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.
Our group set out, with funding from NSF, to determine the feasibility of oral delivery of a new class of artificial - yet medically important - synthetic drug candidates invented by Longevity Biotech called Hybridtides. Nearly all natural and engineered protein drugs (including insulin and other various diabetes, arthritis or cancer treatments) are required to be delivered to patients via repeated injections because these products are not able to survive the harsh environment inside the stomach and intestines, where other types of drugs (such as aspirin) are typically absorbed by the body. These organs are designed to break down food and nutrients into smaller fragments that are specifically absorbed into the body. Likewise, traditional protein drugs, including peptides (small protein drugs, typically <50 amino acids in length) are also digested by these organs and thus unable to deliver the intended therapeutic benefit to patients. Longevity Biotech is developing a new class of synthetic proteins and peptides called Hybridtides (including natural and non-natural amino acids) that are highly stable in these harsh environments and are able to resist the digestive process. This project was designed to evaluate the preliminary oral delivery performance of representative Hybridtide drug-candidates targeting Type 2 Diabetes (T2DM), Triple Negative Breast Cancer (TNBC), Cardiovascular Hypertension (CV) and Human immunodeficiency Virus (HIV). During the Phase I effort, Longevity established baseline oral delivery performance for each of these drug candidates and initiated formulation and other delivery optimization activities. The exciting preliminary results generated during this NSF Phase I SBIR have led to multiple commercial collaboration opportunities with global pharmaceutical and biotechnology firms for both partnerships around our current portfolio. In addition, the NSF-supported studies stimulated collaborative opportunities to apply the Hybridtide platform technology to development programs at partner companies. The long-term objective of this research and development effort at Longevity Biotech is to replace needles with pills in multiple therapeutic areas using the Hybridtide platform. Achieving this goal would increase patient convenience and compliance, thereby improving health outcomes and lowering costs.
