Anavex Life Sciences : Corporate presentation November 2020
11/20/2020 | 04:07pm EST
Corporate Presentation
Christopher U Missling, PhD | President & CEO
Nasdaq: AVXL | November 2020
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," "intends," "believes," "will," "estimates," "forecasts," "projects," or words of similar meaning, and by the fact that they do not relate strictly to historical or current facts. Forward-looking statements frequently are used in discussing potential product applications, potential collaborations, product development activities, clinical studies, regulatory submissions and approvals, and similar operating matters. Many factors may cause actual results to differ from forward-looking statements, including inaccurate assumptions and a broad variety of risks and uncertainties, some of which are known and others of which are not. Known risks and uncertainties include those identified from time to time in reports filed by Anavex Life Sciences Corp. with the Securities and Exchange Commission, which should be considered together with any forward-looking statement. No forward-looking statement is a guarantee of future results or events, and one should avoid placing undue reliance on such statements. Anavex Life Sciences Corp. undertakes no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. Anavex Life Sciences Corp. cannot be sure when or if it will be permitted by regulatory agencies to undertake clinical trials or to commence any particular phase of any clinical trials. Because of this, statements regarding the expected timing of clinical trials cannot be regarded as actual predictions of when Anavex Life Sciences Corp. will obtain regulatory approval for any "phase" of clinical trials. We also cannot be sure of the clinical outcome for efficacy or safety of our compounds. Potential investors should refer to the risk factors in our reports filed on Edgar.
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Broad Pipeline Targeting Neurodegenerative and
Neurodevelopmental Diseases with Significant Unmet Medical Need
Phase 1 of ANAVEX®3-71 with focus on Frontotemporal Dementia (ClinicalTrials.gov Identifier: NCT04442945)
5
Catalysts to Drive Value
The company has multiple near-term clinical milestones
Full enrollment Phase 2 Parkinson's disease dementia (PDD)
Rett syndrome program received FDA Fast Track Designation and is eligible for FDA Pediatric Priority Review Voucher
Initiate EXCELLENCE Phase 2/3 in pediatric Rett syndrome (RTT) Initiate Phase 1 ANAVEX®3-71
Full enrollment U.S. Phase 2 RTT Topline data Phase 2 PDD
Topline data U.S. Phase 2 RTT - Q4 2020 Topline data AVATAR Phase 2 RTT - 1H 2021 Topline data Phase 1 ANAVEX®3-71 - 1H 2021
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Clinical Trials - MoA and First Clinical Data:
Rett Syndrome (RTT)
Alzheimer's Disease (AD)
Parkinson's Disease Dementia (PDD)
ANAVEX®2-73 MoA: S1R Activation is Upstream from other Therapeutic Targets
Neural cells suffer functional loss in neurological disorders which causes cellular stress
Pathologies include:
ü Aβ, Tau and ApoE fragmentation and dysfunction
ü Proteinopathy
üMicroglia activation, migration, and dysregulation
üApoptosis feedback loops that lead to neuronal degradation
üAutophagy dysfunction
ü Mitochondrial Dysfunction and Oxidative Stress that leads to further neuronal degradation
üNeurodegeneration that spreads through a cascade of stress responses
S1R activates neuroprotective signals that help neurons return to homeostasis
S1R = Sigma-1 Receptor
8
ANAVEX®2-73 Establishes Human Proof-of-Concept and SIGMAR1
Target Occupancy
2D [18F]FTC-146-PET imaging of ANAVEX®2-73: Dose-
dependent ANAVEX®2-73 Target Engagement
0 mg /kg
1 mg/kg
10 mg/kg
30 mg/kg
Receptor1-SigmaPercent
Occupancy
100
80
60
40
20
0
0
5
10
15
20
25
30
mg/kg of ANAVEX2-73
ANAVEX®2-73 positive response in functional
(ADCS-ADL*) outcome in Alzheimer's disease patients
correlate with SIGMAR1 mRNA levels
p=0.015
p-value of Mann-Whitney U test
SIGMAR1 RNA expression (TPM)
All n=20 patients in study. Slope of
ADCS-ADL* from baseline to week 57
with available genomic data
Decrease (Negative)
Increase (Positive)
Source: Reyes S et al, AAIC 2018; Hampel H et al. Alzheimer's Dement. 2020;00:1-14; *Alzheimer's Disease Cooperative Study Activities of Daily Living 23-item scale (ADCS-ADL)
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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
Sigma-1 receptor agonists have a neuroprotective effect in neurodegenerative disease models
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What is Rett Syndrome?
