Vistagen Therapeutics, Inc. · NASDAQ:VTGN
Vistagen Therapeutics — Investor Presentation (February 2025)
59 slides from Vistagen Therapeutics's investor presentation, Feb 13, 2025
Slide 1: Pioneering neuroscience with nose-to-brain neurocircuitry
Nasdaq: VTGN Pioneering neuroscience with nose-to-brain neurocircuitry February 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: Investment Highlights
3 Investment Highlights - Broad and diverse neurocircuitry-focused pherine pipeline differentiated from all approved therapies - Ongoing U.S. registration-directed Phase 3 studies in Social Anxiety Disorder - Multibillion-dollar peak sales potential across multiple neuroscience indications - Multipl
Slide 4: Lead Clinical-stage Neuroscience Programs
Product Candidate Lead Indication Preclinical Phase I Phase II Phase III Fasedienol Itruvone Acute Treatment of Social Anxiety Disorder Major Depressive Disorder • U.S. registration-directed Phase 3 program underway • First positive Phase 3 study reported in 2H 2023 • FDA Fast Track designation gran
Slide 5: Pherines
Pherines A new medication class harnessing the therapeutic potential of nose-to-brain neurocircuitry
Slide 6: Pherines: A new class of intranasal neuroscience product candidates
Pherines 6 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 7: 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,
Slide 8: Fasedienol: Acute Treatment of Social Anxiety Disorder
Acute Treatment of Social Anxiety Disorder Fasedienol
Slide 9: Social Anxiety Disorder
Social Anxiety Disorder 9 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 Chronic me
Slide 10: SAD Affects ~12% 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 10 Social Anxiety Disorder (SAD) Affects ~12% of U.S. Adults Sources: Oracle Life Sciences. May 2024. U.
Slide 11: U.S. Social Anxiety Disorder Prevalence Continues to Grow
11 U.S. Social Anxiety Disorder Prevalence 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 12: There is no FDA-approved Acute Treatment of SAD
12 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 13: Fasedienol Brings New Optimism for SAD Patients
Fasedienol Brings New Optimism for SAD Patients ‐ Compelling 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
Slide 14: High Intent to Prescribe a Product with Fasedienol's Profile
14 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 15: Fasedienol's Novel Neurocircuitry-focused 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 Neurocircuitry-focused MOA A microgram-level dose of fasedienol is administered intranasally 1 A ctivity D ecrease
Slide 16: PALISADE-2 Phase 3 Trial for Acute Treatment of SAD
16 16 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 acute treatment of anxiety in adult
Slide 17: 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 PALISADE 2 Phase 3 Top-line Efficacy Results CGI-I proportion of responders vs. placebo PGI-C proportio
Slide 18: PALISADE-2 Primary Efficacy Endpoint: Change in SUDS Scores
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 18 N=70
Slide 19: 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 20: 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 21: 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 22: 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 23: PALISADE-3 and PALISADE-4 Phase 3 SAD Trials with OLE
23 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 24: Fasedienol U.S. Registration-directed Phase 3 Program
24 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 Phase 3 program for the acute treatment of SAD PALISADE-3 and PALISADE-4 Phase 3 Trials
Slide 25: PALISADE-3 and PALISADE-4 Study Enhancements
‐ Increased surveillance by Vistagen clinical site-facing staff, reduced reliance on CRO ‐ Recurring in-person training of clinical site personnel ‐ Expanded subject eligibility review at screening ‐ No mask-wearing during the public speaking challenges ‐ Treatment administration by clinical site he
Slide 26: Itruvone: Major Depressive Disorder
Major Depressive Disorder Itruvone
Slide 27: 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 28: Itruvone has Potential to Transform Treatment of MDD
Itruvone has Potential to Transform Treatment of MDD ‐ Non-systemic, neurocircuitry-focused pherine 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 ‐
Slide 29: Itruvone's Novel Neurocircuitry-focused 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 Neurocircuitry-focused MOA Microgram-level intranasal dose of itruvone is administered intranasally 1 A ct iv it y I
Slide 30: Rapid-onset antidepressant effects with itruvone in MDD
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 31: Itruvone Phase 2A Study in MDD
31 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 32: Itruvone Phase 2B Clinical Plan
32 Itruvone Phase 2B Clinical Plan* Planning and preparation 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
Slide 33: PH80: Vasomotor Symptoms (Hot Flashes) due to Menopause
