ARNI Arno Therapeutics Inc (CE)

Studies to determine recommended Phase II dose and safety profile of lead compound

Will analyze relationship of biomarker to any anti-tumor activity observed

Arno Therapeutics, Inc. (OTCQB:ARNI), a clinical stage biopharmaceutical company focused on the development of oncology therapeutics, today announced two, separate abstracts outlining the study designs of ongoing Phase I clinical trials evaluating its investigational lead compound onapristone to be presented at the upcoming 50th American Society of Clinical Oncology (ASCO) Annual Meeting, being held May 30 – June 3, 2014 in Chicago, Illinois.

Arno will present the objectives, methods and study designs for its two ongoing studies, a Phase I trial in women with progesterone receptor (PR) expressing tumors and a Phase I/II trial in men with advanced castration-resistant prostate cancer (CRPC), who have failed treatment with abiraterone or enzalutamide. Each study is two-stage with an expansion component; the first stage evaluates dose selection and the second expands the number of patients at the determined recommended Phase II dose to confirm the safety profile and provide a preliminary assessment of anti-tumor activity.

"The strategically-planned study designs of both trials enable us to advance the clinical evaluation of targeted therapy onapristone with the goal of determining the recommended Phase II dose and safety profile in the most efficient and effective means possible," said Glenn Mattes, President and Chief Executive Officer of Arno Therapeutics. "Perhaps even more importantly, we intend to analyze the relationship of the biomarker, that being the activated form of the progesterone receptor, to any anti-tumor activity that is observed. Earlier this year, we began actively enrolling patients in both trials and also began the development of a companion diagnostic for the selection of patients more likely to benefit from treatment with onapristone. We are encouraged by the significant potential of onapristone to be a first-in-class anti-progestin compound for oncology indications."

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

• A randomized, parallel-dose Phase I study of onapristone (ONA) in patients (pts) with progesterone receptor (PR)-expressing canceri

The multi-center, open-label, randomized, parallel-dose Phase I study is an active, two-stage study with an expansion component in a total of about 60 women with tumors expressing PR. Tumor tissue is required to determine PR and transcriptionally activated PR (APR) status.

The primary endpoint of the study is to determine the recommended Phase II dose (RP2D) of extended-release onapristone, including a period for observation of dose-limiting toxicity. Secondary endpoints include safety and tolerability, efficacy, and real-time pharmacokinetic (PK) data. In addition, tissue specimens will be used to determine relationship of APR to preliminary efficacy.

Actively enrolling, dose-escalation Stage 1 of the trial evaluates six dose cohorts randomized in parallel. In each cohort, six patients receive extended release onapristone tablets at one of five doses (10, 20, 30, 40 or 50 mg BID) or immediate-release onapristone tablets at 100 mg QD until progressive disease or intolerable safety. A data review committee (DRC) monitors safety signals and dose limiting toxicities. Stage 2 of the study will enroll an additional 24 patients at the RP2D; this cohort will confirm the safety profile and potentially provide a preliminary assessment of anti-tumor activity. The DRC will continue to review all safety, PK and efficacy data.

• A Phase I-II study of the type I progesterone receptor (PR) antagonist onapristone (ONA) in patients (pts) with advanced castration-resistant prostate cancer (CRPC)ii

The open-label, Phase I/II study is an active, two-stage study with an expansion component in a total of about 60 men with metastatic or recurrent advanced castration-resistant prostate cancer (CRPC) who have failed treatment with abiraterone or enzalutamide. Because PR expression in prostate cancer increases with resistance to castration, the transcriptional, activated PR (APR) offers a potential target in advanced CRPC. Patients are evaluated at baseline to determine PR status and paired biopsies at day eight through 28 and upon progression are collected if possible.

The primary endpoints of this study include, determination of the RP2D and response rate based on Response Evaluation Criteria In Solid Tumors (RECIST) rules, circulating tumor cell (CTC) count conversion and/or more than 50% decline in prostate-specific antigen (PSA), a protein indicative of prostate cancer. Secondary endpoints include safety and PK data.

Currently enrolling, dose-selection Stage 1 evaluates patients randomized to 10 or 20 mg of extended release onapristone tablets BID, with three to six patients per cohort. Upon confirmation of safety, based on a dose-limiting toxicity (DLT) observation period of eight weeks, a data review committee (DRC) will open randomization in parallel to the 30, 40 or 50 mg cohorts, with six patients per cohort. The DRC will determine RP2D based on tolerability and PK.

At Stage 2, 36 patients will be treated at RP2D with an interim analysis after 21 patients have been enrolled. The adaptive design for biomarker-driven patient selection allows for a substantial proportion of the patients treated at the RP2D to have CRPC tumors that express APR.

Onapristone is an oral anti-progestin 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 breast, endometrial and other tumors driven by aberrant function of the PR. 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 currently under development.

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.iii 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 (body of the uterus) are expected to be diagnosed in 2014. These usually 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.iv 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 the potential of onapristone as a treatment for breast, prostate and other cancers, statements regarding whether Arno's clinical studies will establish a relationship of activated PR as a predictive biomarker to preliminary efficacy of an anti-progestin, 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, 2013. 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.

References

_____________________

i Cottu, P.H. et al. "A randomized, parallel-dose phase 1 study of onapristone (ONA) in patients (pts) with progesterone receptor (PR)-expressing cancers." Abstract TPS2643 / Poster 98B to be presented at the ASCO Annual Meeting during a poster session on June 1, 2014.

ii Mateo, J. et al. "A phase 1-2 study of the type I progesterone receptor (PR) antagonist, onapristone (ONA), in patients (pts) with advanced castration-resistant prostate cancer (CRPC)." Abstract TPS5097 / Poster 224B to be presented at the ASCO Annual Meeting during a poster session on June 2, 2014.

iii American Cancer Society. Cancer Facts & Figures 2014. Available at: http://www.cancer.org/acs/groups/content/@research/documents/webcontent/acspc-042151.pdf

iv 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

CONTACT: The Ruth Group
         Lee Roth (investors)
         lroth@theruthgroup.com
         (646) 536-7012
         
         Kirsten Thomas (media)
         kthomas@theruthgroup.com
         (646) 536-7014
         
         Arno Therapeutics
         Glenn Mattes
         gm@arnothera.com
         (862) 703-7176

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