corporate presentation - anavex4 addressing unmet needs in significant populations 1) alzheimer’s...

Nasdaq: AVXL | June 2020

Corporate Presentation

Christopher U Missling, PhD | President & CEO

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This presentation contains forward-looking statements made within the meaning of the Private Securities LitigationReform Act of 1995 by Anavex® Life Sciences Corp. and its representatives. These statements can be identified byintroductory words such as “expects,” “plans,” “intends,” “believes,” “will,” “estimates,” “forecasts,” “projects,” or words ofsimilar meaning, and by the fact that they do not relate strictly to historical or current facts. Forward-looking statementsfrequently 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 actualresults to differ from forward-looking statements, including inaccurate assumptions and a broad variety of risks anduncertainties, some of which are known and others of which are not. Known risks and uncertainties include thoseidentified from time to time in reports filed by Anavex Life Sciences Corp. with the Securities and ExchangeCommission, which should be considered together with any forward-looking statement. No forward-looking statement isa guarantee of future results or events, and one should avoid placing undue reliance on such statements. Anavex LifeSciences Corp. undertakes no obligation to update publicly any forward-looking statements, whether as a result of newinformation, future events or otherwise. Anavex Life Sciences Corp. cannot be sure when or if it will be permitted byregulatory agencies to undertake clinical trials or to commence any particular phase of any clinical trials. Because ofthis, statements regarding the expected timing of clinical trials cannot be regarded as actual predictions of when AnavexLife Sciences Corp. will obtain regulatory approval for any “phase” of clinical trials. We also cannot be sure of the clinicaloutcome for efficacy or safety of our compounds. Potential investors should refer to the risk factors in our reports filedon Edgar.

Forward Looking Statement

* = Orphan Drug Designation by FDA

PRECLINICAL PHASE 1 PHASE 2 PHASE 3

ANAVEX®2-73(Blarcamesine)

ALZHEIMER’S DISEASE

FRAGILE X

CANDIDATE

ANAVEX®3-71(AF710B)

*FRONT. DEMENTIA (FTD)


PARKINSON’S DISEASE

ANAVEX®1-41DEPRESSION

STROKE

PARKINSON’S DISEASE


ANGELMAN’S

ANAVEX®1066ACUTE & NEUROPATHIC PAIN

*RETT SYNDROME

*INFANTILE SPASMS

PARKINSON’S DISEASE DEMENTIA

VISCERAL PAIN

Anavex Expanding Pipeline: Potential for SignificantValue Creation Near and Long Term

Fast Track, Rare Pediatric, Orphan Drug (U.S./EU)

*RETT SYNDROME

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U.S. ANAVEX®2-73-RS-001

AVATAR ANAVEX®2-73-RS-002

ANAVEX®2-73-PDD-001

AD ANAVEX®2-73-AD-004

ANAVEX®3-71-001

*RETT SYNDROME EXCELLENCE ANAVEX®2-73-RS-003

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Addressing Unmet Needs in Significant Populations

1) Alzheimer’s Disease Facts and Figures. Alzheimers Dement 2018;14(3):367-429.2) Marras C et al 2018. npj Parkinson's Disease volume 4, Article number: 213) Based on prevalence number on orphanet

• Rett syndrome program Fast Track Designation and eligible for Pediatric Priority Review Voucher

• Pursuing Large Markets With High Unmet Need by Applying Genetic Precision Medicine

• Novel CNS Mechanism of Action Upstream of Neurodevelopment and Neurodegeneration

• Compelling first Human Patient Data in Rett Syndrome and Alzheimer’s Disease

• 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

We Anticipate Significant Value-creating Events with Several Clinical Readouts in 2020:

• Phase 2 Parkinson’s Disease Dementia (ClinicalTrials.gov Identifier: NCT03774459)

• Two Phase 2 Rett Syndrome Trials (ClinicalTrials.gov Identifier: NCT03758924, NCT03941444)

• Phase 2/3 Rett Syndrome Trial updates (ClinicalTrials.gov Identifier: NCT04304482)

• Phase 2b/3 Alzheimer’s Disease updates (ClinicalTrials.gov Identifier: NCT03790709)

• Phase 1 with ANAVEX®3-71 with focus on Frontotemporal Dementia

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A Transformative Year for Anavex

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The company expects to achieve key clinical milestonesCatalysts to Drive Value

Full enrollment Phase 2 Parkinson’s disease dementia (PDD)Topline data Phase 2 Parkinson’s disease dementia (PDD) – MID 2020FDA Fast Track designation for Rett syndrome program (RTT) Initiate EXCELLENCE Phase 2/3 in pediatric Rett syndrome (RTT)Full enrollment U.S. Phase 2 Rett syndrome (RTT)Full enrollment AVATAR Phase 2 Rett syndrome (RTT)Topline data U.S. Phase 2 Rett syndrome (RTT)Topline data AVATAR Phase 2 Rett syndrome (RTT)Initiate Phase 1 ANAVEX®3-71Data publications in 2020

