Hollis-Eden Pharmaceuticals Reports Initial Results in Phase I Clinical Trial of HE3286 as New Type II Diabetes TreatmentSAN DIEGO--(BUSINESS WIRE)--Jul 16, 2007 - Hollis-Eden Pharmaceuticals, Inc. (NASDAQ:HEPH) reported today that initial results from its ongoing single-dose Phase I study of HE3286 for the treatment of metabolic disorders demonstrate the compound is orally bioavailable in humans, with significant drug concentrations detected in the blood at the lowest dose tested. The Company's findings also show that all doses of HE3286 (10mg to 100mg) appear to be safe and well tolerated in healthy volunteers with no reported drug related adverse side effects to date. In addition the Company announced that certain of its preclinical data with HE3286 is being published by the New York Academy of Sciences. The published work demonstrates that HE3286, an orally bioavailable small molecule adrenal steroid hormone, produced a statistically significant reduction in disease in a rodent model of arthritis.
Hollis-Eden believes these initial results from the ongoing Phase I clinical study with HE3286, combined with continued positive data in animal models of autoimmune conditions, bodes well as the Company plans to file in the third quarter of 2007 an additional investigational new drug application (IND) with HE3286 for treating inflammatory conditions. A Phase I/II clinical trial of HE3286 is planned in rheumatoid arthritis patients for the fourth quarter of 2007, as is a separate multi-dose Phase I study of HE3286 for metabolic disorders under the Company's open IND.
The blood drug concentration profiles observed in the Phase I study thus far are consistent with drug levels in the blood associated with glycemic control and anti-inflammatory activity that the Company has observed in completed preclinical models of metabolic disorders and diseases of inflammation, respectively. HE3286 also appears to have a longer half-life in humans than in rodents (5-8 hours versus 2 hours, respectively). As reported in a forthcoming paper being published in Annals of The New York Academy of Sciences, the Company found that similar blood levels of HE3286 in rodents produced a statistically significant reduction of disease in a model of collagen-induced arthritis. Together, these data suggest the potency of HE3286 may be similar to other anti-inflammatory steroid hormone therapies but without the unwanted side effects. Dr. Halina Offner, Professor of Neuroimmunology at Oregon Health and Sciences University, conducted the work being published by The New York Academy of Sciences.
"These findings, along with additional data which we plan to present at the upcoming Second International Congress, Immune-Mediated Diseases: Better Living Through Immunology being held in Moscow, Russia September 10th through 15th, have convinced us that HE3286 may represent the first in a new class of anti-inflammatory smart steroids, addressing similar markets as the corticosteroids and NSAIDS, but without the serious side effects," stated Dr. Halina Offner. "These adrenal steroid hormones may provide the body's fundamental hormonal signal that regulates the stress/inflammatory response feedback loop. If HE3286 demonstrates both safety and efficacy in human clinical trials, then this molecule may represent a significant breakthrough in modern medicine to treat diseases associated with inflammation."
As reported in the paper, the reduction of arthritis in treated animals was attributed to a partial down regulation of NFkappaB, which significantly reduces key pro-inflammatory cytokines including TNF-alpha and Interleukin-6 without completely blocking them. Benefit was also associated with a doubling in the frequency of regulatory T cells. Regulatory T cells have been shown to play major roles in the control of all immune responses. Specifically, deficiencies in regulatory T cell activity are thought to play a crucial role in the development of many autoimmune diseases, including arthritis and multiple sclerosis. Histological analysis of joint tissue conducted at the end of the study indicated a marked reduction of tissue damage in the HE3286-treated animals compared to placebo.
HE3286 was also reported in the paper not to be immune suppressive in any of the classic models of immune suppression. Consequently, the Company believes HE3286 is unlike current corticosteroids or other down-regulators of NFkappaB, which can cause severe immune suppression and bone loss. The Company also believes HE3286 is unlike monoclonal antibodies to TNF-alpha that are associated with immune suppression, and which have been linked to causing opportunistic infections and even tumors. HE3286 does not appear to interact with any of the known nuclear hormone receptors, including the glucocorticoid receptor or any of the sex steroid receptors, suggesting a novel mechanism of action and an attractive safety profile.
"We are pleased that the interim Phase I study results have demonstrated HE3286 to be well tolerated at all dosing levels and that we were able to achieve pharmacologically relevant concentrations of HE3286 in the blood, even in subjects exposed to the lowest doses," said James M. Frincke, Chief Scientific Officer of Hollis-Eden Pharmaceuticals. "Additionally, this data is a gratifying outcome of five years of work in developing HE3286 through our own internal medicinal chemistry program. We believe this drug exposure profile in humans with an oral compound that has demonstrated remarkable efficacy in our preclinical animal models, reduces our risk and gives us increased confidence as we advance HE3286 toward Phase II trials aimed at demonstrating efficacy."
"Our scientific team is working diligently to bring our second generation drug candidates into human clinical trials," said Richard B. Hollis, Chairman and Chief Executive Officer of Hollis-Eden Pharmaceuticals. "Our major discoveries over the last several years in both animal models and human clinical studies have led us to a new generation of adrenal steroid hormones that may yield innovative, first-in-class pharmaceuticals. Research and development programs at Hollis-Eden are now focused on anti-inflammatory conditions, metabolic disorders, and cancer. Our investment in the research of the pharmacology and metabolism of this class of adrenal steroid hormones over the last five years has resulted in the optimization of our second generation pharmaceutical candidates such as HE3286. By improving the pharmacology of these compounds we have the potential to offer a new way to radically alter disease outcomes for improved patient care by hormonally controlling inflammatory immune responses. This has been our vision since the inception of our company, and we have been investing the necessary resources in these programs since 2001 to bring new drug candidates forward in multiple indications. New drug candidates like HE3286 represent the future of Hollis-Eden Pharmaceuticals, and position our company to create value for our shareholders in some of the largest medical markets in the world with unique pharmaceutical properties that if demonstrated in our human clinical trials, will enjoy competitive advantages in the marketplace and secure our goal of being the world leader in a new class of adrenal steroid hormones."
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 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. A second next-generation candidate, HE3235, has been selected for clinical development in 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 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: July 2007