Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Investor Presentation (February 2025)
38 slides from Actinogen Medical's investor presentation, February 2025
Slide 1: Oral Xanamem (emestedastat) Corporate Presentation
Oral Xanamem® (emestedastat) Controlling brain cortisol to slow progression in Alzheimer’s disease and treat depression Corporate Presentation February 2025 ® 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 Corporate Presentation February 2025 3
Slide 4: Xanamem is now in advanced stages of development
Xanamem is now in advanced stages of development Novel 11β-HSD1 cortisol control mechanism, oral, attractive safety profile • Brain cortisol has long been proposed as a pathogenic mechanism in Major Depressive Disorder (MDD) and Alzheimer’s (AD) • Unique brain-penetrant tissue cortisol synthesis inh
Slide 5: 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 6: Corporate snapshot
Corporate snapshot ASX-listed company founded in 2014 • Market Cap ~$100 million • Cash balance of $22.9 million at Dec 31 2024 provides runway to at least mid 2026 • Conducted three phase 1 (Australia) and four phase 2 trials (Australia, US and UK) Key shareholders • Biotech Value Fund (BVF) ~7% •
Slide 7: Advancing Xanamem programs
Advancing Xanamem programs First-in-class INN name awarded by the WHO, “emestedastat” with the unique suffix “-stedastat” that highlights Xanamem’s unique mechanism of action and the lack of direct competition for CNS cortisol control Evidence of durable benefit on depression from control of brain c
Slide 8: Xanamem – AD and MDD Program Timelines
Xanamem – AD and MDD Program Timelines* 2024 2025 2026 H1 H2 H1 H2 H1 H2 Phase 2b/3 Alzheimer’s Interim data Final results Phase 3 Alzheimer’s Phase 2a Depression Final results Phase 2b Depression Expert, partner & Phase 3 Depression FDA discussions Ancillary Clinical Pharmacology and Non-clinical S
Slide 9: Xanamem
Xanamem Corporate Presentation February 2025 9
Slide 10: 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 ~400 treated Brain-penetrant at low doses Potentially disease-modifying in AD Anti-depressant activity in phase 2 Low drug interaction potential
Slide 11: Xanamem controls cortisol by inhibition of 11β-HSD1
Xanamem controls cortisol by inhibition of 11β-HSD11 Controlling brain cortisol2 has potential durable benefits Reduction of “stress response” in brain RAPID changes in kinases, cell function, “Lower stress” shorter term e.g. neurotransmitters over hours to days • Reducing inflammation lead to short
Slide 12: 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 13: Intellectual property protection
Intellectual property protection Corporate Presentation February 2025 13
Slide 14: Protection from patents and data exclusivity
Protection from patents and “data exclusivity” Core “composition of matter” patent granted worldwide to 2031 with standard extensions to at least 2036 in major markets Additional protection is afforded from patents in the “national phase” of approvals covering the treatment of cognitively normal peo
Slide 15: Alzheimer's disease program
Alzheimer’s disease program Corporate Presentation February 2025 15
Slide 16: Alzheimer's disease
Alzheimer’s disease Strong cortisol control scientific rationale to address huge unmet medical need Rationale Growing 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 pat
Slide 17: 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 18: Xanamem benefit in pTau181-positive AD patients
Xanamem benefit in pTau181-positive AD patients 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 Bas
Slide 19: XanaMIA phase 2b/3 trial in Alzheimer's disease
XanaMIA phase 2b/3 trial in Alzheimer’s disease Initial, interim results in Q4 2025, final results H2 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 20: Depression program
Depression program Corporate Presentation February 2025 20
Slide 21: There remains significant unmet need in depression
There remains significant unmet need in depression Xanamem’s unique mechanism and safety differentiate it from older drugs Scientific rationale U.S. Depression market large unmet need • More than 50 years of research associates • 21M patients have had ≥ 1 MDD episode cortisol with depression • Eleva
Slide 22: XanaCIDD trial design and methods – completed CY2024
