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Hollis-Eden Researchers Present New Findings on Mechanism of Action for Anti-Cancer Drug Candidate Apoptone (HE3235)

SAN DIEGO--(BUSINESS WIRE)--Jan 23, 2009 - Hollis-Eden Pharmaceuticals, Inc. (NASDAQ:HEPH), the world leader in the development of a new class of small molecule compounds based on endogenous adrenal steroid hormones, today presented new findings regarding the potential mechanism of action of APOPTONE™ (HE3235), the Company's drug candidate in development for the treatment of prostate cancer. New preclinical data presented today demonstrate the ability of APOPTONE to activate a naturally occurring regulatory pathway known as Raf/MEK/ERK, which is known to down-regulate PI3K/AKT, the growth pathway that is hyper-activated in prostate cancer cells. The Company believes that APOPTONE's activation of Raf/MEK/ERK may, in part, be contributing to the compound's ability in preclinical models to date to cause prostate cancer cells to undergo apoptosis, or die. The Company's new findings were reported this week at the American Association of Cancer Research (AACR) Advances in Prostate Cancer Research Conference, being held in San Diego, California from January 21st through January 24th, by Dr. Richard Trauger, Senior Director of Infectious Diseases and Cancer at Hollis-Eden Pharmaceuticals.

Recent reports from the scientific literature indicate that androgen receptor signaling is active in all stages of prostate cancer, including late-stage castration-resistant prostate cancer, and that castration-resistant prostate cancer may be driven by the prostate tumor cell's ability to synthesize the production of its own androgens within the tumor in order to continue proliferating. In light of this finding, the Company also presented previously reported data generated by Dr. Trauger and Dr. Eva Corey, Research Associate Professor, Department of Urology, at the University of Washington. Dr. Trauger reported that using the castration-resistant LuCaP 35V xenograft model (human prostate tumors implanted in immunodeficient mice), APOPTONE treatment significantly reduced tumor volume (p < 0.05), and delayed tumor-doubling time relative to that in vehicle-treated animals. An analysis of tumor samples from these mice also demonstrated that APOPTONE lowered levels of androgen receptor protein and significantly reduced gene expression relative to the vehicle controls (p < 0.05). In addition, tumors in mice treated with APOPTONE had reduced levels of testosterone and dihydrotestosterone (DHT) relative to the vehicle-treated animals, suggesting that APOPTONE suppressed hormone synthesis directly within the tumors. Data were also presented from a separate model of prostate-mediated bone disease, where C4-2B castration-resistant tumor cells were implanted directly into the tibia of castrated SCID mice. APOPTONE treatment significantly lowered the tumor bearing tibia weight and reduced PSA levels relative to the vehicle-treated animals (p < 0.05).

“We believe the data presented today suggesting that the preclinical anti-proliferative activity of APOPTONE may be due to the activation of Raf/MEK/ERK help further explain APOPTONE's potential mechanism of action in these pre-clinical models of late-stage prostate cancer,” stated Dr. Trauger. “Inhibition of the AKT pathway by activation of Raf/MEK/ERK has been reported in the scientific literature to induce apoptosis in prostate cancer cells and these new findings are consistent with the previously reported cytotoxic activity of APOPTONE. In summary, these new results, along with APOPTONE's ability to down-regulate the androgen receptor as well as expression of intra-tumoral androgen synthesis, preclinically, further help to distinguish APOPTONE as a novel and exciting drug candidate for the treatment of late-stage prostate cancer, if successfully developed.”

APOPTONE Clinical Trial

Hollis-Eden is currently enrolling late-stage prostate cancer patients in a dose-ranging, Phase I/II clinical study under an open IND with APOPTONE for the treatment of hormone sensitive cancers, at multiple sites across the United States. The protocol for this study allows for expansion of additional patients in any dosing cohort upon signs of safety, activity or adequate concentrations of APOPTONE found in the plasma of patients in a dosing cohort. In order for the expansion of additional patients in any dosing cohort, the concentration of APOPTONE will need to be consistent with the drug exposure found in the Company's in-vitro preclinical studies that exhibited anti-tumor activity without compromising the safety levels determined in preclinical toxicity studies. If the Company and its clinical investigators elect to expand a dosing cohort to 20 or more patients upon satisfying the protocol's criteria, this could essentially initiate the evaluation of APOPTONE in a Phase II study. The Company currently plans to report data from this on-going clinical study during the first half of 2009.

The Phase I/II open-label dose ranging study is being conducted with select clinical sites that are members of the Prostate Cancer Clinical Trial Consortium (PCCTC). The PCCTC membership sites currently participating in the Phase I/II trial are: Memorial Sloan-Kettering Cancer Center, New York, University of California San Francisco and the University of Washington, Seattle. Additional clinical sites outside the PCCTC consortium have recently been opened to allow for more rapid enrollment of patients into the planned expanded cohort(s).

