Anavex Life Sciences Corp. · NASDAQ:AVXL

Anavex Life Sciences — CTAD 2015

18 slides from Anavex Life Sciences's conference presentation, Nov 7, 2015

Slide 1: CTAD Presentation: New Exploratory Alzheimer's Drug ANAVEX 2-73
CTAD Presenta-on New Exploratory Alzheimer’s Drug ANAVEX 2-‐73: Assessment of Safety and Cogni-ve Performance in a Phase 2a Study in mild-‐to-‐moderate Alzheimer’s Pa-ents Steve Macfarlane, Paul Maruﬀ, Marco Cecchi, Dennis Moore, Tasos Zograﬁdis, Christopher Missling November 7th 2015 Associate P
Slide 2: ANAVEX 2-73
ANAVEX 2-‐73 ▪ ANAVEX 2-‐73 is an orally available small molecule with a favorable safety proﬁle in Phase 1 ▪ ANAVEX 2-‐73 ac-vates the Sigma-‐1 Receptor, a key upstream cellular modulator media-ng clearance of misfolded proteins including Aβ and Tau ▪ As such, may have potenLal to modify protei
Slide 3: ANAVEX 2-73 Significantly Improves Memory in Transgenic Alzheimer's Mouse Model
ANAVEX 2-‐73 Signiﬁcantly Improves Memory in Transgenic Alzheimer's Disease Mouse Model (Tg2576) P<0.01 ▪ 10 month-‐old Tg2576 and WT male mice administered p.o. (oral) with tap water or ANAVEX 2-‐73 (3 mg/kg/day); A[er 2 months, tested for place learning in the water-‐maze; N = 6-‐12 per group
Slide 4: Protocol Summary ANAVEX 2-73
Protocol Summary ANAVEX 2-‐73 ▪ Phase 2a study of 32 paLents with mild-‐moderate AD ▪ 5 weeks’ duraLon, randomized, open label, with main inclusion criteria ▪ MMSE 16-‐28, ▪ CT or MRI within 12 months consistent with AD ▪ Either AChEI-‐naïve (n = 7), or on a stable AChEI dose for at least 3 mont
Slide 5: ANAVEX 2-73: Phase 2a with Adaptive Trial Design
ANAVEX 2-‐73: Phase 2a with Adap-ve Trial Design ANAVEX 2-‐73 starLng dose 30mg/50mg (oral) or 3mg, 5mg (IV) Mild-‐Mod AD ANAVEX 2-‐73 starLng dose 30mg/50mg (oral) or pa-ents 3mg, 5mg (IV) + Donepezil Healthy control, Donepezil/ AchEI# No. of Pts ▪ 32 mild-‐moderate AD pa6ents (MMSE 16-‐28),
Slide 6: Part A: Bioavailability Cross-Over Design and Part B: 52-Week Extension
PART A: Bioavailability Cross-‐Over Design and PART B: 52-‐Week Open-‐Label Voluntary Extension ORAL ORAL ORAL Screening RandomizaLon ORAL IV IV IV wash out 12d 12d 12d 5 week 26 week 52 week 1st Period 2nd Period 12 week 38 week [Lme] Part A Completed Ongoing Part B PK - Study Extension ▪ Once d
Slide 7: Baseline Patient Characteristics and Disposition
Baseline Pa-ent Characteris-cs and Disposi-on Baseline Pa-ent Characteris-cs n = 32 Age years, mean 71 ApoE4 n (%) Carriers 17 (53%) Non-‐carriers 15 (47%) MMSE, median, (±SD) 20.5 (4.0) AD Medica6on use,* n (%) 25 (78%) Disposi-on Randomized 32 Dosed 32 Discon6nued Treatment: AE not related to stu
Slide 8: Adverse Events (AEs)
Adverse Events (AEs) ▪ The most common AE was dizziness (20 events in 15 paLents) followed by headache (16 events in 10 paLents) ▪ Events were mild or moderate and reversible with 80% being grade 1 ▪ Most (94.4%) observed within ﬁrst 8 days ▪ AE proﬁle similar to that of healthy volunteer Phase 1 da
Slide 9: Adverse Events (AEs) Details
Adverse Events (AEs) Details Mild Moderate Severe AE Body System Total N=Events (Grade 1) (Grade 2) (Grade3) Nervous system disorders (36 of 47 dizziness and headache) 35 (74%) 12 (26%) 0 (0%) 47 (46%) General disorders and administraLon site condiLons 14 (88%) 2 (13%) 0 (0%) 16 (16%) GastrointesLna
Slide 10: Efficacy Data Measurements Cognition and Function
Eﬃcacy Data Measurements Cogni-on and Func-on § Exploratory cogniLve measures Cogstate baoery; (MMSE) § FuncLonal measures (ADCS-‐ADL) § ERP (P300): fundamental measures of synapLc network performance § ERP target detecLon task measures: direct measure of aoenLon, speed of brain processing, and
Slide 11: ANAVEX 2-73 Increases MMSE by +1.5 Points at Week 5
ANAVEX 2-‐73 Increases MMSE by +1.5 Points at Week 5 24 23 22 MMSE score 21 Δ = +1.5 points# 20 19 18 MMSE (BASELINE) MMSE (WEEK 5) § ANAVEX 2-‐73 improved median MMSE by +1.5 points at week 5 § n= 30 at baseline and week 5 with on-‐oﬀ-‐on ANAVEX 2-‐73 dosing regimen without any dose opLmizaL
Slide 12: ANAVEX 2-73 Significantly Improves Components of Cogstate Tasks at Week 5
ANAVEX 2-‐73 Signiﬁcantly Improves Components of Cogstate Tasks at Week 5: Eﬀect sizes for Change from Baseline CogniLve CogniLve Decline Improvement *p<0.05, **p<0.001 § ANAVEX 2-‐73 improved 5 of 6 Cogstate Tasks at week 5 § n= 30 at baseline and week 5 with on-‐oﬀ-‐on ANAVEX 2-‐73 dosing r
Slide 13: Cogstate Tasks at Week 5: Data Relative to AD Control Group
ANAVEX 2-‐73 Signiﬁcantly Improves Components of Cogstate Tasks at week 5: Data Rela-ve to Change in AD Control Group CogniLve CogniLve Decline Improvement DetecLon 0.33 * Meta-‐analyses indicate IdenLﬁcaLon* high dose of 0.40* donepezil ~0.28 in similar One Back** 0.86** paLents# Visual Learning
Slide 14: ANAVEX 2-73 Reverses Cognitive Deficits Measured by Standard ERP Methods
ANAVEX 2-‐73 Reverses Cogni-ve Deﬁcits Measured by Standard ERP Methods at Week 5 P300 Amplitude Task Accuracy! False Alarms! Reac-on Time! (µV) (%) (%) (ms) Baseline 5.99±0.58 83.8±.3.9 3.4±1.0 559.0±24.0 Week 5 7.09±0.72 92.6±2.4 1.0±0.5 492.6±23.8* Healthy Control* 7.36±0.39 94.1±1.1 1.1±0.2 458
Slide 15: Interim Data: ANAVEX 2-73 Increases ADCS-ADL by +3.21 Points at Week 12
Interim Data: ANAVEX 2-‐73 Increases ADCS-‐ADL by +3.21 Points at Week 12 70.00 68.00 66.00 Δ = +3.21 points# ADCS-ADL score 64.00 62.00 60.00 58.00 ADCS-ADL (Baseline PART B) ADCS-ADL (Week 12) § Interim data: ANAVEX 2-‐73 improved ADCS-‐ADL signal in 11 out of 14 (78.6%) paLents § # p = not
Slide 16: Summary
Summary ▪ Primary endpoints met with favorable safety and tolerability ▪ Despite the Phase 2a trial not being designed to demonstrate sta-s-cal signiﬁcance, improvement on cogni-on at all doses: ▪ StaLsLcally signiﬁcant improvement in Cogstate IdenLﬁcaLon Task and Cogstate One Back Task at week 5 ▪
Slide 17: Future Development
Future Development ▪ Phase 2a (PART A) results demonstrate an acceptable safety, bioavailability and tolerability/risk proﬁle to conLnue development ▪ SupporLve evidence (Cogstate, MMSE, ERP) indicaLng a cogniLve beneﬁt associated with ANAVEX 2-‐73 already at 5 week treatment including a washout pe
Slide 18: Acknowledgments
Acknowledgments Thanks to: ▪ Principal InvesLgators & clinical sites’ study staﬀ ▪ Data safety review commioee ▪ Anavex SAB Jeﬀrey Cummings, MD Paul Aisen, MD Harald Hampel, MD, PhD Norman Relkin, MD, PhD Michael Gold, MD John Harrison, PhD Ooavio Arancio, MD, PhD ▪ Most of all, grateful acknowledge

