Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Investor Presentation (August 2024)
34 slides from Actinogen Medical's investor presentation, August 2024
Slide 1: Oral Xanamem: Controlling brain cortisol to treat depression and slow Alzheimer's
Oral Xanamem® Controlling brain cortisol to treat depression and slow progression in Alzheimer’s disease Corporate Presentation August 2024 ® Xanamem is a registered trademark 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 m
Slide 3: Overview
Overview Novel mechanism and attractive oral profile • Xanamem is a unique brain-penetrant tissue cortisol synthesis inhibitor (11β-HSD1 enzyme) • Once-daily oral therapy with potential efficacy, safety and ease of use greater than competitors • More than 380 people treated with promising safety pro
Slide 4: Once-daily oral treatment with a unique mechanism
Once-daily oral treatment with a unique mechanism Xanamem is a small molecule tissue cortisol synthesis inhibitor (11β-HSD1 enzyme) Good safety profile in >380 treated Brain-penetrant at low doses Potentially disease-modifying in AD Anti-depressant activity in phase 2 Low drug interaction potential
Slide 5: Human PET study shows full target engagement
Human PET study shows full target engagement Other 11β-HSD1 enzyme inhibitors have not achieved adequate brain levels Baseline After 7 days of daily dosing 5 mg Xanamem 10 mg Xanamem 20 mg Xanamem Xanamem extensively binds SUVRcarotid to the 11β-HSD1 enzyme throughout the brain, with high post-treat
Slide 6: Xanamem pipeline
Xanamem pipeline Indication Preclinical Phase 1 Phase 2 Phase 3 Alzheimer’s disease On-going phase 2b MDD Topline results phase 2a Open INDs Phase 2 trials Fragile X syndrome Phase 2a paused Schizophrenia - CIAS Frontotemporal dementia Potential next indications Lewy-body dementia CI and dementia PD
Slide 7: Experienced board and management team
Experienced board and management team Board of Directors Dr. Geoff Brooke Dr. Steven Gourlay Mr. Malcolm McComas Dr. George Morstyn Dr. Nicki Vasquez Chairman CEO & MD Non-Executive Director Non-Executive Director Non-Executive Director MBBS; MBA MBBS; FRACP; PhD; MBA BEc, LLB; FAICD; SF Fin MBBS; P
Slide 8: Stock price and key shareholders
Stock price and key shareholders* ASX: ACW – YTD CY24 Key Data 52 Week Range $0.015 – $0.099 YTD CY24 change 30% Shares on issue 2.7b Unlisted options 367m Closing price $0.027 Closing market cap* $73m 30 June cash balance $9.45m* Key Shareholders Biotech Value Fund 9.2% CEO Steven Gourlay 3.6% Top
Slide 9: Depression
Depression Corporate Presentation August 2024 9
Slide 10: Depression
Depression Strong scientific rationale to address the large unmet medical need Scientific rationale U.S. Depression market large unmet need • Elevated cortisol associated with severe, • 21M patients have had ≥ 1 MDD episode melancholic depression • Cortisol levels associated with treatment outcomes,
Slide 11: XanaCIDD phase 2a trial cognitive impairment & MDD
XanaCIDD phase 2a trial cognitive impairment & MDD Topline results announced 12 August 2024 10mg Xanamem +/- Existing Antidepressant Follow-up Screening Placebo +/- Existing Antidepressant -4 0 6 Weeks 10 Weeks Double-blind, randomised treatment period (N=167) Primary Endpoint Key Secondary Endpoint
Slide 12: XanaCIDD statistical methods
XanaCIDD statistical methods Statistical considerations reflect industry standard for proof-of-concept trials • Primary & secondary endpoints analyzed using a standard Mixed Model for Repeated Measures (MMRM) • Three pre-specified subgroups for efficacy: current anti-depressant therapy (yes/no), bas
Slide 13: Results summary
Results summary • The trial was well-conducted, with excellent data quality, no major differences between Australia and the UK or at high enrolling clinical sites • Xanamem was safe and well tolerated (n=165 treated) • No serious adverse events thought related to Xanamem have occurred in any trial t
Slide 14: Clinically and statistically significant benefits over placebo on MADRS depression scale
Clinically and statistically significant benefits over placebo on MADRS depression scale • Xanamem treatment performed better than placebo, to a clinically, and in many cases, statistically significant extent, on the key secondary endpoint of depression (MADRS score) overall and in key pre-specified
Slide 15: MADRS curves separate at Week 6 & 10
MADRS curves separate at Week 6 & 10 All randomized participants (n = 165) Xanamem Placebo Baseline Week 2 Week 4 Week 6 Week 10 PT 0 BETTER -2 PT 2.7-point difference -4 Cohen’s d = 0.43 p < 0.05 MADRS LS mean change -6 from baseline (± SE) -8 EOT 1.5-point difference -10 Cohen’s d = 0.24 p = 0.23
Slide 16: Persistent anti-depressant effect in patients with less severe depression
