Safety, Tolerability, and Pharmacokinetics of Exidavnemab in Patients with Parkinson's Disease

Inclusion Criteria:

1. Male and female participants 40 to 85 years of age.

2. Body weight more than or equal to 50 kg and less than or equal to 120 kg.

3. Have Idiopathic PD (i.e., not induced by drugs or other diseases) as defined bybradykinesia combined with at least 1 of resting tremor and rigidity, as per theMovement Disorder Society Criteria for PD (Postuma, et al. 2015).

4. Classified as Stage 1 to 2.5 on the modified Hoehn and Yahr scale for the staging ofPD severity.

5. Participants must have cognition inconsistent with dementia as confirmed by a scoreof more than or equal to 22 on the MoCA.

6. Stable and optimized symptomatic PD medication, defined as the same list ofmedications for at least 3 months prior to the Screening Visit with no change in thedose for at least 1 month prior to the Baseline Visit, and no planned changes indose-regimen during trial participation.

7. Prior (any time; i.e., no time limit) or current DaT-SPECT or DaT-PET consistentwith dopamine transporter deficit, as per the Movement Disorder Society Criteria forPD(Postuma, et al. 2015). For participants who have not undergone DaT-SPECT orDaT-PET prior to Screening, or who have previously undergone DaT-SPECT or DaT-PETscan(s) but without results consistent with dopamine transporter deficit, DaT-SPECTor DaT-PET should be performed and read locally as part of the Screening procedures.

8. Positive smell test showing hyposmia, as defined by UPSIT scores of around or belowthe 15% percentile for their relevant sex and age group. Cut-off scores are providedbelow for reference (Table 5.1; based on Brumm, et al. 2023) Ability to use a tabletdevice to measure cognitive function, as per Investigator judgment.

Exclusion Criteria:

1. Known hypersensitivity to trial medication, the infusion solution, or excipients.

2. More than 5 years of symptomatic treatment for PD.

3. History of neurosurgical intervention for PD including implantation of brainstimulation.

4. Diagnosis of PD dementia or another dementia.

5. Any psychiatric diagnosis or symptoms (e.g., hallucinations, major depression, ordelusions) that could interfere with trial procedures.

6. Freezing episodes occurring on a weekly basis or more frequently.

7. Motor fluctuations occurring on a weekly basis or more frequently.

8. Levodopa-induced troublesome dyskinesia of a severity that would significantlyinterfere with the participant's ability to participate or perform trial proceduresas determined by the Movement Disorder Society-Sponsored Revision of the UnifiedParkinson's Disease Rating Scale (MDS-UPDRS) Subscale IV.