Isis Pharmaceuticals' Antisense Drug Normalizes Blood Glucose Levels In Diabetic Animals

First of Several Compounds in Isis' Metabolic Disease Program Advancing Toward

Clinic



Apr 02, 2001, 01:00 ET from Isis Pharmaceuticals

    CARLSBAD, Calif., April 2 /PRNewswire/ -- ISIS 113715, an antisense
 inhibitor of the PTP-1B gene, has produced significant therapeutic benefit in
 multiple animal models of diabetes by normalizing blood glucose and insulin
 levels.  Data were presented today at the 221st American Chemical Society
 (ACS) National Meeting in San Diego by Isis Pharmaceuticals (Nasdaq:   ISIP).
 Isis is developing ISIS 113715 as a treatment for Type 2 diabetes and plans to
 initiate Phase I clinical trials this year.  PTP-1B is a phosphatase that
 negatively regulates insulin receptor signaling and is an exciting gene target
 for diabetes that is actively being pursued by the industry.
     In studies in multiple rodent models of type 2 diabetes and obesity, ISIS
 113715 produced a dose-dependent reduction in blood glucose levels that
 resulted in normalization of glucose in the diseased animals.  These
 well-accepted models of diabetes are considered good predictors of efficacy in
 humans.  The dramatic decrease in blood glucose levels occurred with a once a
 week dosing regimen and was accompanied by reduced circulating insulin levels,
 indicating that the antisense inhibitor was acting as an insulin sensitizer.
 No hypoglycemia was observed in either the diabetic or normal mice at any of
 the doses studied.  In additional preclinical trials in primates, ISIS 113715
 reduced PTP-1B expression in key tissues known to be important in the
 regulation of glucose homeostasis.
     "The results of studies in multiple animal models supporting the activity
 of ISIS 113715 as a potential diabetes therapy are compelling," said Brett P.
 Monia, Ph.D., Isis' Vice President of Antisense Drug Discovery, who presented
 the data at ACS.  "We are particularly excited to have demonstrated
 antisense-dependent reduction of PTP-1B protein levels in primates.  Gene
 knock-down in primates is a key step on the way to human clinical trials,
 which we are planning to begin later this year."
     Dr. Monia also discussed Isis' approach to metabolic disease research,
 which employs Isis' GeneTrove(TM) technology to rapidly evaluate the role of
 individual genes in biological pathways and prioritize genes as drug targets
 using antisense technology.  To date in its metabolic disease program, Isis
 has evaluated more than 20 diabetes gene targets in animal models of disease
 and has prioritized the genes as drug targets based on in vivo data.  Isis
 scientists are actively pursuing several of the most promising leads that are
 showing activity similar to that of PTP-1B as potential drug targets.  Dr.
 Monia described an example of such data for PTEN, a novel target in the
 insulin signaling pathway, in his presentation today.
     Gene targets such as PTP-1B and PTEN, which are both phosphatases, have
 been challenging targets for traditional small molecule drugs because there
 are a number of closely related phosphatases that are difficult for small
 molecules to selectively discriminate.  Drugs with a high degree of
 specificity are needed to act selectively on one and not several phosphatases.
 Substantial data suggest that antisense drugs may be ideal tools to inhibit
 difficult targets like PTP-1B and other phosphatases, as they offer far
 greater selectivity than small molecules.
     Isis Pharmaceuticals, Inc. is exploiting its expertise in RNA to discover
 and develop novel human therapeutic drugs.  The company has commercialized its
 first product, Vitravene(TM) (fomivirsen), to treat CMV-induced retinitis in
 AIDS patients.  In addition, Isis has 11 products in its development pipeline,
 with two in late-stage development and four in Phase II human clinical trials.
 ISIS 3521, an inhibitor of PKC-alpha, is in Phase III trials for non-small
 cell lung cancer.  Isis is preparing to initiate a Phase III program for ISIS
 2302, an ICAM-1 inhibitor, in Crohn's disease.  Isis has a broad and
 proprietary patent estate of more than 700 issued and allowed patents
 worldwide.  Isis' GeneTrove(TM) division uses antisense to assist
 pharmaceutical industry partners in validating and prioritizing potential gene
 targets through customized services and access to an extensive gene function
 database.  Ibis Therapeutics(TM) is a division focused on the discovery of
 small molecule drugs that bind to RNA.
 
     This press release contains forward-looking statements concerning Isis'
 research and development efforts and functional genomics program.  Such
 statements are subject to certain risks and uncertainties, particularly those
 inherent in the process of discovering, developing and commercializing drugs
 that are safe and effective for use as human therapeutics and financing such
 activities.  Actual results could differ materially from those projected in
 this release.  As a result, the reader is cautioned not to rely on these
 forward-looking statements.  These and other risks concerning Isis' research
 and development programs are described in additional detail in Isis' Annual
 Report on Form 10K for the year ended December 31, 2000, which is on file with
 the U.S. Securities and Exchange Commission, copies of which are available
 from the company.
 
