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Arvinas Presents First-in-Human Data for Investigational Oral PROTAC ARV-102 Demonstrating Blood-Brain Barrier Penetration, and Central and Peripheral LRRK2 Degradation
– Data demonstrate that ARV-102 was well tolerated, orally bioavailable, and brain-penetrant; ARV-102 achieved central and peripheral LRRK2 reduction
About this update from Arvinas, Inc.
[{"type":"text","content":"– Data demonstrate that ARV-102 was well tolerated, orally bioavailable, and brain-penetrant; ARV-102 achieved central and peripheral LRRK2 reduction indicating substantial LRRK2 protein degradation in healthy volunteers – – Findings support continued evaluation of ARV-102 in neurodegenerative diseases associated with LRRK2 dysfunction; a Phase 1 trial in patients with Parkinson's disease has been initiated and is currently enrolling – NEW HAVEN, Conn., April 04, 2025 (GLOBE NEWSWIRE) -- Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company working to develop a new class of drugs based on targeted protein degradation, today presented data from the first-in-human clinical trial of ARV-102, the Company’s investigational PROteolysis TArgeting Chimera (PROTAC) leucine-rich repeat kinase 2 (LRRK2) degrader. In the trial, ARV-102 demonstrated substantial reduction of LRRK2, a multifunctional protein that has been implicated in Parkinson’s disease (PD) and progressive supranuclear palsy (PSP), in cerebral spinal fluid (CSF), with a promising safety/tolerability profile and favorable pharmacodynamic outcomes. Results from the randomized, double-blind, placebo-controlled single ascending dose (SAD) cohort of the Phase 1 healthy volunteer trial, and initial results from the multiple ascending dose (MAD) cohort, were shared in a presentation at the 2025 International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD™ 2025) in Vienna, Austria. The SAD cohort evaluated ARV-102 doses ranging from 10 mg to 200 mg. The MAD cohort evaluated doses ranging from 10 mg to 80 mg. Key findings from the trial showed: ARV-102 was generally safe and well tolerated with no serious adverse events reported after single or multiple doses.ARV-102 exposure in the CSF increased in a dose-dependent manner after single and multiple doses, indicating brain penetration.At a single oral dose of at least 60 mg, and once daily repeated oral doses of at least 20 mg, ARV-102 achieved greater than 50% LRRK2 reduction in the CSF and greater than 90% LRRK2 reduction in the peripheral blood mononuclear cells (PBMCs), indicating substantial central and peripheral LRRK2 protein degradation.Inhibition of Rab10 phosphorylation in PBMCs and reduction of bis(monoacylglycerol)phosphate (BMP) in urine following single doses of ARV-102, signifying downstream L...