Slide 1: 2024 Summer Series of R&D Webinars Part V – CNS Programs
2024 Summer Series of R&D Webinars Part V – CNS Programs October 07, 2024 2024 Summer Series – CNS
Slide 2: Safe Harbor Statement
Safe Harbor Statement This presentation contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results ma
Slide 3: Welcome and Introductions
CNS Programs Webinar – October 7, 2024 Welcome and Introductions Vince Anzalone, CFA Vice President, Finance and IR
Slide 4: 2024 Summer Series of R&D Webinars
2024 Summer Series of R&D Webinars Obesity/ Central Nervous Muscle Cardiometabolic Pulmonary Metabolic System ARO-DM1 and Plozasiran and ARO-RAGE, ARO-INHBE and Platform and ARO-DUX4 Zodasiran ARO-MUC5AC, New Adipose Pipeline Updates ARO-MMP7 Target May 23, 2024 June 25, 2024 July 16, 2024 August 14
Slide 5: 2024 Summer Series Goals
2024 Summer Series Goals Provide focused time to cover underappreciated parts of our pipeline Detail advances in the TRiM platform Hear directly from the Arrowhead team that worked on the programs Get external physician perspective on each disease area 2024 Summer Series – CNS 5
Slide 6: CNS Webinar Agenda
CNS Webinar Agenda Topic Presenter Introductions and Agenda Vince Anzalone, CFA CNS Portfolio Overview and IT Platform Christy Esau Ph.D. ARO-ATXN2 James Hamilton M.D., MBA Subcutaneous Administration for CNS Tao Pei Ph.D. Targeting Tau for Neurodegenerative Disease Christy Esau Ph.D. Early CNS Pipe
Slide 7: Neurology Key Opinion Leader
Neurology Key Opinion Leader Jose Soria, M.D. Director of Clinical Research, The Neuron Clinics Assistant Clinical Professor of Neurosciences and Attending Neurologist, UC San Diego Dr. Jose Soria is a board-certified neurologist specializing in Alzheimer’s disease and cognitive impairments. He curr
Slide 8: CNS Portfolio Overview IT Platform
CNS Programs Webinar – October 7, 2024 CNS Portfolio Overview IT Platform Christy Esau, Ph.D. Vice President, Biology
Slide 9: Neurodegenerative Diseases Are an Enormous Burden Uniquely Addressable by RNA Therapeutics
Neurodegenerative Diseases Are an Enormous Burden Uniquely Addressable by RNA Therapeutics SOD1 (ALS) TDP-43 proteinopathies Over 50 million neurodegeneration patients • Amyotrophic Lateral Sclerosis (ALS) worldwide1 and few disease modifying therapies • Fronto-temporal dementia (FTD) Tauopathies •
Slide 10: First Gen CNS-Targeting TRiM Platform Intrathecal (IT) Administration
First Gen CNS-Targeting TRiM Platform Intrathecal (IT) Administration We Have Developed an Optimized Intrathecal Delivery Platform for CNS • Simple lipid-conjugate design • Potent target mRNA reduction • Broad distribution throughout the brain and to all relevant cell types in rodent and monkey • Lo
Slide 11: Potent Reduction of Target mRNA in Rodent Models
Potent Reduction of Target mRNA in Rodent Models Transgenic Rat Transgenic Mouse Single Dose IT – 4 Weeks Post Dose Single Dose ICV – 2 Weeks Post Dose 100 100 Thoracic Thoracic Spinal Cord 75 ED50=33ug Spinal Cord 75 ED50=13ug SOD1 mRNA [SOD1 ASO1 ED50=48ug*] SOD1 mRNA [SOD1 ASO1 ED50=64ug*] (% con
Slide 12: Target Knockdown Throughout the CNS and Distribution to All Relevant Cell Types in Non-Human Primate
Target Knockdown Throughout the CNS and Distribution to All Relevant Cell Types in Non-Human Primate SOD1 mRNA Reduction in NHP siRNA Delivery to Relevant Cell Types in NHP Cortex Single Intrathecal Dose of SOD1 siRNA, 45mg, Neurons, Astrocytes, Microglia Day 29, n=3 100 50 0 c d s SuHyp M am ulla n
Slide 13: Long Duration of Action in NHP Supports Up to Half-Yearly Dosing
