Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Investor Presentation (September 2024)
45 slides from Actinogen Medical's investor presentation, Sep 18, 2024
Slide 1: Oral Xanamem: Controlling brain cortisol to treat depression and Alzheimer's
Oral Xanamem® Controlling brain cortisol to treat depression and slow progression in Alzheimer’s disease - a novel therapeutic mechanism in late phase trials Capital Raising – $11.1 million to accelerate Alzheimer’s phase 2b/3 trial 18 September 2024 ® Xanamem is a registered trademark of Actinogen
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 Novel mechanism and attractive oral profile • Xanamem is a unique brain-penetrant tissue cortisol synthesis inhibitor (11β-HSD1 enzyme) • Once-daily oral therapy with potential efficacy, safety and ease of use greater than competitors • More than 380 people treated with promising safety pro
Slide 4: Experienced board and management team
Experienced board and management team 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; PhD; FRACP CD PhD M
Slide 5: Alzheimer's disease phase 2b/3
Alzheimer’s disease phase 2b/3 Fundraising Presentation September 2024 5
Slide 6: Recent developments increase confidence in XanaMIA
Recent developments increase confidence in XanaMIA XanaMIA Alzheimer’s disease trial moving to full enrolment and full phase 2b/3 design • Recently released data showing clinically and statistically significant improvement in depression symptoms validate Xanamem’s mechanism of action and 10 mg dose
Slide 7: Alzheimer's disease
Alzheimer’s disease Strong scientific rationale to address huge unmet medical need Scientific rationale 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 patients Cost to t
Slide 8: 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 9: Xanamem slows AD progression markedly
Xanamem slows AD progression markedly Phase 2a data in biomarker-positive patients with mild AD (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 Baseline Wee
Slide 10: 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 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 Criteria Primary
Slide 11: Positive phase 2a depression data
Positive phase 2a depression data Fundraising Presentation September 2024 11
Slide 12: XanaCIDD trial design
XanaCIDD trial design Phase 2a, 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=167) Primar
Slide 13: Results summary
Results summary • Clinically and statistically significant treatment benefits on depression symptoms • Cognition improved markedly in both Xanamem and placebo groups without evidence of greater Xanamem benefit vs. placebo • Xanamem was safe and well tolerated (n=165 treated) • The trial was well-con
Slide 14: MADRS & PGI-S depression benefits
MADRS & PGI-S depression benefits Montgomery-Åsberg Depression Rating Scale, Patient Global Impression-Severity • Xanamem treatment performed better than placebo, to a clinically, and in many cases, statistically significant extent: ✓ In all patients (n=165) a clinically significant MADRS benefit wa
Slide 15: MADRS from baseline
Xanamem MADRS separation from Week 6 All randomized participants (n = 165) 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
Slide 16: PGI-S from baseline
Xanamem PGI-S separation from Week 2 All randomized participants (n = 165) 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 =
Slide 17: Xanamem major improvement in depression response
Xanamem major improvement in depression response 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 1
Slide 18: Broad & durable subgroup effects - MADRS & PGI-S
Broad & durable subgroup effects - MADRS & PGI-S Measured at Weeks 2, 4, 6 & 10 (green favors Xanamem, red placebo) Response/variable *No anti- Yes anti- *MADRS MADRS *Cog. < Cog. ≥ All D D < 26 ≥ 26 0.07 0.07 (n=165) (n=31) (n=134) (n=81) (n=83) (n=82) (n=82) MADRS (Cd ≥ 0.3) (week) 10 2,6 10 2,6,1
Slide 19: 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 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: Offer Summary
Offer Summary Fundraising Presentation September 2024 21
Slide 22: Capital raising overview
Capital raising overview Actinogen is seeking to raise up to approximately A$11.1m via a Placement and SPP ▪ Institutional Placement to raise approximately A$7.0m under Actinogen’s existing L.R. 7.1 placement capacity (Institutional Placement) and; ▪ Placement to Directors of $1.1m, including CEO, D
Slide 23: Use of funds
Use of funds XanaMIA phase 2b/3 trial and other activities Details A$m Full enrolment of phase 2b/3 XanaMIA trial for 220 participants 9.5 ▪ Additional site and patient costs 0.5 ▪ Additional data management, data monitoring committee and statistical costs 0.5 ▪ Additional quality activities ▪ Offer
Slide 24: Offer timetable
Offer timetable Indicative capital raising timetable1 Date Trading halt Monday, 16 September 2024 Record Date for SPP Tuesday, 17 September 2024 Placement and SPP announced, and trading halt lifted Wednesday, 18 September 2024 Settlement of Placement Shares Monday, 23 September 2024 Allotment of Pla
Slide 25: Conclusions
Conclusions Fundraising Presentation September 2024 25
Slide 26: Controlling brain tissue cortisol really works!
