Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Clinical Trials Science Forum 2023
36 slides from Actinogen Medical's conference presentation, May 24, 2023
Slide 1: ASX Announcement: XanaMIA Phase 2b trial amendment and Science Forum slides
ASX ANNOUNCEMENT Actinogen XanaMIA Phase 2b Alzheimer’s disease (AD) trial amendment and Clinical Trials Science Forum 2023 presentation slides Sydney, 24 May 2023. Actinogen Medical ASX: ACW (“ACW” or “the Company”) announces specific amendments to the upcoming XanaMIA Phase 2b clinical trial in pa
Slide 2: ASX announcement continued: webinar topics and CEO comments
therapy but this approach does not halt disease progression, requires intravenous infusion, and is associated with serious but rare side effects. Actinogen is a leader in clinical AD research having the only oral therapy to have demonstrated benefits on cognition in multiple placebo-controlled trial
Slide 3: About Actinogen Medical and Xanamem
About Actinogen Medical Actinogen Medical (ACW) is an ASX-listed, biotechnology company developing a novel therapy for neurological and neuropsychiatric diseases associated with dysregulated brain cortisol. There is a strong association between cortisol and detrimental changes in the brain, affectin
Slide 4: Alzheimer's disease: amyloid therapies are only part of the answer
For personal use only FOLLOWING THE SCIENCE Clinical Trials Science Forum Alzheimer’s disease: amyloid therapies are only part of the answer Xanamem® targets brain cortisol and is one of a few programs that has demonstrated clinical benefit Wednesday 24 May 2023 | 11.00am AEST ® Xanamem is a registe
Slide 5: 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 For personal use only does not contain all inform
Slide 6: Introduction and welcome
For personal use only Introduction and welcome Michael Roberts BEc Hons, CPA, Ffin Dr Steven Gourlay MBBS FRACP PhD MBA Investor Relations Chief Executive Officer • 25+ years' business experience • Industry physician with more than 25 years • Senior IR & comms professional in top-50 listed experienc
Slide 7: For personal use only
For personal use only Clinical Trials Science Forum 4
Slide 8: Agenda
Agenda For personal use only Michael Roberts Welcome Investor Relations Dr Steven Gourlay Introduction Chief Executive Officer Dr Fujun Li Introduction of Xanamem drug product Head of Manufacturing Dr Dana Hilt The treatment of Alzheimer’s disease: Amyloid is not the Chief Medical Officer entire pro
Slide 9: Introduction
For personal use only Introduction Dr Steven Gourlay Chief Executive Officer Clinical Trials Science Forum 6
Slide 10: Actinogen is a leader in clinical Alzheimer's research
Actinogen is a leader in clinical Alzheimer’s research Only amyloid antibody infusions and oral Xanamem have multiple, positive cognitive trial data1 For personal use only Actinogen • Safely targets brain tissue cortisol • 2 trials: improved attention & working memory Oral Xanamem • 1 trial: trends
Slide 11: Introduction of Xanamem drug product
For personal use only Introduction of Xanamem drug product Dr Fujun Li, Ph.D. Head of Manufacturing Clinical Trials Science Forum 8
Slide 12: Xanamem is a promising small molecule pharmaceutical
Xanamem is promising small molecule pharmaceutic • Small molecule, once-a-day pill or capsule for oral administration For personal use only • High solubility and high membrane permeability - well absorbed through gastrointestinal tract (intestines) • Crystalline material and stable at room temperatu
Slide 13: Xanamem capsules and now (commercial) tablets
Xanamem capsules and now (commercial) tablets Xanamem was initially formulated in gelatin As Actinogen prepares for and implements late For personal use only capsules that were used in early Phase 1 and phase clinical studies, a tablet formulation has been Phase 2 clinical studies developed that pro
Slide 14: Advantages of Xanamem tablets over injectables like anti-amyloid antibodies
Advantages of Xanamem tablets over injectables like anti-amyloid antibodies For personal use only • Xanamem tablets are manufactured using a conventional tablet manufacturing process according to Good Manufacturing Practice (GMP) standards • Small pill and easy to swallow for elderly patients • Once
Slide 15: The treatment of Alzheimer's disease: amyloid is not the entire problem
For personal use only The treatment of Alzheimer’s disease (AD) Amyloid is not the entire problem … so, it is only part of the solution Dr Dana C Hilt MD Chief Medical Officer Clinical Trials Science Forum 12
Slide 16: Alois Alzheimer and amyloid
Alois Alzheimer and amyloid The historical background of amyloid in AD For personal use only In November 1901, Dr. Alois Alzheimer, a German neurologist, The pathological hallmarks of AD include: made his first examination of a 51-year-old woman named • amyloid plaques - deposits of extracellular am
Slide 17: Amyloid as the cause of AD: A closer look
Amyloid as the cause of AD: A closer look For personal use only Reducing amyloid to treat AD Amyloid can not be the entire solution • All genetic cases of AD are associated with some defect in • Mutations in amyloid and enzymes processing amyloid amyloid protein processing: mutation in the amyloid g
Slide 18: Amyloid as the cause of AD: A closer look
