Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Technical Presentation (August 2024)
30 slides from Actinogen Medical's technical presentation, Aug 29, 2024
Slide 1: Actinogen updated positive depression results - webinar at 11am today
ASX ANNOUNCEMENT Actinogen updated positive depression results - webinar at 11am today Sydney, 29 August 2024. Actinogen Medical ASX: ACW (“ACW” or “the Company”) is pleased to announce that CEO, Dr Steven Gourlay, CMO Dr Dana Hilt and commercial leader Mr Andy Udell will present at a webinar this m
Slide 2: About Actinogen Medical
ENDS Investors Media Dr. Steven Gourlay Michael Roberts George Hazim CEO & Managing Director Investor Relations Media & Public Affairs Australia P: +61 2 8964 7401 M: +61 423 866 231 M: +61 417 516 262 E. steven.gourlay@actinogen.com.au E. michael.roberts@actinogen.com.au E: georgehazim@mediaaffairs
Slide 3: Disclaimer
positive mild AD. Previously, 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. A series of Phase 2 studies in multiple diseases is being conducted to further confirm and characterize Xanamem’s therapeutic potential. Xa
Slide 4: Further positive depression results from XanaCIDD phase 2a trial
For personal use only Further positive depression results from XanaCIDD phase 2a trial Clinically & statistically significant Xanamem® benefits on depression validate the biological activity of Xanamem 10 mg daily and the “cortisol hypothesis” Dr Dana Hilt MD, Chief Medical Officer Mr Andy Udell, He
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: 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-HSD1 For personal use only “STRESS” in the brain becomes “CHILL” RAPID changes in kinases, cell function, “Lower stress” shorter term e.g. neurotransmitters over
Slide 7: Xanamem has a unique class name
Xanamem has a unique class name Reflecting the drug’s unique tissue cortisol control mechanism For personal use only • The World Health Organization administers the procedure for selecting Nonproprietary or “generic” names for pharmaceutical substances • This INN name (International Nonproprietary N
Slide 8: XanaCIDD updated results
For personal use only XanaCIDD updated results XanaCIDD updated results 29 August 2024 5
Slide 9: XanaCIDD trial design and methods
XanaCIDD trial design and methods Phase 2, double-blind, proof-of-concept controlled trial to assess safety and efficacy For personal use only 10mg Xanamem +/- Existing Antidepressant Follow-up Screening Placebo +/- Existing Antidepressant 10 Weeks -4 0 6 Weeks post-treatment Double-blind, randomise
Slide 10: How do MADRS and PGI-S differ?
How do MADRS and PGI-S differ? Two very different measurement systems for depressive symptoms For personal use only Endpoint Domains How assessed MADRS Apparent sadness, reported sadness, inner Rater interview 60-point scale tension, reduced sleep, reduced appetite, concentration difficulties, lassi
Slide 11: XanaCIDD statistical methods
XanaCIDD statistical methods Statistical considerations reflect industry standard for proof-of-concept trials For personal use only • Primary endpoint of the Attention composite was analyzed using a standard Mixed Model for Repeated Measures (MMRM) • Secondary endpoints (including depression by MADR
Slide 12: MADRS & PGI-S depression benefits
MADRS & PGI-S depression benefits Montgomery-Åsberg Depression Rating Scale, Patient Global Impression-Severity For personal use only • Xanamem treatment performed better than placebo, to a clinically*, and in many cases, statistically significant extent: ✓ In all patients (n=165) a clinically signi
Slide 13: Typical, broad, moderate depression trial population
Typical, broad, moderate depression trial population All patients on or previously treated with anti-depressants For personal use only 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) % o
Slide 14: 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 15: 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 16: 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 17: 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) For personal use only 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)
Slide 18: Stronger MADRS response in patients with milder MDD
Stronger MADRS response in patients with milder MDD Clinically significant in both subgroups at Week 10 For personal use only 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 me
Slide 19: Positive PGI-S responses both MADRS groups
Positive PGI-S responses both MADRS groups Clinically significant at Weeks 6 & 10 For personal use only 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 differe
Slide 20: 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 21: Conclusions & next steps
For personal use only Conclusions & next steps XanaCIDD updated results 29 August 2024 18
Slide 22: 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 For personal use only • Clinically, statistically significant and durable treatment benefits on depression o Key secondary endpoint, MADRS, at EOT and four weeks of po
Slide 23: Positive implications for Alzheimer's
Positive implications for Alzheimer’s XanaMIA phase 2b – a 36-week trial in 220 biomarker-positive patients For personal use only • Evidence of durable benefit on depression from control of brain cortisol validates Xanamem’s mechanism of action at a 10 mg daily dose • Durable clinical activity on de
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 For personal use only Scientific rationale U.S. Depression market large unmet need • More than 50 years of research associates • 21M patients have had ≥ 1 MDD episode cortisol w
Slide 25: AUVELITY MDD recent sales launch example
AUVELITY MDD recent sales launch example Axsome Therapeutics • Combination product of dextromethorphan and buproprion – two generic drugs For personal use only • 3.8-point MADRS benefit vs. placebo6 • Indicated for the treatment of major depressive disorder (MDD) in adults • Unique Selling Propositi
Slide 26: Axsome's successful AUVELITY launch
Axsome’s successful AUVELITY launch Last quarter net sales US$65 million, estimated peak US sales US$ 1 to 3 billion* For personal use only Source: https://axsometherapeuticsinc.gcs-web.com/static-files/5fdf5d50-57da-4655-872b-d8b302cc470d XanaCIDD updated results 29 August 2024 23
Slide 27: Next steps for Xanamem
Next steps for Xanamem For personal use only ✓ Enrol XanaMIA phase 2b in Alzheimer’s as quickly as possible ✓ Implement product development plan for both Alzheimer’s disease and depression with focus on speed to marketing approvals ✓ Finalize data analysis e.g. detail of MDD responder patient popula
Slide 28: Two promising phase clinical programs
Two promising phase 2 clinical programs 2024 2025 2026 For personal use only H1 H2 H1 H2 H1 H2 Phase 2b Alzheimer’s (AD) Interim data Final results Phase 3 AD Phase 2a Final results Phase 2b/3 Depression Cog/Depression Expert, partner & Phase 3 Depression FDA discussions Ancillary Clinical Pharmacol
Slide 29: References and links
References and links For personal use only 1. Ramamoorthy S, Cidlowski JA Rheum Dis Clin North Am 2016;42(1):15-31. doi:10:10.1016/j.rdc.2015.08.002 https://pubmed.ncbi.nlm.nih.gov/26611548/ 2. Seckl J. 11β-Hydroxysteroid dehydrogenase and the brain: Not (yet) lost in translation. J Intern Med. 2024
Slide 30: 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 XanaCIDD updated results 29 August 2024 27
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