Vistagen Therapeutics, Inc. · NASDAQ:VTGN
Vistagen Therapeutics — Investor Presentation (October 2023)
62 slides from Vistagen Therapeutics's investor presentation, Oct 4, 2023
Slide 1: Healthy minds make healthy communities
Healthy minds make healthy communities, and we are innovating to change the trajectory of glok mental health ca
Slide 2: Forward-looking Statements
Forward-looking Statements ‘This presentation contains “forward-looking statements” within the meaning of the Private Securities Ltgaion Reform Act of 1995. These forward:Jookng statements involve known and unknown risks ‘hat ae dfclt to predict and include all maters that are not historical acts, T
Slide 3: Mission and Investment Highlights
Mission and Investment Highlights We are focused on delivering a new generation of CNS therapies with novel mechanisms of action targeting a broad and diverse range of CNS disorders with high unmet medical need Six CNS clinical programs, lead @ candidate with recent positive Phase 3 Gata ln'sacial a
Slide 4: Clinical-stage Pipeline
Clinical-stage Pipeline luct Candidate Lead Indication(s) Preclinical Phase | Phase It Phase Il Fasedienol Social Anxiety Disorder O) (ensae) Positive toptine results from PALISADE-2 trial (Aug 2023) i FA Fast Track designation herevene Major Depressive Disorder on, FDA Fast Track designation Menopa
Slide 5: Pherines: A new class of neuroactive nasal sprays
Slide 6: Pherines
Pherines Anew class of neuroactive nasal sprays Fast-acting, non-systemic, odorless, tasteless Selectively engage chemosensory receptors in the nasal passages to induce rapid-onset pharmacological and behavioral effects Selectively modulate brain areas, including the limbic amygdala, hypothalamus, h
Slide 7: Fasedienol Nasal Spray for Social Anxiety Disorder
Slide 8: Social Anxiety Disorder is a Serious Mental Health Condition
Social Anxiety Disorder is a Serious Mental Health Condition SAD is not simply medicalized shyness. It is a chronic disorder characterized by ... Debilitating emotional and physical symptoms © Emotional Symptoms Overwhelming fear + Surges of anxiety + Extreme self-consciousness Isolation leading to
Slide 9: SAD Affects ~10% of the US Population
SAD Affects ~10% of the US Population, with only ~20% of SAD Patients Helped by Current Pharmacotherapy Future Patients © Patients suffering but unaware of SAD as a condition or not yet motivated to seek professional help Underserved Patients Patients unsatisfied with or unwilling to use current tre
Slide 10: It has been ~2 decades since a New SAD Therapy was Approved
It has been ~2 decades since a New SAD Therapy was Approved SAD burden in the US continues to grow, but scientific innovation has been lacking US Adult SAD Prevalence (in Millions)? | ll TTT 2003 +2005 +2007 2009 aot 2013 2015 2017 2019 SAD is a highly prevalent condition which continues to affect i
Slide 11: Current Standard of Care for SAD is Inadequate
Current Standard of Care for SAD is Inadequate There is currently no FDA-approved, fast-acting, acute treatment for SAD Desired Product Profile of Treatments For Social Anxiety Disorder ‘Drug Fast-acting. Non-systemic. No Long-term Side Non- No Cognitive/ No Withdrawal No Abuse Effects sedating® Mot
Slide 12: Physician Satisfaction with Current Therapies is Modest
Physician Satisfaction with Current Therapies is Modest Satisfaction with current treatments for acute episodes of SAD from a large online survey Psychiatrists (n=125) sss/ Sis Beta Blockers 0% = KKK OK 10K 1§9% Extremely or Very Satisfied 1% Partially Satisfied/Unsatstied Primary Care Physicians (n
Slide 13: Fasedienol Brings New Optimism for SAD Treatment
Fasedienol Brings New Optimism for SAD Treatment a Dextisked potential NDA*-enabling pathway with positive results of PALISADE-2 Phase 3 trial reported in August 2023 O05 Novel mechanism of action, differentiated from all current therapies ‘Y Designed for patient-tailored as-needed administration, w