Long Duration of Action in NHP Supports Up to Half-Yearly Dosing SOD1 Protein Reduction SOD1 Protein in CSF Single 45mg IT dose, n=3-5/group, mean±SEM Up to CSF SOD1 protein 100 70% (% pre-dose) 150 reduction Lumbar Spinal Cord after single SOD1 protein 50 (% control) 100 Thoracic Spinal Cord 45mg d
Slide 14: ARO-ATXN2 for Spinocerebellar Ataxia 2 - IT Administration
CNS Programs Webinar – October 7, 2024 ARO-ATXN2 for Spinocerebellar Ataxia 2 - IT Administration James Hamilton, M.D., MBA Chief of Discovery and Translational Medicine
Slide 15: ARO-ATXN2 for Spinocerebellar Ataxia (SCA2)
ARO-ATXN2 for Spinocerebellar Ataxia 2 (SCA2) • SCA2 is a dominantly inherited repeat expansion disorder which makes up ~15-20% of all SCA cases (~5 people in 100,000) • Caused by gain of function of mutant expanded polyQ ATXN2 protein • It is a progressive cerebellar ataxia w/ instability of stance
Slide 16: ARO-ATXN2 Potency in Cerebellum of BAC-Q22 ATXN2 Transgenic Mouse
ARO-ATXN2 Potency in Cerebellum of BAC-Q22 ATXN2 Transgenic Mouse Human ATXN2 mRNA Human ATXN2 protein ARWR vs ASO 100 ug dose % ATXN2 mRNA Remaining 1.5 1.5 150 (Relative to aCSF treated) (Relative to aCSF control) (Relative to CSF treated) hATXN2 mRNA hATXN2 protein 1.0 IC50<10ug 1.0 100 0.5 0.5 5
Slide 17: ARO-ATXN2 Shows Dose-Dependent ATXN2 Protein Reduction in Relevant NHP CNS Regions
ARO-ATXN2 Shows Dose-Dependent ATXN2 Protein Reduction in Relevant NHP CNS Regions Non-Human Primate ATXN2 RNAscope in Purkinje Cells: Day 29 Post-IT Dose, n=3-5/Group 200 5 mg 15 mg 150 Yellow: calbindin stain for Purkinje Neurons 30 mg Purple: ATXN2 mRNA ATXN2 protein 60 mg 100 (% control) ATXN2 P
Slide 18: ARO-ATXN2 Long Duration of Action in NHP Supports Up to Half-Yearly IT Dosing
ARO-ATXN2 Long Duration of Action in NHP Supports Up to Half-Yearly IT Dosing ATXN2 Protein Reduction Single 60mg IT Dose, n=3-4/Group, Mean±SEM • Reproducible PK/PD profile 150 Lumbar Spinal Cord • CTA has been Cervical Spinal Cord filed Frontal Cortex 100 Cerebellum ATXN2 protein (% control) 50 0
Slide 19: Phase 1 Study Planned for ARO-ATXN2
Phase 1 Study Planned for ARO-ATXN2 Placebo-Controlled Single Ascending Dose in SCA2 Patients Key Objectives: • Safety, PK • Proof of target engagement: ATXN2 protein in CSF • Proof of mechanism: Serum and CSF Neurofilament light (NfL) SAD 36 SCA2 patients to be enrolled C1 (10 mg): 4:2 Active:PBO E
Slide 20: ARO-ATXN2 Clinical Trial Endpoints and Sites
ARO-ATXN2 Clinical Trial Endpoints and Sites Primary Endpoint Key Exploratory Endpoints Sites Safety and • CSF ATXN2 protein levels New Zealand tolerability of (received regulatory ARO-ATXN2 in • CSF and plasma NfL levels approval) patients with SCA2 • Functional Testing Australia • Scale for Assess
Slide 21: Next Generation CNS TRiM Platform Subcutaneous Administration
CNS Programs Webinar – October 7, 2024 Next Generation CNS TRiMTM Platform Subcutaneous Administration Tao Pei, Ph.D. Senior Vice President, Discovery Chemistry
Slide 22: Next Gen. CNS-Targeting TRiM Platform via Subcutaneous Administration
Next Gen. CNS-Targeting TRiM Platform via Subcutaneous Administration We Have Developed an Optimized Systemic Delivery Platform for CNS Linker • Ligand-driven delivery via noninvasive BBB penetration and cellular uptake in brain tissue • Effective and durable reduction in expression levels of therap
Slide 23: TRiM CNS-SC Platform Leverages Noninvasive TfR1-Binding for CNS Delivery
TRiM CNS-SC Platform Leverages Noninvasive TfR1-Binding for CNS Delivery Blood • TfR1 highly H+ Recycling Tfr1 (high pH) enriched in Fe2+ Tfr1 (low pH) endothelium of Fe3+ Apo-Tf (-Fe) the blood-brain Endothelial Cell EE barrier (BBB) holo-Tf (+Fe) • Fast kinetics of Proton pump internalization LE/L
