First Subject Dosed in Phase I Clinical Trial of Investigational Protein Degrader for Neurodegenerative Disease

Image Credit: © putilov_denis - stock.adobe.com

Arvinas has announced that the first subject was dosed in its Phase I clinical trial of ARV-102, according to a company press release.¹ ARV-102 is the company’s first oral PROTAC (PROteolysis-TArgeting Chimera) protein degrader in development to treat neurodegenerative diseases.

In preclinical studies, ARV-102 has been shown to cross the blood-brain barrier and degrade leucine-rich repeat kinase 2 (LRRK2), which is a large multidomain scaffolding kinase. Increased activity and expressions of LRRK2 is genetically involved in the pathogenesis of neurological diseases including Parkinson’s disease and progressive supranuclear palsy.

According to the press release, orally administered ARV-102 has been shown to reach deep-brain regions and degrade LRRK2 by nearly 90% in non-human primates.

“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,” said Angela M. Cacace, PhD, senior vice president, neuroscience and platform biology, Arvinas in the press release. “There is a high unmet need in many neurologic diseases, and unlike other therapeutic modalities designed to inhibit LRRK2 activity, ARV-102 is an investigational oral PROTAC degrader uniquely designed to cross the blood-brain barrier and degrade the LRRK2 protein. 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.”

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

Reference

1. Arvinas Announces First-in-Human Dosing of ARV-102, an Investigational PROTAC® Protein Degrader for Neurodegenerative Disease. News release. February 20, 2024. Accessed February 21, 2024. https://www.globenewswire.com/news-release/2024/02/20/2831684/0/en/Arvinas-Announces-First-in-Human-Dosing-of-ARV-102-an-Investigational-PROTAC-Protein-Degrader-for-Neurodegenerative-Disease.html