Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Earnings Presentation (April 2022)
22 slides from Actinogen Medical's earnings presentation, Apr 27, 2022
Slide 1: XanaMIA Phase 1b trial achieves primary endpoints: topline results
XanaMIA Phase 1b trial achieves primary endpoints: topline results Dr. Steven Gourlay MBBS PhD MBA, CEO & MD Professor Paul Rolan MBBS MD, CMO April 27, 2022 Authorised by the Board of Directors 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: Actinogen is a neurotherapeutics developer realizing a revolutionary therapy
Actinogen is a neurotherapeutics developer realizing a revolutionary therapy so patients and their families can live their best lives XanaMIA Part A Topline Results Presentation 3
Slide 4: Xanamem: oral, low dose, once-a-day treatment with a unique mechanism
Xanamem: oral, low dose, once-a-day 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 • Disease-modifying (s
Slide 5: Cognition Clinical Advisory Board
Cognition Clinical Advisory Board Renowned global thought leaders in clinical trials for assessment of Cognition 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 development • 20+ years researc
Slide 6: Key implications from the results
Key implications from the results • Trial met its primary safety, efficacy (cognition) and pharmacodynamic endpoints • Second consecutive double-blind trial to show improvement in attention and working memory with Xanamem • Confirms the target dose range of ≤10 mg suggested by imaging of Xanamem act
Slide 7: Previously
Previously XanaMIA Part A Topline Results Presentation 7
Slide 8: 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 • 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 effects on “attention” d
Slide 9: PET data supports exploring a lower Xanamem dose range of ≤10mg daily
PET data supports exploring a lower Xanamem dose range of ≤10mg daily 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 (absence of colour) after
Slide 10: XanaMIA Phase 1b/2 trial design
XanaMIA Phase 1b/2 trial design Targeting the first stages of Alzheimer’s Disease (AD) XanaMIA - Part A: XanaMIA - Part B: Double-blind Phase 1b Phase 2 H12022: minimally effective dose level 2023: experimental study design in patients with early stages of Alzheimer’s Disease 107 healthy older subje
Slide 11: Statistical methods
Statistical methods • 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) • “Intention-to-treat” analyses with no imput
Slide 12: Effect size statistics measure “signal to noise”
Effect size statistics measure “signal to noise” 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 Biogen presentation 20
Slide 13: XanaMIA dose-ranging topline results
XanaMIA dose-ranging topline results XanaMIA Part A Topline Results Presentation 13
Slide 14: The XanaMIA Part A trial met its objectives
The XanaMIA Part A trial met its objectives • 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 endpoint criterion of Coh
Slide 15: ACTH hormone response suggests similar Xanamem biological activity at 5 mg and 10 mg dose levels
ACTH hormone response suggests similar Xanamem biological activity at 5 mg and 10 mg dose levels 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 studies 2.5 2 Multipl
Slide 16: Attention Composite improved at Week 4 and 6 vs. placebo
Attention Composite improved at Week 4 and 6 vs. placebo Pooled working memory/visual attention/psychomotor speed (mean, SE) 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 Placebo 16
Slide 17: Effect Sizes Attention Composite & domains
Effect Sizes Attention Composite & domains Magnitude of treatment effect (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 N=29 N=29 Attention C
Slide 18: 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 (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 Improvement Week 4 Week
Slide 19: Xanamem was safe and well-tolerated
Xanamem was safe and well-tolerated • 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 people studied in trial
Slide 20: Summary
Summary • 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 disease modifier • This Ph
Slide 21: Next steps
Next steps Actinogen continues its Phase 2 trial program with greater confidence: • In its choice of a lower minimally effective dose range of ≤ 10 mg • Utility of the Cogstate CTB to measure cognitive effects of Xanamem The next steps for Alzheimer’s Disease include: • Full analysis of trial data •
Slide 22: Questions
Questions XanaMIA Part A Topline Results Presentation 22
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