Dosing begun in clinical trial of novel oral chimeric protein degrader

The first subject has been dosed in a phase 1 clinical trial of an oral proteolysis-targeting chimera protein degrader to treat neurodegenerative diseases, according to the manufacturer.

According to a release from Arvinas, ARV-102 was shown to cross the blood-brain barrier and degrade leucine-rich repeat kinase 2 (LRRK2) in preclinical studies. This property was crucial to efficacy as increased activity and expressions of LRRK2 is a sign of pathogenesis of neurological diseases — including Parkinson’s disease and progressive supranuclear palsy — at the genetic level, per the release.

The current study, which is enrolling healthy volunteers at the Centre for Human Drug Research in Leiden, the Netherlands, will evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of ARV-102, including the evaluation of LRRK2 degradation and exploratory LRRK2 pathway biomarkers.

“Parkinson’s disease and progressive supranuclear palsy are devastating diseases and this important step of dosing the first healthy volunteer with ARV-102 marks a significant milestone in our commitment to develop transformative therapies for patients living with neurodegenerative diseases,” Angela M. Cacace, PhD, senior vice president of neuroscience and platform biology at Arvinas, said in the release. “As a pioneer in targeted protein degradation, we believe that PROTAC degraders have great potential to change the treatment paradigm for patients with neurodegenerative diseases.”