Alterity Therapeutics Ltd. · ASX:ATH
Alterity Therapeutics — MSA Trust Symposium 2025, London (UCL)
24 slides from Alterity Therapeutics's conference presentation, Apr 28, 2025
Slide 1: Alterity Presents ATH434-201 Phase 2 Results at European MSA Symposium
Alterity Therapeutics Presents ATH434-201 Phase 2 Clinical Trial Results at European MSA Symposium MELBOURNE, AUSTRALIA AND SAN FRANCISCO, USA – 28 April 2025: Alterity Therapeutics (ASX: ATH, NASDAQ: ATHE) (“Alterity” or “the Company”), a biotechnology company dedicated to developing disease modify
Slide 2: About ATH434 and the ATH434-201 Phase 2 Trial
at both dose levels compared to placebo. Overall, the study results support continued advancement of ATH434 for the treatment of MSA. About ATH434 Alterity’s lead candidate, ATH434, is an oral agent designed to inhibit the aggregation of pathological proteins implicated in neurodegeneration. ATH434
Slide 3: About Alterity Therapeutics and Contacts
characterized by a variable combination of slowed movement and/or rigidity, autonomic instability that affects involuntary functions such as blood pressure maintenance and bladder control, and impaired balance and/or coordination that predisposes to falls. A pathological hallmark of MSA is the accum
Slide 4: Forward Looking Statements
U.S. Remy Bernarda remy.bernarda@iradvisory.com +1 (415) 203-6386 Forward Looking Statements This press release contains "forward-looking statements" within the meaning of section 27A of the Securities Act of 1933 and section 21E of the Securities Exchange Act of 1934. The Company has tried to ident
Slide 5: A Randomized, Double Blind, Placebo Controlled Phase 2 Study of ATH434 in MSA
For personal use only A Randomized, Double Blind, Placebo Controlled Phase 2 Study of ATH434 in Multiple System Atrophy David Stamler1, Cynthia Wong1, Paula Trujillo2, Margaret Bradbury1, Christine Lucas1 and Daniel Claassen2 1 Alterity Therapeutics, Newark, CA, USA 2 Department of Neurology, Vander
Slide 6: Disclosures
Disclosures The authors are either employees of Alterity Therapeutics or received research support for their participation in the study. For personal use only 2
Slide 7: ATH434 Reduces α-syn Aggregation
ATH434 Reduces α-syn Aggregation Study Rationale • Labile iron essential for key cellular functions For personal use only • Iron accumulation occurs in MSA affected brain areas (putamen, pallidum, s. nigra) ATH434 Reduces Oxidative Injury • Indicative of impaired iron trafficking 250 80% ↓ Menadione
Slide 8: Iron accumulation in MSA affected brain regions
For personal use only • Histopathology data • MRI data The close association of iron accumulation with distinct α-synuclein-pathology-related anatomical regions of the two disease subtypes supports the critical involvement of pathological iron in disease progression… doi 10.3233/JAD-170601 (2018) do
Slide 9: Excess Labile Iron and Misfolding α-Synuclein Are Drivers of MSA Pathology
Excess Labile Iron and Misfolding α-Synuclein are Important Drivers of MSA Pathology Oxidative Injury For personal use only Vicious cycle of Pathology Driver Effect cellular injury Alpha-synuclein aggregation Excess Free radical production labile iron DNA, lipid, mitochondria damage Stored iron Cell
Slide 10: Development Approach: Address Underlying Pathology
Development Approach: Address Underlying Pathology For personal use only Reduce Preserve Redistribute Stabilize or α‐synuclein neurons and excess labile iron Improve in the CNS aggregation and ODGs Function oxidative injury 6
Slide 11: Study Objectives
Study Objectives • Evaluate the efficacy, biomarker response, and safety of ATH434 For personal use only treatment in MSA patients 7
Slide 12: ATH434-201 Study Design
