Slide 1: XanaMIA Phase 1b trial achieves primary endpoints: topline results & strategic update
XanaMIA Phase 1b trial achieves primary endpoints: topline results & strategic update Dr. Steven Gourlay MBBS PhD MBA, CEO & MD May 4, 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 results and Strategic Update 3
Slide 4: Actinogen snapshot
Actinogen snapshot Actinogen Medical (ASX:ACW) is developing a novel oral treatment with rapid onset of clinical activity to address a range of central nervous system (CNS) diseases Demonstrated target engagement in brain and HPA axis in human trials Favourable pharmaceutical properties Low dose
Slide 5: 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 6: 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 7: Key implications from the new XanaMIA results
Key implications from the new XanaMIA 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
Slide 8: Previously
Previously XanaMIA results and Strategic Update 8
Slide 9: 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 10: 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 11: 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 12: 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 13: 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 14: XanaMIA dose-ranging topline results
XanaMIA dose-ranging topline results XanaMIA results and Strategic Update 14
Slide 15: 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 16: 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 17: 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 XanaMIA resul
Slide 18: 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 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 (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 20: 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 21: 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 22: 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 23: Next: Moving Xanamem trials into AD patients with a focus on cognitive enhancement
Next: Moving Xanamem trials into AD patients with a focus on cognitive enhancement No functional impairment XanaMIA XanaMIA Functional impairment & loss of independence Part A Part B Healthy 50-80 MCI/early AD* patients years • Randomized, placebo- Mild • Safe & well-tolerated controlled v data Mode
Slide 24: Next: Moving Xanamem trials into AD patients with a focus on cognitive enhancement
Next: Moving Xanamem trials into AD patients with a focus on cognitive enhancement No functional impairment XanaMIA XanaMIA Functional impairment & loss of independence Part A Part B Healthy 50-80 MCI/early AD* patients years • Randomized, placebo- Mild controlled v data Moderate Severe v • Safe & w
Slide 25: Actinogen Strategy
Actinogen Strategy 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 potential partners with new results • Depression Phase 2
Slide 26: Xanamem Clinical Development Pipeline
Xanamem Clinical Development Pipeline Phase 2 Pathway Outlook XanaMIA (IND) Cognitive impairment in Part A: 10mg, 5mg, Placebo Older Volunteers: Cognition “Big-to-market” early Alzheimer’s disease Part B: Patients with early stage AD: Cognitive enhancement & Multiple Phase 2b/3 trials supporting ass
Slide 27: Key catalysts
Key catalysts Clinical trials Alzheimer’s Disease o XanaMIA Part A cognition & safety results positive o Expert review of XanaMIA data and next steps o Commence XanaMIA Part B trial in patients in 2022, results 2023-4 o Regulatory interactions Depression o Commence trial setup o Commence program l
Slide 28: Thank you and Questions
Thank you and Questions XanaMIA results and Strategic Update 28