2X-121 is a small molecule targeted inhibitor of Poly ADP ribose polymerase (PARP), a key enzyme involved in DNA damage repair in cancer cells.

This orally-bioavailable, brain penetrable 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).

2X-121 is also active in P-glycoprotein expressing cells, suggesting it may overcome PARP inhibitor resistance.

Based on prior study response data, separate Phase 2 studies are planned with this compound in metastatic breast cancer (initiated Q2 2018), relapsed ovarian cancer, and pancreatic cancer patients.  Each will enroll >30 patients, guided by the validated DRP® Dx for this drug.  Significant response rates (>30%) are anticipated.  We expect data from these planned studies in Q4 2018 and Q1 2019.

In a prior Phase 1 study conducted without a DRP®, 31.7% had stable disease and two ovarian cancer patients had a durable partial response of 281 and 208 days, respectively. 2X-121 was well tolerated, with no myelotoxicity observed.  This data was presented at ASCO 2018 by Dr. Elizabeth Ruth Plummer. (access abstract)

In-licensed from Eisai, the molecule was formerly called E7449.