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Isis Adds New Drug to Its Development Pipeline: ISIS 388626 Targeting SGLT2 for the Treatment of Type 2 Diabetes
Date:10/18/2007

one marrow and spleen, so selecting targets in these tissues is part of our strategy for developing effective drugs. We plan to move ISIS 388626 forward toward human proof-of-concept as rapidly as possible, and we look forward to continuing to populate our metabolic disease pipeline with drugs arising from our prolific research program."

ABOUT SGLT2 AND ISIS 388626

The sodium dependent glucose transporter type 2 (SGLT2) is substantially responsible for glucose re-absorption in the kidney. Decreasing SGLT2 function promotes glucose excretion to help reduce blood sugar levels, making it an attractive target for the treatment of diabetes. In preclinical studies, Isis has demonstrated in several animal species that ISIS 388626 and other antisense inhibitors of SGLT2 effectively reduce target mRNA levels, increase urinary glucose excretion and consequently lower blood glucose levels and HbA1c without causing dangerously low levels of blood sugar known as hypoglycemia. This is consistent with expectations based on human subjects who have mutations in the SGLT2 gene and have increased urine glucose levels but are otherwise asymptomatic. ISIS 388626 effectively and specifically inhibits the production of SGLT2 in the kidney tissue, without having any effect on a related gene product, SGLT1. In addition to being Isis' first second-generation antisense drug for a kidney target, ISIS 388626 is also unique due to its 12 nucleotide length rather than the more typical 18 - 21 nucleotide sequences that comprise Isis' other drugs. This attribute simplifies manufacturing and has the potential to substantially reduce related expenses. The short sequence may also contribute to ISIS 388626's unusually high potency; it is among the most potent antisense drugs Isis has yet evaluated in preclinical models.

ABOUT ISIS PHARMACEUTICALS, INC.

Isis is exploiting its expertise in RNA to discover and develop novel drugs for its product pipeline and for its partners. The C
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SOURCE Isis Pharmaceuticals, Inc.
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