Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Actinogen Clinical Trials Science Forum 2024
34 slides from Actinogen Medical's conference presentation, May 23, 2024
Slide 1: Actinogen Clinical Trials Science Forum 2024 today – Pipeline in a Pill
ASX ANNOUNCEMENT Actinogen Clinical Trials Science Forum 2024 today – Pipeline in a Pill Actinogen CMO, Dr Dana Hilt and guests explore the unique properties of Xanamem ® for the potential treatment of cognitive impairment in multiple diseases at 3pm AEST today Sydney, 23 May 2024. Actinogen Medical
Slide 2: About 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 association between cortisol and detrimental changes in the brain, affectin
Slide 3: For personal use only
reflect the occurrence of or non-occurrence of any future events. Past performance is not a reliable indicator of future performance. Actinogen Medical does not make any guarantee, representation or warranty as to the likelihood of achievement or reasonableness of any forward-looking statements and
Slide 4: Clinical Trials Science Forum 2024
For personal use only Clinical Trials Science Forum 2024 Xanamem® – A pipeline in a pill for the potential treatment of cognitive impairment in multiple diseases 23 May 2024 ® Xanamem is a registered trademark of Actinogen Medical Limited
Slide 5: 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 For personal use only and does not contain all inform
Slide 6: Pipeline in a Pill – Clinical Trials Science Forum
For personal use only CTSF_Pipeline in aScience Clinical Trials pill_23 Forum May 2024 33
Slide 7: Current state of Xanamem development
For personal use only Current state of Xanamem development: Enhancement of cognition in three studies with excellent safety and tolerability Dr Dana C Hilt MD FAAN ACW Chief Medical Officer CTSF_Pipeline in a pill_23 May 2024 4
Slide 8: Xanamem Summary
Xanamem Summary • Xanamem is an oral 11β-HSD1 inhibitor: safe, well tolerated, pro-cognitive effects For personal use only • Designed to lower brain cortisol with rapid onset of clinical activity • Cortisol target validation in animal models of Alzheimer’s disease (AD) and by cognitive benefit shown
Slide 9: Targeting large clinical opportunities with unmet need
Targeting large clinical opportunities with unmet need For personal use only Current clinical focus of Xanamem development: AD and CIDD • Alzheimer’s Disease global prevalence: 33 million patients • Major Depressive Disorder: 280 million patients, ~70% associated with cognitive impairment, average c
Slide 10: Actinogen Xanamem Phase trials underway
Actinogen Xanamem Phase 2 trials underway Supported by extensive existing clinical data from four previous trials of Xanamem 10mg For personal use only Phase 2a proof-of-concept trial in patients with Results early Q3 2024 Cognitive Impairment & Depression (n=167) Interim results Phase 2b confirmato
Slide 11: Xanamem: oral, low-dose, once-a-day treatment with a unique mechanism
Xanamem: oral, low-dose, once-a-day treatment with a unique, non-amyloid/tau mechanism Rodent experimental studies & clinical trials validate cortisol target for treatment of AD1-4 For personal use only Brain penetrant 11β-HSD1 small molecule enzyme inhibitor reduces cortisol inside brain cells3,4 -
Slide 12: Anti-amyloid antibodies slow but not halt progression of AD
Newer anti-amyloid “immunotherapy” antibodies shown to slow but not halt progression of AD1 Ideally patients would not worsen on treatment For personal use only Worsening of 0 CDR-SB2 over 18 months -0.5 Large area of -1 unmet need requires non- amyloid therapies -1.5 -2 Benefit of donanemab 0.45 po
Slide 13: Xanamem slows the rate of CDR-SB functional decline in mild AD
Xanamem slows the rate of CDR-SB functional decline in mild AD1 Patients with elevated plasma pTau181 indicating progressive, amyloid- positive disease (n=34): Xanamem slows CDR-SB worsening For personal use only Xanamem Placebo 0 0 0 0.2 0.4 0.36* CDR-SB units * Difference vs. placebo Change from 0
Slide 14: Cognitive improvements suggest potential clinical benefits across dementia patient sub-types
Cognitive improvements suggest potential clinical benefits across dementia patient sub-types* Positive trends in both high and low plasma pTau biomarker groups For personal use only 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.