Slide 24: TRiM CNS-SC Platform's TfR1-Binding Does Not Interfere with Binding of Endogenous Ligand
TRiM CNS-SC Platform’s TfR1-Binding Does Not Interfere with Binding of Endogenous Ligand Helical Apical Tf Protease Like Transferrin (up to 4 mg/mL in serum) occludes helical and protease like domains Front Immunol. 2021; 12: 607692. 2024 Summer Series – CNS 24
Slide 25: TRiM CNS-SC Platform Demonstrated to Achieve BBB Penetration in Mouse
TRiM CNS-SC Platform Demonstrated to Achieve BBB Penetration in Mouse siRNA Visualization in Hippocampus siRNA Concentration in Half Brain WT Mouse B-hTFR1 Mouse SC, 1.5 mpk, D1 Sac 24 h post-dose 56x 100 Relative Concentration 80 60 40 20 10 8 6 siRNA signal in red 4 SC, 1.5 mpk, D1; 2 24 h post-do
Slide 26: TRiM CNS-SC Platform Achieves Improved Delivery to Deep Brain Region
TRiM CNS-SC Platform Achieves Improved Delivery to Deep Brain Region siRNA Concentrations in siRNA Concentrations in NHP Brain Regions by IT NHP Brain Regions by SC IT, 15 mg, D1 SC, 3 x 3 mpk, qw: Sac D29 D1, D8, D15 Sac D29 5 25 Relative Concentration 21.6 Relative Concentration 20 4 3.6 < 2x 3.3
Slide 27: TRiM CNS Delivery Platforms Show Different Knockdown Profiles in Deep Brain Regions in NHP
TRiM CNS Delivery Platforms Show Different Knockdown Profiles in Deep Brain Regions in NHP MAPT mRNA Reduction in MAPT mRNA Reduction in NHP Brain Regions by IT NHP Brain Regions by SC SC, 3 x 3 mpk, qw: IT, 15 mg, D1 D1, 8, 15 Sac D85 Sac D99 1.75 Ligand-siRNA 1.75 Ligand-siRNA PBS aCSF Conjugate C
Slide 28: TRiM CNS-SC Platform Maintains Knockdown Duration Throughout CNS Regions in NHP
TRiM CNS-SC Platform Maintains Knockdown Duration Throughout CNS Regions in NHP KD Duration of MAPT mRNA in NHP • Duration supports monthly to quarterly SC, 3 x 3 mpk, qw dosing regimen 1.5 • Formulation supports Relative Expression Thoracic Spinal Cord SC administration in human to Control 1.0 Temp
Slide 29: ARO-MAPT SC for Alzheimer's Disease/Tauopathies
CNS Programs Webinar – October 7, 2024 ARO-MAPT SC for Alzheimer’s Disease/Tauopathies Christy Esau, Ph.D. Vice President, Biology
Slide 30: Toxic Tau Protein Aggregation: Key Driver in Tauopathies Including Alzheimer's Disease
Toxic Tau Protein Aggregation: Key Driver in Tauopathies Including Alzheimer’s Disease Tau Protein: • Encoded by the MAPT gene • Abundant in neurons, where it promotes stabilization of microtubules in axons • Intrinsically disordered and subject to many post-translational modifications • Hyperphosph
Slide 31: ARO-MAPT SC for Alzheimer's Disease
ARO-MAPT SC for Alzheimer’s Disease Amyloid Plaque Precedes Tau Pathology • In Alzheimer’s disease, Tau neurofibrillary in Alzheimer’s Disease tangle pathology but not amyloid predicts cognitive decline • Anti-amyloid therapies have shown minimal Tau reduction, are less effective in patients with hi
Slide 32: ARO-MAPT SC Targets All Tauopathies
ARO-MAPT SC Targets All Tauopathies • Intracellular tau neurofibrillary tangles in the CNS cause a range of tauopathies in addition to Alzheimer’s • Each tauopathy affects different brain regions and functions and are associated with different Tau isoforms – making it difficult to drug with other th
Slide 33: ARO-MAPT SC Achieves Deep Knockdown of MAPT mRNA Throughout the CNS with Subcutaneous Administration
ARO-MAPT SC Achieves Deep Knockdown of MAPT mRNA Throughout the CNS with Subcutaneous Administration MAPT mRNA in NHP RNAscope for MAPT mRNA in Hippocampus 1.5 aCSF Control 1.0 MAPT mRNA (Relative to Control) 0.5 0.0 3 x 3mg/kg oc Po a Sp al c T am s ed e al or er us ta ex au n Sp ina ord ala us ot
