Anavex Life Sciences Corp. · NASDAQ:AVXL
Anavex Life Sciences — Investor Presentation (July 2021)
43 slides from Anavex Life Sciences's investor presentation, July 2021
Slide 1: Corporate Presentation
Corporate Presentation Christopher U Missling, PhD | President & CEO Nasdaq: AVXL | July 2021
Slide 2: Forward Looking Statement
Forward Looking Statement This presentation contains forward-looking statements made within the meaning of the Private Securities Litigation Reform Act of 1995 by Anavex® Life Sciences Corp. and its representatives. These statements can be identified by introductory words such as “expects,” “plans,”
Slide 3: ANAVEX Platform for Neurological Diseases
ANAVEX Platform for Neurological Diseases Neurological chronic conditions: SIGMAR1 activation Impaired as compensatory housekeeping function mechanism to chronic and impaired CNS diseases1 homeostasis 1 Brimson JM, Brimson S, Chomchoei C, et al. Using Sigma-ligands as part of a multi-receptor approa
Slide 4: Large Markets by Applying Precision Medicine Platform
Large Markets by Applying Precision Medicine Platform Today Tomorrow The Future • SIGMAR1 activation established as a • SIGMAR1 technology to • SIGMAR1 to open up new New Platform Class Succeed Traditional Modalities opportunities Beyond the Horizon - ANAVEX®2-73 (blarcamesine) - Alzheimer’s disease
Slide 5: Precision Medicine
Precision Medicine Biomarkers Increase Probability of Success 68.2% • Patient selection biomarkers 57.1% 46.3% • Higher therapeutic response 28.3% • Lower variability in the target population Phase II to Phase III Phase III to NDA/BLA Without Biomarkers With Patient Selection Biomarkers Thomas DW et
Slide 6: ANAVEX2-73 Establishes SIGMAR1 mRNA Predictive Biomarker of Efficacy
ANAVEX®2-73 Establishes SIGMAR1 mRNA Predictive Biomarker of Efficacy in Alzheimer’s, Parkinson’s and Rett Syndrome ANAVEX®2-73 improves functional ANAVEX®2-73 positive response in functional outcome in (ADCS-ADL*) outcome in Alzheimer’s disease patients patients with Parkinson’s disease correlate w
Slide 7: Aiming to Change the Course of Dementia
Aiming to Change the Course of Dementia … … Dementia is progressive and over time and a patient’s cognition will worsen ▶ Trajectory changed with ANAVEX®2-73 4.0-point calculated ADAS-Cog score improvement Direction of (p = 0.015) Improvement Visualize the improvement in calculated ADAS-Cog scores i
Slide 8: AI Powered, Biomarker Driven, Accelerated Development
AI Powered, Biomarker Driven, Accelerated Development Built on in- depth Molecular Understanding of SIGMAR1 Pathway Goal: Data from ~700 study participants, 3 indications, 6 trials Expedited Regulatory Process Pr ec isi Increased Probability on MMSE, ADCS-ADL M of Phase II / III MoCA, CDR MDS-UPDRS
Slide 9: Broad SIGMAR1 Platform Targeting Significant Unmet Medical Need
Broad SIGMAR1 Platform Targeting Significant Unmet Medical Need CANDIDATE PRECLINICAL PHASE 1 PHASE 2 PHASE 3 ALZHEIMER’S DISEASE AD ANAVEX®2-73-AD-004 ANAVEX®2-73 (Blarcamesine) PARKINSON’S DISEASE PARKINSON’S DISEASE DEMENTIA ANAVEX®2-73-PDD-001 *RETT SYNDROME EXCELLENCE ANAVEX®2-73-RS-003 Fast Tr
Slide 10: Worldwide Dementia Cases Projected to Grow to Over 130M by 2050
