Slide 1: ANAVEX2-73 (blarcamesine) Analysis of Cognitive Outcome Measures in Parkinson's Disease Dementia
Wanevex Bea _anrd ..... LIFE SCIENCES Corp. University of London BARCELONA 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
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 (SIGMAR1) on ER Stress Regulation in Neurodegenerative Disorders
Fundamental Functions of Sig-1R (SIGMAR1) on ER Stress Regulation in Neurodegenerative Disorders ©): Misfolded proteins increasing with age induce ER stress and modification in calcium homeostasis [Pema | tates @®: Calcium depletion in ER activates Sig-1R, which separates oral from BiP Pathway a: IP
Slide 7: ANAVEX2-73 Established Human Proof-of-Concept and SIGMAR1 Target Occupancy
ANAVEX®2-73 (blarcamesine) Established Human Proof-of-Concept and SIGMAR1 Target Occupancy ANAVEX®2-73 positive response in functional (ADCS-ADL*) outcome in Alzheimer’s disease patients correlate with SIGMAR1 mRNA levels 2D [18F]FTC-146-PET imaging of ANAVEX®2-73: Dose- dependent ANAVEX®2-73 Target
Slide 8: Rationale to Advance ANAVEX2-73 into a PoC Phase 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 stimulation
Slide 9: ANAVEX2-73-PDD-001 Proof of Concept Phase 2 Trial in PDD
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 than
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 I 2-week baseline period Il 3-week up-titration period 11-week target dose treatme
Slide 12: Cognition is Multidimensional
Cognition is Multidimensional spatial wo sustaine@atte
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 dementias’ + 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 3 t=
Slide 16: 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 Aaaeeeents Paw cognitive domains when diagnosing MCI-AD: Phase 2 PDD Study (a) Episodic mem
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 Carriers‘ Quality of Episodic Memory Quality of Episodic Memory = Population: common SIGMAR1 WT carriers, N = 87 Population: all allo
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 p= 0.047* Direction of Improvem
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 Unmet need Parkinson =~ n nol ¢ re} Oo o n ~ oa £ = 2 Log (2) n Increased Task Complexity Source: Mahurin, R. K., & Pirozzolo, F. J. (1993). Application of Hick’s law of r
Slide 20: Improvements in Core Cognitive Functions
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 syndrome" and Alzheimer's disease? * Data of cognitive domain improvements highly
Slide 26: Upcoming: Application of Artificial Intelligence Methodologies to ANAVEX2-73-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 , Kings Ef Sanevex Bi ont nate LIFE SCIENCES Corp. University of
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 AD prevalence in US:~5,700,000 Estimated 50 million people live with dementia world
Slide 30: ANAVEX2-73 Demonstrated 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 SohbkHR ON & OD p-value < 0.0008 Adjusted change in ADCS-ADL?(+SE) ity n + i o % = => : & © - D < oc. x= o 3 ® 2 an 24 5S) <x p-value < 0.0001 5; 148 ch 57 7 96 96 Time(weeks) Time(weeks) High mean co
Slide 31: 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 Randomization 1:14:01 *# Oral capsule once daily; Dose restricted to maintain complete blinding ANAVEX
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 3 ANAVE 73 (Blarcamesine) > Fast Track, Rare Pediatric, Orphan Drug (U.S./EU) *FRONTOTEMPORAL DEMENTIA (FTD) ANAVEX®3-71-001 ANAVEX®3-71, (AF710B) ALZHEI
Slide 33: : eee Scienc se Corp.
: eee Scienc se Corp. st 52nd Street, 7th floor