Devastating neuro-developmental disease in girls with both movement impairment and cognitive
impairment
Rett Syndrome (RTT)
Non-inheritedgenetic postnatal disorder caused by mutations in the MECP2 gene
Occurs almost exclusively in girls
Leads to severe impairments, affecting nearly every aspect of the child's life
Impairment includes ability to speak, walk, eat and even breathe easily
Hallmark of RTT is near constant repetitive hand movements while awake
Occurs worldwide in approximately one in every 10,000 to 15,000 live female births
Response Biomarker*: Glutamate, GABA; Genetic biomarker: DNA & RNA profiles
RSBQ Total
RSBQ Hand Behaviors
0
Baseline
Week 7
0
Baseline
Week 7
10
Behaviors
1
2
Total
20
3
p = 0.027
30
4
RSBQ
RSBQHand
5
40
RSBQ
8
6
50
7
60
p = 0.042
improves by
9
70
over 30%
10
*Preliminary evaluation of efficacy: two-tailed, nonparametric tests (conservative)
RSBQ Breathing Problems
Baseline
Week 7
0
Problems
2
Breathing
4
8
RSBQ
6
10
p = 0.042
12
Sleep - CSHQ-Waking During the Night
0
Baseline
Week 7
During
0.5
1
Waking-CSHQ
Nightthe
1.5
2
2.5
3
-
3.5
p = 0.042
4.5
Sleep
4
5
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Precision Medicine
Biomarkers Increase Probability of
Success
76%
55%
46%
28%
Phase II to Phase III
Phase III to NDA/BLA
Without Biomarkers
With Patient Selection Biomarkers
Thomas DW et al. Clinical Development Success Rates 2006-2015. BIO Industry Analysis
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In patients with RTT, MeCP2 deficiency leads to increased levels of Glutamate, in comparison to healthy controls1,2,3, which results in excitatory-inhibitory imbalance and further synaptic dysfunction
Loss of synaptic homeostasis can impair nerve cells (neurons) and their connections
Glutamate as potential biomarker of microglia activation and
synaptic dysfunction
Hamberger, A., et al., Elevated CSF glutamate in Rett syndrome. Neuropediatrics, 1992. 23(4): p. 212-3.;2) Lappalainen, R. and R.S. Riikonen, High levels of cerebrospinal fluid glutamate in Rett syndrome. Pediatr Neurol, 1996. 15(3): p. 213-6; 3) J.L. Neul at al., Metabolic signatures differentiate Rett syndrome from unaffected siblings.
