Arvinas, Inc. announced it presented new preclinical data from its investigational BCL6 PROTAC degrader ARV-393 at the European Hematology Association (EHA) 2024 Annual Congress that took place June 13-16, 2024 in Madrid, Spain, and presented new preclinical data from its PROTAC LRRK2 degrader program at the Biennial International LRRK2 Meeting that took place June 18-21, 2024 in Crete, Greece. Data presented at EHA showed anti-tumor activity for the company?s investigational PROTAC BCL6 degrader, ARV-393, in preclinical models of B-cell lymphoma. In these preclinical models, ARV-393 potently and rapidly degraded the BCL6 protein and inhibited cell growth in diffuse large B-cell lymphoma (DLBCL) and Burkitt cell lines.

ARV-393 showed tumor growth inhibition, including tumor regression, in various DLBCL cell line-derived xenograft (CDX) models and in multiple patient-derived xenograft (PDX) models of non-Hodgkin lymphoma (NHL), including germinal center B-cell-like (GCB), activated B-cell (ABC), GCB/ABC, BCL not otherwise specified (BCL/NOS) subtypes of DLBCL, and Burkitt lymphoma. Preclinical data presented at the Biennial LRRK2 Meeting highlighted the potential of the company?s oral PROTAC LRRK2 degraders to treat neurodegenerative diseases. Preclinical studies in mice demonstrated full target engagement of LRRK2 kinase inhibitor and near-complete LRRK2 degradation with PROTAC LRRK2 degraders, but substantially less Type II pneumocyte enlargement compared to an experimental LRRK2 kinase inhibitor.

In addition, the more noticeable Type II pneumocyte enlargement phenotype observed with the experimental LRRK2 kinase inhibitor was substantiated by the accumulation of surfactant protein C in lung, which was not observed after treatment with a PROTAC LRRK2 degrader. Arvinas? oral PROTAC BCL6 degrader ARV-393 is currently in a phase 1 clinical trial in patients with NHL, and Arvinas also has an oral PROTAC LRRK2 degrader, ARV-102, currently being investigated in a phase 1 clinical trial in healthy volunteers.