Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Technical Presentation (August 2022)
79 slides from Actinogen Medical's technical presentation, Aug 3, 2022
Slide 1: Actinogen Clinical Trials Science Forum presentation slides
For personal use only ASX ANNOUNCEMENT Actinogen Clinical Trials Science Forum presentation slides Sydney, 3 August 2022. Actinogen Medical ASX: ACW (“ACW” or “the Company”) is pleased to release the presentation slides for this morning’s Clinical Trials Science Forum commencing at 11am AEST. Event
Slide 2: About Actinogen Medical and Xanamem
Announcement authorised by the Board of Directors of Actinogen Medical About Actinogen Medical Actinogen Medical (ACW) is an ASX-listed, biotechnology company developing a novel therapy for neurological and neuropsychiatric diseases associated with dysregulated brain cortisol. There is a strong asso
Slide 3: Following the Science: Clinical Trials Science Forum
For personal use only FOLLOWING THE SCIENCE Clinical Trials Science Forum Wednesday 3 August 2022 | 11.00am to 1.00pm AEST
Slide 4: For personal use only
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 information neces
Slide 5: Introduction and welcome
For personal use only Introduction and welcome Michael Roberts BEc Hons, CPA, Ffin Dr Steven Gourlay MBBS FRACP PhD MBA Investor Relations Chief Executive Officer • 25+ years' business experience • Industry physician with more than 25 years • Senior IR & comms professional in top-50 listed experienc
Slide 6: For personal use only
For personal use only Clinical Trials Science Forum | 3 Aug 2022 4
Slide 7: Agenda
Agenda For personal use only Introduction and welcome Dr Steven Gourlay Michael Roberts Chief Executive Officer Investor Relations The challenges and opportunities in Dr Dana Hilt drug development for neurology Neurologist and International Neurology Trials Expert How to measure cognition in clinica
Slide 8: Actinogen snapshot
Actinogen snapshot Actinogen Medical (ASX:ACW) is developing a novel oral treatment with rapid onset of clinical activity to improve cognition and quality of life For personal use only Demonstrated target engagement in brain and HPA axis1 in human trials Favourable pharmaceutical properties Low
Slide 9: The challenges and opportunities in drug development for neurology
For personal use only The challenges and opportunities in drug development for neurology Dr Dana Hilt MD Neurologist and International Neurology Trials Expert • 25+ years of drug development experience, primarily of Central Nervous System (CNS) drugs • Phases 1 to 4 drug development • CMO at Frequen
Slide 10: Neurologic diseases: the disease burden
Neurologic diseases A DALY from neurological diseases The disease burden For personal use only • Globally, in 2016, The Global Burden of Disease Project analyzed the impact of neurological diseases • Leading cause of Disability-Adjusted Life-Years (DALYs) - 276 million • Second leading cause of deat
Slide 11: Neurologic diseases: the disease burden (cont.)
Neurologic diseases Global DALYs by age for neurological disorders A Male The disease burden (cont.) For personal use only • As life expectancy increases - neurological disease burden increases • After the age of 50 yo, the fractional burden of neurodegenerative diseases dramatically increases compa
Slide 12: Neurologic diseases: the disease burden economic impact
Neurologic diseases The disease burden economic impact US Alzheimer’s Disease: Economic Impact For personal use only • > One billion people worldwide suffer from Central Nervous System (CNS) diseases1 • The economic burden of all CNS diseases - including direct medical costs, non-medical costs, and
Slide 13: Neurologic drug development has been challenging
Neurologic drug development has been challenging For personal use only Drug development phase transition success rates by disease area CNS drug development Phase I to II Phase II to III Phase III to ND NDA to App has been challenging Phase Success (positive rate) (positive rate) (positive rate) (pos
Slide 14: Neurologic diseases: why the gap and how to close it?
