Vistagen Therapeutics, Inc. · NASDAQ:VTGN
Vistagen Therapeutics — Investor Presentation (April 2020)
46 slides from Vistagen Therapeutics's investor presentation, Apr 3, 2020
Slide 1: Looking Beyond Current Treatments for CNS Diseases and Disorders
Ke) VistaGene Therapeutics www.vistagen.com j* Nasdaq: VTGN Spring 2020 LOOKING BEYOND CURRENT TREATMENTS FOR CNS DISEASES AND DISORDERS WITH HIGH UNMET NEED
Slide 2: Forward-looking Statements
www.vistagen.com Forward-looking Statements This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements concern our product candidates, our development efforts, our collaborations, our intellectu
Slide 3: Looking Beyond Current Treatments for CNS Diseases and Disorders with High Unmet Need
Looking Beyond Current Treatments for CNS Diseases and Disorders with High Unmet Need VistaGen is developing differentiated new generation medications for large and growing mental health and neurology markets where current treatments are inadequate to meet the needs of millions of patients worldwide
Slide 4: Looking beyond current therapies for CNS diseases and disorders
www.vistagen.com Looking beyond current therapies for CNS diseases and disorders with high unmet need 3 differentiated clinical-stage product candidates Rapid-onset Each candidate has potential in multiple markets Key, VistaGen ‘Therapeutics
Slide 5: Our CNS Pipeline
Our CNS Pipeline Product ie of Social Anxiety Disorder"? _TCCCTCSCSS ZZ Generstzed Ansety Deore? Postpartum Anxiety® =a 677 )> Preoperative Anxiety® rrr f 7 £5 8> Panic Disorder* Dn fF 755> PTs? : Dn PF 7Fs> Major Depressive Disorde! PG Treatment-Resistant Depression’ — UY Na» Suicidal Ideation? Ey
Slide 6: PH94B: Novel, fast-acting, non-systemic therapy
VistaGenoe Novel, fast-acting, non-systemic therapy for: Therapeutics * Social Anxiety Disorder * Generalized Anxiety Disorder * Postpartum Anxiety » Preoperative/Pre-testing (MRI) Anxiety » Panic Disorder + PTSD
Slide 7: Social Anxiety Disorder (SAD) in the U.S.
£ g 8 g $ i 123 National institutes of Health Social Anxiety Disorder (SAD) in the U.S. Ke) VistaGens Therapeutics More than Just Shyness the most prevalent Men, of is OmF calth conditions in the y..°9/ Affects as many as 20 million’ Americans anxiety and fear in everyday social and performance situ
Slide 8: Current SAD Drug Treatments Fall Short
& ¢ \( } Current SAD Drug Treatments Fall Short Ie 3 Therapeutics i EDA Not FDA-Approved re * Prescribed Off-label * APPROVED Antidepressants (2 SSRIs, 1 SNRI) Benzodiazepines & Beta Blockers * Slow onset, chronic administration x Addiction risk x May worsen anxiety initially x Significant potential
Slide 9: PH94B: First-in-class SAD therapy
VistaGenoe Therapeutics First-in-class; different from all SAD therapies Successful Phase 2 completed U.S. Phase 3 launch in 2H 2020 Rapid onset efficacy (10-15 minutes), exceptional safety Microgram dosing (3.2 ug), non-systemic Well-tolerated, non-sedating, non-addictive FDA Fast Track designation
Slide 10: PH94B Mechanism of Action
www.vistagen.com PH94B Mechanism of Action = Engages nasal chemosensory receptors, which activate neural circuits in the brain that suppress fear and anxiety = Nasal chemosensory receptors activate olfactory bulb (OB) neurons that project to the limbic amygdala = Modulates activity of the limbic-hyp
Slide 11: PH94B Reduced Social Anxiety in Published Phase 2 Study
PH94B Reduced Social Anxiety Produced by Public Speaking ie. and Social Interaction Challenges in Published Phase 2 Study nas www.vistagen.com Phase 2 multi-center, randomized, double-blind, placebo-controlled, parallel design laboratory study 91 female patients with SAD, ages 19-60 1.6 pg of PH94B
Slide 12: Published PH94B Phase 2 Study — Public Speaking (n = 91)
Published PH94B Phase 2 Study — Public Speaking (n = 91) Visit 3 (Treatment Phase) 70 Placebo Subjective Units of Distress Score 60 Ke) VistaGens ‘Therapeutics PH94B Rapidly Reduced Anxiety in Response to Public Speaking Challenge (SUDS) so Active Group: Placebo Group: Mean Difference = 26.7 Mean Di
