University of California San Diego Researchers Present Preclinical Data Demonstrating Benefits of Triolex (HE3286) in Model of Obesity Induced Metabolic Disorders

SAN DIEGO--(BUSINESS WIRE)--Jan 26, 2009 - Hollis-Eden Pharmaceuticals, Inc. (NASDAQ:HEPH) today announced that researchers from the Department of Medicine, University of California San Diego (UCSD), presented preclinical data demonstrating that the Company's oral drug candidate TRIOLEX™ (HE3286) exhibited anti-diabetic, anti-inflammatory and cholesterol lowering properties in Zucker Diabetic Fatty (ZDF) rats, a commonly used preclinical model of diabetes. TRIOLEX is a proprietary pharmaceutical drug candidate derived from a naturally occurring hormone. The findings were presented by UCSD researchers Min Lu, Ph.D., David A. Patsouris, Ph.D., and Jerrold M. Olefsky, M.D., at the Type 2 Diabetes and Insulin Resistance Keystone Symposia Meeting held January 21st through January 25th, in Banff, Alberta.

“Based on our findings, these results provide additional strong support to the proposal that TRIOLEX is a novel compound that may serve as a viable drug candidate for treatment of obesity-related metabolic disorders,” stated Dr. Olefsky, Associate Dean for Scientific Affairs and Professor of Medicine, Division of Endocrinology and Metabolism, UCSD School of Medicine.

In the ZDF model, animals typically exhibit hyperphagic behavior (overeating) due to a genetic lesion, causing them to become obese, which over time contributes to progressive deterioration of glucose homeostasis resulting from insulin resistance and defective beta-cell function. In the data presented, treatment of ZDF rats with TRIOLEX was associated with complete normalization of fasting and fed blood glucose levels throughout the study. Glucose tolerance tests demonstrated that insulin sensitivity was improved by treatment with TRIOLEX as indicated by markedly blunted blood glucose elevation after an oral glucose load. In addition, TRIOLEX reduced the concentration of pyruvate and glycerol in the blood, two important precursor molecules that the liver normally utilizes to make more glucose, a process called gluconeogenesis. Since excessive glucose production by the liver is a major contributor to fasting hyperglycemia in the diabetic state, the observation that TRIOLEX blocks hepatic glucose output in ZDF rats provides an additional piece of information to understand the physiological mechanism of action of the compound. In these animals, there was also a decrease in the concentration of free fatty acids in the blood after treatment with TRIOLEX, which when considered together with the observed reduction in glycerol levels, suggests that TRIOLEX may suppress excessive lipolysis in adipose tissue, an effect consistent with a drug-induced improvement in insulin sensitivity in fat tissue.

In addition to these beneficial effects of TRIOLEX on glucose homeostasis, liver cholesterol and triglyceride content was also reduced after drug treatment, causing the activation of a physiological feedback loop whereby the expression levels of the LDL receptor are elevated, thereby facilitating cholesterol uptake by the liver. Accordingly, treatment with TRIOLEX caused a marked decrease in total serum cholesterol. Previously reported preclinical work in vitro and in other animal models had indicated that TRIOLEX attenuates proinflammatory pathways in macrophages, leading to the hypothesis that TRIOLEX improves insulin action as a result of an anti-inflammatory effect that reduces the negative impact of obesity-induced inflammation on insulin signaling. Consistent with this hypothesis, treatment of ZDF rats with TRIOLEX down-regulates expression of a number of cytokines and other inflammatory effectors in liver and adipose tissue, including MCP-1, which is involved in macrophage infiltration in fat. Accordingly, TRIOLEX reduced the degree of macrophage infiltration in adipose tissue, which is consistent with an anti-inflammatory effect that curbs the contribution that macrophage inflammatory pathways are thought to have in causing insulin resistance.

Hollis-Eden is currently conducting a Phase II clinical trial with TRIOLEX in type 2 diabetes patients. The Phase II, double-blinded placebo controlled 12-week dosing trial has enrolled approximately 90 patients who are stable on metformin treatment only, the current first-line therapy for type 2 diabetes, with a hemoglobin A1c (HbA1c) level in excess of 7.5 percent. The primary endpoints for the trial are safety and a reduction in HbA1c. Hollis-Eden plans to release data from this trial in the first half of 2009.

Type 2 Diabetes Market

There are approximately 20 million Americans and over 160 million people worldwide with type 2 diabetes. As a result of an aging population and a rise in obesity rates, a common risk factor in this disease, the prevalence of type 2 diabetes is increasing rapidly. Included among the therapeutic approaches to type 2 diabetes are drugs designed to increase insulin production by the pancreas, drugs to reduce glucose production by the liver, and drugs to increase the body's sensitivity to insulin, thereby improving glucose disposal by the blood stream. The global annual sales of oral anti-diabetic drugs exceed $11 billion annually. Of these insulin sensitizers, Avandia® and Actos® represent the largest class of oral anti-diabetic agents, currently garnering over $5 billion in worldwide sales annually. However, patient control of glucose levels remains a large unmet medical need as 64% of this patient population fails to achieve optimal glucose levels. Furthermore, now that it is increasingly understood that inflammation is at the root cause of insulin resistance, there is a need to address inflammation in type 2 diabetes.

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 the treatment of 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 and the benefits to be derived therefrom including the potential advantages of TRIOLEX compared to other treatment approaches, how TRIOLEX is believed to work and its potential for use in the treatment of type 2 diabetes. The inclusion of forward-looking statements should not be regarded as a representation by the Company that any of its plans will be achieved. 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 outcome of final analysis of data from the Company's phase I/II clinical trial of TRIOLEX once it is completed may vary from the Company's initial analysis and findings, and the FDA may not agree with the Company's interpretation of such results; the ability to complete preclinical and clinical trials successfully and within specified timelines, if at all; the risks and uncertainties inherent in clinical trials, and drug development and commercialization, including the uncertainty of whether results in clinical testing of TRIOLEX to date will be predictive of results in later stages of development; 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 obtain and protect its intellectual property rights and to not infringe the intellectual property rights of others; the development of competitive products by other companies, the market potential for type 2 diabetes, and the Company's ability to compete; 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. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All forward-looking statements are qualified in their entirety by this cautionary statement. 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. None of the Company's drug candidates has been approved for sale, significant additional animal and human testing is required in order to seek marketing approval for any of its drug candidates, and the Company cannot assure you that marketing approval can be obtained for any of its drug candidates or that, even if such marketing approval were received, such drug candidates would ultimately achieve commercial success. Furthermore, as is typically the case at this stage of the regulatory review process, the FDA has not yet performed an in-depth review of the Company's preclinical and clinical data, so its views remain subject to change.

 

 

 

Contact: Hollis-Eden Pharmaceuticals, Inc.
Scott Rieger, Vice President, Corporate Communications, 858-587-9333

 

 

Posted: January 2009

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