Hollis-Eden Pharmaceuticals Presents Positive Updated Data from ...

Tag : Pharmaceuticals
Hollis-Eden Pharmaceuticals, Inc. (NASDAQ:HEPH) today presentedadditional positive interim data from its on-going Phase I/IIclinical trial with its investigational oral drug candidateTRIOLEX(TM) (HE3286) in obese insulin resistant subjects at the 6thWorld Congress on Insulin Resistance Syndrome, being held September25th - 27th in Los Angeles, California. Dr. Jaime Flores-Riveros,Vice President, Endocrinology and Metabolism at Hollis-EdenPharmaceuticals, presented the data.

The additional data extend findings previously reported in acorporate symposium held in conjunction with the 68th ScientificSessions of the American Diabetes Association demonstrating thatTRIOLEX is safe and well tolerated to date, and that itsignificantly improved insulin sensitivity and lowered fastingblood glucose and insulin levels in obese insulin resistantsubjects treated orally with 5 or 10 milligrams of the compoundadministered twice daily for 28 days, as compared toplacebo-treated subjects.

Dr. Flores-Riveros presented additional data showing that insulinresistant subjects (as defined by a physiological index of glucosedisposal or M-value less than 5), displayed a significantlyexacerbated inflammatory response characterized by higher levels ofthe pro-inflammatory cytokines MCP-1, TNF-alpha, IL-6 and IL-1betaproduced in LPS stimulated peripheral blood mononuclear cells(PBMC) from these patients. In contrast to more insulin sensitivesubjects (M greater than 5), treatment of these insulin resistantsubjects (M less than 5) with TRIOLEX was associated with apositive trend towards lowering these inflammatory cytokines, whichin turn was accompanied by signs of glucose lowering in the samesubjects.

Dr. Flores-Riveros also presented new data showing thatretinol-binding protein 4 (RBP4), a protein secreted by fat cellsthat is associated with insulin resistance, was markedly decreasedin the insulin resistant subjects (M less than 5) treated withTRIOLEX compared to placebo-treated subjects. In addition,C-reactive protein (CRP) was significantly decreased in the insulinresistant subjects (M less than 5) compared to placebo-treatedsubjects (p = 0.018). CRP is a well-known serum marker ofinflammation, which has been linked to cardiovascular risk.

"The findings to date from this on-going clinical trial suggestingthat initial serum CRP and levels of MCP-1, TNF-alpha, IL-6 andIL-1beta secreted by PBMC are elevated in insulin resistantsubjects provide further rationale for the belief that insulinresistance is closely linked with inflammation," stated WilliamCefalu, M.D., of Pennington Biomedical Research Center in BatonRouge, Louisiana. "The trend observed to date in this on-goingstudy that TRIOLEX appears to decrease these elevated inflammatorymarkers, as well as the previously reported interim data showingthat TRIOLEX significantly improved insulin sensitivity in thesesubjects when compared to placebo-treated subjects, lend supportfor the continued clinical development of TRIOLEX. If successfullydeveloped, TRIOLEX has the potential to be an anti-inflammatorypharmaceutical that may provide benefit in type 2 diabetes withoutthe side effects associated with the current glitazone class ofinsulin sensitizing agents as well as potentially providing benefitfor diabetes-associated cardiovascular events."

TRIOLEX may represent a novel, first-in-class insulin sensitizerthat Hollis-Eden believes acts by modulating inflammatory pathways.Leading academic researchers have linked inflammation and type 2diabetes, reporting that chronic, subclinical inflammation canresult in impaired insulin signaling by a variety of mechanisms.The involvement of inflammation through this pathway in causinginsulin resistance and type 2 diabetes is well described in thescientific literature. In addition, activation of NF-kappaB due toinflammatory mediators or oxidative stress leads to a feed forwardcycle of increased production of inflammatory cytokines such asMCP-1, TNF-alpha, IL-6 and IL-1beta.

