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Hollis-Eden Reports Update on Autoimmunity Program with Triolex (HE3286) at International Autoimmunity Meeting

SAN DIEGO--(BUSINESS WIRE)--Sep 12, 2008 - Hollis-Eden Pharmaceuticals, Inc. (NASDAQ:HEPH) today presented data from the Company's autoimmunity program with its investigational drug candidate TRIOLEX(TM) (HE3286) at the 6th International Congress on Autoimmunity, held in Porto, Portugal, September 10th to the 14th. Dr. Christopher L. Reading, Chief Scientific Officer at Hollis-Eden Pharmaceuticals and Dr. Dominick L. Auci, Director of Allergy, Autoimmunity and Inflammation, presented the data during a dedicated plenary session. Hollis-Eden conducted the session to further inform the scientific community on the potential role of the Company's new class of adrenal steroid hormones in autoimmune and other inflammatory disorders. Data presented included positive findings generated to date from extensive research in preclinical models of numerous autoimmune conditions, as well as preliminary findings from the Company's ongoing Phase I/II dose ranging clinical trial with TRIOLEX in patients with active, mild-to-moderate ulcerative colitis (UC).

Positive Preclinical Data With TRIOLEX in Models of Autoimmune Conditions

Dr. Reading summarized data, previously reported, demonstrating a number of benefits with TRIOLEX in various preclinical models of autoimmune disease. In three distinct animal models of acute inflammation (collagen-induced arthritis, experimental pleurisy and lung injury), decreased disease scores were accompanied by reduced neutrophil tissue infiltration. Likewise, in two models of chronic autoimmune inflammation (lupus erythematosus and multiple sclerosis), disease scores were reduced after treatment with TRIOLEX compared to vehicle controls. Finally, in a widely accepted mouse model of autoimmune diabetes (NOD mice), which emulates human type 1 diabetes, TRIOLEX was found to decrease the incidence of conversion to active disease over time.

These widespread anti-inflammatory effects are also thought to provide en explanation for the previously reported benefit observed in four models of metabolic disease (diabetic db/db mice, genetically obese ob/ob mice, diet-induced obese, insulin resistant mice and Zucker diabetic rats) in which inflammation is a key element in the loss of insulin sensitivity leading to dysregulated glucose homeostasis. In these animal models, TRIOLEX was shown to improve insulin sensitivity and glucose tolerance, whereas in vitro, the drug was shown to attenuate (but not obliterate) the activity of key signaling pathways involved in the inflammatory response. These pathways include the master regulator protein NF-kappaB and certain enzymes of the mitogen-activated protein kinase family such as JNK and p38, which have been implicated in the inflammation-induced impairment of insulin signaling and insulin resistance. Consistent with this paradigm, previously reported interim data from an ongoing Phase I/II clinical trial in obese, insulin resistant subjects, in which treatment with TRIOLEX resulted in enhanced insulin sensitivity demonstrated in glucose clamp studies while abating pro-inflammatory cytokine production, lend further credence to the core hypothesis that the multiple therapeutic effects of TRIOLEX stem primarily from its anti-inflammatory properties.

Importantly, these anti-inflammatory actions of TRIOLEX preclinically were not associated with the typical immune suppressive side effects of glucocorticoids (e.g. dexamethasone) as demonstrated in specific preclinical models of immune suppression (mouse delayed type hypersensitivity; mouse lymphocyte mitogen induced proliferation; mouse immunization; and mouse antibody production). In addition, treatment with TRIOLEX in these preclinical models was not accompanied by bone loss, a commonly observed side effect with corticosteroids, and in fact, a positive change in bone mass balance was found.

Potential Mechanism For TRIOLEX

Dr. Reading also presented data demonstrating that TRIOLEX regulates the activation of NF-kappaB in vitro and in vivo. 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 rheumatoid arthritis (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 only results in a partial inhibition of the NF-kappaB pathway without immune suppression or bone loss because it does not interact with the glucocorticoid receptor.

