Press Release

Tranzyme Pharma’s Ghrelin Agonist Demonstrates a Unique Selectivity Profile for the Treatment of Gastrointestinal Disorders

Data Presented at the 20th International Symposium on Neurogastroenterology & Motility

RESEARCH TRIANGLE PARK, N.C. and SHERBROOKE, Québec (July 6, 2005) - Tranzyme Pharma Inc., a leading biopharmaceutical company developing small molecule therapeutics for the treatment of gastrointestinal (GI) disorders, announced today new and exciting efficacy data for TZP-101, the Company’s lead product for the treatment of post-operative ileus and diabetic gastroparesis. TZP-101 is a small molecule ghrelin receptor agonist, which has been shown to selectively stimulate motility of the GI tract. In a presentation at the 20th International Symposium on Neurogastroenterology & Motility (Toulouse, France), Tranzyme Pharma presented new in vivo data demonstrating that the potent and selective gastroprokinetic activity of TZP-101 takes place without the release of growth hormone.

Ghrelin is a peptide hormone known to stimulate both gastrointestinal motility and growth hormone release. Tranzyme Pharma has applied its proprietary chemistry technology to dissociate these two aspects of ghrelin pharmacology resulting in a product profile with selectivity for the treatment of gastrointestinal disorders.

“Our discovery that TZP-101 effectively separates the gastroprokinetic and endocrine effects of ghrelin is a significant breakthrough in ghrelin receptor pharmacology,” said Graeme L. Fraser, Ph.D., Vice President of Drug Discovery. “By eliminating the growth hormone secretagogue aspects of ghrelin receptor stimulation, we expect that TZP-101 will avoid significant potential side-effects when it is used for chronic therapeutic indications such as gastroparesis.”

“These data further validate the ability of Tranzyme Pharma’s small molecule chemistry to design compounds with great selectivity towards multimeric targets such as GPCRs, kinases and ion channels,” said Lindsay N. Donald, DABT, Vice President of Business and Preclinical Development. “Traditionally, this sort of selectivity has only been possible with peptide or protein therapeutics. Our chemistry technology allows us to maintain the favorable binding characteristics of large biomolecules while eliminating their drawbacks such as low oral bioavailability, high manufacturing costs, and antigenicity.”

About the role of ghrelin in GI motility

Ghrelin is the most potent endogenous peptide known to stimulate gastric motility. Recent independent clinical studies have clearly demonstrated that infused ghrelin peptide potently stimulates gastric emptying in both human volunteers and diabetic gastroparesis patients. However, the ghrelin peptide has limited utility as a therapeutic product for GI indications due to its brief pharmacokinetic half-life, poor oral bioavailability, and potent growth hormone-releasing activity.

About post-operative ileus (POI) and diabetic gastroparesis

POI is an impairment of gastrointestinal motility that is an inevitable consequence of major abdominal surgery, especially under conditions of bowel resection. POI has an annual economic impact of $1.75 billion. There are no FDA-approved products for the treatment of POI. Diabetic gastroparesis is the impairment of stomach motility observed in both Type I and Type II diabetics. Up to 10% of these patients require hospitalization for nausea, vomiting abdominal pain and malnutrition. Existing therapies for this condition offer poor efficacy and/or severe side effects. TZP-101 is under development in both intravenous and oral formulations for the treatment of these disorders.