- Data Expand Support for Development of Diagnostic to Identify Patients With Biomarkers of Anti-Progestin and Anti-Estrogen Activity -

- Bolster Findings Presented at ASCO and ECC 2013 -

Poster Session 6
Saturday, December 14; 7:30 - 9:00 a.m. CT
Abstract #1282
Poster #P6-05-13

FLEMINGTON, N.J., Dec. 14, 2013 (GLOBE NEWSWIRE) -- Arno Therapeutics, Inc. (OTCQB:ARNI), a clinical stage biopharmaceutical company focused on the development of oncology therapeutics, today announced that data from a biomarker study supporting its lead compound onapristone will be presented at a poster session at the 2013 CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) annual meeting, being held December 10-14, 2013 in San Antonio, Texas. The symposium is hosted by the American Association for Cancer Research, The Cancer Therapy & Research Center at The University of Texas Health Sciences Center at San Antonio, and Baylor College of Medicine.

Findings from the study "Tumor and Cellular Distribution of Activated Forms of ERα and PR in Breast Cancers" (Abstract #1282) will be presented during Poster Session 6 on Tumor Cell and Molecular Biology: Biomarkers on Saturday, December 14 from 7:30 – 9:00 a.m. CT in Exhibit Hall C of the Henry B. Gonzalez Convention Center. Data analysis from primary breast cancers further support the development of a diagnostic test to identify patient tumors with activated progesterone receptor (APR) and activated estrogen receptor (AER) as potential biomarkers of anti-progestin and anti-estrogen activity, respectively.

Onapristone is an oral, anti-progestin hormone blocker that has been shown to have anti-tumor activity in breast cancer. Onapristone appears to have a unique ability to block the APR, which is believed to be a mechanism that may inhibit the growth of breast, endometrial and other tumors. APR has the potential to function as a biomarker of anti-progestin activity.

Poster Title: Tumor and cellular distribution of activated forms of ER and PR in breast cancers

Study Authors: Bonneterre J, Bosq J, Valent A, Gilles E, Zukiwski A.

The study evaluated 397 archived breast cancer tumor specimens and aimed to describe and quantify the histological sub-nuclear morphology of activated and inactive progesterone receptor (PR) and estrogen receptor (ER) using an immunohistochemical (IHC) diagnostic technique to identify the activated forms of steroid receptors as well as analyze the relationship between activated PR and ER, and relate them via multivariate analysis to anti-estrogen treatment outcomes.

Progesterone and estrogen receptors can be categorized into two patterns, non-activated and activated, depending upon the sub-nuclear morphological distribution of the receptors. There are two isoforms of PR, PRA and PRB, and balanced expression is observed in normal human tissues, while deregulated expression is observed in malignant tissues; some cancers may express only PRA or PRB. The tumor specimens were analyzed with isotype-specific antibodies for ERα (a subtype of ER), PRA or PRB.

The study evaluated 397 archived breast cancer specimens from consenting women with invasive ductal breast cancer from Oscar Lambret Cancer Center in Lille, France. Of these specimens, 365 were from patients with early stage disease, and the majority of the patients had received prior anti-estrogen/aromatase inhibitors.

In this series of primary breast cancer, IHC staining demonstrated that 19 percent of tumors are PR negative, 18 percent are ERα negative and 12 percent are both PR and ERα negative. The study also concluded that breast cancer tumors commonly express both ERα and PR, but co-expression in malignant cells is relatively uncommon (median 4% of cells). The same applies to the activated forms of the receptors. In addition, determination of PR by isotype-specific antibodies for PRA and PRB demonstrated a higher incidence of PR expression in this series than that described in the literature.

The study found that the activated form of the steroid receptors are present in 18 percent of tumors for AERα, 18 percent of tumors for APR and 13 percent of tumors for both AERα and APR. 

The study also found that PR positivity correlates with better outcomes, while the activated form of the PR does not appear to correlate with anti-estrogen treatment outcomes. The authors concluded that activated PR does not predict for treatment outcome with anti-estrogens and aromatase inhibitors in patients with early stage breast cancer. Activated PRA may correlate with better outcomes similarly to ERα, while activated PRB appears associated with worse outcomes, suggesting that PRB has a different role than PRA.

However, ERα positivity correlates with better outcomes while the activated form of the ERα significantly correlates with better outcomes, as confirmed by logistic regression analysis. This led the authors to conclude that activated ERα may correlate with improved outcomes from anti-estrogen and aromatase inhibitor treatment.  If this exploratory analysis is confirmed, determination of the activated form of ERα may indicate which patients with early breast cancer are most likely to benefit from long term aromatase inhibitor or anti-estrogen treatment.

The authors concluded that activated forms of ERα and the PRs are independent targets at the cellular and tumor level and therefore activated ERα and the PRs may be suitable markers for tailoring treatment with anti-estrogens and anti-progestins.

"These data demonstrate the potential of two predictive biomarkers in the treatment of breast cancer and further support the development of a diagnostic test to identify patients with activated progesterone receptor (APR) and activated estrogen receptor (AER) most likely to respond to treatment with anti-progestins and anti-estrogens, respectively," said Glenn Mattes, President and Chief Executive Officer of Arno Therapeutics. "We are encouraged by these results and continue to move forward in a clearly-defined development program for our lead compound onapristone and an accompanying companion diagnostic."

About Breast Cancer

In the United States, over 232,300 new cases of invasive breast cancer are expected to be diagnosed in women and over 2,200 new cases are expected in men during 2013. After cancers of the skin, breast cancer is the most frequently diagnosed cancer in women. More than 40,000 breast cancer deaths are expected in 2013, with the majority in women. Breast cancer ranks second as a cause of cancer death in women, following lung cancer.ⁱ

About Arno Therapeutics

Arno Therapeutics is a clinical stage biopharmaceutical company developing innovative products for the treatment of cancer.  Arno has exclusive worldwide rights to develop and market three innovative anti-cancer product candidates.  These compounds are in clinical or preclinical development as product candidates to treat hematologic malignancies and solid tumors.  For more information about the company, please visit www.arnothera.com. 

Forward-Looking Statements

This press release contains forward-looking statements that involve substantial risks and uncertainties. These statements are often, but not always, made through the use of words or phrases such as "anticipates," "expects," "plans," "believes," "intends," and similar words or phrases. These forward-looking statements include, without limitation, statements regarding the potential of APR and AER as effective biomarkers for the treatment of breast cancer, statements regarding the Company's belief that onapristone blocks the APR, statements regarding the timing, progress and anticipated results of the clinical development of onapristone, statements regarding Arno's use and development of a diagnostic test to identify patients with APR tumors, as well as statements regarding Arno's strategy, future operations, outlook, milestones, future financial position, future financial results, plans and objectives. We may not actually achieve these plans, intentions or expectations and Arno cautions investors not to place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. Various important factors could cause actual results or events to differ materially from the forward-looking statements that we make. Such factors include, among others, risks that the results of clinical trials will not support our claims or beliefs concerning the effectiveness of onapristone or any of our other product candidates, our ability to successfully develop a diagnostic to identify APR tumors, our ability to finance the development of our product candidates, regulatory risks, and our reliance on third party researchers and other collaborators. Additional risks are described in the company's Annual Report on Form 10-K for the year ended December 31, 2012. Arno is providing this information as of the date of this press release and does not undertake any obligation to update any forward-looking statements as a result of new information, future events or otherwise.

ⁱ American Cancer Society. Cancer Facts & Figures 2013. Available at: http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-036845.pdf

Last accessed: September 25, 2013.