Lead product candidate shown to be superior to rituximab in pre-clinical tests. Further candidate antibodies under evaluation.

Copenhagen, Denmark; October 28, 2002 - Genmab A/S (CSE: GEN and FSE: GE9D) announced today its new HuMax-CD20 program. Antibodies in this program target the CD20 antigen on B-cells and initially Genmab will focus on using the antibody for the treatment of Non Hodgkin’s Lymphoma (NHL), a cancer involving B-cells. Antibodies targeting CD20 also have the potential to treat illnesses such as Crohn’s disease, Wegener’s Granulomatosis, other B-cell lymphomas, including mantle cell lymphoma and autoimmune diseases such as rheumatoid arthritis.

The lead candidate antibody in the HuMax-CD20 program uses a similar mechanism of action to rituximab, currently considered an effective treatment for NHL. In laboratory tests and animal models, Genmab’s lead candidate in the HuMax-CD20 program was shown to be superior in binding to the disease target and is more efficient at inducing the killing of B-cell targets than rituximab. The antibody also activates complement-dependent cytotoxicity, a process which is believed to significantly contribute to the clearance of tumor cells by CD20 antibodies.

Other antibody candidates with an entirely different mechanism of action were also generated. This type of CD20 antibody induces apoptosis (or programmed cell death) of B-cell tumor cells more efficiently than rituximab-like antibodies. A final candidate will be chosen on the basis of efficacy in killing B-cell targets in animal disease models. Genmab aims to file an IND during 2003.

Professor Jan van de Winkel will present full data from laboratory studies and animal disease models in Genmab’s HuMax-CD20 program on February 7, 2003 at the Keystone Symposium ‘Antibody-based Therapeutics for Cancer’ in Banff, Alberta, Canada.

“The pre-clinical data is extremely encouraging in this program and particularly for our lead candidate, a rituximab-like antibody,” said Professor Jan van de Winkel, Chief Scientific Officer at Genmab. “This antibody appears far more efficient in a number of mechanisms. The Genmab antibody also appears to kill tumor cells that are resistant to rituximab”.

“The HuMax-CD20 program is an important part in Genmab’s strategy to focus on strong products to create a broad pipeline,” said Lisa N. Drakeman, Ph.D., Chief Executive Officer at Genmab. “The number of possible diseases where this antibody can be used means the market size for an antibody from the HuMax-CD20 program is potentially large.”

About the Models
Genmab tested its CD20 antibodies using biological assays which assessed the capacity of the antibodies to bind to tumor targets. Assays were also used to characterize their effects on tumor cell signaling and on the mechanism of tumor cytotoxicity. SCID mice (mice with deficient immune systems) engrafted with human B-cell tumors were used to evaluate the therapeutic capacity of the new antibodies in animal disease models.

About CD20
The CD20 antigen is a transmembrane protein on pre-B and mature B lymphocytes. CD20 appears to act as a calcium ion channel, and to regulate early steps in B lymphocyte activation. The molecule is not shed from the cell surface, and is not internalized upon antibody binding. CD20 is found on over 90 percent of B-cell lymphomas, as well as other lymphoid tumors of B cell origin.

About Non Hodgkin’s Lymphoma
Like all cancers NHLs are diseases of the body’s cells. Cells repair and reproduce themselves in the same way throughout the body, but if for some reason this process becomes out of control the cells continue to divide and develop into a lump or tumor. NHL are cancers of the lymphatic system. Lymphocytes are a type of white blood cell and are therefore part of the body’s immune system. They move around the body as part of their role in defending against infection and can also enter the bloodstream which carries them to various organs. NHL’s are also classified according to their cell type – effecting either B-cells or T-cells. A large number of NHLs are classified as B-cell NHLs.