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Hollis-Eden Pharmaceuticals Announces Filing of IND for Phase I/II Clinical Trials With HE3286 in Diseases of Inflammation

Posted on: Monday, 17 September 2007, 09:00 CDT

Hollis-Eden Pharmaceuticals, Inc. (NASDAQ:HEPH) announced today that it has filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) to begin clinical trials with its drug candidate HE3286 for the treatment of diseases of inflammation. Assuming clearance of the IND by the FDA, Hollis-Eden plans to initiate a Phase I/II clinical trial of HE3286 in rheumatoid arthritis (RA) patients during the fourth quarter of 2007. Additionally, upon clearance of this IND Hollis-Eden may also consider commencing exploratory studies in the fourth quarter of 2007 to evaluate HE3286 in one or more acute inflammatory conditions, where evidence of activity against well-accepted clinical endpoints could potentially be generated with 28-day dosing.

As previously announced, Hollis-Eden completed a Phase I single dose clinical study of HE3286 in healthy volunteers earlier this year under a previously filed and cleared IND for the use of HE3286 in treating metabolic disorders. The findings from that study showed HE3286 to be orally bioavailable in humans and well tolerated with no serious adverse side effects. The Company believes the findings from this previous study will serve to support the initiation of Phase I/II clinical studies in patients with RA and other inflammatory conditions under the IND filing announced today.

Over the last several years reports in the scientific literature suggest that inflammation is one of the important underlying causes of many major diseases, including autoimmune disorders, metabolic disorders, cardiovascular, pulmonary/respiratory conditions, cancer and in general, the process of aging. Pro-inflammatory cytokines are thought to be the key mediators of the pathological processes in these diseases that eventually lead to pain and tissue destruction. Many of the genes involved in the inflammatory signaling pathway include TNF-alpha, IL-1-beta and IL-6, which are under the control of the transcription factor NF-kappaB. To date, HE3286 has demonstrated activity in animal models of rheumatoid arthritis, multiple sclerosis, lupus, ulcerative colitis and cystic fibrosis. In these experiments, the effect of HE3286 on the signaling pathway was evaluated and observations over several diverse experimental conditions led to the conclusion that HE3286 may act by limiting NF-kappaB activation. Unlike corticosteroids that act through the glucocorticoid receptor to completely block NF-kappaB activation and cause immune suppression and bone loss, HE3286 does not interact with the glucocorticoid receptor and only partially inhibits NF-kappaB without immune suppression or bone loss.

Review of Activity of HE3286 in Preclinical Models of Rheumatoid Arthritis

In a DBA mouse model of collagen-induced arthritis, mice were immunized to induce disease and were then treated orally with HE3286 or placebo beginning one week after disease onset. While the severity of arthritis worsened steadily in the placebo-treated group, it nearly resolved or remained at a minimum in the HE3286-treated group (p < 0.001). Treatment resulted in a difference in arthritis severity that was on average 45% lower in the HE3286-treated group than in the placebo-treated group. The DBA mouse model of collagen-induced arthritis is a model widely used in industry and academia to test new agents as potential treatments for rheumatoid arthritis.

Hollis-Eden previously published data from preclinical models elucidating potential mechanisms of action for HE3286 that include partial inhibition of NF-kappaB and increasing the production of regulatory T cells (Treg cells). Treg cells are referred to in the scientific literature as the "peacekeepers of the body," charged with keeping the immune system from attacking the body itself. Recent third party studies of Treg cells indicate that they may play a broader role than simply preventing autoimmune conditions. The medical literature is now suggesting that the manipulations of Treg cells could offer new treatments for conditions ranging from diabetes to organ rejection.

"We are excited to be filing an IND for HE3286 in diseases of inflammation as HE3286 may represent the next generation of steroid hormones for a variety of inflammatory medical conditions," said Richard Hollis, Chairman and CEO of Hollis-Eden Pharmaceuticals. "We congratulate our Chief Scientific Officer Dr. James Frincke and his entire team for their outstanding accomplishment in discovering this promising new molecule and advancing it into the clinical development process. HE3286 has performed well in a variety of animal models of inflammation and in human testing to date the compound has shown good oral bioavailability and is well tolerated. This new IND is designed to enable us to evaluate HE3286 in a phase I/II clinical trial in rheumatoid arthritis patients, but it will also strategically position us to consider initiating additional clinical trials in one or more acute inflammatory conditions before the end of the year. This strategy will allow us to study the compound's effects both on inflammatory markers in a chronic inflammatory condition, as well as to evaluate its ability to show benefit relative to a clinical endpoint for an acute inflammatory condition. If we are successful in developing HE3286, the potential new mechanism of action of this compound may provide an attractive alternative to the current therapeutic options available to patients with inflammatory conditions and autoimmune diseases, since we believe HE3286 will avoid the side effects associated with approved corticosteroid therapies. This benefit of HE3286 may be attributed to the fact that it does not interact with the glucocorticoid receptor, and our class of adrenal steroid hormones is known to oppose the catabolic effects of corticosteroids."

Approximately 67 million prescriptions are written each year for corticosteroids for a variety of inflammatory diseases. The current market for proprietary corticosteroids is approximately $7.4 billion in annual sales despite their inherent side effects. The combined market for the anti-inflammatory agents Celebrex and Vioxx, known as the Cox-2 inhibitors, was approximately $5.0 billion in annual sales before Vioxx was pulled from the market in 2004. Novel anti-inflammatory agents with new mechanisms of action and fewer side effects could garner a significant market share.

Hollis-Eden Pharmaceuticals

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 HE3286, a next-generation compound currently in a clinical trial for the treatment of type 2 diabetes and being prepared for potential clinical trials in rheumatoid arthritis, and HE3235, a next-generation compound selected for 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 www.holliseden.com.

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. Any statements 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 ability to obtain regulatory approval for HE3286, 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 protect its intellectual property rights and to not infringe the intellectual property rights of others; the development of competitive products by other companies; 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. 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.

Source: Business Wire

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