TRIOLEX Demonstrates Activity in Model of Type 1 Diabetes

In a separate oral presentation, Dr. Auci showed preclinical data demonstrating benefit of TRIOLEX in a murine model of type 1 diabetes, or autoimmune diabetes. Treatment of 15-week old female NOD mice with TRIOLEX significantly reduced the incidence of disease over a 10-week period. These studies were conducted by Dr. Ferdinando Nicoletti at the University of Catania, Italy and confirmed by Dr. Michelle Kosiewicz at the University of Louisville, Kentucky. These findings are encouraging because few therapeutic agents provide benefit when given so late in the course of this spontaneous model of autoimmune diabetes. Dr. Auci also presented additional safety data demonstrating that 14-day oral treatment with even high doses of TRIOLEX did not impair survival or immune function in mice subsequently challenged with a lethal bacterial infection. On the contrary, animals given TRIOLEX showed reduced weight loss and slightly improved survival following bacterial challenge. These observations are consistent with the Company's previously published work demonstrating to date that preclinically TRIOLEX acts as an anti-inflammatory agent but is not immune suppressive. Taken together, the data from both UC and type 1 diabetes suggest a mechanism for TRIOLEX involving active induction of the resolution phase of inflammation as opposed to the highly immune suppressive action of corticosteroids, NSAIDS and biologics that reduce inflammation by blocking its induction phase.

"In addition to the continued success TRIOLEX therapy has demonstrated in models of autoimmune disease, it was exciting to see that TRIOLEX was active in this well characterized animal model of type 1 diabetes," stated Dr. Reading. "This bodes well as we are also employing the anti-inflammatory activity of TRIOLEX to target metabolic disorders such as type 2 diabetes. Last June we reported at a corporate symposium held in conjunction with the annual meeting of the American Diabetes Association positive interim data with TRIOLEX from our ongoing Phase I/II clinical trial in healthy obese insulin resistant subjects. Our phase II clinical trial with TRIOLEX in patients with type 2 diabetes is currently enrolling subjects and we hope to be able to report an interim analysis from that study before the end of the year or early in the first quarter of 2009."

TRIOLEX Clinical Trial Programs Underway

Given the extensive positive preclinical data generated to date with TRIOLEX in a variety of animal models of autoimmune and metabolic disorders, Hollis-Eden has initiated clinical trials with TRIOLEX in type 2 diabetes, ulcerative colitis and rheumatoid arthritis. As mentioned above, interim data has been reported from the ongoing Phase I/II clinical trial in obese, insulin resistant subjects, and enrollment has begun in the Phase II 90-day type 2 diabetes clinical trial as well as in the Phase I/II rheumatoid arthritis trial.

Regarding the Company's ongoing dose ranging clinical trial with TRIOLEX in mild-to-moderate ulcerative colitis (defined as a baseline ulcerative colitis activity score, or Mayo physician's score, greater than or equal to 6 and less than or equal to 12). Dr. Reading reported at the Porto meeting preliminary findings from an initial set of five patients. Of the five patients, three were treated with the lowest dose of TRIOLEX (5 mg. administered once daily for 28 days), and two received placebo. TRIOLEX was safe and well tolerated in the treated patients through 42 days of observation. Dr. Reading reported at the meeting that the information received to date from this trial indicated there was a clinical response in one of the three TRIOLEX-treated subjects, where the Mayo score was improved from a baseline score of 9 to a score of 2 by the end of the dosing period. There was no clinical improvement observed in the two placebo-treated patients. In addition to the improved Mayo score in the patient that appeared to benefit from treatment, endoscopic analysis before and after treatment showed a substantial improvement in the ulceration and inflammatory condition of the mucosal tissue in the patient's colon. In addition, in this patient evidence of decreases in serum and cellular inflammatory cytokines was also observed. The patient also had an elevated TSH (thyroid-stimulating hormone) level, indicating hypothyroidism. Autoimmune (Hashimoto's) thyroiditis was confirmed by elevated antibodies to thyroglobulin and thyroperoxidase. The TSH level dropped to within normal levels by day 15 and remained low through day 56.

