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Re: 20 Years in the Future
May 18, 2003

Progenics Discovers First Liver-specific Receptor for Hepatitis C Virus

Scientists from Progenics Pharmaceuticals may have solved a longstanding riddle concerning hepatitis C disease: How does HCV target the liver for infection?

Researchers today reported discovering the first-ever liver-specific receptor, called L-SIGN, for hepatitis C virus (HCV). The company also reported the identification of specific inhibitors, including a monoclonal antibody, which blocked HCV from binding to the L-SIGN receptor.

Preventing HCV from binding L-SIGN on liver cells represents a new and targeted strategy for treating this serious disease. The studies are reported in a paper published today in the Proceedings of the National Academy of Sciences USA. The publication is scheduled to be available online this week in the PNAS Early Edition.

"In recent years, various cellular receptors for HCV have been proposed, but until now, none had been found that occurred specifically in the liver and was capable of binding with HCV," said the paper's senior author William C. Olson, Ph.D., Progenics' Vice President of Research and Development.

"As we reported in today's PNAS article, L-SIGN efficiently binds and captures naturally occurring hepatitis C virus particles. We further demonstrated that L-SIGN binds to a viral protein called E2 that is present on the surface of the HCV particle. L-SIGN is found on specialized liver cells. These cells are the first to contact HCV as it enters the liver via the bloodstream.

Thus, L-SIGN is uniquely positioned to capture blood-borne virus and concentrate it in the liver, thereby potentially facilitating initial and subsequent rounds of infection."

HCV infection afflicts nearly 3% of the world's population and causes serious liver disease, including cirrhosis and cancer. No vaccine is available to prevent new infections. Current therapies are largely non-specific, effective in only about half of all cases, and have a high relapse rate. New treatment strategies are urgently needed to combat this debilitating disease.

The research further demonstrated that HCV bound to a related receptor, known as DC-SIGN, that is expressed on dendritic cells, which are specialized cells of the immune system. L-SIGN and DC-SIGN are also expressed in placental tissue, and thus the findings may also explain why HCV is readily passed from mothers to their newborn children."

"Our previous discoveries of the cellular receptors utilized by HIV have translated directly into novel therapeutic agents, and we are eager to leverage this expertise for HCV therapy," added Dr. Olson.

"We have shown that HCV binding to L-SIGN can be blocked in the laboratory using specific inhibitors, including monoclonal antibodies. In addition, HCV appears to bind L-SIGN at a site different from that of its natural ligand (ICAM-3), which is a protein that mediates adhesion between cells.

"Thus, it may be possible to block HCV without blocking the natural activity of L-SIGN. These findings provide proof-of-concept for targeted therapy. Our current goals are to develop increasingly potent and drug-like inhibitors while concurrently exploring the role of L-SIGN in natural infection."

About Progenics

Progenics Pharmaceuticals, Inc. of Tarrytown, NY, is a biopharmaceutical company focusing on the development and commercialization of innovative therapeutic products to treat the unmet medical needs of patients with debilitating conditions and life-threatening diseases.

The Company applies its expertise in immunology and molecular biology to develop biopharmaceuticals to fight viral diseases, such as human immunodeficiency virus (HIV) infection, and cancers, including malignant melanoma and prostate cancer. In symptom management and supportive care, therapies are being developed to provide patients with an improved quality of life. Progenics' most clinically advanced product is methylnaltrexone, a compound in phase-3 clinical testing that is designed to block the debilitating side effects of opioid analgesics without interfering with pain palliation.

The Company is conducting multi-dose phase-2 clinical trials with its lead HIV product, PRO 542, a viral-entry inhibitor and is in preclinical development with PRO 140 and other follow-on product candidates in HIV infection. The Company is developing cancer immunotherapies based on PSMA (prostate-specific membrane antigen) technology and currently is conducting phase-1 clinical studies of a therapeutic prostate cancer vaccine. GMK is a cancer vaccine in phase-3 clinical trials for the treatment of malignant melanoma.

This letter was written by a drug company
attempting to get people to invest in there stock.

This info is flawed. One item that stands out is the reference to "HCV readily passed to children". This is an extreme exaggeration. Less than one percent pass the virus to children and this is almost always because of blood transfer during birth.

The items discussed are pointed to the liver and only the liver.

HCV uses the pancreas as an alternate breeding ground and most likely many other sites. This info was known in 1994. This company is really reaching.

Your immune system is your best bet.

15 to 20% of all people with hep c do not develop chronic liver disease (CDC) because there immune system fights off the disease. Most of the rest of us can do this at least enough to regain our health by boosting our immune system.

My statement has not been reviewed by the FDA
Lloyd Wright


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