Pipeline

PARG is a glycohydrolase that removes poly-ADP-ribose (PAR) from proteins to release free ADP-ribose or PAR chains. PARG plays a pivotal role in the regulation of DNA repair mechanisms and cooperates with PARP to carry out the single-strand break (SSB) repair cycle. Pharmacological inhibition of PARG results in hyperPARylation, which leads to cell death in the context of cancer cells undergoing replication stress. We have discovered novel and potent small molecule inhibitors of PARG that demonstrate significant tumor growth inhibition in multiple solid tumor models, including enhanced efficacy in biomarker-defined settings. We initiated a phase 1 trial for our PARG inhibitor ETX-19477 in 2024. For more information, visit www.clinicaltrials.gov (NCT06395519)