Frontiers in Integrative Neuroscience (2020) Vol14, Art 7, doi:10.3389/fnint.2020.00007
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Phase 2 PART A: Reported Improvements Correlate with Biomarkers
U.S. Rett Syndrome ANAVEX®2-73-RS-001 Trial (NCT03758924)
REPORT on PART A: INTENSIVE PK SUBCOHORT
Plasma levels of the biomarker Glutamate decreased significantly (Week 0 vs. Week 7; 2-tailed Wilcoxon signed rank test, p = 0.046)
Levels of Glutamate at Week 7 directly correlated with CGI-I scores at Week 7 (2-tailed Spearman's rho = 0.837, p = 0.038)
Greater decreases in Glutamate associated with greater improvement in these efficacy scores
GABA changes demonstrated an inverse correlation of the magnitude of Glutamate changes (2- tailed Spearman's rho = -0.829, p = 0.042)
Glutamate (∝mo/L)
0
10
20
30
40
50
60
70
Glutamate
Baseline
Week 7
p = 0.046
Glutamate
decreases by
over 40%
Significant Correlations: RSBQ & CGI-I
7
5
Iat Week
4
3
CGI-
2
p = 0.003
1
0
20
40
RSBQ Total at Week 7
Improvement
Glutamate & CGI-I
5
Week 7
4
3
CGI-I
2
60
p = 0.038
1
10.00
20.00
30.00
40.00
Glutamate ∝mol/L Week 7
RSBQ Hand Behaviors Week 7
Glutamate & Hand Behaviors
Glutamate & Sleep
8
40
7
7
Visit
35
6
5
Total
30
4
CSHQ-
25
3
20
2
p = 0.021
Sleep
p = 0.005
1
15
0
-100
-50
0
50
10
% Change in Glutamate
10.00
20.00
30.00
40.00
Glutamate ∝mol/L Week 7
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ANAVEX®2-73 Phase 2 U.S. Rett Syndrome Study
N=31*
RTT patient population
ANAVEX®2-73
Active dose#
Diagnosis of confirmed RTT
•
Patients age >18
Randomization
•
Entire DNA and RNA
3:2
sequencing
ANAVEX®2-73-RS-001 STUDY ()*
Placebo
Includes a 6 patient cohort undergoing a 7-week pharmacokinetic (PK) assessment with safety, tolerability, pharmacokinetic and efficacy evaluation of ANAVEX®2-73
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Primary and Secondary Endpoints
PK, safety and tolerability of ANAVEX®2-73
Behavioral symptoms
Sleep function
Seizure activity
Pre-specified Endpoints
Genetic variants SIGMAR1 (rs1800866), COMT (rs113895332/rs61143203) with influence on treatment effect
# Oral liquid solution once daily; Dose restricted to maintain complete blinding
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ANAVEX®2-73 Phase 2 Rett Syndrome AVATAR Study
N=33*
RTT patient population
ANAVEX®2-73
Active dose#
Diagnosis of confirmed RTT
•
Patients age >18
Randomization
•
Entire DNA and RNA
3:2
sequencing
ANAVEX®2-73-RS-001 STUDY (NCT0
Placebo
Includes a 3 patient cohort undergoing a 3-week pharmacokinetic (PK) assessment with safety, tolerability, pharmacokinetic and efficacy evaluation of ANAVEX®2-73
7
Primary and Secondary Endpoints
Safety and tolerability of ANAVEX®2-73
Behavioral symptoms
Sleep function
Seizure activity
Pre-specified Endpoints
Genetic variants SIGMAR1 (rs1800866), COMT (rs113895332/rs61143203) with influence on treatment effect
# Oral liquid solution once daily; Dose restricted to maintain complete blinding
17
ANAVEX®2-73-RS-003 Rett Syndrome EXCELLENCE Study
N>69
RTT patient population
ANAVEX®2-73
Active dose#
Diagnosis of confirmed RTT
•
Patients age 5-18
Randomization
•
Entire DNA and RNA
2:1
sequencing
ANAVEX®2-73-RS-001 STUDY (NCT037
Placebo
12
Primary and Secondary Endpoints
Safety and tolerability of ANAVEX®2-73
Behavioral symptoms
Sleep function
Seizure activity
Pre-specified Endpoints
Genetic variants SIGMAR1 (rs1800866), COMT (rs113895332/rs61143203) with influence on treatment effect
# Oral liquid solution once daily; Dose restricted to maintain complete blinding
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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 worldwide
