Anavex Life Sciences Corp. · NASDAQ:AVXL
Anavex Life Sciences — Investor Presentation (September 2021)
43 slides from Anavex Life Sciences's investor presentation, Sep 13, 2021
Slide 1: Anavex Life Sciences Corp. September 2021
ei] an avex LIFE SCIENCES Corp. iq: AVXL | September 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 \ Ni EPP =s wae re Neurological chronic conditions: Impaired housekeeping function and impaired homeostasis SIGMAR1 activation as compensatory mechanism to chronic CNS diseases’
Slide 4: Large Markets by Applying Precision Medicine Platform
Large Markets by Applying Precision Medicine Platform ‘6 Today morrow The Future IGMAR1 activation establis + SIGMAR1 technology to + SIGMARY to open up new w Platform Class ceed Traditional Mi 5 opportunities © - ANAVEX®2-73 (blarcamesine) = Alzheimer's disease - Expanded CNS indications Clinical s
Slide 5: Precision Medicine
ad Precision Medicine Biomarkers Increase Probability of Success 68.2% 57.1% 46.3% 28.3% | Phase II to Phase Ill Phase Ill to NDA/BLA =Without Biomarkers = With Patient Selection Biomarkers Thomas DWet al. Clinical Development Success Rates 2011-2020. BIO | QLS Advisors | Informa UK Ltd 2024
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
Slide 7: Aiming to Change the Course of Dementia
Aiming to Change the Course of Dementia ... ... Dementia is progressive and over time a patient’s cognition will worsen > Trajectory changed with ANAVEX®2-73 Calculated ADAS-Cog Improvement Phase 2 ANAVEX2-73-PDD-001, ‘ANAVEN2-72.°00-001 ‘ANAVER2-73 50m Calculated ADAS-Cog Phase 2a ANAVEX2-73 vs oth
Slide 8: AI Powered, Biomarker Driven, Accelerated Development
Al Powered, Biomarker Driven, Accelerated Development Built on in- depth Molecular Understanding of SIGMAR1 Pathway Data from ~700 study participants, eoe ORR 3 indications, 6 trials “ecee] OO We] fe Clinical Scores Dose! Arm Ciinical Impact B | +H Whole Exome DNA Detailed PK Radom Impact wr Transcr
Slide 9: Broad SIGMAR1 Platform Targeting Significant Unmet Medical Need
Broad SIGMAR1 Platform Targeting Significant Unmet Medical Need CANDIDATE PRECUNICAL PHASE Prasea "ANAVEX®2-73 /ALZHEIMER'S DISEASE (Blarcamesine) PARKINSON'S DISEASE Sa PARKINSON'S DISEASE DEMENTIA "ANAVEX®: *RETTSYNOROME (SSO EXCELLENCE ANAVEX®2-73-RS-003 5 — Fast Track, Rare Pediatric, RETTSYNDRO
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 People living with dementia around the world 131.5m Ee UEAIn) 2050 XI) 2030 (=) 2015 Americas i Europe ‘Source: World Alzheimer’s Report
Slide 11: Costs Associated with Alzheimer's Treatment and Care
Costs Associated with Alzheimer’s Treatment and Care in the U.S. are Unsustainable Age Prevalence of Global Alzheimer’s Disease and Dementias >$20 tril lion 10 hall Cumulative costs of Alzheimer’s and dementia care from 2015 to 2050 1in3 Medicare dollars will be spent on people living with Alzheimer
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 Alzheimer’s Disease ___ Alzheimer's Disease (AD) ~5,700,000 patients’ Parkinson’s Disease (PD) ~1,000,000 patients? ~_Rett Syndrome (RTT) ~11,000 ee Additional Indications - Frontotemporal dementia (FTD
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 Mechanism o
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 2021
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: SIGMAR1 Activation Modulates Multiple Aspects of Neurodegenerative Processes
SIGMAR1 Activation has been Shown to Modulate Multiple Aspects of Neurodegenerative Processes Sigma-1 receptor agonists have been shown to restore neuronal functions in neurodegenerative processes | ANAVEX®2-73 enhances autophagy and alleviates Tau pathology in neurodegenerative disease models eens
Slide 17: ANAVEX2-73 MoA: SIGMAR1 Activation Prevents Cellular Stress
ANAVEX®2-73 MoA: SIGMAR1 Activation Prevents Cellular Stress Before and After RNA Gene Transcription v Chromatin Chromatin Proteins a Nucleus / / Cytoplasm \ ANAVEX®2-73 ‘SIGMAR1 prevents toxic RNA from translating into proteins (post-transcription) SIGMAR1 protects healthy gene expression through C
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 5 : es 88 5 é 10 16 20 mgrkg of ANAVEX2-73 Set al, Sci Rep. 2021 Aug
Slide 19: 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 Differential Gene Expression ==> ~700 Patients X 26K genes X 2 timepoints ANAVEX®2-73, Molecular Pathway Signatures
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 Occurs almost exclusively in girls Leads to severe impairments, affectin
Slide 21: Rett Syndrome U.S. ANAVEX2-73-RS-001 Phase 2 Trial Design
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 (ence dai Sm Haus dose) Placebo n=10 , Week 0 Week 7 (Baseline) (End of Trial [EOT]) Efficacy Assessments: » Primary: RSBQ (Rett
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-l, ADAMS RSBQ CGI-I Responder = Non Responder ssecpander aNontepnder 130075) 10 (66.7%) (600%) p=0.011 5 (833%
