Slide 1: ACW Alzheimer's Disease biomarker study clinical results presentation slides
ASX ANNOUNCEMENT ACW Alzheimer’s Disease biomarker study clinical results presentation slides Sydney, 10 October 2022. Actinogen Medical ASX: ACW (“ACW” or “the Company”) is pleased to release the attached presentation slides relating to the positive Phase 2a clinical data from its Alzheimer’s Disea
Slide 2: About Xanamem
cortisol inside brain cells could have a positive impact in these and many other diseases. The cognitive dysfunction, behavioural abnormalities, and neuropsychological burden associated with these conditions is debilitating for patients, and there is a substantial unmet medical need for new and impr
Slide 3: Alzheimer's Disease biomarker study validates Xanamem program
Alzheimer’s Disease biomarker study validates Xanamem® program Positive Phase 2a clinical data Dr. Steven Gourlay MBBS PhD MBA, CEO & MD Professor Paul Rolan MD FRACP, CMO 10 October 2022 Authorised by the Board of Directors of Actinogen Medical Limited ® Xanamem is a registered trademark of Actinog
Slide 4: Disclaimer
Disclaimer This presentation has been prepared by Actinogen Medical Limited. (“Actinogen” or the “Company”) based on information available to it as at the date of this presentation. The information in this presentation is provided in summary form and does not contain all information necessary to mak
Slide 5: Company's Representatives
Company’s Representatives Dr. Steven Gourlay Prof. Paul Rolan Michael Roberts CEO & MD CMO Investor Relations Phase 2a clinical biomarker results 3
Slide 6: Online Q&A
Online Q&A 3. Hit enter on your 1. Click on the Q&A icon 2. Type your question in keyboard to submit your the new Q&A window message To contact support: Please call 1300 816 159 (within Australia) or +61 2 8072 1479 (outside of Australia)
Slide 7: Alzheimer's Disease biomarker study validates Xanamem program
Alzheimer’s Disease biomarker study validates Xanamem® program Positive Phase 2a clinical data Dr. Steven Gourlay MBBS PhD MBA, CEO & MD Professor Paul Rolan MD FRACP, CMO 10 October 2022 Authorised by the Board of Directors of Actinogen Medical Limited ® Xanamem is a registered trademark of Actinog
Slide 8: Alzheimer's Disease key clinical findings
Alzheimer’s Disease (AD) key clinical findings Major points • Phase 2a placebo-controlled trial of Xanamem 10 mg vs. placebo over 12 weeks was re-run in 72 biomarker-positive patients with mild AD • Used a pre-specified protocol & analysis plan to avoid bias • Patients with elevated blood pTau showe
Slide 9: Xanamem Phase 2 & 3 program
Xanamem Phase 2 & 3 program Building on four independent Phase 1 and 2 studies showing activity Current Phase 1 & 2a, biomarker Safety, cognition activity (n~300) Phase 2b Phase 2a Cognitive Impairment Alzheimer’s Disease (AD) in Depressive Disorder (CIDD) Phase 3 Phase 3 Alzheimer’s Disease with fo
Slide 10: AD biomarker study fundamentals
AD biomarker study fundamentals Assessment of efficacy in the Xanamem AD program is based on the proven use of clinical endpoints of cognition and function for regulatory approvals without reliance on biomarkers However, as a supplement to clinical data, biomarkers have one major and two lesser pote
Slide 11: Xanamem: Oral, low dose, once-a-day treatment
Xanamem: Oral, low dose, once-a-day treatment with a unique non-amyloid mechanism Brain penetrant 11β-HSD1 small molecule enzyme inhibitor reduces cortisol inside brain cells - modulating signaling pathways and underlying disease processes1,2 Potential to be: • Rapidly cognitive enhancing • Disease-
Slide 12: Xanamem's mechanism is different to anti-amyloid antibodies
