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{\pard\sa900\fs50\f0\i Media Release\par}
{\pard\f0\li0\ri0\sa360\sl360\fs22 Basel, 18 July 2003 \line \line {\b Roche Researchers Discover Potential New Treatment for Type 2 Diabetes} \line Researchers Identify New Class of Drugs\par}
{\pard\f0\li0\ri0\sa360\sl360\fs22 Tomorrow\u8217?s issue of {\i Science}  reports that researchers at Roche have discovered a new class of drugs which, in preclinical studies, increase the efficiency of an enzyme critical to maintaining the normal balance of glucose in the body. This discovery represents a potential new treatment for the more than 135 million people who are afflicted with type 2 diabetes worldwide.\par}
{\pard\f0\li0\ri0\sa360\sl360\fs22 Patients with type II diabetes have too little insulin and produce too much glucose. \u8220?The glucokinase (GK) enzyme is the body\u8217?s first step in breaking down or metabolizing glucose,\u8221? explained Joseph Grippo, Ph.D., Roche vice president, Metabolic Diseases. \u8220?When the enzyme is functioning normally, GK helps the body maintain glucose levels by controlling the release of insulin from the pancreas as well as the disposal of glucose in the liver.\u8221? \par}
{\pard\f0\li0\ri0\sa360\sl360\fs22 Grippo and his team of scientists identified and developed a new class of drugs - called glucokinase activators (GKAs) - that increase the efficiency, or activate, this pivotal enzyme, and in doing so lowers blood sugar in preclinical models of type 2 diabetes.\par}
{\pard\f0\li0\ri0\sa360\sl360\fs22 He said the GKA compound is unique because it stimulates the pancreas to release more insulin and also keeps the liver from producing too much glucose. Currently many diabetic patients are given two medications to achieve this dual action: sulfonylureas and metformin. Both of these drugs were discovered over 25 years ago, and are still used as first-line anti-diabetes treatments. \par}
{\pard\f0\li0\ri0\sa360\sl360\fs22 \u8220?By being able to activate the GK enzyme, we may be able to provide a mechanism to improve both defects commonly found in type 2 diabetes, namely insulin release and hepatic [liver] glucose metabolism,\u8221? said Joseph Grimsby, Ph.D., Roche\u8217?s preclinical GKA project leader and primary author of the Science article, {\i Allosteric Activators of Glucokinase: Potential Role in Diabetes Therapy} .\par}
{\pard\f0\li0\ri0\sa360\sl360\fs22 \u8220?Roche\u8217?s discovery and preclinical findings support the important role GK plays as a glucose sensor and suggest that pharmacological activation of GK activity could have important clinical benefits in type 2 diabetes,\u8221? added Franz Matschinsky, M.D., of the Department of Biochemistry and Diabetes Center, University of Pennsylvania School of Medicine, and editor-in-chief of Diabetes. He also contributed to the {\i Science}  paper.\par}
{\pard\f0\li0\ri0\sa360\sl360\fs22 {\b Rationale} \line Roche\u8217?s interest in the GK enzyme followed a key discovery made in 1992 that showed a small subset of diabetes, known as maturity onset diabetes of the young type 2 (MODY2), is caused by mutations in the GK gene.\par}
{\pard\f0\li0\ri0\sa360\sl360\fs22 Preclinical findings provided strong biological rationale for considering GK as a target for drug discovery efforts. The Roche team screened 120,000 compounds and found one that seemed to activate GK. An important test with this early compound proved that GK activation works, giving the green light to move additional generations of GKA compounds through the Roche pipeline. \par}
{\pard\f0\li0\ri0\sa360\sl360\fs22 Even though there is much work ahead, confidence is strong that this new class of glucose activators could play an important role as hypoglycemic agents in the treatment of type 2 diabetes. Type 2 diabetes is such a huge unmet medical need. It is predicted that 300 million people will be diagnosed with this serious disease by 2025. \u8220?It is quite rare and very exciting to be involved in a drug with this kind of potential to dramatically impact the lives of patients,\u8221? added Grimsby.\par}
{\pard\f0\li0\ri0\sa360\sl360\fs22 \u8220?The GK enzyme is pivotal as a key controller of glucose homeostasis (balance) in all people, so being able to activate this natural control point has enormous potential for all patients with type 2 diabetes,\u8221? said Grippo.\par}
{\pard\f0\li0\ri0\sa360\sl360\fs22 {\b Roche Diabetes Care} \line Roche has a strong commitment to diabetes care, with products and services that help people better manage their disease, including a leading weight loss medication indicated for obese. Along with its breakthrough pharmaceutical research with the new class of GKA drugs, Roche has several other anti-diabetes medications in clinical trials. \line In addition, Roche Diagnostics is the global leader in diabetes care, and a pioneer in the development of blood glucose monitoring systems. With total annual sales of 2,511 million Swiss Francs and a growth rate of 14% in local currencies (2002), Roche Diabetes Care is the market leader in its segment. Its main products are the Accu-Chek\u8482? family of blood glucose meters and test strips, including Accu-Chek Compact, Accu-Chek Advantage and Accu-Chek Active. For more information on Roche Diagnostics, visit their website (http://www.roche.com/div_diag.htm).\par}
{\pard\f0\li0\ri0\sa360\sl360\fs22 {\b Roche Innovation} \line Roche\u8217?s commitment to innovation, research and development has been its key to scientific and commercial success for more than a century. To ensure we maintain a level of innovation, the company currently has a very strong development portfolio, which includes both Roche discoveries and compounds from our many alliance deals. In fact, Roche led the pharmaceutical industry in this area in 2002. Roche\u8217?s pipeline includes compounds to alleviate conditions such as arthritis, ovarian cancer, stress urinary incontinence, asthma, and depression, along with a host of other disease areas.\par}
{\pard\f0\li0\ri0\sa360\sl360\fs22 {\b About Roche} \line Headquartered in Basel, Switzerland, Roche is one of the world\u8217?s leading innovation-driven healthcare groups. Its core businesses are pharmaceuticals and diagnostics. Roche is number one in the global diagnostics market, the leading supplier of pharmaceuticals for cancer and a leader in virology and transplantation. As a supplier of products and services for the prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people\u8217?s health and quality of life. Roche employs roughly 62,000 people in 150 countries. The Group has alliances and R&D agreements with numerous partners, including majority ownership interests in Genentech and Chugai. \par}
{\pard\f0\li0\ri0\sa360\sl360\fs22 {\b Additional information:} \par}
{\pard\f0\li440\ri0\sl360\fs22 - Influencing the body\u8217?s regulatory mechanisms in order to treat type 2 diabetes ( http://www.roche.com/diabetes_in_transition.pdf)\par}
{\pard\f0\li440\ri0\sl360\fs22 - Roche Health Kiosk (http://www.health-kiosk.ch)\par}\line 

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{\pard\sb180\f1\fs22 {\b F. Hoffmann-La Roche Ltd}\line 4070 Basel\line Switzerland \par}
{\pard\sb180\f1\fs22 Corporate Communications\line Roche Group Media Relations \par}
{\pard\sb180\f1\fs22 Tel. +41 61 688 88 88\line Fax +41 61 688 27 75\line www.roche.com \par}
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