Actinogen Medical Limited · ASX:ACW
Actinogen Medical — 6th International Conference on Cognitive and Behavioral Neurosciences (September 2026)
26 slides from Actinogen Medical's conference presentation, Sep 9, 2026
Slide 1: ASX Announcement: Xanamem oral presentation at international neuroscience conference
ASX ANNOUNCEMENT Xanamem oral presentation at the 6th International Conference on Cognitive and Behavioral Neurosciences by Actinogen’s Chief Medical Officer Dr Dana Hilt Sydney, 9 September 2026. Actinogen Medical ASX: ACW (“ACW” or “the Company”) is pleased to announce the international presentati
Slide 2: About Actinogen Medical and clinical trials
Announcement authorised by the Disclosure Committee of Actinogen Medical Limited About Actinogen Medical Actinogen Medical (ACW) is an ASX-listed, biotechnology company developing a novel therapy for neurological and neuropsychiatric diseases associated with dysregulated brain cortisol. There is a s
Slide 3: Disclaimer
with biomarker-positive Alzheimer’s disease and cognitively normal volunteers. High levels of target engagement in the brain with doses as low as 5 mg daily have been demonstrated in a human PET imaging study. Xanamem is an investigational product and is not approved for use outside of a clinical tr
Slide 4: Controlling cortisol in CNS disease – Xanamem
For personal use only Controlling cortisol in CNS1 disease – Xanamem;® a selective 11β-HSD1 inhibitor as a potential new therapeutic for neuropsychiatric diseases. Dana C Hilt MD CMO, Actinogen Medical Limited 6th International Conference on Cognitive and Behavioral Neurosciences September 8, 2026 1
Slide 5: Disclaimer
Disclaimer This presentation is dated June 2026 and 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 infor
Slide 6: The potential role of brain cortisol in Alzheimer's disease (AD)
For personal use only The potential role of brain cortisol in Alzheimer’s disease (AD) 6th International Conference on Cognitive and Behavioral Neurosciences September 8, 2026 3
Slide 7: Cortisol and the Alzheimer's brain
Cortisol and the Alzheimer’s brain “Stress” and/or genetic factors may drive multiple AD mechanisms via cortisol For personal use only Widely expressed in neurons and microglia Seckl J 2024 (left panel); Milligan Armstrong et al. 2021 https://doi.org/10.1111/brv.12750 6th International Conference on
Slide 8: Impact of cortisol on cognition
Impact of cortisol on cognition Abnormal brain cortisol levels alter cognition For personal use only Memory Performance Stress Addison’s Aging Cognition/ Disease Depression Alzheimer’s Cushing’s syndrome Low Optimal High Brain Cortisol Levels Optimal cognition requires ‘normal’ brain cell cortisol l
Slide 9: Elevated human brain cortisol levels linked to AD
Elevated human brain cortisol levels linked to AD Brain fluid cortisol measurements best reflect the tissue cortisol environment For personal use only German Dementia Competency Network study 0.7 p<0.001 0.6 0.5 CSF cortisol (μg/dl) 0.4 0.3 0.2 0.1 0 Cognitive Normal MCI Other MCI AD AD dementia Pop
Slide 10: ApoE4 associated with elevated brain cortisol levels
Major AD genetic risk factor of ApoE4 associated with elevated brain cortisol levels ~67% of patients in AD trials have one or two copies of the ApoE4 gene For personal use only a) CSF cortisol level by disease classification (SCI: subjective cognitive impairment; SMCI stable mild cognitive impairme
Slide 11: Cortisol excess is toxic to the brain
Cortisol excess is toxic to the brain Literature from clinical use as a therapeutic and excess cortisol in Cushing’s syndrome For personal use only Symptom or sign of brain toxicity Trends to worsening Alzheimer’s disease Shrinkage to hippocampus General brain shrinkage Memory impairment Executive f
Slide 12: Therapeutic cortisol worsened AD over months
Therapeutic cortisol worsened AD over 12 months Historical trial of 10mg prednisone in patients with mild to moderate disease (n=138) For personal use only 9 8 7 Placebo Prednisone 6 Point 5 Change In 4 Score Worsening 3 2 1 0 Cognition Dementia Depression ADAS-cog CDR-SB Ham-D P=0.16 P=0.07 P=0.25
Slide 13: Summary: Cortisol: guilty by association
Summary: Cortisol: guilty by association • Multiple studies support the association between cortisol and AD For personal use only development and progression1-5 • Cognitive impairment in patients with neuroendocrine dysfunction6-9 • Compelling evidence provided by the Australian Imaging, Biomarker &
