This Small Business Innovation Research (SBIR) Phase I project is motivated by fundamental questions about the way drug molecules are processed in the human body. Drug candidates cannot address a human disease unless they reach the appropriate sites within the body and then persist in those sites. The proposed research focuses on a particular class of bioactive compounds called "peptides." Peptides can act in powerful and favorable ways within the body, with high specificity of action (which minimizes "side effects"), but they are subject to very rapid destruction after administration. This weakness of peptides requires that they be injected regularly, but peptide drugs would be much more useful if they could be taken orally. This SBIR Phase I project examines unique peptide-like molecules that are designed to retain the favorable pharmaceutical action of peptides themselves but to resist degradation mechanisms within the body that rapidly destroy peptides. The stomach is the most destructive site for peptides, and this project aims to generate peptide-like molecules that are sufficiently robust to survive the stomach and reach the small intestine, where they can be absorbed. Achieving these molecular design goals would have high intellectual merit in addition to advancing drug design. The broader impact/commercial potential of this project is significant. Current peptide-based drugs constitute important tools in human healthcare, and development of new peptide-based drugs represents a growing proportion of the pharmaceutical research effort in the U.S. and worldwide. Several current peptide drugs, addressing widespread diseases such as type 2 diabetes (T2DM) and osteoporosis, have sales in excess of $1 billion. These drugs must be delivered by injection. If new drugs featuring the same health benefits became available in pill form, the convenience of orally delivered drugs would rapidly capture most of the market. Moreover, the high stability engendered by our new design strategy would enable the development of drugs for diseases that currently cannot be addressed. Thus, the commercial potential of this project is quite high. Orally delivered replacements for currently injectable drugs would have a substantial broader impact because they would enhance patient compliance. Inadequate treatment of T2DM for example, leads to many adverse health consequences that degrade productivity and quality of life for patients. Increased compliance resulting from a generalized ability to deliver peptide drugs in pill form would vastly improve outcomes for patients, including the specific patients populations targeted by our current programs.