Neurologic diseases For personal use only Why the gap and how to close it? • Psychiatric conditions - faulty ‘activity’ Neurological conditions - faulty ‘wiring’ • It may be easier to correct faulty ‘activity’ rather than correct faulty ‘wiring’ • Diagnosis by symptoms (eg depression, cognitive impa
Slide 15: Optimizing Xanamem development
Optimizing Xanamem development Xanamem now well positioned for larger clinical outcome studies in multiple indications For personal use only Optimal target selection Selective 11β-HSD1 Inhibitor CNS penetration Demonstrated CNS penetration at target oral doses (5-10 mg/d) Target engagement Pos
Slide 16: Neurologic diseases: the regulatory climate
Neurologic diseases: The regulatory climate For personal use only Regulatory agencies have recognized the treatment gaps: New focus to CNS drug development by regulators • Scott Gottlieb MD, former FDA Director, led an effort to streamline the team structure that reviews and guides Neurological Drug
Slide 17: A current summary of drug development in CNS diseases
A current summary of drug development in CNS diseases For personal use only • A growing clinical burden and treatment need exists worldwide in neurological conditions • As the world’s population ages - this need will only grow • Both more effective symptomatic treatments as well as drug that can imp
Slide 18: How to measure cognition in clinical trials – state of the art
For personal use only How to measure cognition in clinical trials – state of the art Prof John Harrison BSc (Hons), PhD, PhD, Dip CS, CSci, CPsychol, AFBPsS International Cognition Expert • Expert in cognitive assessment • Chartered psychologist with two PhDs and author/co-author of more than 80 boo
Slide 19: How to measure cognition in clinical trials – state of the art
Mετιs Cognition Ltd For personal use only How to measure cognition in clinical trials – state of the art John Harrison BSc (Hons), PhD, PhD, Dip CS, CSci, CPsychol, AFBPsS Associate Professor, Alzheimer Center, AUmc, Amsterdam Visiting Professor IoPPN, King’s College London Consultant Psychologist,
Slide 20: Content
Content For personal use only • About cognition • The usual, suspect measures • State of the art mετιs 18
Slide 21: Domains, deficit detection, and diseases: about cognition
For personal use only DOMAINS, DEFICIT DETECTION, AND DISEASES ABOUT COGNITION mετιs 19
Slide 22: About cognition
About cognition For personal use only Episodic memory Executive function Working memory Praxis Attention Language mετιs 20
Slide 23: The MMSE and the ADAS-cog
For personal use only The MMSE and the ADAS-cog THE USUAL SUSPECT, MEASURES mετιs 21
Slide 24: Study participant selection using the MMSE
Study participant selection using the MMSE For personal use only • Orientation to place 5 • Orientation to time 5 • Word registration 3 • Attention 5 • Word recall 3 • Language (naming objects) 2 • Repeating a phrase 1 • 3-step command 3 • Command 1 • Writing a sentence 1 • Figure copying 1 mετιs 22
Slide 25: ADAS-cog performance in early AD
ADAS-cog performance in early AD For personal use only Total Subscore Worst possible score = 10 Control MCI AD CDR=0.5 AD CDR=1 Grundman MPH et al. (2004). Mild cognitive impairment can be distinguished from Alzheimer’s disease and normal aging for clinical trials. Archives of Neurology;61: 59-66. m
Slide 26: Focusing on reliability, validity and sensitivity
For personal use only Focusing on reliability, validity and sensitivity STATE OF THE ART mετιs 24
Slide 27: What should we measure?
What should we measure? For personal use only Episodic memory Executive function Working memory Processing speed Attention Language & praxis mετιs 25
Slide 28: Getting the right study participants
Getting the right study participants For personal use only mετιs
Slide 29: Target engagement
Target engagement For personal use only • Phase 2a - Identify cognitive domains benefitted by treatment • Phase 2b - Confirmatory evidence of target engagement • Phase 3 – Replication mετιs Wessels AM, Edgar CJ, Nathan PJ, Siemers ER, Maruff P, Harrison JE (2021) Cognitive Go/No-Go decision-making c
Slide 30: Getting the study participants right
Getting the study participants right For personal use only 950 900 Healthy young adults 850 800 One Back Task (working memory) Reaction time (msecs) 750 700 650 600 550 500 450 400 Detection (attention) 350 300 250 0 30min 60min 90min one week Faletti MG et al (2006) Practice effects associated with
Slide 31: Getting test selection right
Getting test selection right For personal use only • Brief, reliable, valid, and sensitive measures, especially: – Temporal reliability – Content validity – Assay sensitivity • Ease of administration • Often a blend of traditional ‘paper-and-pencil’ and digital tests mετιs 29
