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Vistagen Corporate Presentation May 2018 Website Corporate Presentation www.vistagen.com May 2018 : VTGN DEVELOPING NEWDEVELOPING GENERATION NEW GENERATION MEDICINES MEDICINES FOR FOR DEPRESSION DEPRESSION AND ANDOTHER OTHERCNS DISORDERS CNS DISORDERS Forward-looking www.vistagen.com Statements This presentation contains “forward-looking statements” Important factors that could cause actual results to differ within the meaning of the Private Securities Litigation Reform materially from those indicated by such forward-looking Act of 1995. These forward-looking statements concern our statements include, among others, those set forth in our product candidates, our development efforts, our Annual Report on Form 10-K for the year ended March 31, collaborations, our intellectual property, our financial 2017, filed with the Securities and Exchange Commission (SEC) condition, our plans and our development programs. These on June 29, 2017, as well as any updates to those risk factors statements involve risks, uncertainties and assumptions, and filed with the SEC from time to time in our periodic and are based on the current estimates and assumptions of the current reports on Forms 8-K and 10-Q. All statements management of VistaGen Therapeutics, Inc. (Company) as of contained in this presentation are made only as of the date of the date of this presentation and are subject to uncertainty this presentation, and the Company undertakes no duty to and changes. Given these uncertainties, you should not place update this information unless required by law. undue reliance on these forward-looking statements. 2 VistaGen Overview www.vistagen.com NASDAQ: VTGN Focused on Central Nervous System (CNS) disorders with high unmet need AV-101 has game-changing potential in depression and pain Long-term support from U.S. National Institutes of Health (NIH) Multiple potentially transformative clinical and corporate catalysts in 2018/2019 3 Past 6 Months – Most Productive in Company History www.vistagen.com December 2017 January 2018 $15 million underwritten public offering FDA Fast Track designation for AV-101 for MDD December 2017 March 2018 USPTO granted AV-101 US patent USPTO NOA for AV-101 US patent November 2017 Solid March 2018 USPTO NOA for AV-101 US patent EPO granted AV-101 EU patent Foundation October 2017 March 2018 AV-101 on cover of Journal of Pain ELEVATE Study Launch October 2017 April 2018 FDA green light for ELEVATE Phase 2 MDD study EPO NOI for AV-101 EU patent 4 Depression in the U.S. www.vistagen.com 1 in 4 women 1 in 6 men 1 in 8 1 diagnosed with depressive disorders age 12 and over takes an antidepressant U.S. DRUG-TREATED DEPRESSION MARKET IS LARGE WITH HIGH UNMET NEED2,3 11.6M 7.3M 5.1M U.S. Drug-Treated Inadequate response Treatment-resistant after 2nd MDD Patients to 1st Line antidepressant line antidepressant 63% treated with 2nd Line 44% treatment-resistant after antidepressant 2nd Line antidepressant 1: CDC – NCHS – National Center for Health Statistics, August 2017; 2: Rush AJ, et al. Am J. Psychiatry. 2006, 163(11): 1905-1917 (STAR*D Study), 3: Decision Resources 2016 5 Current Drug Treatment Options for Depression Fall Short www.vistagen.com Current Antidepressants Current Adjunctive Atypical Antipsychotics • Often do not work • Often do not work ‒ Initial treatment effective in 1 of 3 patients ‒ Only 10 to 20% of MDD patients respond • Slow to work • Safety concerns ‒ May take 4 to 6 weeks or more to achieve ‒ “Black Box” warnings, mortality in elderly, antidepressant effects cardiovascular complications, stroke • Numerous side effects • Numerous side effects ‒ Agitation, irritability, sexual dysfunction, ‒ Weight gain, metabolic syndrome, nausea, insomnia, dizziness, fatigue akathisia, tardive dyskinesia, anxiety 6 Current Depression Drug Treatment Paradigm: www.vistagen.com “Wait and See, Rinse and Repeat …” FIRST LINE SECOND LINE THIRD LINE SSRI/SNRI SSRI/SNRI SSRI/SNRI 4-6 Weeks or more 4-6 Weeks or more 4-6 Weeks or more Adjunctive Atypical Antipsychotics 7 The Ketamine Story: www.vistagen.com A Breakthrough Shift in the Depression Treatment Paradigm FUNDAMENTALLY FASTER-ACTING THAN HAS SIDE EFFECTS & DIFFERENT MOA ALL CURRENT DRUGS SAFETY CONCERNS § FDA-approved “[K]etamine, given § DEA Schedule III Drug anesthetic intravenously, might § Risk of Abuse § NMDAR antagonist be the most important § Dissociation § Works on a different breakthrough in § Hallucinations neurotransmitter antidepressant than antidepressants treatment in decades.” § Confusion § Dizziness § IV only (intranasal Thomas Insel spray in Phase 3) § Increased BP Former Director, U.S. National § Must be given in a Institute of Mental Health1 medical setting 8 NIMH Ketamine Study in Treatment-Resistant Depression www.vistagen.com BREAKTHROUGH RESULTS WITHIN 1 DAY OF A SINGLE TREATMENT 80% % Response Ketamine % Response Placebo 70% 71% ¥ Ketamine Responder Rates at 60% 1 Day in Patients with Treatment-resistant Depression 50% 53% 40% 35% ¥ Proportion of patients with treatment- 30% resistant depression with at least 50% improvement in depression rating 20% 1Zarate, C. A., Jr., et al. (2006) "A randomized trial of an 10% N-methyl-D-aspartate antagonist in treatment-resistant major depression." Arch Gen Psychiatry 63:856-864. 