October 2018 Corporate Presenta3on Christopher U Missling, PhD President & CEO Nasdaq: AVXL

Transcription

1 October 2018 Corporate Presenta3on Christopher U Missling, PhD President & CEO Nasdaq: AVXL

2 Safe Harbor This presenta3on contains forward-looking statements made within the meaning of the Private Securi3es Li3ga3on Reform Act of 1995 by Anavex Life Sciences Corp. and its representa3ves. These statements can be iden3fied by introductory words such as expects, plans, intends, believes, will, es3mates, 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 poten3al product applica3ons, poten3al collabora3ons, product development ac3vi3es, clinical studies, regulatory submissions and approvals, and similar opera3ng ma]ers. Many factors may cause actual results to differ from forward-looking statements, including inaccurate assump3ons and a broad variety of risks and uncertain3es, some of which are known and others of which are not. Known risks and uncertain3es include those iden3fied from 3me to 3me in reports filed by Anavex Life Sciences Corp. wit the Securi3es 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 obliga3on to update publicly any forward-looking statements, whether as a result of new informa3on, future events or otherwise. Anavex Life Sciences Corp. cannot be sure when or if it will be permi]ed by regulatory agencies to undertake clinical trials or to commence any par3cular phase of clinical trials. Because of this, statements regarding the expected 3ming of clinical trials cannot be regarded as actual predic3ons 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. Poten3al investors should refer to the risk factors in our reports filed on Edgar. 2

3 Novel Target, New Approach to Trea3ng CNS Anavex u3lizes genomic biomarkers in precision medicine to treat severe and devasta3ng neurological disorders. Anavex is focusing on rare diseases with no available therapy (Re] syndrome) and high risk CNS pa3ent popula3ons (Alzheimer s disease, Parkinson s disease) 3

4 Sources: GlobalGenes.org 1, PhRMA, NIBR 4 4

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6 Summary Focus Finding effec3ve treatments for neurodevelopmental and neurodegenera3ve diseases, areas of high unmet need Mechanism SIGMAR1 targe3ng cellular homeostasis Approach Applying precision medicine to CNS ANAVEX 2-73, orally available SIGMAR1 agonist with strong IP (COM 2033) U3lizing pa3ent genomic analysis as well as clinical PK/PD data to effec3vely incorporate into three clinical trials ini3a3ng in 2018: Phase 2 clinical trial in Re] syndrome* IND filed Phase 2 clinical trial in Parkinson s disease demen3a study approved to ini3ate Phase 2b/3 clinical trial in Alzheimer s disease study ini3ated *FDA granted ANAVEX 2-73 Orphan Drug DesignaLon (ODD) for ReP syndrome 6

7 Evidence that Ac3va3on of SIGMAR1 Impacts Relevant Pathophysiological Pathways Sigma-1 receptor ac3va3on has been shown to modulate mul3ple aspects of neurodegenera3ve processes 7

8 Quan3ta3ve PET Scan: Dose-dependent ANAVEX 2-73 Target Engagement with the Sigma-1 Receptor 2D [ 18 F]FTC-146-PET imaging of ANAVEX 2-73 Frontal Cortex Brain Stem Dose of ANAVEX2-73: 0 mg /kg 1 mg/kg 10 mg/kg 30 mg/kg Percent Sigma-1 Receptor Occupancy Reyes S et al, AAIC mg/kg of ANAVEX2-73 Sigma-1 receptor target occupancy study with quan3ta3ve PET scan of ANAVEX

9 Poten3al Protein Trafficking Implica3ons of the SIGMAR1 Gene Variant SIGMAR1 structure and the rs variant Cri3cal for protein trafficking rs variant might affect protein trafficking The SIGMAR1 rs variant might affect endoplasmic re3culum protein trafficking The majority of the popula3on (~80%) does not carry the SIGMAR1 rs variant Hence the majority of pa3ents (~80%) is expected to benefit from SIGMAR1 ac3va3on with ANAVEX 2-73 Adapted from: Laurini E., Marson D., Fermeglia M., Pricl S. (2017) 3D Homology Model of Sigma1 Receptor. Evolution of the Concept of Sigma Receptors. Handbook of Experimental Pharmacology, vol 244. Springer, Cham; Sources: Schmidt H.R. et al, Nature Apr 28; 532(7600): ;

10 Iden3fica3on of Gene Signature from ANAVEX 2-73 Pa3ents Corresponding approach to oncology precision medicine ANAVEX 2-73 treatment Gene3c signatures (WT SIGMAR1 gene) of the strongest responders to ANAVEX 2-73 Majority of popula3on, about 80% is expected to benefit from ANAVEX 2-73 Applies to all indica3ons involving ANAVEX

