2X-121 is an investigational, orally-available small molecule targeted inhibitor of Poly ADP ribose polymerase (PARP), a key enzyme involved in DNA damage repair in cancer cells.
How it Works
The drug candidate has a novel dual-inhibitory action against both PARP 1/2 and Tankyrase 1/2 (important regulators of canonical Wnt/β-catenin, a critical checkpoint in metastases, particularly in triple-negative breast cancer).
The molecule is also active in P-glycoprotein expressing cells, suggesting it may overcome PARP inhibitor resistance.
Based on its ability to pass through the blood-brain barrier, 2X-121 has potential to treat brain metastases and primary brain tumors.
A molecular model of 2X-121
The mRNA-driven multiple biomarker DRP for this product candidate was validated in 2017 in a 13-patient blinded study. The DRP correctly predicted response to treatment with 2X-121 and overall survival with a p-value of 0.07 and a hazard ratio on overall survival of 0.26 in this study. Notably, this study also established the ability of the 2X-121 DRP to predict responders irrespective of BRCA mutation status (Plummer ER et al 2018; Access abstract).
Plummer ER et al. First-in-human phase 1 study of the PARP/tankyrase inhibitor 2X-121 (E7449) as monotherapy in patients with advanced solid tumors and validation of a novel drug response predictor (DRP) mRNA biomarker. J Clin Oncol 36, 2018 (suppl; abstr 2505).