June 2011 Safe Harbor This presentation contains forward looking - - PowerPoint PPT Presentation

June 2011

Safe Harbor

This presentation contains forward‐looking statements made within the meaning

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the Private Securities Litigation Reform Act

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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''

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words

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similar meaning, and by the fact that they do not relate strictly to historical

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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

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risks and uncertainties, some

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which are known and

• thers of which are not. Known risks and uncertainties include those identified from time to

time in the 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

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such statements. Anavex Life Sciences Corp. undertakes no

• bligation

to update publicly any forward‐looking statements, whether as a result

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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 clinical trials. Because of this, statements regarding the expected timing

• f 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

• utcome

for efficacy

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safety

• f
• ur

compounds. Potential investors should refer to the risk factors in our reports filed on Edgar.

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Confidential Nature Of Material

This presentation contains material information about Anavex Life Sciences Corp. which has not been disseminated to the

• public. This

document and the information contained herein is confidential and should not be communicated to any

• ther

person except as permitted in writing by Anavex Life Sciences Corp.. By viewing this presentation, the recipient hereby acknowledges that the recipient is aware that applicable securities laws prohibit any person who has material, non‐public information about Anavex Life Sciences Corp. from purchasing

• r

selling securities

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Anavex Life Sciences Corp. (or any public company with whom Anavex Life Sciences Corp. has agreed to be acquired) or from communicating such information to any other person under circumstances in which it is reasonably foreseeable that such person is likely to purchase or sell such securities. A person who violates insider trading or tipping rules is subject to severe criminal and civil penalties.

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Company Overview

• Anavex

focuses on developing novel treatments for upstream causes

• f Alzheimer’s disease
• Alzheimer’s is a huge and growing market with significant unmet

medical needs

• Anavex

2‐73 (lead product) shows behavioral, pharmacologic and histologic evidence with robust neuroprotection

• Named “#1 most promising trial drug”

by Dementia and Alzheimer’s Weekly

• Phase I/IIa

data this year

• Recent big pharma

deals for early Alzheimer drugs have been in the 100’s of millions

• Strong IP portfolio with patents going to 2027
• Capital raise secures further evidence to prepare for

partnership/acquisition

4

Sources: Cell, Volume 131, Issue 3, 596‐610, November 2007, Teruo Hayashi and Tsung‐Ping Su, Cellular Neurobiology Research Branch, National Institutes of Health; JPsychopharmacology, September 9, 2010, Villard et al, Anti‐amnesic and neuroprotective potentials of the mixed muscarinic receptor/sigma1 ligand ANAVEX2‐73, a novel aminotetrahydrofuran derivative; Dementia and Alzheimer’s Weekly January 2011

Key Near‐Term Milestones

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Product Indication Event Timing 2-73 Alzheimer’s Initiate Enrollment for Phase 1 trial 1Q 2011 2-73 Alzheimer’s Complete Enrollment of Phase 1 Trial 1/2Q 2011 2-73 Alzheimer’s Announce Data for Phase 1 Trial 2/3Q 2011 2-73 Alzheimer’s Initiate Enrollment for Phase 2a trial 3/4Q 2011 2-73 Alzheimer’s Complete Enrollment of Phase 2a Trial 4Q 2011 2-73 Alzheimer’s Announce Data for Phase 2a Trial 1/2Q 2012 2-73 Alzheimer’s Initiate Phase 2bTrial 3Q 2012 19-144 Alzheimer’s/Epilepsy Toxicology Study Initiation FY 2012 19-144 Alzheimer’s/Epilepsy IND/CTA Submission FY 2012 1-41 Alzheimer’s/Depression Toxicology Study Initiation 3/4Q 2011 1-41 Alzheimer’s/Depression IND/CTA Submission FY 2012

Anavex Team

6

• Former big pharma

executive (Merck, GSK, Pharmacia, J&J)

• CEO specialty pharma

and drug delivery/development (PediaMed, Spherics)

Cameron Durrant, MD, MBA

Executive Chairman, Acting CEO

• BMO Nesbitt, Burns, TD Bank, Assure Energy,

Quarry Oil & Gas

Harvey Lalach

President, COO, Director

• Worldwide Commercial Head Oncology (Pfizer)
• Previously Pharmacia, BMS, Merck, Lederle

Alison Ayers, MSc

Independent Director

• Clinical, Product Development,

Pharmacovigilance, Regulatory , CMC (PAION AG, Accentia, BioVest,Genesis BioPharma)

