Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Investor Presentation (March 2024)
31 slides from Actinogen Medical's investor presentation, Mar 25, 2024
Slide 1: Phase 2-stage clinical company with near-term trial results
Phase 2-stage clinical company with near-term trial results mid 2024 and Q2 2025 De-risked oral therapy for dementia and depression Corporate Presentation March 2024
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: Experienced Leadership and Management
Experienced Leadership and Management Extensive drug development and commercial experience Talented management team… …with an experienced Board Dr. Geoff Brooke Chairman MBBS; MBA Mr. Malcolm McComas Dr. Steven Gourlay Dana Hilt Will Souter Cheryl Townsend Fujun Li Michael Roberts Non-Executive Dire
Slide 4: Company Highlights
Company Highlights Positioned to leverage the wider biotech market tailwinds Xanamem® lowers brain cortisol and is in Phase 2 trials to treat patients with cognitive impairment associated with 1 Clinical-stage depression and Alzheimer’s disease Strong biological Elevated brain cortisol is strongly a
Slide 5: Attractive product profiles in Depression and Alzheimer's
Attractive product profiles in Depression and Alzheimer’s Rapidly acting oral therapy with dual action on cognitive Xanamem $2 billion1 impairment / depression Cognitively enhancing and disease modifying oral Xanamem therapy for all stages of Alzheimer’s disease $5 billion1 1. Peak sales 2034 https:
Slide 6: Opportunity across two key markets
Opportunity across two key markets Significant market opportunity across both Alzheimer’s disease (AD) and Depression Alzheimer’s Disease Market Depression Market US$14 billion market1 with peak sales potential of US$5 billion3 US$17 billion market2 with peak sales potential of US$2 billion3 Total m
Slide 7: Xanamem: Oral, once-a-day treatment with a unique mechanism
Xanamem: Oral, once-a-day treatment with a unique mechanism Xanamem is a brain penetrant 11β-HSD1 small molecule enzyme inhibitor which reduces brain cortisol3,4 Potential to be: Rapidly cognitive enhancing Disease-modifying (slowing progression)1,3 Anti-depressant effects Mouse experimental s
Slide 8: PET data shows full target engagement in the brain at low doses
PET data shows full target engagement in the brain at low doses Previous enzyme inhibitors1 have not achieved adequate brain concentrations Baseline After 7 days of daily dosing PET data2 demonstrates that Xanamem extensively binds 5 mg Xanamem 10 mg Xanamem 20 mg Xanamem to the 11β-HSD1 enzyme SUVR
Slide 9: Market Exclusivity
Market Exclusivity Strong IP portfolio Strong patent position with over 12 years patent protection for composition of matter in all major markets, broad international cover Other patents extend potential patent life protection including ”methods of use” patents and manufacturing patents Rare pediatr
Slide 10: Actinogen Xanamem Phase 2 trials underway
Actinogen Xanamem Phase 2 trials underway De-risked by extensive existing clinical data from four previous trials of Xanamem 10mg Phase 2a proof-of-concept trial in patients with Results mid 2024 Depression & Cognitive Impairment (n=160) Interim results Phase 2b confirmatory trial in patients with m
Slide 11: Targeting brain cortisol with Xanamem is a promising strategy in depression
Targeting brain cortisol with Xanamem is a promising strategy in depression Elevated cortisol associated with severe, melancholic depression2 Cortisol levels associated with treatment outcomes, relapse, & cognition3 80-90% of MDD patients report neurocognitive symptoms1 Cognitive symptoms of
Slide 12: XanaCIDD proof-of-concept Phase 2a trial in Depression and Cognitive Impairment
XanaCIDD proof-of-concept Phase 2a trial in Depression and Cognitive Impairment Final results mid 2024, primary endpoint validated in prior trials of Xanamem 10mg Xanamem +/- existing antidepressant Follow-up Screening Placebo +/- existing antidepressant -4 0 6 Weeks 10 Weeks Double-blind, randomise
Slide 13: Actinogen Xanamem Phase 2 trials underway
Actinogen Xanamem Phase 2 trials underway De-risked by extensive existing clinical data from four previous trials of Xanamem 10mg Phase 2a proof-of-concept trial in patients with Results mid 2024 Depression & Cognitive Impairment (n=160) Interim results Phase 2b confirmatory trial in patients with m
Slide 14: The answers to Alzheimer's Disease are starting to emerge in the clinic
The answers to Alzheimer’s Disease are starting to emerge in the clinic… Alzheimer’s proteins amyloid and tau are the pathology – not the cause… Clearing amyloid produces a very modest benefit Other causal processes are involved like inflammation, lipids and glucose handling… Corporate presentation
Slide 15: Quotes: Dr Howard Fillit
