"Alba Therapeutics Presents Data from Positive Phase Ib Clinical Trial at the XII International Celiac Disease Symposium"
New York, November 10, 2006 - Data presented on November 11th at the XII International Celiac Disease Symposium in New York City show 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. Key findings from this Phase Ib study include:
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 (L-to-M) ratio.
AT-1001 was generally safe and well tolerated, and no serious adverse events were reported.
AT-1001 plasma concentrations were unmeasureable (< 0.5 ng/ml), indicating little to no systemic absorption when administered orally.
The biological effect of AT-1001 persisted beyond the drugs residence time, suggesting that AT-1001 modulates both persistent leak and immune activation.
Symptoms of acute gluten toxicity were inhibited in the AT-1001 arm when compared to placebo.
"AT-1001’s inhibitory effect is most likely related to its capacity to prevent zonulin binding to its receptor on the lining of the gut, reducing exposure to gliadin and immune activation” stated Blake Paterson, M.D., Alba’s Co-founder and CEO. "We are excited by the demonstration of a systemic immunological benefit arising from a physiological event at a mucosal surface of the small bowel, and look forward to completion of our Phase II clinical trial to further assess AT-1001’s impact in this debilitating disease.”
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. AT-1001 is currently under investigation in a multicenter, double blind, placebo controlled Phase II dose ranging study to evaluate the safety, tolerability and efficacy of AT-1001 in 79 CD subjects during gluten challenge.
Zonulin is an endogenous signaling protein that transiently and reversibly opens the tight junctions between the cells of epithelial and endothelial tissues such as the intestinal mucosa, blood brain barrier and pulmonary epithelia. Discovered by Alba’s co-founder, Dr. Alessio Fasano, zonulin appears to be involved in many disease states in which leakage occurs via paracellular transport across epithelial and endothelial tight junctions, and thus may play an important potential role in the treatment of autoimmune and inflammatory diseases.
About Celiac Disease
Celiac disease is a T-cell mediated auto-immune disease that occurs in genetically susceptible individuals and is characterized by small intestinal inflammation, injury and intolerance to gluten. According to the National Institutes of Health, CD affects approximately 3 million Americans. The only current treatment for CD is complete elimination of gluten from the diet, which results in remission for some patients.
Alba Therapeutics Corporation is a privately held biopharmaceutical company based in Baltimore, Maryland. Alba is dedicated to commercializing disease-modifying therapeutics and vaccine and drug delivery adjuvants based on the zonulin pathway. Alba’s lead molecule, AT-1001, is targeted towards the treatment of Celiac Disease and Type 1 Diabetes and other autoimmune diseases.
Contact: Stuart Sedlack, SVP, Corporate Development
Web site: http://www.albatherapeutics.com