Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Investor Presentation (July 2025)
32 slides from Actinogen Medical's investor presentation, July 2025
Slide 1: Oral Xanamem (emestedastat) Corporate Presentation July 2025
Oral Xanamem® (emestedastat) Controlling brain cortisol to slow progression in Alzheimer’s disease and treat depression Corporate Presentation July 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 July 2025 3
Slide 4: XanaMIA Alzheimer's phase 2b/3 trial progressing well
XanaMIA Alzheimer’s phase 2b/3 trial progressing well Full enrolment Q4 2025, final results late 2026 • More than 100 participants now enrolled • Interim analysis scheduled for January 2026 • Full enrolment of 220 participants on-track for Q4 2025 • Final results on-track for Q4 2026 • 35 active cli
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 ~$70 million • Cash balance of ~$16.4m at 30 June 2025, provides runway to at least mid 2026 • Conducted three phase 1 (Australia) and four phase 2 trials (Australia, US and UK) Key shareholders • CEO Steve Gourlay ~5% (including via
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 July 2025 9
Slide 10: Xanamem's unique mechanism of action animation
Xanamem’s unique mechanism of action animation Click here for animation video Corporate Presentation July 2025 10
Slide 11: 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 12: 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 13: 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 14: Alzheimer's disease program
Alzheimer’s disease program Corporate Presentation July 2025 14
Slide 15: 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 16: 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 17: 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 18: 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 19: Depression program
Depression program Corporate Presentation July 2025 19
Slide 20: 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 21: 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 22: Conclusion
Conclusion Corporate Presentation July 2025 22
Slide 23: Building momentum toward Alzheimer's results
Building momentum toward Alzheimer’s results Numerous value-add near-term milestones • On-track with XanaMIA trial in patients with mild-moderate Alzheimer’s disease ✓ Full enrolment of 220 participants in XanaMIA pivotal trial Q4 2025 ✓ Interim analysis of XanaMIA safety and efficacy data January 2
Slide 24: Multiple completed and near-term milestones
Multiple completed and near-term milestones Milestone Likely Timing 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 ADPD conference AD presentation in Vienna Q2 25 Completed All 20
Slide 25: Appendix
Appendix Corporate Presentation July 2025 25
Slide 26: 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 27: 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 28: 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 29: 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 30: 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 31: 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 32: 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 July 2025 32
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