Actinogen Medical Limited · ASX:ACW
Actinogen Medical — BIO International Convention 2022
34 slides from Actinogen Medical's conference presentation, Jun 14, 2022
Slide 1: ASX Announcement: Actinogen presentation for meetings at BIO International Convention
For personal use only ASX ANNOUNCEMENT Actinogen presentation for meetings at BIO International Convention Sydney, 14 June 2022. Actinogen Medical ASX: ACW (“ACW” or “the Company”) announces that the Company’s CEO and Head of Business Development will be attending the BIO International Convention in
Slide 2: Disclaimer
Chronically elevated cortisol is associated with cognitive decline in Alzheimer’s Disease, and Xanamem has shown the ability to enhance cognition in healthy, older volunteers. Cognitive impairment is also a feature in Depression and many other diseases. Cortisol itself is also associated with depres
Slide 3: XanaMIA confirmatory trial results, Phase 2 trial designs for Alzheimer's Disease and Depression
For personal use only XanaMIA confirmatory trial results, Phase 2 trial designs for Alzheimer’s Disease and Depression Dr. Steven Gourlay MBBS PhD MBA, CEO & MD June 14, 2022 Presented at BIO, San Diego June 14-16, 2022
Slide 4: Disclaimer
Disclaimer For personal use only 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 inform
Slide 5: Actinogen snapshot
Actinogen snapshot For personal use only Actinogen Medical (ASX:ACW) is developing a novel oral treatment with rapid onset of clinical activity to improve cognition and quality of life Demonstrated target engagement in brain and HPA axis1 in human trials Favourable pharmaceutical properties Low
Slide 6: Leadership and Management
Leadership and Management Extensive drug development and commercial experience For personal use only 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 Development M.Med Sci; BSc; MSc
Slide 7: International Cognition Clinical Advisory Board
International Cognition Clinical Advisory Board Global thought leaders in clinical trials for assessment of cognition For personal use only Prof. John Harrison Dr Dana C. Hilt Dr Christina Kurre Olsen Prof. Paul Maruff Metis Cognition Ltd • Expert psychologist with a special • 25+ years of drug deve
Slide 8: International Scientific Advisory Boards
International Scientific Advisory Boards For personal use only 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
Slide 9: Xanamem: oral, low dose, once-a-day treatment with a unique mechanism
Xanamem®: oral, low dose, once-a-day For personal use only treatment with a unique mechanism Brain penetrant 11β-HSD1 small molecule enzyme inhibitor reduces cortisol inside brain cells - modulating signaling pathways and underlying disease processes1,2 Potential to be: • Rapidly cognitive enhancing
Slide 10: Previously
For personal use only Previously XanaMIA results and Phase 2 designs 8
Slide 11: Cognitive improvement vs. placebo in healthy, older volunteers in XanaHES trial in 2019
Cognitive improvement vs. placebo in healthy, older volunteers in XanaHES trial in 2019 For personal use only • Cogstate Cognitive Test Battery (CTB) with 20 mg daily, 12-week treatment; effect size (ES) estimated with the same MMRM statistical model as the current trial1 • Clinically significant ef
Slide 12: High target engagement confirms brain activity at Xanamem doses of ≤10mg
High target engagement confirms brain activity For personal use only at Xanamem doses of ≤10mg Baseline After Dose PET data demonstrates that Xanamem extensively binds 5 mg Xanamem 10 mg Xanamem 20 mg Xanamem to the 11β-HSD1 enzyme SUVRcarotid throughout the brain, with high post-treatment effects (
Slide 13: XanaMIA Phase 1b/2 trial design
XanaMIA Phase 1b/2 trial design For personal use only Targeting the earliest stages of Alzheimer’s Disease (AD) XanaMIA - Part A: XanaMIA - Part B: Double-blind Phase 1b Phase 2 H12022: minimally effective dose level 2023: robust Phase 2 study design in patients with early stages of Alzheimer’s Dise
Slide 14: XanaMIA Part A dose-ranging topline results
For personal use only XanaMIA Part A dose-ranging topline results XanaMIA results and Phase 2 designs 12
Slide 15: The XanaMIA Part A trial met its objectives
The XanaMIA Part A trial met its objectives For personal use only • Clinically significant improvements were seen in the attentional domains, including working memory, of the Cogstate CTB with both doses, including visual attention with 5 mg at the end of treatment achieving the a priori primary end
Slide 16: ACTH hormone response suggests similar Xanamem biological activity at 5 mg and 10 mg
ACTH hormone response suggests similar Xanamem biological activity at 5 mg and 10 mg dose levels For personal use only ACTH is the brain hormone that regulates cortisol production in the adrenal gland Mean (times) increase from baseline in ACTH hormone level at end of treatment* by dose level across
Slide 17: Attention Composite improved vs. placebo
Attention Composite improved at Week 4 and 6 vs. placebo Pooled working memory/visual attention/psychomotor speed (mean, SE) For personal use only 0.35 ON-TREATMENT VISITS 0.3 BETTER 0.25 Mean change from baseline 0.2 (Units) 0.15 0.1 0.05 0 Baseline Week 2 Week 4 Week 6 Week 10 Xanamem pooled doses
Slide 18: Effect Sizes Attention Composite & domains