Slide 15: Xanamem has excellent safety/tolerability profile
Xanamem has excellent safety/tolerability profile No emerging safety signals For personal use only 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 (
Slide 16: XanaMIA Phase 2b trial in Alzheimer's Disease
XanaMIA Phase 2b trial in Alzheimer’s Disease Initial, interim results in mid 2025, final results H1 2026 For personal use only 10mg Xanamem Screening from Dec 23 Follow-up & open label Placebo -4 0 36 weeks 40 Weeks Double-blind, randomised treatment period (N=220) Interim analysis N=100 @ 24 weeks
Slide 17: Targeting brain tissue cortisol is a promising strategy in cognitive impairment & depression
Targeting brain tissue cortisol with Xanamem is a promising strategy in cognitive impairment & depression For personal use only ✓ Elevated cortisol associated with severe, melancholic depression2 ✓ Cortisol levels associated with treatment outcomes, relapse, & cognition3 ✓ 80-90% of MDD patients rep
Slide 18: XanaCIDD proof-of-concept Phase 2a trial in Cognitive Impairment & Depression
XanaCIDD proof-of-concept Phase 2a trial in Cognitive Impairment & Depression (MDD) For personal use only 10mg Xanamem +/- existing antidepressant Follow-up Screening Placebo +/- existing antidepressant -4 0 6 10 Weeks Double-blind, randomised treatment period (N=167) Key inclusion/exclusion criteri
Slide 19: Xanamem in CIDD and Alzheimer's Disease
Xanamem in CIDD and Alzheimer’s Disease CIDD For personal use only • The XanaCIDD phase 2a trial will provide topline data in early Q3 2024 • Xanamem could have pro-cognitive effects and/or anti-depressant effects in MDD • Cognitive benefits can be extrapolated to AD and other diseases AD • The prev
Slide 20: The clinical pharmacology of Xanamem
For personal use only The clinical pharmacology of Xanamem Professor Paul Rolan MBBS MD FRACP FFPM(UK) FFPMANZCA Clinical Pharmacologist CTSF_Pipeline in a pill_23 May 2024 17
Slide 21: Key Xanamem properties – pharmacology and pharmacokinetics
Key Xanamem properties – pharmacology and pharmacokinetics • Highly potent at target enzyme IC50 28nM For personal use only • Highly selective compared to other enzymes / receptors • The combination of high potency and high selectivity mean very low likelihood of off-target effects • enhances safety
Slide 22: Key Xanamem properties – pharmacodynamics
Key Xanamem properties – pharmacodynamics For personal use only • Confirmed high binding to brain target on PET scan at low doses 5-10mg • 2x ACTH hormonal counterresponse (largely within laboratory normal limits) consistent across all doses studied, including 5 mg daily • No durable effect on circu
Slide 23: PET trial shows full target engagement in the brain at low doses
PET trial shows full target engagement in the brain at low doses Target inhibition 30-60% per rodent efficacy models of cognition1 For personal use only Previous enzyme inhibitors2 have not achieved adequate brain concentrations Baseline After 7 days of daily dosing PET data3 demonstrates that 5 mg
Slide 24: Regional %Occupancy Exceeds 30-60% target
Regional %Occupancy Exceeds 30-60% target Cognitively Normal (n=16) and Alzheimer’s disease (n=15) Cog Norm AD For personal use only Neocortex Medial Temp Lobe Basal Ganglia Cerebellum 100% 100% 100% 100% 80% 80% 80% 80% 60% 60% 60% 60% 40% 40% 40% 40% 20% 20% 20% 20% 0% 0% 0% 0% 5mg 10mg 20mg 30mg
Slide 25: No effect on plasma cortisol levels in AD patients – XanADu study
No effect on plasma cortisol levels in AD patients over 12 weeks – XanADu study For personal use only Plasma cortisol concentration pre- and post-dose over 12 weeks treatment with Xanamem or placebo. Error bars represent +/- standard deviation. CTSF_Pipeline in a pill_23 May 2024 22
Slide 26: Improvement in cognitive function (Attention Composite) in two clinical studies
Improvement in cognitive function (Attention Composite) in two clinical studies For personal use only XanaHES phase 1b trial (n=42) XanaMIA-DR phase 1b trial n=107 CTSF_Pipeline in a pill_23 May 2024 23
Slide 27: Making a successful new medicine
Making a successful new medicine For personal use only ✓ Hits the right target in the right part of the body ✓ Does not hit off-target systems ✓ Low potential for interaction with other drugs ✓ Simple dosing regimen ✓ Good safety profile ✓ Studied at the right dose CTSF_Pipeline in a pill_23 May 202
Slide 28: Cognitive impairment in multiple neurologic & neuropsychiatric conditions
For personal use only Cognitive impairment in multiple neurologic & neuropsychiatric conditions - how Xanamem might aid treatment Professor John Harrison PhD, PhD, CPsychol, CSci, AFBPsS Chief Scientific Officer, Scottish Brain Sciences Visiting Professor at the Institute of Psychiatry, Psychology &
Slide 29: Cognitive deficits in psychiatric disorders
Cognitive deficits in psychiatric disorders For personal use only * Cognitive deficits in the absence of treatment are depicted. CTSF_Pipeline in a pill_23 May 2024 26 Millan MJ et al. (2012) Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy.
Slide 30: Pipeline in a Pill – Clinical Trials Science Forum
For personal use only CTSF_Pipeline in aScience Clinical Trials pill_23 Forum May 2024 27 27
Slide 31: Appendix
For personal use only Appendix CTSF_Pipeline in a pill_23 May 2024 28
Slide 32: Selected glossary
Selected glossary 1 11β-HSD1 11 beta HydroxySteroid Dehydrogenase-1 enzyme. Selectively expressed in brain, liver, adipose. Aβ Amyloid beta – a type of amyloid protein associated with Alzheimer’s Disease, 42 and 40 are different forms For personal use only ACTH Adrenocorticotropic hormone that regul
Slide 33: Selected glossary
Selected glossary 2 IQCODE Informant Questionnaire on Cognitive Decline in the Elderly MCI Mild Cognitive Impairment – memory, executive function deterioration with retained functional abilities For personal use only MDD Major Depressive Disorder MMSE Mini Mental State Examination – a 30-point scale
Slide 34: Contacts
For personal use only Contacts Michael Roberts Steven Gourlay Investor Relations CEO & Managing Director P: +61 2 8964 7401 P: +61 2 8964 7401 M: +61 423 866 231 E. steven.gourlay@actinogen.com.au E. michael.roberts@actinogen.com.au CTSF_Pipeline in a pill_23 May 2024 31
Actinogen Medical — Actinogen Clinical Trials Science Forum 2024 on 6ix