Slide 14: Fasedienol Profile is Rated Highly by Physicians
Fasedienol Profile is Rated Highly by Physicians and Recognized as a Valuable and Individualized Approach to Treat SAD Episodes On-demand Physician assessment of blinded fasedienol product profile from large online survey Fulfils unmet need _ ome a em came ot san added benefit ee ee ed Psychiatrist
Slide 15: Physicians Indicate High Intent to Prescribe Fasedienol
Physicians Indicate High Intent to Prescribe Fasedienol and Note it would be Appropriate for the Majority of their SAD Patients Physician assessment of blinded fasedienol product profile from large online survey LUkely to prescribe Ce ee ee ee mPsychiatrist lm Primary Care Physician {top 2-box of 5
Slide 16: Fasedienol's Potential Mechanism of Action
Fasedienol’s Potential Mechanism of Action Novel and differentiated from all current therapies for anxiety disorders © olfactory Bulb y a 7) Oo © Locus coeruleus Nasal Chemosensof e Area S © © Microgram-level intranasal dose of fasedienol is administered Fasedienol engages peripheral receptors in na
Slide 17: PALISADE-2 Phase 3 Trial
PALISADE-2 Phase 3 Trial ‘A randomized, multi-center, double-blind, placebo-controlled, single-dose administration Phase 3 trial to evaluate the efficacy, safety, and tolerability of fasedienol for the acute treatment of anxiety induced by a public speaking challenge in adult subjects with social an
Slide 18: PALISADE-2 Phase 3 Trial Top-line Efficacy Results
] PALISADE-2 Phase 3 Trial Top-line Efficacy Results Sao Positive results across primary, secondary, and exploratory endpoints : 5 LS Mean SUDS change from baseline vs. placebo _ Met Primary Endpoint (SUDS change from Visit 2 to Visit 3) p=0.015 ‘ CGI proportion of responders vs. placebo 7 Met Secon
Slide 19: Primary Efficacy Endpoint: PALISADE-2
9 : W, Primary Efficacy Endpoint: PALISADE-2 Change in LS Mean* SUDS Scores from V2 to V3 vs. Placebo Met primary endpoint with a change from Baseline in LS Mean of 5.8 points better than placebo (p=0.015) oo Absolute Change in LS Mean SUDS (V3-V2) (p=0.015) 19S Mean= Least-squares Mean mFasedienol
Slide 20: Secondary Endpoint: CGI-I Responders vs. Placebo at V3
Secondary Endpoint: CGI-| Responders vs. Placebo at V3 PALISADE-2 Met secondary endpoint with a proportion of responders 16.3% points greater than placebo (p=0.033) CGI-I % Responders* (Rating of 1 or 2) 40% 37.7% 35% 20% T= Very Much Less Anxious 2.= Much Less Anxious 25% '3=A Little Less Anxious A
Slide 21: Exploratory Endpoint: PGI-C Responders vs. Placebo at V3
P Ww Exploratory Endpoint: PGI-C Responders vs. Placebo at V3 PALISADE-2 Met exploratory endpoint with a proportion of responders 22.0% points greater than placebo (p=0.003) 45% + in accordance with FDA algne pre-specified statistical analysis plan, missing PI-C value for ore subject on placebo and
Slide 22: Exploratory Endpoint: SUDS Responders vs. Placebo at V3
Exploratory Endpoint: SUDS Responders vs. Placebo at V3 PALISADE-2 Met exploratory endpoint with a proportion of responders 17.1% points greater than placebo (p=0.020) SUDS % Responders* 40% 35.7% 35% is SUDS Responders 25% 2 20-point improvement from Visit 2 baseline to Visit 3 20% 12.6% 15% 10% 5%
Slide 23: Tolerability Profile Summary
Tolerability Profile Summary L hoe The tolerability profile of fasedienol was favorable and consistent with results from fasedienol trials completed to date + No severe or serious adverse events were reported in this trial * There were no discontinuations due to adverse events following the single d
Slide 24: PALISADE Open Label Safety Study