Today, there are no commercially available therapies to address the underlying cause of Alzheimer's
The current annual cost of dementia is estimated at $1 trillion, a figure set to double by 2030
ANAVEX®2-73 Demonstrated Improved MMSE1 and ADCS-ADL2 Scores in Phase 2a AD
Study through 148 Weeks
Adjusted change in MMSE1(±SE)
N=8
N=13
p-value < 0.0008
Adjusted change in ADCS-ADL2(±SE)
N=8
N=13
p-value < 0.0001
Source: Hampel et al. A precision medicine framework using artificial intelligence for the identification and confirmation of genomic biomarkers of response to an Alzheimer's disease therapy: Analysis of the blarcamesine (ANAVEX2-73) Phase 2a clinical study. Alzheimer's Dement. 2020;00:1-14
Mini Mental State Examination (MMSE)
2 Alzheimer's Disease Cooperative Study Group - Activities of Daily Living Inventory (ADCS-ADL)
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ANAVEX®2-73 Phase 2b/3 Alzheimer's Disease and ATTENTION-AD OLE Study
Genetic variants SIGMAR1 (rs1800866), COMT (rs113895332/rs61143203) with influence on treatment effect
# Oral capsule once daily; Dose restricted to maintain complete blinding
21
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 age 65
PD prevalence in US:~1,000,000
The brain changes caused by Parkinson's disease begin in a region that plays a key role in movement
Highly heterogeneous multisystem disorder
Etiology of cognitive impairment in PD has not yet been fully elucidated
As Parkinson's brain changes gradually spread, they often begin to affect mental functions, including memory and the ability to pay attention, make sound judgments and plan the steps needed to complete a task
Source: Aarsland D, Creese B, Politis M, Chaudhuri KR, Ffytche DH, Weintraub D, Ballard C. Cognitive decline in Parkinson disease. Nat Rev
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-weekup-titration period
11-week target dose treatment period
Study data collected
at Baseline, Week 8
Screening
Baseline
Week 3
Week 8
Week 14
and 14
N=44
ANAVEX®2-73 High Dose
(10, 20, 30, then 50 mg QD)
2-week baseline
ANAVEX®2-73 Medium Dose
N=132
including
N=44
actigraphy
(10, 20, then 30 mg QD)
N=44
Placebo
(QD)
QD = once per day
PDD Patient Population
Diagnosis of probable Parkinson's disease dementia
Diagnosis of idiopathic Parkinson's disease
Patients aged ≥ 50 years
MoCA score 13-23
Key Primary and Secondary Endpoints
Safety and tolerability
CDR Cognitive Domain of Attention
Sleep function
MDS-UPDRS
Actigraphy (24-hour monitoring)
Entire DNA and RNA sequencing
Pre-specifiedEndpoints
Genetic variants SIGMAR1 (rs1800866),
COMT(rs113895332/rs6114320 3) with influence on treatment effect
ANAVEX®2-73-PDD- 001 is a Proof of Concept (PoC) Phase 2, multicenter, randomized, double- blind, placebo- controlled, parallel- group, 3-arm, 14- week study
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✅
✅
✅
✅
✅
Addressed in PoC Phase 2 PDD Study
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 cognitive domains when diagnosing MCI-AD:
Episodic memory
Attention
Language
Visuospatial skills
Executive functions
Related CDR
system
domains
Episodic memory
Choice reaction time
Word recognition
Picture recognition
Numeric working memory
Source: Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH.
The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups
on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21. PMID: 21514249;
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PMCID: PMC3312027.