Anavex Life Sciences — CTAD 2015 on 6ix

Anavex Life Sciences — CTAD 2015

Slide 1: CTAD Presentation: New Exploratory Alzheimer's Drug ANAVEX 2-73

Slide 2: ANAVEX 2-73

Slide 3: ANAVEX 2-73 Significantly Improves Memory in Transgenic Alzheimer's Mouse Model

Slide 4: Protocol Summary ANAVEX 2-73

Slide 5: ANAVEX 2-73: Phase 2a with Adaptive Trial Design

Slide 6: Part A: Bioavailability Cross-Over Design and Part B: 52-Week Extension

Slide 7: Baseline Patient Characteristics and Disposition

Slide 8: Adverse Events (AEs)

Slide 9: Adverse Events (AEs) Details

Slide 10: Efficacy Data Measurements Cognition and Function

Slide 11: ANAVEX 2-73 Increases MMSE by +1.5 Points at Week 5

Slide 12: ANAVEX 2-73 Significantly Improves Components of Cogstate Tasks at Week 5

Slide 13: Cogstate Tasks at Week 5: Data Relative to AD Control Group

Slide 14: ANAVEX 2-73 Reverses Cognitive Deficits Measured by Standard ERP Methods

Slide 15: Interim Data: ANAVEX 2-73 Increases ADCS-ADL by +3.21 Points at Week 12

Slide 16: Summary

Slide 17: Future Development

Slide 18: Acknowledgments