Open Competition 3 - Biotechnology

A Novel Transcellular System for Effective Oral Drug Administration

Sponsor: XenoPort, Inc.

• Project Performance Period: 10/1/2001 - 9/30/2004
• Total project (est.): $3,110,119.00
• Requested ATP funds: $2,000,000.00

Many therapeutic drugs are absorbed poorly or not at all in the intestinal tract and therefore require frequent dosing by other methods, such as injection, that are inconvenient, costly, and may have side effects. Furthermore, existing delivery methods and daily dose requirements do not always provide adequate bioavailability -- drug levels usable by the body -- nor do they enjoy adequate patient compliance. XenoPort Inc. plans to develop and demonstrate technology that will make possible the oral administration of poorly absorbed drugs by harnessing the normal capability of the intestinal lining to ferry nutrients from the intestinal cavity to the bloodstream. Many nutrients are absorbed this way. The process is usually initiated by binding of the cargo molecule to a specific cell surface receptor, inducing the formation of tiny enclosed vesicles, which then are directed to specific places within the cell where their contents are emptied. In the three-year project, the company will identify and characterize intestinal pathways capable of handling larger quantities of drugs than can be transported by known routes. The risk is high because it is not certain such that natural pathways exist, or that they have enough transport capacity to be useful in the face of natural barriers to the passage of harmful entities such as bacteria and viruses. The company's Epitope-Capture Antibody Display library technology will be extended and used to identify receptors, and combinatorial chemistry and screening methods will be used to optimize other molecules that activate the pathways. XenoPort will validate the discovered pathways by delivering model drug compounds in animals. ATP support will enable the company to accelerate and expand the scope of the project. If successfully developed and commercialized, the new technology will remove a major impediment to the development of new drugs with substantially improved pharmacokinetic properties, and provide means of improving drug delivery across tissue barriers such as the blood-brain barrier. The project also will increase the value and use of existing drugs not previously available in oral form. Improved patient compliance with prescriptions made possible by oral dosing will help reduce the billions of dollars in health care costs annually due to hospitalizations, lost productivity, and premature deaths associated with incorrect administration of drugs; and consumers and health care workers will benefit from reductions in needle-stick injuries.

For project information:

Juan M. E. Harrison, (650) 855-1698
jharrison@xenoport.com

ATP Project Manager

Andrew Klein, (301) 975-4292
andrew.klein@nist.gov