Slide 14: Potential benefits of 11β-HSD1 inhibition affect multiple disease pathways
Potential benefits of 11β-HSD1 inhibition affect multiple disease pathways For personal use only 11β-HSD1 inhibitors limit tissue synthesis of cortisol Aging, genetics Chronic Stress 11β-HSD1 ↑HPA axis ↑11β-HSD1 expression Inhibitors ↑systemic cortisol Xanamem may counteract ↓ cortisol the deleterio
Slide 15: Once-daily oral treatment with a unique mechanism
Once-daily oral treatment with a unique mechanism Xanamem is a selective cortisol synthesis inhibitor (11β-HSD1 enzyme) For personal use only Good safety profile in ~400 treated Brain-penetrant at low doses (5-10mg) Potentially disease-modifying in AD Anti-depressant activity in phase 2 Low drug int
Slide 16: Xanamem achieves high brain target occupancy
Xanamem achieves high brain target occupancy Distribution of cortisol synthesis enzyme 11β-HSD1 shown in left panel For personal use only Baseline After 7 days of daily dosing 5 mg Xanamem 10 mg Xanamem 20 mg Xanamem SUVRcarotid Reduction in tracer signal (loss of color) indicates high 11β-HSD1 occu
Slide 17: Large Xanamem benefit in high pTau181 patients (1)
Large Xanamem benefit1 in high pTau1812 patients (1) Phase 2a biomarker study: major slowing of CDR-SB decline over 12 weeks (n=34) For personal use only 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 •
Slide 18: Large Xanamem benefit in high pTau181 patients (2)
Large Xanamem benefit in high pTau181 patients (2) For personal use only Twice as many patients in the Xanamem group had stable or improved disease compared with placebo1 … meaning 56% of patients treated with Xanamem were stable or improved vs. 28% in placebo Large effect size vs. placebo of 0.6 –
Slide 19: XanaMIA phase 2b/3 trial in Alzheimer's disease
XanaMIA phase 2b/3 trial in Alzheimer’s disease Final study results November 2026 For personal use only 10mg Xanamem Follow-up & open label Screening from Dec 23 Placebo -4 0 36 Weeks 40 Weeks Double-blind, randomised treatment period (N=247) Key Inclusion Criteria Primary Endpoint Key Secondary End
Slide 20: Xanamem for the treatment of Major Depressive Disorder (MDD)
Xanamem for the treatment of Major Depressive For personal use only Disorder (MDD) Phase 2 study of difficult-to-treat MDD patients with: 1. Significant residual depression (HamD > 17) 2. Measurable cognitive deficit (≥0.5 SD deficit on a coding test vs. normal) 6th International Conference on Cogni
Slide 21: XanaCIDD trial design and methods
XanaCIDD trial design and methods – completed CY2024 Phase 2, double-blind, proof-of-concept controlled trial to assess safety and efficacy Enrolled MDD patients that have both depression and measurable cognitive deficit For personal use only 10mg Xanamem +/- Existing Antidepressant Double-blind Fol
Slide 22: Durable antidepressant activity in phase 2a MDD trial
Durable antidepressant activity in phase 2 MDD trial Separation from placebo overall and on background SSRI therapy* For personal use only Baseline Week 2 Week 4 Week 6 Week 10 0 -2 PT 4.2-point difference Cohen’s d = 0.64 EOT 2.6-point difference p = 0.03 -4 Cohen’s d = 0.38 from baseline (± SE) p
Slide 23: Self-reported benefit in patients taking SSRI
Self-reported benefit in patients taking SSRI (n=75)* Measured by Patient Global Impression – Severity score (PGI-S) For personal use only Baseline Week 2 Week 4 Week 6 Week 10 PT 0 -0.2 EOT 0.41-point difference Cohen’s d = 0.43 -0.4 PT 0.59-point difference PGI-S LS mean change from p = 0.08 Cohen
Slide 24: Phase 2a MDD summary
Phase 2a MDD summary For personal use only Clinical benefit observed on both MADRS and PGI-S: Clinically significant benefits commencing at the end of 6 weeks therapy maintained/increased after 4 weeks of blinded, off-treatment follow up Improvements observed in cognition in both treatment gro
Slide 25: Summary: Xanamem - a potential new therapeutic in neuropsychiatry
Summary: Xanamem - a potential new therapeutic in neuropsychiatry An oral, selective and CNS-penetrant 11β-HSD1 inhibitor For personal use only Xanamem is a selective 11β-HSD1 inhibitor that inhibits brain cortisol synthesis Safe and well tolerated in more than 500 people treated Clinical acti
Slide 26: Thank you
Thank you For personal use only Dana C Hilt MD CMO, Actinogen Medical Limited Sydney, Australia Dana.Hilt @actinogen.com.au 6th International Conference on Cognitive and Behavioral Neurosciences September 8, 2026 23