Angelos Stergiou, MD

VP, Clinical and Medical Affairs

• Venture capital, portfolio manager, IR (Work

Brain) , Striker

Sean Lowry

Independent Director

Robert Chisholm

Director

• Emprise Capital Corp, Savary

Capital Corp., Windamere Ventures Ltd. (formerly Advanced Vision Systems Corp.), Brookwater Ventures, Seymour Ventures

Scientific Advisory Board

7

Professor, Department of Neurosciences, University California San Diego School of Medicine, Director

• f the Alzheimer’s Disease Cooperative Study, Associate Editor of Alzheimer’s Research and Therapy

Professor of Neurology and Director of the Alzheimer's Disease and Memory Disorders Center at Baylor College of Medicine, which has conducted studies on all of the marketed Alzheimer's drugs to date Professor of Neurotherapeutics and Drug Development in the Neurological Institute, Cleveland Clinic and member of the Alzheimer’s Disease Cooperative Study Chief Scientific Officer with 30 years in research, focusing on the therapeutic/pharmacological areas of anti‐neurodegenerative, anti‐epileptic and anti‐depressive molecules Institut national de la santé et de la recherche médicale at INSERM, Montpellier, France 15 years in the field of neurosciences, including sigma receptors, normal/pathological aging models for Alzheimer’s, and behavioral and molecular neuropharmacology

Alexandre Vamvakides, PhD Tangui Maurice, PhD Rachelle Doody, MD, PhD Paul Aisen, MD Jeffrey Cummings, MD Christopher Shackleton, MD

Ttriple specialist credentials in both medical and surgical disciplines, an established record of success in the development and deployment of programs at the forefront of the intersection of laboratory and clinical innovation.

Alzheimer’s Market Overview

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Diagnosis accelerating

• 5 million+ Americans currently diagnosed
• 11 million by 2040
• 1 million new cases per year by 2050

Sources: Alzheimer’s Association, ICAD, UC Davis Alzheimer’s Disease Center, IMS

Millions Thousands

Aging strongest predictor

• 40 million Americans are over the age of 65
• First ‘Baby Boomers’

turn 65

• 80 million Americans over 65 by 2040

Huge Market Potential

• $183 billion spent caring for those suffering from Alzheimer’s disease, plus

$202 billion in unpaid care

• Market leading drug (Aricept) annual sales of $4 billion
• Total

drug sales were $8 billion – none

• f

these drugs are disease‐ modifying

• More effective treatments will create a multibillion dollar product market
• pportunity
• Existing Alzheimer’s disease treatments are not disease modifying, all are
• ff patent or soon will be

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Source: Alzheimer’s Association, ICAD, UC Davis Alzheimer’s Disease Center, IMS, Orange Book

Donepezil Memantine Rivastigmine Galantamine

Amyloid Plaque Not Correlated With Cognition

Flurizan Semagacestat Alzamed Monoclonals Vaccines IgIV Posiphen

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Pathophysiology

• f Alzheimer’s

 Amyloid may be a consequence rather than causative  Amyloid interrupts calcium signaling, causes (or is a consequence of) inflammation and neuronal cell death  Amyloid combines with caspase‐3 (and EphB2) to interrupt dendritic function  Stressed neurons double genetic material and more prone to apoptosis  Endoplasmic reticulum, mitochondrial and oxidative stress correlates with amyloid and vice versa

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• Sigma‐1 receptors regulate

calcium and control gene expression of a protein which preserves cells

• Agonism
• f Sigma‐1 receptors

(via 2‐73) leads to:

• Modulation of calcium

flow and ATP formation

• Enhanced cholinergic

function

• Growth of nerve cells
• Leads to neuroprotective

properties

Sigma‐1 Receptor Chaperones at the ER‐ Mitochondrion Interface Regulate Ca2+ Signaling and Cell Survival Cell, Volume 131, Issue 3, 596‐610, 2 November 2007 Hayashi and Su, Cellular Neurobiology Research Branch, National Institutes of Health (NIH) The sigma‐1 receptor chaperone as an inter‐organelle signaling modulator Trends in Pharmacological Sciences, 2010 (1‐10), Su et al

MOA of Sigma Receptor Agonists

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Anavex 2‐73: First Of A New Class

 Lead compound from wholly owned and patent‐protected new chemical class  Oral, small molecule(s)  Unique and novel mechanism of action: sigma‐1 receptor agonist  Potentially disease‐modifying  Sole metabolite (19‐144) confers additional beneficial effects  Outstanding potential based on pre‐clinical results:  Potent neuroprotection  Reverses learning deficits & amnesia  Effective in short‐term and long‐term memory tests  Multiple peer‐reviewed publications offer strong validation

