Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Dementia Trials Australia Annual Scientific Meeting 2024
28 slides from Actinogen Medical's conference presentation, Oct 11, 2024
Slide 1: ASX Announcement: Actinogen CEO presents at Dementia Trials Australia Meeting
ASX ANNOUNCEMENT Actinogen CEO presents at Dementia Trials Australia Annual Scientific Meeting in Sydney Sydney, 11 October 2024. Actinogen Medical ASX: ACW (“ACW” or “the Company”) is pleased to announce that its CEO, Dr Steven Gourlay, will present at the Dementia Trials Australia Annual Scientifi
Slide 2: About Actinogen and current clinical trials
Cognitive function means how a person understands, remembers and thinks clearly. Cognitive functions include memory, attention, reasoning, awareness and decision-making. Actinogen is currently developing its lead compound, Xanamem, as a promising new therapy for Alzheimer’s Disease and Depression an
Slide 3: Go paperless notice
ACTINOGEN MEDICAL ENCOURAGES ALL CURRENT INVESTORS TO GO PAPERLESS BY REGISTERING THEIR DETAILS WITH THE DESIGNATED REGISTRY SERVICE PROVIDER, AUTOMIC GROUP. For personal use only Actinogen Medical Limited ACN 086 778 476 3 Suite 901, Level 9, 109 Pitt Street, Sydney NSW 2000 +61 2 8964 7401 | actin
Slide 4: Oral Xanamem: Controlling brain cortisol to treat depression and slow Alzheimer's
For personal use only Oral Xanamem® Controlling brain cortisol to treat depression and slow progression in Alzheimer’s disease - a novel therapeutic mechanism in late phase trials How Xanamem’s benefit in depression translates to possible efficacy in Alzheimer’s Dementia Trials Australia Annual Scie
Slide 5: 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 6: Once-daily oral treatment with a unique mechanism
Once-daily oral treatment with a unique mechanism Xanamem controls tissue cortisol via inhibition of the 11β-HSD1 enzyme For personal use only Knockout mice protected against age-related cognitive decline Memory improvements shown in mice with 27-60% enzyme inhibition Murine AD model with 30% enzyme
Slide 7: Cortisol: guilty by association in humans in many ways
Cortisol: guilty by association in humans in many ways • 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 Imagin
Slide 8: Xanamem controls cortisol by inhibition of 11β-HSD1
Xanamem controls cortisol by inhibition of 11β-HSD11 Controlling brain cortisol2 has potential durable benefits For personal use only “STRESS” in the brain becomes “CHILL” RAPID changes in kinases, cell function, “Lower stress” shorter term e.g. neurotransmitters over hours to days • Reducing inflam
Slide 9: 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 For personal use only 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
Slide 10: Positive phase 2a depression data
For personal use only Positive phase 2a depression data Actinogen DTAus 2024 7
Slide 11: Background to development in depression
Background to development in depression Xanamem’s unique mechanism and safety differentiate it from other anti-depressants For personal use only Scientific rationale Promising Xanamem clinical data • More than 50 years of research associated • Good tolerability 5mg to 70mg daily cortisol with depres
Slide 12: XanaCIDD trial design
XanaCIDD trial design Standard phase 2a design with 6 weeks treatment For personal use only 10mg Xanamem +/- Existing Antidepressant Follow-up Screening Placebo +/- Existing Antidepressant 10 Weeks -4 0 6 Weeks post-treatment Double-blind, randomised treatment period (N=167) Primary Endpoint Key Sec
Slide 13: Xanamem MADRS separation from placebo
Xanamem MADRS separation from Week 6 All randomized participants (n = 165) For personal use only Xanamem Placebo Baseline Week 2 Week 4 Week 6 Week 10 PT 0 BETTER -2 from baseline (± SE) PT 2.7-point difference LS mean change -4 Cohen’s d = 0.43 p < 0.05 MADRS -6 -8 EOT 1.5-point difference -10 Cohe
Slide 14: Xanamem PGI-S separation from placebo
Xanamem PGI-S separation from Week 2 All randomized participants (n = 165) For personal use only Xanamem Placebo Baseline Week 2 Week 4 Week 6 Week 10 PT 0 BETTER -0.2 from baseline (± SE) -0.4 PT 0.28-point difference LS mean change Cohen’s d = 0.29 p = 0.12 -0.6 PGI-S -0.8 -1 EOT 0.22-point differ
Slide 15: Xanamem major improvement in depression response
Xanamem major improvement in depression response Increased rates of remission (MADRS < 10) and large (50%) improvements For personal use only % 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
Slide 16: Excellent safety profile consistent with prior trials
Excellent safety profile consistent with prior trials Summary of Treatment-Emergent Adverse Effects (TEAE) For personal use only Xanamem Placebo Overall N = 82 N = 83 N = 165 Any TEAE 69 (84.1%) 67 (80.7%) 136 (82.4%) TEAE related to trial drug 27 (32.9%) 24 (28.9%) 51 (30.9%) Serious adverse event
Slide 17: Clinically and statistically significant benefits
Clinically and statistically significant benefits Depression phase 2a summary For personal use only • Heavily pre/co-treated population with moderately severe MDD • Treatment benefits on depressive symptoms for MADRS and patient-reported outcome of severity • Consistent depression efficacy across su
Slide 18: Alzheimer's disease phase 2b/3
For personal use only Alzheimer’s disease phase 2b/3 Actinogen DTAus 2024 15
Slide 19: Donanemab only modestly slows AD progression
Donanemab only modestly slows AD progression Ideally patients with AD would not worsen on treatment at all 0.5 For personal use only 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
Slide 20: Xanamem slows AD progression markedly over weeks
Xanamem slows AD progression markedly over 12 weeks Phase 2a data in biomarker (pTau181)-positive patients used to design next AD trial (n=34)1 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
Slide 21: XanaMIA phase 2b/3 trial in Alzheimer's disease
XanaMIA phase 2b/3 trial in Alzheimer’s disease Interim results mid 2025, final results mid 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=220) Interim analysis N=100 @ 24 weeks Key Incl
Slide 22: Conclusions
For personal use only Conclusions Actinogen DTAus 2024 19
Slide 23: Validation of cortisol mechanism supports AD program
Validation of cortisol mechanism supports AD program XanaMIA Alzheimer’s disease trial implemented as a pivotal, phase 2b/3 design For personal use only • XanaMIA AD trial is now being conducted as one of two potential “pivotal” trials by: • CDR-SB amended as the primary endpoint • 220 participants
Slide 24: Appendix
For personal use only Appendix Actinogen DTAus 2024 21
Slide 25: Xanamem pipeline
Xanamem pipeline For personal use only Indication Preclinical Phase 1 Phase 2 Phase 3 Next Milestone Alzheimer’s disease On-going phase 2b/3 Results 25-26 MDD Phase 2a complete, Phase 2b/3 in planning Open INDs FDA meeting Fragile X syndrome Phase 2a on hold On hold Bipolar disorder PTSD Potential n
Slide 26: Experienced board and management team
Experienced board and management team Board of Directors For personal use only 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;
Slide 27: 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 28: Contacts
Contacts For personal use only 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 Actinogen DTAus 2024 25
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