ARNI Arno Therapeutics Inc (CE)

Arno Therapeutics, Inc. (OTCQB:ARNI), a clinical stage biopharmaceutical company focused on the development of oncology therapeutics, today announced new data from three research programs which support its investigational lead compound onapristone to be presented at the American Association for Cancer Research (AACR) Annual Meeting 2014, being held April 5-9 in San Diego, California.

Results from the three investigational studies add to the growing body of scientific knowledge enabling the clinical evaluation of onapristone – an oral, anti-progestin hormone blocker that has been shown in previous Phase II clinical trials to exhibit anti-tumor activity in patients with breast cancer. In pre-clinical testing, onapristone has been shown to block the activation of the progesterone receptor (PR), which is believed to be a mechanism that inhibits the growth of APR-driven breast, endometrial and other tumors. Tests for the activated form of the progesterone receptor (APR) have the potential to function as a biomarker of anti-progestin activity, as detected by a companion diagnostic under development. 

Alex Zukiwski, MD, Chief Medical Officer of Arno Therapeutics, remarked, "We continue to take steps to explore pathways indicating which patient populations could potentially benefit from treatment with onapristone. We are encouraged by these results as they collectively add to the knowledge base enabling the further clinical development of this anti-progestin therapy. Separately, the studies led to the development of a Good Manufacturing Product production process for carbon 11 labeling of onapristone for use in future clinical trials, determination of the effect of food on the absorption of onapristone and demonstration that immunohistochemistry with two specific progesterone receptor antibodies may help identify patients with triple-negative breast cancer whose tumors express the progesterone receptor. The understandings from the pharmacokinetic/food effect study in particular allow us to provide a dosing recommendation for patients to take onapristone on an empty stomach."  

The findings, outlined below from the accepted abstracts, will be presented during three separate poster sessions:

• Synthesis of [11C]onapristone for clinical investigation i Abstract # 1646; Poster # 29 Session Category: Chemistry 2 Session Title: Small Molecule Design, Identification, and Optimization 1 Date, Location: Monday, April 7, 8:00 am – 12:00 pm; Hall A-E, Poster Section 27

 The study aimed to develop a rapid Good Manufacturing Product (GMP) synthesis of parentally-administered Carbon-11 [11C] radiolabeled onapristone and successfully developed a fully-automated production of [11C] onapristone ready for use in clinical trials.  

Carbon-11 radiolabeled onapristone and its visualization via a positron emission tomography (PET) scan, coupled with pharmacokinetic (PK) studies, has the potential to determine tissue-specific and blood PK parameters including tumor tissue and plasma concentrations, whole body distribution and half-life of onapristone.

• Pharmacokinetic (PK) food effect study of immediate-release onapristone and its primary metabolite (M1) in healthy female subjects: implications for design of a new formulation ii Abstract # 4636; Poster # 12 Session Category: Experimental and Molecular Therapeutics 37 Session Title: Pharmacokinetics and Pharmacodynamics Date, Location: Tuesday, April 8, 1:00 – 5:00 pm; Hall A-E, Poster Section 35 The study was conducted to determine the pharmacokinetic (PK) profile of onapristone and mono-desmethyl onapristone (M1), with and without food.

The study employed a two-period, two-sequence, random assignment cross-over design. Twelve healthy female subjects were given 10 mg of an oral immediate release formulation of onapristone either after an overnight fast, or within 30 minutes after a high-fat high-calorie meal, with a 2 week washout between dosing periods.

Results show the prescribed diet had an impact on maximum concentration (Cmax), time to reach maximum concentration (tmax) and population PK analysis demonstrated there was a food effect on overall exposure.

