Slide 1: AVATAR Phase 3 Rett Syndrome Top-Line Clinical Trial Data
fanevex LIFE SCIENCES Corp. IATAR Phase 3 02 Rett Jrome Top-Line Cli | Trial Data IAVEX®2-73 (blarcamesine) x ae J “W m Ban | Clinical Data _ AVXL | February 2022
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: What is Rett Syndrome?
What is Rett Syndrome? Devastating Neuro-developmental Disease in Girls with both Movement Impairment and Cognitive Impairment ot Rett Syndrome (RTT) = Non-inherited genetic postnatal disorder caused by mutations in the MECP2 gene > Occurs almost exclusively in girls Leads to severe impairments, aff
Slide 4: ANAVEX2-73 MoA: SIGMAR1 Activation Prevents Cellular Stress
ANAVEX®2-73 MoA: SIGMAR1 Activation Prevents Cellular Stress Before and After Gene Transcription ww Chromatin Chromatin Remodeling ” i Mm Mm pee Remodeling Proteins : : Nucleus Cytoplasm \ ANAVEX®2-73 SIGMAR1 prevents toxic RNA from translating into proteins (post-transcription) SIGMAR1 protects hea
Slide 5: ANAVEX Rett Syndrome Program
ANAVEX® Rett Syndrome Program Completed and ongoing late-stage clinical studies for Rett Syndrome in 2022: U.S. Phase 2 Adult Rett Syndrome Trial (ClinicalTrials.gov Identifier: NCT03758924) - completed AVATAR Phase 3 Adult Rett Syndrome Trial (ClinicalTrials.gov Identifier: NCT03941444) - completed
Slide 6: Phase 3 AVATAR Trial in Adult Patients with Rett Syndrome - Design Overview
Phase 3 AVATAR ANAVEX®2-73-RS-002 Trial in Adult Patients with Rett Syndrome - Design Overview Randomized, Double-blind, Placebo-controlled Multi-center Clinical Trial Arm Number of participants ANAVEX2-73 n=20 ves (once daily up to 30mg liquid dose) week OLE Placebo n=13 study (ence daily PBO liqui
Slide 7: Baseline Characteristics
Baseline Characteristics ANAVEX®2-73 (n=20)] PLACEBO (n=13) TOTAL (n=33) Age (years) — Median 24.8 23.6 24.3 Range - Min, Max 18.20, 38.35 19.53, 40.78 18.20, 40.78 Weight (kg) — Median 41.6 54.8 46.8 Range - Min, Max 33.0, 76.0 29.0, 84.0 29.0, 84.0 Baseline AED medications, % 80% 85% 82% Baseline
Slide 8: Appropriate Primary Endpoint for Rett Syndrome
Appropriate Primary Endpoint for Rett Syndrome Background for Pivotal Trial Endpoint ° Statistical significance alone not sufficient for determining whether an individual patient has experienced a meaningful clinical benefit e Asa Stand-alone caregiver reported primary outcome assessment, the RSBQ d
Slide 9: Primary Endpoint for Phase 3 AVATAR Clinical Trial
Primary Endpoint for Phase 3 AVATAR Clinical Trial for Adult Patients with Rett Syndrome Capturing Clinically Meaningful Treatment Effect and Disease Progression The RSBQ AUC (area under the effect curve) is a summary measure that combines both treatment effect and disease progression into one compo
Slide 10: CGI-I Scale
CGI-I Scale Clinical Global Impression of Improvement (CGI-I) The Clinical Global Impression of Improvement Scale (CGI-I) is a measure developed for use in clinical trials to provide a brief, stand-alone assessment of the clinician's view of the patient's global functioning prior to and after initia
Slide 11: ADAMS Scale
ADAMS Scale Anxiety, Depression, and Mood Scale (ADAMS) The Anxiety, Depression, and Mood Scale (ADAMS) is a measure of anxiety and mood symptoms in individuals with intellectual disability.’ It has been clinically validated for use in Rett syndrome? and in Fragile X syndrome? The ADAMS generates a
Slide 12: Primary Endpoint
Primary Endpoint Primary Efficacy Endpoint x 3 2 3 r) w 3} N 3 SS 2 2 o o Ss x © 2 40 6 i 2 oy S 4 g a a 2 ° ANAVEX2-73 Placebo « ANAVEX®2-73 induces a clinical meaningful improvement of RSBQ AUC?* in 72.2% of patients as compared to 38.5% on placebo; (p = 0.037) * Cohen’s d effect size 1.91 (very l
Slide 13: Secondary Endpoints