Amyloid as the cause of AD: A closer look For personal use only Reducing amyloid to treat AD Amyloid can not be the entire solution • The amyloid gene is contained on chromosome 21 • >15 anti-amyloid therapies have been taken into large clinical • Trisomy (3 copies) of chromosome 21 causes Down tria
Slide 19: The effects of clearing amyloid in AD
The effects of clearing amyloid in AD Correlations between amyloid clearance and clinical benefit in anti-amyloid antibody For personal use only studies are modest • A number antibodies have shown clearance of amyloid but few have shown benefit1 • In some antibody studies (e.g. aducanumab and donane
Slide 20: Anti-amyloid approach leaves significant unmet medical need
Anti-amyloid approach leaves significant unmet medical need Lecanemab1 slows progression modestly during the first 12 months For personal use only CDR-SB units Blue area = treatment effect 1. Lecanemab is an anti-amyloid antibody given as an intravenous infusion every 2 weeks and largely clears brai
Slide 21: Anti-amyloid approach leaves significant unmet medical need
Anti-amyloid approach leaves significant unmet medical need For personal use only Area of unmet need for newer CDR-SB* and novel non-amyloid units therapies like Xanamem ~1.2 points Area of treatment effect ~0.4 points Drugs targeting other mechanisms like Xanamem will be required to fill this gap *
Slide 22: The road forward to better treatment
The road forward to better treatment • Reducing amyloid to treat AD can provide modest clinical benefit (lecanemab and donanemab antibodies) For personal use only • The benefit seen for lecanemab and donanemab is likely to be the maximal effect of anti-amyloid therapy as they clear amyloid rapidly a
Slide 23: Xanamem: Oral, low dose, once-a-day treatment with a unique non-amyloid/tau mechanism
Xanamem: Oral, low dose, once-a-day treatment with a unique non-amyloid/tau mechanism For personal use only Only known brain penetrant 11β-HSD1 small molecule enzyme inhibitor Reduces cortisol in brain - modulating signalling pathways and potentially underlying disease processes1,2 11β-HSD1 is prefe
Slide 24: Elevated cortisol leads to human brain dysfunction
Elevated cortisol leads to human brain dysfunction • Multiple studies support the association between elevated cortisol and For personal use only AD development and progression1-5 • Cognitive impairment in patients with neuroendocrine dysfunction6-9 • Compelling evidence provided by the Australian I
Slide 25: Xanamem clinical trial data
Xanamem clinical trial data For personal use only Two separate normal volunteer Oral Xanamem 5 and 10 mg/d have New analyses of the Phase 2 studies have shown positive excellent CNS penetration and XanADu AD study show procognitive effects of Xanamem: target occupancy by PET scanning procognitive an
Slide 26: PET data shows full target engagement in the brain
PET data shows full target engagement in the brain in the dose range of 5-30 mg (5-20 mg shown) Previous drug candidates to this target have not achieved adequate brain For personal use only concentrations as they were poorly CNS penetrant Baseline After Dose PET data demonstrates that 5 mg Xanamem
Slide 27: Xanamem prevents decline in CDR-SB in biomarker-positive AD patients
Xanamem prevents decline in CDR-SB (global functional score) in biomarker-positive AD patients1 Using pre-specified protocol, statistical analysis plan and blinded biomarker analysis For personal use only Xanamem Placebo(X) -1 -0.5 CDR-SB units 0 00 Change from Baseline (SE) 0.36 * * Difference 10 m
Slide 28: Xanamem provides clinical and procognitive benefit in mild/moderate AD patients
Xanamem provides clinical and procognitive benefit in mild/moderate AD patients Response analysis in biomarker-positive1 XanADu patients (patients more likely to progress) For personal use only Twice as many AD patients in the Xanamem group had stable or improved disease compared with placebo2 56% o
Slide 29: Xanamem Phase 2 & 3 programs
Xanamem Phase 2 & 3 programs Building on three independent Phase 1 and 2 studies showing safety and procognitive activity For personal use only Current Phase 1 & 2a studies Safety, cognition, clinical activity demonstrated (n~300 patients) Phase 2b Phase 2a Cognitive Impairment Alzheimer’s Disease (
Slide 30: XanaMIA Phase 2b trial in Alzheimer's Disease
XanaMIA Phase 2b trial in Alzheimer’s Disease Matching patients and endpoints used in the positive Phase 2a analysis 10mg Xanamem For personal use only Screening 5mg Xanamem Follow-up & open label Placebo -4 0 36 40 Weeks Double-blind, randomised treatment period (N=330) Interim analysis Key inclusi
Slide 31: For personal use only
For personal use only Clinical Trials Science Forum 28
Slide 32: Questions
For personal use only Questions Clinical Trials Science Forum 29
Slide 33: Thank you
Thank you For personal use only If you have any questions following the event please contact: Michael Roberts Investor Relations M. +61 423 866 231 E. michael.roberts@actinogen.com.au Clinical Trials Science Forum 30
Slide 34: Appendix
For personal use only Appendix Clinical Trials Science Forum 31
Slide 35: 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 For personal use only ACTH Adrenocorticotropic hormone that regulates blood levels of cortisol ADAS-Cog Alzheimer’
Slide 36: 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 For personal use only MDD Major Depressive Disorder MMSE Mini Mental State Examination – a 30-point scale
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