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Arno Therapeutics to Present Promising Data From Phase I Trial of Onapristone at AACR Annual Meeting 2015

FLEMINGTON, N.J., April 21, 2015 (GLOBE NEWSWIRE) -- Arno Therapeutics, Inc. (OTCQB:ARNI), a clinical stage biopharmaceutical company primarily focused on the development of therapeutics for cancer and other life threatening diseases, today announced data from three posters supporting the ongoing clinical development program for lead compound onapristone at the American Association for Cancer Research (AACR) Annual Meeting 2015, being held April 18-22 in Philadelphia, Pa.

Alex Zukiwski, MD, Chief Executive Officer of Arno Therapeutics, commented, "The AACR Annual Meeting offers members of the oncology community an important opportunity to highlight new cancer research and discoveries that advance the field toward improved therapeutic options for patients. This year, we are pleased to present data from our preclinical and clinical studies that support the continued development of our lead oncology drug candidate onapristone – particularly the data from our Phase I study demonstrating that onapristone exhibits a well-tolerated safety profile at the highest evaluated extended-release dose level – and the continued development of a companion diagnostic for onapristone that identifies activated progesterone receptor (APR) tumor status as a predictor of anti-progestin activity."

Data results from the three studies being presented are as follows:

Abstract #4512 (Poster #10) – Onapristone in patients (pts) with progesterone receptor (PR)-expressing cancers: PK results from part 1 of a randomized, parallel-dose phase 1 study

Poster Session: PO.ET05.01. Pharmacokinetics and Pharmacodynamics
Date, Location: Tuesday, April 21; 1:00-5:00 p.m. ET

Validated pharmacokinetic (PK) data from 35 of 52 enrolled patients in stage 1 of the multi-center, open-label, randomized, parallel-group Phase 1 study (NCT02052128) evaluating onapristone in women with progesterone receptor (PR) expressing tumors demonstrate a longer onapristone half-life (T1/2) which supports using an extended-release formulation of the compound. Arno has developed the extended release formulation to mitigate high concentration spikes that may have contributed to the previously described adverse events of liver function test (LFT) elevations observed in patients receiving an immediate-release formulation in prior clinical trials. The study showed that drug release rate (AUC) and drug concentration (Cmax) are dose proportional and allow dosing flexibility. In addition, the study showed prolonged exposure-minimizing concentration spikes is best achieved with a twice-daily, extended-release formulation. There were no clinically significant LFT elevations in the absence of liver metastases in 30 patients exposed to the extended-release formulation.

The recommended Phase 2 dose (RP2D) was established at the highest extended-release dose level – 50 mg twice daily (BID) – based on safety and PK data, and is being further explored in the expansion phase of the study. The Phase II component of the modified Phase I/II clinical study is evaluating onapristone in women with recurrent or metastatic endometrioid tumors that have been shown to express the activated progesterone receptor (APR).

Abstract #4523 (Poster #21) – Population pharmacokinetic (PPK) modeling of onapristone in patients (pts) with progesterone receptor (PR)-expressing cancers

Poster Session: PO.ET05.01. Pharmacokinetics and Pharmacodynamics
Date, Location: Tuesday, April 21; 1:00-5:00 p.m. ET

Validated pharmacokinetic (PK) data from 42 patients were analyzed from the completed Stage 1 portion of the multi-center, open-label, randomized, parallel-group Phase 1 study (NCT02052128) evaluating onapristone in women with progesterone receptor (PR) expressing tumors. During the study, blood samples from patients receiving extended-release or immediate-release formulations of onapristone were taken at regular intervals and the onapristone plasma concentrations were measured.

The study showed that a two-compartment open population pharmacokinetic (PPK) model adequately described the total plasma onapristone time-concentration curve with linear elimination. A central volume equivalent to the circulating blood volume and a large volume of the deep compartment suggest a substantial tissue diffusion. No detectable PK/safety signal was detected and, as anticipated, concentration fluctuations were less with the extended release versus immediate release formulation.

Abstract #3471 (Poster #24) – Comparative assessment of in vitro activity and activated progesterone receptor (APR) biomarker predictivity for multiple antiprogestins

Poster Session: PO.EN02.01. Hormonal Regulation of Tumor Growth and Metastasis
Date, Location: Tuesday, April 21; 8:00 a.m. - 12:00 p.m. ET

The study examined the correlation of activated progesterone receptor (APR) – which is predictive of onapristone anti-proliferative effects – to the anti-proliferative effects of several different anti-progestins, including Type I & Type II, and steroidal/non-steroidal chemical structures (growth supplements), in two progesterone receptor (PR) expressing breast cancer cell lines, T47D and CAMA-1.

The study found that the cell line T47D expresses APR and is sensitive to direct anti-progestin effect in steroidal growth supplement (FBS) and to estradiol and progesterone growth stimulation in non-steroidal growth supplement (SFFBS). In the T47D cell line, there was an antagonism by all anti-progestins, and APR positive status was reversed at 30 hours completely in 3 of 6 cases and incompletely in 3 of 6 cases. The study showed that the CAMA-1 cell line does not express APR, is weakly stimulated by estradiol and progesterone, and anti-progestins have inconsistent effects in this cell line. The study concluded that APR status is a predictor of anti-progestin action.

Arno is currently enrolling patients in a Phase II clinical trial of onapristone in patients with metastatic or recurrent endometrioid tumors that express the activated progesterone receptor (APR), and in a separate Phase I/II clinical trial of onapristone in patients with castration resistant prostate cancer whose tumors are progesterone receptor (PR) positive.

Onapristone is an oral, anti-progestin hormone blocker that has been shown in previous Phase II clinical trials (not sponsored by Arno) to exhibit anti-tumor activity in patients with breast cancer. In pre-clinical testing, onapristone has been shown to block the activation of PR, which is believed to be a mechanism that inhibits the growth of APR driven breast, endometrial and other, primarily gynecological, tumors. APR has the potential to function as a biomarker of anti-progestin activity, as detected by a companion diagnostic currently under development with Arno's partner, Leica Biosystems.

About Arno Therapeutics

Arno Therapeutics is a clinical stage biopharmaceutical company developing innovative products for the treatment of cancer and other life threatening diseases. Arno has exclusive worldwide rights to develop and market three innovative product candidates. These compounds are in clinical or preclinical development as product candidates to treat hematologic malignancies and solid tumors, as well as infectious diseases. 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, including the ability to identify and treat those patients most likely to benefit from onapristone, as well as Arno's strategy, future operations, outlook, milestones, future financial position, future financial results, plans and objectives. Arno 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 made here. Various important factors could cause actual results or events to differ materially from these forward-looking statements. Such factors include, among others, risks that the results of clinical trials will not support claims or beliefs concerning the effectiveness of onapristone or any other product candidates, the ability to successfully develop a diagnostic to identify APR tumors, the ability to finance the development of Arno's product candidates, regulatory risks, and 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, 2014. 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.

CONTACT: The Ruth Group Lee Roth (investors) lroth@theruthgroup.com (646) 536-7012 Kirsten Thomas (media) kthomas@theruthgroup.com (646) 536-7014 Arno Therapeutics Lawrence Kenyon lk@arnothera.com (862) 703-7171

Source:Arno Therapeutics Inc.