More MS news articles for Sep 2001

Hollis-Eden Presents Data Demonstrating HE2000 Regulates a Broad Array of Inflammatory Mediators Implicated in Disease Progression in HIV Patients

Findings Also Have Implications for Other Inflammatory Conditions

http://finance.individual.com/display_news.asp?doc_id=CT2001253p2286&page=news

September 10, 2001  8:05am
Source: PR Newswire

SAN DIEGO, Sep 10, 2001 /PRNewswire via COMTEX/ -- Hollis-Eden Pharmaceuticals, Inc. (Nasdaq: HEPH) today announced presentation of additional clinical results from its South African studies of investigational drug candidate HE2000, an immune regulating hormone (IRH). Highlights from the results demonstrate that HE2000 administered to HIV infected patients had a significant effect on multiple genes implicated in inflammation and immune suppression associated with HIV progression to AIDS, and in a variety of other diseases and conditions of immune dysregulation. The data were presented at the 2001 International Meeting of the Institute of Human Virology held September 9 to 13 in Baltimore, Maryland, and hosted by Robert C. Gallo, M.D.

The primary results presented were from a preliminary analysis through the first cycle of dosing of HE2000 administered subcutaneously as a monotherapy to HIV patients in South Africa. The study, conducted in 24 patients, compares to placebo two different doses of HE2000 administered once per day for five days every 6 weeks. Prior to dosing with HE2000, HIV patients had dramatically elevated transcript levels of inflammatory mediators including TNF alpha (11 fold increase), COX-2 (8 fold increase), IL-1 beta (10 fold increase) and IL-6 (43 fold increase) relative to healthy South African volunteers (p<0.001 for all changes). This indicated that these HIV infected patients were experiencing broad-based systemic inflammatory immune dysregulation before treatment with HE2000. After dosing with HE2000, these same patients experienced significant declines in transcripts for TNF alpha, COX-2, IL-1 beta and IL-6 as well as other inflammatory mediators. In the highest dose group, after 5 days of dosing the number of transcripts were reduced to levels close to those seen in healthy volunteers. The declines in each of these transcripts were statistically significant for both doses through the 35-day analysis period (p<=0.001).

A preliminary analysis of data from a subset of patients from a separate ongoing clinical study in South Africa with a buccal tablet formulation of HE2000 also showed before treatment similar increases in inflammatory mediators in HIV patients compared to healthy South African volunteers and that HE2000 treatment in this study was also able to decrease levels of these transcripts. In addition, a similar preliminary analysis from a clinical trial in late stage AIDS patients showed increases at baseline in a number of inflammatory mediators in these patients and that treatment with an intramuscular formulation of HE2000 reduced the number of these transcripts produced. A second cycle of dosing in these AIDS patients also appeared to produce significant decreases in inflammatory transcript numbers.

HE2000 treatment appears to be generally well tolerated. To date, serious drug related adverse events with HE2000 have been pain and swelling at the injection site in four patients with an intramuscular formulation of this compound. The subcutaneous and buccal formulations of HE2000 to date appear to be less irritating than the intramuscular formulation.

A number of studies in the medical literature have shown that increases in inflammatory cytokines such as TNF alpha, IL-1 beta, IL-6 and the enzyme COX-2 can lead to an increase in HIV viral replication and decreases in dendritic cells and hematopoiesis, which, in turn, lead to a progressive loss of innate and cell-mediated (Th1) immunity. It is this chronic inflammatory dysregulation and progressive loss of innate and cell-mediated immunity that is believed to ultimately lead to AIDS and the life threatening opportunistic infections, cancers, wasting and dementia that compromise the patient. By quieting down this rampant systemic inflammation, Hollis-Eden believes that immune regulating hormones have the potential to induce the immune system to mount appropriate innate and cell-mediated immune responses that will keep the virus in check and slow or prevent the progression to AIDS-related conditions.

