Synergy Pharmaceuticals, Inc., a developer of new drugs to treat gastrointestinal (GI) disorders, has started oral dosing of healthy volunteers in a phase I clinical trial of SP-333, a guanylate cyclase C (GC-C) agonist for the treatment of inflammatory bowel disease (IBD) including ulcerative colitis (UC). The present trial, designed as a placebo-controlled, dose-escalating, multiple-dose study in 64 healthy adult volunteers, is focused on exploring the safety profile of SP-333.

The study will take place in one site in the United States.

SP-333 has exhibited potent anti-inflammatory activity in animal studies of colitis, displaying a novel mechanism-of-action that the company believes could provide a new way to treat UC patients with mild-to-moderate disease.

"We're pleased with the results of our SP-333 single-dose-ascending trial in healthy volunteers, which was completed in late 2012, and are eager to move forward with further development of SP-333," said Dr Gary S Jacob, president and CEO of Synergy Pharmaceuticals. "This second trial is an important step in ultimately evaluating SP-333's potential to treat GI inflammatory diseases such as UC."

"SP-333 is our first clinical candidate for evaluating the anti-inflammatory potential of GC-C receptors to treat GI anti-inflammatory conditions such as UC," said Dr Kunwar Shailubhai, Synergy's Chief Scientific Officer. "In experimental models of colitis in mice, we have found that treatment with SP-333 ameliorates GI inflammation, likely through inhibition of NF-kappa B signaling to suppress production of pro-inflammatory cytokines."

SP-333 is a synthetic analog of uroguanylin, a natriuretic peptide hormone normally produced in the lumen of the intestinal tract. Deficiency of uroguanylin is likely to be one of the primary causes for the formation of polyps, as well as debilitating and difficult-to-treat GI inflammatory disorders such as UC and Crohn's disease. Orally-administered SP-333 binds to and activates the GC-C receptor expressed on epithelial cells lining the GI mucosa, thereby stimulating cyclic GMP in target tissues. SP-333 was shown to be highly stable against proteolysis in simulated intestinal fluid for up to 24 hours. Its stability profile has made this peptide an extremely potent GC-C agonist in studies of mice and monkeys. SP-333 promoted bowel movement in studies of monkeys and ameliorated GI inflammation in studies of mice.

UC is a type of IBD that causes chronic inflammation of the colon. Along with Crohn's disease, the other major form of IBD, UC is painful and debilitating. Patients with UC are at increased risk for colon cancer and may ultimately require surgical removal of the colon. There are no medical cures for UC, and long-term remission with current treatments is limited. New treatments for UC patients are urgently needed.