Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Investor Presentation (June 2023)
25 slides from Actinogen Medical's investor presentation, June 2023
Slide 1: First-in-class/best-in-class Phase 2 oral drug candidate for Alzheimer's Disease & Depression
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 June, 2023 Non-confidential Dr Steven G Gourlay, CEO ® Xanamem is a registered trademark of Ac
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 (ACW.AX) & Xanamem Summary
Actinogen (ACW.AX) & Xanamem Summary • Xanamem is an oral treatment with rapid onset of clinical activity • Cortisol target validation in animal models and by cognitive benefit shown in multiple controlled trials of Xanamem • Excellent safety profile, low drug interaction potential • Commercial tabl
Slide 4: Targeting large clinical opportunities with unmet need
Targeting large clinical opportunities with unmet need Current clinical focus: • Alzheimer’s Disease global prevalence: 33 million patients • Major Depressive disorder: 280 million patients, 70% associated with cognitive impairment Potential future indications: • Other neurodegenerative diseases suc
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 AD 1-4 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: 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 8: 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 AD Area of unmet need for newer CDR-SB* and novel non-amyloid units lecanemab therapies like Xanamem ~1.2 points Area of treatment effect ~0.45 points placebo Drugs targeting other mechanisms like Xanamem are needed * Lecanemab
Slide 9: Xanamem clinical activity data
Xanamem clinical activity data ✓ Phase 1b (n=42) ✓ Phase 1b (n=107) ✓ Phase 2a (n=185) ✓ Phase 2a-pTau (n=34) Corporate presentation June 2023 9
Slide 10: 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 One Back Test (working memory) Identification Test (visual attention) Detection Test (psychomotor function) 0.02 0.1 0.055 0.01 0.08 0.035 0.06 Mean change from baseline 0
Slide 11: Second trial confirms improved attention/working memory at lower doses of 5-10 mg
Second trial confirms improved attention/working memory at 4-6 weeks using lower doses of 5 – 10 mg Computerized cognitive testing in cognitively normal older people, 5, 10 mg daily vs. placebo XanaMIA Phase 1b trial (n=107, Xanamem 10 mg & 5 mg combined) 0.5 ON-TREATMENT VISITS BETTER 0.4 Attention
Slide 12: Xanamem slows the rate of CDR-SB (functional) decline in mild AD
Xanamem slows the rate of CDR-SB (functional) decline in 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) 0.36 * * Difference vs. placebo 0.5 • Mean 0.6 units • Median 0.8 units
Slide 13: Cognitive composite scores suggest potential clinical benefit across dementia patient sub-types
Cognitive composite 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
Slide 14: 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 15: 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=330) Phase 2a (n=160) Cognitive Impairment Alzheimer’s Disease (AD)
Slide 16: Upcoming catalysts
Upcoming catalysts 2023 • Phase 2b trial in AD to commence • Results of FDA End-of-Phase 2, EMA, UK regulatory interactions • pTau Phase 2a and Phase 1b peer-reviewed publications • AAIC and CTAD (AD) presentations 2024 • Depression Phase 2a trial results H1 • Phase 2b AD interim analysis late H2 /
Slide 17: Summary
Summary Xanamem • Oral treatment with rapid onset of clinical activity • Cortisol target validation from cognitive benefit shown in multiple clinical trials • Encouraging safety profile suited to mono- or combination therapy • Intellectual property protection including composition of matter Alzheime
Slide 18: Appendix
Appendix Corporate presentation June 2023 18
Slide 19: 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 5mg Xanamem Follow-up & open label Placebo -4 0 36 40 Weeks Double-blind, randomised treatment period (N=330) Interim analysis Key inclusion/exclusion criteria Pri
Slide 20: XanaCIDD proof-of-concept trial in Depression
XanaCIDD proof-of-concept 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 Implementati
Slide 21: 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 22: 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 23: Experienced Leadership and Management
Experienced Leadership and Management Extensive drug development and commercial experience, two new key appointments in 2023 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 Develop
Slide 24: 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 25: 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
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