Vistagen Therapeutics, Inc. · NASDAQ:VTGN
Vistagen Therapeutics — Investor Presentation (September 2023)
57 slides from Vistagen Therapeutics's investor presentation, Sep 8, 2023
Slide 1: Fasedienol Nasal Spray for Social Anxiety Disorder
Healthy minds make healthy communitie and we are innovatii to change the trajectory of global
Slide 2: Forward-looking Statements
Forward-looking Statements Thispresentation contains “forward-looking statements" within the meaning ofthe Private Secures Litation Reform Actof 1995. These forward-looking statements Involve known and unknown rks that avedlfficlt to predictand include allmattersthatare nothistorical facts. These fo
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 data in social anx
Slide 4: Clinical-stage Pipeline
Clinical-stage Pipeline Product Candidate Lead Indication(s) Preclinical Phase | Phase tt Phase il Fasedienol Social Anxiety Disorder ee (eH949) Positive Topline Results from PALISADE-2 Trial (Aug 2023) FDA Fast Track designation Itruvone Major Depressive Disorder ——————ees bata) FDA Fast Track desi
Slide 5: Pherine: A new class of nasal sprays
Pherine A new class 0 nasal sprays
Slide 6: Pherines: A new class of neuroactive nasal sprays
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
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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 Ineveryday socialor performance situations Emotional Symptoms | Os + Overwhelmingfear 000 + Surgesof anxiety
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 “25M Patients suffering but unaware of SAD asa condition hed or not yet motivated to seek professional help. Patient: ‘ “12M Underserved Patients * or Diagnosed Patients unsatisfie
Slide 10: We Believe Current Standard of Care for SAD is Inadequate
We Believe Current Standard of Care for SAD is Inadequate There is currently no FDA-approved, fast-acting, non-systemic treatment for SAD Desired Product Profile of Treatments For Social Anxiety Disorder Drug Fast-é Non-systemic No Long-term Side | Non- No Cognitive/ No Withdrawal, No Abuse Effects
Slide 11: We Believe Fasedienol Brings New Optimism for SAD Treatment
We Believe Fasedienol Brings New Optimism for SAD Treatment De-risked potential NDA-enabling pathway with positive results of PALISADE-2 Phase 3 trial reported in August 2023 Novel mechanism of action, differentiated from current therapies Designed for patient-tailored as-needed administration, with
Slide 12: Fasedienol's Potential Mechanism of Action
Fasedienol’s Potential Mechanism of Action Novel and differentiated from all current therapies for anxiety disorders ©) Microgram-tevel intranasal dose of fasedienol is administered © Fasedenol engages peripheral receptors in nasal chemosensory neurons (NCNs) Olfactory Bulb. yo Once stimulated with
Slide 13: 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 (6) evaluate the efficacy, safety, and tolerability of fasedienol for the acute treatment of anxiety induced by a (QZ publicspeaking challenge in adult subjects with Soc
Slide 14: PALISADE-2 Phase 3 Trial Top-Line Efficacy Results
PALISADE-2 Phase 3 Trial Top-Line Efficacy Results Positive results across primary, secondary, and exploratory endpoints (much or very much less anxious from Visit 2 to Visit 3) —_ —$ 5 - LS Mean SUDS change from baseline vs. placebo 3 Met Primary Endpoint (SUDS change from Visit 2 to Visit 3) p=0.0
Slide 15: Primary Efficacy Endpoint: Change in LS Mean SUDS Scores
Primary Efficacy Endpoint: 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) Absolute Change in LS Mean SUDS (V3-V2) 15 (p=0.015) 15 "1S Mean= Least-squares Mean mFasedienol_m Placebo Vista
Slide 16: Secondary Endpoint: CGI-I responders vs. Placebo at V3
Secondary Endpoint: CGI-I responders vs. Placebo at V3 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% 30% 25% 21.4% 20% u 6 = Much More Anxious 15% 7 = Very Much More Anxious 10% 5% N=70 % (p=0.03
Slide 17: Exploratory Endpoint: PGI-C responders vs. Placebo at V3
Exploratory Endpoint: PGI-C responders vs. Placebo at V3 Met exploratory endpoint with a proportion of responders 22.0% points greater than placebo (p=0.003) PGI-C % Responders (Rating of 1 or 2) 40.6% 40% 35% 30% 4=No Change 25% 5 =ALittle More Anxious om 18.6% 6 = Much More Anxious 7 = Very Much M
Slide 18: Exploratory Endpoint: SUDS responders vs. Placebo at V3
Exploratory Endpoint: SUDS responders vs. Placebo at V3 Met exploratory endpoint with a proportion of responders 17.1% points greater than placebo (p=0.020) SUDS % Responders 35.7% 35% 30% ‘SUDS Responders 25% 20% 18.6% 15% 10% 5% N=70 0% (p=0.020) as mFasedienol = Placebo Vistagen
Slide 19: Tolerability Profile: Overall Summary
