Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Corporate Update (September 2022)
30 slides from Actinogen Medical's corporate update, Sep 13, 2022
Slide 1: ASX Announcement: Alzheimer's Disease biomarkers - context & history
For personal use only ASX ANNOUNCEMENT Actinogen Alzheimer’s Disease biomarkers - context & history Sydney, 13 September 2022. Actinogen Medical ASX: ACW (“ACW” or “the Company”) is pleased to attach a presentation on the Xanamem ® clinical development program that includes some background on the us
Slide 2: About Xanamem
About Xanamem Xanamem’s novel mechanism of action is to block the production of cortisol inside cells through the inhibition of the 11β- HSD1 enzyme in the brain. Xanamem is designed to get into the brain after it is absorbed in the intestines upon swallowing its capsule. Chronically elevated cortis
Slide 3: Xanamem Clinical Program Update: AD biomarkers - context and history
For personal use only Xanamem® Clinical Program Update: Alzheimer’s Disease (AD) biomarkers - context and history Dr. Steven Gourlay MBBS PhD MBA, CEO & MD 13 September 2022 ® Xanamem is a registered trademark of Actinogen Medical Limited
Slide 4: Disclaimer
Disclaimer For personal use only 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 inform
Slide 5: Actinogen snapshot
Actinogen snapshot Actinogen Medical (ASX:ACW) is developing a novel oral treatment with rapid onset of clinical activity to improve cognition and quality of life For personal use only Demonstrated target engagement in brain and HPA axis1 in human trials Favourable pharmaceutical properties Low
Slide 6: Xanamem Clinical Development Pipeline
Xanamem Clinical Development Pipeline For personal use only Phase 2 Pathway Outlook Biomarker analysis in patients with mild AD Cognitive impairment in - Phase 2 dataset of 10mg vs. placebo over 12 weeks, H2 2022 “Big-to-market” early Alzheimer’s disease Cognitive benefit in patients with early stag
Slide 7: Clinical trials program overview
Clinical trials program overview For personal use only Phase 2 and 3 trials to achieve marketing approvals Current Phase 1 & 2 datasets Safety, cognition activity (n~300) Phase 2 Phase 2 Cognitive Impairment Alzheimer’s Disease in Depression 2 x Phase 3 2 x Phase 3 Alzheimer’s Disease Cognitive Impa
Slide 8: ACW top stockholders and stock price
ACW top stockholders and stock price For personal use only Share price chart at 12 Sep 2022 Trading Information 52 week high A$0.20 52 week low A$0.04 25.0m Number of issued shares 1,796M 0.19 Market capitalisation (12 Sep 2022) A$126M 0.17 Cash Balance at 30 Jun 2022 A$16.4M 20.0m 0.15 Major Shareh
Slide 9: Leadership and Management
Leadership and Management Extensive drug development and commercial experience For personal use only Experienced Board of Directors... …with a talented management team in place Jeff Carter Chief Financial Officer B. Fin Admin; M. App. Fin; CA Tamara Miller SVP Product Development M.Med Sci; BSc; MSc
Slide 10: International Cognition Clinical Advisory Board
International Cognition Clinical Advisory Board Global thought leaders in clinical trials for assessment of cognition For personal use only Prof. John Harrison Dr Dana C. Hilt Dr Christina Kurre Olsen Prof. Paul Maruff Metis Cognition Ltd • Expert psychologist with a special • 25+ years of drug deve
Slide 11: AD biomarker fundamentals
AD biomarker fundamentals For personal use only Xanamem biomarker profile to be assessed September/October 2022 The Xanamem program in AD is based on the proven use of clinical endpoints of cognition and function for regulatory approvals without reliance on biomarkers. AD biomarkers have no relevanc
Slide 12: Xanamem: Oral, low dose, once-a-day treatment with a unique mechanism
Xanamem: Oral, low dose, once-a-day For personal use only treatment with a unique mechanism in Phase 2 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
Slide 13: A brief history of Alzheimer's Disease drug development
For personal use only A brief history of Alzheimer’s Disease drug development See also Actinogen Clinical Trials Science Forum August 2022 https://youtu.be/Bm9ATZx1zEk Xanamem Development Program Update 11
Slide 14: A small number of drugs to tackle cognition have worked in AD
A small number of drugs to tackle cognition have worked and been approved in AD For personal use only Approved on clinical scales1 in mild-moderate AD, 6-month trials Mechanism First Benefit Comments Approval Oral anticholinesterase inhibitors 1996 Cognitive & functional Gastrointestinal side effect
Slide 15: FDA opened accelerated approval pathway in AD using biomarkers
