Hollis-Eden Pharmaceuticals Presents Positive Data Demonstrating HE3286 Provides Benefit in Animal Model of Ulcerative Colitis
The data were presented at the 3rd International Conference on Autoimmunity: Mechanisms and Novel Treatments, in Rhodes, Greece, by Ferdinando Nicoletti, MD, professor of biomedical sciences at the University of Catania School of Medicine, Catania, Italy, and a leading expert on autoimmune diseases. Dr. Nicoletti reported that HE3286 showed significant (p less than 0.05) benefit in the Wistar rat model of dinitrobenzene sulfonic acid (DNBS) induced colitis, a preclinical model widely used in industry and academia to test agents as potential treatments for ulcerative colitis. DNBS challenged rats with induced colitis were treated orally for approximately seven days with either HE3286 or placebo (n = 10 per group). At the end of the treatment period, HE3286-treated animals had significantly reduced disease, as judged by reduced colon weight and reduced area of necrosis, compared to the placebo-treated animals.
In animal studies conducted to date, HE3286 has demonstrated activity in multiple models of inflammatory conditions, including rheumatoid arthritis, multiple sclerosis, lupus, and cystic fibrosis. As previously reported, HE3286 produced a statistically significant reduction in disease in mouse models of rheumatoid arthritis, both at onset of the disease as well as after the disease was well established. Additional new data being presented this week by Dr. Nicoletti show that HE3286 provided significant benefit (p less than 0.05) in an animal model of adjuvant arthritis, even when treatment was delayed until disease was well established. In that model, rodents treated orally with HE3286, beginning either at disease onset or one week after disease onset, showed markedly reduced disease score and paw edema as compared to placebo-treated animals.
"We were impressed that in our animal model of ulcerative colitis, HE3286, even at relatively low doses, performed as well or better than sulfasalazine, which is the standard of care and the positive control in this model," said Dr. Nicoletti. "The therapeutic potential of HE3286 is particularly exciting because of the consistent demonstration of anti-inflammatory activity without the immune suppressive side effects associated with the corticosteroids. If successfully developed, HE3286 could offer an alternative to conventional corticosteroid therapy with a potentially more attractive safety profile."
Hollis-Eden has previously announced that it has filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) to enable the initiation of a clinical trial with HE3286 for the treatment of rheumatoid arthritis. In addition to studying the compound's effects in a chronic inflammatory condition such as rheumatoid arthritis, the Company may consider evaluating the ability of HE3286 to show benefit relative to a clinical endpoint for an acute inflammatory condition. Earlier this year, the Company completed a Phase I single dose clinical study of HE3286 in healthy volunteers 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.
Ulcerative Colitis (UC) is a chronic inflammation of the large intestine (colon). Ulcerative colitis is related to another condition of inflammation of the intestines called Crohn's disease. UC and Crohn's disease are frequently referred to together as inflammatory bowel disease, or IBD. UC and Crohn's disease together affect approximately 500,000 to 2 million people in the United States.
Current first line anti-inflammatory medications for the treatment of UC are topical 5-ASA compounds such as sulfasalazine, olsalazine and mesalimine based treatments. Additionally, UC is treated with corticosteroids and immunomodulators. The current worldwide market for 5-ASA intestinal anti-inflammatory agents is approximately $2 billion annually. Hollis-Eden believes HE3286 may act by limiting activation of NF-kappaB, 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 act through the glucocorticoid receptor to completely block NF-kappaB activation and that can cause immune suppression and bone loss, HE3286 does not interact with the glucocorticoid receptor and only partially inhibits NF-kappaB without causing immune suppression or bone loss when tested in animals.
"We are pleased that leading scientific investigators such as Dr. Nicoletti are presenting their results at major international conferences demonstrating the broad nature of the anti-inflammatory activity of HE3286 in models of inflammation," said Richard Hollis, Chairman and CEO of Hollis-Eden Pharmaceuticals. "These researchers are thought leaders in their respective fields and they are educating the scientific community about the potential application of a new class of adrenal steroid hormones to treat inflammatory conditions. These new positive data in a model of ulcerative colitis with HE3286 demonstrate the activity of the compound in an additional model of inflammation, providing further evidence of its inherent anti-inflammatory properties. The data also further validate our rationale to potentially test the compound in one or more acute clinical inflammatory indications in the future. The rapid progression of the disease flairs in acute inflammatory conditions such as UC and the clearly defined clinical endpoints holds the potential to demonstrate efficacy in humans with a short treatment course of HE3286. This strategy could enable us to rapidly demonstrate the safety and efficacy of HE3286 in human clinical trials and to accelerate its potential commercialization.
"There is a great need for safer anti-inflammatories for patients suffering from diseases of inflammation and autoimmunity," added Hollis. "HE3286 represents a potential medical breakthrough for those patients, and a significant commercial opportunity for Hollis-Eden Pharmaceuticals. The data presented this week, along with the previously presented positive data with HE3286 in other preclinical models of inflammation, demonstrate that this compound holds the potential to provide broad spectrum anti-inflammatory benefit in a variety of unmet medical needs. It is gratifying that our ongoing efforts to leverage our hormonal signaling technology platform, based on naturally occurring adrenal steroid hormones, continue to yield potential opportunities in each of our major programs - inflammatory diseases, metabolic disorders and cancer. We believe our investments in these programs are now strategically positioning us to create shareholder value as we rapidly advance our drug development pipeline into the clinic."
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.
Hollis-Eden Pharmaceuticals, Inc.
Scott Rieger, Director, Corporate Communications
Posted: October 2007