Tolerability Profile: Overall Summary 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 exposure
Slide 20: PALISADE Open Label Safety Study
PALISADE Open Label Safety Study Over 30,000 doses self-administered by 481 SAD patients 1 Design Long-term intranasal administration of 3.2 ug of fasedienol as-needed, up to 4x/day prior to anxiety-provokingsocial and performance stressors in daily life, with a mean study duration of 4 months, and
Slide 21: Planned Next Step: PALISADE-3 Phase 3 Trial with OLE
Planned Next Step: PALISADE-3 Phase 3 Trial with OLE* Grtera (Fry ‘Outcome Measures 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
Slide 22: Itruvone: Looking beyond the standard of care for depression disorders
yond the standard of for d&pression disor¢ y
Slide 23: Itruvone is a Potential Differentiated Monotherapy Treatment of MDD
Itruvone is a Potential Differentiated Monotherapy Treatment of Major Depressive Disorder i Innovative odorless, tasteless synthetic neuroactive nasal spray cS) Designed for rapid-onset antidepressanteffects Novel and differentiated MOA from all approved antidepressants Designed to be non-systemic,
Slide 24: Itruvone's Potential Mechanism of Action
Itruvone’s Potential Mechanism of Action Novel and differentiated from all current therapies for depression disorders ©) Microgram-tevel intranasal dose of itruvone is administered © Mtwwone engages peripheral receptors in nasal chemosensory neurons (NCNs) © bree stimulated with itruvone, NCNSs then
Slide 25: 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 clinicalstudy (n=30) Dosing: 3.2 j1g or 6.4 j1g of itruvoneor placeboi.n., 2 times per day for 8 weeks 4 Primary Endpoint: Change in HAMD-17 scores from baselineco
Slide 26: Itruvone Phase 2A MDD Study
Itruvone Phase 2A MDD Study Hamilton Depression (HAMD-17) Score Reduction From Baseline 6.4 jg dose produced 5.0 rapid-onset and sustained antidepressant effects in g 7 MDD patients with minimal side 3 effects & 00 5 3 us = trwvone Dose te = placebo) = a0 © 22ue(towdese [163 [tor for & © capa ivanoo
Slide 27: 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 ca. 200 total male and female subjects (18 to 65 years old) wit
Slide 28: PH80 Nasal Spray for Vasomotor Symptoms (Hot Flashes)
PH80 Nasal Spray for Vasomotor (Hot Flashes)d
Slide 29: PH80 Nasal Spray
PH80 Nasal Spray Potential Treatment for Vasomotor Symptoms (Hot Flashes) due to Menopause v v v 2 Innovative, rapid-onset product candidate Novel and differentiated MOA from all approved products Taken as-needed for treatment of multiple menopausal hot flashes daily, use analogous to a rescue inhal
Slide 30: PH80's Potential Mechanism of Action
PH80’s Potential Mechanism of Action Novel and differentiated from all currently approved VMS therapies Microgram-level intranasal dose of PH80 is administered PH80 engages peripheral receptors in nasal chemosensory neurons (NCNs) Once stimulated with PH80, NCNs then trigger subgroups of neurons in
Slide 31: PH80 Phase 2A Study in Hot Flashes: Summary
PH80 Phase 2A Study in Hot Flashes: Summary lo 10 Jo [Y @ 2 a Objective: Proof-of-principle evaluation of PH80 efficacy and tolerability for the acute management of vasomotor symptoms (hot flashes) due to menopause Study Details: Randomized, double-blind, placebo-controlled, exploratory Phase 2A stu
Slide 32: 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<0.001) Daily Mean Number of Hot Flashes Gaming Week1 Week? —WeekS Week Followup =PHEO (n=18) | —e-Placeb
Slide 33: PH80 Phase 2A Study in Hot Flashes: Efficacy
PH80 Phase 2A Study in Hot Flashes: Efficacy PH80 also significantly reduced patient- reported severity, disruption in function, and sweating associated with hot flashes during the treatment period as compared with placebo (
Slide 34: PH15 Nasal Spray for Acute Treatment of Cognitive Impairment
PH15 Nasal Spray for Acute Treatment Cognitive Impair caused by Mer
Slide 35: PH15 Nasal Spray
PH15 Nasal Spray Potential for Improvement of Cognitive Impairment caused by Mental Fatigue v v 35 Innovative, rapid-onset PRN product candidate User-friendly intranasal administration, taken as needed for acute improvement of cognition Expected to provide rapid onset and activation of brain areas N
Slide 36: PH15 Proposed Mechanism of Action
PH15 Proposed Mechanism of Action Novel and differentiated from all currently approved therapies Microgram-level intranasal dose of PH1 administered neurons (NCNs) ean ~ ‘ Once stimulated with PH15, NCNs then trigger subgroups © Hippocampus of neurons in the olfactory bulbs (OBs) © PH15 engages peri
Slide 37: PH284 Nasal Spray for Acute Treatment
PH284 Nasal Spray for Acute Treatmen
Slide 38: PH284 Nasal Spray