Xanamem’s mechanism is different to anti-amyloid antibodies Corticotrophin Releasing Factor Xanamem ACTH Proteins may Cortisone Cortisol Neuro-inflammation be a secondary phenomena not related to biological causation Dendritic spine Amyloid & pTau GABA, glutamate pruning proteins Neuron death Cognit
Slide 13: Previously: evidence of Xanamem activity in cognition
Previously: evidence of Xanamem activity in cognition from multiple sources Protection against cognitive decline in animal model of AD using a Xanamem analogue independent of amyloid plaque Human PET scan study showing high levels of target binding at doses of 5 mg and above Consistent target
Slide 14: A brief history of Alzheimer's Disease drug development
A brief history of Alzheimer’s Disease drug development See also Actinogen Clinical Trials Science Forum 03 August 2022 https://youtu.be/Bm9ATZx1zEk Phase 2a clinical biomarker results 12
Slide 15: A small number of drugs to tackle cognition have worked
A small number of drugs to tackle cognition have worked and been approved in AD Approved on clinical scales1 in mild-moderate AD, 6-month trials Mechanism First Benefit Comments Approval Oral anticholinesterase inhibitors 1996 Cognitive & functional Gastrointestinal side effects e.g. donepezil, riva
Slide 16: Clinical Dementia Rating – Sum of Boxes endpoint
Clinical Dementia Rating – Sum of Boxes (CDR-SB) endpoint to assess dementia in early-stage AD Test domain Impairment None Questionable Mild Moderate Severe 0 0.5 1 2 3 Memory Orientation Judgment & Problem Solving Community Affairs Home & Hobbies Personal Care Score is sum of each line i.e. score b
Slide 17: Amyloid antibodies are disease modifying
Amyloid antibodies are “disease modifying” based on Positron Emission Tomography (PET) brain scan and CDR-SB Use of blood and cerebrospinal fluid (CSF) levels is in development Predictive How Observations FDA Impact of drug treatment biomarker measured for target Brain amyloid PET scan Aducanumab -
Slide 18: Elevated pTau181 diagnostic for AD type dementia
Elevated pTau181 diagnostic for AD type dementia1 Blood pTau proposed to select patients with confirmed AD in Phase 2b 1. Data shown from Thijssen et al 2020; ADpath Alzheimer’s Disease pathology diagnosis; FTLD Frontotemporal Dementia pathology diagnosis; TAU FTLD type Phase 2a clinical biomarker r
Slide 19: Elevated blood pTau is the single best predictor of progression in AD
Elevated blood pTau is the single best predictor of progression in AD1 Better All have some prognostic benefit Blood pTau proposed to select AD patients likely to progress in Phase 2b 1. Data shown from Cullen et al. 2022; Thijssen et al 2020 showed similar findings for pTau181; similar findings Cul
Slide 20: Phase 2a biomarker study methods and results
Phase 2 biomarker study methods and results Phase 2a clinical biomarker results 18
Slide 21: Phase 2a blood biomarker study design & methods
Phase 2 blood biomarker study design & methods Uses a pre-specified protocol and analysis plan Assess efficacy trends on clinical endpoints Measure disease biomarkers Week 0 & 12 • Prespecified analysis to avoid bias • Select by baseline pTau181, MMSE 72 patients with • pTau181 and amyloid ratio lev
Slide 22: Baseline characteristics of patients confirms similar populations
Baseline characteristics of patients confirms similar populations Slightly higher ADASCog14, CDR-SB & ADCOMS, lower MMSE in biomarker study Biomarker Study XanADu Phase 2a N=72 N=185 Age (mean, SD) 71 (8) 71 (8) % female 54% 57% ADASCog14 (mean, SD) 33 (8) 29 (9) ADCOMS (mean, SD) 0.52 (0.19) 0.50 (
Slide 23: Higher pTau subgroup shows clinically significant effect on CDR-SB
