Hollis-Eden Pharmaceuticals Commences Phase I/II Clinical Trial In Ulcerative Colitis With Novel Oral Anti-Inflammatory Drug Candidate TRIOLEX(TM)

Main Category: GastroIntestinal / Gastroenterology
Also Included In: Clinical Trials / Drug Trials
Article Date: 11 Feb 2008 - 2:00 PDT

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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, announced that it has commenced a Phase I/II clinical trial with its oral drug candidate TRIOLEX™ (HE3286) in ulcerative colitis (UC) under an Investigational New Drug application (IND) cleared by the U.S. Food and Drug Administration (FDA) for this indication. The Phase I/II dose ranging study will evaluate the safety, tolerance, pharmacokinetics and activity of TRIOLEX when administered orally for 28 days to patients with active, mild-to-moderate UC.

In previously reported data presented at the 3rd International Conference on Autoimmunity last October, TRIOLEX showed significant (p <0.05) benefit in the Wistar rat model of dinitrobenzene sulfonic acid (DNBS) induced colitis, a preclinical model widely used by industry and academia to test agents as potential treatments for UC. DNBS challenged rats with induced colitis were treated orally for seven days with either TRIOLEX or placebo (n=10 per group). At the end of the treatment period, TRIOLEX-treated animals had significantly reduced disease, as judged by reduced colon weight and reduced area of necrosis, compared to the placebo-treated animals.

TRIOLEX performed as well as or better than Sulfazalazine, the standard of care used as a positive control in this model.

TRIOLEX is a novel orally bio-available adrenal steroid hormone analogue with anti-inflammatory and insulin sensitizing properties currently in clinical trials under an open IND for the treatment of metabolic disorders. The Company has also been cleared under a separate IND with the FDA to begin clinical trials with TRIOLEX for the treatment of rheumatoid arthritis (RA). A safety and pharmacokinetic phase I/II clinical trial in stable RA patients on methotrexate, a commonly used chemotherapy treatment, is currently planned to begin in the second quarter of 2008. The Company believes that certain aspects of the pathology driving UC are similar to those driving RA. Therefore, data obtained in this UC study could potentially help support the design of the Company's planned Phase II RA clinical study and help to accelerate the development of TRIOLEX for potential use in patients with RA.

Hollis-Eden believes the broad-based anti-inflammatory activity of TRIOLEX may relate to a partial inhibition of the NF-kappaB pathway. NF-kappaB is a transcription factor that controls genes whose products are involved in the inflammatory signaling pathway, including TNF-alpha and IL-6. These cytokines are thought to be involved in the pathogenesis of certain autoimmune diseases such as UC and RA, and are also implicated in the pathogenesis of metabolic diseases, cardiovascular disorders, cancer and in general, diseases associated with aging. Unlike currently prescribed corticosteroids that act through the glucocorticoid receptor to completely block NF-kappaB activation and cause immune suppression and bone loss, preclinical models to date show that TRIOLEX does not interact with the glucocorticoid receptor and only results in a partial inhibition of the NF-kappaB pathway without immune suppression or bone loss.

The blood-drug concentration profiles observed in a previous Phase I study with TRIOLEX were consistent with drug levels in the blood associated with glycemic control and anti-inflammatory activity that the Company has observed in previously reported preclinical models of metabolic disorders and diseases of inflammation, respectively. TRIOLEX also appears to have a longer half-life in humans than in rodents (5-8 hours versus 2 hours, respectively).

"Given the rapid progression of the disease flares and the clearly defined clinical endpoints in UC, this study may potentially enable us to demonstrate activity in humans with a short treatment course of TRIOLEX in an acute inflammatory condition, and thereby accelerate its potential commercialization," said Richard B. Hollis, Chairman and CEO, Hollis-Eden Pharmaceuticals, Inc. "There are certain understood similarities between UC and RA disease processes, so the results from this UC trial should also enable us to optimize our Phase II clinical trial in RA. This strategy could enable the Company to demonstrate the safety and efficacy of TRIOLEX in acute and chronic inflammatory conditions, both of which are treated today with currently prescribed anti-inflammatory drugs."

Ulcerative colitis is a chronic inflammation of the large intestine, or colon, and 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 drugs 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.

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 TRIOLEX™ (HE3286), a next-generation compound currently in clinical trials for the treatment of metabolic disorders as well as ulcerative colitis and being prepared for clinical trials in rheumatoid arthritis under another IND, and APOPTONE™ (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 http://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.

Hollis-Eden Pharmaceuticals