Slide 1: bioMUSE Data Release Webinar
David Stamler, MD CEO Webinar – bioMUSE Data Release May 29/30, 2024
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation may contain some statements that may be considered “Forward - Looking Statements”, within the meaning of the US Securities Laws . Thus, any forward - looking statement relating to financial projections or other statements relating to the Company’s plans,
Slide 3: Objectives of Today's Webinar
Objectives of Today’s Webinar • Review new data from bioMUSE natural history study • Discuss relevance of bioMUSE for ATH434 - 202 study • Expert perspective on Multiple System Atrophy (MSA) • Review timing of Phase 2 data 3
Slide 4: Promising Portfolio in Neurodegenerative Diseases
PARTNER Promising Portfolio in Neurodegenerative Diseases PARTNER PHASE ASSET PARTNER / COLLABORATOR PHASE 2 PHASE 1 NATURAL HISTORY PRE - CLINICAL DISCOVERY INDICATION PROGRAM mplete Enrollment Co Multiple System Atrophy Early Stage ATH434 - 201 mplete Enrollment Co Multiple System Atrophy Advanced
Slide 5: Multiple System Atrophy (MSA): Rare, Highly Debilitating and Rapidly Progressive Neurodegenerative Disease
Multiple System Atrophy (MSA): Rare, Highly Debilitating and Rapidly Progressive Neurodegenerative Disease • Parkinsonian disorder with no approved treatment • Orphan disease • Disease characteristics • Motor: Parkinsonism, uncoordinated movements, balance problems/falls • Autonomic dysfunction: blo
Slide 6: Iron is Critical in Disease Pathogenesis
Sources: Kaindlstorfer, J. Alzheimers Dis. 2018; Bengoa - Vergniory N, Acta Neuropathol. 2017 6 Iron is Critical in Disease Pathogenesis Iron and α - Synuclein are important contributors to MSA pathology • Adverse impact of excess labile iron • Leads to α - synuclein aggregation ڮ neuronal dysfuncti
Slide 7: Accumulated Evidence of ATH434 Efficacy
7 Clinical Observations Preserve Neurons/ Function α - Synuclein Midbrain* Iron Model Target Disease Improved motor performance á â â Mouse MPTP Parkinson’s disease Improved motor performance á â â Mouse A53T Parkinson’s disease Improved motor performance á â â Mouse tau knockout Parkinson’s disease
Slide 8: Approach: Address Underlying Pathology of Disease
Approach: Address Underlying Pathology of Disease Potential Disease Modifying Therapy for MSA Redistribute excess labile iron in the CNS Reduce α - synuclein aggregation and Oxidative stress Rescue brain cells/ neuronal function 8
Slide 9: Multiple System Atrophy Clinical Development Program
Multiple System Atrophy Clinical Development Program 9
Slide 10: Clinical Studies in MSA
Clinical Studies in MSA ATH434 - 202 – Phase 2 ATH434 - 201 – Phase 2 bioMUSE – Natural History Study Single arm, open - label Randomized, double - blind Observational Design Efficacy and safety of ATH434 Efficacy and safety of ATH434 Characterize early - stage MSA Objectives Advanced MSA Early - st
Slide 11: BioMUSE Natural History Study Learnings to Date
11 Sources: Presentations/Posters on file, including Claassen et al, MDS Conference 2021 and 2022. BioMUSE Natural History Study Learnings to Date Advanced MRI methods Optimize Patient Selection Precision Endpoint Assessment 100 1000 10000 100000 1000000 Fluorescence PD MSA Time → Differentiate MSA
Slide 12: Participant Flow in bioMUSE
25 Adults 30 to 78 yo with MSA assessed for eligibility 4 Excluded • 2 Unable to complete procedures • 1 Exclusionary MRI findings • 1 Unreliable 21 Enrolled 17 Early Stage (Clinically Probable MSA) 4 Advanced (Clinically Established MSA) Followed for 12 months 10 MSA 5 Parkinson 2 Undefined Partici
Slide 13: BioMUSE Brain Imaging Biomarkers Assessed in MSA Regions
