Monday, November 19, 2007
Hollis-Eden Pharmaceuticals Presents Data Demonstrating TRIOLEX(TM) Provides Benefit in Additional Animal Model of Rheumatoid Arthritis
Findings Presented at 36th Annual Autumn Immunology Conference
SAN DIEGO--(BUSINESS WIRE)--Nov. 19, 2007--Hollis-Eden Pharmaceuticals, Inc. (NASDAQ:HEPH), the world leader in the development of a new class of small molecule compounds based on endogenous steroid hormones, is presenting new data this week at the 36th Annual Autumn Immunology Conference, held in Chicago, Illinois, November 16-19, showing that its drug candidate TRIOLEX(TM) (HE3286) provided benefit in an animal model of collagen antibody induced arthritis (CAIA). As previously reported, TRIOLEX, a novel orally bio-available anti-inflammatory cleared by the U.S. Food and Drug Administration for a Phase I/II clinical trial in rheumatoid arthritis (RA), has also demonstrated benefit to date in animal models of collagen induced arthritis (CIA), systemic lupus erythematosus, multiple sclerosis and ulcerative colitis without immune suppressive side effects.
The new data, presented in an oral presentation, are from studies performed by Dr. David Boyle at The University of California, San Diego (UCSD) showing that treatment with TRIOLEX significantly reduced disease in the murine model of CAIA in a dose dependent fashion, with the highest dose completely eliminating disease. In the CAIA model, disease is induced by injecting animals with arthrogenic antibodies, a method that largely bypasses the animal's own cellular immune system. Severe joint inflammation occurs within hours after the injection of antibodies. TRIOLEX was highly effective in this model whether treatment began 1 day or 5 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, the current standard of care in RA, is far less effective in the CAIA model than in models of collagen induced arthritis (CIA), where disease is driven by the animal's own cellular immune system.
Methotrexate, a chemotherapy treatment, is focused on treating the cellular infiltration aspect of RA, while other treatments such as corticosteroids and non-steroidal anti-inflammatory agents focus on treating the antibody aspect of the disease. Due to the previously reported activity of TRIOLEX in the CIA animal model and this newly reported activity in the CAIA model, the Company believes that TRIOLEX may be effective at treating both aspects of RA without the immune suppressive side effects associated with some currently prescribed drugs.
Hollis-Eden believes TRIOLEX may act by inhibiting the activation of the NF-kappaB pathway. NF-kappaB is a transcription factor that controls many of the genes involved in the inflammatory signaling pathway, including TNF-alpha, IL-1-beta and IL-6. These cytokines are thought to be key inflammatory mediators that play an important underlying role in many major diseases, including autoimmune disorders. 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.
Rheumatoid arthritis 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 U.S. of drugs to treat RA are expected to reach $14 billion by 2009, driven by the increase in the aging population and use of new expensive biological treatments. Celebrex, a commonly used drug for RA that inhibits the cox-2 enzyme, recorded U.S. annual sales in excess of $2 billion in 2006.
"We are extremely encouraged by these new data in the CAIA model of rheumatoid arthritis," said Dr. James M. Frincke, Chief Scientific Officer at Hollis-Eden Pharmaceuticals. "In our first clear look into the inflamed joint tissue itself, we found that TRIOLEX virtually eliminated messenger RNA to IL-6 and MMP-3 in this animal model, key players thought to drive inflammation and tissue destruction in RA and other autoimmune disorders."
"These findings provide additional, impressive preclinical evidence of the anti-inflammatory activity of TRIOLEX," said Richard Hollis, Chairman and CEO of Hollis-Eden Pharmaceuticals. "The observation that TRIOLEX treats both collagen induced arthritis and collagen antibody induced arthritis in animal models bodes well for the compound's potential efficacy since it appears able to address both cell and antibody mediated elements of RA. Inflammation is increasingly understood to play a role in multiple diseases of aging, including RA and other autoimmune disorders, metabolic disorders, cardiovascular diseases and cancer, and we believe that this work furthers validates the potential of our compounds to possibly provide therapeutic benefit in these major clinical applications. We are currently conducting a Phase I/II clinical trial with TRIOLEX for type 2 diabetes and are evaluating the ability to use safety and dosing data from that trial to accelerate development of the compound for rheumatoid arthritis."
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, a next-generation compound currently in a clinical trial for the treatment of type 2 diabetes and being prepared for 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 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.
CONTACT: Hollis-Eden Pharmaceuticals, Inc.
Scott Rieger, Director, Corporate Communications
SOURCE: Hollis-Eden Pharmaceuticals, Inc.