Secondary Endpoints Secondary Efficacy Endpoints ADAMS and CGI-I CGI-I responders at Week 7 (%) w 8 g g : é Z 3 7 ANAVEND-73, Placebo ANAVEX2-73 Placebo Clinically meaningful and statistically significant reduction of Significantly more patients achieve clinically meaningful CGI-I Ona peavioral symp
Slide 14: Other Endpoints
Other Endpoints Quality of Life (QoL) Assessment and Distribution of Seizure Count by Treatment Arm Child Health Questionnaire-Parent ANVENIS lscobe Form 50 (CHQ-PF50) The CHQ-PF50 is an internationally recognized general health-related global measure of Quality of Life (QoL) encompassing physical a
Slide 15: Biomarkers Increase Probability of Success
Biomarkers Increase Probability of Success Precision Medicine ‘Aust Gesemics in Conta Pracice Precision Medicine 76% 55% 46% , Phase |! to Phase III Phase III to NDA/BLA m= Without Biomarkers = With Patient Selection Biomarkers Thomas DW et al. Clinical Development Success Rates 2006-2015. BIO Indus
Slide 16: ANAVEX2-73 Mechanism of Action for Rett Syndrome
ANAVEX®2-73 Mechanism of Action for Rett Syndrome SIGMAR1 Activation is Beneficial in Restoring Neuronal Homeostasis MECP2 mutation alters SIGMAR7 activation closes ANAVEX®2-73 reverses synaptic development and chromatin to counteract chronic behavioral, motor, and drives chronic cellular stress cel
Slide 17: GABA a Potential Biomarker, Predicting Clinical Outcome
GABA a Potential Biomarker, Predicting Clinical Outcome in ANAVEX®2-73 Rett Syndrome Study In patients with RTT, MECP2 AVATAR efficacy endpoints deficiency disrupts the demonstrated statistically significant GABAergic cycle’, resulting in and clinically meaningful reductions , . . in Rett syndrome s
Slide 18: Safety and Adverse Events During Treatment Period
Safety and Adverse Events During Treatment Period ANAVEX®2-73 was well tolerated with ae, good medication compliance of Adverse Events During the Treatment Period ‘0 Similar TEAE rates observed in ANAVEX®2-73 (n=20) Placebo (n=13) ANAVEX®2-73 and placebo arms number (%) number (%) AEs 210% were pred
Slide 19: Overall Summary
Overall Summary Phase 3 AVATAR Clinical Trial for Adult Patients with Rett Syndrome Primary (RSBQ AUC; p = 0.037) and secondary (ADAMS; p = 0.010); (CGI-I; p = 0.037) efficacy and safety endpoints met Efficacy endpoints demonstrated statistically significant and clinically meaningful reductions in R
Slide 20: Acknowledgments
Acknowledgments We thank all the patients and their family members participating in the Rett syndrome ANAVEX®2-73-RS-002 study, as well as the investigators and their staff conducting these studies and the global Rett Syndrome Associations.
Slide 21: Broad Pipeline Platform Targeting Neurodegenerative and Neurodevelopmental Disorders
Broad Pipeline Platform Targeting Neurodegenerative and Neurodevelopmental Autism Spectrum Disorders with Significant Unmet Medical Need CANDIDATE PRECLINICAL PHASE 1 PHASE 2 PHASE 3 ANAVEX®2-73 ALZHEIMER'S DISEASE ‘AD ANAVEX®2-73-AD-004 (Blarcamesine) PARKINSON’S DISEASE = || PARKINSON’S DISEASE DE
Slide 22: Anavex is the only Company pursuing Precision Medicine
Anavex is the only Company pursuing ==> by Applying Precision Medicine to Develop Treatments for both ~ 6556 64 56 CNS diseases (Alzheimer’s, Parkinson’s), as well as catastrophic Orphan Genetically caused diseases, Rett Syndrome with High Unmet Needs $ 277B Economic burden 2018 Alzheimer'sAssociati
Slide 23: New York, NY
w York, NY 101 1 1 ol va | 9-3939
Slide 24: References
References Crouzier L, Couly S, Roques C, Peter C, Belkhiter R, Arguel Jacquemin M, Bonetto A, Delprat B, Maurice T. Sigma-1 (01) receptor activity is necessary for physiological brain plasticity in mice. Eur Neuropsychopharmacol. 2020 Oct;39:29-45. doi: 10.1016/j.euroneuro.2020.08.010 Hayashi T, Su