FLEMINGTON, N.J.—Arno Therapeutics Inc. and the University of Minnesota have kicked off their first agreement in pursuit of a new cancer diagnostic. The two organizations have signed an exclusive, worldwide license agreement for technology related to a gene expression signature derived from breast cancer tissue samples, a technique that could identify progesterone-stimulated pathway activation, which could aid in the identification of patients most likely to benefit from treatment with onapristone, Arno’s lead compound.
Per the terms of the agreement, which was negotiated through the University’s Office for Technology Commercialization, Arno will further develop this PR gene signature as a potential companion diagnostic for antiprogestins, including onapristone. The agreement also enables the potential for including said companion diagnostic in ongoing and future clinical studies of onapristone. No financial details were disclosed.
Gene expression studies primarily seek to identify one or more gene signatures in breast and other tumor types, specifically genes whose transcriptional levels are associated with a specific biological phenotype. It is hoped that this gene signature, which denotes the presence of aberrant progesterone receptor activity, can be used to pinpoint patients with cancers that are most likely to benefit from antiprogestin therapy.
“As progesterone receptors are implicated in cancer progression, we are excited by the possible outcomes resulting from investigation of the PR gene signature in breast cancer tissue samples, as illustrated by the expression pattern. The study of this gene signature may enable better, more targeted selection of patient candidates who will benefit most from antiprogestin therapeutics such as onapristone,” Dr. Carol Lange, professor of Medicine at the University of Minnesota, commented in a statement. “We believe that the advent of personalized medicine in oncology represents a meaningful advancement in the area of cancer therapeutics. Onapristone is specifically aimed at targeting the aberrant actions of progesterone receptors. The potential development of a companion diagnostic for Arno’s lead compound from this technology represents a significant step forward in our ability to truly realize the potential of personalized medicine.”
Onapristone is an oral, antiprogestin hormone blocker being developed for the treatment of men’s and women’s cancers. In preclinical testing, the compound proved capable of blocking activation of the progesterone receptor, which is believed to be a mechanism that inhibits the growth of APR-driven breast, endometrial and other tumors. In Phase 2 clinical trials, onapristone demonstrated antitumor activity in patients with breast cancer. Tests for the activated form of the progesterone receptor (APR) could potentially serve as a biomarker of anti-progestin activity.
The development of onapristone is proceeding on schedule, says David Jackson, vice president of diagnostics at Arno, who adds that the company has reached several milestones so far in 2014, including the active enrollment of patients in two Phase 1 trials: one in women with progesterone receptor-expressing tumors, and one in men with advanced castration-resistant prostate cancer who have failed treatment with abiraterone or enzalutamide.
Jackson notes that “In personalized medicine, we see more and more often that companion diagnostics are being developed in parallel to the development of personalized therapies.” It’s a trend he expects to persist “as we continue to identify biomarkers for select cancers.” Gene expression technology, he says, “is another way of approaching the challenge of identifying a specific biomarker. At Arno, we are working to identify the best way to identify patients who exhibit a biomarker.”
“Ultimately, it is our goal to be able to help physicians make more informed treatment decisions by identifying those patients who express the progesterone-stimulated gene expression and would be more likely to benefit from this targeted therapy,” he adds.