HEPH Hollis-Eden Pharmaceuticals (MM)

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, announced that it has commenced a Phase I/II open label dose ranging clinical trial with its investigational oral drug candidate TRIOLEX� (HE3286) in patients diagnosed with rheumatoid arthritis (RA) and receiving a stable dose of methotrexate, the current standard of care in RA. The purpose of the Phase I/II clinical trial is to evaluate the safety and tolerance of TRIOLEX when administered orally for 28 days at three different dose levels. The study will also evaluate the pharmacokinetics (PK) and metabolism profiles of methotrexate and TRIOLEX when used in combination, and assess any potential anti-inflammatory activity of TRIOLEX. �The commencement of this clinical trial caps six years of international collaborations with world renowned experts working on the development of a new treatment for RA,� commented Dr. Dominick L. Auci, Director of Allergy, Autoimmunity and Inflammation at Hollis-Eden Pharmaceuticals. �This body of work, presented over the years at numerous international meetings and published in peer reviewed journals, clearly documents the remarkable activity of TRIOLEX across several animal models of RA, each emphasizing different aspects of the pathophysiology thought to drive the human disease. We are particularly excited to begin this trial because TRIOLEX, without being immune suppressive, has consistently performed as well or better than the biologics in these models and works where methotrexate fails.� Preclinical Data in Models of Rheumatoid Arthritis Hollis-Eden has conducted extensive preclinical study with TRIOLEX in models of rheumatoid arthritis with striking results. The Company previously reported positive results from preclinical studies with TRIOLEX in models of collagen induced arthritis (CIA) and collagen antibody induced arthritis (CAIA). These models represent both the cell-mediated and antibody-mediated aspects of human rheumatoid arthritis. In a model of CIA, mice were immunized to induce disease and were then treated orally with TRIOLEX 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 TRIOLEX-treated group (p < 0.001). Treatment resulted in a difference in arthritis severity that was on average 45% lower in the TRIOLEX-treated group than in the placebo-treated group. The DBA mouse model of CIA is a model widely used in industry and academia to test new agents as potential treatments for RA. In the murine model of CAIA, TRIOLEX significantly reduced disease in a dose dependent fashion, with the highest dose completely eliminating disease. In the CAIA model, disease is induced by injecting animals with atherogenic antibodies, a method that largely bypasses the animals� own cellular immune systems. Severe joint inflammation occurs within hours after the injection of antibodies. TRIOLEX was highly effective in this model whether treatment began one day or five days after injection with antibodies. Benefit at the peak of disease was associated with a significant reduction of interleukin-6 (IL-6) and matrix metalloproteinase-3 (MMP-3) messenger RNA from the joints of TRIOLEX-treated animals when compared to placebo-treated controls. IL-6 and MMP-3 are thought to be among the most important drivers of disease and tissue destruction in human RA. Methotrexate is far less effective in the CAIA model than in models of CIA, where disease is driven by the animal�s own cellular immune system. Hollis-Eden believes that the benefit of TRIOLEX in animals was associated with expansion of regulatory T cells, an important subset of immune cells thought to be critical in controlling autoimmunity. The Company also believes that TRIOLEX may induce resolution in pro-inflammatory pathways, such as those governed by NF-kappaB. NF-kappaB is a transcription factor that controls many of the genes involved in the inflammatory signaling pathway, including TNF-alpha, IL-1beta and IL-6. These cytokines are thought to be key inflammatory mediators that play an important underlying role in RA and other autoimmune and inflammatory diseases. Unlike currently prescribed corticosteroids that can cause immune suppression and bone loss, animal studies to date show that TRIOLEX does not interact with the glucocorticoid receptor and only partially inhibits the NF-kappaB pathway without causing immune suppression or bone loss. These observations suggest that rather than blocking the inductive phase of the inflammatory response, which historically leads to profound immune suppression, TRIOLEX may drive the active resolution of unproductive inflammation. �Advancing TRIOLEX into rheumatoid arthritis patients represents years of preclinical studies that produced consistently impressive results,� stated Richard Hollis, Chairman and CEO of Hollis-Eden Pharmaceuticals. �We believe a big breakthrough in medicine would be to deliver a pharmaceutical that has the ability to regulate unproductive inflammation without the side effects of currently approved anti-inflammatories. Given its biochemical structure and signaling pathways, TRIOLEX potentially represents such a breakthrough product. TRIOLEX is a stabilized, synthetic analog of a naturally occurring molecule metabolized by the body from dehydroepiandrosterone (DHEA) and whose role in nature we believe is to regulate stress-inflammatory responses to maintain homeostasis. Translating our preclinical data into human clinical trials would be a major triumph in our efforts to develop a novel therapy for patients suffering from RA. We look forward to a possible renaissance in the use of smarter, safer steroid hormones to treat diseases of inflammation and autoimmunity as well as other conditions associated with aging.� About Rheumatoid Arthritis Rheumatoid arthritis affects more than 1.3 million people in the United States and is driven by both a cellular and antibody mediated autoimmune response and, as a result, combinations of highly immune suppressive drugs are commonly used to treat both aspects of active disease. Annual sales in the United States of drugs to treat RA are expected to reach $14 billion by 2009, driven by the increase in the aging population and the use of new expensive biological treatments. For example, Celebrex�, a commonly used anti-inflammatory drug for RA that inhibits the cox-2 enzyme currently has annual sales in excess of $2 billion. 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 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 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 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 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 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.