Thus, rather than the traditional antiviral approach of directly attacking the virus, the goal of immune regulating hormone therapy is to increase the percentage of patients who are "long-term non-progressors" -- those who, while still having detectable viral load and potentially depressed CD4 count, remain clinically stable and avoid AIDS-defining conditions. Two differentiating factors between long-term non-progressors and rapid progressors are the ability of long-term non-progressors to continue to mount a strong Th1 response as well as the ability to continue producing sufficient quantities of specific types of dendritic cells (CD11c+ and CD123+ cells) that are known to be important in innate immunity. Hollis-Eden has previously shown that HE2000 can improve a number of markers of Th1 immunity and increase the number of both CD11c+ and CD123+ dendritic cells that are known to be depleted as a result of disease progression. These data now provide a further important mechanistic rationale for how HE2000 can achieve these effects, as systemic inflammation has been clearly linked in the medical literature to loss of Th1 immunity and dendritic cell numbers and function.

Chronic inflammatory dysregulation has also been linked to marrow suppression in HIV patients, particularly as it relates to neutrophils and platelets. Hollis-Eden has previously shown that intramuscular administration of HE2000 led to statistically significant increases in neutrophils and platelets in HIV patients. Data presented at this meeting showed that subcutaneous and buccal administration of HE2000 also lead to increases in neutrophils and platelets in HIV patients.

These findings have implications for the potential use of HE2000 and other immune regulating hormones in cancer therapy, where these blood elements can be critically suppressed as a result of radiation or chemotherapy. Published preclinical studies with Hollis-Eden's immune regulating hormones have demonstrated striking survival advantages in models of radiation-induced immune suppression. In addition to the effects on marrow suppression, increases in inflammatory mediators such as COX-2 have been linked to cancer progression, and Th1 immunity as well as both CD11c+ and CD123+ dendritic cells have been shown to be progressively depleted as cancer progresses. Studies with immune regulating hormones performed by the National Cancer Institute have also shown that these compounds are effective in preclinical models of cancer prevention.

The clinical data presented at this meeting also have potential implications for a wide variety of other indications associated with chronic inflammatory dysregulation. Drugs designed to inhibit a single inflammatory mediator have been shown in clinical trials to be effective agents in treating a variety of autoimmune conditions, including arthritis, inflammatory bowel disease and psoriasis. As an example, monoclonal antibody drugs which inhibit only TNF alpha are projected to generate sales in excess of $1 billion in 2001, and sales of drugs which inhibit only COX-2 are projected to approach $5 billion annually this year. As described above, immune regulating hormones appear to affect multiple mediators (including TNF alpha and COX-2) involved in the inflammatory cascade in patients with systemic inflammation, and appear to do so without causing immunosuppression, a problem with many current anti- inflammatory drugs. Immune regulating hormones have shown impressive preclinical activity in models of a number of autoimmune conditions including arthritis, lupus, inflammatory bowel disease and multiple sclerosis. Additional preclinical studies are currently being conducted and the Company anticipates conducting clinical studies in one or more of these conditions.

"Given that immune regulating hormones are chemical cousins of the corticosteroids that are used widely to treat a broad array of inflammatory conditions, it is perhaps not surprising that these compounds would retain many of the anti-inflammatory properties of corticosteroids," stated James Frincke Ph.D., Executive Vice President of Research and Development at Hollis- Eden. "What is really exciting about this finding is that immune regulating hormones may have the ability to achieve these effects while at the same time boosting Th1 immunity. In contrast, one of the hallmarks (and dose limiting side effects) of corticosteroid therapy is a shift toward Th2 immunity, which can result in immunosuppression. Thus we believe immune regulating hormones may be useful in conjunction with or instead of corticosteroids in most of the applications where corticosteroids are now being used."