Vasomotor Symptoms (Hot Flashes) due to Menopause PH80
Slide 34: VMS (Hot Flashes): Highly Prevalent and Disrupts Daily Life
VMS (Hot Flashes): Highly Prevalent and Disrupts Daily Life 34 • 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 • Frequency
Slide 35: VMS (Hot Flashes): Current Treatments
VMS (Hot Flashes): Highly Prevalent and Disrupts Daily Life 35 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, cl
Slide 36: PH80 potential to transform treatment of VMS
PH80 potential to transform treatment of VMS (Hot Flashes) 36 PH80 Nasal Spray ‐ Neurocircuitry-focused pherine MOA differentiated from all approved treatments ‐ Non-systemic and non-hormonal ‐ Rapid-onset potential to be taken as-needed to provide relief in the moment ‐ Potential for differentiated
Slide 37: PH80's Novel Neurocircuitry-focused MOA
PH80’s Novel Neurocircuitry-focused MOA Microgram-level intranasal dose of PH80 is administered1 A ctivity D ecreases 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 neur
Slide 38: PH80 Phase 2A Study in Menopausal Hot Flashes
PH80 Phase 2A Study in Menopausal Hot Flashes 38 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-administe
Slide 39: PH80 Phase 2A Study: 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 40: PH80 Phase 2A Study: Met Secondary Efficacy Endpoint
PH80 Phase 2A Study in Hot Flashes: Met Secondary Efficacy Endpoint H o t Fl as h es - B o th er H o t Fl as h es - S w ea t H o t Fl as h es - S ev er it 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
Slide 41: Additional Clinical-stage Neuroscience Product Candidates
Additional Clinical-stage Neuroscience Product Candidates
Slide 42: Additional Clinical-stage Neuroscience Product Candidates
Indications Preclinical Phase I Phase II Phase III AV-101 Disorders involving NMDAR FDA Fast Track designation in major depressive disorder and neuropathic pain PH15 PH284 Cognitive/Psychomotor Impairment due to Mental Fatigue1 Cancer Cachexia1 Additional Clinical-stage Neuroscience Product Candidat
Slide 43: PH80: Premenstrual Dysphoric Disorder
Premenstrual Dysphoric Disorder PH80
Slide 44: PH80 Phase 2A Study in PMDD
PH80 Phase 2A Study in Premenstrual Dysphoric Disorder (PMDD) 44 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 45: 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) 45 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 46: PH15: Cognitive/Psychomotor Impairment due to Mental Fatigue
Acute Treatment of Cognitive/Psychomotor Impairment due to Mental Fatigue PH15
Slide 47: PH15 Potential for improvement of cognitive and psychomotor impairment
PH15 47 Potential for improvement of cognitive and psychomotor impairment caused by mental fatigue PH15 Nasal Spray ‐ Innovative, rapid-onset pherine product candidate ‐ User-friendly nasal spray, taken as needed for acute improvement of cognition due to mental fatigue ‐ Potential to provide rapid-o
Slide 48: PH15's Novel Neurocircuitry-focused MOA
PH15’s Novel Neurocircuitry-focused MOA Microgram-level intranasal dose of PH15 is administered intranasally 1 A ct iv it y 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
Slide 49: 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 50: PH284: Acute Treatment of Cancer Cachexia
Acute Treatment of Cancer Cachexia PH284
Slide 51: PH284 Nasal Spray: Potential acute treatment for cancer cachexia
PH284 Nasal Spray 51 Potential acute treatment for cancer cachexia ‐ Innovative, non-systemic neurocircuitry-focused pherine product candidate with rapid-onset potential for appetite enhancement ‐ Intranasal administration, taken before meals ‐ Potential to increase subjective feelings of hunger and
Slide 52: PH284's Novel Neurocircuitry-focused MOA
PH284’s Novel Neurocircuitry-focused MOA Microgram-level intranasal dose of PH284 is administered intranasally 1 A ct iv it y 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) neuron
Slide 53: 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 54: AV-101: Potential for Collaborative Phase 2A Development
Potential for Collaborative Phase 2A Development AV-101
Slide 55: AV-101 for Multiple Neuroscience Disorders
AV-101 for Multiple Neuroscience Disorders 55 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 56: AV-101's Proposed Mechanism of Action
AV-101’s Proposed Mechanism of Action 56 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 57: AV-101: Potential to partner for clinical development and commercialization
AV-101 for Multiple Neuroscience Disorders 57 Potential to partner for clinical development and commercialization Neuropathic PainLevodopa-Induced Dyskinesia Associated with Parkinson’s therapy
Slide 58: Distinguished Clinical and Regulatory Advisors
58 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 59: Contact us
59 Contact us: Investors: IR@Vistagen.com Media: media@vistagen.com Business Development: BD@Vistagen.com Tel: (650) 577-3600
Vistagen Therapeutics — Investor Presentation (February 2025) on 6ix