Anavex Life Sciences Corp. · NASDAQ:AVXL
Anavex Life Sciences — 2016 Rett Syndrome Symposium
30 slides from Anavex Life Sciences's conference presentation, Jun 23, 2016
Slide 1: Rett Syndrome Research Symposium 2016
Sil TM ALI SU wall : UNITY: STRENGTH « HOPE RETTSYNDROME.ORG * EAGLEWOOD RESORT, ILLINOIS + 2016 RESEARCH SYMPOSIUM (JUNE 22-24) Nothing replaces the experience of meeting jace-to-face 14th org Rett Syndrome ium, an i ie interdisciplinary meeting focused on recent advances in Rett syndrome research
Slide 2: ANAVEX 2-73 as a Potential Treatment for Rett Syndrome and Other Pediatric Disorders
Wanevex. LIFE SCIENCES Corp.™ ANAVEX 2-73 as a Potential Treatment for Rett Syndrome and Other Pediatric or Infantile Disorders with Seizure Pathology N. REBOWE!, J SPROUSE’,D. BRUNNER®,P. KABITZKE?,L VELISEK M. BENSON? J. VELISKOVAY. C. MISSLING! New York,NY: Tarnow, Vara, WY 2016 Rett Syndrome Sym
Slide 3: Disclosure
Disclosure a = Employee of Anavex Life Sciences = Shareholder of Anavex Life Sciences = Options of Anavex Life Sciences Wonayex.
Slide 4: Safe Harbor
Safe Harbor This ion contains forward-lookit 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,” * will," “estimates, 2 7
Slide 5: ANAVEX 2-73
ANAVEX™ 2-73 x Currently in a Phase 2a clinical trial for Alzheimer’s disease (AD) ANAVEX 2-73 is an orally available small molecule targeting protein misfolding, oxidative stress, mitochondrial dysfunction, inflammation and cellular stress, factors in f ‘ive and diseases through activation of the S
Slide 6: Sigma-1 Receptor: Upstream Pluripotent Modulator
Sigma-1 Receptor: Upstream Pluripotent Modulator ay = Reducing mitochondrial dysfunction = Reducing oxidative stress = Reducing protein misfolding = Reducing inflammation = Modulating Ca?* = Enabling neuroprotection suctal 016 Feb 8 7 sesso, ome 10 2013 ages 2726; se
Slide 7: Common in Neurodegenerative Diseases: ER-Mitochondria Axis Disruption
Common in Neurodegenerative Diseases: ER-Mitochondria Axis Disruption ... Sigma-1R Restores Association ... Disease situation Normal situation ey ANAVEX 2.73 ‘TOP-43 e /ANAVEX 2-73 Mitochondrion \drion Endoplasmic reticulum (ER)-Mitochondria associations are disrupted in neurodegenerative diseases .
Slide 8: Mitochondrial Dysfunction: Convergence of Pathological and Genetic Lesions
Mitochondrial Dysfunction: Convergence of Pathological and Genetic Lesions in Neur I | and Neurod: ‘ative Diseases ey tanta Tends inNeuroscences cata na = CelPress ‘Neuroscience and Biobehavioral Reviews: i. Review aswe po ' : ; = There's Something Wrong with “Mitochonerial dysfunction asa central a
Slide 9: ANAVEX 2-73: Confirmed Targeted Indications
ANAVEX™ 2-73: Confirmed Targeted Indications: From Rare Disease Indications to Largest CNS Indication ... éS 4 Rett Syndrome (RTT) 4 Alzheimer’s Disease (AD) Rare neurodevelopmental disease Neurodegenerative disease Preclinical validation, RettSyndrome.org Clinical validation Phase 2a ica Planning b
Slide 10: Neurodevelopmental and Neurodegenerative Disease Pipeline
Neurodevelopmental and Neurodegenerative Disease Pipeline a PRECLINICAL, PHASE 1 PHASE 2 PHASE 2 ANAVEX™ 2:73 ALZHEIMER'S ‘COGNITION IN NEUROPSYCHIATRIC EPILEPSY PARKINSON'S MULTIPLE SCLEROSIS (MS) RARE DISEASE, FRAGILE X > RARE DISEASE, RETT SYNDROME 5 RARE DISEASE, INFANTILE SPASMS. ANAVEX" 3.71 (
Slide 11: ANAVEX 2-73 Pre-Clinical Epilepsy Data
ANAVEX™ 2-73 Pre-Clinical Epilepsy Data Significant Seizure Reduction with ANAVEX2-73 in Long-Lasting Effect Shown in PTZ- both MES and PTZ-Induced Seizure Models Induced Seizures 100 100 + 90 *** p<0.001 90 80 | = MES-induced 80 8 10 convulsions § 70+ g g Zz 0- ZB 0) 2 5 50) Eso = 4hours B40 ™ PTZ-
Slide 12: Anti-Depressant and Anti-Anxiety Effect of ANAVEX 2-73
Anti-Depressant and Anti-Anxiety Effect of ANAVEX™ 2-73 in Porsolt Swim Test (PST) and in Open Field Test e No observed “sedative” effect of ANAVEX 2-73 1 os . Bm . Tw i a 5 ] 3” {= bo dw | H : v = 100 ANAVEX2-73 v : 50 7 100 . ANAVEX2.73 (mg/kg p.0) mpkere) = Effect of ANAVEX2-73 on immobility time
Slide 13: Autism Spectrum Disorders and Fragile X Syndrome
Autism Spectrum Disorders and Fragile X Syndrome ES = Autism spectrum disorders (ASD) occur in up to 2/3 of males and 1/3 of females with Fragile X syndrome (FXS) = FXS is the most common form of inherited intellectual disability and the most frequent single gene cause of autism, affecting approxima
Slide 14: ANAVEX 2-73 Reverses Hyperactivity and Deficits in Fragile X Model
ANAVEX 2-73™ Significantly Reverses the Hyperactivity and Deficits in Learning and Memory in Fragile X — Autism-Related Disorders Model SS 5 AV2-73 Reverses Hyperactivity of AV2-73 Normalizes the Impairment in AV2-73 Reduces Impairments in Fmr1-KO2 mice to Normal Associative Learning Characteristic
Slide 15: Infantile Spasms
Infantile Spasms A rare yet devastating condition, infantile spasms (IS) is a seizure disorder that typically occurs during the first 4-11 months of childhood Children who develop IS are at great risk for developmental disability and autism Most children who have infantile spasms will have a very ab
Slide 16: Preclinical Infantile Spasms
Preclinical Infantile Spasms x The infantile spasms rat model represents a clinically relevant animal model of infantile spasms since the phenotype is developmentally specific and semiologically similar to human infantile spasms, including clustering of spasms* The phenotype of spasms persists only
Slide 17: ANAVEX 2-73 Significantly Reduces Spasms in Infant Rat Model
ANAVEX 2-73™ Significantly Reduces the Number of Spasms in an Infant Rat Model of Infantile Spasms és C3 Vehicle 150 OF 7 an eo 2 100 § 8 3 : 8 3 2 5 3 Ss 0 Treatment with ANAVEX 2-73 significantly reduced the number of spasms by 55 percent compared to vehicle (p=0.0002) 17 WNonayex.