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Aβ25‐35 ‐ induced memory deficits are reversed when 2‐73 administered 7 days after Aβ25‐35

Meunier

• J. et al., (2007). “Anti‐amnesic and neuroprotective

activities of ANAVEX 2‐73, a new aminotetrahydrofuran derivative acting as a mixed muscarinic/sigma‐ 1 ligands, in pharmacological and pathological models of amnesia”. Poster presentation, Neuroscience 2007, Nov. 3‐7, San Diego, California Villard V., Maurice T, (2007). “Anti‐amnesic and neuroprotective activities of ANAVEX compounds in animal models of Alzheimer’s disease”. Progress report #2, Contract #06122A10, INSERM/Univ. Montpellier II/Anavex, July 2007

2‐73 Reverses Learning Deficits

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Meunier

• J. et al., (2007). “Anti‐amnesic and neuroprotective

activities of ANAVEX 2‐73, a new aminotetrahydrofuran derivative acting as a mixed muscarinic/sigma‐ 1 ligands, in pharmacological and pathological models of amnesia”. Poster presentation, Neuroscience 2007, Nov. 3‐7, San Diego, California Villard V., Maurice T, (2007). “Anti‐amnesic and neuroprotective activities of ANAVEX compounds in animal models of Alzheimer’s disease”. Progress report #2, Contract #06122A10, INSERM/Univ. Montpellier II/Anavex, July 2007

2‐73 Also Protects From Learning Deficits

2‐73 protects against Aβ25‐35 ‐ induced memory deficits when administered before Aβ25‐35 15

Clinical Development

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Anavex 2‐73 Phase I/IIa ‐ adaptive study design, Germany (CRO – ABX):  Safety and efficacy data in:

 healthy human volunteers  mild/moderate Alzheimer’s patients  mild cognitive impairment

 Single and multiple ascending doses  Pharmacokinetics, pharmacodynamics, state‐of‐the‐art imaging and biomarkers Objectives:  Safety and efficacy data to prepare for full Phase II  Utilize as ‘bridge’ data to FDA and pre‐IND meeting – fast track possible Milestones Timings  Dosing in humans In progress  Complete Phase I Q2/3 2011  Enroll Phase IIa Q3 2011  FDA pre‐IND meeting Q3 2011  Complete Phase IIa Q4 2011/Q1 2012

Fundraise delivers Phase II ready asset in 12 months

Alzheimer’s Disease Select Deals

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2006 2007 2008 2009 2010 2011

4 5 7 8 9 2 3 6 1 10

Company Upfront and total deal value (where known) $MM Partner Phase Year

• 1. EPIX

35 / 120 GSK Discovery 2006

• 2. Idera

30 / 366 Merck Phase I 2006

• 3. AC Immune

300 Genentech Preclinical 2006

• 4. Co‐mentis

100 / 760 Astellas Phase I and Discovery 2008

• 5. Myriad

100 / 250 (option) Lundbeck Phase II 2008

• 6. Medivation

225 / 725 Pfizer Phase II 2008

• 7. Vitae

42 / 200 Boehringer‐ Ingelheim Discovery 2009

• 8. Elan

1,000 J+J Phase II 2009

• 9. ReMYND

637 Roche Preclinical 2010

• 10. Alectos

289 Merck Discovery 2010

Use Of Capital

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 $5‐10 million takes Anavex through important Phase I and Phase IIa trials for 2‐73.  The burn rate ~$450k/month  Final pre‐clinical work on 19‐144 and 1‐41 can be accomplished with raising capital at the high end of the target range. $MM

• 2‐73

2.2

• Phase 1

1.2

• Phase 2a

0.8

• Stability – Ongoing

0.2

• Working Capital

2.8 Total 5.0

Company Summary

 Micro‐cap, specialty pharmaceutical company with a focus on Alzheimer’s disease  Incorporated in Nevada, HQ in New Jersey, traded OTC as AVXL  Drug discovery, drug design and pre‐clinical in Athens, Greece

19 Common 25.2MM Fully Diluted 31.1MM Float 17.9MM Recent Price ~$3.00 Options 2.8MM Insiders 7.3MM Market Cap. ~$75MM Warrants 3.1MM 3m Ave Vol. 42K

Note: In the past 120 days, Anavex has raised $100,000 offering of units including 29,851 shares of common stock at $3.35 and 14,926 warrants at $4.50 expiring in December 2012 and another $228,800 in an offering of units including 61,014 shares