PALISADE Open Label Safety Study paListbetrss Over 30,000 doses self-administered by 481 SAD patients f Design Long-term intranasal administration of 3.2 ug of fasedienol as-needed, up to 4x/day prior to anxiety-provoking social and performance stressors in daily life, with a mean study duration of
Slide 25: Overview of Planned Fasedienol US NDA-Enabling Clinical Plan
Overview of Planned Fasedienol US NDA-Enabling Clinical Plan* To complement the positive results from PALISADE-2, planning is underway to initiate three clinical studies in 2024. If successful, we believe either PALISADE-3 or PALISADE-4, together with PALISADE-2, may establish substantial evidence o
Slide 26: Planned Phase 3 Trials: PALISADE-3 and PALISADE-4 with OLE
Planned Phase 3 Trials: PALISADE-3 and PALISADE-4 with OLE* Study Goat Study Design Outcome Measures 26 Randomized, multi-center, double-blind, placebo-controlled, single-dose administration Phase 3 trial to evaluate the efficacy, safety, and tolerability of fasedienol for the acute treatment of anx
Slide 27: Planned PALISADE Re-dose Study with OLE
Planned PALISADE Re-dose Study with OLE* Randomized, multi-center, double-blind, placebo-controlled, repeat-dose administration Phase 2 trial to evaluate the efficacy, safety, and tolerability of fasedienol for the acute treatment of anxiety induced by a public speaking challenge in adult subjects w
Slide 28: Beyond the standard of care for depression disorders
=) ond the standard of for d&pression disor¢ ?
Slide 29: Itruvone is a Potential Differentiated Monotherapy Treatment for MDD
Itruvone is a Potential Differentiated Monotherapy Treatment for Major Depressive Disorder i Innovative odorless, tasteless synthetic neuroactive nasal spray Designed for rapid-onset antidepressant effects Novel and differentiated MOA from all approved antidepressants Designed to be non-systemic, no
Slide 30: Itruvone's Potential Mechanism of Action
Itruvone’s Potential Mechanism of Action Novel and differentiated from all current therapies for depression disorders ©) Microgram-level intranasal dose of itruvone is administered Itruvone engages peripheral receptors in nasal chemosensory neurons (NCNs) © olfactory Bulb @ Ome stimulated with itruv
Slide 31: Itruvone Antidepressant Effects in Phase 2A MDD Study
Itruvone Antidepressant Effects in Phase 2A MDD Study Design: Phase 2A randomized, double-blind, placebo-controlled, parallel design POC clinical study (n=30) f Dosing: 3.2 1g or 6.4 1g of itruvone or placebo i.n., 2 times per day for 8 weeks 6 Primary Endpoint: Change in HAMD-17 scores from baselin
Slide 32: Itruvone Phase 2A MDD Study
Itruvone Phase 2A MDD Study Hamilton Depression (HAMD-17) Score Reduction From Baseline 6.4 ug dose produced 50 rapid-onset and sustained antidepressant effects in g MDD study participants with g minimal side effects & 100 E £ 8 zs 3 2 z = 04 @2v2Kowvoe [ass [orn — jor 2 @ kaye (nehooe) [are [aor [o
Slide 33: Itruvone Potential Next Step — Phase 2B Trial
Itruvone Potential Next Step — Phase 2B Trial* Advanced planning for potential Phase 2B development of itruvone as a monotherapy MDD treatment is underway Potential Design: Double-blind, randomized, placebo-controlled, parallel study in approximately 200 total male and female subjects (18 to 65 year
Slide 34: PH80 Nasal Spray for Vasomotor Symptoms
PH80 Nasal Spray — ; for Vasomoto
Slide 35: PH80 Nasal Spray
PH80 Nasal Spray Potential treatment for vasomotor symptoms (hot flashes) due to menopause and premenstrual dysphoric disorder Innovative, rapid-onset product candidate 4@: Novel and differentiated MOA from all approved products Taken as-needed for treatment of multiple menopausal hot flashes daily,
Slide 36: PH80's Potential Mechanism of Action
