Arvinas Announces Presentations for Two of its PROTAC® Investigational Programs Targeting BCL6 and LRRK2

Core Insights - Arvinas, Inc. presented promising preclinical data for its investigational PROTAC BCL6 degrader ARV-393, demonstrating anti-tumor activity in B-cell lymphoma models [1][2][3] - The company also highlighted the potential of its PROTAC LRRK2 degraders for treating neurodegenerative diseases at the Biennial International LRRK2 Meeting [1][4] Group 1: ARV-393 and B-cell Lymphoma - ARV-393 effectively degraded the BCL6 protein and inhibited cell growth in various B-cell lymphoma models, including diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma [2][3] - The investigational drug showed tumor growth inhibition and regression in multiple patient-derived xenograft (PDX) models of non-Hodgkin lymphoma (NHL) [2][3] - The results suggest that ARV-393 could be a potential new treatment for patients with certain types of NHL, particularly those unresponsive to existing therapies [3] Group 2: PROTAC LRRK2 Degraders - Preclinical studies indicated that the oral PROTAC LRRK2 degraders demonstrated full target engagement and near-complete LRRK2 degradation in mouse models [4] - Compared to experimental LRRK2 kinase inhibitors, PROTAC LRRK2 degraders showed a more favorable safety profile with less Type II pneumocyte enlargement [4] - These findings suggest a wide therapeutic index and manageable safety profile for PROTAC degraders in treating neurodegenerative diseases [4] Group 3: Clinical Development - ARV-393 is currently in a phase 1 clinical trial for patients with non-Hodgkin lymphoma [4][5] - Arvinas is also investigating ARV-102, an oral PROTAC LRRK2 degrader, in a phase 1 clinical trial involving healthy volunteers [4][6]