ALBA PRESENTS POSITIVE DATA FROM CELIAC DISEASE STUDY

Alba Therapeutics has presented data showing that when AT- 1001, an investigational oral zonulin receptor antagonist being developed for treatment of celiac disease (CD), was assessed in a double-blind, placebo-controlled study of CD patients, the product induced a positive result on the trial's primary endpoint, intestinal permeability. The objective of the Phase Ib proof-of-concept study was to establish the safety, tolerability and effectiveness of single doses of oral AT-1001 in adult CD patients in remission that are challenged with a large dose of gluten.

CD is a T-cell mediated autoimmune disease that occurs in genetically susceptible individuals and is characterized by small-intestinal inflammation, injury and intolerance to gluten. According to the NIH, CD affects approximately 3 million Americans, the company said. The only current treatment for CD is complete elimination of gluten from the diet.

In the trial, intestinal barrier function was maintained by AT-1001 despite a supramaximal stimulus with gluten. There was a significant increase in permeability in placebo recipients but not in AT-1001 recipients following the 2.5-gram gluten challenge, as determined by urinary lactulose-to-mannitol ratio. Also, AT-1001 plasma concentrations were unmeasureable, indicating little to no systemic absorption when administered orally. The biological effect of AT-1001 persisted beyond the drug's residence time, suggesting that AT-1001 modulates both persistent leak and immune activation. Additionally, Symptoms of acute gluten toxicity were inhibited in the AT-1001 arm when compared to placebo. Finally, the drug was generally safe and well-tolerated, and no serious adverse events were reported.

AT-1001 is an orally administered octapeptide zonulin receptor antagonist that appears to exert its inhibitory effect on gliadin-induced tight junction disassembly by blocking putative zonulin receptors on the luminal surface of the small intestine. Pretreatment with the peptide fails to inhibit gliadin induced zonulin release, while administration of zonulin analogues or gliadin in the presence of AT-1001 fail to significantly affect intestinal permeability, confirming the effect of the molecule is specific to the zonulin receptor.