Slide 32: Case study: Vortioxetine Lundbeck
Case study: Vortioxetine Lundbeck For personal use only Harrison JE, Lophaven S, Olsen CK (2016) Which cognitive domains are improved by treatment with vortioxetine? Intl J Neuropsychopharm, Jun 8. pii: pyw054. http://dx.doi.org/10.1093/ijnp/pyw054 mετιs 30
Slide 33: Summary
Summary For personal use only • Traditional instruments can lack content validity • We must be sure to assess all relevant cognitive domains • Enrich study cohorts for rescuable deficits in target domains • Employ reliable, sensitive and valid measures mετι ετιss 31
Slide 34: Thanks for listening
Thanks for listening For personal use only john@metiscog.com linkedin.com/in/drjohnharrison open.academia.edu/JohnHarrison @johncpc mετιs 32
Slide 35: Following the clinical science of Xanamem
For personal use only Following the clinical science of Xanamem Prof Paul Rolan MBBS MD FRACP FFPM(UK) FFPMANZCA Chief Medical Officer • Clinical pharmacologist • Pharmaceutical physician • Principal investigator in over 750 clinical studies Clinical Trials Science Forum | 3 Aug 2022 33
Slide 36: Overview
Overview For personal use only Scientific basis for our Benchmarking Planned development pipeline Xanamem clinical trials Clinical Trials Science Forum | 3 Aug 2022 34
Slide 37: Making a successful new medicine
Making a successful new medicine For personal use only • Hits the right target • The drug has the right properties • The right biomarkers and assessments are used to guide development • The right trial participants are selected • The right trial design is used • The right dose • The right safety pro
Slide 38: 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 – the right target 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
Slide 39: The role of cortisol in health
The role of cortisol in health For personal use only • Cortisol is an essential hormone for health in humans • Its key function is to modulate the response to stress: • physical stress such as infection • psychological stress • Outside the brain, cortisol controls the amount of inflammation due to d
Slide 40: The role of elevated cortisol in brain disease
The role of elevated cortisol in brain disease For personal use only High levels of brain cortisol are associated with: • depressed mood (Major Depressive Disorder) • shrinking parts of the brain needed for new memory formation (hippocampus) Cortisol synthesis inhibitors have been shown to improve d
Slide 41: The right properties
The right properties For personal use only • Well absorbed, small dose (5-10 mg), once-a-day dosing, little affected by food • Penetrates brain well • High binding to target enzyme from 5mg (right biomarker) • Safe and very well tolerated • Good candidate for combination therapy due to low potential
Slide 42: High target engagement confirms brain activity at Xanamem doses ≤10mg
High target engagement confirms brain activity at Xanamem doses of ≤10mg For personal use only Baseline After Dose PET brain scan data demonstrates that Xanamem 5 mg Xanamem 10 mg Xanamem 20 mg Xanamem extensively binds to the SUVRcarotid 11β-HSD1 enzyme throughout the brain, with high post-treatmen
Slide 43: Alzheimer's Disease
For personal use only Alzheimer’s Disease Targeting cognitive enhancement and disease- modification in the early stages of disease Clinical Trials Science Forum | 3 Aug 2022 41
Slide 44: Characteristics of early Alzheimer's Disease
Characteristics of early Alzheimer’s Disease For personal use only AD is common1 ~500,000 Australians have dementia, with AD the commonest type AD patients initially suffer memory loss As AD progresses, memory worsens and other problems develop e.g. language, problem solving, ability to live indepen
Slide 45: Cognitive improvement vs. placebo in healthy, older volunteers in XanaHES
Previously: 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 si
Slide 46: Attention composite improved vs. placebo
Recently: Attention composite improved at weeks 4 and 6 vs. placebo – the right assessments For personal use only 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 Wee
Slide 47: Moving Xanamem trials into AD patients
Now: 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 MCI/early AD* patients 50-80 years Mild AD • N~300, placebo-controlled • Sa
Slide 48: October: planned analysis of Phase 2 plasma samples for AD biomarkers
October: Planned analysis of Phase 2 plasma samples for Alzheimer’s Disease biomarkers For personal use only Bringing disease biomarker data readout forward into 2022 XanADu Phase 2 Trial ~70/185 patients 10mg daily Mild Alzheimer’s Disease without available for analysis biomarker or imaging confirm
