First Phase II Short-Term Study on Dapagliflozin Shows Results on Safety, Tolerability and Glycemic Markers in Subjects With Type 2 Diabetes -- Additional Findings Reported on Glucose Homeostasis Effects in Normal and Diabetic Rats -- CHICAGO, June 25, 2007 -- In a 14-day, Phase IIa study of the safety profile of multiple doses of the investigational compound dapagliflozin, a selective inhibitor of the Sodium-Glucose Transporter 2 (SGLT2) administered alone or concomitantly with metformin in subjects with Type 2 diabetes, no discontinuations due to adverse events and no serious adverse events were reported. The study, presented this week at the annual meeting of the American Diabetes Association, also reported that dapagliflozin, in development by Bristol-Myers Squibb Company and AstraZeneca , statistically significantly reduced fasting serum glucose (FSG) and post challenge glucose excursion in subjects with Type 2 diabetes. The data were from a double-blind, placebo-controlled, randomized, parallel-group study of 47 subjects with an established diagnosis of Type 2 diabetes (ages 18-77) who were either drug-naive or on a stable dose of metformin for at least 4 weeks prior to randomization with hemoglobin A1C levels between 6 and 10 percent with a FSG of less than or equal to 240 mg/dL. Subjects were randomized to receive either placebo (n=8) or dapagliflozin 5 mg (n=11), 25 mg (n=12), or 100 mg (n=16) once daily for 14 days in addition to their stable metformin dose and/or diet alone in an in-patient clinical research unit. The primary endpoint of the study was to assess both the safety and tolerability profiles of multiple doses of dapagliflozin in subjects with Type 2 diabetes. The secondary endpoints of the study included assessing the fasting serum glucose and post challenge glucose excursion. The presentation, "Dapagliflozin, a Selective Inhibitor of the Sodium-Glucose Uptake Transporter 2 (SGLT2), Reduces Fasting Serum Glucose and Glucose Excursion in Type 2 Diabetes Mellitus Patients Over 14 Days", was presented by Bernard Komoroski, PharmD, Ph.D., Senior Research Investigator, Bristol-Myers Squibb. On Day 13, the FSG was significantly reduced in participants receiving dapagliflozin with or without metformin as compared to their FSG levels two days prior to first dose: -14.5 percent (p-value less than 0.05), -17.3 percent (p-value less than 0.05), -21.9 percent (p-value less than 0.001) for dapagliflozin at 5 mg, 25 mg and 100 mg, respectively. FSG was reduced by -6.3 percent in participants receiving placebo with or without metformin. There were no discontinuations due to adverse events and no serious adverse events were reported. Adverse events included two events of hypoglycemia in subjects receiving dapagliflozin co-administered with metformin. There were two events of vulvovaginal infection in the study (one subject receiving dapagliflozin alone and one subject receiving dapagliflozin+metformin). Adverse events occurred with similar frequency in subjects receiving dapagliflozin or placebo. The most frequently reported adverse events were: constipation (n=7; 1/19 on dapagliflozin+metformin, 3/20 on dapagliflozin alone, 2/6 on placebo+metformin, 1/2 on placebo alone), nausea (n=5; 4/19 on dapagliflozin+metformin, 1/6 on placebo+metformin), and diarrhea (n=4; 3/19 on dapagliflozin+metformin, 1/6 on placebo+metformin). Preclinical Data Also Presented at 2007 American Diabetes Association Annual Meeting In a second presentation this week - "Dapagliflozin, A Selective SGLT2 Inhibitor, Improves Glucose Homeostasis in Normal and Diabetic Rats" by Jean Whaley, Sc.D., Director, Diabetes Drug Discovery, Bristol-Myers Squibb, the effect of dapagliflozin on glucose homeostasis in normal and diabetic rats was reported. In diabetic rats, dapagliflozin acutely induced renal glucose excretion at doses ranging from 0.01-1.0 mg/kg of body weight without inducing hypoglycemia. Additionally, as early as two hours after a single oral dose, there was a statistically significant reduction in plasma glucose levels in diabetic rats treated with dapagliflozin compared to untreated diabetic rats at doses of 0.1 mg/kg and 1.0 mg/kg (-101 mg/dL and -128 mg/dL), respectively (p-value less than 0.0001 at both doses). About Type 2 Diabetes Type 2 diabetes is the most common form of diabetes, accounting for approximately 90-95 percent of diabetes cases. Having Type 2 diabetes increases the risk of many serious complications, including heart disease or