PROTAC degrader for neurodegeneration enters trials

Protein degrader

Arvinas has commenced dosing in the Phase I clinical trial of ARV-102, its 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.

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

The Phase I clinical trial of ARV-102 will evaluate the 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,” said Angela Cacace, Senior Vice President, Neuroscience and Platform Biology.

“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.”

Earlier this month, Arvinas and Pfizer’s PROTAC degrader vepdegestrant (ARV-471) received Fast Track Designation from the US Food and Drug Administration (FDA) for the treatment of patients with ER+/HER2- metastatic breast cancer.

Diana Spencer, Senior Digital Content Editor, DDW

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