Clinical Trials – MoA and First Clinical Data:• Rett Syndrome (RTT) • Alzheimer’s Disease (AD)

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ANAVEX®2-73 MoA: S1R Activation is Upstream from other Therapeutic TargetsNeural cells suffer functional loss in neurological disorders which causescellular stress

Pathologies include:

ü Aβ, Tau and ApoE fragmentation and dysfunction

ü Proteinopathy

ü Microglia activation, migration, and dysregulation

ü Apoptosis feedback loops that lead to neuronal degradation

ü Autophagy dysfunction

ü Mitochondrial Dysfunction and Oxidative Stress that leads to further neuronal degradation

ü Neurodegeneration that spreads through a cascade of stress responses

S1R activates neuroprotective signals that help neurons return to homeostasis

S1R = Sigma-1 Receptor

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ANAVEX®2-73 Establishes Human Proof-of-Concept and SIGMAR1 Target Occupancy

0 mg /kg 1 mg/kg 10 mg/kg 30 mg/kg

2D [18F]FTC-146-PET imaging of ANAVEX®2-73: Dose-dependent ANAVEX®2-73 Target Engagement

0

20

40

60

80

100

0 5 10 15 20 25 30

Perc

ent S

igm

a-1

Rec

epto

r O

ccup

ancy

mg/kg of ANAVEX2-73

Source: Reyes S et al, AAIC 2018; H Hampel et al., AAIC 2018; *Alzheimer's Disease Cooperative Study Activities of Daily Living 23-item scale (ADCS-ADL)

p=0.015

SIG

MAR

1 R

NA

expr

essi

on (T

PM)

Decrease (Negative) Increase (Positive)

ANAVEX®2-73 positive response in functional(ADCS-ADL*) outcome in Alzheimer’s disease patients

correlate with SIGMAR1 mRNA levels

p-value of Mann–Whitney U testAll n=20 patients in study. Slope of ADCS-ADL* from baseline to week 57 with available genomic data

Sigma-1 receptor agonists have been shown to restore neuronal functions in neurodegenerative processes

ANAVEX®2-73 enhancesautophagy and alleviates Tau pathology in neurodegenerative disease models

Sigma-1 receptor agonists have a neuroprotective effect in neurodegenerative disease models

SIGMAR1 Activation has been Shown to Modulate Multiple Aspects of Neurodegenerative Processes

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Devastating neuro-developmental disease in girls with both movement impairment and cognitive impairment

Rett Syndrome (RTT)

§ Non-inherited genetic postnatal disorder caused by mutationsin the MECP2 gene

Ø Occurs almost exclusively in girlsØ Leads to severe impairments, affecting nearly every aspect of the child’s lifeØ Impairment includes ability to speak, walk, eat and even breathe easilyØ Hallmark of RTT is near constant repetitive hand movements while awakeØ Occurs worldwide in approximately one in every 10,000 to 15,000 live female

births

What is Rett Syndrome?

11Source: https://www.rettsyndrome.org/about-rett-syndrome

0

10

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30

40

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60

70

Baseline Week 7

RSB

Q T

otal

Phase 2 PART A: Improvement in All Key Domains

SUMMARY• Phase 2, safety, tolerability, efficacy for 7 weeks, oral, liquid formulation,

5 mg daily (relatively low dose)• Part A: Intensive PK, n=6, Completed• Part B: Randomized, double-blind, placebo-controlled, n=15, ongoing• Females > 18 years, classic RTT w/MECP2 mutation• Evaluations at baseline (Week 0), Week 4 & Week 7 (End of Treatment)• Good safety and tolerability: No serious adverse events, only three grade 1-2 adverse events

U.S. Rett Syndrome ANAVEX®2-73-RS-001 Trial (NCT03758924)

EFFICACY* • Global severity RSBQ and CGI-I

RSBQ = Rett Syndrome Behavior QuestionnaireCGI-I = Clinical Global Impressions – Improvements

• Secondary: Behavior (ADAMS), Sleep (CSHQ), VAS (top caregiver concerns), Seizure diary

• Response Biomarker*: Glutamate, GABA; Genetic biomarker: DNA & RNA profiles

*Preliminary evaluation of efficacy: two-tailed, nonparametric tests (conservative)