Slide 34: MAPT mRNA Reduction Translate into Long-Lasting Tau Protein Reduction After ARO-MAPT SC Treatment in NHP
MAPT mRNA Reduction Translate into Long-Lasting Tau Protein Reduction After ARO-MAPT SC Treatment in NHP MAPT/Tau Reduction in NHP MAPT mRNA/Tau protein 1.00 Relative to Control Hippocampus mRNA Frontal Cortex mRNA 0.75 Hippocampus protein 0.50 Frontal Cortex protein 0.25 0.00 1 8 15 29 43 99 Study
Slide 35: PK/PD Modeling Projects Sustained Tau Inhibition with Quarterly Dosing of ARO-MAPT SC
PK/PD Modeling Projects Sustained Tau Inhibition with Quarterly Dosing of ARO-MAPT SC ARO-MAPT-SC 3x3 mg/kg Q1W SC NHP Tissue Conc.Conc. vs Tau mRNA Level NHP Tissue vs Tau mRNA Level with ARO-MAPT-SC 3x3 Q3MQ1W mg/kg SCSC with Q3M SC 150 Tau mRNA (% of Control) Tau mRNA (% of Control) 100 Mean CNS
Slide 36: ARO-MAPT SC Program Status
ARO-MAPT SC Program Status • siRNA targeting of MAPT has potential to treat most common (Alzheimer’s) and rare forms of neurodegeneration caused by tauopathy • Systemically delivered ARO-MAPT showed potent and long-lasting MAPT suppression in NHP, with potential for monthly or less frequent dosing •
Slide 37: CNS Early Pipeline Programs
CNS Programs Webinar – October 7, 2024 CNS Early Pipeline Programs
Slide 38: Huntington's Disease
Huntington’s Disease • Huntington’s disease is the most common monogenic neurological disorder in the world with a prevalence of 8–13 per 100,000 in the US and Europe • Symptoms include motor dysfunction, cognitive impairment, and neuropsychiatric problems. There are no disease modifying treatments
Slide 39: ARO-HTT SC for Huntington's Disease
ARO-HTT SC for Huntington’s Disease Effective Delivery to Disease-Relevant Deep Brain Regions with CNS-SC TRiM • Huntington’s disease is caused by expansion of the CAG repeat (>36) in exon 1 of the HTT gene • The expanded polyglutamine (polyQ) in the HTT protein leads to protein aggregation and neur
Slide 40: Potency of ARWR HTT Lead Compound Superior to Competing RNA Approaches
Potency of ARWR HTT Lead Compound Superior to Competing RNA Approaches Intrathecal Delivery Systemic Delivery YAC128 HD Mice of Lead HTT siRNA 1.5 Model: YAC128 HD Mice Model: hTfr Transgenic Mice Tfr Ligand: Mouse Tfr Ligand: Human Normalized mutHTT (1C2) 1.5 1.5 mutant hHTT protein 1.0 mouse HTT p
Slide 41: HTT Protein Reduction Throughout the NHP CNS After Treatment with ARO-HTT SC
HTT Protein Reduction Throughout the NHP CNS After Treatment with ARO-HTT SC >75% KD in Disease Relevant Brain Regions HTT Protein in NHP ARO-HTT SC: 1.5 • Effectively targets deep brain regions HTT protein (relative to control) important for 1.0 Huntington’s disease Temporal Cortex pathogenesis Fro
Slide 42: Toxic Aggregation of α-synuclein Causes Parkinson's Disease and a Range of Synucleinopathies
Toxic Aggregation of -synuclein Causes Parkinson’s Disease and a Range of Synucleinopathies • -synuclein is encoded by the SNCA gene • Mutations or gene duplication of SNCA cause an autosomal dominant form of Parkinson's disease • Abundant in neurons, -synuclein is normally involved in synaptic v
Slide 43: ARO-SNCA SC for Synucleinopathies
ARO-SNCA SC for Synucleinopathies • As synucleinopathies are caused by a toxic gain of function, inhibition of -synuclein protein production by siRNA has potential to be disease- modifying • Targeting -syn with other modalities has been unsuccessful to date, due to intracellular siRNA localization
Slide 44: Deep Reduction of SNCA mRNA with Systemically Delivered siRNA in Mouse
Deep Reduction of SNCA mRNA with Systemically Delivered siRNA in Mouse SNCA mRNA in Mice • Lead candidate selection 1.5 expected end Cortex of 2024 Relative expression Brainstem SNCA mRNA 1.0 0.5 0.0 0 25 50 75 100 125 Days Post Dose 4 x 2.5mg/kg qd subcutaneous doses n=4/group, mean±SEM Surrogate m