11 Overview ANAVEX 2-73 Clinical Trials ANAVEX Study: Randomized, double-blind, placebocontrolled Phase 1 (oral) Single ascending dose (SAD) 22 healthy subjects ANAVEX Study # : Randomized, Phase 2a (iv/oral) 32 mild-to-moderate AD pa3ents MMSE baseline (mean 21) Adap3ve trial with Popula3on PK Bioavailability, dose finding (PART A), and exploratory efficacy with 52 week open-label extension (PART B) ANAVEX Study ## : 208-week extension study aver PART B Popula3on PK, i.e. nonlinear mixed effect (NLME) modeling, noncompartmental analysis and formal concept analysis (FCA) and both RNA and whole exome DNA genome sequencing using Illumina HiSeq 2500 Next Genera3on Sequencing (NGS) technology Ini3a3on of subsequent randomized, doubleblind, placebo-controlled ANAVEX 2-73 studies: Re] syndrome Parkinson s disease demen3a Alzheimer s disease ClinicalTrials.gov IdenLfier: # NCT ; ## NCT Prepara3on underway 11

12 ANAVEX 2-73 Primary and Secondary Endpoints Met in Phase 2a Clinical Trial of Mild-to-Moderate Alzheimer s Pa3ents Phase 2a results demonstrate a favorable safety, bioavailability, dose-response curve and tolerability/risk profile at doses between 10mg and 50mg of oral daily ANAVEX 2-73 Primary endpoints met with favorable safety and tolerability Secondary endpoints met with suppor3ve exploratory biomarker, cogni3on and func3on measures correla3ng Dose-response rela3onship was sta3s3cally significant to affect MMSE-Δ and EEG/ERP-Δ scores with MMSE-Δ (p=0.0285) and EEG/ERP-Δ (p=0.0168), respec3vely Macfarlane, presented at CTAD

13 Significant Rela3on between ANAVEX 2-73 Concentra3on and Response Alzheimer's Disease Coopera3ve Study Ac3vi3es of Daily Living 23-item scale (ADCS-ADL) Concentra3on ANAVEX2-73 High => ADCS-ADL Delta High p=0.03 p = p-value of Mann Whitney U test ADCS-ADL Delta from Baseline (Week57) Low (n=9) Medium (n=8) High (n=9) Concentra6on AV2-73 (ng/ml), Part B All n=26 pa*ents in study at week 57

14 Data Driven Precision Medicine Unbiased, data driven, analysis using machine learning (AI) for analyzing DNA & RNA data of pa3ents exposed to ANAVEX

15 Gene Data Analy3cs Strategy It is essen3al to be able to Handle small pa3ent popula3on and very large amount of diverse data and combina3ons Analyze the data without a priori or bias: Anavex implemented a data driven (in contrast to hypothesis driven) approach >100 Million of associa3ons are systema3cally evaluated and ranked in an unbiased fashion in order to iden3fy hidden drivers of response KEM (Knowledge Extrac3on and Management) is a machine learning pla{orm u3lized to perform the analysis 15

16 Comprehensive Phase 2a Pa3ent Characteriza3on to Iden3fy Ac3onable Phase 2/3 Clinical Trial Parameters Popula3on PK MMSE ADCS-ADL COGSTATE EEG/ERP HAM-D Scores Baseline Scores EvoluLon MMSE ADCS-ADL COGSTATE EEG/ERP HAM-D Clinical assessment, Vital signs, co-medicalon, == DNA FGS RNA FGS FGS: Full Exome Genomic Sequencing Gut Microbiota # Ariana s KEM data analy3cs: Systema3c unbiased analysis of all combined parameters Iden3fica3on of ac3onable parameters Design of op3mized Phase 2/3 clinical trial # Collec3on ongoing 16

17 SIGMAR1 Gln2 (WT) Gene Associated with Improved Response Delta MMSE (Week 57 from Baseline) p=0.048 Delta ADCS-ADL (Week 57 from Baseline) p=0.023 SIGMAR1 Pro2 variant (n=5) (rs ) SIGMAR1 Gln2 (n=15) SIGMAR1 Pro2 variant (n=5) (rs ) SIGMAR1 Gln2 (n=15) p = p-value of Mann Whitney U test All n=20 pa*ents in study at week 57 with available genomic data 17

18 Confirma3on: Significant Correla3on of ADCS-ADL Response and SIGMAR1 RNA expression levels p = p-value of Mann Whitney U test All n=20 pa*ents in study at week 57 with available genomic data 18

