APRs in CTCs
Arno Therapeutics to collaborate with J&J’s Veridex to develop diagnostic test
FLEMINGTON, N.J.—Arno Therapeutics Inc., a four-personclinical-stage biopharmaceutical company focused on the development of oncologytherapeutics, has signed an agreement with Veridex LLC, a Johnson & Johnsoncompany, to develop a diagnostic test to detect the presence of activatedprogesterone receptors (APRs) as a potential biomarker of anti-progestinactivity in circulating tumor cells (CTCs). The diagnostic will help identifypatients who could potentially benefit from treatment with anti-progestinsincluding onapristone, an orally administered, investigational type 1 progestinreceptor antagonist being developed by Arno.
CTCs are cancer cells that have detached from a solid tumorin the body and are found in the bloodstream. The collaboration will allow Arnoto utilize Veridex's proprietary technology, CELLSEARCH, which usesmicrofluidic separation integrated with magnetic sorting, to isolate CTCs andfurther analyze the cells for the presence of APR. The CELLSEARCH CTC system isthe first and only standardized, FDA-cleared, semi-automated system thatcaptures, isolates and counts CTCs with a high level of sensitivity andspecificity, says Dr. Alexander Zukiwski, vice president and chief medicalofficer at Arno.
Both Zukiwski and Arno CEO Glenn Mattes once worked atJohnson & Johnson and were familiar with Veridex and CELLSEARCH. Zukiwskinotes that the system is approved and reimbursed and is already running on acommercial basis. Arno will continue to explore other CTC technologies, headds.
"Systems under development may allow us to archive and storesamples on a long-term basis and/or address multiple biomarkers in a singlesample. The goal is to allow us to maximize the information from each and everypatient," he says.
"We are pleased to work with Veridex as we believe itspioneering technology for isolating circulating tumor cells will serve as animportant tool for the continued development and study of onapristone," Mattesadds. "By taking blood samples from patients rather than obtaining tissuesamples, we hope to create a simplified and less invasive process foridentifying patients that are most likely to benefit from treatment withonapristone."
The diagnostic test will be used in future clinical studiesof onapristone, which the company is planning to begin in the second half of2013.
In preclinical studies, the presence of APR has shown to bepredictive of onapristone activity. Onapristone is believed to work by bindingto progesterone receptor proteins, thereby inhibiting dimerization,phosphorylation and DNA transcription activity. Progesterone receptors (PRs)are found in particular cells including those of the female reproductive tissueand some cancers. The hormone progesterone binds to the receptors and may causethe cells to grow. Preclinical studies have shown that PRs can play a role asdrivers of malignant cell growth in certain cancers.
"These data add to the growing body of knowledge indicatingthe potential of the compound to fill a high unmet medical need, and we plan topursue a global orphan drug designation in endometrial cancer," says Mattes.
Arno has exclusive worldwide rights to develop and marketthree other anticancer product candidates. AR-42 is an orally available, broad-spectruminhibitor of both histone and non-histone deacetylation proteins (a "pan-DAC"),that is currently enrolling patients in a Phase I clinical study. Preclinicaldata showed that AR-42 potently and selectively inhibits leukemic stem cells inacute myeloid leukemia (AML).
AR-12 is an orally available inhibitor of the PI3K/Aktpathway that causes cell death through the induction of endoplasmic reticulumstress. A Phase I clinical trial is currently enrolling patients with solidtumors or lymphoma. Both AR-42 and AR-12 were in-licensed from the Ohio StateUniversity.
AR-67 is a novel, third-generation camptothecin analoguethat inhibits topoisomerase I activity. Arno is currently enrolling patients ina Phase II clinical study of AR-67 in patients with glioblastoma multiforme(GBM), a highly aggressive form of brain cancer. AR-67 was in-licensed from theUniversity of Kentucky and University of Pittsburgh, which were co-developers.