Slide 45: CNS-SC TRiM Platform Expands Opportunity for siRNA Therapeutics
CNS-SC TRiM Platform Expands Opportunity for siRNA Therapeutics Systemically delivered CNS-SC TRiM platform can achieve deep knockdown of multiple targets in non-human primates at clinically relevant dose levels Expands CNS-targeting feasibility to include larger patient populations (e.g., Alzheimer
Slide 46: Clinical Evaluation and Unmet Needs in Alzheimer's
CNS Programs Webinar – October 7, 2024 Clinical Evaluation and Unmet Needs in Alzheimer’s Jose Soria, M.D. Director of Clinical Research, The Neuron Clinics Assistant Clinical Professor of Neurosciences and Attending Neurologist, UC San Diego
Slide 47: Clinical Evaluation and Unmet Needs in Alzheimer's Disease Treatment
Clinical Evaluation and Unmet Needs in Alzheimer’s Disease Treatment Jose Soria MD • Director of Clinical Research at The Neuron Clinic • Assistant Clinical Faculty at UC San Diego Neuroscience 10.07.2024
Slide 48: Disclosures
Membership on Biogen, Eisai, Lilly, Merck and Genentech Advisory Disclosures Boards. Arrowhead, Biogen, Eisai, and Lilly Speaker. Clinical Trial Research Support from Biogen, AriBio, Karuna/Bristol Myers Squibb, and Alzheimer’s Association. 2024 Summer Series – CNS
Slide 49: Objectives
Objectives • Review definitions of Review Alzheimer’s Disease • Discuss clinical aspects of Discuss care and treatment • The impact of Tau Explain pathology • Unmet needs, challenges, Summarize and opportunities
Slide 50: What is dementia?
What is dementia? • Dementia refers to decline in cognitive abilities • Probable AD Dementia leading to impaired daily function compared to a • Meets criteria for dementia previously established baseline. • Insidious onset • There are many different causes of dementia • “Clear-cut” history of worsen
Slide 51: The Most Common Form of Dementia
The Most Common Form of Dementia Vascular Alzheimer’s Disease Chronic Traumatic Encephalopathy Lewy Body Hippocampal Sclerosis Frontotemporal Dementia Alzheimer’s Association. Alzheimers Dement. 2020;16(3):391-485. 2. Zarow C et al. Brain Behav. 2012; 2(4):435-442. 2024 Summer Series – CNS
Slide 52: Underlying Neuropathologic Changes: Phases Of Beta Amyloidosis And Neurofibrillary Tangles
Underlying Neuropathologic Changes: Phases Of Beta Amyloidosis And Neurofibrillary Tangles Neuropathologic criteria and assessment for AD were updated in 2012 to be more specific and inclusive of comorbid neuropathologies that may also contribute to clinical dementia. It established protocols for th
Slide 53: The Alzheimer's Disease Continuum
The Alzheimer’s Disease Continuum •Cognitively Preclinical Unimpaired Mild •Independent in Activities Cognitive of Daily Impairment Living Mild •Functional Impact on Dementia Daily Life Moderate • Extensive and Severe functional impact Dementia Jack CR et al. Alzheimers Dement. 2018;14(4):535-562. A
Slide 54: Revised Criteria
• Definition of Alzheimer’s Disease as a “biological process” • Disease progresses through a preclinical period Revised Criteria • Inclusion of blood-based biomarkers • Treatment Related Amyloid Clearance (TRAC) • Biological Staging of Disease (The impact of Tau pathology) Jack CR, Andrews JS, Beach
Slide 55: Biological and Clinical Staging
Biological and Clinical Staging Jack CR, Andrews JS, Beach TG, et al. Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup. Alzheimer's Dement. 2024; 20: 5143–5169. https://doi.org/10.1002/alz.13859 2024 Summer Series – CNS
Slide 56: Aging Population Continues To Grow And Burden Of Disease Is Substantial