Significant Improvements in Episodic Memory with Increased Dose
improvement of Quality of Episodic Memory with ANAVEX®2-73 (blarcamesine)
Direction of
Improvement
(counts)
Quality of Episodic Memory (counts)
All participants
Time: 14 weeks change from baseline
• A high score reflects
ability to store, hold
and retrieve
information of an
episodic nature (e.g.,
21.40
an event or name)
-1.20
+42.22
• CDR system Quality
of Episodic Memory
-20.82
highly correlated
(70%) with ADAS-Cog
(r = 0.7)1
1. Wesnes K, Edgar C, Andreasen N, Annas P, Basun H, Lannfelt L, et al. Computerized cognition assessment during acetylcholinesterase inhibitor treatment in Alzheimer's disease. Acta Neurol Scand 2010; 122:270-7
All participants; ANAVEX2-73 = Active 30 mg, Active 50 mg vs Placebo
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J-T test based on actual maintenance dose: p = 0.003
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 to ANAVEX®2-73 (blarcamesine) confirming SIGMAR1 activation as mechanism of action
Broad and statistically significant improvements in CDR system Cognitive Domain of Attention assessed by Choice Reaction Time (p = 0.039) and Digital Vigilance (p = 0.008) and CDR system Episodic Memory (p = 0.047), representing complex cognitive tasks with impact on quality of life such as making a choice between similar objects and remembering daily personal experiences, which are mostly impaired in both PD and AD1
Statistically significant dose-dependent (p = 0.003) improvement of CDR system Episodic Memory, which has been shown to be highly correlated (70%) with the Alzheimer's Disease Assessment Scale-Cognitive score (ADAS-Cog; r = 0.7)2
ANAVEX®2-73 (blarcamesine) does not impair sleep and has a positive effect on REM sleep behavior disorder
ANAVEX®2-73 (blarcamesine) was generally safe, well tolerated, and improved safety profile compared to dementia drugs associated with typical adverse effects
These results support continued development in PDD / PD as well as currently ongoing Phase 2 and Phase 2/3 clinical studies with ANAVEX®2-73 (blarcamesine) in Rett syndrome3 and Alzheimer's disease4
Data will be submitted to the U.S. Food and Drug Administration to seek regulatory guidance
Mahurin, R. K., & Pirozzolo, F. J. (1993). Application of Hick's law of response speed in Alzheimer and Parkinson diseases. Perceptual and Motor Skills, 77(1), 107-113
Wesnes K, Edgar C, Andreasen N, Annas P, Basun H, Lannfelt L, et al. Computerized cognition assessment during acetylcholinesterase inhibitor treatment in Alzheimer's disease. Acta Neurol Scand 2010; 122:270-7
Anavex is pursuing Large Markets by Applying Precision Medicine to Develop Treatments for bothGlobal Aging 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'sAssociation
OVERARCHINGMESSAGE
A novel approach is needed to address the totality of CNS diseases
PRECISION MEDICINE IMPROVES CHANCE OF CLINICAL SUCCESS
Testing for biomarkers demonstrated improved clinical response to ANAVEX®2-73 in Rett syndrome correlated with glutamate and for Alzheimer's and Parkinson's patients carrying wild-type (WT) SIGMAR1 gene
NOVEL CNS MECHANISM OF ACTION
ANAVEX®2-73, an orally available Sigma-1 receptor agonist, is upstream of neurodevelopment and neurodegeneration and has been shown to restore homeostasis
COMPELLING INITIAL HUMAN DATA
ANAVEX®2-73 Phase 2 Parkinson's disease dementia, ongoing Phase 2 in Rett syndrome and Phase 2a trial in Alzheimer's with favorable safety and initial efficacy results through 148 weeks
WORLDWIDE COMMERCIAL RIGHTS AND STRONG IP FOUNDATION
We retain global commercial rights to all of our product candidates and our lead product candidate, ANAVEX®2-73, including patent protection to 2030-2039
SUFFICIENT CASH TO ACHIEVE KEY MILESTONES Sufficient cash for >24 months to achieve key milestones, including non-dilutive cash from Australian government for Alzheimer 's trial and from Rettsyndrome.org for Rett syndrome trial
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Anavex Life Sciences Expertise
Management Team
Christopher U. Missling PhD - President & CEO
Walter E Kaufmann, MD - Chief Medical Officer
Stephan Toutain, MS, MBA - Chief Operating Officer
Emmanuel O Fadiran, RPh, PhD - SVP of Regulatory Affairs
Daniel Klamer, PhD - VP of Business Development & Scientific Strategy
Scientific Advisory Board Members
Jeffrey Cummings, MD
Paul Aisen, MD
Corinne Lasmezas, PhD
Norman Relkin, MD, PhD
Ottavio Arancio, MD, PhD
Jacqueline French, MD
Andrew Cole, MD
Dag Aarsland, MD, PhD
Daniel Weintraub, MD
Tangui Maurice, PhD
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Contact Us
Corporate Office
Anavex®Life Sciences Corp. 51 West 52nd Street, 7th floor
Anavex Life Sciences Corp. published this content on 10 November 2020 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 20 November 2020 21:06:00 UTC
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