stroke, high blood pressure, amputation (particularly legs), blindness, nerve damage, and kidney failure. The risk of stroke and the rate of deaths due to heart disease are two to four times higher among people with diabetes, and about 65 percent of deaths among people with diabetes are due to heart disease and stroke. The A1C test (also known as hemoglobin A1C) is used primarily to monitor the glucose control of diabetics over time. The goal of those with diabetes is to keep their blood glucose levels as close to normal as possible. This helps to minimize the complications caused by chronically elevated glucose levels, such as progressive damage to body organs like the kidneys, eyes, cardiovascular system, and nerves. The A1C test gives a picture of the average amount of glucose in the blood over the last few months. It can help a patient and his doctor know if the measures they are taking to control the patient's diabetes are successful or need to be adjusted. About Dapagliflozin Dapagliflozin (previously referred to as BMS-512148) is an investigational drug under development by Bristol-Myers Squibb and AstraZeneca. It is being studied as a once-daily oral antidiabetic. The compound has a novel proposed mechanism of action, selectively inhibiting sodium glucose cotransporter 2 (SGLT2) versus SGLT1, decreasing reabsorption of glucose by the kidneys without affecting SGLT1 in the GI tract. Dapagliflozin has a C-glucoside chemical structure, which prolongs the pharmacokinetic half-life and duration of action. Dapagliflozin is currently in Phase IIb development. About SGLT2 Inhibitors Glucose is normally filtered by the kidney, but nearly all of it is reabsorbed in the proximal tubule by SGLT2, which is located almost exclusively in the kidney. For patients with diabetes, retention of excess glucose by this pathway contributes to persistent high blood glucose levels, or hyperglycemia. Inhibiting SGLT2 activity modulates reabsorption of glucose in the kidney, resulting in excretion of glucose in the urine. Research, in animal models, indicates that modulation of renal glucose absorption with SGLT2 inhibition reduces blood glucose independent of insulin secretion or action. Bristol-Myers Squibb and AstraZeneca Partnership In January 2007, Bristol-Myers Squibb and AstraZeneca entered into a collaboration to develop and commercialize saxagliptin and dapagliflozin, two compounds under investigation by Bristol-Myers Squibb for the treatment of diabetes. Both companies will jointly set development and commercial strategy for the two compounds. AstraZeneca will provide funding for the majority of currently planned development activities; additional development activity will be funded equally. About Bristol-Myers Squibb Bristol-Myers Squibb is a global pharmaceutical and related healthcare products company whose mission is to extend and enhance human life. Bristol-Myers Squibb Forward-Looking Statement This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995, regarding the development and commercialization of products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the development of the products described in this release will be successful, that the products described in this release will receive regulatory approval, or that if approved, will be commercially successful. Forward-looking statements in the press release should be evaluated together with the many uncertainties that affect Bristol- Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2006, its Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. About AstraZeneca AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the world's leading pharmaceutical companies with healthcare sales of $26.47 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index. In the United States, AstraZeneca is a $12.44 billion healthcare business with more than 12,000 employees. For nearly three decades, AstraZeneca has offered drug assistance programs side by side with its medicines, and over the past five years, has provided over $3 billion in savings to more than 1 million patients throughout the US and Puerto Rico. AstraZeneca has been named one of the "100 Best Companies for Working Mothers" by Working Mother magazine and is the only large pharmaceutical company named to FORTUNE magazine's 2007 list of "100 Best Companies to Work For." In 2006, for the fifth consecutive year, Science magazine named AstraZeneca a "Top Employer" on its ranking of the world's most respected biopharmaceutical employers.