Higher pTau (> 6.74 pg/mL1) subgroup shows clinically significant effect on CDR-SB (n=34) Group most likely to have pathological AD Assessment Desired change Xanamem Placebo Cohen’s p value (n=16) (n=18) d ADASCog14 total (mean) Down 1.5 0.8 0.00 0.74 ADCOMS (mean) Down 0.07 0.09 0.13 0.57 ADASCog14
Slide 24: Benefit on CDR-SB in both high pTau subgroups
Benefit on CDR-SB in both high pTau subgroups Groups most likely to have pathological AD N CDR-SB Group Desired Xanamem Placebo Cohen’s p value change d pTau >6.74 pg/mL1 (mean) 34 Down 0.4 1.0 0.41 0.09 pTau >6.74 pg/mL (median) 34 Down 0.0 0.8 - - pTau >10.2 pg/mL1 (mean) 9 Down 0.1 0.8 0.62 0.33
Slide 25: Xanamem doubled rate of disease stabilization
Xanamem doubled rate of disease stabilization Response analysis in pTau-positive patients Twice as many patients in the Xanamem group had stable or improved disease compared with placebo1 56% of patients treated with Xanamem were stable or improved 0.6-point effect size represents a 60% relative red
Slide 26: MMSE shows Xanamem effect measurable in more impaired dementia
MMSE shows Xanamem effect measurable in more impaired dementia More clinically impaired subgroup N MMSE score Group Desired Xanamem Placebo Cohen’s p value change d MMSE 20-23 (mean) 46 Up 1.7 -0.3 0.93 0.02 MMSE 20-23 (median) 46 Up 2.0 -1.0 - - Clinically & statistically significant effect size of
Slide 27: No change observed over 12 weeks consistent with non-amyloid mechanism
No change observed over 12 weeks consistent with non-amyloid mechanism 10mg vs. placebo, mean (standard error bars), published test-retest range in boxes % change pTau AB42/40 GFAP 20 Cd 0.08 Cd 0.00 Cd 0.04 15 p = 0.40 p = 0.84 p = 0.71 10 5 n=15 0 n=28 n=26 n=19 n=13 n=23 -5 -10 -15 -20 Xanamem Pl
Slide 28: Efficacy conclusions
Efficacy conclusions This analysis validates and de-risks the AD program by showing: Clinical activity of Xanamem in AD patients Large clinical effect size Utility of blood pTau levels to select suitable patients for next Phase 2b trial Utility of CDR-SB to measure the benefit of Xanamem in
Slide 29: Moving forward rapidly in Cognitive Impairment in AD and Depression
Moving forward rapidly in Cognitive Impairment in AD and Depression Biomarker data validate planned Phase 2b protocol in Mild Cognitive Impairment / mild AD with positive blood pTau Phase 2a clinical biomarker results 27
Slide 30: Focus on speed to market as a cognitive enhancing treatment
Focus on speed to market as a cognitive enhancing treatment No functional impairment XanaMIA XanaMIA Functional impairment & loss of independence Phase 1b Phase 2b Healthy 50-80 MCI/early AD1 patients years Mild • N=330, placebo-controlled • pTau patient selection • 10 mg vs. placebo • Safe & well-t
Slide 31: XanaMIA Phase 2b trial design & implementation model
XanaMIA Phase 2b trial design & implementation model: selecting AD patients by blood pTau level 10mg Xanamem Screening 5mg Xanamem Follow-up Placebo -4 0 24 28 Weeks Double-blind, randomised treatment period (N=330) Key inclusion/exclusion criteria Primary Endpoints Key Secondary Endpoints Key Imple
Slide 32: The Xanamem opportunity in depression
The Xanamem opportunity in depression Current anti-depressants work slowly (3 weeks) and do not target cognition multiple adverse effects initial suicide risk blood pressure, sexual function, appetite… Xanamem improves cognition quickly Xanamem may improve both depression and cognitive impairment Ph
Slide 33: XanaCIDD trial design & implementation model