Aging Population Continues To Grow And Burden Of Disease Is Substantial 2024 Alzheimer’s Disease Facts and Figures 2024 Summer Series – CNS
Slide 57: Clinical Practice: Evaluation of Cognitive Decline
The clinical diagnosis of AD dementia (Alzheimer’s clinical syndrome) or amnestic MCI (mostly likely due to AD) does not require measuring biomarkers (not yet) Clinical Practice: The presence of functional impairment, amnestic clinical profile, deficit in another cognitive domain, and absence Evalua
Slide 58: Diagnostic Guidelines Using Biomarkers: Framework for AD Based on Biomarkers
Diagnostic Guidelines Using Biomarkers: Framework for AD Based on Biomarkers (Clinical Practice) Diagnosis of dementia by core clinical criteria Biomarkers used to classify patients as having AD and / or likelihood of Mild Cognitive Impairment being due to AD Diagnosis is dependent on both clinical
Slide 59: Challenges and Opportunities Bringing New Therapies to Clinical Practice
Challenges and Opportunities Bringing New Therapies to Clinical Practice
Slide 60: 2024 Summer Series – CNS
Alzheimer's disease: The right drug, the right time, Volume: 362, Issue: 6420, Pages: 1250-1251, DOI: (10.1126/science.aau0437) 2024 Summer Series – CNS
Slide 61: Impact of Tau Pathology on the Efficacy of Anti-Amyloid Monoclonal Antibodies
Impact of Tau Pathology on the Efficacy of Anti-Amyloid Monoclonal Antibodies CLARITDY AD STUDY TRAILBLAZER-ALZ 2 • Over 50% of participants with no • Donanemab slowed clinical or low tau had no decline in progression at 76 weeks in measures of cognition and participants with low/medium tau function
Slide 62: How Are Tau-Targeted Therapies Expected to Differ from Current Treatment Approaches?
How Are Tau-Targeted Therapies Expected to Differ from Current Treatment Approaches? • There is limited efficacy of amyloid beta targeting therapies • Tau is more likely to be efficacious once cognitive decline begins • Targeting Tau pathology is anticipated to shorten the time needed to reach prima
Slide 63: How Might Tau-Targeted Therapies Be Utilized in Clinical Practice?
How Might Tau-Targeted Therapies Be Utilized in Clinical Practice? • Expand treatment to include patients with moderate stage of disease (large patient population) • Leverage biological stage of disease to identify window for therapy (Tau PET Imaging) • Allow treatment of patients with comorbid vasc
Slide 64: Current Clinical Practice
Current Clinical Practice The Alzheimer’s disease definitions have evolved to include biomarkers and identify patients early in the disease process Early clinical detection begins with MCI due to AD (Tau correlates with decline) Treatment options are needed for patients with mild to moderate dementi
Slide 65: Key Takeaways and Timelines
CNS Programs Webinar – October 7, 2024 Key Takeaways and Timelines Vince Anzalone, CFA Vice President, Finance and IR
Slide 66: Key Takeaways
Key Takeaways • Two Routes of Administration • Intrathecal – Broad distribution to cord and brain • Subcutaneous – Better distribution to deep brain regions • Growing Pipeline and Compelling Data • Addressing Previously Difficult to Drug Targets • Arrowhead Has First Mover Advantage • siRNA is Promi
Slide 67: CNS Pipeline and Timelines
CNS Pipeline and Timelines Route Program Next Milestone ARO-ATXN2 First Patient Dosed 1st Quarter Intrathecal Spinocerebellar Ataxia 2 2025 ARO-MAPT CTA 2nd Half 2025 Alzheimer’s Disease and tauopathies Subcutaneous ARO-HTT CTA 2nd Half 2025 Huntington’s Disease ARO-SNCA Candidate Selection YE 2024
Slide 68: Questions? Answers.
Questions? Answers. 2024 Summer Series – CNS 68