19 Gene Markers Improve Effect Size (Cohen s d) with ANAVEX 2-73 Improvement of scores in week 57 from baseline Combined exclusion of SIGMAR1 Pro2 variant + COMT L146 variant and MMSE baseline 20 Exclusion of SIGMAR1 Pro2 variant and MMSE baseline 20 All pa3ents (before marker pre-specifica3on) Higher Cohen s d implies less pa3ents are needed to show a significant difference between placebo arm and ANAVEX 2-73 arm in clinical studies 19

20 Using Precision Medicine to Increase Clinical Trial Success Rate +64% +38% Thomas DW et al. Clinical Development Success Rates BIO Industry Analysis 20

21 Ac3onable Precision Medicine for Targeted Clinical Studies Confirmed safety & dose-dependent target engagement with SIGMAR1 using PET Exome sequencing showed response-linked gene variants Targeted therapy benefit on SIGMAR1/COMT WT variants is expected for about 80% of pa3ent popula3on These signatures can be applied to neurological indica3ons tested with ANAVEX 2-73 including Alzheimer s disease, Re] syndrome and Parkinson s disease demen3a Iden3fied ac3onable gene3c variants support enrichment with gene based biomarkers in the clinical development of ANAVEX 2-73 The newest weapon in the fight against neurological diseases might be your own body Anavex has enough cash for 2 years Precision medicine for targeted clinical studies ini3a3ng: ü Alzheimer s Disease - Phase 2b/3 ü Parkinson s Disease Demen3a - Phase 2 21

22 ANAVEX 2-73 Phase 2b/3 Alzheimer's Disease Study Design N=450 Early AD pa3ent popula3on Confirmed amyloid pathophysiology (CSF/ amyloid PET) Pa3ents aged 60 to 85 years MMSE score DNA and RNA sequencing Randomiza3on 1:1:1 ANAVEX 2-73 High dose # ANAVEX 2-73 Medium dose # Placebo Primary Endpoints at 48 Weeks ADAS-Cog ADCS-ADL Safety and tolerability of ANAVEX 2-73 Key Secondary Endpoints CDR-SB Structural and func3onal MRI Biomarkers: Abeta 40 /Abeta 42, T-tau, P-tau, NFL, YKL-40, neurogranin, BACE1 Pre-specified Endpoints Gene3c variants SIGMAR1 (rs ), COMT (rs / rs ) with influence on treatment effect # Restricted to maintain complete blinding 22

23 Parkinson s Disease Demen3a (PDD): A Devasta3ng Demen3a Disorder Parkinson s disease demen3a: Demen3a occurs a year or more aver the onset of motor symptoms Parkinson's disease is a fairly common neurological disorder in older adults, es3mated to affect nearly 2 percent of those older than age 65 About 1 million Americans have Parkinson's disease It is es3mated that 50 to 80 percent of those with Parkinson's disease eventually experience Parkinson's disease demen3a The brain changes caused by Parkinson's disease begin in a region that plays a key role in movement As Parkinson's brain changes gradually spread, they oven begin to affect mental func3ons, including memory and the ability to pay a]en3on, make sound judgments and plan the steps needed to complete a task 23

24 ANAVEX 2-73 Phase 2 Parkinson s Disease Demen3a Study Design N=120 PDD pa3ent popula3on Diagnosis of probable Parkinson s disease demen3a (PDD) Diagnosis of idiopathic Parkinson s disease Pa3ents aged 50 years MoCA score DNA and RNA sequencing Randomiza3on 1:1:1 ANAVEX 2-73 High dose # ANAVEX 2-73 Medium dose # Placebo Primary Endpoints at 14 Weeks CDR Con3nuity of A]en3on Safety and tolerability of ANAVEX 2-73 Key Secondary Endpoints MDS-UPDRS Sleep func3on Ac3graphy MoCA Other CDR ba]ery measures Pre-specified Endpoints Gene3c variants SIGMAR1 (rs ), COMT (rs / rs ) with influence on treatment effect # Restricted to maintain complete blinding 24

25 Re] Syndrome (RTT): A Devasta3ng Monogenic Disorder Rare gene3c postnatal progressive neurodevelopmental disorder Re] syndrome (RTT) is caused by spontaneous (de novo) muta3on in the MECP2 gene located on the X chromosome For males the gene muta3on is lethal since males have only one X chromosome (females have two X chromosomes) Affects approximately 16,000 females in U.S. 1:10-15K females worldwide For females who survive infancy, RTT leads to a deficiency in motor func3on, cogni3ve impairment and seizures There are no approved treatments for RTT FDA granted ANAVEX 2-73 Orphan Drug Designa3on for Re] syndrome Maria Chahrour, Huda Zoghbi., The Story of ReP Syndrome: From Clinic to Neurobiology, Science Direct (2007); D.ValenL et al., Neuroscience and Biobehavioral Reviews 46 (2014)