For personal use only In 2021 the FDA opened the door to an ‘accelerated’ approval pathway in AD, previously used for cancer, using biomarkers as endpoints Actinogen is investigating the use of this strategy for Xanamem with a panel of blood biomarkers to choose the right patients for trials and fur
Slide 16: Amyloid measured by PET brain scan used for FDA approvals
Amyloid measured by Positron Emission Tomography (PET) brain scan used for FDA approvals For personal use only Use of blood and cerebrospinal fluid (CSF) levels is in development Predictive How Observations FDA Impact of drug biomarker measured treatment for target Brain amyloid PET scan Aducanumab
Slide 17: Blood biomarkers predict brain amyloid in AD
Blood biomarkers predict brain amyloid in AD High specificity and sensitivity approaching the maximum ROC AUC1 of 1.0 For personal use only Actinogen’s biomarker study includes amyloid (Aβ42 & 40), p-tau181 and GFAP. Blood biomarkers may replace brain scanning in the near future. Palmqvist et al. 20
Slide 18: Blood P-tau is the best single predictor of progression
Blood P-tau is the best single predictor of progression in early stages of AD1 For personal use only Better All have some prognostic benefit Improving biomarkers likely to predict clinical response to treatment in AD 1. Data shown from Cullen et al. 2022; similar findings Cullen et al. 2021, Aβ amyl
Slide 19: Only non-amyloid mechanism drug in development with credible cognitive data
Actinogen has the only non-amyloid mechanism drug in development with credible cognitive data For personal use only It is potentially* one of only three worldwide AD clinical trial programs for an oral medication with credible cognitive activity data and biomarker improvement data Mechanism Stage Be
Slide 20: Upcoming plasma biomarker study design
Upcoming plasma biomarker study design For personal use only Assess efficacy trends on clinical endpoints Evaluate change in • Include baseline biomarker levels disease biomarkers • Include baseline severity • Evaluate subscales of Phase 2 trial ~70 patients with • pTau181 ADAS-Cog most sensitive to
Slide 21: Biomarker conclusions
Biomarker conclusions For personal use only Xanamem biomarker profile to be assessed September-October 2022 The Xanamem program in AD is focused on the proven use of clinical endpoints of cognition and A positive biomarker treatment profile for function for regulatory approvals Xanamem versus placeb
Slide 22: Regulatory consultations and pivotal Phase trials
Regulatory consultations and pivotal Phase 3 trials For personal use only No functional impairment XanaMIA XanaMIA Functional impairment & loss of independence Part A Part B Healthy 50-80 MCI/early AD1 patients years Mild • N=300, placebo-controlled • 10 mg vs. placebo • Safe & well-tolerated • 5 mg
Slide 23: XanaMIA Part B trial design & implementation model
XanaMIA Part B trial Phase 2 trial design & implementation model For personal use only 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 Implementation
Slide 24: Cognitive Impairment in Depression is a major unmet medical need
For personal use only Cognitive Impairment in Depression is a major unmet medical need See also Actinogen Clinical Trials Science Forum August 2022 https://youtu.be/Bm9ATZx1zEk Xanamem Development Program Update 22
Slide 25: Science behind the Xanamem Depression Program
Science behind the Xanamem Depression Program Unmet medical need for rapid, safe treatment For personal use only 80-90% report neurocognitive symptoms1 Cognitive symptoms often persist during remission1 Elevated cortisol associated with severe, melancholic depression2 Cortisol associated wit
Slide 26: The Xanamem opportunity in depression
The Xanamem opportunity in depression For personal use only 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 c
Slide 27: XanaCIDD trial design & implementation model
XanaCIDD trial design & implementation model For personal use only 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
Slide 28: Timeline for Xanamem data & catalysts
Timeline for Xanamem data & catalysts For personal use only • September/October Biomarker data (disease-modification, efficacy) • November CTAD XanaMIA presentation 2022 • Q4 New trials commence in Alzheimer’s Disease and Cognition/Depression • Q4 Key global regulatory submissions/meetings with FDA,
Slide 29: Selected glossary
Selected glossary For personal use only 11β-HSD1 11 beta HydroxySteroid Dehydrogenase-1 enzyme Aβ Amyloid beta – a type of amyloid protein associated with Alzheimer’s Disease ADAS-Cog Alzheimer’s Disease Assessment Score- Cognition ApoE4 Apoprotein genotype associated with genetic risk of Alzheimer’
Slide 30: Selected glossary (cont.)
Selected glossary (cont.) For personal use only 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
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