Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — American Academy of Neurology Annual Meeting 2025
16 slides from Alterity Therapeutics's conference presentation, Apr 10, 2025
Slide 1: Topline Data from a Randomized, Double Blind, Placebo Controlled Phase 2 Study of ATH434 in MSA
Topline Data from a Randomized, Double Blind, Placebo Controlled Phase 2 Study of ATH434 in MSA David Stamler1, Cynthia Wong1, Paula Trujillo2, Margaret Bradbury1, Christine Lucas1 and Daniel Claassen2 1 Alterity Therapeutics, Newark, CA, USA 2 Department of Neurology, Vanderbilt University Medical
Slide 2: Disclosures
Disclosures Authors are either employees of Alterity Therapeutics or received research support for their participation in the study. 2
Slide 3: Background
Background ATH434 Reduces α‐synuclein • Labile iron essential for key cellular functions Aggregation • Excess labile iron promotes • Alpha-synuclein aggregation • Oxidative injury • MSA associated with reduced ability to control levels of labile iron Iron accumulation in areas of pathology • ATH43
Slide 4: Study Objectives
Study Objectives • Evaluate the efficacy, biomarker response, and safety of ATH434 treatment in MSA patients 4
Slide 5: ATH434-201 Study Design
ATH434-201 Study Design 75 mg bid 12 mo treatment MSA 50 mg bid 12 mo treatment (N=60) • Clinical diagnosis of MSA Placebo 12 mo treatment • Motor symptoms ≤4 years • Elevated plasma NfL Quantitative MRI to • No severe impairment measure iron levels Visit Schedule • Clinic visits at Weeks 2, 6, 13,
Slide 6: Populations and Key Endpoints
Populations and Key Endpoints 6 no post Baseline UMSARS I 77 Randomized 71 (Clinical analysis population) 5 neg. CSF α-syn SAA 10 d/c before week 26 1 completed week 26 w/o MRI 61 (Imaging analysis population) Endpoint Change from BL to Week 52 Population Criteria* Primary ≥ 1 post-baseline MRI (26
Slide 7: Baseline Characteristics (mITT)
Baseline Characteristics (mITT) Placebo 50mg BID 75mg BID Overall Parameter (n = 19) (n = 21) (n = 21) (n = 61) 61.5 62.9 64.0 62.8 Age (y) (7.0) (6.3) (6.3) (6.5) Gender (% male) 63.2% 57.1% 57.1% 59.0% Race (% white) 94.7% 81.0% 95.2% 90.2% 16.8 15.4 14.4 15.5 Modified UMSARS I (4.2) (4.6) (4.7) (
Slide 8: Modified UMSARS Part I
Modified UMSARS Part I 26 24 Placebo (n=22) ATH434 50 mg BID (n=25) Modified UMSARS I 22 ATH434 75 mg BID (n=24) Worsening 20 18 Relative Treatment Effect* vs Placebo at 52 weeks 16 P=0.02 for 50 mg P=0.07 50 mg bid 48% 14 for 75 mg 75 mg bid 30% 12 * ChangeATH434 – ChangePlacebo 0 13 26 39 52 Chang
Slide 9: Clinical Global Impression of Severity
Clinical Global Impression of Severity Change from Baseline to Week 52 Change in CGIS (W52 - BL) 1.5 1.0 Worsening * Placebo P=0.0088 ATH434 50 mg BID 0.5 ATH434 75 mg BID 0.0 Mean (SE) • CGI-S is a single-item questionnaire that uses a 7-point Likert Scale ranging from 1 to 7 where a higher score i
Slide 10: Orthostatic Hypotension Symptom Assessment (OHSA)
Orthostatic Hypotension Symptom Assessment (OHSA) Change from Baseline to Week 52 10 Change in OHSA (week 52 - BL) Placebo Worsening 5 ATH434 50 mg BID ATH434 75 mg BID P=0.08 P=0.14 0 • OHSA: Component of the Orthostatic Hypotension Questionnaire • Assesses severity of following • Dizziness/lighthe
Slide 11: Wearable Sensors: Activity in Outpatient Setting
Wearable Sensors: Activity in Outpatient Setting Change from Baseline to Week 52 Step Count Total Time Walking 0 0 Placebo Change in Minutes/day -10 ATH434 50 mg BID Change in steps/day Worsening ATH434 75 mg BID Worsening -1000 -20 P=0.1267 P=0.1535 P=0.0437 -2000 -30 * P=0.1041 -40 -3000 Bouts of
Slide 12: Group Change in Iron Content
Group Change in Iron Content (Week 52 − Baseline) Placebo • No statistically significant changes to iron levels in predefined ROI (s. nigra) • Evidence for reduced iron in globus pallidus 50 mg bid • Iron increases in key regions over time in placebo > ATH434 75 mg bid 12 Reduced Increased
Slide 13: ATH434 Demonstrated Trends in Reduced Brain Atrophy
ATH434 Demonstrated Trends in Reduced Brain Atrophy Change from Baseline in Brain Volume – MSA Atrophy Index^ 26 weeks 52 weeks 0.0000 -0.1000 -0.2000 Z-score -0.3000 -0.4000 -0.5000 -0.6000 Placebo ATH434 50 mg BID ATH434 75 mg BID ^ Composite z-score of the putamen, globus pallidus, cerebellum and
Slide 14: Summary of Adverse Events
Summary of Adverse Events Placebo BID 50mg BID 75mg BID Number (%) of Subjects1 (n=26) (n=25) (n=26) Any Adverse Event (AE) 24 (92.3%) 21 (84.0%) 25 (96.2%) AE by Severity Mild 10 (38.5%) 10 (40.0%) 8 (30.8%) Moderate 6 (23.1%) 8 (32.0%) 11 (42.3%) Severe 8 (30.8%) 3 (12.0%) 6 (23.1%) Serious AEs2 1
Slide 15: Conclusions
Conclusions • ATH434 demonstrates clinically significant efficacy in modifying disease progression • UMSARS I and several additional clinical outcomes • Study results support continued advancement of ATH434 for the treatment of MSA • Baseline differences in pathology and disease severity may explain
Slide 16: Acknowledgements
Acknowledgements The authors would like to thank the study participants, their care partners and the clinical site staff for their contributions to the study. Country Investigator Study Coordinator Institution Wassilios Meissner Sandrine Villars Groupe Hospitalier Pellegrin, Bordeaux Jean-Christophe
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