Slide 49: XanaMIA Part B – patients with early Alzheimer's Disease
XanaMIA Part B – Patients with early Alzheimer’s Disease For personal use only Key design considerations Double-blind randomized parallel-groups design: Patients with: • Placebo, 5 and 10 mg Xanamem once daily • Clinical diagnosis of early-stage AD • Approx. 100 per group • Demonstrated cognitive im
Slide 50: Key outcomes
Key outcomes For personal use only Primary outcome Secondary outcomes • Cogstate attention composite • Amsterdam Activity of Daily Living scale (more sensitive (same as XanaMIA Part A and XanaHES) than ADAS-Cog) • Cogstate • Executive Function Composite • Episodic Memory Function Composite • Individ
Slide 51: Cognitive Impairment associated with Major Depressive Disorder - XanaCIDD
For personal use only Cognitive Impairment associated with Major Depressive Disorder - XanaCIDD Targeting dual cognitive enhancement and anti-depressant activity Clinical Trials Science Forum | 3 Aug 2022 49
Slide 52: Characteristics of Major Depressive Disorder (MDD)
Characteristics of Major Depressive Disorder (MDD) For personal use only MDD is common1,2 ~5% prevalence globally, 1 in 7 lifetime risk Neurocognitive symptoms are a typical feature (>80%)3 Difficulty thinking and concentrating, unable to make decisions Only one anti-depressant has a statement re co
Slide 53: The Xanamem opportunity in depression
The Xanamem opportunity in depression For personal use only Current anti-depressants work slowly (3 weeks) and do not target cognition multiple adverse effects initial suicide risk blood pressure, sexual function, appetite… Xanamem improves cognition quickly Xanamem may improve both depression and c
Slide 54: XanaCIDD trial design & implementation model
XanaCIDD trial design & implementation model For personal use only Double-blind randomized parallel-groups design: Patients with: • Placebo and 10 mg Xanamem once daily • Clinical diagnosis of MDD • Approx. 80 per group • Demonstrated cognitive impairment by coding test • 6 weeks treatment • Persist
Slide 55: Key outcomes
Key outcomes For personal use only Primary outcome Secondary outcomes • Cogstate CTB attentional composite (attention and working • Montgomery-Åsberg Depression Rating Scale (MADRS) memory) • Executive Function Cognitive Composite (One-Back, COWAT, iDSST) • Episodic Memory Cognitive Composite (OCL,
Slide 56: Safety data Xanamem Phase 2 mild Alzheimer's Disease trial
Safety data Xanamem Phase 2 Mild Alzheimer’s Disease trial For personal use only 10mg daily over 12 weeks in patients with mild AD (MMSE* 20-26) TEAE** term 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%) Diarrhoea 1 (1.1%) 4 (4.3%
Slide 57: Potential for Xanamem
Potential for Xanamem For personal use only To be first-in-class To be first-in-class cognitive enhancer / in early stages of AD dual label claim therapy in depression Actinogen clinical trials have been designed to demonstrate these effects Based on cognitive In collaboration with world’s With exec
Slide 58: Making a successful new medicine
Making a successful new medicine For personal use only Hits the right target The drug has the right properties The right biomarkers and assessments are used to guide development The right trial participants are selected The right trial design is used The right dose The right safety pro
Slide 59: Integrated operational excellence
For personal use only Integrated operational excellence Tamara Miller MS, BSc, PMP, DipBus Cheryl Townsend RN, PG Clin Research, MLaw Senior Vice President Vice President Product Development Clinical Operations • BSc, MSc, and project management certification • Registered nurse with post graduate de
Slide 60: Clinical operations excellence is essential for success
Right target For personal use only Right drug Right biomarkers/assessments Right clinical trial Right participants Right dose Right safety profile Clinical Operations excellence is essential for success: Innovative implementation of the right trial design Recruiting the right participants Clinical T
Slide 61: 'Hands-on' clinical operations team at Actinogen
‘Hands-on’ clinical operations team at Actinogen For personal use only Administrative role, called a Clinical Trial Assistant (CTA), who supports the day-to-day activities for the trial Field-based monitors, called Clinical Research Associates, who travel to different trial sites to ensure the trial
Slide 62: Leveraging strategic clinical operations partners
Leveraging strategic clinical operations partners For personal use only Biostatistics partner Clinical Trials Science Forum | 3 Aug 2022 60
Slide 63: Delivering operational excellence in Phase 2