PH80’s Potential Mechanism of Action Novel and differentiated from all ©) Microgram-tevel intranasal dose of PH80 is administered currently approved VMS therapies @)_PH8O engages peripheral receptors in nasal chemosensory neurons (NCNs) © Once stimulated with PHBO, NCNSs then trigger subgroups ~ of
Slide 37: PH80 Phase 2A Study in Hot Flashes
PH80 Phase 2A Study in Hot Flashes (55) Objective: Proof-of-principle evaluation of PH80 efficacy and tolerability for the acute management of \G7Z hot flashes due to menopause Study Details: Randomized, double-blind, placebo-controlled, Phase 2A study. Participants self- administered PH80 (3.2 g/do
Slide 38: PH80 Phase 2A Study in Hot Flashes: Efficacy
PH80 Phase 2A Study in Hot Flashes: Efficacy Statistically and clinically significant improvement vs. placebo in the number of hot flashes at 1 week and maintained through 4 weeks of treatment (p<.001) Daily Mean Number of Hot Flashes #PH80 (n=18) Placebo (n=18) Lobb owe ‘Change From Baseline in Dai
Slide 39: PH80 Phase 2A Study in Hot Flashes: Efficacy
PH80 Phase 2A Study in Hot Flashes: Efficacy PH80 also significantly reduced participant-reported Severity, Disruption in function (Bother), and Sweating associated with hot flashes during the treatment period as compared with placebo ———— 7 7 | os ee = Se ee ee Pe » Vistagen
Slide 40: PH80 Phase 2A Study in Premenstrual Dysphoric Disorder (PMDD)
PH80 Phase 2A Study in Premenstrual Dysphoric Disorder (PMDD) @ C7 iY Fe © Objective: Proof-of-principle evaluation of PH80 efficacy and tolerability for the acute management of the symptoms of PMDD Study Details: Randomized, double-blind, placebo-controlled, exploratory Phase 2A study. Subjects who
Slide 41: PH80 Phase 2A Study in PMDD: Efficacy
PH80 Phase 2A Study in PMDD: Efficacy PH80 treatment resulted in significant separation in PMDD DSR scores vs Placebo from Day 4 through Day 6 (p=.008) x @8) 2 » 2 ae 2] -oPlacebo -O- pH8O Daya Day? Day Dov Days Day 6 e027 (9-035) (02 (o-0034) (9-0.005") (0.008% ‘i Vistagen * Denotes Statistical Sig
Slide 42: PH80 Phase 2A Study in PMDD: Efficacy
PH80 Phase 2A Study in PMDD: Efficacy PH80 resulted in clinically significant reduction in PMTS from baseline vs Placebo (p=.006) een Baseline and Treatment at Day 6 MiPlacebo Ml PHO HRD WEE & ear * Denotes Satistical Significance Vistagen
Slide 43: PH15 Nasal Spray for Acute Treatment of Cognitive Impairment
Slide 44: PH15 Nasal Spray
PH15 Nasal Spray Potential for improvement of cognitive impairment caused by mental fatigue if Innovative, rapid-onset PRN product candidate ys. User-friendly intranasal administration, taken as-needed for acute improvement of cognition © Expected to provide rapid-onset and activation of brain areas
Slide 45: PH15 Proposed Mechanism of Action
PH15 Proposed Mechanism of Action Novel and differentiated from all currently approved therapies ©) Microgram-level intranasal dose of PH15 is administered ©) PHIS engages peripheral receptors in nasal chemosensory neurons (NCNs) © Once stimulated with PH15, NCNs then trigger subgroups of neurons in
Slide 46: PH284 Nasal Spray for Acute Treatment
PH284 Nasal Sp: for Acute Tre
Slide 47: PH284 Nasal Spray
PH284 Nasal Spray Potential acute treatment for wasting syndrome (cachexia) if Innovative, fast-acting therapy for appetite enhancement » User-friendly intranasal administration, taken before meals Potential to increase subjective feelings of hunger and caloric intake in G patients diagnosed with wa
Slide 48: PH284 Proposed Mechanism of Action
PH284 Proposed Mechanism of Action Novel and differentiated from current treatment options ©) Microgram-level intranasal dose of PH284 is administered ipheral receptors in nasal chemosensory © PH284 engages p neurons (NCNs) © _ Once stimulated with PH2B4, NCNs then trigger subsets of neurons in the
Slide 49: AV-101 for Potential Pipeline Opportunities
AV-101 for Potential P
Slide 50: AV-101 for CNS Disorders