"This new human clinical trial data, drawn from several ongoing studies, is a critical advance for the Company," stated Richard Hollis, Chairman and CEO of Hollis-Eden. "We believe these results provide an additional compelling scientific basis for further clinical studies not just in HIV, but also in a number of indications where immune dysregulation and systemic inflammation are present. The data suggest that we are affecting cytokines and enzymes that are known to be important drug targets in a number of diseases. The fact that we are regulating a number of these different inflammatory mediators in a physiologic way in humans is validating our scientific approach of using immune regulating hormones to correct the body's inability to mount an appropriate immune response to pathogenic infections and known diseases of immune dysregulation. This is particularly promising when combined with the extensive preclinical work indicating that immune regulating hormones provide significant functional benefit in models of a number of these same diseases. This data may also provide clear commercial pathways to conduct clinical trials with our drug candidates in several disease conditions. To this end, we are currently accelerating our other clinical programs and have recently added key scientists to our growing team of experts in cellular immunology and in diseases that result from immune dysregulation."

"At the same time, however, results with HE2000 in HIV patients indicate the compound has the potential to prevent or delay the loss of cell mediated immunity which leads to opportunistic infections and death. Therefore, it is a goal of the Company to provide a truly implementable world compound for HIV that is safe, efficacious, not prone to resistance, easy to use, and cost- effective for patients globally. We are excited to share this data with the medical and scientific communities. We will also aggressively present our data to health authorities around the world that are challenged with managing infectious disease epidemics and work with them in designing and conducting the further human clinical trials necessary to establish patient safety and benefit required for commercial approvals."

Background on the Immune System

The initial response to an infection is through the innate portion of the immune system. Innate immunity involves the non-specific antimicrobial response to newly encountered pathogens and is very important in fighting a variety of opportunistic infections. In addition to fighting off infections, innate immune responses activate the adaptive immune system. In healthy young adults, there are two types of adaptive immunity that exist in balance: Th1 type, or cell-mediated immunity, and Th2 type, or humoral immunity. The Th1 branch of the immune system is responsible for controlling intracellular invaders such as viruses and certain parasites, while Th2 immunity includes the humoral response necessary for controlling extracellular pathogens such as certain bacteria. Both types of immunity are critical to a well functioning immune system; however, the ability to mount a strong cell-mediated (Th1 type) response is frequently lost in patients suffering from chronic infectious diseases such as HIV. This loss of cell-mediated immunity and the rapid progression from HIV to AIDS is directly associated with the dysregulation of a number of Th2 and Th1 cytokines which are believed to be regulated by immune regulating hormones. Immune dysregulation is also seen in other infectious diseases and cancer as well as a number of autoimmune conditions.

Hollis-Eden Pharmaceuticals, Inc. is a development-stage pharmaceutical company based in San Diego, California, engaged in the development of products for the treatment of infectious diseases and immune systems disorders. The Company's vision is to become the world leader in immune regulating hormones and their application to numerous diseases. In addition to the other studies described above, Hollis-Eden is also conducting a Phase I/II clinical trial with HE2000 in the United States in HIV infected patients failing at least their second antiviral drug regimen. Phase II studies are also in the process of being initiated with HE2000 in the treatment of malaria in Thailand, and additional studies are planned in other conditions of immune dysregulation including hepatitis B and hepatitis C. The Company is also conducting a Phase I clinical trial in the United States with another of its immune regulating hormones, HE2200. In addition, through its relationship with Aeson Therapeutics, the Company also has access to HE2500, which is in Phase II clinical trials in cardiovascular disease and actinic keratosis. For more information on Hollis-Eden, contact the Company's website at http://www.holliseden.com.

Statements made in this press release may constitute forward-looking statements and are subject to numerous risks and uncertainties, including the failure to successfully complete clinical trials, the Company's future capital needs, the Company's ability to obtain additional funding and required regulatory approvals, 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. The actual results may differ materially from those contained in this press release.

SOURCE Hollis-Eden Pharmaceuticals, Inc.

CONTACT:    Dan Burgess of Hollis-Eden Pharmaceuticals, +1-858-587-9333, ext. 218

URL:              http://www.holliseden.com
 

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