Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Investor Presentation (October 2024)
34 slides from Actinogen Medical's investor presentation, October 2024
Slide 1: Oral Xanamem: Controlling brain cortisol to treat depression and slow progression in Alzheimer's disease
Oral Xanamem® Controlling brain cortisol to treat depression and slow progression in Alzheimer’s disease - a novel therapeutic mechanism Corporate Presentation October 2024 ® 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 2024 3
Slide 4: Xanamem
Xanamem 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 inhibitor that leaves adrenal cortisol synth
Slide 5: 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 6: Company
Company ASX-listed company founded in 2014 • Market Cap A$80-100 million • Cash runway to late 2026 • Conducted three phase 1 (Australia) and four phase 2 trials (Australia, US and UK) Key shareholders • Biotech Value Fund (BVF) ~8% • CEO Steve Gourlay ~5% (in part via $2 million invested personally
Slide 7: State of play for Xanamem programs
State of play for Xanamem programs Evidence of durable benefit on depression from control of brain cortisol validates the Xanamem program in terms of: ✓ “Cortisol control” mechanism of action ✓ 10 mg daily proof-of-concept dose being used in Alzheimer’s phase 2b/3 trial ✓ 10 mg daily dose is also su
Slide 8: Xanamem - Pipeline
Xanamem - Pipeline Indication Preclinical Phase 1 Phase 2 Phase 3 Next Milestone Results 25-26 Alzheimer’s disease (AD) On-going phase 2b/3 FDA Type C MDD Phase 2a complete, Phase 2b/3 in planning Open INDs in Q1 25 Fragile X syndrome Phase 2a on hold On hold Bipolar disorder PTSD Potential next ind
Slide 9: Xanamem – AD and MDD Program Timelines
Xanamem – AD and MDD Program Timelines 2024 2025 2026 H1 H2 H1 H2 H1 H2 Phase 2b/3 Alzheimer’s Interim data Final results Phase 3 Alzheimer’s Phase 2a Final results Phase 2b/3 Depression Depression Expert, partner & Phase 3 Depression FDA discussions Ancillary Clinical Pharmacology and Non-clinical
Slide 10: Xanamem
Xanamem Corporate Presentation October 2024 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 >380 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 “STRESS” in the brain becomes “CHILL” RAPID changes in kinases, cell function, “Lower stress” shorter term e.g. neurotransmitters over hours to days • Reducing inflammation lead to short-t
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 2024 14
Slide 15: Alzheimer's disease
Alzheimer’s disease Strong cortisol control scientific rationale to address huge unmet medical need Rationale Growing Alzheimer’s Disease market – U.S. • Cortisol levels are elevated in brain fluid in Large unsatisfied and growing market early AD • Chronic corticosteroid treatment leads to # of pati
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: Xanamem benefit in pTau181-positive AD patients
Xanamem benefit in pTau181-positive AD patients Phase 2a biomarker study: major slowing of CDR-SB decline (n=34)1 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 1.4 Worse Ba
Slide 18: XanaMIA phase 2b/3 trial in Alzheimer's disease
XanaMIA phase 2b/3 trial in Alzheimer’s disease Initial, interim results in mid 2025, final results mid 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 Crit
Slide 19: Depression program
Depression program Corporate Presentation October 2024 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: XanaCIDD trial design and methods
XanaCIDD trial design and methods Phase 2, double-blind, proof-of-concept controlled trial to assess safety and efficacy 10mg Xanamem +/- Existing Antidepressant Follow-up Screening Placebo +/- Existing Antidepressant 10 Weeks -4 0 6 Weeks post-treatment Double-blind, randomised treatment period (N=
Slide 22: MADRS from baseline (± SE)
Xanamem MADRS separation from Week 6 (n=165) All randomized participants 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 Cohen’s d = 0.24 p = 0.23 -1
Slide 23: MADRS in subgroup taking concurrent SSRI (n=76)
MADRS in subgroup taking concurrent SSRI* (n=76) Baseline Week 2 Week 4 Week 6 Week 10 0 -2 PT 4.16-point difference Cohen’s d = 0.64 p = 0.03 -4 -6 -8 EOT 2.56-point difference -10 Cohen’s d = 0.38 p = 0.15 -12 Xanamem (n=37) Placebo (n=39) * SSRI: selective serotonin reuptake inhibitor Corporate P
Slide 24: PGI-S from baseline (± SE)
Xanamem PGI-S separation from Week 2 (n=165) All randomized participants 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 difference -1.2 Cohen’s d = 0.
Slide 25: Xanamem improves MADRS response rates (n=165)
Xanamem improves MADRS response rates (n=165) Increased rates of remission (MADRS < 10) and large (50%) improvements % 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 2 Week 4 Week 6 Week 10 X
Slide 26: Excellent safety profile consistent with prior trials
Excellent safety profile consistent with prior trials Summary of Treatment-Emergent Adverse Effects (TEAE) 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 0 1 (1.2%) 1 (0.6%) Re
Slide 27: Depression phase 2a conclusions and next steps
Depression phase 2a conclusions and next steps • Clinically and statistically significant treatment benefits on depressive symptoms for MADRS and patient-reported outcome of severity • Heavily pre/co-treated population with moderate MDD • Consistent depression efficacy across subgroups • Cognition i
Slide 28: Conclusion
Conclusion Corporate Presentation October 2024 28
Slide 29: Positive depression data a boost to both AD and MDD
Positive depression data a boost to both AD and MDD Evidence of durable benefit on depression from control of brain cortisol validates the Xanamem program in terms of: ✓ “Cortisol control” mechanism of action ✓ 10 mg daily proof-of-concept dose being used in Alzheimer’s phase 2b/3 trial ✓ 10 mg dail
Slide 30: Appendix
Appendix Corporate Presentation October 2024 30
Slide 31: 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 32: 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 33: 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 34: 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 October 2024 34
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