Actinogen Medical Limited · ASX:ACW
Actinogen Medical — Investor Presentation (September 2024)
39 slides from Actinogen Medical's investor presentation, September 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 Corporate Presentation September 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 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: 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 5: 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 6: 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 7: Xanamem pipeline
Xanamem pipeline Indication Preclinical Phase 1 Phase 2 Phase 3 Alzheimer’s disease On-going phase 2b MDD Topline results phase 2a Open INDs Phase 2 trials Fragile X syndrome Phase 2a paused Schizophrenia - CIAS Frontotemporal dementia Potential next indications Lewy-body dementia CI and dementia PD
Slide 8: 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 9: Stock price and key shareholders
Stock price and key shareholders* ASX: ACW – YTD CY24 Key Data 52 Week Range $0.015 – $0.099 YTD CY24 change 103% Shares on issue 2.7b Unlisted options 367m Closing price $0.044 Closing market cap* $119m 30 June cash balance $9.45m* Key Shareholders Biotech Value Fund 9.2% CEO Steven Gourlay 3.6% To
Slide 10: Depression
Depression Corporate Presentation September 2024 10
Slide 11: 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 12: 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 13: 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 14: Results summary
Results summary • The trial was well-conducted, with excellent data quality, no major differences between Australia and the UK or at high enrolling clinical sites • Clinically and statistically significant treatment benefits were seen on depression • No treatment benefit was observed for cognitive d
Slide 15: 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 w
Slide 16: 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 17: 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 18: 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 19: 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 20: Stronger MADRS response in patients with milder MDD
Stronger MADRS response in patients with milder MDD Clinically significant in both 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 from Cohen’s
Slide 21: Positive PGI-S responses both MADRS groups
Positive PGI-S responses both MADRS groups Clinically significant 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 Cohen’s d = 0.34 -
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 • Clinically, statistically significant and durable treatment benefits on depression o Key secondary endpoint, MADRS, at EOT and four weeks of post-treatment follow up
Slide 23: Positive implications for Alzheimer's
Positive implications for Alzheimer’s XanaMIA phase 2b – a 36-week trial in 220 biomarker-positive patients • 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 depression increases the
Slide 24: Alzheimer's disease
Alzheimer’s disease Corporate Presentation September 2024 24
Slide 25: 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 26: 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 27: Xanamem in pTau181-positive patients with mild AD
Xanamem in pTau181-positive patients with mild AD 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
Slide 28: XanaMIA phase 2b trial in Alzheimer's disease
XanaMIA phase 2b 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 Criter
Slide 29: Recent transactions in neuroscience
Recent transactions in neuroscience Corporate Presentation September 2024 29
Slide 30: 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 31: 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 32: Milestones & summary
Milestones & summary Corporate Presentation September 2024 32
Slide 33: Two promising phase 2 clinical programs
Two promising phase 2 clinical programs 2024 2025 2026 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 Pharmacology and Non-clinical S
Slide 34: Next steps for Xanamem
Next steps for Xanamem ✓ 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 population ✓ Consultation on
Slide 35: Appendix
Appendix Corporate Presentation September 2024 35
Slide 36: 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 37: Selected Glossary 1
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 38: Selected Glossary 2
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 39: 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. [email protected] E. [email protected] Corporate Presentation September 2024 39
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