On August 9, 2017 2X Oncology, Inc. ("2X" or the "Company"), a precision medicine company developing targeted therapeutics to address significant unmet needs in women’s cancer, reported the successful validation of the Drug Response Predictor (DRP) for 2X-121, its Phase 2 PARP inhibitor recently licensed from Eisai (Press release, 2X Oncology, AUG 9, 2017, View Source [SID1234526102]).

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"It is of great interest to see the Drug Response Predictor work for 2X-121, and the clear separation between responders and non-responders. This bodes well for the future role of 2X-121 in the treatment of cancer," stated Dr. Mansoor R. Mirza, chief oncologist, Department of Oncology, Copenhagen University Hospital-Rigshospitalet.

"In this DRP validation study, the diagnostic identified responders irrespective of BRCA mutation status, indicating that our compound may have broader application including tumors resistant to other PARP inhibitors," said George O. Elston, CEO of 2X Oncology.

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. The drug candidate has a novel dual-inhibitory action against both PARP 1/2 and Tankyrase 1/2. The molecule is also active in P-glycoprotein expressing cells, suggesting it may overcome PARP inhibitor resistance.

"PARP inhibitors are the most exciting new class of agent for the treatment of many gynecologic cancers," said Ursula Matulonis, M.D., Director, Gynecologic Oncology at the Dana-Farber Cancer Institute and Professor of Medicine, Harvard Medical School. "Therapeutics such as 2X-121 that can overcome PARP inhibitor resistance, an important clinical problem today, will be a significant and welcome addition to the oncologists’ toolkit."

The drug candidate demonstrated clinical activity in a Phase 1 study in a number of cancers, including ovarian and breast. 2X-121 also has potential to treat brain metastases and primary brain tumors based on its ability to pass through the blood-brain barrier.

Separate, targeted Phase 2 studies of 2X-121 are planned using the validated DRP biomarker in metastatic breast cancer and recurrent ovarian cancer to identify patients likely to respond to and benefit from treatment with the drug.

"We look forward to the initiation of the Phase 2 clinical trials for 2X-121, leveraging the initial Phase 1 responder data and the validated DRP, later this year," Elston added.

Positive data from these studies will position the program for a pivotal Phase 2 study initiation as early as 2018.

In a blinded study of 13 patients, five of seven patients in the DRP-predicted responder group survived (Overall Survival-OS) at 400 days from commencement of treatment, compared with only one out of six patients surviving at 400 days for those predicted by the DRP score to be non-responders. This equates to a four-fold difference in overall survival between the patients predicted to respond and those not predicted to respond to treatment.

The DRP correctly predicted response to treatment and overall survival with a p-value of 0.07 and a hazard ratio on overall survival of 0.26 in this study.

About the Drug Response Predictor (DRP) Companion Diagnostic

Developed by and in-licensed from Medical Prognosis Institute A/S (MPI.ST), the DRP screening platform utilizes messenger RNA (mRNA) gene expression signatures from patient biopsies to identify patients with a high likelihood of responding to specific cancer-fighting therapies. This DRP method builds on the comparison of sensitive vs. resistant human cancer cell lines, including genomic information from cell lines, combined with clinical tumor biology and clinical correlates in a systems biology network. Specific DRPs are developed for each pipeline product, which will enable 2X Oncology to identify and predict which patients are most likely to respond and thereby benefit from a given pipeline product. This would enable likely responders to receive appropriate treatment while expediting the decision path for predicted non-responders, saving them critical time and money in their cancer fight.