Slide 13: Published PH94B Phase 2 Study — Social Interaction (n = 91)
Published PH94B Phase 2 Study — Social Interaction (n = 91) Ke) Visit 3 (Treatment Phase) 60 55 50 Subjective Units of Distress Score 45 (SuDS) 40 PHO4B 35 30 i 2 i} oa Anticipatior Performance ‘Anxiety i Chall Challenge D t-=>| Challenge 8 eens J 15-min "| instructions Patient is told that will joi
Slide 14: PH94B Reduced Anxiety in Pilot Phase 2 Real World SAD Study
Ke) PH94B Reduced Anxiety in a Pilot Phase 3 “Real World” VIsaGerie SAD Cross-over Study www.vistagen.com Randomized, double-blind, 4 week (two 2-week periods), cross-over study 22 male and female patients ages 18-65 with social anxiety disorder (SAD) Before a potentially stressful social situation,
Slide 15: PH94B Pilot Phase Cross-over Study
www.vistagen.com PH94B Pilot Phase 3 Cross-over Study Peak Suds at Baseline and Weeks 1-4 P1045, MEE Placebo Ke) VistaGens ‘Therapeutics * Early suggestions of drug/placebo differences were seen in week 1 and week 2 SUDS scores: average change in SUDS at week 1 was 16.1 for PH94B vs. 3.4 for placebo
Slide 16: PH94B Pilot Phase Cross-over Study
www.vistagen.com Ke) PH94B Pilot Phase 3 Cross-over Study agate * In the sample as a whole, drop in LSAS scores after treatment did not differ between groups because subjects receiving PH94B before receiving placebo continued to improve when crossed over to placebo LSAS at Baseline and Weeks 1-4 * A
Slide 17: PH94B U.S. Phase 3 Study for SAD
Ke) VistaGens Therapeutics www.vistagen.com PH94B U.S. Phase 3 Study for SAD Principal Investigator: Dr. Michael Liebowitz, Columbia University, New York * Randomized, double-blind, placebo-controlled, parallel design monotherapy study * 3.2 1g of PH94B or placebo for 4 weeks * Multi-center, ca. 15
Slide 18: PH94B Commercial Opportunity — U.S. SAD Market
www.vistagen.com SUBSTANTIAL UNMET NEED Though SAD is highly prevalent with a significant impact on quality of life recognition, diagnosis and treatment remain low. There are few novel medications in development. PH94B promotion, SAD disease education and DTC efforts will drive physician urgency to
Slide 19: The "Benzo Epidemic"
Ke) VistaGens ‘Therapeutics The “Benzo Epidemic” www.vistagen.com “It's not just opioids: What doctors want you to know about benzos” EMhealth “Benzodiazepines: Primary Care’s New Drug Problem” Psychiatry Advisor “Use of Opioids, Benzodiazepines at Same Time is Skyrocketing.” FORTUNE
Slide 20: Impact of Social Media on Mental Health
Impact of Social Media on Mental Health Ke VistaGens ‘Therapeutics www.vistagen.com “Why Instagram is the Worst Social Media for Mental Health” “Association between Social Media Use and “How ‘Keeping Up With TIME Depression among U.S. The Joneses’ On Social “How Removing ‘Likes’ Young Adults” Media
Slide 21: PH94B: Additional Indications Beyond SAD
PH94B: Additional Indications Beyond SAD www.vistagen.com Postpartum Anxiety Panic Disorder Generalized Anxiety Disorder PH94B Preoperative Post- & Traumatic Pre-testing Stress (mri) Disorder Anxiety Ke) VistaGens Therapeutics Potential Next Steps: Phase 2a POC studies 21
Slide 22: PH10: Novel, safe, fast-acting therapy for depression
Ke) VistaGene Therapeutics Novel, safe, fast-acting therapy for: Major Depressive Disorder Treatment-Resistant Depression \ Postpartum Depression Suicidal Ideation
Slide 23: Major Depressive Disorder in the U.S.
www.vistagen.com Ke) VistaGens Major Depressive Disorder in the U.S. meen 1in 4 women 1in6men 1in8 ee = RAG So He a diagnosed with depressive disorders age 12 and over takes an antidepressant’ LARGE ADDRESSABLE MARKET WITH HIGH UNMET NEED? 11.6M Drug-treated patients with Major Depressive Disorder 7
Slide 24: FDA-Approved MDD Treatments Fall Short
Ke) VistaGens Therapeutics www.vistagen.com FDA-Approved MDD Treatments Fall Short Current Oral Antidepressants Atypical Antipsychotics * Often do not work; slow to work * Often do not work — Initial ADT effective in 1 of 3 patients — Only ca. 20% of patients respond to — May take 4 to 6 weeks or mo
Slide 25: but is it a long-term solution?
