Company: ARVN
Filing Date: 2025-02-11
Form Type: 10-K
Source: 0001655759-25-000016
Chunk: 114

Company: ARVINAS, INC.
Filing Date: 2025-02-11
Form: 10-K
Item: Item 1
Chunk 114
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 which often leads to patients progressing with time to death within 5 to 7 years. 

Preclinical and Clinical Development

ARV-102, our oral PROTAC LRRK2-targeting protein degrader clinical candidate, has been shown preclinically to broadly bio-distribute to deep brain regions and degrade LRRK2 more than 85% in non-human primates, or NHPs. 

In the second quarter of 2024, we presented preclinical data at the Biennial International LRRK2 Meeting, which further supported PROTAC-induced LRRK2 degradation as a potential treatment for neurodegenerative diseases. The preclinical data presented highlighted, with our PROTAC LRRK2 degrader, near complete LRRK2 target engagement, as well as LRRK2 degradation, in mouse and NHP lung and brain. The preclinical data also showed differing effects of the PROTAC LRRK2 degraders in the lungs compared to kinase inhibitors, suggesting reduced pulmonary function risk, including:

•substantially less Type II pneumocyte enlargement compared to MLi-2, an experimental LRRK2 kinase inhibitor;

•surfactant protein accumulation in mouse lung was observed after treatment with the LRRK2 kinase inhibitor MLi-2, but not after treatment with the PROTAC LRRK2 degrader; and

•no evidence of collagen deposition in lung to date with PROTAC LRRK2 degraders in NHPs.

In October 2024, we presented preclinical data at the 2024 Michael J. Fox Foundation Parkinson’s Disease Conference further supporting the potential of PROTAC-induced LRRK2 degradation as a potential treatment for patients with neurodegenerative diseases. New findings presented included data demonstrating:

•orally delivered ARV-102 crossed the blood-brain barriers and degraded LRRK2 in the cerebrospinal fluid, or CSF, of NHPs;

•degradation of LRRK2 by ARV-102 induced changes in pathway (lysosomal and inflammation) biomarkers in the CSF of NHPs, which has not previously been demonstrated by kinase inhibitors of LRRK2; and

•in murine tauopathy models, oral PROTAC LRRK2 degrader treatment led to ~50% pathologic tau reduction.

The European Medicines Agency cleared our clinical trial application for ARV-102 in the fourth quarter of 2023. We currently are conducting two