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 dose (5 mg)* trofinetide high | dose (400 mg/kg)** ANAVEX®2-73 Phase 2 RSBQ Total Score compares favorably with other published historic
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 11% (400 mg/kg)** | E ° ANAVEX®2-73 Phase 2 Adverse Event profile compares favorably with other published historical trial * All participants ITT “* Glaze DG,
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 p=0.009 Clinically meaningful and statistically significant Improvement for ANAVEX®2-73 treated adult patients with Rett syndrome vs placebo 14.5-point improve
Slide 26: RSBQ Subscale Scores
RSBQ Subscale Scores Significant and Balanced Improvements across all Subscales (observed at End of Trial) RSBQ Subscale Score Body Repetitiv Rocking Night- General Breathing Hand eFace “ye EE Mood Problems Behaviors Moveme ey 0 ion Behaviors nts less Face Placebo 20% “ 1% -16% WANAVEX2-73 -23% =~ -
Slide 27: ADAMS Total Score
ADAMS Total Score Clinically Validated Efficacy Endpoint ADAMS Total Score Improvement with ANAVEX2-73 [ADAMS Total Change from Baseline (USmean £ SEM * Clinically meaningful and statistically significant Improvement for ANAVEX®2-73 treated adult patients with Rett syndrome vs placebo * 12.9-point i
Slide 28: ADAMS Subscale Scores
ADAMS Subscale Scores ant and Balanced Improvements across all Subscales (observed at End of Trial) ADAMS Subscale Scores Manic/Hyper Obsessive Depressed Social General active Mood Avoidance Anxiety Behavior Placebo. 3% 3% -11% 9% 33% MANAVEX2-73, —-25% -37% 41% -31% Compulsive Behavior * Cohen’s d
Slide 29: ANAVEX2-73-RS-002 Phase 2/3 Rett Syndrome AVATAR Study
ANAVEX®2-73-RS-002 Phase 2/3 Rett Syndrome AVATAR Study Diagnosis of confirmed RTT Patients age >18 Randomization DNA and RNA sequencing * Includes a 3 patient cohort undergoing a 3-week pharmacokinetic (PK) assessment with safety, tolerability, pharmacokinetic and efficacy evaluation of ANAVEX®2-73
Slide 30: ANAVEX2-73-RS-003 Phase 2/3 Rett Syndrome EXCELLENCE Study
ANAVEX®2-73-RS-003 Phase 2/3 Rett Syndrome EXCELLENCE Study 1 WEEK STUDY and Open Label Extension (OLE) 48 weeks Diagnosis of confirmed RTT Patients age 5-18 Randomization DNA and RNA 2:1 sequencing * Oral liquid solution once daily; Dose restricted to maintain complete blinding ANAVEX®2-73, Active
Slide 31: Parkinson's Disease Dementia (PDD)
Parkinson’s Disease Dementia (PDD) 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 than age 65 PD prevalence in US:~1,000,000 The brain changes caused by Parkinson's disease begin in a re
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 4: randomization | Zweek baseline period | 3-week up-titration period ‘L1-week target dose treatment p
Slide 33: ANAVEX2-73 Improved MDS-UPDRS Total Score in PDD Phase 2 Study
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 ) Episodic mem
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) Al participants Time: 14 weeks change from baseline + Ahi
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 AD prevalence in US: ~5,700,000 Estimated 50 million people live with dementia worl
Slide 38: ANAVEX2-73 Improved MMSE and ADCS-ADL Scores in Phase 2a AD Study
ANAVEX®2-73 Demonstrated Improved MMSE’ and ADCS-ADL? Scores in Phase 2a AD Study through 148 Weeks MMSE? (SE) Adjusted change in ADCS-ADL?(+SE) p-value < 0.0001 a 7 % 148 Time(weeks) Time(weeks) o D = G £ Go ao] 2 a = Z <x — tiigh mean concentration ANAVEX2-79 (&4.0ngimL) Source: Hampel ef al. A pr
Slide 39: ANAVEX2-73 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 Patient Clinical Data 148 weeks for all patients (t uD iu i} 4 hy Cognitive Scores ( ; { Genomic Data Novel Genomic Biomarkers of Response Identified in Phase 2a AD study -> Pre-s
Slide 40: ANAVEX2-73 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 Confirmed amyloid pathophysiology (CSF/amyloid PET) Patients aged 60 to 85 years MMSE score 20-28 Entire DNA and RNA sequencing * Oral capsule once daily; Dose restricted to maintain complete blinding Randomization aleilpaL High d
Slide 41: Anavex is Pursuing Precision Medicine for CNS Diseases
Anavex is pursuing) = > by Applying = 0 re ~ > o>» to Develop Treatments for both 99> ©... CNS diseases (Alzheimer’s, Parkinson’s), as well as catastrophic Orphan Genetically ~> 50° diseases, Rett Syndrome with High Unmet Needs $ 277B Economic burden uh OVERARCHING MESSAGE Anovel platform ag _ toadd
Slide 42: Anavex Life Sciences Expertise
Anavex Life Sciences Expertise Management Team Christopher U. Missling PhD - President & CEO cuas t@8IMMUNOGEN, INC. Aventis Walter E Kaufmann, MD - Chief Medical Officer oS HARVARD JOHNS FIOPKINS MEDICAL SCHOOL, Stephan Toutain, MS, MBA — Chief Operating Officer i ¢ SAREPTA Emmanuel O Fadiran, RPh,
Slide 43: Corporate Offices
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