Targeted protein degraders: a call for collective action to advance safety assessment

This short piece published in Nature Reviews Drug Discovery is a call for collective action to advance the safety assessment of Targeted Protein Degraders (TPDs). The publication was born out of the HESI PROTACs and Molecular Glues Safety Workshop held October 14-15, 2021.

Targeted protein degraders (TPDs) are emerging classes of therapeutics that have the potential to address difficult drug targets in new ways. In 2021, experts convened to discuss challenges in TPD safety evaluation, and supported supplementing individual efforts to address these challenges with collective development of novel decision frameworks, tools and a shared evidence base.

Recommendations:
• Develop novel decision frameworks that integrate in silico, in vitro and in vivo data to inform the clinical risk profile.
• Advance accepted methods to characterize the unique pharmacokinetics of heterobifunctional protein degrader therapeutics.
• Build a shared evidence base for translational safety species selection

Link to full article: Targeted protein degraders: a call for collective action to advance safety assessment. Jones LH, Mitchell CA, Loberg L, Pavkovic M, Rao M, Roberts R, Stamp K, Volak L, Wittwer MB, Pettit S. Nature Review Drug Discovery (March 23, 2022)

For more information on HESI's Targeted Protein Degrader Safety Committee visit the committee webpage HERE.