Diabetes/obesity
In January 2007, we announced a worldwide (except Japan) collaboration with Bristol-Myers Squibb Company (BMS) to develop and commercialise two investigational compounds discovered by BMS being studied for the treatment of Type 2 diabetes – saxagliptin and dapagliflozin. We will set the development and commercial strategy for the two compounds jointly with BMS.

Saxagliptin is being studied as a once-daily oral anti-diabetic to determine its efficacy and safety profile.

Saxagliptin was specifically designed to be a selective and durable inhibitor of the DPP-4 enzyme, which regulates hormones that control plasma glucose levels.
Phase III clinical trials to evaluate the efficacy and safety of saxagliptin are fully recruited.

We plan to file a regulatory application for saxagliptin in the US in the second quarter of 2008.

Results from a phase III trial were announced at the American Diabetes Association meeting in June 2007 and demonstrated that saxagliptin, when used as an add-on therapy to metformin, improved glycaemic control in adult patients with Type 2 diabetes, compared with the use of metformin alone, during 24 weeks of treatment.

Dapagliflozin is being studied as a once-daily oral anti-diabetic in the class of sodiumglucose contransporter 2 (SGLT2) inhibitors.

Dapagliflozin is a selective SGLT2 inhibitor, and has the potential to be first in this novel class of anti-diabetics. It is designed to be used both as monotherapy and in combination with other therapies for Type 2 diabetes.

Phase IIa data presented at the 2007 American Diabetes Association meeting demonstrated that administration of dapagliflozin reduced fasting serum glucose in patients with Type 2 diabetes when administered for 14 days alone or concomitantly with metformin.

In addition to saxagliptin and dapagliflozin, we have compounds in the area of diabetes and obesity in the cannabinoid receptor inhibitor class, as well as glucose kinase activating compounds in early patient testing.

Atherosclerosis/dyslipidaemia
In August 2007, we confirmed that the fixed dose combination treatment of Abbott’s next generation fenofibrate (ABT-335) and Crestor will progress into phase III development. The single pill would target all three major blood lipids: LDL-C ‘bad cholesterol’, HDL-C ‘good cholesterol’ and triglycerides.

In April 2007, we terminated our licensing and collaboration agreement with AtheroGenics, Inc. for AGI-1067. AGI-1067, an investigational anti-atherosclerotic agent, was studied in the ARISE phase III clinical outcomes trial involving more than 6,000 patients with coronary artery disease, but the trial failed to meet its primary endpoint.

Thrombosis
AZD6140 is the first reversible, oral, adenosine diphosphate (ADP) receptor antagonist. AZD6140 selectively and reversibly binds to the platelet receptor, in contrast to the irreversible binding seen with thienopyridines. The selective and reversible binding of AZD6140 means that platelet function recovers as drug plasma levels decline. AZD6140 is being developed to reduce the risk of thrombotic events in patients diagnosed with acute coronary syndromes (ACS). AZD6140 is currently being studied in the phase III PLATO clinical trial. This is a head-to-head outcomes study to determine if AZD6140 is superior to clopidogrel for reducing the risk of thrombotic events in patients with ACS. It is being conducted in over 40 countries at up to 1,000 investigational centres and will include approximately 18,000 ACS patients.

In anti-coagulation, our principal project is AZD0837, an oral, direct thrombin inhibitor in late phase II testing. An extended release formulation is being developed, giving the possibility to use once daily dosing without significant peak-trough variability, in other words reduced variability in anti-coagulation effect throughout the dosing interval.

Atrial fibrillation
Our lead compound is AZD1305, an atrial repolarisation-delaying agent, which has progressed into phase I testing in man.