Delivering operational excellence in Phase 2 For personal use only XanaMIA XanaCIDD Part B TO HIGH ON ON TIME QUALITY BUDGET Clinical Trials Science Forum | 3 Aug 2022 61
Slide 64: Implementing with efficiency, speed and quality
Implementing with efficiency, speed and quality The Actinogen difference For personal use only • REDUCED COSTS SMALL, EFFICIENCY HIGH-IMPACT • REDUCED TIME TEAM • ANTICIPATION OF RISKS Actinogen’s Clinical Operations team has INNOVATION • TECHNOLOGY- >80 years ADAPTABILITY & CREATIVITY BASED RESOURC
Slide 65: The Actinogen difference
The Actinogen difference For personal use only Healthy volunteer studies: OPERATIONAL XanaHES: 42 participants recruited in 4 months EFFICIENCY XanaMIA-DR: 106 participants recruited in 6 months In collaboration with Actinogen’s Clinical Science team ensure the: • trial design is as close to real-wo
Slide 66: The Actinogen difference
The Actinogen difference For personal use only Leveraging the newest technology to reduce costs and increase quality: • Electronic pre-screening & e-consent • Centralised rating (diagnosis & endpoints) OPERATIONAL ADAPTABILITY • Remote monitoring • GP / Psychologist / Psychiatrist Referral Networks
Slide 67: The right science, the right implementation
The right science Target For personal use only Drug Biomarkers/Assessments Clinical Trial Participants Dose Safety Profile The right implementation Right team and partners Innovative clinical trials management Contemporary recruitment strategies Clinical Trials Science Forum | 3 Aug 2022 65
Slide 68: Questions
For personal use only Questions Clinical Trials Science Forum | 3 Aug 2022 66
Slide 69: For personal use only
For personal use only Clinical Trials Science Forum | 3 Aug 2022 52
Slide 70: Thank you
For personal use only Thank you For any additional enquiries or questions contact us: Michael Roberts Investor Relations E: michael.roberts@actinogen.com.au M: +61 423 866 231
Slide 71: Appendix
For personal use only Appendix Clinical Trials Science Forum | 3 Aug 2022 69
Slide 72: Selected glossary
Selected glossary For personal use only 11β-HSD1 11 beta HydroxySteroid Dehydrogenase-1 enzyme CNS Central nervous system CRO Contract Research Organization - Clinical Double-blind Investigators, participants and company do not know who has active vs placebo treatment during a trial EMA European Med
Slide 73: Dr Steven Gourlay
Dr Steven Gourlay MBBS FRACP PhD MBA For personal use only Chief Executive Officer and Managing Director Dr Gourlay has more than 30 years of experience in the development of novel therapeutics and brings considerable skills and experience to Actinogen as the Company moves into further clinical deve
Slide 74: Dr Dana Hilt
Dr Dana Hilt MD For personal use only Neurologist and International Neurology Trials Expert Dr Dana C. Hilt MD has more than 25 years of drug development experience, primarily of Central Nervous System (CNS) drugs. Dr Hilt has deep experience in Phases 1 to 4 development of drugs for conditions incl
Slide 75: Prof John Harrison
Prof John Harrison BSc (Hons), PhD, PhD, Dip For personal use only CS, CSci, CPsychol, AFBPsS International Cognition Expert Prof John Harrison is an expert psychologist with a special interest in cognition whose principal mετιs professional interest is in helping people understand, maintain, and en
Slide 76: Prof Paul Rolan
Prof Paul Rolan MBBS MD FRACP FFPM FFPMANZCA For personal use only Chief Medical Officer Professor Paul Rolan is a clinical pharmacologist and drug development consultant and one of Australia’s most experienced clinical trial investigators and drug developers, having taken drugs from first human adm
Slide 77: Tamara Miller
Tamara Miller MS, BSc, PMP, DipBus For personal use only Senior Vice President Product Development Tamara Miller joined Actinogen in September 2017 and has over 20 years of international clinical operations and product development experience. She holds a Masters and a Bachelor’s Degree in Biomedical
Slide 78: Cheryl Townsend
Cheryl Townsend RN, PG Clin Research, MLaw For personal use only Vice President Clinical Operations Cheryl Townsend joined Actinogen in March 2022 as Vice President of Clinical Operations and is responsible for Actinogen’s clinical operations and the successful delivery of the company’s clinical tri
Slide 79: Michael Roberts
Michael Roberts BEc Hons, CPA, FFin For personal use only Investor Relations Michael Roberts heads the investor relations and corporate communications function at Actinogen Medical in Sydney. He is a corporate communications specialist with more than 25 years’ experience working with prominent ASX 5
Actinogen Medical — Technical Presentation (August 2022) on 6ix