Controlling brain tissue cortisol really works! Proof of 11β-HSD1 as a therapeutic target is a major scientific and clinical advance • Clinically, statistically significant and durable treatment benefits on depression • Xanamem was safe and well tolerated; no significant safety issues were observed
Slide 27: Two promising late-phase clinical programs
Two promising late-phase clinical programs 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 Cog/Depression Expert, partner & Phase 3 Depression FDA discussions Ancillary Clinical Pharmacology and Non-c
Slide 28: Appendix – corporate
Appendix – corporate Fundraising Presentation September 2024 28
Slide 29: Stock price and key shareholders
Stock price and key shareholders* ASX: ACW – Last 12 months Key data 52 Week Range $0.015 - $0.099 140.00mm YTD CY24 change +75% 0.09 120.00mm 0.08 Shares on issue 2.7Bn 0.07 100.00mm Unlisted options 349m Closing price $0.035 Share price 0.06 80.00mm Volume 0.05 Closing market cap* $94.9m 60.00mm 0
Slide 30: Xanamem pipeline
Xanamem pipeline Indication Preclinical Phase 1 Phase 2 Phase 3 Alzheimer’s disease On-going phase 2b/3 Open INDs MDD Phase 2a complete, Phase 2b/3 in planning Phase 2/3 trials Fragile X syndrome Phase 2a paused Bipolar disorder Frontotemporal dementia Potential next indications Lewy-body dementia C
Slide 31: Recent neuroscience acquisitions and IPOs
Recent neuroscience acquisitions and IPOs Caraway PIPE-307 Lead Drug(s) TRPML1 KarXT Emraclidine ALTO-100 RAP-219 PIPE-791 Phase Preclinical Phase 3 Phase 2 Phase 2 Phase 2 Phase 1 Epilepsy, BPD, Lead asset PD, other neuro Schizophrenia Schizophrenia MDD MS & MDD other neuro Transaction Acquisition
Slide 32: Active licensing for clinical neuroscience assets
Active licensing for clinical neuroscience assets ulotaront, Drug ACI – 24.060 PRX-005 NBI-1117567 SEP- 378614 AL-001 BIIB-124 Bepranemab and others Phase Phase 1b/2 Phase 1 Phase 2 Phase 3 Phase 3 Phase 3 Phase 1 Alzheimer’s Dementias Alzheimer’s Alzheimer’s Schizophrenia/ Indication (amyloid beta
Slide 33: Appendix – other Xanamem
Appendix – other Xanamem Fundraising Presentation September 2024 33
Slide 34: Controlling brain cortisol has durable benefits
Controlling brain cortisol1 has durable benefits Xanamem inhibits local tissue production of cortisol in key regions of the brain via 11β-HSD12 “STRESS” in the brain becomes “CHILL” RAPID changes in kinases, cell function, “Lower stress” shorter term e.g. neurotransmitters over hours to days • Reduc
Slide 35: 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 36: Appendix – depression data
Appendix – depression data Fundraising Presentation September 2024 36
Slide 37: XanaCIDD statistical methods
XanaCIDD statistical methods Statistical considerations reflect industry standard for proof-of-concept trials • Primary & secondary endpoints analyzed using a standard Mixed Model for Repeated Measures (MMRM) • Three pre-specified subgroups for efficacy: current anti-depressant therapy (yes/no), bas
Slide 38: Typical, broad, moderate depression trial population
Typical, broad, moderate depression trial population All XanaCIDD patients were either on, or previously treated with, anti-depressants Xanamem Placebo (n=82) (n=83) Mean age (SD) 49 (13) 49 (15) % female 63 61 Mean screening HAM-D depression score (SD) 21 (3) 21 (3) Mean MADRS (SD) 24 (6) 26 (7) %
Slide 39: Stronger MADRS response in patients with milder MDD
Stronger MADRS response in patients with milder MDD Clinically significant in both XanaCIDD subgroups at Week 10 MADRS < 26 at Baseline MADRS ≥ 26 at Baseline Week 10 Week 10 Baseline Week 2 Week 4 Week 6 PT Baseline Week 2 Week 4 Week 6 PT 0 0 PT 3.6-point difference BETTER MADRS LS mean change fro
Slide 40: Positive PGI-S responses both MADRS groups
Positive PGI-S responses both MADRS groups Clinically significant XanaCIDD findings at Weeks 6 & 10 MADRS < 26 at Baseline MADRS ≥ 26 at Baseline Week 10 Week 10 Baseline Week 2 Week 4 Week 6 PT Baseline Week 2 Week 4 Week 6 PT 0 0 BETTER PGI-S LS mean change from -0.2 -0.2 PT 0.29-point difference
Slide 41: Appendix – references
Appendix – references Fundraising Presentation September 2024 41
Slide 42: 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 43: 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 44: 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 45: 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 Fundraising Presentation September 2024 45
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