Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Investor Presentation (October 2025)
39 slides from Actinogen Medical's investor presentation, October 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 October 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 October 2025 3
Slide 4: Xanamem: Clear pathway to Alzheimer's approval
Xanamem: Clear pathway to Alzheimer’s approval Phase 2b/3 trial on track, FDA agreement streamlines development • FDA confirms development pathway to US marketing approval using one additional pivotal trial of 10 mg vs. placebo and open-label safety studies • Clear guidance on minimal ancillary nonc
Slide 5: First-in-class therapy with strong IP and large market potential
First-in-class therapy with strong IP and large market potential Novel 11β-HSD1 cortisol control mechanism, oral, attractive safety profile • Brain cortisol has been proposed as pathogenic mechanism in Alzheimer’s & major depressive disorder • 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 runway to at least mid 2026 • Seasoned Board and Management team with a track-record of success Key shareholders • CEO Steve Gourlay ~5% (including via ~$2 million invested personally) • Top 20 ex-Gourlay ~23% Ph
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 Ongoing phase 2b/3 Non-dilutive MDD Phase 2b/3-ready Open INDs funding Fragile X syndrome Phase
Slide 9: Xanamem
Xanamem Corporate Presentation October 2025 9
Slide 10: Clinically validated and differentiated Alzheimer's program
Clinically validated and differentiated Alzheimer's program ✓ Mouse experimental studies, brain cortisol levels & human clinical trials validate cortisol as a target for the treatment of AD ✓ Excellent safety profile, 400+ patients treated, no related serious adverse events ✓ Fully brain-penetrant o
Slide 11: Xanamem's unique mechanism of action animation
Xanamem’s unique mechanism of action animation Click here for animation video Corporate Presentation October 2025 11
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 October 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 January 2026, 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 = 110 Key Inclusion Criteria
Slide 19: Commercial readiness
Commercial readiness Corporate Presentation October 2025 19
Slide 20: Direct insights from the front line of Alzheimer's care
Direct insights from the front line of Alzheimer’s care Physician perspectives on current practice, unmet needs, and future therapies* • Market research with over 100 general neurologists and dementia/geriatric specialists • Representative of the AD-treating physician population as it relates to geo
Slide 21: Strong physician response to Xanamem's target profile
Strong physician response to Xanamem’s target profile Over half of their current AD patients fall within Xanamem’s addressable market Corporate Presentation October 2025 21
Slide 22: Driving awareness of Xanamem and cortisol biology
Driving awareness of Xanamem and cortisol biology Expanding education, engagement and visibility • Educational need identified: Qualitative research and advisory boards revealed limited physician understanding of the role of cortisol in the brain and its link to Alzheimer’s pathology • Action taken:
Slide 23: Depression program
Depression program Corporate Presentation October 2025 23
Slide 24: 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 25: 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 • Predominantly co-treated population with
Slide 26: Conclusion
Conclusion Corporate Presentation October 2025 26
Slide 27: On track to deliver transformative Alzheimer's data
On track to deliver transformative Alzheimer’s data Multiple catalysts ahead as Xanamem advances towards pivotal results • On-track with XanaMIA trial in patients with mild-moderate Alzheimer’s disease ✓ FDA confirms development pathway to US marketing approval ✓ Full enrolment of 220 participants i
Slide 28: Multiple near-term milestones in coming year
Multiple near-term milestones in coming year Milestone Likely Timing Screening activities close, XanaMIA AD trial Q4 25 Full enrolment, 220 patients with AD, XanaMIA AD trial Q4 25 XanaCIDD MDD peer-reviewed journal publication Q4 25 / Q1 26 CTAD conference AD presentation in San Diego Q4 25 Meeting
Slide 29: Appendix
Appendix Corporate Presentation October 2025 29
Slide 30: Early commercial planning drives strategy and impact
Early commercial planning drives strategy and impact “Typical” partnering process Launch / Preclinical Phase 1: Phase 2 (2a/2b): Phase 3: Discovery Registration Post Development Clinical Trials Clinical Trials Clinical Trials Registration Xanamem (emestedastat) current stage Biotechs typically initi
Slide 31: Current Alzheimer's treatments
Current Alzheimer’s treatments Significant unmet need persists despite two approved anti-amyloid mAbs Though acknowledging ▪ Neurologists are conscious of the advances current DMTs offer in a field that has seen sparse advance of current innovation for decades and they acknowledge the potential bene
Slide 32: AD Pipeline: Opportunity for differentiated therapies
AD Pipeline: Opportunity for differentiated therapies Combination approaches likely needed for meaningful impact • Amyloid-targeting therapies: Demonstrated limited efficacy; market differentiation remains modest • Anti-Tau programs: Many early candidates have not achieved clinical success, highligh
Slide 33: 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 34: 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 35: 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 36: 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 37: 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
Slide 38: 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 si
Slide 39: 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 Join the Actinogen Investor Hub: https://investors.actinogen.com.au/ Corporate Presentati
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