Worldwide Dementia Cases Projected to Grow to Over 130M by 2050 Targeting Large Market: Global Dementia Source: World Alzheimer’s Report 10
Slide 11: Costs Associated with Alzheimer's Treatment and Care are Unsustainable
Costs Associated with Alzheimer’s Treatment and Care in the U.S. are Unsustainable Age Prevalence of Global Alzheimer’s Disease and Dementias >$20 trillion Cumulative costs of Alzheimer’s and dementia care from 2015 to 2050 1 in 3 Medicare dollars will be spent on people living with Alzheimer’s and
Slide 12: Targeting Large Market Opportunities with Significant Unmet Medical Need
Targeting Large Market Opportunities with Significant Unmet Medical Need All U.S. Patient Numbers 1) Alzheimer’s Disease Facts and Figures. Alzheimers Dement 2018;14(3):367-429 2) Marras C et al 2018. npj Parkinson's Disease volume 4, Article number: 21 3) Based on prevalence number on orphaned 12
Slide 13: Anavex's Transformative Precision Medicine Platform
Anavex’s Transformative Precision Medicine Platform ! ANAVEX®2-73 (Blarcamesine) Rett Syndrome Program Received Fast Track Designation and is Eligible for Pediatric Priority Review Voucher ! Pursuing Large Markets with High Unmet Need by Applying Genetic Precision Medicine ! Novel Upstream CNS Mecha
Slide 14: Catalysts to Drive Value
Catalysts to Drive Value The company has multiple clinical milestones ✅ Complete data ANAVEX®2-73 U.S. Rett syndrome Phase 2 study ✅ Complete data ANAVEX®2-73 Parkinson’s disease dementia (PDD) Phase 2 study ! Top-line data AVATAR: Potentially pivotal Phase 2/3 adult RTT clinical trial – expected 2H
Slide 15: Clinical Trials
Clinical Trials Mechanism of Action (MoA) and Clinical Data: • Rett Syndrome (RTT) • Parkinson’s Disease Dementia (PDD) • Alzheimer’s Disease (AD)
Slide 16: ANAVEX2-73 MoA: SIGMAR1 Activation Prevents Cellular Stress
ANAVEX®2-73 MoA: SIGMAR1 Activation Prevents Cellular Stress Before and After RNA Gene Transcription Source: Couly et al., Knocking Out Sigma-1 Receptors Reveals Diverse Health Problems. Cell Mol Neurobiol (2020); Lee et al., Sigma-1 receptor chaperones rescue nucleocytoplasmic transport deficit see
Slide 17: SIGMAR1 Activation Modulates Multiple Aspects of Neurodegenerative Processes
SIGMAR1 Activation has been Shown to Modulate Multiple Aspects of Neurodegenerative Processes Sigma-1 receptor agonists ANAVEX®2-73 enhances Sigma-1 receptor agonists have been shown to restore autophagy and alleviates Tau have a neuroprotective effect neuronal functions in pathology in neurodegener
Slide 18: ANAVEX2-73 Establishes Proof-of-Concept and SIGMAR1 Target Occupancy
ANAVEX®2-73 Establishes Proof-of-Concept and SIGMAR1 Target Occupancy 2D [18F]FTC-146-PET imaging of ANAVEX®2-73: Dose- dependent ANAVEX®2-73 Target Engagement 0 mg /kg 1 mg/kg 10 mg/kg 30 mg/kg 100 Percent Sigma-1 Receptor Occupancy 80 60 40 20 0 0 5 10 15 20 25 30 mg/kg of ANAVEX2-73 Source: Reyes
Slide 19: Interface of ANAVEX2-73-activated Pathway Analysis and Disease Biology
Interface of ANAVEX®2-73-activated Pathway Analysis and Disease Biology Using mRNA Differential Gene Expression with Focus on SIGMAR1 Pathway Differen'al Gene Expression Baseline t1 Genes of interest ~700 Patients X 26K genes X 2 timepoints mRNA0 mRNA1 ANAVEX®2-73 Molecular Patient Pathway Biology Si
Slide 20: What is Rett Syndrome?