Status How Assessed Biomarker 12 mo data reported today MRI/QSM Iron content 12 mo data reported today MRI/T1w Volumes Preliminary data reported in 2023 MR spectroscopy N - acetylaspartate/ myoinositol In process MRI Neuromelanin BioMUSE Brain Imaging Biomarkers Assessed in MSA Regions 14
Slide 14: MRI Methods to Measure Brain Iron
15 • Based on routine (e.g., structure/volume) and specialized MRI techniques • Bioengineer evaluated MRI processing algorithms to optimize measurement 1,2 • Method selected which is reproducible and minimizes artifacts between MRIs 1 Marques. QSM reconstruction challenge 2.0. Magn Reson Med . 2021
Slide 15: BioMUSE: Change in Iron Content by MRI
6M 12M - 0.02 0.00 0.02 0.04 0.06 Substantia Nigra Change from BL ** 6M 12M - 0.02 - 0.01 0.00 0.01 0.02 Putamen Change from BL 6M 12M - 0.02 - 0.01 0.00 0.01 0.02 Pallidum Change from BL 6M 12M - 0.02 - 0.01 0.00 0.01 0.02 Cerebellar Dentate Nucleus Change from BL Statistically significant increase
Slide 16: Optimizing MRI Methods to Measure Brain Volumes
• Multiple System Atrophy = atrophy (shrinking) of brain structures • Routine MRI are analyzed in 2 dimensions (2D) • We are interested in measuring brain volume (in 3D) • Needed a new method to measure volumes in MSA affected areas Method Development • Neuroradiologist manually traced 2D images for
Slide 17: BioMUSE: Change in Brain Volume by MRI
18 Statistically significant decreases in brain volume observed in all regions at 12 months and in 3 of 4 regions at 6 months 6M 12M - 6 - 3 0 Cerebellum % Change from BL ** ** 6M 12M - 8 - 6 - 4 - 2 0 Brainstem % Change from BL ** ** 6M 12M - 12 - 9 - 6 - 3 0 Putamen % Change from BL ** 6M 12M - 12
Slide 18: BioMUSE: Change in Brain Volume by MRI - Brain Atrophy in MSA
6M 12M - 6 - 4 - 2 0 MSA % Change from BL ** ** New Imaging Biomarker MSA Volume Index 6M 12M - 6 - 4 - 2 0 PD % Change from BL Combine volume of these 4 regions affected in MSA BioMUSE: Change in Brain Volume by MRI Brain Atrophy in MSA 19
Slide 19: BioMUSE Summary
• Observational Study in MSA • Goals: improve patient selection and choose endpoints for Phase 2 • Iron content: Significant increase in iron observed at 12 months in one brain region (s. nigra) • Brain volume: Significant decrease in volume observed over 12 months in all four MSA regions ❖ Novel Im
Slide 20: Implications of bioMUSE Data on ATH434 Study
Implications of bioMUSE Data on ATH434 - 202 Study 21
Slide 21: Endpoint Selection in Treatment Trials
We target endpoints with the largest change over the planned study period to more readily demonstrate a drug effect Endpoint Selection in Treatment Trials Biomarker Endpoint Selection Relevant to Tracks with disease Preclinical indication underlying disease progression of drug effect 22
Slide 22: ATH434-202 Key Study Endpoints
ATH434 - 202 Key Study Endpoints Change in MSA Volume Index by MRI at 12 months • Based on the significant decrease in volume in relevant brain regions in MSA Primary Endpoint Change in Iron content in the substantia nigra by MRI at 12 months • Based on the significant increase in iron in relevant b
Slide 23: ATH434 Phase 2 Trial Key Milestones
ATH434 - 201 Phase 2 Trial Study Complete Feb 25 Jan 24 Feb 24 Mar 24 Apr 24 May 24 Jun 24 Jul 24 Aug 24 Sep 24 Oct 24 Nov 24 Dec 24 Jan 25 Key Milestones ATH434 MoA data BioMUSE Data ATH434 - 202 Preliminary 6 mo Data Scientific Meeting Presentations ATH434 - 201 Phase 2 Trial Topline Data 24
Slide 24: Daniel Claassen, M.D., M.S.
Professor of Neurology Vanderbilt University Medical Center Research focus: Neuroimaging/Therapeutics Principal Investigator of bioMUSE Coordinating Investigator of the ATH434 - 201 Clinical Trial Daniel Claassen, M.D., M.S. 25
Slide 25: Alterity Therapeutics
ofifo Alterity THERAPEUTICS ASX:ATH | NASDAQ:ATHE