XanaCIDD trial design & implementation model 10mg Xanamem Follow-up Screening Placebo -4 0 6 10 Weeks Double-blind, randomised treatment period (N=160) Key inclusion/exclusion criteria Primary Endpoints Key Secondary Endpoints Key Implementation Features • Primary diagnosis of MDD • Cogstate CTB att
Slide 34: Xanamem's unique value proposition
Xanamem’s unique value proposition Many other opportunities such as other types of dementia and neuropsychiatric conditions Phase 2a clinical biomarker results 32
Slide 35: Actinogen has the only non-amyloid mechanism drug in development
Actinogen has the only non-amyloid mechanism drug in development with credible cognitive data It is one of only three worldwide AD clinical trial programs for an oral medication with credible cognitive activity data Mechanism Stage Cognitive endpoint Company market cap. ($AU)1 Oral Xanamem to lower
Slide 36: Xanamem Strategy & Timeline
Xanamem Strategy & Timeline Phase 2a clinical biomarker results 34
Slide 37: Actinogen strategy validated by new results
Actinogen strategy validated by new results Accelerate clinical development Create value from partnerships • Focus on cognitive enhancement: Pharma/biotech engagement • Patients with early Alzheimer’s Disease • Actively engage large and mid-size • Use pTau for patient selection potential partners wi
Slide 38: Xanamem timeline & catalysts
Xanamem timeline & catalysts • October multiple partnering presentations of new results • November CTAD XanaMIA presentation • Trial enrollment starts for XanaCIDD trial in Depression 2022 • Key global regulatory submissions in AD with FDA, EMA, other • Phase 2b XanaMIA AD trial preparation • Partne
Slide 39: Eminent world-leading authority on dementia commented
Eminent world-leading authority on dementia, Associate Professor Michael Woodward, commented: “The positive data for CDR-SB and other endpoints are encouraging and indicate a likely therapeutic effect of Xanamem in patients with the early stages of Alzheimer’s Disease. The use of pTau blood levels t
Slide 40: Questions
Questions Phase 2a clinical biomarker results 38
Slide 41: Online Q&A
Online Q&A 3. Hit enter on your 1. Click on the Q&A icon 2. Type your question in keyboard to submit your the new Q&A window message To contact support: Please call 1300 816 159 (within Australia) or +61 2 8072 1479 (outside of Australia)
Slide 42: Thank you
Thank you If you have any questions following the webcast please contact: Dr. Steven Gourlay Michael Roberts CEO & Managing Director Investor Relations P. +61 2 8964 7401 M. +61 423 866 231 E. steven.gourlay@actinogen.com.au E. michael.roberts@actinogen.com.au Phase 2a clinical biomarker results 40
Slide 43: Appendix
Appendix Phase 2a clinical biomarker results 41
Slide 44: Xanamem Clinical Development Pipeline
Xanamem Clinical Development Pipeline Phase 2 Pathway Outlook Biomarker/efficacy analysis in patients with mild AD Cognitive impairment in - Phase 2 dataset of 10mg vs. placebo over 12 weeks, October 2022 “Big-to-market” early Alzheimer’s disease Cognitive benefit in patients with early stages of AD
Slide 45: Selected glossary
Selected glossary 1 11β-HSD1 11 beta HydroxySteroid Dehydrogenase-1 enzyme Aβ Amyloid beta – a type of amyloid protein associated with Alzheimer’s Disease, 42 and 40 are different forms ACTH Adrenocorticotropic hormone that regulates blood levels of cortisol ADAS-Cog Alzheimer’s Disease Assessment S
Slide 46: Selected glossary
Selected glossary 2 IQCODE Informant Questionnaire on Cognitive Decline in the Elderly MCI Mild Cognitive Impairment – memory, executive function deterioration with retained functional abilities MDD Major Depressive Disorder MMSE Mini Mental State Examination – a 30-point scale of simple questions t