What is Rett Syndrome? Devastating neuro-developmental disease in girls with both movement impairment and cognitive impairment Rett Syndrome (RTT) § Non-inherited genetic postnatal disorder caused by mutations in the MECP2 gene Ø Occurs almost exclusively in girls Ø Leads to severe impairments, affe
Slide 21: Rett Syndrome U.S. Phase 2 Trial Design Overview
Rett Syndrome U.S. ANAVEX®2-73-RS-001 Phase 2 Trial Design Overview Randomized, Double-blind, Placebo-controlled Clinical Trial Arm Number of participants ANAVEX2-73 n=15 (once daily 5mg liquid dose) Placebo n=10 (once daily PBO liquid dose) Week 0 Week 4 Week 7 (Baseline) (End of Trial [EOT]) Effic
Slide 22: Phase 2: Improvement in All Key Domains
Phase 2: Improvement in All Key Domains ANAVEX®2-73 Treatment Resulted in a Statistically Significant Improvement for All Patients with Rett Syndrome in the RTT-Relevant Endpoints RSBQ, CGI-I, ADAMS RSBQ CGI-I Responder Non-Responder Responder Non-Responder 12 10 (66.7%) 15 13 (86.7%) Number of Pati
Slide 23: Favorable Efficacy Already at Low ANAVEX2-73 Doses
Favorable Efficacy Already at Low ANAVEX®2-73 Doses Estimated Difference Age, y Weight, kg between Active and Placebo median median RSBQ Total Score ANAVEX2-73 low -14.5 24.00 45.10 dose (5 mg)* trofinetide high -4.4 9.41 23.05 dose (400 mg/kg)** ANAVEX®2-73 Phase 2 RSBQ Total Score compares favorab
Slide 24: Favorable Adverse Event Profile of ANAVEX2-73
Favorable Adverse Event Profile of ANAVEX®2-73 Adverse Events (>10%) Diarrhea Vomiting Fever (Pyrexia) ANAVEX2-73 0% 0% 0% (5 mg)* trofinetide 56% 22% 11% (400 mg/kg)** ANAVEX®2-73 Phase 2 Adverse Event profile compares favorably with other published historical trial * All participants ITT ** Glaze
Slide 25: Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score
Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score Prespecified Primary Efficacy Endpoint RSBQ Total Score Improvement with ANAVEX2-73 15.00 RSBQ Total Change from Baseline 10.00 (LS mean ± SEM) 5.00 Change from Baseline Placebo 0.00 p=0.009 -5.00 p=0.006 Improvement -10.00 Change from Baselin
Slide 26: RSBQ Subscale Scores
RSBQ Subscale Scores Significant and Balanced Improvements across all Subscales (observed at End of Trial) RSBQ Subscale Score 40% 20% 0% -20% Improvement -40% -60% -80% Body Repetitiv Rock ing Night- General Breathing Hand e Face Fear/Anxi Walki ng/ and time Mood Problems Behavi ors Mov eme ety Sta
Slide 27: ADAMS Total Score
ADAMS Total Score Clinically Validated Efficacy Endpoint ADAMS Total Score Improvement with ANAVEX2-73 8.00 6.00 ADAMS Total Change from Baseline 4.00 2.00 (LS mean ± SEM) 0.00 Change from Baseline Placebo -2.00 Improvement -4.00 p=0.005 -6.00 -8.00 -10.00 -12.00 Change from Baseline ANAVEX2-73 -14.
Slide 28: ADAMS Subscale Scores
ADAMS Subscale Scores Significant and Balanced Improvements across all Subscales (observed at End of Trial) ADAMS Subscale Scores 40% 30% 20% 10% 0% -10% Improvement -20% -30% -40% -50% Manic/Hyper Obsessive Depressed Social General active Compulsive Mood Avoidance Anxiety Behavi or Behavi or Placeb
Slide 29: Phase 2/3 Rett Syndrome AVATAR Study
ANAVEX®2-73-RS-002 Phase 2/3 Rett Syndrome AVATAR Study N=33 * 7 … and Open Label Extension (OLE) 48weeks ClinicalTrials.gov: NCT03941444 RTT pa&ent popula&on ANAVEX®2-73 Primary and Secondary Endpoints Active dose# • RSBQ, CGI-I • ADAMS, Sleep function • Diagnosis of • Seizure activity confirmed RT
Slide 30: Phase 2/3 Rett Syndrome EXCELLENCE Study
ANAVEX®2-73-RS-003 Phase 2/3 Rett Syndrome EXCELLENCE Study N=84 12 … and Open Label Extension (OLE) 48weeks ClinicalTrials.gov: NCT04304482 RTT pa&ent popula&on ANAVEX®2-73 Primary and Secondary Endpoints Active dose# • RSBQ, CGI-I • ADAMS, Sleep function • Diagnosis of • Seizure activity confirmed
Slide 31: Parkinson's Disease Dementia (PDD)
Parkinson’s Disease Dementia (PDD) Up to 80 percent of those with Parkinson’s disease eventually experience Parkinson’s disease dementia Parkinson’s Disease Dementia § Parkinson’s disease is a fairly common neurological disorder in older adults, estimated to affect nearly 2 percent of those older th
Slide 32: ANAVEX2-73 PoC Phase 2 PDD Study Design