• f common stock at $3.75 and 30,508 warrants at $5.25 expiring in August 2012

Company Summary

• Anavex

focusing on developing disease‐modifying treatments for upstream causes of Alzheimer’s disease

• Alzheimer’s is a huge and growing market with significant unmet

needs

• 2‐73 shows behavioral, pharmacologic and histologic evidence with

robust neuroprotection

• 2‐73 named “#1 most promising trial drug”

by Alzheimer’s Weekly

• Phase I/IIa

data this year

• Strong IP
• Big pharma

deals substantial in Alzheimer’s category

• Capital raise secures further evidence to prepare for a

partnership/acquisition

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Scientific Appendix

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 ANAVEX 2‐73 is the first of a new class, acts via sigma‐1 receptor agonism and has muscarinic and cholinergic effects; active drug and pro‐drug  Sigma‐1 receptors function as sensor/regulators of calcium homeostasis by regulating activity of inositol‐1,2,4 trisphosphate (InsP3) receptors (Hayashi et al, 2000)  Modification of ion channel signaling at the ER‐mitochondrial level modulates intracellular calcium mobilization (Hayashi et al, 2000), ion channel activation (Aydar, 2002) and membrane recomposition in lipid rafts (Hayashi and Su, 2001)  Muscarinic M1 acetylcholine receptor agonism and M2/3 receptor antagonism  Facilitates glutamate release and activates glutamate receptors (Dong et al, 2000)  Increases acetylcholine release via pre‐synaptic sigma‐1 and M2 autoreceptors (Vamvakides, 2002)  Activates phospholipase C via muscarinic receptors but amplified by sigma‐1 protein mediated activity (Felder, 1995)  Induces InsP3 formation and ER InsP3 receptor activation (Fernandez de Savilla, 2008)

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Pharmacological Evidence

Anavex 2‐73 Properties

23  Disease‐modifying, neuroprotective potential therapeutic for neurodegenerative diseases, including Alzheimer’s disease.  Mixed muscarinic/Na+ & Ca+ channel/ NMDA and sigma‐1 receptor pharmacological activity.  Anti‐apoptotic for neurons via agonistic sigma‐1 regulation of the volume regulated chloride channels (VRCC) and Bcl‐2 pathway.  Dampens caspase‐3 and potentially anti‐inflammatory  Selective ligand for σ‐1 receptors with a high nanomolar affinity (pKi=6.3) and no affinity for σ‐2 receptors  Due to sigma‐1 selectivity, there are no interactions with σ‐2 agonistic action and therefore no related adverse effects seen to date  Anti‐amnesic action (antagonistic action against scopolamine and dizocilpine (MK‐801) induced amnesia or amyloid peptide (Αβ25‐35) at low doses (from 0.3mg/kg administered orally in mice)

O N .HCI Me Me

Source: Company information and publications

Neuroprotection: Histology

ANAVEX 2‐73 blocks loss of neurons

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Automated cell counting shows 23% loss of neurons with insult mimicking Alzheimer’s disease

Neuroprotection may be mediated by mechanisms involving Bcl‐2 transcription and preservation of a favorable Bcl‐2/bax ratio in injured neurons, as well as dampening of micro‐inflammation via down‐ regulation of caspase‐3

Competitive Pipeline And Marketed Sigma‐1 Agonists

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Symptomatic Treatments

Source: Pipeline sources, company press releases and websites, Evaluate Pharma, BioMedTracker, Analyst reports Estimates: Ph2 = 2y; Ph3 = 3.5y; Filing = 1.5y

2009 2010 2011 2012 2013 2014 2015 2016 2017+

Generic Rivastigmine 5HT6 antago (GSK-742457, GSK / SAM531, Wyeth 7 nicotinic (MEM3454, Roche) PDE4 (HT0712, Helicon) GABA-A/PDE4 (EHT0202, ExonHit) PARP (AL-108, Allon) H3 inverse ago (MK-0249, Merck) Compounds currently in phase 1: 5HT1A (Avera) M1 ago (Mithridion; GSK) NMDA NR2B (Evotec) α4β2 (AZ/Targacept) HDAC (EnVivo) PDE9 (Pfizer) mGluR2 (Roche) Generic Donepezil Generic Memantine AMPA (CX717, Cortex) H3 antagonist (GSK239512, GSK)

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Disease Modifiers

Source: Pipeline sources, company press releases and websites, Evaluate Pharma, BioMedTracker, Analyst reports Estimates: Ph2 = 2.5y; Ph3 = 3y; Filing = 1.5y