Slide 18: Rett Syndrome
Rett Syndrome és What is Rett Syndrome? Rare non-inherited genetic postnatal progressive neurodevelopmental disorder Caused by mutation of MECP2 gene Occurs almost exclusively in girls and leads to severe impairments One in 10,000 to 15,000 girls Seizures Anxiety disorder Cognitive impairment Loss o
Slide 19: Preclinical Rett Syndrome
Preclinical Rett Syndrome Breeding info Female mice with heterozygous (HET) MECP2-null mutation* A mouse with a MECP2-null mutation causes neurological symptoms that mimic Rett syndrome Breeding done at Jackson Laboratories, mice provided at 4-5 weeks of age MECP2 females testing at 8 and 12 weeks o
Slide 20: Clasping
Clasping ay = Mice are lifted gently by the tail with front limbs remaining on surface = Clasping of hind legs is noted (normal is a spread in the hind legs) Impaired 20
Slide 21: Clasping at 8 and 12 Weeks
Clasping at 8 and 12 Weeks ey = Vehicle-treated mutant (HET) mice clasped more than vehicle-treated wild type (WT) mice (p<0.001 at 8 weeks; p<0.01 at 12 weeks) Mice treated with AV2-73 (30 mg/kg) clasped less than vehicle-treated mutant mice (p<0.05 at 8 and 12 weeks) Clasping at 8 weeks Clasping a
Slide 22: Startle
Startle ay = The acoustic startle measures an unconditioned reflex response to external auditory stimulation = Wild type mice have a higher startle response compared to impaired mice Image: www.med-associates.com Source: PsychoGenics, Inc.
Slide 23: Startle at 12 Weeks
Startle at 8 Weeks és = Vehicle-treated mutant (HET) mice startled less compared to vehicle- treated wild type (WT) mice (p<0.001) = AV2-73 (30 mg/kg) treated mice showed an increased startle response compared to vehicle-treated mutant mice (p<0.05) p<0.001 p<0.05 * ‘Mean Startle Response vecp2_WT V
Slide 24: Rotarod
Rotarod Source: PsychoGenies, Inc rm x 24
Slide 25: Rotarod at 8 and 12 Weeks
Rotarod at 12 Weeks ey Vehicle-treated mutant (HET) mice fell significantly more rapidly and at lower speeds compared to vehicle-treated wild type (WT) mice (p<0.001) = AV2-73-treated mice at both doses (10 and 30 mg/kg) took significantly more time to fall off the rod and fell at higher speeds comp
Slide 26: NeuroCube
NeuroCube A platform that employs computer vision to detect changes in gait geometry and gait dynamics in rodent models of neurological disorders, pain & neuropathies Mice are allowed to walk in the chamber for 5 min When the paw touches the screen, LED light reflects creating bright spots Images ar
Slide 27: NeuroCube Body Motion Features
NeuroCube Body Motion Features a Bad) Mowment Features Measurment Amplitude = Shift the difference between the first and the last values = Amplitude — the difference between maximal and minimal values = Volatility = Shift / Amplitude > Mino a a a a a acd 27 Source: PsychoGenics, Inc Monavex.
Slide 28: NeuroCube at 8 Weeks
NeuroCube at 8 Weeks Some gait differences appear to be rescued <0.05 70 p<0.01 38 Stride Length (mm) Front Step Length (mm) fer Av2-7 (10 mg) Ml usep2_HET AV2-73 90 moa) <0.05 Wonavex 28
Slide 29: NeuroCube at 12 Weeks: Comprehensive Analysis
NeuroCube at 8 Weeks Comprehensive Analysis: Gait, Correlation, Body Motion d és p' wrvehice v. Het vehicle v. Het vehicle v. Het vehicle Het AV2-73, 10, Het AV2-73, 30 Overall 90, p=0 53, p> 0.69 62, p> 0.24 GAIT 78, p< 0.01 63, p> 0.09 69, p< 0.05 Paw Features 91, p< 0.001 52, p> 0.78 55, p> 0.56
Slide 30: Summary
Summary és Administration of ANAVEX 2-73 results in both significant and dose related improvements in an array of behavioral paradigms in the MECP2 HET Rett syndrome disease model These behavioral paradigms measure different aspects of muscular coordination, balance, motor learning and muscular stre