Vistagen Therapeutics, Inc. · NASDAQ:VTGN
Vistagen Therapeutics — Investor Presentation (December 2024)
58 slides from Vistagen Therapeutics's investor presentation, Dec 6, 2024
Slide 1: Pioneering neuroscience with nose-to-brain neurocircuitry
Nasdaq: VTGN Pioneering neuroscience with nose-to-brain neurocircuitry
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 - Multiple partnership opportunities - Funded U.S. registration-directed Phase 3 program in Social Anxiety Disorder - Broad and diverse neuroscience pipeline - Non-systemic, neurocircuitry-focused pherines with differentiated efficacy and safety - Multi-billion-dollar peak sa
Slide 4: Lead Neuroscience Programs
Product Candidate Lead Indication Preclinical Phase I Phase II Phase III Fasedienol Itruvone Social Anxiety Disorder Major Depressive Disorder • U.S. registration-directed PALISADE Phase 3 program underway • First positive Phase 3 study reported in 2H 2023 • FDA Fast Track designation • FDA Fast Tra
Slide 5: Pherines
Vistagen Pherines
Slide 6: Pherines: A new class of neuroscience product candidates
Pherines 6 A new class of neuroscience product candidates - Nose-to-brain neurocircuitry-focused - Non-systemic MOAs are differentiated from all FDA-approved drugs for target indications - Rapidly activated neural connections regulate multiple areas of the brain - Therapeutic effects without binding
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: Acute Treatment of Social Anxiety Disorder: Fasedienol
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: Social Anxiety Disorder 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. SAD Disease Burden
11 U.S. SAD Disease Burden 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 Prevalence of SAD continues to grow
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: Physicians Indicate High Intent to Prescribe a Product with Fasedienol's Profile
14 Psychiatrists and Primary Care Physicians Indicate High Intent to Prescribe a Product with Fasedienol’s Profile and Note it Would Be Appropriate for the Majority of their SAD Patients Sources: Vistagen Proprietary Market Research, Online Survey, Jan 2022 (n=251) 51% 56% 0% 20% 40% 60% 80% 100% %
Slide 15: Fasedienol's Proposed Mechanism of Action
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 Proposed Mechanism of Action A microgram-level dose of fasedienol is administered intranasally 1 A ctivity D ecreases 5
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: 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 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 trial to evaluate the efficacy, safety, and tolerability of fasedienol for acute treatment of anxiety in adult subjects with SAD induced by a public speakin
Slide 24: Study Enhancements for PALISADE-3 and PALISADE-4
‐ Increased Vistagen site-facing staff and reduced reliance on CRO surveillance ‐ Focused and recurring in-person training of clinical site personnel ‐ Expanded subject eligibility review at screening ‐ No mask-wearing during the public speaking challenge ‐ Treatment administration by clinical site
Slide 25: Fasedienol U.S. Registration-directed Phase 3 Program
25 Fasedienol U.S. Registration-directed Phase 3 Program To complement PALISADE-2, Vistagen is conducting two additional PALISADE Phase 3 studies as part of its U.S. registration-directed PALISADE Phase 3 program for acute treatment of SAD PALISADE-3 and PALISADE-4 Phase 3 Trials with Open-label Ext
Slide 26: Major Depressive Disorder: Itruvone
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 Proposed Mechanism of Action
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 Proposed Mechanism of Action Microgram-level intranasal dose of itruvone is administered intranasally 1 A ct iv it y In cr
Slide 30: Itruvone Phase 2A Study 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: HAMD-17 Results
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 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 33: Vasomotor Symptoms (Hot Flashes) due to Menopause: PH80
Vasomotor Symptoms (Hot Flashes) due to Menopause PH80
Slide 34: VMS (Hot Flashes): Highly Prevalent and Disrupt Daily Life
VMS (Hot Flashes): Highly Prevalent and Disrupt 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 Proposed Mechanism of Action
PH80’s Novel Proposed Mechanism of Action 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 ne
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- administ
Slide 39: PH80 Phase 2A Study in Hot Flashes: 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 in Hot Flashes: 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 Wasting Syndrome (e.g. Cachexia)1 Additional Clinical-stage Neuroscience
Slide 43: Premenstrual Dysphoric Disorder: PH80
Premenstrual Dysphoric Disorder PH80
Slide 44: PH80 Phase 2A Study in Premenstrual Dysphoric Disorder (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: Acute Treatment of Cognitive/Psychomotor Impairment due to Mental Fatigue: PH15
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 Novel Proposed Mechanism of Action
PH15 Novel Proposed Mechanism of Action 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 Improvement of Psychomotor Impairment
PH15 Phase 2A Study for Improvement of Psychomotor Impairment Caused by Mental Fatigue 49 Objective: Explore efficacy, safety, and tolerability of intranasal administration of PH15 on psychomotor performance as measured by reaction time in sleep-deprived participants Study Details: Randomized, doubl
Slide 50: Acute Treatment of Wasting Syndrome (Cachexia): PH284
Acute Treatment of Wasting Syndrome (Cachexia) PH284
Slide 51: PH284 Nasal Spray
PH284 Nasal Spray 51 Potential acute treatment for wasting syndrome (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 o
Slide 52: PH284 Novel Proposed Mechanism of Action
PH284 Novel Proposed Mechanism of Action 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: Potential Collaborative Phase 2A Development: AV-101
Potential Collaborative Phase 2A Development AV-101
Slide 54: AV-101 for Multiple Neuroscience Disorders
AV-101 for Multiple Neuroscience Disorders 54 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 55: AV-101's Proposed Mechanism of Action
AV-101’s Proposed Mechanism of Action 55 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 56: AV-101 Potential partnering opportunities for Phase 2 development
AV-101 for Multiple Neuroscience Disorders 56 Potential partnering opportunities for Phase 2 clinical development Neuropathic PainLevodopa-Induced Dyskinesia Associated with Parkinson’s therapy
Slide 57: Distinguished Clinical and Regulatory Advisors
57 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
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