Vistagen Therapeutics, Inc. · NASDAQ:VTGN
Vistagen Therapeutics — Investor Presentation (November 2022)
44 slides from Vistagen Therapeutics's investor presentation, Nov 23, 2022
Slide 1: Healthy minds make healthy communities
Healthy. minds make healthy communities, and we are innovating to change the trajectory of gl
Slide 2: Forward Looking Statements
Forward Looking Statements ‘This presentation contains “forward-looking statements within the meaning of the Private Secures Litigation Reform Act of 1955. These forward-looking statements involveknown and unknown seks that ae diffiulto predct and include allmaters that are nt historical facts, Thes
Slide 3: Our Pipeline
Our Pipeline Product Candidate Potential Indicators Preclinical Phase! Phase ll Phase Ill PH94B FDA Fast Track designation granted ‘Adjustment Disorder? PH1O Major Depressive Disorder® AV-101 & & Potential CNS Indications* FDA Fast Track designation granted in 2 indications ibeoneymasianatasnomena o
Slide 4: d the standard of for
d the standard of for d 7
Slide 5: 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 disabling disorder characterized by ... Debilitating emotionaland physical symptoms In everyday social or performance situations Emainal Symptoms = akin 53) Orn xqRe * suresofanity 2 Barta ol
Slide 6: SAD affects ~10% of the US population, with only ~20% helped by current pharmacotherapy
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 asa condition ‘ornot yet motivated to seek professionalhelp. Underserved Patients * Patients unsatisfied with or unwillingto use current tre
Slide 7: 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 disease burden in the US continues to grow, but scientific innovation has been lacking US Adult SAD Prevalence (in Millions)? ‘008 2005 2007 2008 zo 201 mais 2017 21s pay SAD isa highly prevalent condition which continues to affect incr
Slide 8: Current Standard of Care for SAD is Inadequate
Current Standard of Care for SAD is Inadequate There is no FDA-approved, fast-acting, acute treatment of anxiety for SAD Treatments For Social Anxiety Order Drug Fast- Acting | No Systemic No Long-term Side Non- ‘No Cognitive/ No Withdrawal | No Abuse Absorption | Effects Sexual Sedating | Motor Syn
Slide 9: SAD Patients Desire New Treatment Options
SAD Patients Desire New Treatment Options Efficacy against symptoms of SAD Fast onset for acute situations Ability to take with other drugs The Ideal SAD Medication is Safe & Works Quickly patient survey “4f | were open to taking medication, | would like it to subside my anxiety for the day and star
Slide 10: 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) sis /SNis beta locke enzos og 80h Therpy resthing OS 208 HOH sms Eremelyor Very Satisfied 15 Partly Sastedunsatstied Primary Care Ph
Slide 11: PH94B has Potential to be 1st FDA-approved Fast-acting Treatment of SAD
PH94B has Potential to be 1*t FDA-approved Fast-acting Treatment of SAD PH94B is a novel synthetic neuroactive steroid nasal spray <"> Differentiated MoA from antidepressants and benzos )_ Designed to be fast-acting, used as-needed and achieve functional improvement in anxiety-provoking social and p
Slide 12: PH94B is rated highly by physicians
PH94B is rated highly by physicians and recognized as a valuable and differentiated approach to treat SAD episodes on-demand Physician assessment of blinded PH94B product profile from large online survey vera Rating Fails unmet need ‘sungue Isanaddedbenet Ce ee ee ee 2 \otagen: Changi the Trajectory
Slide 13: Physicians indicate high intent to prescribe PH94B
Physicians indicate high intent to prescribe PH94B and note it would be appropriate for the majority of their SAD patients Physician assessment of a blinded PH94B product profile from large online survey ely to prescribe sapsych mCP (top2-boxof's ptscale) _vstagen: Changing the Traectoryof Mental He
Slide 14: PH94B's Innovative MOA via Olfactory-amygdala Circuit
PH94B’s Innovative MOA via Olfactory-amygdala Circuit ‘Microgram-level intranasal dose of PH94B (3.2 mcg) is administered PH94B engages peripheral receptors in nasal chemosensory neurons (ICN). Orfactory Bulb Once stimulated with PH94B, NCNs then trigger subsets of interneurons in the olfactory bulb
Slide 15: PH94B Phase 1 Data
PH94B Phase 1 Data Well-tolerated, reduced autonomic biomarkers and increased EGNR Statistically significant reduction in the autonomic biomarkers heart rate, respiratoryrate, and electrodermal activity in both men (n=8) and women (n=8). Also, 0.4 meg intranasal PH94B significantly increased the amp
Slide 16: Dose-dependent electrical depolarization of human nasal chemosensory receptors
