Synergy Pharmaceuticals, Inc., a developer of new drugs to treat gastrointestinal (GI) disorders and diseases, has submitted an Investigational New Drug (IND) application for clinical evaluation of SP-333 to treat inflammatory bowel disease (IBD). SP-333 is a second-generation guanylate cyclase-C (GC-C) agonist with the potential to treat GI disorders and diseases.

"SP-333, to our knowledge, represents the most potent and stable uroguanylin analog ever developed," stated Dr Gary S Jacob, president and CEO of Synergy Pharmaceuticals. "The submission of the IND on SP-333 is a major milestone for the company, as it broadens our clinical portfolio of GC-C agonists for treatment of GI disorders and diseases."

"The science behind SP-333 marks a new approach to the treatment of GI inflammatory diseases," said Dr Kunwar Shailubhai, chief scientific officer of Synergy Pharmaceuticals. "We are excited with SP-333's impressive anti-inflammatory activity. In studies with experimental models of colitis in mice, SP-333 at an oral dose as low as 0.05 mg/kg body weight demonstrated superior anti-inflammatory activity compared to 5-aminosalicylic acid (5-ASA) given at a dose of 100 mg/kg."

SP-333 is a synthetic analog of uroguanylin, a natriuretic hormone which is normally produced in the body's intestinal tract. Deficiency of uroguanylin is likely to be one of the primary reasons associated with formation of polyps as well as debilitating and difficult-to-treat GI inflammatory disorders such as ulcerative colitis and Crohn's disease. Orally-administered SP-333 binds to and activates guanylate cyclase C (GC-C) expressed on epithelial cells lining the GI mucosa, resulting in stimulation of cyclic GMP in target tissues. SP-333 has been found to be highly stable against proteolysis in simulated intestinal fluid for up to 24 hours.  Its enhanced stability makes this peptide an extremely potent GC-C agonist in animal studies in mice and monkeys, promoting bowel movement in monkeys, and ameliorating GI inflammation in mice, respectively.