RSBQ Total

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Baseline Week 7

RSB

Q H

and

Beh

avio

rs

0

0.5

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1.5

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2.5

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3.5

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4.5

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Baseline Week 7

Slee

p -C

SHQ

-Wak

ing

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ing

the

Nig

ht

RSBQ Hand Behaviors

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Baseline Week 7

RSB

Q B

reat

hing

Pro

blem

s

Sleep – CSHQ-Waking During the NightRSBQ Breathing Problems

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RSBQ improves by

over 30%

p = 0.027

p = 0.042p = 0.042

p = 0.042

28%

55%

46%

76%

Phase II to Phase III Phase III to NDA/BLA

Patient Selection with BiomarkerIncreases Probability of Success

Without Biomarkers With Patient Selection Biomarkers

Precision Medicine

Thomas DW et al. Clinical Development Success Rates 2006-2015. BIO Industry Analysis

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1) 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 14

Loss of synaptic homeostasis can impair nerve cells (neurons) and their connections

In patients with RTT, MeCP2 deficiency leads to increasedlevels of Glutamate, in comparison to healthy controls1,2,3, which results in excitatory-inhibitory imbalance and further synaptic dysfunction

Glutamate as potential biomarker of microglia activation and synaptic dysfunction

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)

1

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4

5

0 20 40 60

CGI-I

at W

eek

7

RSBQ Total at Week 7 1

2

3

4

5

10.00 20.00 30.00 40.00

CGI-I

Wee

k 7

Glutamate µmol/L Week 7 10

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10.00 20.00 30.00 40.00

Slee

p -C

SHQ

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al V

isit

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Glutamate µmol/L Week 7

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-100 -50 0 50

RSBQ

Han

d Be

havi

ors

Wee

k 7

% Change in Glutamate

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Baseline Week 7

Glu

tam

ate

(µm

o/L)

Glutamate

RSBQ & CGI-I Glutamate & CGI-I Glutamate & Hand Behaviors Glutamate & Sleep

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p = 0.046

p = 0.003

p = 0.038p = 0.021 p = 0.005

Improve-ment

Glutamate decreases by

over 40%

Significant Correlations:

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ANAVEX®2-73 Phase 2 U.S. Rett Syndrome Study

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

N>21 7RTT patient population

Randomization3:2

ANAVEX®2-73Active dose#

Placebo

• Diagnosis of confirmed RTT

• Patients age >18• Entire DNA and RNA

sequencingANAVEX®2-73-RS-001 STUDY ()*

# Oral liquid solution once daily; Dose restricted to maintain complete blinding

* 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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ANAVEX®2-73 Phase 2 Rett Syndrome AVATAR Study

Primary and Secondary Endpoints• Safety and tolerability of




N=33 7RTT patient population

Randomization3:2


Placebo


• Patients age >18• Entire DNA and RNA

sequencingANAVEX®2-73-RS-001 STUDY (NCT0


*

* Includes a 3 patient cohort undergoing a 3-week pharmacokinetic (PK) assessment with safety, tolerability, pharmacokinetic and efficacy evaluation of ANAVEX®2-73

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ANAVEX®2-73-RS-003 Rett Syndrome EXCELLENCE Study

Primary and Secondary Endpoints• Safety and tolerability of




N>69 12RTT patient population

Randomization2:1


Placebo


• Patients age 5-18• Entire DNA and RNA

sequencingANAVEX®2-73-RS-001 STUDY (NCT037


Alzheimer’s disease, progressive, irreversible neurological disease and most common cause of dementia

Alzheimer’s Disease (AD)

§ Alzheimer’s disease incidence highly correlates with age

Ø AD prevalence in US:~5,700,000Ø Estimated 50 million people live with dementia worldwideØ Today, there are no commercially available therapies to

address the underlying cause of Alzheimer’sØ The current annual cost of dementia is estimated at $1 trillion,

a figure set to double by 2030

Alzheimer’s Disease (AD)

19Source: www.alz.org/alzheimers-dementia/what-is-dementia/types-of-dementia/parkinson-s-disease-dementia

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ANAVEX®2-73 Demonstrated Improved MMSE1 and ADCS-ADL2 Scores in Phase 2a AD Study through 148 Weeks

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

1 Mini Mental State Examination (MMSE)2 Alzheimer’s Disease Cooperative Study Group - Activities of Daily Living Inventory (ADCS-ADL)

Adju

sted

cha

nge

in A

DC

S-AD

L2(±

SE)

Adju

sted

cha

nge

in M

MSE

1(±

SE)

p-value < 0.0008 p-value < 0.0001

N=8

N=13

N=8

N=13

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ANAVEX®2-73 Phase 2b/3 Alzheimer's Disease and ATTENTION-AD OLE Study

Primary Endpoints• ADAS-Cog• ADCS-ADL• Safety and tolerability of

ANAVEX®2-73

Key Secondary Endpoints• CDR-SB• Structural and functional MRI• Biomarkers: Abeta40/Abeta42, T-tau,

P-tau, NFL, YKL-40, neurogranin, BACE1



# Oral capsule once daily; Dose restricted to maintain complete blinding

N=450 48Early AD patient population

Randomization1:1:1

ANAVEX®2-73High dose#

ANAVEX®2-73Medium dose#

Placebo

• Confirmed amyloid pathophysiology (CSF/amyloid PET)