ATH434-201 Study Design For personal use only 75 mg bid 12 mo treatment MSA* 50 mg bid 12 mo treatment (N=60) • Clinical diagnosis of MSA Placebo 12 mo treatment • Elevated plasma NfL • MRI evidence of Iron • Motor symptoms ≤4 years • No severe impairment Quantitative MRI Target engagement/efficac
Slide 13: Populations and Key Endpoints
Populations and Key Endpoints 6 no post Baseline UMSARS I 77 Randomized 71 (Clinical analysis population) For personal use only 5 negative CSF α-syn SAA 10 discontinued before week 26 1 completed week 26 w/o MRI 61 (Imaging analysis population)* Protocol Endpoint Change BL to Week 52 Population Crit
Slide 14: Baseline Characteristics (mITT)
Baseline Characteristics (mITT) Placebo 50mg BID 75mg BID Parameter (n = 19) (n = 21) (n = 21) For personal use only 61.5 62.9 64.0 Age (yr) (7.0) (6.3) (6.3) Gender (% male) 63.2% 57.1% 57.1% 16.8 15.4 14.4 Modified UMSARS I1 (4.2) (4.6) (4.7) 57.9 48.6 49.1 Motor score of NNIPPS2 (15.2) (16.0) (17
Slide 15: Modified UMSARS Part I
Modified UMSARS Part I 26 For personal use only 24 Placebo (n=22) ATH434 50 mg BID (n=25) Modified UMSARS I 22 ATH434 75 mg BID (n=24) Worsening 20 18 Mean difference Relative treatment Dose vs. placebo effect* 16 P=0.02 for 50 mg 50 mg - 3.8 48% P=0.07 14 for 75 mg 75 mg - 2.4 30% 12 * ChangeATH434
Slide 16: Clinical Global Impression of Severity
Clinical Global Impression of Severity Change from Baseline to Week 52 For personal use only 1.5 Placebo Change in CGIS (W52 - BL) ATH434 50 mg BID 1.0 ATH434 75 mg BID Worsening * P=0.009 0.5 7-point Likert scale • Higher score = worse outcome • Total picture of patient over 28 days 0.0 Mean (SE) C
Slide 17: Orthostatic Hypotension Symptom Assessment
Orthostatic Hypotension Symptom Assessment Change from Baseline to Week 52 For personal use only 10 Change in OHSA (W52 - BL) Placebo Worsening ATH434 50 mg BID 5 ATH434 75 mg BID P=0.08 P=0.14 0 Patient reported outcome Assesses severity of 6 items • Dizziness/lightheadedness/feeling faint/like bla
Slide 18: Wearable Sensors: Activity in Outpatient Setting
Wearable Sensors: Activity in Outpatient Setting Change from Baseline to Week 52 Step Count Total Time Walking For personal use only 0 0 Placebo Change in Minutes/day -10 ATH434 50 mg BID Change in steps/day Worsening Worsening -1000 ATH434 75 mg BID -20 P=0.1267 P=0.1535 P=0.0437 -2000 -30 * P=0.10
Slide 19: Summary of Adverse Events
Summary of Adverse Events Placebo BID 50mg BID 75mg BID Number (%) of Subjects (n=26) (n=25) (n=26) For personal use only Any Adverse Event (AE)1 24 (92.3%) 21 (84.0%) 25 (96.2%) UTI 14 (53.8%) 10 (40.0%) 7 (26.9%) Fall 8 (30.8%) 7 (28.0%) 8 (30.8%) Covid-19 1 (3.8%) 6 (24.0%) 4 (15.4%) Fatigue 2 (7
Slide 20: Change in Iron Content by MRI (QSM)
Change in Iron Content by MRI (QSM) By-subject analysis of iron content 50 mg BID 75 mg BID For personal use only Region Week 26 Week 52 Week 26 Week 52 By-subject analysis • Evidence for reduced/stabilized iron content S. nigra in Pallidum > Putamen Putamen ^ • Reductions in iron in s. nigra a
Slide 21: 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 For personal use only 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 17 ^ Composite z-score of the putamen, globus
Slide 22: Summary and Conclusions
Summary and Conclusions • ATH434 showed clinically significant efficacy in modifying disease progression • UMSARS I plus important secondary clinical outcomes For personal use only • Baseline differences in disease severity and pathology likely explain different response in 50 mg and 75 mg treatment
Slide 23: 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 For personal use only Wassilios Meissner Sandrine Villars Groupe Hospitalier Pellegrin, B
Slide 24: Thank You
For personal use only Thank You 20
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