Anavex Life Sciences Corp. · NASDAQ:AVXL
Anavex Life Sciences — CTAD 2020
33 slides from Anavex Life Sciences's conference presentation, Nov 6, 2020
Slide 1: ANAVEX2-73 (blarcamesine) Analysis of Cognitive Outcome Measures in PDD Phase 2 Trial
ANAVEX®2-73 (blarcamesine) Currently in Phase 2b/3 Early Alzheimer’s Disease (AD): Analysis of Cognitive Outcome Measures Relevant to AD of Double-blind, Multicenter, Placebo- controlled Phase 2 Clinical Trial in 132 Patients with Parkinson’s Disease Dementia Dag Aarsland1, Jaime Kulisevsky2, Mohamm
Slide 2: Disclosures
Disclosures: Dag Aarsland has served as consult or has received research support and/or honoraria from Astra-Zeneca, H. Lundbeck, Novartis Pharmaceuticals, Biogen, Evonik, Anavex, GE Health, Eisai, Acadia, Heptares, Mentis Cura. No patents, or stocks or ownerships in relevant companies.
Slide 3: 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 4: 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 5: Sig-1R (SIGMAR1) & ANAVEX2-73 (blarcamesine)
Sig-1R (SIGMAR1) & ANAVEX®2-73 (blarcamesine)
Slide 6: Fundamental Functions of Sig-1R on ER Stress Regulation in Neurodegenerative Disorders
Fundamental Functions of Sig-1R (SIGMAR1) on ER Stress Regulation in Neurodegenerative Disorders ①: Misfolded proteins increasing with age induce ER stress and modification in calcium homeostasis ②: Calcium depletion in ER activates Sig-1R, which separates from BiP Pathway a: IP3R and ATP Production
Slide 7: Established Human Proof-of-Concept and SIGMAR1 Target Occupancy
ANAVEX®2-73 (blarcamesine) Established Human Proof-of-Concept and SIGMAR1 Target Occupancy 2D [18F]FTC-146-PET imaging of ANAVEX®2-73: Dose- ANAVEX®2-73 positive response in functional dependent ANAVEX®2-73 Target Engagement in mouse model (ADCS-ADL*) outcome in Alzheimer’s disease patients correlat
Slide 8: Rationale to Advance ANAVEX2-73 into a PoC Phase 2 PDD Study
Rationale to Advance ANAVEX®2-73 into a PoC Phase 2 PDD Study ANAVEX®2-73 (blarcamesine) normalizes pathophysiological biomarkers in experimental Parkinsonism Collaboration with MJFF ANAVEX®2-73 demonstrated critical mediation of These results support the hypothesis that pharmacological nigrostriata
Slide 9: ANAVEX2-73-PDD-001 Proof of Concept Phase 2 Trial in PDD – Design & Top-Line Results
ANAVEX®2-73-PDD-001 Proof of Concept (PoC) Phase 2 Trial in PDD (Parkinson’s Disease Dementia) – Design & Top-Line Results
Slide 10: 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 11: 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 12: Cognition is Multidimensional
Cognition is Multidimensional 12
Slide 13: CDR System Core Domains And Tests
CDR System Core Domains And Tests Cognitive Drug Research Computerized Assessment (CDR) System Dimensions • Cognitive Drug Research computerized assessment (CDR) system is an automated test battery validated for use in PDD, AD and other dementias1 • The battery is modular, covering episodic memory,
Slide 14: Key Cognitive Domains
Key Cognitive Domains Episodic memory: Key feature that points to AD-related MCI The criteria from the National Institute on Aging and Alzheimer’s Association (NIA-AA) workgroup mention the following five cognitive domains when diagnosing MCI-AD: (a) Episodic memory (b) Attention “An impairment in e
Slide 15: 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 hi
Slide 16: Key Cognitive Domains Addressed by ANAVEX2-73
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 17: Positive Impact of Pre-specified Common SIGMAR1 WT Carriers
Positive Impact of Pre-specified Common SIGMAR1 WT Carriers ANAVEX®2-73-PDD-001 Study: Improvements of Quality of Episodic Memory with Pre-specified Common SIGMAR1 WT Carriers1 Common SIGMAR1 WT carriers only 1. Common SIGMAR1 Wild Type (WT) gene, represents 80%-84% of the worldwide population exclu
Slide 18: Improvements in Core Cognitive Functions
