Company: ARVN
Filing Date: 2025-11-05
Form Type: 10-Q
Source: 0001628280-25-049527
Chunk: 190

Company: ARVINAS, INC.
Filing Date: 2025-11-05
Form: 10-Q
Item: Part I, Item 8
Chunk 190
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, LRRK2 reduction of greater than 90% in peripheral blood mononuclear cells was observed.

•ARV-102 at single doses of greater than or equal to 30 mg induced greater than 50% decreases in peripheral phospho-Rab10T73, a LRRK2 substrate and biomarker for downstream LRRK2 activity; data for this endpoint in the MAD cohort is pending.

•ARV-102 at single doses of greater than or equal to 30 mg resulted in greater than 90% decrease of bis(monoacylglycerol)phosphate in urine, a biomarker of lysosomal function; data for this endpoint in the MAD cohort is pending.

•In CSF, ARV-102 induced dose-dependent LRRK2 reduction, with greater than 50% LRRK2 reduction at single doses of greater than or equal to 60 mg and repeated doses of greater than or equal to 20 mg.

In the fourth quarter of 2025, we presented late breaking positive Phase 1 data from our first-in-human clinical trial of ARV-102 in healthy volunteers, and from the SAD cohort of our Phase 1 clinical trial of ARV-102 in patients with PD at the 2025 International Congress of Parkinson’s Disease and Movement Disorders®, or MDS. Data presented at MDS included the following:

Data from the Phase 1 SAD and MAD Clinical Trial in Healthy Volunteers

•Safety: ARV-102 was generally well tolerated at single doses up to 200 mg and multiple daily doses up to 80 mg, with no discontinuations due to adverse events, or AEs, or serious adverse events, or SAEs, observed in the study population.

•Pharmacokinetics: ARV-102 exposure increased in a dose-dependent manner in plasma and CSF, the latter indicating brain penetration.

•Pharmacodynamics: Repeated daily doses of greater than or equal to 20 mg resulted in greater than 90% reductions of LRRK2 protein in peripheral blood mononuclear cells, or PBMCs, and greater than 50% reductions in CSF.

•Pathway Biomarkers: Repeated daily doses of ARV-102 resulted in reduced plasma concentrations of phospho-Rab10T73 and urine concentrations of bis(monoacylglycerol)phosphate, a sensitive biomarker for modulation of the lysosomal pathway downstream of LRRK2.

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