PPMI Beyond 2018

Study Goals beyond 2018 Continue to follow original cohort focusing on long-term outcomes Cognition Falls Functional status Fully enroll and follow genetic cohorts Possibly expand prodromal cohort Pursue sub-studies when there are good opportunities Other biologicals Wearables and other new clinical assessment technologies

PPMI Amendment 13 Extend visits through 2023 Subjects will now have 5-13 years of follow-up dependent on cohort Modified schedule of activities for visits post 2019 Genetic Cohort and Prodromal (RBD & hyposmics) subjects to complete 5 years of visits on current SOA and then switch to modified SOA following month 60 visit

Modified Schedule of Activities Annual in person visits No imaging Lumbar puncture every other year New assessments: Determination of Falls NeuroQOL Boston Naming Test Trails A & B Lexical fluency

Modified Schedule of Activities Phone calls at 6 month point in between annual visits Confirmation of vital status Update contact information Clinical Diagnosis review

Phenoconversion visits If a subject is diagnosed with PD- a phenoconversion visit (PV) should be performed PV visit is similar to an annual visit in the modified SOA If it is determined a subject has phenoconverted between annual visits, subject should be brought in within 45 days of site’s awareness for a PV visit

Other Changes in Amendment 13 Healthy Control cohort-change in SOA: month 72 and 96 now in person visits Visits with Genetic Registry subjects will be discontinued with Genetic Registry subjects continuing follow up through FOUND in PPMI Sites will complete one final phone visit with Genetic Registry subjects by phone before discontinuing visits

Enrollment in Genetic cohorts Current LRRK2 affected 141 unaffected 190 GBA 73 129 Alpha-synuclein 19 6 Recruitment goal is 300 patients with a genetic mutation and 300 unaffected carriers

Publicly available data Analysis Principal Investigator Matrix Cohort(s) Visit(s) NeuroX genotyping Andrew Singleton, PhD DNA Original BL Immunochip genotyping Whole exome sequencing CSF total aSyn (Covance/BioLegend immunoassay) Peggy Taylor, PhD CSF BL, 3 mo, 6 mo, and 12 mo CSF Aβ, tau, and p-tau181 (Innogenetics INNO-BIA AlzBio3 immunoassay) Les Shaw, PhD αSyn transcripts Clemens Scherzer, MD RNA PD and HC ApoA1 and EGF Alice Chen-Plotkin, MD, MSc Plasma BL, 6 mo, and 12 mo IGF-1 Maria Teresa Pellecchia, PhD Serum mRNA transcripts Judith Potashkin, PhD SNCA genotyping Matthew Farrer, PhD Martin Rabey BL, 12 mo, 24 mo, and 36 mo

Ancillary study update Type/Description Status Florbetaben PET imaging Imaging Ongoing data collection VMAT-2 imaging Resting state MRI Gait device Motor FOUND Customizable remote follow-up of participants Ongoing enrollment; anticipated increased activity in 2018 iPSC collection Biologic Ongoing enrollment; samples available for request

Wearables: Key Goals Assess prodromal PD cohorts Assess progression Assess drug response Comparison with in-clinic assessments

Wearable Plans for 2018 and beyond Verily Watch and bed sensor Passive collection of Data US based Shared data Roche Phone App Passive and Active collection of Data EU based Shared Data

Study Goals for 2018 and beyond Summary: Study Goals for 2018 and beyond Assess long-term PD progression outcomes focusing on: Progression of identified PD subsets Dopa non-responsive milestones Assess predictability of biomarkers identified at earlier stage Continued acquisition of fluid /imaging biomarkers Follow up of new cohorts Comparison of PD and Genetic cohorts Assess progression during prodromal PD Integration of new markers