Improvements in Core Cognitive Functions ANAVEX®2-73-PDD-001 Study: Change in (CDR) System Quality of Episodic Memory Prevention of on-going decline observed in placebo group Quality of Episodic Memory (counts) Common SIGMAR1 WT carriers Estimated change from baseline 20 p = 0.047* 10 0 -2.74 -10 Di
Slide 19: Choice Reaction Time Increases with Complex Tasks
Choice Reaction Time Increases with Complex Tasks Affected in Alzheimer’s and Parkinson’s Diseases Group Mean Card Sorting Tasks 160.0 140.0 Alzheimer 120.0 Unmet need Parkinson Time (Seconds) 100.0 80.0 Elderly 60.0 Young 40.0 20.0 0.0 0 1 2 3 4 Log (2) n Increased Task Complexity Source: Mahurin,
Slide 20: Improvements in Core Cognitive Functions: Choice Reaction Time and Digit Vigilance
Improvements in Core Cognitive Functions ANAVEX®2-73-PDD-001 Study: Change in (CDR) System Individual Task Measures Choice Reaction Time and Digit Vigilance Reaction Time Prevention of on-going decline observed in placebo group Choice Reaction Time (ms) Digital Vigilance Reaction Time (ms) Common SI
Slide 21: Effects in Sleep Impairment Symptoms
Effects in Sleep Impairment Symptoms ANAVEX®2-73-PDD-001 Study: Insomnia Severity Index (ISI) and the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) • Two key prespecified sleep instruments, the Insomnia Severity Index (ISI) and the REM Sleep Behavior Disorder Screening Questionnaire (R
Slide 22: Safety Profile of ANAVEX2-73 (blarcamesine) in PDD
Safety Profile of ANAVEX®2-73 (blarcamesine) in PDD ANAVEX®2-73-PDD-001 Study: Summary • The were no TEAEs of clinical importance in the ANAVEX®2-73 (blarcamesine) cohort • Subjects with at least one TEAE leading to study discontinuation in the maintenance phase were 4.9% in the active cohort versus
Slide 23: Conclusions & Next Steps
Conclusions & Next Steps
Slide 24: Phase 2 Trial Results
Phase 2 Trial Results ANAVEX®2-73-PDD-001 Study: Summary • ANAVEX®2-73 (blarcamesine) at 30mg and 50mg doses improved key symptoms of dementia in this proof-of-concept study with good safety profile in patients with Parkinson’s disease dementia (PDD) • Broad and statistically significant improvement
Slide 25: Next Steps
Next Steps ANAVEX®2-73-PDD-001 Study: Next Steps • These results support continued development in PDD / PD as well as the currently ongoing Phase 2 and Phase 2/3 clinical studies with ANAVEX®2-73 (blarcamesine) in Rett syndrome1 and Alzheimer’s disease2 • Data of cognitive domain improvements highly
Slide 26: Upcoming: Application of Artificial Intelligence Methodologies to PDD-001 Study
Upcoming: Application of Artificial Intelligence Methodologies to ANAVEX®2-73- PDD-001 Study Unbiased, data-driven analysis of the heterogenous PDD patient population using DNA and RNA Whole Exome Genomic Sequencing Parkinson's disease dementia (PDD): Highly heterogeneous neurodegenerative disorder
Slide 27: Acknowledgements
Acknowledgements • Principal Investigators & clinical sites’ study staff • Michael J Fox Foundation (MJFF) • Anavex SAB • Most of all, grateful acknowledgement of the contribution of the participating PDD patients and their caregivers 27
Slide 28: Supplemental
Supplemental
Slide 29: 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 dementia
Slide 30: Improved MMSE and ADCS-ADL Scores in Phase 2a AD Study through 148 Weeks
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 31: 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 Primary Endpoints Early AD patient population • ADAS-Cog ANAVEX®2-73 • ADCS-ADL High dose# • Confirmed amyloid • Safety and tolerability of pathophysiology ANAVEX®2-73 (CSF/amyloid
Slide 32: Broad Pipeline Targeting Neurodegenerative and Neurodevelopmental Diseases
Broad Pipeline Targeting Neurodegenerative and Neurodevelopmental Diseases with 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 DEMENTIA ANAVEX®2-73-PDD-001 *RETT SYNDROME EXCELLENCE
Slide 33: 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 33