Dose-dependent electrical depolarization of human nasal chemosensory receptors in response to PH94B PH94B (49) 08 od Ne | = Doses between 1.6 micrograms and 3.2 micrograms expected to be efficacious bas EGNR traces recorded from the nasal chemosensory ‘a tomy _ feceptorarea ina human volunteer durin
Slide 17: Dose-dependent effect of PH94B on intracellular calcium
Dose-dependent effect of PH94B on intracellular calcium in human nasal chemosensory cells suggests PH94B potential efficacy in both men and women 70 10" “0” [PH948] (M) (A) Concentration dependent effect of PH94B in isolated living human nasal chemosensory cells. Half maximal effective concentration
Slide 18: PH94B Significant Phase 2 Data in First SAD Study
PH94B Significant Phase 2 Data in First SAD Study PH94B demonstrated potential to be a fast-acting, well-tolerated SAD treatment Public speaking and social interaction challenges in clinical setting Phase 28 randomized, double-blind, placebo-controlled multi-center study (n=91) Primary efficacy endp
Slide 19: PH94B Phase 2 SAD Study: Public Speaking Challenge
PH94B Phase 2 SAD Study — Public Speaking Challenge Minute-by-minute SUDS scores at 2 (Bose ceo) 3 renient Pee ee A wemovteence | 267 0 g bcpenene and g ‘Standard Deviation a i (© P1948 group § as ° - ae ‘patients received 7+) Number of subjects | 45 6 g placebo atviit 210 3 $ Eran buen sv0s |S ia s
Slide 20: PH94B Phase 2 SAD Study: Social Interaction Challenge
PH94B Phase 2 SAD Study — Social Interaction Challenge Minute-by-minute SUDS scores ® ss Porto goon | A (© mst group wesnoiterence | 103 66 standadoevaton | 174 26 1 aceb rop number sayecs | * 1 Pea group 1-267 p=0.0009 coe 2 (elec Stess as # 2 subjectistothatwithaveojona grouper player aparthe onvr
Slide 21: PH94B PALISADE-1 and PALISADE-2 Phase 3 Clinical Trials
PH94B PALISADE-1 and PALISADE-2 Phase 3 Clinical Trials Public speaking challenges oy _ Principal investigator: Dr. Michael Liebowitz, Columbia University Objectives: Evaluate efficacy, safety, and tolerability of PH948 for the acute treatment of anxiety in adults with social anxiety disorder ‘Study
Slide 22: PH94B Significant Phase 2 Data in Second Published SAD Study
PH94B Significant Phase 2 Data in Second Published SAD Study PH94B demonstrated potential to be a novel, fast-acting treatment of anxiety in adults Outpatient self-administration up to 4x/day as-needed prior to anxiety- provoking social and performance situations in daily life Phase 2 randomized, do
Slide 23: Phase 2 Outpatient Cross-over Study Results (SUDS)
Phase 2 Outpatient Cross-over Study Results (SUDS) Multiple administrations as-needed in anxiety-provoking social and performance situations in daily life suos a ” Peak SUDS at Baseline and Weeks 1-4 “BES, | + Peak SUDS score for the PH94B group increased after é crossover to placebo, though not bac
Slide 24: Phase 2 Outpatient Cross-over Study Results (LSAS)
Phase 2 Outpatient Cross-over Study Results (LSAS) sas 2 100 LSAS at Baseline and Weeks 1-4 = mee “a Pscebo _vstagen: Changing the Traectoryof Mental HealthCare One Mindat Time + After the first 2 weeks of treatment, subjects who received PH94B dropped an average of 23.2 points on the LSAS, while th
Slide 25: Subjective Units of Distress Scale (SUDS)
Subjective Units of Distress Scale (SUDS) Primary efficacy endpoint in Phase 2 and Phase 3 clinical trials The SUDS measures the self-reportedintensity of anxiety and/or distressin patients with SAD Patients are asked torate theirlevelof anxiety/distress ona scale of 0-100. Physiological signs of di
Slide 26: Liebowitz Social Anxiety Scale (LSAS)
Liebowitz Social Anxiety Scale (LSAS) Efficacy endpoint required by the FDA for all prior SAD approvals The LSASis a 24-item (13 concerning performance anxiety and 11 pertaining to social situations) self-rated scale used to assess how social The LSASis scored by summing the item ratings. Below are
Slide 27: PH94B PALISADE Open Label Study
PH94B PALISADE Open Label Study Robust functional improvement in anxiety-provoking social and performance situations in daily life, as measured by the LSAS 1 Design: As needed administration of PH94B prior to acute anxiety-provoking social and performance situations in daily ~' fife, up to four time
Slide 28: PH94B Opportunities Beyond Social Anxiety Disorder
PH94B Opportunities Beyond Social Anxiety Disorder ~0.6M -7™M Adjustment Prevalence: Disorder ~18M Post-Traumatic Prevalence: Stress Disorder ~oM ProceduralAnxiety Prevalence: ~oM Post-Partum Anxiety Prevalence: Prevalence: Current treatment paradigm lacksmajor studies to support pharmacotherapy. ‘A
