LOS ANGELES and NEW YORK, May 24 /PRNewswire/ -- Intercept Pharmaceuticals, Inc., a clinical stage biopharmaceutical company focused on developing small molecule drugs for the treatment of chronic liver and metabolic diseases, today reported that researchers affiliated with the company presented data at the Digestive Disease Week annual meeting highlighting the role of the farnesoid X bile acid receptor (FXR) in inflammatory bowel disease. Intercept's lead FXR agonist, INT-747, is in Phase 1 clinical trials to treat liver damage caused by fibrosis and cholestasis in chronic liver disease. These new data suggest that INT-747 may also have therapeutic utility in inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis.
In a plenary session address, Intercept co-founder and University of Perugia researcher Dr. Stefano Fiorucci presented the results of studies demonstrating the role of FXR in the intestine in modulating the expression of genes involved in inflammation and fibrosis. The researchers showed that FXR knockout mice develop spontaneous inflammation and fibrosis in the colon, along with an increase in the severity of colitis generated in response to an inflammatory stimulus. They also demonstrated that FXR activation by INT-747 prevents the development of intestinal inflammation and fibrosis in IBD mouse models. Dr. Fiorucci and his colleagues concluded that agents activating FXR, such as INT-747, may have utility in the treatment of chronic inflammatory and fibrotic conditions of the gut.
These results were confirmed in a second DDW session that examined the role of FXR in modulating innate immunity and regulating inflammation in a rodent model of chronic colitis. This study also found that FXR activation by INT-747 was protective, preventing the development of induced colitis.
"Since FXR is a bile acid receptor that is highly expressed in both the liver and gastrointestinal (GI) tract, we have long suspected it might play a key protective role in chronic inflammatory bowel diseases, just as it does in the liver," said Professor Fiorucci. "The data we are presenting today, along with a paper published in PNAS earlier this year, demonstrate that FXR activation modulates immune responses in the gut with significant anti-inflammatory and anti-fibrotic effects."
Similar findings were reported in the March 7, 2006 edition of the Proceedings of the National Academy of Sciences (PNAS)*. Intercept co-founder Dr. Steven Kliewer and colleagues from UT Southwestern Medical Center at Dallas, the Howard Hughes Medical Institute and the Salk Institute for Biological Studies reported findings from animal studies demonstrating a central role for FXR in protecting the small intestine when bile flow is impaired and suggesting that FXR agonists may have a protective effect when this occurs.
"The FXR data presented at DDW and recently published in PNAS provide a strong rationale for testing the utility of INT-747 in diseases such as Crohn's," said Mark Pruzanski, M.D., President and CEO of Intercept. "There are over one million IBD patients in the US alone and current treatments for these disorders are inadequate. We will continue to assess whether our FXR compounds might offer therapeutic benefit to these patients, given the growing body of evidence that they may have significant protective effects in the bowel."
Digestive Disease Week is being held this year in Los Angeles from May 19-25, 2006. Researchers affiliated with Intercept presented at the following sessions:
An essential role of Farnesoid-X-Receptor (FXR) in regulating intestinal fibrosis in murine model of chronic colitis, Piero Vavassori, Andrea Mencarelli, Barbara Renga, Giovanni Rizzo, Antonio Morelli, Mark Pruzanski, Roberto Pellicciari, Stefano Fiorucci; AGA Basic Science Plenary Session, May 22 at 9:05 am in Room 501A/B/C
Essential counter-regulatory role of Farnesoid-X-Receptor for intestinal innate immunity, Stefano Fiorucci, Barbara Renga, Giovanni Rizzo, Andrea Mencarelli, Moises Di Sante, Mark Pruzanski, Roberto Pellicciari; Research Forum, May 23, 2006 at 11:45 am in Room 301A/B
*The cited publication can be found at: Proceedings National Academy of Sciences. 2006 Mar 7;103(10):3920-5. Epub 2006 Feb 10. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Inagaki T, Moschetta A, Lee YK, Peng L, Zhao G, Downes M, Yu RT, Shelton JM, Richardson JA, Repa JJ, Mangelsdorf DJ, Kliewer SA.
About Intercept Pharmaceuticals
New York City-based Intercept Pharmaceuticals, Inc. is a clinical stage biopharmaceutical company focused on developing small molecule drugs for the treatment of chronic liver and metabolic diseases. Since 2002, Intercept researchers have published extensively on the key role of the farnesoid X receptor (FXR) as a regulator of bile and cholesterol metabolism in the liver, with preclinical data from numerous studies providing strong rationale for the advancement of FXR agonists as hepatoprotective therapeutics in chronic liver disease. The company intends to lead in the advancement of drug candidates acting on FXR and other bile acid receptors and is developing a pipeline of novel lead compounds for multiple indications.
Contacts: Media: Intercept Pharmaceuticals GendeLLindheim BioCom Partners Mark Pruzanski, M.D. Barbara Lindheim 917 744-4043 212 918-4650
Intercept Pharmaceuticals, Inc.CONTACT: Mark Pruzanski, M.D. of Intercept Pharmaceuticals,+1-917-744-4043; or Media: Barbara Lindheim of GendeLLindheim BioComPartners, +1-212-918-4650