Effect Sizes Attention Composite & domains Magnitude of treatment effect For personal use only (on-treatment MMRM ES1 > 0.9 in green) Effect size1 5 mg Effect size1 10 mg XanaMIA trial Desired Cognitive Evaluation (Test) improvement Week 4 Week 6 Follow up Week 4 Week 6 Follow up N=35 N=35 N=33 N=30
Slide 19: Effect Sizes non-attentional domains, IDSST-S
Effect Sizes non-attentional domains, IDSST-S Mixed positive & negative effects similar to previous XanaHES trial; no effect on IDSST-S For personal use only (on treatment MMRM ES1 > 0.9 in green and -0.9 in pink) Effect Size1 Effect Size1 XanaMIA trial Desired 5 mg 10 mg Cognitive Evaluation Test I
Slide 20: Xanamem was safe and well-tolerated
Xanamem was safe and well-tolerated For personal use only • No treatment-related serious adverse events • Other predominantly mild events were generally equally distributed across the three groups including placebo • No adverse events of concern, consistent with program safety database of over 300 p
Slide 21: Summary
Summary For personal use only • There is a strong unmet need for new and safer treatments for many diseases where dysregulated cortisol is a target - Xanamem is designed to reduce cortisol inside brain cells • Xanamem is potentially a rapidly-acting cognitive enhancer and, in the longer term, a dise
Slide 22: Strategy & Next Trials
For personal use only Strategy & Next Trials XanaMIA results and Phase 2 designs 20
Slide 23: Actinogen Strategy
Actinogen Strategy For personal use only Accelerate clinical development Create value from partnerships • Focus on cognitive enhancement: Pharma/biotech engagement • Early stages of Alzheimer’s Disease • Actively engage large and mid-size • Implement XanaMIA Part B Phase 2 potential partners with ne
Slide 24: Moving Xanamem trials into AD patients with a focus on cognitive enhancement & biomarkers
Moving Xanamem trials into AD patients with a focus on cognitive enhancement & biomarkers For personal use only No functional impairment XanaMIA XanaMIA Functional impairment & loss of independence Part A Part B Healthy 50-80 MCI/early AD* patients years Mild • N~300, placebo-controlled • Safe & wel
Slide 25: Regulatory consultations and pivotal studies
Regulatory consultations and pivotal studies For personal use only No functional impairment XanaMIA XanaMIA Functional impairment & loss of independence Part A Part B Healthy 50-80 MCI/early AD* patients years Mild • N~300, placebo-controlled • 10 mg vs. placebo • 5 mg & 10 mg dose levels Moderate S
Slide 26: XanaMIA Part B trial design & implementation model
XanaMIA Part B trial design & implementation model For personal use only 10mg Xanamem Screening 5mg Xanamem Follow-up Placebo -4 0 24 28 Weeks Double-blind, randomised treatment period N~300 (~100 per group) Key inclusion/exclusion criteria Primary Endpoints Key Secondary Endpoints Key Implementatio
Slide 27: Science Behind the Xanamem Depression Program
Science Behind the Xanamem Depression Program Unmet medical need for rapid, safe treatment For personal use only 80-90% report neurocognitive symptoms1 Cognitive symptoms often persist during remission1 Elevated cortisol associated with severe, melancholic depression2 Cortisol associated wit
Slide 28: XanaMDD trial design & implementation model
XanaMDD trial design & implementation model For personal use only 10mg Xanamem Follow-up Screening Placebo -4 0 6 10 Weeks Double-blind, randomised treatment period N~120 (~60 per group) Key inclusion/exclusion criteria Primary Endpoints Key Secondary Endpoints Key Implementation Features • Primary
Slide 29: Xanamem Clinical Development Pipeline
Xanamem Clinical Development Pipeline For personal use only Phase 2 Pathway Outlook Biomarker analysis in patients with mild AD Cognitive impairment in - Phase 2 dataset of 10mg vs. placebo over 12 weeks, H2 2022 “Big-to-market” early Alzheimer’s disease Cognitive benefit in patients with early stag
Slide 30: Timeline for Xanamem data & catalysts
Timeline for Xanamem data & catalysts For personal use only 2022 - Q2 XanaMIA Part A confirmed cognitive enhancement - Q2 BIO in-person pharma/biotech meetings with new data - Q3/4 Biomarker data to assess disease-modifying potential - Q4 CTAD XanaMIA presentation - Q4 New trials commence in Alzheim
Slide 31: Appendix
For personal use only Appendix • XanaMIA results and Phase 2 designs XanaMIA results and Phase 2 designs 29
Slide 32: ACW top stockholders and stock price
ACW top stockholders and stock price For personal use only Share price chart at 10 Jun 2022 Trading Information 52 week high A$0.20 0.20 25.0 52 week low A$0.056 Number of issued shares 1,796M 0.18 Market capitalisation (10 Jun 2022) A$108M 0.16 20.0 Cash Balance at 31 Mar 2022 A$19.0M 0.14 0.12 15.
Slide 33: XanaMIA Part A statistical methods
XanaMIA Part A statistical methods For personal use only • Double-blind, randomized design, industry best standard statistical analysis for smaller sample size trials: computerized cognitive testing with the Cogstate CTB1 with International Digit Symbol Substitution Test - Symbols (IDSST-S) • “Inten
Slide 34: Effect size statistics measure "signal to noise"
Effect size statistics measure “signal to noise” For personal use only Ratios commonly used in trials of Alzheimer’s Disease using raw or statistical model data Cohen’s d Z-score is a standardization method for a normal distribution 1. ADASCog endpoint using ES as Cohen’s d (Aduhelm: estimated from
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