Hollis-Eden is continuing to enroll patients in its Phase I/II UC clinical trial to include additional dosing levels. The initial cohort of nine patients receiving either 5 mg. of TRIOLEX administered once daily, or placebo, is expected to be fully enrolled by the end of September. The second cohort of patients receiving either 5 mg. of TRIOLEX administered twice daily, or placebo, is expected to commence in October.

Added Dr. Reading: "In our dose ranging study with TRIOLEX in UC patients, TRIOLEX appears to be safe and well tolerated to date at the initial dose level, which is consistent with the favorable safety findings we have seen in our previously reported interim Phase I/II study results with the compound in obese, insulin resistant subjects. While our findings in the UC trial are too preliminary to draw any specific conclusions regarding activity, we find the response in one patient treated at the lowest dose level, where a significant improvement in Mayo score and substantial improvement in the condition of the mucosal tissue in the colon was observed, to be striking. We are also encouraged by the evidence in that patient of decreases in serum and cellular inflammatory cytokines, again consistent with our findings with TRIOLEX in obese, insulin resistant subjects. These observations, coupled with the extensive preclinical data we have generated to date in multiple animal models of autoimmune disorders, are encouraging."

"Data presented at this conference represent a body of scientific accomplishments demonstrating in preclinical models that TRIOLEX is a novel molecule with unique signaling capabilities that regulates unproductive inflammation without causing immune suppression and serious side effects associated with other commonly prescribed anti-inflammatories," stated Richard Hollis, Chairman and CEO of Hollis-Eden Pharmaceuticals. "TRIOLEX is a synthetic drug candidate modified from a naturally occurring hormone derived from the adrenal glands that we believe is the body's natural signaling molecule to maintain stress inflammatory basal homeostatic set points. We are now in several clinical trial programs with the goal of demonstrating the utility of this novel molecule as a potent regulator of inflammation without the side effects associated with current therapies, and to provide a safer drug to treat multiple diseases related to inflammation and metabolic diseases. TRIOLEX, one of many DHEA metabolites and analogs we have under development in our pipeline, potentially represents a breakthrough therapy that may, if successfully developed, offer medicine a new and safer alternative to manage both acute and chronic unproductive inflammation, which is the root cause of so many diseases, and diseases related to the aging process itself. In our current and future clinical trials we hope to confirm our scientific hypothesis that the value of DHEA, the most abundant circulating steroid hormone in the body, is not DHEA itself, but rather its metabolic conversions of downstream metabolites which are the active chemical messengers that can be utilized to treat and prevent maladaptive inflammatory conditions that are associated with modern human diseases."

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(TM) (HE3286), a next-generation compound currently in clinical trials for the treatment of type 2 diabetes ulcerative colitis and rheumatoid arthritis, and APOPTONE(TM) (HE3235), a next-generation compound in a clinical trial for 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

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 and APOPTONE compared to other treatment approaches, how TRIOLEX and APOPTONE are believed to work and their respective potential for use in the targeted indications. 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 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, clinical trials, and drug development and commercialization including, but not limited to: the outcome of final analysis of data from the Company's phase I/II clinical trial of TRIOLEX in healthy obese insulin resistant subjects once it is completed may vary from the Company's initial analysis, and the FDA may not agree with the Company's interpretation of such results; whether the preliminary findings from the initial set of five patients in the Company's ongoing dose ranging clinical trial with TRIOLEX in mild-to-moderate ulcerative colitis reported at this meeting will be predictive of later results from this trial as the Company continues to enroll patients and add additional dosing levels to the trial; 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 or APOPTONE 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 the indications the Company is targeting, 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 investigational 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.


Hollis-Eden Pharmaceuticals, Inc.
Scott Rieger, Vice President, Corporate Communications

Posted: September 2008