• Patients aged 60 to 85 years

• MMSE score 20-28• Entire DNA and RNA

sequencing

… and Open Label Extension (OLE) 96 weeks

Up to 80 percent of those with Parkinson’s disease eventually experience Parkinson’s disease dementia

Parkinson’s Disease Dementia (PDD)§ Parkinson’s disease is a fairly common neurological

disorder in older adults, estimated to affect nearly 2 percent of those older than age 65

Ø PD prevalence in US:~1,000,000Ø The brain changes caused by Parkinson’s disease begin in a

region that plays a key role in movementØ 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

Parkinson’s Disease Dementia (PDD)

22Source: www.alz.org/alzheimers-dementia/what-is-dementia/types-of-dementia/parkinson-s-disease-dementia

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ANAVEX®2-73 Phase 2 Parkinson’s Disease Dementia (PDD) Study

Primary Endpoints• CDR Continuity of Attention• Safety and tolerability of

ANAVEX®2-73

Key Secondary Endpoints• MDS-UPDRS• Sleep function• Actigraphy• MoCA• Other CDR battery measures



# Oral capsule once daily; Dose restricted to maintain complete blinding

N=120 14PDD patient population

Randomization1:1:1

ANAVEX®2-73High dose#

ANAVEX®2-73Medium dose#

Placebo

• Diagnosis of probable Parkinson’s disease dementia (PDD)

• Diagnosis of idiopathic Parkinson’s disease

• Patients aged ≥ 50 years

• MoCA score 13-23• Entire DNA and RNA

sequencing

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Identification (IDN) in Cogstate battery assessed in ANAVEX®2-73 Ph2a AD Study comparable to CDR Continuity of Attention (choice reaction time paradigm)

Primary Endpoint ‘CDR Continuity of Attention’ of PDD ANAVEX®2-73 Ph2 Study:Confirmed Beneficial Effect in Previous Ph2a AD Study

CDR battery Cogstate brief battery

PDD AD

Continuity ofAttention

Power of Attention

Quality of WorkingMemory

Quality of EpisodicMemory

Speed Memory

IDN

DET

ONB

OCL

ISL

ISRL

Choice reaction Time

Accuracy

Choice reaction Time

Digit Vigilance

Eli Lilly and Company uses ‘Continuity of

Attention’ as Primary Endpoint in D1PAM’s dementia associated

with Parkinson's disease trial

(ClinicalTrials.gov Identifier:

NCT03305809)

Anavex is the only Companypursuing 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

COMPELLING INITIAL HUMAN DATAANAVEX®2-73 undergoing Phase 2 in Rett syndrome and Phase 2a trial in Alzheimer’s disease with favorable safety and exploratory efficacy results through 148 weeks

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 patients carrying wild-type (WT) SIGMAR1 and COMT genes

SUFFICIENT CASH TO ACHIEVE KEY MILESTONESCash on hand and non-dilutive cash from Australian government for Alzheimer ’s study, and from Rettsyndrome.orgfor Rett syndrome study

OVERARCHINGMESSAGE

A novel approach is needed to address thetotality of CNS diseases

STRONG IP POSITION AROUND NOVEL MECHANISM OF ACTIONANAVEX®2-73, is an orally available Sigma-1 receptor agonist that has been shown to restore homeostasis (composition of matter patent protection to 2037)

VALUE-CREATING CATALYSTSClinical data readouts from two Phase 2 Rett syndrome studies and Phase 2 Parkinson’s disease dementia study anticipated in 2020. Clinical data publications and additional indications to be announced in 2020

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$ 277BEconomic burden2018 Alzheimer’sAssociation

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Anavex Life Sciences ExpertiseManagement Team

Scientific Advisory Board Members

Christopher U. Missling PhD - President & CEO

Daniel Klamer, PhD - VP of Business Development & Scientific Strategy

Walter E Kaufmann, MD - Chief Medical Officer

Stephan Toutain, MS, MBA – Chief Operating Officer

Emmanuel O Fadiran, RPh, PhD - SVP of Regulatory Affairs

Jeffrey Cummings, MD

Corinne Lasmezas, PhD

Ottavio Arancio, MD, PhD

Andrew Cole, MD

Daniel Weintraub, MD

Paul Aisen, MD

Norman Relkin, MD, PhD

Jacqueline French, MD

Dag Aarsland, MD, PhD

Tangui Maurice, PhD

Corporate OfficeAnavex®Life Sciences Corp.51 West 52nd Street, 7th floorNew York, NY 100191-844-689-3939

Shareholder & Media [email protected] NASDAQ: AVXL

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corporate presentation - anavex4 addressing unmet needs in significant populations 1) alzheimer’s...

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