2010 2011 2012 2013 2014 2015 2016 2017+

Sigma (2-73, Anavex) Vaccine (ACC001, Wyeth/Elan) Anti-Aß mAb (PF-4360365, Pfizer) RAGE (TTP-488, Pfizer) MPAC (PBT2, Prana) Tau agg inh (Trx0014, TauRx)

Oral Parenteral

Anti-Aß mAb (Bapineuzumab, Wyeth/Elan) Anti-Aß mAb (Solanezumab, Lilly) Anti-Aß Ab (Gammagard, Baxter) GSI/Insulin (NIC515, Humanetics) BACE (ACI-91, AC Immune) Amyloid Agg inh (ELND-005, Elan) Compounds currently in Phase 1: Vaccine (Affitope) Vaccine (V950, Merck) Anti-Aß mAb (GSK-933776A, GSK) Anti-Aß mAb (MABT5102A, AC Immune) Anti-Aß mAb (R1450, Roche) Cell therapy NGF (NsG0202, NsGene) Compounds currently in Phase 1: BACE (CTS-21166, CoMentis/Astellas) GSI (begacestat, Wyeth) GSI (ELND-006, Elan) GSM (E2012, Eisai) Aß fibrillogen inh (Exebryl, ProteoTech) Aß fibrillogen inh (Oxigon, Intellect) Vaccine (CAD106, Novartis) IVIG(Octagam, Octapharma) NGF gene therapy (CERE-110, Ceregene) GSI (BMS708163, BMS) GSK3ß (NP-12, Noscira)

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Select Marketed Sigma‐1 Agonists

 Aricept/donepezil (plus cholinesterase inhibitor)  Namenda/memantine (plus NMDA antagonist)  Neudextra (dextromethorphan+quinidine) – pseudo bulbar affect  Celexa/citalopram (plus SSRI)  Flovox/fluvoxamine (plus SSRI)  Insidon/opipramol

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Depression, anxiety Alzheimer’s

Intellectual Property

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30

Intellectual Property

Title of Applications/ Patent No./ Jurisdiction Filing/ Expiration Claims

Patent No. 1002616/Greece PCT International Extension: WO 9730983 February 21, 1996 February 20, 2017 Invention related to the synthesis and the method of synthesis of molecules of a novel formula. This method is to be applied for the obtention

• f anticonvulsant,

antidepressant and nootropic pharmaceuticals Patent No. 1004208/Greece October 15, 2001 April 4, 2023 Aminotetrahydrofuran derivatives, muscarinic/sigma/sodium channel ligands, with synergic sigma/muscarinic (neuroactivating) and sigma/sodium channel (neuroprotective) components, as prototypical activating – neuroprotectors and neuroregenerative drugs Patent No. 1004868/Greece April 22, 2003 April 26, 2025 Aminotetrahydrofuran derivatives, muscarinic/sigma/sodium channel ligands, ortho‐and allo‐ sterically

• perating, as prototypical neuromodulating and

neuroregenerative drugs Patent No. 1005865/Greece January 17, 2007 January 18, 2027 New sigma receptor ligands with anti‐apoptotic and/or pro‐apoptotic properties over cellular biochemical mechanisms, with neuroprotective, anti‐cancer, anti‐ metastatic and anti‐(chronic) inflammatory action Patent Application 20090100115 / Greece February 26, 2009 February 27, 2029 Sigma(σ) receptors ligands with anti‐apoptotic and/or pro‐ apoptotic properties, over cellular mechanisms, exhibiting prototypical cytoprotective and also anticancer activity Patent Application Pending / Greece February , 2010 (pending) Synthesis and method of synthesis of molecules 1‐ methylo‐4‐ [4,4‐difainylo‐4‐ (Adantylo 1‐boutylo] piperazine and its structural analogues with anticancer properties

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Intellectual Property ‐ International

PATENTS AND APPLICATIONS REGISTERED WITH THE WORLD INTELLECTUAL ORGANISATION (WIPO) PCT (Patent Cooperation Treaty) Request based on Greek Patent 1005865 January 17, 2007 Request GR 2008/ 000002 National Phases opened on ‐ Request GR 2008/ 000002 May 28, 2009 European Patent Application 08702158.0 June 26, 2009 Russia Patent Application S/N 2009125211 June 29, 2009 IP India Application S/N 2392/KOLNP/2009 July 10, 2009 US Patent and Trademark Application 12/522.761 July 16, 2009 China Patent Application 2004800011111 PCT (Patent Cooperation Treaty) Request based on Greek Patent Application 20090100115 February 26, 2009 Request # Pending National Phases Pending on: USA, EU, Canada, Japan, China, India, Russia, Australia, Israel