PH284 Nasal Spray Potential Acute Treatment for Wasting Syndrome (Cachexia) v Innovative, fast-acting therapy for appetite enhancement v User-friendly intranasal administration, taken before meals v Potential to increase subjective feelings of hunger and caloric intake in patients diagnosed with was
Slide 39: 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 , : Vn ©) PH284 engages peripheral receptors in nasal chemosensory neurons (NCNs) y » © _Lnce stimulated with PH284, NCNs then trigger subsets of neur
Slide 40: AV-101 for Potential Phase 2A
AV-101 for Potential Phase 2A aia Looking beyond th for disorders invol receptor
Slide 41: 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 antagonistat the glycine site of the NMDA receptor * Potential to inhibit the function of the NMDA receptor, without fully blocking NMDA receptor function like
Slide 42: AV-101's Potential Mechanism of Action
AV-101’s Potential Mechanism of Action 4201 - Oral Prodrug 4-C1.K¢N) wood JOq Non4 coon | | | on Vistagen
Slide 43: Distinguished Clinical and Regulatory Advisors
Distinguished Clinical and Regulatory Advisors Representing Premier Institutions and Deep CNS and Regulatory Expertise HARVARD MaurizioFava,M.D. Professor of Psychiaty, Havard Medical School: Director, Drision of Cinical Research, Massachusetts General Hospital (UGH) Research Institute, and Execute
Slide 44: For further information please contact
For further information please contact: Mark McPartland — Senior 2 President, Investor Relations markmcp@vistagen.com
Slide 45: Fasedienol Nasal Spray for Social Anxiety Disorder (Additional Information)
Vistagen
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Slide 47: 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 their level of anxiety/distress on a scale of 0-100 Physiolog
Slide 48: Fasedienol Efficacy in Phase 3 Public Speaking Challenge Trial
Fasedienol Efficacy in Phase 2 Public Speaking Challenge Trial Minute-by-minute SUDS scores Vist 2 (Baseine/Placebo) Vist 3 (Treatment Phase) © font ge - m Placebo group Ps i § © fasedienol group 5 2 Al patents recened $° z placebo at ist 2 to g $ establish baseline SUDS S | ane z z ee sing TS Calar
Slide 49: 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 50: 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 51: Fasedienol Phase 1/1b Data
Fasedienol Phase 1/1b Data Well-tolerated, reduced autonomic biomarkers, increased EGNR, anxiety effects @ Reduction in Autonomic Biomarkers Statistically significant reduction in heart rate, respiratory rate, and electrodermal activity in both men and women in several studies. Intranasal 0.4 1g fas
Slide 52: Fasedienol Reduction in Autonomic Biomarkers: Study Design
Fasedienol Reduction in Autonomic Biomarkers: Study Design (6) To study impact of fasedienol or placebo administered 30 min apart in a randomized fashion on heart rate (HR), WW respiratory rate (RR) and electrodermal activity (EDA) as well as electrogram of nasal receptors (EGNR) Study Goa! Clinical
Slide 53: Fasedienol Reduction in Autonomic Biomarkers: Study Results
Fasedienol Reduction in Autonomic Biomarkers: Study Results * Three similarly designed Phase 1 studies were conducted in healthy volunteers (Total N=64; 32 male, 32 female) ina placebo-controlled crossover study design * Doses ranging from 0.2 pg to 0.4 ug were administered across these studies usin
Slide 54: Fasedienol Electrogram of Nasal Receptors (EGNR): Study Design
Fasedienol Electrogram of Nasal Receptors (EGNR): Study Design Fasedienol is administered intranasally while subjects are connected to sensors st i Simultaneous recordings of | the _ receptor potential, EEG evoked potentials and galvanic skin response in a healthy human subject. Local administration
Slide 55: 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 58 PH94B (ug) 0.0 04 16 1) is aa ee. 128 |-100w Dose-dependent electrical depolarization of human nasal chemosensory receptor cells in response to fasedienol
Slide 56: Fasedienol Generalized Anxiety Disorder: Phase 1B Study Design
Fasedienol Generalized Anxiety Disorder: Phase 1B Study Design €) To study the pharmacological effects of fasedienol in anxious female patients Psychometrics ond —_Pintsho respanders Psychometrics and Electrophysiology at 30 and 60 mins Electaphyology cused 7 | ad | improves) N=12 Non-responders ran
Slide 57: Fasedienol Generalized Anxiety Disorder: Phase 1B Study Results
Fasedienol Generalized Anxiety Disorder: Phase 1B Study Results Proof of concept in GAD led to the identification of SAD as the ideal indication for further clinical development 37 45 40 351 30 25 20 HAMILTON-A SCORE — 5 — CONTROL TREATED 8 melt Source: Montit and Groser 81, 2006 Significant decreas
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