Actinogen Medical Limited · ASX:ACW
Actinogen Medical — BIO Investor Forum 2023
29 slides from Actinogen Medical's conference presentation, Oct 18, 2023
Slide 1: ASX Announcement: CEO presentation for BIO Investor Forum
ASX ANNOUNCEMENT Actinogen CEO presentation for meetings at BIO Investor Forum in San Francisco, USA Sydney, 18 October 2023. Actinogen Medical ASX: ACW (“ACW” or “the Company”) is pleased to announce that its CEO, Dr Steven Gourlay, will conduct meetings at the BIO Investor Forum in San Francisco t
Slide 2: Xanamem overview and clinical trials
Actinogen is currently developing its lead compound, Xanamem, as a promising new therapy for Alzheimer’s Disease and Depression and hopes to study Fragile X Syndrome and other neurological and psychiatric diseases in the future. Reducing cortisol inside brain cells could have a positive impact in th
Slide 3: Xanamem: Suppression of CNS cortisol
For personal use only 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 ® Xan
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 For personal use only and does not contain all inform
Slide 5: 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. For personal use only Attractive disease Strong cortisol rationale for treatment of mul
Slide 6: Actinogen Trials Underway
Actinogen (ACW.AX) Trials Underway For personal use only 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 7: Xanamem: oral, low-dose, once-a-day treatment with unique 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 For personal use only Brain penetrant 11β-HSD1 small molecule enzyme inhibitor reduces cortisol inside brain cells3,4 -
Slide 8: PET data shows full target engagement in the brain
PET data shows full target engagement in the brain at low doses Previous enzyme inhibitors1 have not achieved adequate brain concentrations For personal use only Baseline After 7 days of daily dosing PET data2 demonstrates that Xanamem extensively binds to the 11β-HSD1 enzyme 5 mg Xanamem 10 mg Xana
Slide 9: 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) For personal use only One Back Test (working memory) Identification Test (visual attention)
Slide 10: Well-demonstrated, excellent safety profile
Well-demonstrated, excellent safety profile No emerging safety signals For personal use only 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%)
Slide 11: Modifying cortisol in depression: strong rationale
Modifying cortisol in depression: strong rationale from clinical data 80-90% report neurocognitive symptoms1 For personal use only Cognitive symptoms often persist during remission1 Elevated cortisol associated with severe, melancholic depression2 Cortisol levels associated with treatment ou
Slide 12: XanaCIDD proof-of-concept Phase 2a trial in Depression
XanaCIDD proof-of-concept Phase 2a trial in Depression For personal use only 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 Secon
Slide 13: The answers to Alzheimer's Disease are starting to emerge
The answers to Alzheimer’s Disease are starting to For personal use only emerge in the clinic…. Amyloid is just part of the story… Tissue cortisol is likely a “bad actor”… Corporate presentation October 2023 11
Slide 14: Newer amyloid antibodies and oral Xanamem compared
Newer amyloid antibodies and oral Xanamem have multiple, positive cognitive trials data1 For personal use only • 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 intera
Slide 15: Anti-amyloid antibodies 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 For personal use only 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
Slide 16: Xanamem slows functional decline (CDR-SB) in 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) For personal use only Xanamem Placebo -1 -0.5 CDR-SB units Change from 0 0 Baseline (SE) 0.5 0.36 * * Difference
Slide 17: Cognitive scores suggest benefit across dementia sub-types
Cognitive scores suggest potential clinical benefit across dementia patient sub-types* Positive trends in both high and low plasma pTau biomarker groups For personal use only 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
Slide 18: 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 For personal use only 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 inclu
Slide 19: Xanamem AD & Depression programs
Xanamem AD & Depression programs Building on three independent Phase 1 and 2 studies showing safety and procognitive activity For personal use only Prior Phase 1 & 2a studies Safety, cognition, clinical activity demonstrated (n~300 patients) Phase 2b (n=220) Phase 2a (n=160) Cognitive Impairment Alz
Slide 20: 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 For personal use only Jeff Carter Chief Financial Officer B. Fin Admin; M. App. Fin; CA Cheryl Townsend VP Clinical Operations RN, M
Slide 21: International Cognition Clinical Advisory Board
International Cognition Clinical Advisory Board Preeminent global thought-leaders in clinical trials for assessment of cognition For personal use only Prof. John Harrison Dr Dana C. Hilt (CMO) Dr Christina Kurre Olsen Prof. Paul Maruff A/Prof Christopher Chen Metis Cognition Ltd • Expert psychologis
Slide 22: International Scientific Advisory Boards
International Scientific Advisory Boards Preeminent thought-leader academics involved in the development of Xanamem For personal use only Alzheimer’s Disease Clinical Advisory Board Scientific Advisory Board Prof. Craig Ritchie Prof. Colin Masters Prof. Jeffrey Cummings Prof. Jonathan Seckl Prof. Br
Slide 23: Appendix
For personal use only Appendix Corporate presentation October 2023 21
Slide 24: Studies supporting association between cortisol and AD
Many studies support the association between elevated cortisol and AD development and progression1-9 Higher cortisol levels in human aging are associated with For personal use only hippocampal atrophy1,2 Chronic corticosteroid medication is associated with hippocampal and amygdalar atrophy and c
Slide 25: Methods for 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 For personal use only Measure disease Assess efficacy trends biomarkers Week 0 & 12 on clinical endpoints 72 patients with • pTau181 • Effects in biomarker-
Slide 26: 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 For personal use only 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 mec
Slide 27: CDR-SB functional endpoint to assess dementia
Clinical Dementia Rating – Sum of Boxes (CDR-SB) functional endpoint to assess dementia in MCI/early-stage AD For personal use only 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 S
Slide 28: 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 29: 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