Oncology Venture - 2x-121
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.
Therapeutic Target Annual Diagnoses (est.)
Breast cancer 2.1 million (worldwide)
Ovarian cancer 295,000 (worldwide)3
Brain metastases from breast cancer
Glioblastoma multiforme

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.

Clinical Trials

A Phase 2, open-label clinical trial is ongoing, to investigate the anti-tumor effect and tolerability of 2X-121 in 30 heavily pre-treated metastatic breast cancer patients regardless of hormone receptor, HER2, or BRCA1 or 2 status, who have relapsed on two or more different prior therapies and who are identified by the 2X-121 DRP as highly likely to respond to treatment with 2X-121.  The first patient was dosed in June 2018.

In this clinical trial, patients receive oral treatment with 600 mg of 2X-121, as a single agent, in a 21-day cycle. The primary endpoint of this study is clinical benefit rate, defined as complete response, partial response, or stable disease at greater than 24 weeks post-treatment using the RECIST criteria1. Secondary endpoints include progression free survival, duration of response (from first response to progression), and overall survival.

Planning is underway for a Phase 2 clinical study in recurrent glioblastoma multiforme (GBM). Separate, targeted Phase 2 studies of 2X-121 are planned using the validated DRP biomarker in recurrent ovarian cancer, castration resistant prostate cancer, and pancreatic cancer to identify patients likely to respond to and benefit from treatment with the drug.

Additionally, OV-U.S. is collaborating with the NCI Pediatric Preclinical Testing Consortium (PPTC), funded by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), to evaluate 2X-121 in pediatric cancers, including rare cancer types seen by the NCI, assuming 2X-121 demonstrates activity in the PPTC models. Positive response prediction signals have been identified, and preclinical studies are underway to evaluate 2X-121 against in vivo panels of certain pediatric tumors including neuroblastoma, sarcoma and renal tumors using different mouse models like SCID or other immunodeficient mice strains.

2X-121 was previously evaluated in an open label, multi-center Phase 1/2 dose-ranging study in 41 patients with advanced solid tumors. Two patients had partial response and 13 patients had stable disease, with eight of these >24 weeks.  No significant hematological toxicity and no Grade 4 or 5 adverse events were seen. The study abstract was presented at the 2018 the American Society for Clinical Oncology Clinical Meeting.

The ongoing and planned studies using the 2X-121 DRP are expected to significantly improve response rates seen in this first-in-human study.

  1. RECIST: Response evaluation criteria in solid tumors. Learn more from the  NIH/National Cancer Institute website.

A molecular model of 2X-121

2X-121 DRP

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).


Oncology Venture entered into an exclusive global license agreement with Eisai Inc. for 2X-121 (formerly E7449) in July 2017.


Other drugs with a comparable method of action: