Arvinas Reports Phase 1 Data Showing ARV-102 Achieves Over 50% LRRK2 Degradation in Parkinson's
Arvinas announced phase 1 results for ARV-102, a PROTAC degrader that achieved more than 50% LRRK2 degradation in cerebrospinal fluid of Parkinson's patients after 28 days, with no serious adverse events reported.
Arvinas announced phase 1 data for its investigational PROTAC degrader ARV-102, showing that the treatment achieved more than 50% degradation of LRRK2 in the cerebrospinal fluid of people with Parkinson's disease after 28 days. The findings were presented at the AD/PD 2026 conference in Copenhagen on March 18, 2026.
The trial demonstrated that ARV-102 reduced endolysosomal and neuroinflammatory biomarkers associated with Parkinson's and progressive supranuclear palsy, while also being well tolerated across all dose levels. The multiple dose cohort assessed daily oral doses ranging from 20 mg to 80 mg.
According to Arvinas, ARV-102 exposure in cerebrospinal fluid increased in a dose-dependent manner, confirming brain penetration. The compound achieved the targeted level of LRRK2 reduction by day 14 at all doses, with effects maintained through day 28. No serious adverse events were reported, and all treatment-emergent events were mild.
The Chief Medical Officer of Arvinas stated that this level of biomarker modulation has not previously been demonstrated by LRRK2 inhibitors, and the company believes these data serve as the first of its kind.
ARV-102 is an investigational, orally bioavailable PROTAC designed to cross the blood-brain barrier and specifically target and degrade leucine-rich repeat kinase (LRRK2), a large, multidomain scaffolding kinase with GTPase activity. Increased activity and overexpression of LRRK2 have been implicated in the pathogenesis of neurological diseases, including Parkinson's disease and progressive supranuclear palsy.
By fully degrading the LRRK2 protein (not just inhibiting its kinase activity), these molecules address both its enzymatic and scaffolding roles. LRRK2 kinase inhibitors once promised to revolutionize Parkinson's disease therapy—until preclinical lung toxicity, believed to be on-target, halted their progress. Initial clinical results show the potential avoidance of the lung fibrosis often seen with kinase inhibitors.
Arvinas plans to begin a phase 1b study in progressive supranuclear palsy in the second quarter of 2026, with the potential to move into a registrational trial later in the year. ARV-102 is currently being evaluated in a Phase 1 clinical trial in patients with Parkinson's disease.