Inhibition of cAbl tyrosine kinase reduces α-synuclein aggregation, protects dopaminergic neurons, and improves motor function in animal models of Parkinson's Disease (PD). PROSEEK was a Phase 2, randomized, double-blind, placebo-controlled study of the effects on disease progression of Vodobatinib, a brain-penetrant c-Abl inhibitor, in 513 participants with early PD not on symptomatic treatment other than a stable dose of a MAO-B inhibitor. Recently diagnosed subjects with confirmatory Dopamine Transporter Single Photon Emission Computed Tomography (DaT-SPECT) scans were randomized to daily Vodobatinib 384 mg, 192 mg, or placebo. The primary endpoint in Part 1 was the change from baseline to Week 40 in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III total score; Part 2 was an optional 36-week extension. There was a high, dose-related rate of early withdrawal. The mean score of completers in the placebo group was slightly lower than at baseline of the entire cohort. Comparisons with either dose group favored the placebo. Serum neurofilament light chains increased significantly in both Vodobatinib groups, supporting inefficacy in PD.