Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Investor Presentation (October 2023)
27 slides from Actinogen Medical's investor presentation, October 2023
Slide 1: Xanamem: Suppression of CNS cortisol
Xanamem: Suppression of CNS cortisol First-in-class/best-in-class Phase 2 oral drug candidate for Alzheimer’s Disease & Depression Four trials validate Xanamem® as a novel, differentiated, safe and efficacious candidate Corporate Presentation October 2023 Non-confidential ® Xanamem is a registered t
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: 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 4: Actinogen (ACW.AX) Trials Underway
Actinogen (ACW.AX) Trials Underway Phase 2a proof-of-concept trial in Depression/Cognitive Impairment n=160, results Q2 2024 Phase 2b confirmatory trial in mild-moderate AD n=220, initial results H1 2025 Corporate presentation October 2023 4
Slide 5: 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 Mouse experimental studies & clinical trials validate cortisol target for treatment of AD1-4 Brain penetrant 11β-HSD1 small molecule enzyme inhibitor reduces cortisol inside brain cells3,4 - modulating signalling
Slide 6: PET data shows full target engagement in the brain at low doses
PET data shows full target engagement in the brain at low doses Previous enzyme inhibitors1 have not achieved adequate brain concentrations Baseline After 7 days of daily dosing PET data2 demonstrates that Xanamem extensively binds to the 11β-HSD1 enzyme 5 mg Xanamem 10 mg Xanamem 20 mg Xanamem thro
Slide 7: Attention/Working Memory improved by weeks
Attention/Working Memory improved by 4 weeks* Cogstate computerized testing in cognitively normal older, 20 mg daily vs. placebo Similar pattern of improvement for 5 mg and 10 mg vs. placebo (data not shown) One Back Test (working memory) Identification Test (visual attention) Detection Test (psycho
Slide 8: Well-demonstrated, excellent safety profile
Well-demonstrated, excellent safety profile No emerging safety signals TEAE term ACW0002* Xanamem (n=91) Placebo (n=94) Total (n=185) Headache 5 (5.5%) 2 (2.1%) 7 (3.8%) Dizziness 4 (4.4%) 3 (3.2%) 7 (3.8%) Diarrhea 1 (1.1%) 4 (4.3%) 5 (2.7%) Fatigue 3 (3.3%) 1 (1.1%) 4 (2.2%) Nerve conduction abnor
Slide 9: Modifying cortisol in depression: strong rationale from clinical data
Modifying cortisol in depression: strong rationale from clinical data 80-90% report neurocognitive symptoms1 Cognitive symptoms often persist during remission1 Elevated cortisol associated with severe, melancholic depression2 Cortisol levels associated with treatment outcomes, relapse, & cog
Slide 10: 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 11: 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…. Amyloid is just part of the story… Tissue cortisol is likely a “bad actor”… Corporate presentation October 2023 11
Slide 12: Newer amyloid antibodies and oral Xanamem have multiple, positive cognitive trials data
Newer amyloid antibodies and oral Xanamem have multiple, positive cognitive trials data1 • Safely targets brain tissue cortisol Actinogen • 2 trials: improved attention & working memory Oral Xanamem • 1 trial: trends to reduce AD progression, improve cognition • Low drug interaction potential – good
Slide 13: Newer anti-amyloid antibodies shown to slow but not halt progression of AD
Newer anti-amyloid antibodies shown to slow but not halt progression of AD1 Ideally patients would not worsen on treatment % worsening 0 CDR-SB2 over -5 18 months -10 Large area of unmet need -15 requires non- amyloid therapies -20 -25 -30 -35 lecanemab donanemab all donanemab subgroup halt progress
Slide 14: 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 -1 -0.5 CDR-SB units Change from 0 0 Baseline (SE) 0.5 0.36 * * Difference vs. placebo • Mean 0.6
Slide 15: 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 16: 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 17: Xanamem AD & Depression programs
Xanamem AD & Depression programs Building on three independent Phase 1 and 2 studies showing safety and procognitive activity Prior Phase 1 & 2a studies Safety, cognition, clinical activity demonstrated (n~300 patients) Phase 2b (n=220) Phase 2a (n=160) Cognitive Impairment Alzheimer’s Disease (AD)
Slide 18: 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 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: Appendix
Appendix Corporate presentation October 2023 21
Slide 22: Many studies support the association between elevated cortisol and AD development and progression
Many studies support the association between elevated cortisol and AD development and progression1-9 Higher cortisol levels in human aging are associated with hippocampal atrophy1,2 Chronic corticosteroid medication is associated with hippocampal and amygdalar atrophy and cognitive impairment3 M
Slide 23: 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 24: 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 Q12024 varoglutamstat pglu-Aβ/QC* Medium mechanisms 2024 Valiltram
Slide 25: 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 26: 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 27: 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
Actinogen Medical — Investor Presentation (October 2023) on 6ix