     Vitravene(TM) is a trademark of Ciba Vision, a Novartis company.
 GeneTrove(TM) and Ibis Therapeutics(TM) are trademarks of Isis
 Pharmaceuticals, Inc
 
 

SOURCE Isis Pharmaceuticals
    CARLSBAD, Calif., April 2 /PRNewswire/ -- ISIS 113715, an antisense
 inhibitor of the PTP-1B gene, has produced significant therapeutic benefit in
 multiple animal models of diabetes by normalizing blood glucose and insulin
 levels.  Data were presented today at the 221st American Chemical Society
 (ACS) National Meeting in San Diego by Isis Pharmaceuticals (Nasdaq:   ISIP).
 Isis is developing ISIS 113715 as a treatment for Type 2 diabetes and plans to
 initiate Phase I clinical trials this year.  PTP-1B is a phosphatase that
 negatively regulates insulin receptor signaling and is an exciting gene target
 for diabetes that is actively being pursued by the industry.
     In studies in multiple rodent models of type 2 diabetes and obesity, ISIS
 113715 produced a dose-dependent reduction in blood glucose levels that
 resulted in normalization of glucose in the diseased animals.  These
 well-accepted models of diabetes are considered good predictors of efficacy in
 humans.  The dramatic decrease in blood glucose levels occurred with a once a
 week dosing regimen and was accompanied by reduced circulating insulin levels,
 indicating that the antisense inhibitor was acting as an insulin sensitizer.
 No hypoglycemia was observed in either the diabetic or normal mice at any of
 the doses studied.  In additional preclinical trials in primates, ISIS 113715
 reduced PTP-1B expression in key tissues known to be important in the
 regulation of glucose homeostasis.
     "The results of studies in multiple animal models supporting the activity
 of ISIS 113715 as a potential diabetes therapy are compelling," said Brett P.
 Monia, Ph.D., Isis' Vice President of Antisense Drug Discovery, who presented
 the data at ACS.  "We are particularly excited to have demonstrated
 antisense-dependent reduction of PTP-1B protein levels in primates.  Gene
 knock-down in primates is a key step on the way to human clinical trials,
 which we are planning to begin later this year."
     Dr. Monia also discussed Isis' approach to metabolic disease research,
 which employs Isis' GeneTrove(TM) technology to rapidly evaluate the role of
 individual genes in biological pathways and prioritize genes as drug targets
 using antisense technology.  To date in its metabolic disease program, Isis
 has evaluated more than 20 diabetes gene targets in animal models of disease
 and has prioritized the genes as drug targets based on in vivo data.  Isis
 scientists are actively pursuing several of the most promising leads that are
 showing activity similar to that of PTP-1B as potential drug targets.  Dr.
 Monia described an example of such data for PTEN, a novel target in the
 insulin signaling pathway, in his presentation today.
     Gene targets such as PTP-1B and PTEN, which are both phosphatases, have
 been challenging targets for traditional small molecule drugs because there
 are a number of closely related phosphatases that are difficult for small
 molecules to selectively discriminate.  Drugs with a high degree of
 specificity are needed to act selectively on one and not several phosphatases.
 Substantial data suggest that antisense drugs may be ideal tools to inhibit
 difficult targets like PTP-1B and other phosphatases, as they offer far
 greater selectivity than small molecules.
     Isis Pharmaceuticals, Inc. is exploiting its expertise in RNA to discover
 and develop novel human therapeutic drugs.  The company has commercialized its
 first product, Vitravene(TM) (fomivirsen), to treat CMV-induced retinitis in
 AIDS patients.  In addition, Isis has 11 products in its development pipeline,
 with two in late-stage development and four in Phase II human clinical trials.
 ISIS 3521, an inhibitor of PKC-alpha, is in Phase III trials for non-small
 cell lung cancer.  Isis is preparing to initiate a Phase III program for ISIS
 2302, an ICAM-1 inhibitor, in Crohn's disease.  Isis has a broad and
 proprietary patent estate of more than 700 issued and allowed patents
 worldwide.  Isis' GeneTrove(TM) division uses antisense to assist
 pharmaceutical industry partners in validating and prioritizing potential gene
 targets through customized services and access to an extensive gene function
 database.  Ibis Therapeutics(TM) is a division focused on the discovery of
 small molecule drugs that bind to RNA.
 
     This press release contains forward-looking statements concerning Isis'
 research and development efforts and functional genomics program.  Such
 statements are subject to certain risks and uncertainties, particularly those
 inherent in the process of discovering, developing and commercializing drugs
 that are safe and effective for use as human therapeutics and financing such
 activities.  Actual results could differ materially from those projected in
 this release.  As a result, the reader is cautioned not to rely on these
 forward-looking statements.  These and other risks concerning Isis' research
 and development programs are described in additional detail in Isis' Annual
 Report on Form 10K for the year ended December 31, 2000, which is on file with
 the U.S. Securities and Exchange Commission, copies of which are available
 from the company.
 
     Vitravene(TM) is a trademark of Ciba Vision, a Novartis company.
 GeneTrove(TM) and Ibis Therapeutics(TM) are trademarks of Isis
 Pharmaceuticals, Inc
 
 SOURCE  Isis Pharmaceuticals