XanaCIDD trial design and methods – completed CY2024 Phase 2, double-blind, proof-of-concept controlled trial to assess safety and efficacy 10mg Xanamem +/- Existing Antidepressant Follow-up Screening Placebo +/- Existing Antidepressant 10 Weeks -4 0 6 Weeks post-treatment Double-blind, randomized t
Slide 23: MADRS from baseline
Xanamem MADRS separation from Week 6 (n=165) All randomized participants Baseline Week 2 Week 4 Week 6 Week 10 PT 0 -2 BETTER PT 2.7-point difference from baseline (± SE) -4 Cohen’s d = 0.43 LS mean change EOT 1.5-point difference Cohen’s d = 0.24 p < 0.05 p = 0.23 MADRS -6 -8 -10 -12 ON TREATMENT F
Slide 24: MADRS in patients taking concurrent SSRI
MADRS in patients taking concurrent SSRI (n=76) Largest co-treatment subgroup Baseline Week 2 Week 4 Week 6 Week 10 0 -2 PT 4.2-point difference BETTER Cohen’s d = 0.64 EOT 2.6-point difference p = 0.03 Cohen’s d = 0.38 from baseline (± SE) -4 p = 0.15 LS mean change MADRS -6 -8 -10 -12 ON TREATMENT
Slide 25: Excellent safety profile consistent with prior trials
Excellent safety profile consistent with prior trials Summary of Treatment-Emergent Adverse Effects (TEAE) Xanamem Placebo Overall N = 82 N = 83 N = 165 Any TEAE 70 (85.4%) 67 (80.7%) 137 (83.0%) TEAE related to trial drug 27 (32.9%) 24 (28.9%) 51 (30.9%) Serious adverse event 0 1 (1.2%) 1 (0.6%) Re
Slide 26: Depression phase 2a: key findings & next steps
Depression phase 2a: key findings & next steps • Clinically and statistically significant treatment benefits on depressive symptoms for MADRS and patient-reported outcome of severity • Heavily pre/co-treated population with moderate MDD • Consistent depression efficacy across subgroups • Cognition i
Slide 27: Conclusion
Conclusion Corporate Presentation February 2025 27
Slide 28: Building positive momentum
Building positive momentum Evidence of durable benefit on depression from control of brain cortisol validates the Xanamem program in terms of: ✓ “Cortisol control” mechanism of action ✓ 10 mg daily proof-of-concept dose being used in Alzheimer’s phase 2b/3 trial ✓ 10 mg daily dose is also suitable f
Slide 29: Selected upcoming milestones
Selected upcoming milestones Milestone Likely Timing First patient randomized and treated in US, XanaMIA trial Q4 24 Meetings at JP Morgan Healthcare conference week, San Francisco Q1 25 Clinical pharmacology manuscript peer-reviewed publication Q1 25 FDA Type C meeting for MDD Q1 25 Clinical Trials
Slide 30: Appendix
Appendix Corporate Presentation February 2025 30
Slide 31: XanaCIDD results - PGI-S separation from baseline
XanaCIDD results - Xanamem PGI-S separation from Week 2 (n=165) All randomized participants Baseline Week 2 Week 4 Week 6 Week 10 PT 0 -0.2 BETTER EOT 0.22-point difference -0.4 Cohen’s d = 0.23 from baseline (± SE) p = 0.19 LS mean change PT 0.28-point difference -0.6 Cohen’s d = 0.29 p = 0.12 PGI-
Slide 32: XanaCIDD results - PGI-S benefit in patients taking SSRI
XanaCIDD results - PGI-S benefit in patients taking SSRI (n=75) Largest co-treatment subgroup Baseline Week 2 Week 4 Week 6 Week 10 PT 0 -0.2 EOT 0.41-point difference Cohen’s d = 0.43 BETTER -0.4 p = 0.08 PT 0.59-point difference Cohen’s d = 0.62 from baseline (± SE) p = 0.03 LS mean change -0.6 PG
Slide 33: XanaCIDD results - Xanamem improves MADRS response rates
XanaCIDD results - Xanamem improves MADRS response rates (n=165) Increased rates of remission (MADRS < 10) and large (50%) improvements % with ≥ 50% reduction in MADRS % with < 10 points on MADRS 40 30 >50% more >50% more 35 25 30 20 25 20 15 15 10 10 5 5 0 0 Week 2 Week 4 Week 6 Week 10 Week 2 Week
Slide 34: Xanamem - Pipeline
Xanamem - Pipeline Indication Preclinical Phase 1 Phase 2 Phase 3 Next Milestone Results 25-26 Alzheimer’s disease On-going phase 2b/3 FDA Type C MDD Phase 2b/3-ready Open INDs in Q1 25 Fragile X syndrome Phase 2a on hold On hold Bipolar disorder PTSD Potential next indications Lewy-body dementia Fr
Slide 35: Key references
Key references Other references see also https://actinogen.com.au/xanamem 11β-HSD1 inhibition Alzheimer’s disease and cortisol • Seckl J. 11β-Hydroxysteroid dehydrogenase and the brain: Not (yet) lost in translation. J Intern Med. 2024 Jan;295(1):20-37. doi: 10.1111/joim.13741. Epub 2023 Nov 8. • Pl
Slide 36: 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 37: 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 38: 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 February 2025 38
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