AV-101 for CNS Disorders Designed to inhibit (but not block) NMDA receptor activity + Oral prodrug of 7-CI-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 and other NMDAR antago
Slide 51: AV-101's Potential Mechanism of Action
AV-101’s Potential Mechanism of Action Vistagen
Slide 52: Distinguished Clinical and Regulatory Advisors
Distinguished Clinical and Regulatory Advisors Representing Premier Institutions and Deep CNS and Regulatory Expertise HARVARD, Maurizio Fava, M.D. tro Pia, arnd MadtDvcm, en st @ Thomas Laughren, M.D. Min ‘de COLUMBIA Michael Liebowitz, M.D. ecto (ered, US Food and nel Resear rote and Eexive We Cha
Slide 53: Senior Vice President, Investor Relations
niof VicePrdithdent, investor Relations “markmcp@vistagen.com_ : ~
Slide 54: Beyond the standard of care for anxiety disorders
ond the standard oft 4 for afxi g
Slide 55: Subjective Units of Distress Scale (SUDS)
Subjective Units of Distress Scale (SUDS) Primary efficacy endpoint in PALISADE Phase 3 trials for acute measurement ‘The SUDS measures the self-reported intensity of anxiety and/or distress in patients with SAD Patients are asked to rate th scale of 0-100 level of anxiety/ Physiological signs of di
Slide 56: Fasedienol Efficacy in Phase 3 Public Speaking Challenge Trial
Fasedienol Efficacy in Phase 2 Public Speaking Challenge Trial Minute-by-minute SUDS scores isi (Basetine/Placebo) iit 3 (Treatment Phase) enol rapidly reduced onse to peaking challenge 1 rhea Pichasons) | iaricsne 6 td oun | . aoe | ae ia . wrote won . 5 gees i smtrsownun | m6 mm @ | z ‘Al parkigan
Slide 57: Liebowitz Social Anxiety Scale (LSAS)
Liebowitz Social Anxiety Scale (LSAS) Primary Efficacy Endpoint for Over Time Measurement The LSAS is a 24-item clinician-rated scale used to assess how SAD impacts a patient's life across a variety of situations 13 situations pertain to performance (P) and 11 pertain to social situations (S) ‘+ Ass
Slide 58: Fasedienol Efficacy Over Time as Measured by the LSAS
Fasedienol Efficacy Over Time as Measured by the LSAS Fasedienol used as-needed over time has demonstrated reduction of LSAS scores in two trials Phase 2 Crossover Study PALISADE Open-label Safety Study Mean LSAS change from baseline vs Mean LSAS reduction of 16 points at one 110 placebo of 15 point
Slide 59: Fasedienol Phase 1/1b Data
Fasedienol Phase 1/1b Data Well tolerated with reduction in autonomic biomarkers, increased electrical activity, and anxiety effects 8 Observed Reduction in Autonomic Biomarkers Statistically significant reduction in heart rate, respiratory rate, and electrodermal activity was observed in both men a
Slide 60: Fasedienol Reduction in Autonomic Biomarkers: Study Results
Fasedienol Reduction in Autonomic Biomarkers: Study Results larly designed Phase 1 studies were conducted in healthy volunteers ; 32 male, 32 female) in a placebo-controlled crossover study design + Doses ranging from 0.2 ug to 0.4 ig were administered across these studies using an experimental nasa
Slide 61: Fasedienol Electrogram of Nasal Receptors (EGNR): Study Results
Fasedienol Electrogram of Nasal Receptors (EGNR): Study Results Dose response led to selection of the effective dose to use in clinical trials Fasedienol (ug) 0.0 04 od \ neem 2) ae o8 a — a Dose-dependent electrical depolarization of human nasal chemosensory receptor cells in response to fasedienol
Slide 62: Fasedienol Dose-dependently Activates Cortical Brain Regions
Fasedienol Dose-dependently Activates Cortical Brain Regions A | ‘SHAM Prener Vanillin Decanoic Propionic. Valeric. Pherine & wt “fp eX, Selective and dose-dependent brain activation induced by odorless pherine fasedienol (A) is different from control (SHAM) and brain activation induced by primary o
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