Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Investor Presentation (November 2023)
26 slides from Actinogen Medical's investor presentation, November 2023
Slide 1: Two near-term major Phase 2 readouts in Alzheimer's Disease & Depression
Two near-term major Phase 2 readouts in Alzheimer’s Disease & Depression in 2024 & 2025 Xanamem® is a low-dose oral therapy targeting reduced tissue cortisol in the brain Corporate Presentation November 2023 Non-confidential ® Xanamem is a registered trademark of Actinogen Medical Limited
Slide 2: 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 3: Xanamem: oral, once-a-day treatment with a unique, non-amyloid/non-tau mechanism
Xanamem: oral, once-a-day treatment with a unique, non-amyloid/non-tau mechanism Mouse experimental studies & clinical trials validate cortisol as a target for the treatment of AD1-4 Inflammation and glucose/lipid dysregulation emerging as causal mechanisms in AD5 Brain penetrant 11β-HSD1 small mole
Slide 4: Two large clinical opportunities
Two large clinical opportunities Rapidly acting oral therapy with dual action on cognitive impairment / depression Depression market size ~$17 billion in 2032 Cognitively enhancing and disease modifying oral therapy for all stages of Alzheimer’s disease Alzheimer’s market ~$14 billion in 2030 Depres
Slide 5: Actinogen Phase 2 trials underway
Actinogen Phase 2 trials underway De-risked by extensive clinical data from 4 trials of Xanamem 10mg Phase 2a proof-of-concept trial in Results Q2 2024 Depression/Cognitive Impairment (n=160) Phase 2b confirmatory trial in mild-moderate Initial results H1 2025 Alzheimer’s disease (n=220) Corporate p
Slide 6: Why targeting brain cortisol with Xanamem is a promising strategy in depression
Why targeting brain cortisol with Xanamem is a promising strategy in depression 80-90% of patients report neurocognitive symptoms1 Cognitive symptoms often persist during remission1 Elevated cortisol associated with severe, melancholic depression2 Cortisol levels associated with treatment ou
Slide 7: XanaCIDD proof-of-concept Phase 2a trial in Depression
XanaCIDD proof-of-concept Phase 2a trial in Depression 10mg Xanamem +/- existing antidepressant Follow-up Screening Placebo +/- existing antidepressant -4 0 6 10 Weeks Double-blind, randomised treatment period (N=160) Key inclusion/exclusion criteria Primary Endpoints Key Secondary Endpoints Key Imp
Slide 8: The answers to Alzheimer's Disease are starting to emerge in the clinic
The answers to Alzheimer’s Disease are starting to emerge in the clinic… Alzheimer’s proteins are the pathology – not the cause… Other causal processes are involved like inflammation, lipids and glucose handling… Corporate presentation November 2023 8
Slide 9: Why targeting brain cortisol with Xanamem is a promising strategy in Alzheimer's disease
Why targeting brain cortisol with Xanamem is a promising strategy in Alzheimer’s disease Many parts of the program have been de-risked Epidemiology, cortisol and animal Clinical trials of Xanamem experiments Cortisol levels are elevated in brain fluid in early Inhibits brain 11β-HSD1 target to a
Slide 10: Newer anti-amyloid antibodies slow but not halt progression of AD
Newer anti-amyloid “immunotherapy” antibodies shown to slow but not halt progression of AD1 Ideally patients would not worsen on treatment Worsening of 0 CDR-SB2 over 18 months -0.5 Large area of -1 unmet need requires non- amyloid therapies -1.5 -2 Benefit of donanemab -2.5 donanemab all placebo al
Slide 11: Xanamem dramatically slows the rate of functional decline (CDR-SB) in patients with mild AD
Xanamem dramatically slows the rate of functional decline (CDR-SB) in patients with mild AD* Patients with elevated plasma pTau181 indicating progressive, amyloid-positive disease (n=34) Xanamem Placebo 0 0 0.2 0.4 0.36 * CDR-SB units Change from 0.6 * Difference vs. placebo Baseline (SE) • Mean 0.6
Slide 12: Cognitive scores suggest potential clinical benefit across dementia patient sub-types