Slide 29: PH94B Phase 2A Adjustment Disorder with Anxiety
PH94B Phase 2A Adjustment Disorder with Anxiety Alarming increase in prevalence of anxiety-related disorders Adjustment disorder with anxiety is an emotional or behavioral reaction considered excessive or disproportionate to a sudden change, stressful event or major life change, such as loss of work
Slide 30: Slide 30
Slide 31: Significant Unmet Need in Major Depressive Disorder (MDD)
Significant Unmet Need in Major Depressive Disorder (MDD) 21 million US Adults had at least one major depressive episode in 2020 Untreated Pts: large percentage of patients remain untreated asa result of lack of options and discontinuations due to severe side effects, First Line Treated Pts: Only 1
Slide 32: PH10 is a Potential Fast-acting Stand-alone Treatment for MDD
PH10 is a Potential Fast-acting Stand-alone Treatment for Major Depressive Disorder PH10 is a novel synthetic neuroactive steroid nasal spray Designed for rapid onset antidepressant effects as a stand- alone monotherapy Differentiated MoA Designed to be non-systemic, non-sedating, non-addictive (doe
Slide 33: PH10's Mechanism of Action
PH10’s Mechanism of Action Microgram-levelintranasal dose of PH10 (3.2 mcg) engages peripheral receptors in nasal chemosensory neurons (NCNs) Chemosensory receptorsin nose Olfactory Bulb ve Trigger subsets of neuronsin the olfactory bulbs ‘Which stimulate “Fear On” neuronsin the limbic amygdala, o <
Slide 34: Similarities and Differences between PH94B and PH10
Similarities and Differences between PH94B and PH10 PH94B and PH10 are chemically distinct, but they are designed to act on different receptors on nasal chemosensory cells, resulting in different pharmacological effects. PHO4B Properties PH10 Nasal Chemosensory Cells Primary target Nasal Chemosensor
Slide 35: PH10 Antidepressant Effects in Published Exploratory Phase 2A Study
PH10 Antidepressant Effects in Published Exploratory Phase 2A Study (5) Study design: Phase 2A randomized, double-blind, placebo controlled, parallel design POC dlinica study J] Boseadmiistred:3.2megor6.4mcgof PH100r placebo given intranasally 2 times per day, every day for 8 weeks Enrollment:n=30 P
Slide 36: PH10 Phase 2A MDD Study (n=30)
PH10 Phase 2A MDD Study (n=30) Hamilton Depression (HAM-D-17) Score Reduction From Baseline 6.4 meg dose produced Sa rapid-onset and sustained antidepressanteffects in . 4s MDD patients with minimal side 3 effects & v0 g Sons 2 z Es = a0 os oe CC 3 @cingiienone) [we [on [ass 2 vs 2 i Poceto 9 i T T
Slide 37: PH10 Clinical Development
PH10 Clinical Development Stand-alone treatment for individuals with major depressive disorder Followinga successful Phase 2A study conducted in Mexico, a small Phase 1 study will be conducted prior to moving to Phase 2B development. Phase 1 Objectives: Evaluate safety and tolerability of PH10 in he
Slide 38: PH10 Opportunity Beyond Major Depressive Disorder
PH10 Opportunity Beyond Major Depressive Disorder Treatment Prevalence: Treatment lacks consistent symptom control, bother-some side effects and Resistant Depression “7M tolerance, and risk of abuse. Options do not provide acute symptomatic relief. Post Partum Prevalence: Concern of PPD treatmentsis
Slide 39: AV-101 For Multiple CNS Disorders
Vistagen <= N ¥ AV-101 Wa For Multiple ; CNS Disorders of _ Looking beyond the standa for CNS disorders
Slide 40: AV-101 + Probenecid for Multiple CNS Disorders
AV-101 + Probenecid for Multiple 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. + Well-tolerated in all clinical studies to date. + Two positive preclinical studies
Slide 41: AV-101's Potential MOA
AV-101’s Potential MOA \itagen: Changing the Trajectory of Mental HealthCare One Mind at Te Vistagen
Slide 42: AV-101 + Probenecid
AV-101 + Probenecid Preclinical data demonstrate substantial increases in brain concentrations of 7-Cl-KYNA Probenecid Increases 7-C-KYNA Brain Levels By > 35-fold” Probenecid Increases 7-Cl-KYNA Brain Levels By > 3.4-fold” ‘7-c-xynurene Ald 12 eet mane 5 Secetnomssiom gH 2 nar Patt z rovereiarany C
Slide 43: Our Mission
Our Mission Radically improve mental health - one mind at a time” Multiple clinical-stage drug candidates. Differentiated MOAs, &S bringing new valueto patients, physicians, and payers. Targeting large anxiety, depression and neurology markets. Cash to achieve multiple potential near-term catalysts.
Slide 44: Vistagen
Vistagen Healthy minds make healthy communities, and we are innovating to change the trajectory of global mental health care ... One Mind ata Time”
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