The therapeutic approach inherent in Hollis-Eden's drug candidateis to restore the biological activity of cellular signalingpathways disrupted by disease and aging. In the setting of type 2diabetes, the Company believes that the mechanism of action forTRIOLEX may be the regulation of the NF-kappaB pathway and otherproinflammatory pathways, particularly when these are stimulatedthrough the TLR4 receptor. TLR4 is a receptor expressed on the cellsurface of macrophages and other cells that is stimulated bycertain pathogens such as bacteria and viruses or certain chemicalssuch as dietary fatty acids. Upon stimulation of the TLR4 receptor,a cascade of proinflammatory kinases that include IKK, JNK and p38is activated, setting off a complex network of signaling pathways,which culminate with the activation of NF-kappaB and a number ofgenes involved in the inflammatory and cell stress response. Basedon experiments conducted to date, TRIOLEX appears to actindependently of the PPAR-gamma pathway and down regulatesproinflammatory kinases JNK, IKK and p38, which have beenassociated with impairment of the insulin receptor substrate-1protein (IRS-1) function, an important cellular mediator of insulinsignaling, ultimately causing inappropriate insulin action. Sincethis mechanism for improving insulin sensitivity does not seem tooccur primarily through the PPAR-gamma pathway, TRIOLEX may avoidthe side effects associated with the current glitazone class ofinsulin sensitizing agents, such as Avandia(R) and Actos(R), whichwork through PPAR-gamma. Side effects reported to date with theglitazone class of drugs include weight gain, edema and increasedcardiovascular events. To date, experiments in vitro have shown noevidence that TRIOLEX directly binds and/or transactivates thePPAR-gamma receptor. Unlike the glitazones, TRIOLEX does not causebody weight gain when administered to mice or rats.

Added Richard Hollis, Chairman and CEO of Hollis-EdenPharmaceuticals, "Data presented today by Dr. Flores-Riveros atthis World Congress on Insulin Resistance Syndrome is relevant toour goal of developing a novel, first-in-class insulin sensitizeraddressing the role of inflammation in driving insulin resistance.We believe this data is exciting because it may reflect theinherent ability of TRIOLEX to down regulate specific inflammatorysignaling pathways that are thought to impair insulin signalingwhen chronically stimulated. We are also examining several otherparameters known to be dysregulated as part of the metabolicsyndrome, which includes both triglycerides and cholesterol. IfTRIOLEX is successfully developed, we believe that the ability toregulate both glucose homeostasis and inflammation may result in abetter and safer insulin sensitizer and make a significantadvancement in the treatment of type 2 diabetes as well aspotentially be beneficial in mitigating the serious consequencesassociated with uncontrolled inflammation in cardiovasculardisease. A new generation of novel steroid hormones that regulateinflammation without serious side-effects could have multiplemedical uses and could offer medicine the ability to better manageimmune-mediated diseases."

Type 2 Diabetes Market

There are approximately 20 million Americans and over 160 millionpeople worldwide with type 2 diabetes. As a result of an agingpopulation and a rise in obesity rates, a common risk factor inthis disease, the prevalence of type 2 diabetes is increasingrapidly. Included among the therapeutic approaches to type 2diabetes are drugs designed to increase insulin production by thepancreas, drugs to reduce glucose production by the liver, anddrugs to increase the body's sensitivity to insulin, therebyimproving glucose disposal by the blood stream. The global annualsales of oral anti-diabetic drugs exceed $11 billion annually. Ofthese insulin sensitizers, Avandia(R) and Actos(R) represent thelargest class of oral anti-diabetic agents, currently garneringover $5 billion in worldwide sales annually. However, patientcontrol 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 thatinflammation is at the root cause of insulin resistance, there is aneed to address inflammation in type 2 diabetes.

About Hollis-Eden Pharmaceuticals, Inc.