6% 6% 0% 0% 80 Minutes 110 Minutes 1 Day 9 Ketamine offers new hope for patients with depression, but is it a convenient and safe long-term solution? www.vistagen.com “Club Drug Ketamine Provides Hope in Fight Against Depression” “Drugs to Lift Depression in Hours Rather Than Weeks” 1: http://www.nimh.nih.gov/about/director/2014/ketamine.shtml 10 AV-101: A New Generation Antidepressant Candidate www.vistagen.com ü ORAL NMDAR GLYB ANTAGONIST ü MOA FUNDAMENTALLY DIFFERENT FROM ALL CURRENT FDA-APPROVED ANTIDEPRESSANTS ü MODULATES NMDAR; ACTIVATES AMPAR ü KETAMINE-LIKE ANTIDEPRESSANT EFFECTS ü NO KETAMINE-LIKE SIDE EFFECTS OR SAFETY O CONCERNS NH2 OH § Very well-tolerated in two NIH-funded Phase 1 safety studies § ELEVATE, Phase 2 depression study, results O expected in 1H 2019 Cl NH2 11 AV-101’s Mechanism of Action www.vistagen.com INHIBITS NMDA RECEPTORS, ACTIVATES AMPA RECEPTORS AV-101 Prodrug (4-Cl-KYN) 7-CI-KYNA L- (full antagonist) Activated Astrocytes AV-101 Active Metabolite (7-Cl-KYNA) Classic channel-blocking antagonists: Ketamine Lanicemine Phencyclidine 12 AV-101 vs. Ketamine in Published Preclinical Studies KETAMINE-LIKE ANTIDEPRESSANT EFFECTS, NO KETAMINE-LIKE SIDE EFFECTS www.vistagen.com Benefits AV-101 Ketamine Forced-swim EQUIVALENT Tail-suspension EQUIVALENT Learned-helplessness EQUIVALENT Novelty-suppressed feeding EQUIVALENT Negative Behavioral Effects AV-101 Ketamine Abusive potential No Yes Hyper movement No Yes Movement sensitization No Yes Circling and rearing No Yes Sensory-motor gating No Yes Zanos, P., et al. (2015). "The Prodrug 4-Chlorokynurenine Causes Ketamine-Like Antidepressant Effects, but Not Side Effects, by NMDA/GlycineB-Site Inhibition.“ J Pharmacol Exp Ther 355(1): 76-85. 13 AV-101 in Published NIH-Sponsored Phase 1 SaFety Studies www.vistagen.com WELL-TOLERATED WITH NO KETAMINE-LIKE SIDE EFFECTS OR SAFETY CONCERNS Phase 1a Phase 1b • Randomized, double-blind, placebo-controlled • Randomized, double-blind, placebo-controlled • Single oral dose, with sequential dose-escalation • Daily oral dose (14 days), sequential dose-escalation • 6 single dose levels: 120, 360, 720, 1,080 & 1,440 mg • 3 dose levels: 360, 1,080 and 1,440 mg • 36 subjects: 18 treatment, 18 placebo; 6 per cohort • 48 subjects: 36 treatment, 12 placebo; 16 per cohort RESULTS RESULTS • Well-tolerated, good bioavailability; no SAEs • Well-tolerated, good bioavailability; no SAEs • At higher doses, some subjects on AV-101 (none on • Multiple subjects on AV-101 (none on placebo) placebo) reported positive feelings of well-being reported positive feelings of well-being similar to similar to antidepressant effects reported with antidepressant effects reported with ketamine, but ketamine, but without ketamine’s side-effects without ketamine’s side-effects Wallace, M., et. al. (2017). “Randomized, Double-Blind, Placebo Controlled, Dose-Escalation Study: Investigation of the Safety, Pharmacokinetics, and Antihyperalgesic Activity of L-4 chlorokynurenine 14 in Healthy Volunteers.” Scand J Pain 17:243-251. NIMH-Sponsored Phase 2 Study www.vistagen.com Study Design Principal Investigator: Dr. Carlos Zarate, Jr., NIMH • Ongoing at NIMH clinic in Maryland • Double-blind, placebo-controlled, crossover design • Single oral dose monotherapy in patients with treatment-resistant depression, once per day/14 days • Emphasis on key biomarkers – CSF analysis, neuroimaging • Target enrollment: ca. 20 adults • Completion anticipated by end of 2018 Primary Endpoint: Secondary Endpoints: Safety and efficacy using standard Change from baseline in widely-accepted Hamilton Rating Scale (HDRS) measures of mood, depression and cognition 15 First Goal for AV-101 www.vistagen.com Displace Atypical Antipsychotics in the Depression Drug Treatment Paradigm FIRST LINE SECOND LINE THIRD LINE SSRI/SNRI SSRI/SNRI SSRI/SNRI 4-6 Weeks or more 4-6 Weeks or more 4-6 Weeks or more Adjunctive AV-101 Adjunctive Atypical Antipsychotics 16 ELEVATE Phase 2 Study for Depression www.vistagen.com Adjunctive Treatment for InadeQuate Response to Current Antidepressants Principal Investigator: Primary Endpoint: Secondary Endpoints: Maurizio Fava, MD, Harvard Efficacy demonstrated by Additional widely-accepted decrease on Montgomery-Asberg measures of mood, depression • Projected enrollment = ca. 180 patients Depression Rating Scale
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