Prostate Cancer and Hormone Receptor-Sensitive Cancer (HRS) Markets

Hormone receptor sensitive cancers are those tumors that require hormone stimulation or the presence of a hormone receptor for growth. HRS tumors are the most common types of malignancy, representing 30% and 38% of all new cancer cases in men and women, respectively. For men in the United States, prostate cancer is the second leading cause of deaths from cancer, following lung cancer. It has been estimated that one in six men will develop prostate cancer and one in 30 will die from this disease. It is well documented that the aberrant growth of prostate cancer cells can be due to a mutation in a tumor suppressor gene called PTEN, a natural inhibitor of the PI3/AKT pathway. In prostate cancer the lack of a functional PTEN gene product allows for hyper-activation of PI3/AKT, resulting in the uncontrolled cell growth that is the hallmark of malignant cells. The Company believes that the activation of the Raf/MEK/ERK pathway and subsequent cytotoxic activity observed with APOPTONE preclinically to date, distinguishes APOPTONE from other steroid hormone based compounds that interrupt the binding of hormones to the cell receptor or block the ability of the body to produce hormones.

Over one million men in the United States have prostate cancer and the prevalence of late stage prostate cancer in the United States is approximately 90 thousand patients of which approximately 28 thousand die each year. There are currently no approved treatments for end-stage prostate cancer and the survival time is estimated to be between 8 and 12 months. Current treatments for prostate cancer focus on blocking testosterone and other hormones associated with disease progression and chemotherapy and range in annual sales from $500 million to $1.8 billion. Unfortunately these agents become ineffective at treating the disease as it is progressing, leaving late-stage prostate cancer an unmet medical need.

About Hollis-Eden Pharmaceuticals, Inc.

Hollis-Eden Pharmaceuticals, Inc. is a world leader in the development of a proprietary class of adrenal steroid hormones as novel pharmaceuticals for human health. Through its Hormonal Signaling Technology Platform, Hollis-Eden is developing a new series of small molecule compounds that are metabolites or synthetic analogs of endogenous hormones derived by the adrenal glands from the body's most abundant circulating adrenal steroid. These steroid hormones, designed to restore the biological activity of cellular signaling pathways disrupted by disease and aging, have been demonstrated in humans to possess several properties with potential therapeutic benefit -- they regulate innate and adaptive immunity, reduce nonproductive inflammation and stimulate cell proliferation. The Company's clinical drug development candidates include TRIOLEX™ (HE3286), a next-generation compound currently in clinical trials for the treatment of type 2 diabetes, ulcerative colitis and rheumatoid arthritis, and APOPTONE™ (HE3235), a next-generation compound in a clinical trial for the treatment of late-stage prostate cancer. In addition to these clinical development candidates, Hollis-Eden has an active research program that is generating additional new clinical leads that are being further evaluated in preclinical models of a number of different diseases. For more information on Hollis-Eden, visit the Company's website at

This press release contains forward-looking statements within the meaning of the federal securities laws concerning, among other things, the potential and prospects of the Company's drug discovery program and its drug candidates and the benefits to be derived therefrom including the potential advantages of APOPTONE compared to other treatment approaches, how APOPTONE is believed to work and its potential for use in the treatment of prostate cancer or other cancers. The inclusion of forward-looking statements should not be regarded as a representation by the Company that any of its plans will be achieved. Any statement included in this press release that are not a description of historical facts are forward-looking statements that involve risks, uncertainties, assumptions and other factors which, if they do not materialize or prove correct, could cause the Company's actual results to differ materially from historical results or those expressed or implied by such forward-looking statements. Such statements are subject to certain risks and uncertainties inherent in the Company's business, including, but not limited to: the ability to complete preclinical and clinical trials successfully and within specified timelines, if at all; the risks and uncertainties inherent in clinical trials, and drug development and commercialization, including the uncertainty of whether results in preclinical and clinical testing of APOPTONE to date will be predictive of results in later stages of development; the ability to obtain regulatory approval for TRIOLEX (HE3286), APOPTONE (HE3235) or any other investigational drug candidate; the Company's future capital needs; the Company's ability to obtain additional funding; the ability of the Company to obtain and protect its intellectual property rights and to not infringe the intellectual property rights of others; the development of competitive products by other companies, the market potential for prostate cancer and the other markets the Company is targeting, and the Company's ability to compete; and other risks detailed from time to time in the Company's filings with the Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All forward-looking statements are qualified in their entirety by this cautionary statement. Except as required by law, the Company undertakes no obligation to update or revise the information contained in this press release as a result of new information, future events or circumstances arising after the date of this press release. None of the Company's drug candidates has been approved for sale, significant additional animal and human testing is required in order to seek marketing approval for any of its drug candidates, and the Company cannot assure you that marketing approval can be obtained for any of its drug candidates or that, even if such marketing approval were received, such drug candidates would ultimately achieve commercial success. Furthermore, as is typically the case at this stage of the regulatory review process, the FDA has not yet performed an in-depth review of the Company's preclinical and clinical data, so its views remain subject to change.


Contact: Hollis-Eden Pharmaceuticals, Inc.
Scott Rieger, Vice President, Corporate Communications
(858) 587-9333


Posted: January 2009