Anavex Life Sciences Corp. · NASDAQ:AVXL
Anavex Life Sciences — CTAD 2019
17 slides from Anavex Life Sciences's conference presentation, December 2019
Slide 1: Novel analytics framework for augmenting single-arm Phase 2a trials with real-world external controls
Novel analytics framework for augmenting single-arm Phase 2a open label trials with Real-World external control data: Application to the Blarcamesine (ANAVEX®2-73) study in Alzheimer’s disease matched with propensity corrected patients from Alzheimer’s Disease Neuroimaging Initiative (ADNI) explorin
Slide 2: Disclosures
Disclosures § MA is an employee and shareholder of Ariana Pharmaceuticals § CW, NS, FP, AE and are employed by Ariana Pharmaceuticals § CM is an employee and shareholder of Anavex Life Sciences
Slide 3: FDA's new Real World Evidence Program Likely to Have a Profound Impact
FDA’s new Real World Evidence Program Likely to have a Profound Impact on the Biopharma Industry Pharma data (observational) Mobile & Lab/biomarkers Device data Consumer Mortality data data Imagery Social data media RWD data Disease Pharmacy registries data Hospital Electronics data medical and heal
Slide 4: Real World "Synthetic" Control Arms
Real World « Synthetic » Control Arms • High quality curated electronic health record (EHR) data collected during routine clinical care of patients have the potential to accelerate drug development • In areas of high unmet need, real world controls could help provide external control for regulatory
Slide 5: Use of Real World Evidence in Regulatory Settings is Gaining Momentum
Use of Real World Evidence in Regulatory Settings is Gaining Momentum • Collection of real-world data is not new • May provide access to patients that may not have been considered in a clinical trial • Ethical question of unnecessarily exposing patients to placebo • Reducing size, duration and costs
Slide 6: Matched-pair analysis using a propensity score
Method used for Identifying Matching Patients at Baseline Propensity Score Matching Superior to Meta Analysis Meta analysis and comparison to Standard of Care (SoC) depends upon similarities in study populations and definitions of outcomes. Heterogeneity across studies presents difficulties in how t
Slide 7: ADNI Provides an Opportunity for Patient Level Matching
Alzheimer’s Disease Neuroimaging Initiative (ADNI) Provides an Opportunity for Patient Level Matching 1) Real-world longitudinal 2) Integration of all available data in ADNI data of 1891 subjects N=345 Change and subjects with Alzheimer disease rate of decline (AD) diagnosis at baseline Baseline in
Slide 8: Extensively Characterized Single Arm Phase 2a Study of ANAVEX2-73 in Alzheimer's
Extensively Characterized single arm Phase 2a Clinical Study Investigating ANAVEX®2-73 in Alzheimer’s Disease Patients Provides a unique Precision Medicine Framework Cohort characterisHcs: Trial no.: NCT02244541 Trial no.: NCT02756858 32 Mild-moderate AD paHents • Age range: 55 to 85 • Clinically di
Slide 9: ANAVEX2-73 Demonstrated Improved MMSE and ADCS-ADL Scores through 148 Weeks
ANAVEX®2-73 Selective Sigma-1 Receptor (SIGMAR1) Agonist Demonstrated Improved MMSE1 and ADCS-ADL2 Scores in Phase 2a AD Study through 148 Weeks Adjusted change in MMSE1 (±SE) Adjusted change in ADCS-AD2 (±SE) N=8 N=8 N=13 N=13 p-value < 0.0001 p-value < 0.0001 Source: Hampel H., Afshar M., Parmenti
Slide 10: ANAVEX2-73 Mechanism of Action: SIGMAR1 Restores Homeostasis
ANAVEX®2-73 Mechanism of Action: SIGMAR1 Restores Homeostasis Caused by Neuro-inflammation and Protein Misfolding • Sigma-1 receptor (SIGMAR1) serves as an intracellular chaperone and functional modulator of calcium homeostasis and synaptic plasticity through targeting neuro-inflammation, protein- m
Slide 11: Simulating a Controlled Clinical Trial with Propensity Score Matching
Simulating a Controlled Clinical Trial: Match Patients at Baseline with Propensity Score Matching (PSM) The propensity score matching (PSM) methodology: PSM attempts to reduce the bias due to confounding variables that could be found in an estimate of the treatment effect obtained from simply compar
Slide 12: Analysis Steps: Matching Patients at Baseline
Analysis Steps: Matching Patients at Baseline ANAVEX ADNI AD patients treated with AD patients ANAVEX®2-73 N = 345 11 Anavex treated patients did N = 32 300 ADNI AD patients did not not have SIGMAR1_p.Q2P have SIGMAR1_p.Q2P information information Analysis cohort: Analysis cohort: N = 21 AD patient
Slide 13: APOE ε4+ Allele Distribution in ANAVEX2-73 Study
APOE ε4+ Allele Distribution in ANAVEX®2-73 Study High ANAVEX®2-73 6 out of 8 patients concentration 75% APOE ε4+ carriers in Cohort High ANAVEX®2-73 concentration cohort Low ANAVEX®2-73 4 out of 13 patients concentration 30.7% APOE ε4+ carriers in Cohort Low ANAVEX®2-73 concentration cohort 10 out
Slide 14: Adjusted Mean change in MMSE from baseline
LME model (3-arms): Alzheimer’s Disease Patients with high Concentration of ANAVEX®2-73 MMSE Performance better over 104 Weeks vs matched ADNI AD Cohort (p-value < 0.01) Cohort of high ANAVEX®2-73 concentration cohort shows significantly smaller decline in MMSE (-1.1) compared to ADNI AD matched coh
Slide 15: Conclusions
Conclusions • Small, data rich, AI-driven adaptive single arm precision medicine clinical studies as designed to assess ANAVEX®2-73 efficacy may be a template for future studies investigating CNS drugs in order to rapidly explore novel SIGMAR1 & mechanism of action, before engaging in larger trials
Slide 16: Acknowledgements
Acknowledgements • Principal Investigators & clinical sites’ study staff • Data safety review committee • Anavex SAB • Most of all, grateful acknowledgement of the contribution of the participating AD patients and their caregivers 16
Slide 17: 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 ir@anavex.com www.anavex.com NASDAQ: AVXL 17