Arvinas has announced positive biomarker, pharmacokinetic and pharmacodynamic data from two Phase I studies assessing ARV-102, an oral investigational PROTAC degrader of leucine-rich repeat kinase 2 (LRRK2).
The data was presented at the International Congress of Parkinson's Disease and Movement Disorders (MDS 2025) in Honolulu, US.
Arvinas chief medical officer Noah Berkowitz said: “We are particularly excited by the CSF proteomics results, which demonstrate modulation of lysosomal and microglial pathways that are known to be associated with neurodegenerative diseases.
“We believe these findings support the intensified development of ARV-102 in ongoing studies of patients with Parkinson's disease, and in future studies of patients with progressive supranuclear palsy.”
Arvinas shared findings from two trials: ARV-102-101, a first-in-human study involving healthy individuals, and ARV-102-103, which focused on subjects with Parkinson's disease.
In the healthy participants, ARV-102 was generally well tolerated, with single doses of up to 200mg and multiple daily doses of up to 80mg.
There were no discontinuations as a result of adverse events (AEs) or serious adverse events.
Furthermore, the exposure to ARV-102 in cerebrospinal fluid and plasma increased in a dose-dependent manner, suggesting effective brain penetration.
Administering repeated daily doses of 20mg or more led to reductions of more than 90% in LRRK2 protein levels in peripheral blood mononuclear cells and more than 50% in cerebrospinal fluid.
ARV-102 also decreased plasma concentrations of phospho-Rab10T73 and urine levels of bis(monoacylglycerol)phosphate, which serves as a biomarker for lysosomal pathway modulation downstream of LRRK2.
The Phase I study involving participants with Parkinson's disease comprised 15 individuals who received ARV-102 and four who were administered a placebo.
Single doses of ARV-102, either 50mg or 200mg, were well tolerated and only mild treatment-related AEs were reported, such as nausea, headache and diarrhoea.
Arvinas intends to present initial outcomes from a multiple-dose cohort of the Phase I study involving patients with Parkinson's disease (ARV-102-103) in 2026.