www.vistagen.com but is it a long-term solution? | “Ketamine Depression Treatment Passes Another Trial, But Isn’t For Everyone” Forbes {©} Janssen Global Servi 4.Johason & Ketamine-based therapy offers new hope to millions with TRD, Ke) VistaGens Therapeutics “In the clinical trials, the most common
Slide 26: PH10: First-in-class antidepressant
Ke) VistaGene First-in-class; different from all antidepressants Therapeutics Successful Phase 2a completed Rapid-onset antidepressant effects Microgram dosing, non-systemic Well-tolerated, minimal side effects Preparing for U.S. Phase 2b in 1H 2021 Potential stand-alone and adjunctive at-home thera
Slide 27: PH10 Mechanism of Action
i } 3 i PH10 Mechanism of Action = Engages nasal chemosensory receptors, which activate neural circuits in the brain leading to antidepressant effects Nasal chemosensory receptors activate olfactory bulb (OB) neurons that project to the limbic amygdala OB neurons stimulate neurons in the limbic amyg
Slide 28: PH10 Demonstrated Antidepressant Effects in MDD Patients
www.vistagen.com Ke) PH10 Demonstrated Antidepressant Effects in MDD Patients VistaGen: ‘Therapeutics in Published Exploratory Phase 2a Study * Phase 2 randomized, double-blind, placebo-controlled, 8-week, parallel design POC study conducted in Mexico City 30 male and female MDD patients, ages 18-65
Slide 29: PH10 Exploratory Phase 2a MDD Monotherapy Study (n = 30)
www.vistagen.com PH10 Exploratory Phase 2a MDD Monotherapy Study (n = 30) Hamilton Depression (HAM D) Score Reduction From Baseline -10.0 712.5 -15.0 Reduction in HAM D from Baseline -17.5 (n=30) Txwki TxwWk2 Txwk3 Txwk4 TxwWkS Txwk6 Txwk7 Txwks 3.2 1g (lV Dose) 01 74, 6.4 11g ( Dose) 22 .95, Placeb
Slide 30: PH10 U.S. Phase 2b Development Plan for MDD
Ke) VistaGens Therapeutics PH10 U.S. Phase 2b Development Plan for MDD www.vistagen.com Principal Investigator: Dr. Michael Liebowitz, Columbia University, New York * Randomized, double-blind, placebo-controlled, multi-center monotherapy study * MDD patients with zero or 1 prior failure on a standar
Slide 31: PH10: Additional Indications Beyond MDD
i) PH10: Additional Indications Beyond MDD MistaGere ‘Therapeutics www.vistagen.com Potential Next Steps: Phase 2a studies PH10 Treatment- Resistant Depression Postpartum Depression 31
Slide 32: AV-101: Novel oral NMDA receptor GlyB antagonist
Ke) VistaGene Novel oral NMDA receptor GlyB antagonist for: Therapeutics » Major Depressive Disorder NH2 » Suicidal Ideation x » Neuropathic Pain » Epilepsy » Levodopa-Induced —— associated with Parkinson’s Therapy Dickens, D., (2019, December). Drug transporters at the blood-brain barrier as target
Slide 33: AV-101
m™ AV-101 Ke) VistaGene « Oral prodrug of 7-Cl-KYNA Therapeutics = Selective NMDA receptor glycine site antagonist = Well-tolerated in all clinical studies to date « No dissociative side effects or treatment-related SAEs = Non-addictive, non-sedating = FDA Fast Track designations in MDD and pain
Slide 34: AV-101's Mechanism of Action
Ke) VistaGens AV-101’s Mechanism of Action Therapeutics 4-CI-KYN (prodrug) — 7-CI-KYNA (active metabolite) www.vistagen.com NMDA Receptor Pharmacology Kt fo) AV-101 Oral Prodrug (4-Cl-KYN) L4-chlorokynurenine (4-CHKYN) (oral delivery to CNS) Activated * Astyoetes OH AV-101 Active Metabolite (7-Cl-KY
Slide 35: AV-101 in Published Phase 1 Clinical Trials
AV-101 in Published Phase 1 Clinical Trials VistaGen- ‘Therapeutics i Ka) 3 H AV-101 is very well-tolerated and orally bioavailable * Plasma half-life is about 2 hr Plasma levels of AV-101 in normal . volunteers following single oral dosing * Dosed up to 1440 mg daily for 2 weeks A 70000 + Adverse e
Slide 36: AV-101 and Adjunctive Probenecid
