Tranzyme Pharma Inc., a leading biopharmaceutical company developing small molecule therapeutics for the treatment of gastrointestinal (GI) disorders, presented positive preclinical data for its lead ghrelin agonists at the Fifth International Symposium on Growth Hormone Secretagogues in Camogli, Italy.
Tranzyme is developing small molecule ghrelin agonists as first-in-class treatments for post-operative ileus (POI) and diabetic gastroparesis-serious medical conditions in which motility of the GI tract is severely impaired.
The data demonstrate that Tranzyme's proprietary ghrelin agonists are potent and selective for the human ghrelin receptor. In a rat model, these compounds stimulated significant gastric emptying in a dose-dependent manner with 100-fold greater potency than metoclopramide, a marketed prokinetic compound currently prescribed to treat gastroparesis, officials informed here.
In addition, the company's compounds exhibit a desirable pharmacokinetic profile and oral bioavailability. The data presented at this meeting were developed by Tranzyme's team led by Graeme L. Fraser, vice president, Pharmacology & Drug Discovery.
"We are very excited to have successfully advanced our programmes into preclinical development," Vipin K Garg, president & CEO for Tranzyme said adding, "We are on track to file an IND for POI by Q4 2005. We expect to initiate phase I clinical trials for this indication by the end of 2005, followed shortly thereafter by Phase I trials for diabetic gastroparesis."
POI is an impairment of GI motility that is an inevitable consequence of major abdominal and pelvic surgery (1.4 million cases per year in US). There are no FDA-approved products for POI. Diabetic gastroparesis affects type I and type II diabetics with up to 10 per cent of these patients requiring hospitalization for nausea, vomiting, abdominal pain and malnutrition. Existing medical and surgical approaches to this condition offer poor efficacy and/or severe side effects. Moreover, the two most popular products for the treatment of gastroparesis (cisapride and domperidone) have been removed from the US market due to adverse side effects.
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 and poor oral bioavailability.
Tranzyme is developing novel orally bio-available, small molecule therapeutics for the treatment of gastrointestinal (GI) diseases. The company's candidate drugs originate from its own discovery pipeline of proprietary compounds with high affinity for validated and druggable targets in the GI tract. It is developing mechanism-based therapeutics for post-operative ileus, diabetic gastroparesis, irritable bowel syndrome (diarrhoea-type) and functional dyspepsia and is on track to enter the clinic with its first product by the end of 2005.