Galapagos NV has completed patient recruitment for the clinical Proof of Concept study with GLPG0974. GLPG0974 presents a novel mode of action for the treatment of ulcerative colitis, a debilitating inflammatory bowel disease. The efficacy and safety of GLPG0974 are being evaluated during a 28-day treatment period.

Topline results from this study are expected in June 2014. GLPG0974 is fully proprietary to Galapagos.

As a potent inhibitor of FFA2 (free fatty acid receptor 2), GLPG0974 aims to reduce migration of neutrophils into the gastro-intestinal tract.  Over-activity of neutrophils damages the bowel tissue and causes chronic inflammation in ulcerative colitis. FFA2 plays an important role in the migration of neutrophils and is over-expressed in ulcerative colitis patients. In healthy volunteers, 14 days of once- or twice-daily oral dosing of GLPG0974 was well-tolerated and safe up to the highest doses tested.  A sustained suppression of a biomarker for neutrophil activation demonstrated the desired pharmacodynamic activity.

The clinical Proof-of-Concept phase II trial for GLPG0974 is designed to recruit 45 patients with mild to moderate ulcerative colitis.  The aim is to evaluate the safety, efficacy, pharmacokinetics and effects on selected biomarkers of GLPG0974 in this patient population. Patients are randomized to receive either 200 mg of GLPG0974 twice-daily or placebo (2:1 ratio), for a period of 28 days.  This double-blind, placebo-controlled study recruited patients in multiple sites in four countries: Belgium, the Czech Republic, Latvia, and Slovakia.

GLPG0974 is an orally available small molecule that reduces migration of neutrophils, one of the critical cell types in inflammatory processes, by potent inhibition of FFA2 (free fatty acid receptor 2, formerly known as GPR43). Over-activity of neutrophils is a cause of tissue damage in illnesses such as inflammatory bowel disease. A reduction of neutrophil activation and migration by inhibition of FFA2 may provide for a novel anti-inflammatory treatment approach. Bacteria produce free fatty acids by fermentation of food fibers in the gut.  These fatty acids attract neutrophils through the activation of the neutrophil FFA2 receptor. By inhibiting FFA2, GLPG0974 prevents free fatty acid-induced activation and migration of neutrophils towards an inflammatory site, such as in the gut of patients with inflammatory bowel disease. GLPG0974 is the first inhibitor of FFA2 to be evaluated clinically.

Galapagos is specialized in novel modes-of-action, with a large pipeline comprising of six phase II studies (three led by GSK), one phase I study, six pre-clinical, and 20 discovery small-molecule and antibody programs in cystic fibrosis, inflammation, antibiotics, metabolic disease, and other indications.