Persistent, statistically significant anti-depressant effect in patients with less severe depression MADRS < 26 at Baseline MADRS ≥ 26 at Baseline Week 10 Week 10 Baseline Week 2 Week 4 Week 6 PT Baseline Week 2 Week 4 Week 6 PT 0 0 PT 3.6-point difference BETTER LS mean change from baseline Cohen’s
Slide 17: Large placebo effect on the attention composite
Large placebo effect on the attention composite Both Xanamem and placebo groups improved greatly over 6 weeks, p = not significant ON TREATMENT POST-TREATMENT 0.6 0.5 BETTER 0.4 0.3 0.2 Attention Composite Maximum prior absolute z-scores (± SE) 0.1 placebo response known 0.15 units 0 -0.1 -0.2 -0.3
Slide 18: Encouraging data on depression & safety
Encouraging data on depression & safety • Xanamem safety profile was excellent, consistent with other trials • Clinically and statistically significant treatment benefits on depression validate the clinical activity of a 10 mg daily dose also used in the Alzheimer’s program • No treatment effect obs
Slide 19: Alzheimer's disease
Alzheimer’s disease Corporate Presentation August 2024 19
Slide 20: Alzheimer's disease
Alzheimer’s disease Strong scientific rationale to address huge unmet medical need Scientific rationale Alzheimer’s Disease market – U.S. • Cortisol levels are elevated in brain fluid in Large unsatisfied and growing market early AD • Chronic corticosteroid treatment leads to # of patients Cost to t
Slide 21: Anti-amyloid therapy modestly slows AD progression
Anti-amyloid therapy modestly slows AD progression Ideally patients with AD would not worsen on treatment at all 0.5 Ideal trajectory Worsening of 0 with disease CDR-SB stabilization over 18 months -0.5 Unmet need -1 despite amyloid therapy -1.5 -2 Benefit of donanemab over 18 months -2.5 Worse perf
Slide 22: Xanamem in pTau181-positive patients with mild AD
Xanamem in pTau181-positive patients with mild AD Phase 2a biomarker study: major slowing of CDR-SB decline (n=34) Xanamem Placebo 0 0.2 0.4 0.36 Xanamem vs. Placebo CDR-SB units 0.6 • Mean 0.6 units Change from • Median 0.8 units Baseline (SE) • p = 0.09 0.8 • Cohen’s d = 0.4 1 0.98 1.2 1.4 Worse B
Slide 23: XanaMIA phase 2b trial in Alzheimer's disease
XanaMIA phase 2b trial in Alzheimer’s disease Initial, interim results in mid 2025, final results mid 2026 10mg Xanamem Follow-up & open label Screening from Dec 23 Placebo -4 0 36 Weeks 40 Weeks Double-blind, randomised treatment period (N=220) Interim analysis N=100 @ 24 weeks Key Inclusion Criter
Slide 24: Recent transactions in neuroscience
Recent transactions in neuroscience Corporate Presentation August 2024 24
Slide 25: Recent neuroscience acquisitions and IPOs
Recent neuroscience acquisitions and IPOs Caraway PIPE-307 Lead Drug(s) TRPML1 KarXT Emraclidine ALTO-100 RAP-219 PIPE-791 Phase Preclinical Phase 3 Phase 2 Phase 2 Phase 2 Phase 1 Epilepsy, BPD, Lead asset PD, other neuro Schizophrenia Schizophrenia MDD MS & MDD other neuro Transaction Acquisition
Slide 26: Active licensing for clinical neuroscience assets
Active licensing for clinical neuroscience assets ulotaront, Drug ACI – 24.060 PRX-005 NBI-1117567 SEP- 378614 AL-001 BIIB-124 Bepranemab and others Phase Phase 1b/2 Phase 1 Phase 2 Phase 3 Phase 3 Phase 3 Phase 1 Alzheimer’s Dementias Alzheimer’s Alzheimer’s Schizophrenia/ Indication (amyloid beta
Slide 27: Milestones & summary
Milestones & summary Corporate Presentation August 2024 27
Slide 28: Two promising phase 2 clinical programs
Two promising phase 2 clinical programs 2024 2025 2026 H1 H2 H1 H2 H1 H2 Phase 2b Alzheimer’s (AD) Interim data Final results Phase 3 AD Phase 2a Final results Phase 2b Depression Cog/Depression Partnering & FDA discussions Phase 3 Depression Ancillary Clinical Pharmacology and Non-clinical Studies
Slide 29: Summary
Summary Unique oral treatment for patients with neuropsychiatric diseases and dementia • Anti-depressant activity in phase 2a validates Xanamem’s tissue cortisol mechanism of action and confirms clinical activity at the 10 mg daily dose • Large opportunity for a safe and effective anti-depressant wi
Slide 30: Appendix
Appendix Corporate Presentation August 2024 30
Slide 31: Key references
Key references Other references see also https://actinogen.com.au/xanamem Preclinical 11β-HSD1 inhibition Alzheimer’s disease and cortisol • Cognitive and disease-modifying effects of 11β-hydroxysteroid dehydrogenase type 1 • Plasma Cortisol, Brain Amyloid-β, and Cognitive Decline in Preclinical Alz
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 • ACTH – Adrenocorticotropic hormone that regulates blood
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 • MDD – Major Depressive Disorder • MMSE – Mini Mental State Examination – a 30-point scale of si
Slide 34: 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. steven.gourlay@actinogen.com.au E. michael.roberts@actinogen.com.au Corporate Presentation August 2024 34
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