§ | AV-101 and Adjunctive Probenecid Recent preclinical studies demonstrate substantial increases in rodent Ke) VistaGens Therapeutics brain concentrations of both AV-101 (4-CI-KYN) and 7-CI-KYNA Probenecid increases AV-101 (4-CI-KYN) brain levels by ~ 7 fold 4-Cl-Kynurenine © Vehicle + vehicle 4 Ve
Slide 37: AV-101 with Adjunctive Probenecid for Multiple Indications
Ke) AV-101 with Adjunctive Probenecid for Multiple Indications V'st2Sen: ‘Therapeutics www.vistagen.com Major Depressive Disorder Suicidal Potential Next Steps: Neuropathic Reston Pain Phase 2a POC studies with AV-101 adjunctive probenecid Levodopa- Induced 8 Dyskinesia tt associated with ee” Parkin
Slide 38: AV-101 for Major Depressive Disorder
www.vistagen.com AV-101 for Major Depressive Disorder agate Ketamine-like antidepressant effects, no ketamine-like side effects in published preclinical studies? No differentiation in initial Phase 2 MDD study (1440 mg with adjunctive ADT) Well-tolerated, no psychotomimetic side effects or serious a
Slide 39: AV-101 for Suicidal Ideation
www.vistagen.com Ke) Medicine aylor VistaGens AV-101 for Suicidal Ideation US.Department BRM VistaGens of Teens Affairs ee Baylor / VA Phase 1b NMDAR Target Engagement Study (n=10) ° Successful target engagement relevant to NMDAR antagonism and suicidal ideation Double-blind, placebo-controlled, cro
Slide 40: AV-101 for Neuropathic Pain in Preclinical Studies
AV-101 for Neuropathic Pain in Preclinical Studies nara Significant dose-response with similar efficacy in a rat model of a mononeuropathy as compared to gabapentin (Neurontin) and pregabalin (Lyrica)? www.vistagen.com Robust analgesic effects, similar to gabapentin and pregabalin, but fewer side ef
Slide 41: AV-101 for Seizures in Preclinical Studies
\} AV-101 for Seizures in Preclinical Studies Mees * Multiple published reports demonstrate that, if delivered by injection into brain, 7-Cl-KYNA substantially reduces the frequency of seizures in animal models www.vistagen.com * AV-101 dramatically reduced seizures in two rodent models of seizures?
Slide 42: AV-101 for Levodopa-induced Dyskinesia in Preclinical Studies
' AV-101 for Levodopa-induced Dyskinesia associated Theis with Parkinson’s Therapy in Preclinical Studies ° Antidyskinetic effects in the MPTP primate model similar to those generally observed with amantadine therapy, but without adverse effects experienced with amantadine * Significantly (p = 0.01)
Slide 43: Distinguished Clinical and Regulatory Advisors
www.vistagen.com HARVARD UNIVERSITY Convama University GY DevartMent or Psycutatey Maurizio Fava, M.D. Professor of Psychiatry, Harvard Medical School; Director, Division of Clinical Research, Massachusetts General Hospital (MGH) Research Institute; Executive Director, MGH Clinical Trials Network an
Slide 44: Experienced Team
www.vistagen.com Ke) Experienced Team VistaGens Leading Execution Shawn K. Singh Chief Executive Officer + 25 years of experience with biopharmaceutical companies, a healthcare venture capital firm and a profitable CRO * Artemis Neuroscience; SciClone Pharmaceuticals; Cato BioVentures; Cato Research
Slide 45: Looking beyond current therapies for CNS diseases and disorders
www.vistagen.com Looking beyond current therapies for CNS diseases and disorders with high unmet need 3 differentiated clinical-stage product candidates Rapid-onset Each candidate has potential in multiple markets Key, VistaGen ‘Therapeutics
Slide 46: Looking Beyond Current Treatments for CNS Diseases and Disorders
Ke) VistaGene Therapeutics LOOKING BEYOND CURRENT TREATMENTS FOR CNS DISEASES AND DISORDERS WITH HIGH UNMET NEED £ g ie & & £ 2 3 3 3 g® Nasdaq:vTen
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