By Randall Osborne

West Coast Editor

Human Genome Sciences Inc. (HGS) found "bliss" last summer, and the discovery is starting to pay off now - not only with a therapeutic protein, but with a monoclonal antibody and a radiolabeled drug candidate as well.

HGS, having gained access to phage display tools from Cambridge Antibody Technology (CAT), said it's entering an exclusive development partnership with the England-based firm to work on the target B-lymphocyte stimulator, known as BLyS and pronounced "bliss."

Discovered by HGS, BLyS is a naturally occurring stimulator of antibodies, and is the focus of a radiolabeled-pharmaceutical agreement with Dow Chemical Co., disclosed Monday with the CAT deal.

"[BLyS] is not going to be the last of these examples," said William Haseltine, chairman and CEO of Rockville, Md.-based HGS. "It's a question that can be asked again and again: If you find a potential growth hormone, as we did with BLyS, what happens if people make too much, if it's over-produced?"

The answer is that disease can happen, Haseltine said. At the American College of Rheumatology's annual meeting Monday, HGS researchers presented data showing high levels of BLyS are involved in rheumatoid arthritis and erythematosus lupus.

"We developed a diagnostic test [to measure BLyS levels] that may be a product in its own right," Haseltine said, adding that BLyS may play a role in other autoimmune and neoplastic disorders, too.

Under the terms of the latest deal with CAT, the latter gets an up-front fee and potential milestones and royalties. Further details were not disclosed. HGS first teamed up with CAT in August 1999, and BLyS was the first protein to be jointly studied. The deal was broadened to the tune of $67 million in March, for the phage display capability to make fully human monoclonal antibodies. (See BioWorld Today, March 2, 2000.)

HGS and CAT have isolated more than 10,000 antibody clones specific to BLyS and characterized more than 1,000 distinct human antibodies. HGS will select one of the candidates for clinical trials.

"We're hopeful it will happen in the second half of next year," Haseltine said.

With Dow, of Midland, Mich., HGS will work on a drug to treat B-cell malignancies, combining BLyS with Dow's bifunctional chelation agents. The plan is to attach radioactive metals to the protein for deadly conditions such as lymphocytic leukemia, multiple myeloma and non-Hodgkin's lymphoma. Terms were not disclosed.

"It's reasonably typical of the arrangements Dow makes with other companies," Haseltine said, but it's different insofar as it involves a new method, devised by HGS, of pairing the protein with the radioactive metal.

The method is "generally applicable to other proteins," Haseltine said, adding that the patent for it has not been published yet.

Since BLyS interacts only with receptors on the surface of B cells, the radiolabeled molecule would carry the therapeutic agent to B-cell tumors, bypassing other cell types. As described by HGS scientists, the protein works like interleukin-2, but without the disadvantages. (See BioWorld Today, July 13, 1999.)

Early stage clinical trials are evaluating the safety of BLyS in patients with common variable immunodeficiency, also known as CVID, characterized by inadequate production of antibodies and thus increased susceptibility to infection.

"We spent about $250 million on new technology last year," Haseltine said. "It's beginning to show in the range of products we're bringing forward."

He called BLyS "a triumph of genomic science in itself," noting that progress was made quickly in the research.

"We looked for something to stimulate the immune system," he said. "From the time we started looking to the time we had a clinical candidate was about 18 months."

Finding a gene, and then developing from the protein a monoclonal antibody and finally making a radiolabeled drug, as HGS intends to do with BLyS, is a sequence likely to repeat, Haseltine said.

"It's possible for either double or triple hits," he said.

The company's stock (NASDAQ:HGSI) closed Monday at $82.875, down $5.25.

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