• Impact of progesterone receptor (PR) isotype-specific immunohistochemistry (IHC) on the diagnosis of triple negative breast cancer (BC)iii Abstract # 5567; Poster # 2 Session Category: Clinical Research 16 Session Title: Clinical Endocrinology Date, Location: Wednesday, April 9, 8:00 am – 12:00 pm; Hall A-E, Poster Section 36

This study evaluated the use of two isotype-specific PR antibodies (Abs) to fully characterize PR status in breast cancer tumor samples reported by standard testing to be triple negative (estrogen receptor, progesterone receptor and Her2 negative).  

The study demonstrates that further evaluation of IHC with specific PRA and PRB Abs is warranted to determine if certain patients, currently classified as having triple-negative breast cancer, express the progesterone receptor and therefore could potentially benefit from anti-progestins, like onapristone.

Glenn Mattes, President and Chief Executive Officer of Arno Therapeutics, commented, "The combined results of the three studies corroborate further clinical evaluation of onapristone as a treatment in women's and men's cancers. Since determining the findings to be presented at this year's AACR Annual Meeting, Arno has continued to make strides in advancing the clinical trials of onapristone by actively enrolling patients in a Phase I trial of women with progesterone positive solid tumors and recently initiating a separate Phase I/II study of men with advanced castration-resistant prostate cancer. We have also continued to make substantial progress in the development of a companion diagnostic that will help identify patients more likely to benefit from onapristone therapy."  

About Breast Cancer

In the United States, over 232,670 new cases of invasive breast cancer are expected to be diagnosed in women and over 2,360 new cases are expected in men during 2014.iv After cancers of the skin, breast cancer is the most frequently diagnosed cancer in women.i  More than 40,430 breast cancer deaths are expected in 2014, with the vast majority in women. Breast cancer ranks second as a cause of cancer death in women, following lung cancer.i

About Endometrial Cancer

In the United States, about 52,630 cases of cancer of the uterine corpus (endometrium) - the body of the uterus - are expected to be diagnosed in 2014 and typically occur in the endometrium (lining of the uterus).i  About 8,590 deaths are expected in 2014.i

About Prostate Cancer

In the United States, prostate cancer is the most frequently diagnosed cancer in men aside from skin cancer. An estimated 233,000 new cases of prostate cancer will be diagnosed during 2014 in the U.S. alone. With an estimated 29,500 deaths expected to occur in 2014, prostate cancer is the second-leading cause of cancer death in men.i

On the global scale, prostate cancer is the fourth most common cancer in both sexes combined and the second most common cancer in men.v Worldwide in 2012, an estimated 1.1 million men were diagnosed – accounting for 15 percent of the cancers diagnosed in men – and there were an estimated 307,000 deaths, making prostate cancer the fifth leading cause of death from cancer in men (6.6% of the total men deaths). ii

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 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 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 Madar, O. et al. "Synthesis of [11 C]onapristone for clinical investigation." Poster to be presented at the American  Association for Cancer Research  (AACR) Annual Meeting 2014 on April 7, 2014. Abstract # 1646; Poster #29.

ii Rezai, K. et al. "Pharmacokinetic (PK) food effect study of immediate-release onapristone and its primary metabolite (M1) in healthy female subjects: implications for design of a new formulation." Poster to be presented at the American  Association for Cancer Research  (AACR) Annual Meeting 2014 on April 8, 2014. Abstract #: 4636; Poster #12.

iii Gilles, E. et al. "Impact of progesterone receptor (PR) isotype-specific immunohistochemistry (IHC) on the diagnosis of triple negative breast cancer (BC)." Poster to be presented at the American  Association for Cancer Research  (AACR) Annual Meeting 2014 on April 9, 2014. Abstract #: 5567; Poster #2.

iv American Cancer Society. Cancer Facts & Figures 2014. Available at:   http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-041770.pdf Last accessed: February 28, 2014.

v International Agency for Research on Cancer. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Available at: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx Last accessed. February 6, 2014.

CONTACT: The Ruth Group
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         Arno Therapeutics
         Glenn Mattes
         gm@arnothera.com
         (862) 703-7176