deCODE genetics Announces Third Quarter 2008 Financi...(ed. First and second generation PDE4 inh...)

cilomilast, and roflumilast caused significant side effects, including

nausea and vomiting, at therapeutic doses in human clinical trials.

Data generated at deCODE suggest that the observed side effects were

closely correlated with the binding of these molecules in the PDE4

enzymatic active site competitively with cAMP. As cAMP is of critical

importance to neuronal signaling, the goal of deCODE's program has been

to discover compounds that would modulate PDE4 activity via an

allosteric mechanism to improve safety and tolerability. Towards this

goal, the decode biostructures team solved multiple novel co-crystal

structures of PDE4D & PDE4B containing regulatory domains with bound

ligands. Those structures allowed the deCODE chemistry team to identify

a novel binding site for allosteric modulators in the PDE4 regulatory

domain. In animal models, DG071 has been shown to significantly improve

learning and long- and short-term memory at doses that offer a wide

margin for safety and tolerability.

- deCODE Breast Cancer. In October, deCODE launched deCODE

BreastCancer(TM), the company's latest DNA-based disease risk test, for

assessing individual risk of the common forms of breast cancer and

personalizing screening and treatment strategies. The seven markers

measured by the test, discovered by deCODE and others, contribute to

the incidence of an estimated 60 percent of all breast cancers. The

test integrates data from discovery and replication studies published

in major peer-reviewed journals and involving nearly 100,000 breast

cancer patients and healthy volunteers from many populations. The test

can identify the roughly 5 percent of women who are at a greater than

20 percent lifetime risk of the common
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