Hollis-Eden Pharmaceuticals, Inc. is a world leader in thedevelopment of a proprietary class of adrenal steroid hormones asnovel pharmaceuticals for human health. Through its HormonalSignaling Technology Platform, Hollis-Eden is developing a newseries of small molecule compounds that are metabolites orsynthetic analogs of endogenous hormones derived by the adrenalglands from the body's most abundant circulating adrenal steroid.These steroid hormones, designed to restore the biological activityof cellular signaling pathways disrupted by disease and aging, havebeen demonstrated in humans to possess several properties withpotential therapeutic benefit -- they regulate innate and adaptiveimmunity, reduce nonproductive inflammation and stimulate cellproliferation. The Company's clinical drug development candidatesinclude TRIOLEX (HE3286), a next-generation compound currently inclinical trials for the treatment of type 2 diabetes and ulcerativecolitis and being prepared for clinical trials in rheumatoidarthritis, and APOPTONE(TM) (HE3235), a next-generation compoundselected for clinical development for cancer. In addition to theseclinical development candidates, Hollis-Eden has an active researchprogram that is generating additional new clinical leads that arebeing further evaluated in preclinical models of a number ofdifferent diseases. For more information on Hollis-Eden, visit theCompany's website at www.holliseden.com.

This press release contains forward-looking statements within themeaning of the federal securities laws concerning, among otherthings, the potential and prospects of the Company's drug discoveryprogram and its drug candidates and the benefits to be derivedtherefrom including the potential advantages of TRIOLEX compared toother treatment approaches, how TRIOLEX is believed to work and itspotential for use in the treatment of type 2 diabetes. Theinclusion of forward-looking statements should not be regarded as arepresentation by the Company that any of its plans will beachieved. Any statement included in this press release that are nota description of historical facts are forward-looking statementsthat involve risks, uncertainties, assumptions and other factorswhich, if they do not materialize or prove correct, could cause theCompany's actual results to differ materially from historicalresults or those expressed or implied by such forward-lookingstatements. Such statements are subject to certain risks anduncertainties inherent in the Company's business, including, butnot limited to: the outcome of final analysis of data from theCompany's phase I/II clinical trial of TRIOLEX once it is completedmay vary from the Company's initial analysis and findings, and theFDA may not agree with the Company's interpretation of suchresults; the ability to complete preclinical and clinical trialssuccessfully and within specified timelines, if at all; the risksand uncertainties inherent in clinical trials, and drug developmentand commercialization, including the uncertainty of whether resultsin clinical testing of TRIOLEX to date will be predictive ofresults in later stages of development; the ability to obtainregulatory approval for TRIOLEX (HE3286), APOPTONE (HE3235) or anyother investigational drug candidate; the Company's future capitalneeds; the Company's ability to obtain additional funding; theability of the Company to obtain and protect its intellectualproperty rights and to not infringe the intellectual propertyrights of others; the development of competitive products by othercompanies, the market potential for type 2 diabetes, and theCompany's ability to compete; and other risks detailed from time totime in the Company's filings with the Securities and ExchangeCommission. Existing and prospective investors are cautioned not toplace undue reliance on these forward-looking statements, whichspeak only as of the date of this press release. This caution ismade under the safe harbor provisions of the Private SecuritiesLitigation Reform Act of 1995. All forward-looking statements arequalified in their entirety by this cautionary statement. Except asrequired by law, the Company undertakes no obligation to update orrevise the information contained in this press release as a resultof new information, future events or circumstances arising afterthe date of this press release. None of the Company's drugcandidates has been approved for sale, significant additionalanimal and human testing is required in order to seek marketingapproval for any of its drug candidates, and the Company cannotassure you that marketing approval can be obtained for any of itsdrug candidates or that, even if such marketing approval werereceived, such drug candidates would ultimately achieve commercialsuccess. Furthermore, as is typically the case at this stage of theregulatory review process, the FDA has not yet performed anin-depth review of the Company's preclinical and clinical data, soits views remain subject to change.