Anavex Life Sciences Corp. · NASDAQ:AVXL
Anavex Life Sciences — 2016 Epilepsy Pipeline Conference
19 slides from Anavex Life Sciences's conference presentation, Feb 26, 2016
Slide 1: Assessment of ANAVEX 2-73 in a MECP2 Rett Syndrome Mouse Model
Assessment of ANAVEX 2-‐73 in a MECP2 Re5 Syndrome Mouse Model 2016 Epilepsy Pipeline Conference February 26th 2016
Slide 2: Safe Harbor
Safe Harbor This presenta,on contains forward-‐looking statements made within the meaning of the Private Securi,es Li,ga,on Reform Act of 1995 by Anavex™ Life Sciences Corp. and its representa,ves. These statements can be iden,fied by introductory words such as ``expects,'' ``plans,'' ``intends,'' `
Slide 3: Rett Syndrome
Re5 Syndrome § ReN syndrome is a rare non-‐inherited gene,c postnatal progressive neurodevelopmental disorder that occurs almost exclusively in girls and leads to severe impairments § Affec,ng nearly every aspect of the child’s life: their ability to speak, walk, eat, and even breathe easily § It
Slide 4: ANAVEX 2-73
ANAVEX™ 2-‐73 § Currently in a Phase 2a clinical trial for Alzheimer‘s disease (AD) § ANAVEX 2-‐73 is an orally available small molecule targe,ng protein misfolding and cellular stress, factors in neurodegeneraKve diseases through ac,va,ng Sigma-‐1 Receptor § Phase 2a (PART A) results demonstr
Slide 5: Sigma-1 Receptor: Upstream Pluripotent Modulator
Sigma-‐1 Receptor: Upstream Pluripotent Modulator ANAVEX2-73 § Enabling neuroprotec,on § Modula,ng Ca2+ § Reducing protein misfolding § Reducing mitochondrial dysfunc,on § Reducing oxida,ve stress § Blocking NOS § Reducing inflamma,on Su et al., Trends Pharmacol Sci. 2016 Feb 8. pii: S0165-‐
Slide 6: ANAVEX 2-73 Pre-Clinical Epilepsy Data
ANAVEX™ 2-‐73 Pre-‐Clinical Epilepsy Data Significant Seizure Reduc,on with ANAVEX2-‐73 in Long-‐Las,ng Effect Shown in PTZ-‐ both MES and PTZ-‐Induced Seizure Models Induced Seizures *** *** *** *** 100 *** *** 100 90 *** p<0.001 90 80 MES-‐induced 80 convulsions # % of Seizure reducKon % of S
Slide 7: Anti-Depressant and Anti-Anxiety Effect of ANAVEX 2-73 in PST and Open Field Test
AnK-‐Depressant and AnK-‐Anxiety Effect of ANAVEX™ 2-‐73 in Porsolt Swim Test (PST) and in Open Field Test No observed “sedaKve” effect of ANAVEX 2-‐73 § Effect of ANAVEX2-‐73 on immobility ,me on § Effect of ANAVEX2-‐73 on the number of PST. P<0.01, *p<0.05 and **p<0.01 for 50 and crosses (mo,l
Slide 8: Preclinical Rett Syndrome
Preclinical Re5 Syndrome Breeding info § Female mice with heterozygous (HET) MECP2-‐null muta,on# § A mouse with a MECP2-‐null muta,on causes neurological symptoms that mimic ReN syndrome § Breeding done at Jackson Laboratories, mice provided at 4-‐5 weeks of age MECP2 females tesKng at 8 and
Slide 9: Clasping
Clasping § Mice are lixed gently by the tail with front limbs remaining on surface § Clasping of hind legs is noted (normal is a spread in the hind legs) Normal Impaired 9
Slide 10: Clasping at 8 and 12 Weeks
Clasping at 8 and 12 Weeks § 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 C
Slide 11: Startle
Startle § The acous,c startle measures an uncondi,oned reflex response to external auditory s,mula,on § Wild type mice have a higher startle response compared to impaired mice Image: www.med-associates.com Source: PsychoGenics, Inc. 11
Slide 12: Startle at 8 Weeks
Startle at 8 Weeks § 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) 600 500 p<0.001 p<0.05 Mean Startle Respons
Slide 13: Rotarod
Rotarod Source: PsychoGenics, Inc. 13
Slide 14: Rotarod at 8 Weeks
Rotarod at 12 Weeks § 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 ,me to fall off the rod and fell at higher speeds
Slide 15: NeuroCube
NeuroCube § A plazorm 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 crea,ng bright spots §
Slide 16: NeuroCube Body Motion Features
NeuroCube Body MoKon Features B ody Movement Features Measurement 120 110 100 Amplitude 90 Shift 80 70 § Shix – the difference between the first 60 and the last values § Amplitude – the difference between 50 maximal and minimal values § Vola,lity = Shix / Amplitude 40 MinDia 500 550 600 650 700 750
Slide 17: NeuroCube at 8 Weeks
NeuroCube at 8 Weeks Some gait differences appear to be rescued p<0.05 p<0.05 70 p<0.01 38 p<0.05 * * F ro n t S te p L e n g th (m m ) S tr id e L e n g th (m m ) 36 60 ** * 34 50 32 40 30 M e c p 2 _ W T V e h ic le M e c p 2 _ H E T V e h icle M e c p 2 _ W T V e h ic le M e c p 2 _ H E T V e h ic
Slide 18: NeuroCube at 8 Weeks: Comprehensive Analysis
NeuroCube at 8 Weeks Comprehensive Analysis: Gait, CorrelaKon, Body MoKon demonstrate significant improvement WT vehicle v. Het vehicle v. Het vehicle v. Het vehicle Het AV2-‐73, 10 mg/kg Het AV2-‐73, 30 mg/kg 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 Feat
Slide 19: Summary
Summary § Administra,on of ANAVEX 2-‐73 results in both significant and dose related improvements in an array of behavioral paradigms in the MECP2 HET ReN syndrome disease model § Taken together, these behavioral paradigms measure different aspects of muscular coordina,on, balance, motor learning a
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