ANAVEX®2-73 PoC Phase 2 PDD Study Design A Phase 2 trial to Assess the Safety, Tolerability and Efficacy of ANAVEX®2-73 (blarcamesine) Oral Capsules in the Treatment of Parkinson’s Disease Dementia 1:1:1 randomization 2-week baseline period 3-week up-titration period 11-week target dose treatment pe
Slide 33: Improved MDS-UPDRS Total Score in Parkinson's Disease Dementia Phase 2
ANAVEX®2-73 Improved MDS-UPDRS Total Score in Placebo-Controlled Parkinson’s Disease Dementia Phase 2 Study MDS-UPDRS Total score -14.51 improvement is clinically relevant and corresponds to a relative improvement of 18.9 % over 14 weeks Estimated Difference between Active and Placebo: -14.51 points
Slide 34: Key Cognitive Domains
Key Cognitive Domains Key cognitive features addressed by ANAVEX®2-73 (blarcamesine) The criteria from the National Institute on Aging and Alzheimer’s Association (NIA-AA) workgroup mention the following five Addressed in PoC cognitive domains when diagnosing MCI-AD: Phase 2 PDD Study (a) Episodic m
Slide 35: Significant Improvements in Episodic Memory with Increased Dose
Significant Improvements in Episodic Memory with Increased Dose ANAVEX®2-73-PDD-001 Study: Dose-dependent, statistically significant improvement of Quality of Episodic Memory with ANAVEX®2-73 (blarcamesine) Quality of Episodic Memory (counts) All participants Time: 14 weeks change from baseline • A
Slide 36: Summary of Topline Results
Summary of Topline Results: Broad and Significant Effects with ANAVEX®2-73 (blarcamesine) in PDD Patients • ANAVEX®2-73 (blarcamesine): a novel, oral, investigational sigma-1 receptor (Sig-1R / SIGMAR1) agonist with multimodal activity • Data confirm SIGMAR1 as gene “signature” biomarker of response
Slide 37: Alzheimer's Disease (AD)
Alzheimer’s Disease (AD) Alzheimer’s disease is a progressive, irreversible neurological disease and the most common cause of dementia Alzheimer’s Disease (AD) § Alzheimer’s disease incidence highly correlates with age Ø AD prevalence in US: ~5,700,000 Ø Estimated 50 million people live with dementi
Slide 38: Improved MMSE and ADCS-ADL Scores in Phase 2a AD Study
ANAVEX®2-73 Demonstrated Improved MMSE1 and ADCS-ADL2 Scores in Phase 2a AD Study through 148 Weeks Adjusted change in ADCS-ADL2 (±SE) Adjusted change in MMSE1 (±SE) N=8 N=8 N=13 N=13 p-value < 0.0008 p-value < 0.0001 Source: Hampel et al. A precision medicine framework using artificial intelligence
Slide 39: Biomarker Driven Development Strategy in Alzheimer's Disease
ANAVEX®2-73 Biomarker Driven Development Strategy in Alzheimer’s Disease Demonstrated Improved MMSE and ADCS-ADL through Pa:ent Clinical Data 148 weeks for all pa'ents Cognitive Scores Sleep Questionnaires Other Scores Dose, PK KEM® Genomic Data Novel Genomic Biomarkers of Response Iden6fied in Phase
Slide 40: Phase 2b/3 Alzheimer's Disease and ATTENTION-AD OLE Study
ANAVEX®2-73 Phase 2b/3 Alzheimer's Disease and ATTENTION-AD OLE Study N=450 48 … and Open Label Extension (OLE) 96weeks ClinicalTrials.gov: NCT03790709 Early AD pa&ent popula&on ANAVEX®2-73 Primary Endpoints High dose# • Confirmed amyloid • ADAS-Cog pathophysiology • ADCS-ADL (CSF/amyloid PET) • Saf
Slide 41: Anavex is pursuing Large Markets by Applying Precision Medicine Platform
Anavex is pursuing Large Markets PRECISION MEDICINE PLATFORM IMPROVES CHANCE OF CLINICAL SUCCESS by Applying Precision Medicine Testing for biomarkers demonstrated improved clinical response to ANAVEX ®2-73 in Rett syndrome, Parkinson’s and Alzheimer’s Platform to Develop Treatments patients correla
Slide 42: Anavex Life Sciences Expertise
Anavex Life Sciences Expertise Management Team Christopher U. Missling PhD - President & CEO Walter E Kaufmann, MD - Chief Medical Officer Stephan Toutain, MS, MBA – Chief Operating Officer Emmanuel O Fadiran, RPh, PhD - SVP of Regulatory Affairs Daniel Klamer, PhD - VP of Business Development & Sci
Slide 43: Contact Us
Contact Us Corporate Office Anavex®Life Sciences Corp. 51 West 52nd Street, 7th floor New York, NY 10019 1-844-689-3939 Shareholder & Media Relations [email protected] www.anavex.com NASDAQ: AVXL 43
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