Genmab A/S - Company Announcement: Novel Insights into HuMax-EGFr Mechanisms of Action Publish... ( COPENHAGEN April 15 /- Summary: G...)

Genmab A/S - Company Announcement: Novel Insights into HuMax-EGFr Mechanisms of Action Published in PNAS

Date:4/15/2008

COPENHAGEN, April 15 /PRNewswire-FirstCall/ -- Summary: Genmab has announced that HuMax-EGFr (zalutumumab) inhibits epidermal growth factor receptor signaling by locking epidermal growth factor receptor (EGFr) molecules into a very compact, inactive conformation. The flexibility of the EGFr is central to its role in signaling, and binding of HuMax-EGFr (zalutumumab) results in effective inhibition of cancer cell growth.

Genmab A/S (OMX: GEN) announced today new insights showing that HuMax-EGFr(TM) (zalutumumab) locks epidermal growth factor receptor (EGFr) molecules into a very compact, inactive conformation. The flexibility of the EGFr is central to its role in signaling, and binding of HuMax-EGFr (zalutumumab) results in effective inhibition of cancer cell growth.

As EGFr activity plays an important role in many cancers, targeting it with HuMax-EGFr (zalutumumab) should make it especially difficult for cancer cells to grow, multiply, and survive.

By using an electron microscope based technique, called protein tomography, the structural rearrangement accompanying inhibition of individual EGFr molecules was studied. Biochemical analyses showed that HuMax-EGFr binds bivalently to the EGFr and, furthermore, was shown to prevent receptor dimerization and to severely limit intermolecular flexibility of EGFr molecules.

"These new insights point out that HuMax-EGFr may employ at least three distinct mechanisms of action leading to inhibition of cancer cell growth. HuMax-EGFr is able to induce potent immune system defense activity known as ADCC, block growth factor binding to EGF receptors, and we now established that HuMax-EGFr inhibits EGFR activation by limiting receptor flexibility. This new data further underlines the potential of HuMax-EGFr for treatment of solid cancers." said Lisa N. Drakeman, Ph.D., Chief Executive Officer of Genmab.

These new findings will be published in the journal Proceedings of the National Academy of
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