Efficacy Endpoint Significant separation in PMDD DSR scores vs. placebo on Day 6 (p=0.015) 43 DSR Scores Day 1 through Day 6 0 2 4 6 8 10 12 14 16 18 20 Day 1 (p=0.963) Day 2 P=0.773 Day 4 (p=0.274) Day 3 (p=0.534) Day 6 (0.015*) Day 5 (p=0.089) -11.6 -4.4 Pl
Slide 44: PH15: Cognitive/Psychomotor Impairment due to Mental Fatigue
Acute Treatment of Cognitive/Psychomotor Impairment due to Mental Fatigue PH15
Slide 45: PH15's potential for improvement of cognitive and psychomotor impairment
PH15’s potential for improvement of cognitive and psychomotor impairment cause by mental fatigue 45 PH15 Nasal Spray - Novel neurocircuitry-focused MOA differentiated from all approved treatments - Non-hormonal and non-systemic - Rapid-onset potential to be taken as-needed to provide relief in the m
Slide 46: PH15's Novel MOA
PH15’s Novel MOA Microgram-level intranasal dose of PH15 is administered intranasally 1 Ac tiv ity In cr ea se s Increased activity in the hippocampus is responsible for improvement in cognitive function Increased activity in the limbic amygdala in turn increases activity in the cerebral cortex, lea
Slide 47: PH15 Phase 2A Study for Psychomotor Impairment Caused by Mental Fatigue
Results: During both isochronous and stochastic reaction time tests, administration of 1.6 µg PH15 nasal spray induced a significantly faster mean reaction time compared to placebo nasal spray across all time points (p<0.001). PH15 demonstrated a statistically significant improvement in reaction tim
Slide 48: PH284: Acute Treatment of Cancer Cachexia
Acute Treatment of Cancer Cachexia PH284
Slide 49: PH284 Nasal Spray
PH284 Nasal Spray 49 Potential acute treatment for cancer cachexia - Novel neurocircuitry-focused MOA differentiated from all approved treatments - Innovative, non-systemic neurocircuitry-focused pherine product candidate with rapid-onset potential for appetite enhancement - Intranasal administratio
Slide 50: PH284's Novel MOA
PH284’s Novel MOA Microgram-level intranasal dose of PH284 is administered intranasally 1 Ac tiv ity In cr ea se s The stimulation of neurons in the arcuate nucleus of the hypothalamus increases activity of aguti-related peptide (AGRP) neurons and neuropeptide Y (NPY) neurons, which increase appetit
Slide 51: PH284 Phase 2A Study in Cancer Cachexia
Safety and Tolerability: No unusual changes in body weight were observed in either the PH284 or placebo groups, though on average, there was a small gain in body weight for PH284 versus a small loss in placebo. PH284 demonstrated no serious adverse events, and adverse events reported for the PH284 g
Slide 52: Potential for Collaborative Phase 2A Development: AV-101
Potential for Collaborative Phase 2A Development AV-101
Slide 53: AV-101 for Multiple Neuroscience Disorders
AV-101 for Multiple Neuroscience Disorders 53 Designed to inhibit (but not block) NMDA receptor activity • Oral prodrug of 7-Cl-KYNA, a potent and selective full antagonist at the glycine site of the NMDA receptor • Inhibition of the NMDA receptor, without fully blocking the receptor like ketamine a
Slide 54: AV-101's Proposed Mechanism of Action
AV-101’s Proposed Mechanism of Action 54 Cytoplasmic side Glutamate Binding Site Glycine Binding Site (Flows Out) K+ L-4-chlorokynurenine (4-Cl-KYN) (oral delivery to CNS) Cl NH2 C O CH2 CH NH2 COOH Activated Astrocytes Cl COOH OH AV-101 - Oral Prodrug (4-Cl-KYN) 7-CI-KYNA (full antagonist) AV-101 -
Slide 55: AV-101: Potential to partner for clinical development and commercialization
AV-101 for Multiple Neuroscience Disorders 55 Potential to partner for clinical development and commercialization Neuropathic PainLevodopa-Induced Dyskinesia Associated with Parkinson’s therapy
Slide 56: Distinguished Clinical and Regulatory Advisors
56 Distinguished Clinical and Regulatory Advisors Maurizio Fava, M.D. Professor of Psychiatry, Harvard Medical School; Director, Division of Clinical Research, Massachusetts General Hospital (MGH) Research Institute; and Executive Vice Chair of the Department of Psychiatry Sanjay Mathew, M.D. Vice C
Slide 57: Contact us
57 Contact us: Investors: IR@vistagen.com Media: media@vistagen.com Business Development: BD@vistagen.com Tel: (650) 577-3600
Slide 58: Appendix
Appendix
Slide 59: Main Areas of the Brain Regulated by Pherine Neurocircuits
Main Areas of the Brain Regulated by Pherine Neurocircuits Fasedienol for Social Anxiety • NCNs (+) • OB (+) • AMY (FearOFF neurons) (+) • LC, RN, VTA, HYP (ant), BNST, PC (-) • HYP (PVN-OXY) (+) Itruvone for Depression • NCNs (+) • OB (+) • AMY (FearON neurons) (+) • LC, RN, VTA, HYP (post), BNST,
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