Human Genome Sciences announces the discovery of a novel immune stimulant

Novel Protein Holds Potential to Enhance Body's Immune Response

Rockville, MD -- July 8, 1999 -- Human Genome Sciences, Inc. (NASDAQ: HGSI) announced today that it has discovered a novel immune stimulant that may have significant medical use for the treatment and prevention of infectious diseases, and may also contribute to the treatment of immune deficiency disorders. The discovery may also lead to new approaches to the treatment of certain types of leukemia and lymphoma. The immune stimulant, called B Lymphocyte Stimulator (BLyS), is a natural component of the immune system. The discovery and characterization of BLyS is described in the July 9, 1999 issue of Science magazine.

BLyS is a naturally occurring substance, a protein, made by the human body. It stimulates the production of high levels of antibodies by causing the antibody producing cells, called B cells, to grow and produce abundant antibodies. Antibodies act to protect the body from infections such as bacteria and viruses. People deficient for B cells are at high risk for infection.

BLyS may be a long sought missing link in the body's ability to protect itself from infection. For many years scientists have searched for substances that stimulate the growth of antibody producing cells. BLyS seems to be one of those substances. The discovery also helps to answer a well-known puzzle. It has been known that another type of immune cell, the monocyte, is involved in B cell stimulation and ultimately antibody production. The precise role of monocytes has been a mystery. The discovery that monocytes produce BLyS, a substance that stimulates B cell growth and activates antibody production, may be the answer to this long-standing riddle.

Full size image available through contact

Potential Medical Uses of BLyS

The potential medical uses of BLyS may include:

Treatment of Certain Immune Deficiency Syndromes
Patients undergoing treatment for organ transplantation or patients recovering from chemotherapy and bone marrow transplantation may often have low levels of antibodies as a result of low numbers of B cells. In such situations antibody deficiency may last from months to years. One potential medical use of BLyS would be to shorten the recovery time for such patients. Another potential use might be to stimulate B cell growth in AIDS patients deficient in B cell production.

Use as a Vaccine Adjuvant
Vaccines work, in part, by inducing the production of antibodies that recognize invading organisms. Used as a vaccine adjuvant, BLyS may enhance the effectiveness of a wide range of vaccine candidates by strengthening the immune response through its ability to stimulate B cell production.

Treatment of B Cell Leukemia and Lymphoma
The discovery of a new growth factor specific for B cells may also lead to new treatments for leukemias and lymphomas that arise from abnormal proliferation of B cells. BLyS interacts with a specific structure on the surface of B cells called a receptor. Drugs that interfere with binding of BLyS to this receptor may kill or at least slow the growth of B cell tumors.

The Discovery of BLyS
BLyS represents the successful application of a new systematic, multi-step approach to drug discovery pioneered by HGS scientists. The first step of this process was to isolate and characterize a virtually complete set of human genes. A task completed at HGS by the end of 1995. The second step was to prepare a subset of human genes, those involved in cell to cell communication for analysis of their potential medical use. Each of these genes is available at HGS as a cDNA capable of producing a full-length protein. The next step in the process was to develop a high throughput system to test the biological function and potential medical utility of each of these proteins. Such a system is now in place at HGS. BLyS, one of the body's signaling molecules was found to be a specific B cell stimulant in such tests. As an extension of this program, HGS scientists discovered and prepared the products of about 14,000 newly discovered human genes believed to be involved in cell to cell signaling. These proteins are currently being evaluated in high throughput screens designed to identify new drug candidates that address unmet medical needs.

"The discovery of BLyS and its potential medical application is a milestone for immunology and medicine," said William Haseltine, Ph.D., Chairman and Chief Executive Officer of Human Genome Sciences. "This discovery helps us to understand how the body fights infection and how vaccines work. It is our hope that we can rapidly apply this discovery to the development of new treatments for several serious immune deficiency diseases. We also hope that this discovery will help to overcome the barriers to the creation of successful vaccines for serious infectious disease problems, such as AIDS and Malaria."

