Released on = January 30, 2006, 2:59 am

Press Release Author = La Merie Business Intelligence

Industry = Biotech

Press Release Summary = The complexity of glucose metabolism and the number of
cellular processes affected by diabetes provides ample space for new drug targets
and for first-in-class molecules. Some of them have reached or are close to early
clinical development in type 2 diabetes.

Press Release Body = The complexity of glucose metabolism and the number of cellular
processes affected by diabetes provides ample space for new drug targets and for
first-in-class molecules. Some of them have reached or are close to early clinical
development in type 2 diabetes. Roche pioneered and leads the field of glucokinase
activators with a phase I compound. Karo Bio has a first-in-class hepatic
glucocorticoid receptor antagonist which is in preclinical development. Bayer is
about to enter phase I in the first half of this year with Bay 76-7171 which has an
undisclosed novel mechanism of action. Sankyo and Metabasis reached clinical proof
of concept with its first-in-class fructose 1,6-bisphosphatase inhibitor. Leaders in
the arena of glycogen phsophorylase inhibitors are Pfizer and Sanofi-Aventis with
clinical stage projects. Isis is ahead in the field of protein tyrosine phosphatase
1B inhibitors with its 2nd generation antisense project. These results were found in
a search conducted by La Merie Business Intelligence. The results were published in
the January 30 issue of R&D Pipeline News, edited by La Merie Business Intelligence.

Glucokinase activators (GKA) enhance glucose-stimulated insulin release from
pancreatic islet cells and glucose disposition by the liver, thus reducing blood
glucose and reducing weight as shown by Innodia's ID1101 in phase I. The compound
had an excellent safety profile and now serves as an anti-obesity drug candidate.
The stimulation of insulin secretion by GKAs is glucose-dependent which should make
it less likely that GKAs cause hypoglycemia. Inhibition of glycogenolysis by
glycogen phosphorylase inhibitors (GPI) is another strategy to reduce blood glucose
and has attracted the interest of many companies with drug discovery activities. The
opposite approach is to inhibit gluconeogenesis by antagonizing the activity of
fructose 1,6-bisphosphatase. Sankyo's and Metabasis' CS-917 was shown to cause a
clinically significant reduction in blood glucose.

Protein tyrosine phosphatase 1B (PTP-1B) downregulates the insulin receptor.
Inhibition of PTP-1B should prevent downregulation of the insulin receptor, thus
improving insulin action. Isis showed clinically that its antisense compound could
induce insulin sensitizing activity in healthy volunteers. Results of 12-weeks
treatment of diabetes patients with ISIS 113715 are expected this year. Small
molecule PTP-1B inhibitors are in the pipeline, but do not lead the field after
failure of Wyeth's phase II compound. Further novel approaches include a beta3
adrenergic agonist in phase II, a phosphodiesterease 11A inhibitor and a dually
acting small molecule in preparation for phase I which increases insulin secretion
and peripheral insulin sensitivity.

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