Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Investor Presentation (May 2025)
31 slides from Actinogen Medical's investor presentation, May 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 May 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 May 2025 3
Slide 4: XanaMIA phase 2b/3 trial in AD accelerating enrolment
XanaMIA phase 2b/3 trial in AD accelerating enrolment Full enrolment Q4 2025, final results late 2026 • 100th patient enrolled expected Q2 2025, triggering interim analysis late 2025 • 220 participants full enrolment Q4 2025 with final results late 2026 • 35 active clinical sites in Australia and th
Slide 5: Xanamem is in advanced stages of development
Xanamem is 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 inhibit
Slide 6: 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 7: Corporate snapshot
Corporate snapshot ASX-listed company founded in 2014 • Market Cap ~$100 million • Cash balance of $18.7 million as of Mar 31, 2025, 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) ~
Slide 8: Xanamem – Pipeline focused on Alzheimer's as lead
Xanamem – Pipeline focused on Alzheimer’s as lead Depression phase 2a results support further development Indication Preclinical Phase 1 Phase 2 Phase 3 Next Milestone Results 2025-26 Alzheimer’s disease On-going phase 2b/3 Non-dilutive MDD Phase 2b/3-ready Open INDs funding Fragile X syndrome Phase
Slide 9: Xanamem
Xanamem Corporate Presentation May 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: Alzheimer's disease program
Alzheimer’s disease program Corporate Presentation May 2025 13
Slide 14: Alzheimer's disease market is large and growing
Alzheimer’s disease market is large and growing Strong cortisol control scientific rationale to address huge unmet medical need Rationale Growing Alzheimer’s Disease market – U.S. • Cortisol levels elevated in brain fluid in Large, unsatisfied and growing market early AD • Chronic corticosteroid tre
Slide 15: 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 16: Large Xanamem benefit in high pTau181 patients
Large Xanamem benefit in high pTau181 patients Phase 2a biomarker study: major slowing of CDR-SB decline over 12 weeks (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
Slide 17: 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 Q4 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 18: Depression program
Depression program Corporate Presentation May 2025 18
Slide 19: 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 20: Phase 2a depression symptom benefits (2024)
Phase 2a depression symptom benefits (2024) - major scientific and drug development achievement Data support further MDD development and are a positive for Alzheimer’s too • Clinically and statistically significant treatment benefits on depressive symptoms for MADRS and patient-reported outcome of s
Slide 21: Conclusion
Conclusion Corporate Presentation May 2025 21
Slide 22: Building momentum toward Alzheimer's results
Building momentum toward Alzheimer’s results Numerous value-add milestones in 2025 and 2026 before final XanaMIA results late 2026 • Positive phase 2a MDD data validates multiple Xanamem programs Clinical activity of unique “cortisol control” mechanism of action Clinical activity of the 10 mg da
Slide 23: Multiple upcoming 2025 milestones
Multiple upcoming 2025 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 Completed FDA Type C meeting for MDD Q1 25
Slide 24: Appendix
Appendix Corporate Presentation May 2025 24
Slide 25: 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 Double-blind Follow-up Screening Placebo +/- Existing Antidepressant 10 Weeks -4 0 6 Weeks post-treatment Double-blind,
Slide 26: MADRS from baseline (± SE)
Xanamem MADRS improvement 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 -4 from baseline (± SE) EOT 1.5-point difference Cohen’s d = 0.43 LS mean change Cohen’s d = 0.24 p < 0.05 p = 0.23 MADRS -6 -8 -10 -12 ON TREATMENT
Slide 27: MADRS benefit in patients also taking SSRI
MADRS benefit in patients also taking 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 -4 Cohen’s d = 0.38 from baseline (± SE) p = 0.15 LS mean change MADRS -6 -8 -10 -12 ON TREATME
Slide 28: 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 29: 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 30: 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 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. steven.gourlay@actinogen.com.au E. michael.roberts@actinogen.com.au Corporate Presentation May 2025 31