26 ANAVEX 2-73 Regulates Gene Expression and Restores BDNF Levels p<0.05 ANAVEX 2-73 fully restores BDNF expression levels in the hippocampus in the Fmr1 KO mouse model (p<0.05, KO vehicle vs. KO ANAVEX 2-73) Presented at AnLepilepLc Drug Trials XIV 2017 Conference 26

27 ANAVEX 2-73 Significantly Reduces Impairment in Mutated MECP2 Re] Syndrome Mouse Model Clasping Hindlimbs (%) Clasping at 8 weeks p<0.001 *** p<0.05 * Normal Impaired Mecp2_WT Vehicle Mecp2_HET Vehicle Mecp2_HET AV2-73 (10 mg/kg) Mecp2_HET AV2-73 (30 mg/kg) 100 Clasping at 12 weeks p<0.01 Clasping Hindlimbs (%) ** p<0.05 * Mecp2_WT Vehicle Mecp2_HET Vehicle Mecp2_HET AV2-73 (10 mg/kg) Mecp2_HET AV2-73 (30 mg/kg) Mice treated with ANAVEX 2-73 (30 mg/kg) clasped less than vehicle-treated mutant mice (p<0.05 at 8 and 12 weeks) Presented at 2016 Epilepsy Pipeline Conference, 2016 ReO Syndrome Symposium 27

28 Tenta3ve ANAVEX 2-73 Phase 2 Re] Syndrome Study Design N = TBD RTT pa3ent popula3on Diagnosis of confirmed RTT Pa3ents age TBD DNA and RNA sequencing Randomiza3on 1:1 ANAVEX 2-73 Ac3ve dose Placebo Primary and Secondary Endpoints <12 Weeks Safety and tolerability of ANAVEX 2-73 Behavioral symptoms Sleep func3on Seizure ac3vity Pre-specified Endpoints Gene3c variants SIGMAR1 (rs ), COMT (rs /rs ) with influence on treatment effect 28

29 Financial Posi3on and Near Term Catalysts Cash (as of June 30, 2018): $25.8M; No debt The company is well capitalized to achieve clinical readouts þ þ þ þ þ Orphan Drug Designa3ons granted ANAVEX 2-73 for the following indica3ons: Re] syndrome, Infan3le spasms Phase 2a Reported 109 week data at CTAD scien3fic mee3ng Phase 2a Reported PK/PD data CTAD scien3fic mee3ng Pa3ent genomics and PET scan S1R target data AAIC 2018 scien3fic mee3ng Phase 2a Repor3ng 148 week data at CTAD 2018 scien3fic mee3ng Phase 2b/3 clinical trial in Alzheimer s disease ini3ated Phase 2 clinical trial in Parkinson s disease demen3a (PDD) Phase 2 clinical trial in Re] syndrome Ongoing in-licensing/out-licensing review to oplmize value of pipeline 29

30 Por{olio of Compounds Varying in SIGMAR1 Binding Ac3vi3es CANDIDATE PRECLINICAL PHASE 1 PHASE 2 PHASE 3 ANAVEX 2-73 *RETT SYNDROME ALZHEIMER S DISEASE PARKINSON S DISEASE *INFANTILE SPASMS FRAGILE X ANGELMAN S ANAVEX 3-71 (AF710B) *FRONT. DEMENTIA (FTD) ALZHEIMER S DISEASE PARKINSON S DISEASE ANAVEX 1-41 DEPRESSION STROKE PARKINSON S DISEASE ALZHEIMER S DISEASE VISCERAL PAIN ANAVEX 1066 ACUTE & NEUROPATHIC PAIN CANCER (PANCREAS) * = Orphan Drug DesignaLon by FDA 30

31 Anavex Life Sciences Exper3se Management Team Christopher U. Missling, PhD President & CEO Emmanuel O Fadiran, RPh, PhD SVP of Regulatory Affairs Stephan Toutain, MS, MBA SVP of Opera6ons Paul Vancutsem, DVM, PhD VP of Preclinical Development Daniel Klamer, PhD VP of Business Development & Scien6fic Strategy FDA Commissioner's Award of Excellence Scien@fic Advisory Board Members Jeffrey Cummings, MD Paul Aisen, MD Harald Hampel, MD, PhD Norman Relkin, MD, PhD O]avio Arancio, MD, PhD Jacqueline French, MD Andrew Cole, MD Tanya Simuni, MD Daniel Weintraub, MD Tangui Maurice, PhD 31

32 Contact Us Corporate Office: Anavex Life Sciences Corp. 51 West 52nd Street, 7th floor New York, NY Shareholder & Media Rela3ons: Core IR Sco] Gordon NASDAQ: AVXL ANAVEX is a trademark of Anavex Life Sciences Corp. 32