Quotes: Dr Howard Fillit Founder & CSO Alzheimer’s Drug Discovery Foundation1 “Seventy-eight percent …. of all drugs in clinical development are non- Xanamem is an easy-to-use, oral, amyloid, non-tau drugs” non-amyloid, non-tau tablet “Multiple targets are being addressed now, which is great for the
Slide 16: Newer anti-amyloid antibodies shown to 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 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 -2.5 donanemab all placebo al
Slide 17: Xanamem significantly slows the rate of functional decline (CDR-SB) in patients with mild AD
Xanamem significantly slows the rate of functional decline (CDR-SB) in patients with mild AD* Patients with elevated plasma pTau181 indicating progressive, amyloid-positive disease (n=34) Xanamem Placebo 0 0 0 0.2 0.4 0.36 * CDR-SB units Change from 0.6 * Difference vs. placebo Baseline (SE) • Mean
Slide 18: 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 Higher pTau biomarker (n=34) Lower pTau biomarker (n=34) 0.3 0.3 Composite Units (SE*) Composite Units (SE) 0.2 0.2 0.1 0.1 0 0 -0.1 -0.1 -0
Slide 19: XanaMIA Phase 2b trial in Alzheimer's Disease
XanaMIA Phase 2b trial in Alzheimer’s Disease Initial, interim results in H1 2025, final results H2 2025 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 Key inclusion criteria
Slide 20: Strong M&A and licensing activity in the CNS sector
Strong M&A and licensing activity in the CNS sector Target/Partner ulotaront, SEP- Drug KarXT Emraclidine BPN-14770 PRX-005 NBI-1117567 378614 and AL-001 BIIB-124 Bepranemab others Phase Phase 3 Phase 2 Phase 2 Phase 1 Phase 2 Phase 3 Phase 3 Phase 3 Phase 1 Fragile X Dementias Alzheimer’s Schizophr
Slide 21: Recent Milestones & Upcoming Catalysts
Recent Milestones & Upcoming Catalysts1 Q1 2024 Human PET study peer-review publication Q2-4 2024 Various peer-review publications, abstracts Q1 2024 UK Innovation Passport granted Q1 2025 Start depression Phase 2b Q1 2024 Phase 2b Alzheimer’s trial first patient screened H1 2025 Interim
Slide 22: Appendix
Appendix Corporate presentation March 25 2024 22
Slide 23: 11β-HSD1 inhibition and attenuated cognitive decline
11β-HSD1 inhibition and attenuated cognitive decline Xanamem has pleiotropic mechanisms of action to reduce or halt cognitive decline Increased synaptic plasticity cortisone Lowers Better working & (inert) X z brain Greater dendritic complexity episodic memory cortisol reduced GR/MR Larger hippocamp
Slide 24: Rationale: Why targeting brain cortisol with Xanamem is promising in Alzheimer's disease
Rationale: Why targeting brain cortisol with Xanamem is a promising strategy in Alzheimer’s disease Multiple streams of data support the hypothesis Epidemiology, cortisol and animal Clinical trials of Xanamem experiments Cortisol levels are elevated in brain fluid in early Inhibits brain 11β-HSD
Slide 25: All major Xanamem development risks mitigated
All major Xanamem development risks mitigated Highly attractive, mid phase 2 profile in dementia and major depression Animal tox studies Completed long-term toxicology studies needed for FDA approval Preclinical Neuroprotection in rodent models of Alzheimer’s with chemically Alzheimer’s mouse mode
Slide 26: Methods for double-blind, prospective assessment of biomarker-positive mild AD patients in Phase 2a
Methods for double-blind, prospective assessment of biomarker-positive mild AD patients in Phase 2a1 Re-examining the 12-week XanADu Phase 2a trial with biomarkers - a simulation of the current 36-week XanaMIA Phase 2b trial Assess efficacy trends Measure disease on clinical endpoints biomarkers Wee
Slide 27: International Cognition Clinical Advisory Board
International Cognition Clinical Advisory Board Preeminent global thought-leaders in clinical trials for assessment of cognition Prof. John Harrison Dr Dana C. Hilt (CMO) Dr Christina Kurre Olsen Prof. Paul Maruff A/Prof Christopher Chen Metis Cognition Ltd • Expert psychologist with a special • 25+
Slide 28: International Scientific Advisory Boards
International Scientific Advisory Boards Preeminent 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 Prof. Scott
Slide 29: Selected glossary 1
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 ACTH Adrenocorticotropic hormone that regulates blood levels of c
Slide 30: Selected glossary 2
Selected glossary 2 IQCODE Informant Questionnaire on Cognitive Decline in the Elderly MCI Mild Cognitive Impairment – memory, executive function deterioration with retained functional abilities MDD Major Depressive Disorder MMSE Mini Mental State Examination – a 30-point scale of simple questions t
Slide 31: Contacts
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. [email protected] E. [email protected] Corporate presentation March 25 2024 31
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