Cognitive scores suggest potential clinical benefit across dementia patient sub-types* Positive trends in both high and low plasma pTau biomarker groups Higher pTau biomarker (n=34) Lower pTau biomarker (n=34) 0.3 0.3 Composite Units (SE*) Composite Units (SE) 0.2 0.2 0.1 0.1 0 0 -0.1 -0.1 -0.2 -0.2
Slide 13: XanaMIA Phase 2b trial in Alzheimer's Disease
XanaMIA Phase 2b trial in Alzheimer’s Disease Matching patients and endpoints used in the positive Ph 2a analysis 10mg Xanamem Screening Follow-up & open label Placebo -4 0 36 40 Weeks Double-blind, randomised treatment period (N=220) Interim analysis N=100 @ 24 weeks Key inclusion/exclusion criteri
Slide 14: Dr Howard Fillit, Founder Alzheimer's Drug Discovery Foundation
Dr Howard Fillit, Founder Alzheimer’s Drug Discovery Foundation in 20221 “Seventy-eight percent …. of all drugs in clinical development are non- amyloid, non-tau drugs. Multiple targets are being addressed now, which is great for the field because I think the way we're going to have to go is combina
Slide 15: Xanamem AD & Depression programs
Xanamem AD & Depression programs Building on multiple Phase 1 and 2 studies showing safety and procognitive activity Prior Phase 1 & 2a studies Safety, cognition, clinical activity demonstrated (n~300 patients) Phase 2a (n=160) Phase 2b (n=220) Cognitive Impairment Alzheimer’s Disease (AD) in Depres
Slide 16: Experienced Leadership and Management
Experienced Leadership and Management Extensive drug development and commercial experience Experienced Board of Directors... …with a talented management team in place Jeff Carter Chief Financial Officer B. Fin Admin; M. App. Fin; CA Cheryl Townsend VP Clinical Operations RN, M Health Law Dana Hilt D
Slide 17: Actinogen summary
Actinogen summary Actinogen Medical (ASX:ACW) is conducting Phase 2 trials of oral Xanamem in patients with cognitive impairment associated with depression and Alzheimer’s disease. Results due in 2024 and 2025. Attractive disease Strong cortisol rationale for treatment of multiple diseases: Alzhei
Slide 18: Appendix
Appendix Corporate presentation November 2023 18
Slide 19: International Cognition Clinical Advisory Board
International Cognition Clinical Advisory Board Preeminent global thought-leaders in clinical trials for assessment of cognition Prof. John Harrison Dr Dana C. Hilt (CMO) Dr Christina Kurre Olsen Prof. Paul Maruff A/Prof Christopher Chen Metis Cognition Ltd • Expert psychologist with a special • 25+
Slide 20: International Scientific Advisory Boards
International Scientific Advisory Boards Preeminent thought-leader academics involved in the development of Xanamem Alzheimer’s Disease Clinical Advisory Board Scientific Advisory Board Prof. Craig Ritchie Prof. Colin Masters Prof. Jeffrey Cummings Prof. Jonathan Seckl Prof. Brian Walker Prof. Scott
Slide 21: Methods for double-blind, prospective assessment of biomarker-positive mild AD patients in Phase 2a
Methods for double-blind, prospective assessment of biomarker-positive mild AD patients in Phase 2a1 A simulation of the Phase 2b XanaMIA trial Measure disease Assess efficacy trends biomarkers Week 0 & 12 on clinical endpoints 72 patients with • pTau181 • Effects in biomarker-positive stored blood
Slide 22: Timetable for trial results for oral AD therapies
Timetable for trial results for oral AD therapies Year Drug or company Target Steve’s1 estimate of probability of success 2023 deferiprone Iron Low TauRx Tau* Low NE3107 ERK1/2 Low CT1812 Sigma-2* Low * Amyloid or tau protein-related 2024 varoglutamstat pglu-Aβ/QC* Medium mechanisms Valiltramprosate
Slide 23: Clinical Dementia Rating – Sum of Boxes (CDR-SB) functional endpoint
Clinical Dementia Rating – Sum of Boxes (CDR-SB) functional endpoint to assess dementia in MCI/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 li
Slide 24: Selected glossary 1
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 25: Selected glossary 2
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
Slide 26: Contacts
Contacts Michael Roberts Steven Gourlay Investor Relations CEO & Managing Director P: +61 2 8964 7401 P: +61 2 8964 7401 M: +61 423 866 231 E. steven.gourlay@actinogen.com.au E. michael.roberts@actinogen.com.au Corporate presentation November 2023 26
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