Synergy Files IND for GI Diseases

Synergy Pharmaceuticals, Inc. recently announced that an Investigational New Drug (IND) application was submitted on September 7, 2012, 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,” said 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 that 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.

Synergy is a biopharmaceutical company focused on the development of new drugs to treat gastrointestinal disorders and diseases. Synergy’s lead proprietary drug candidate plecanatide is a synthetic analog of the human gastrointestinal hormone uroguanylin, and functions by activating the guanylate cyclase C receptor on epithelial cells of the GI tract. Synergy completed a Phase I study of plecanatide in healthy volunteers and a Phase IIa clinical trial in CIC patients. In October, 2011, Synergy initiated dosing of patients in a major Phase II/III clinical trial of plecanatide to treat chronic idiopathic constipation.

Plecanatide is also being developed to treat constipation-predominant irritable bowel syndrome, with the first trial in IBS-C patients planned for the second half of 2012. Synergy’s second GC-C agonist SP-333 is currently in preclinical development to treat inflammatory bowel diseases. For more information, visit www.synergypharma.com.

Plecanatide is a member of a new class of essentially non-systemic drugs, referred to as guanylate cyclase C (GC-C) agonists, which are currently in development to treat CIC and IBS-C. Plecanatide is a synthetic analog of uroguanylin, a natriuretic hormone that regulates ion and fluid transport in the GI tract. Orally administered plecanatide binds to and activates GC-C receptors expressed on epithelial cells lining the GI mucosa, resulting in activation of the cystic fibrosis transmembrane conductance regulator (CFTR), and leading to augmented flow of chloride and water into the lumen of the gut.

Activation of the GC-C receptor pathway is believed to facilitate bowel movement as well as producing other beneficial physiological responses, including improvement in abdominal pain and inflammation. In animal models, oral administration of plecanatide promotes intestinal secretion and also ameliorates GI inflammation.