Craig Rosen, Ph.D., Senior Vice President Research and Development of HGS said, "The discovery of BLyS represents an exciting application of the integrated set of new genomic technologies that we have developed at HGS over the past three years. We believe that many important new drugs will result from the systematic study of genes and proteins that control cell to cell communication. I am very pleased that our human gene discovery efforts, coupled with our high-throughput systems, resulted in the discovery of this missing component of the immune system. I view this success as validation of a new and fundamentally different approach to the discovery of medical uses of human genes."

The authors of the paper published by Science include: Paul A. Moore, Ph.D.; Ornella Belvedere, M.D.; Amy Orr; Krystyna Pieri; David W. LaFleur; Ping Feng, Ph.D.; Daniel Soppet, Ph.D.; Meghan Charters; Reiner L. Gentz, Ph.D.; David Parmelee, Ph.D.; Yuling Li; Olga Galperina; Judith G. Giri, Ph.D.; Viktor Roschke, Ph.D.; Bernadetta Nardelli, Ph.D.; Jeffrey Carrell; Svetlana Sosnovtseva; Wilbert Greenfield; Steven M. Ruben, Ph.D.; Henrik S. Olsen, Ph.D.; James Fikes, Ph.D.; and, David M. Hilbert, Ph.D., all of Human Genome Sciences, Inc.

The Role of B Cells in the Immune System
B lymphocytes are white blood cells that travel throughout the body. Without them, the immune system cannot function properly. Their primary function is to secrete soluble substances called antibodies in response to recognizing foreign cells or organisms. Anything that triggers this immune response is called an antigen. An antigen can be a germ, such as a virus or bacteria, or part of a virus. Tissues or cells from another person act as antigens, which is why transplanted tissues are rejected. In some situations, the immune system mistakes its own cells as antigens, which results in autoimmune disease, such as some forms of arthritis and diabetes. Each B lymphocyte produces one specific antibody. For instance, one B lymphocyte will make an antibody to block a virus that causes the common cold, while another produces an antibody that attacks a bacterium that causes pneumonia. When a B lymphocyte encounters its triggering antigen, it gives rise to many large cells known as plasma cells. Every plasma cell is essentially a factory for producing a unique antibody. Each of the plasma cells descended from a given B lymphocyte manufactures millions of identical antibody molecules and pours them into the bloodstream.

Antibodies belong to a family of large molecules known as immunoglobulins. Different types play different roles in the immune defense strategy. Immunoglobulin G, or IgG, works efficiently to coat microbes, speeding their uptake by other cells in the immune system. Immunoglobulin M is very effective in killing bacteria. Immunoglobulin A is concentrated in body fluids -- tears, saliva, the secretions of the respiratory tract and the digestive tract -- guarding the entrances to the body. Immunoglobulin E, whose natural job probably is to protect against parasite infections, is responsible for the symptoms of allergy.

When the immune system is missing one or more of its components, the result is an immunodeficiency disorder. These can be acquired through infection, inherited, or produced unintentionally by drugs such as those used to treat cancer or transplant patients, as well as a consequence of the aging process.

Temporary immune deficiencies can develop in the wake of common virus infections, including influenza, infectious mononucleosis and measles. Blood transfusions, surgery, malnutrition, and stress can also depress immune responses.

Human Genome Sciences is a company with the mission to develop products to predict, prevent, detect, treat and cure disease based on its leadership in the discovery and understanding of human and microbial genes.

HGS and Human Genome Sciences are registered trademarks of Human Genome Sciences, Inc. For additional information on Human Genome Sciences, Inc., visit the company's web site at www.hgsi.com.

Any statements released by Human Genome Sciences, Inc. that are forward looking are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Readers are cautioned that forward looking statements involve risks and uncertainties which may affect the company's business prospects and performance. These include economic, competitive, governmental, technological and other factors discussed in the company's filings with the Securities and Exchange Commission on forms 10-K, 10-Q and 8-K.

EDITORS' NOTE: For more information about HGS' program to discover cell to cell signaling molecules and high throughput functional genomics program, visit the HGS website and click on "Functional Genomics Program."