SBIR-STTR Award

This Small Business Innovation Research (SBIR) Phase I project builds on the rapid FDA approval success of recent cancer therapeutics that act on a specific conformation state of their target protein. Biodesy has developed a new optical technique, Second Harmonic Generation that measures protein conformation in real time and addresses the challenge of rapidly identifying and discriminating ligands that bind to or induce different protein conformations. They are applying this technique to understanding the critical protein conformations that distinguish the different classes of inhibitors against protein kinases. Biodesy plan to use site-specific mutations of cysteines within Abl kinase to identify and measure conformation changes at discrete areas within the protein and study how these are modified in the presence and absence of different classes of inhibitors. The broader/commercial implications of this research are to provide a comprehensive, high throughput platform that will enable the rapid identification of novel therapeutics. The FDA recently provided accelerated approval to a structure-specific inhibitor of BRaf, Vemurafenib, which functions by holding its targeted protein in an inactive conformation state. Gleevec (revenue in excess of $4B), functions in a similar fashion. Interest in techniques that can identify this mechanism of action has grown markedly. Biodesy?s platform has the potential to greatly accelerate identification and development of similar therapeutics. There are more than 500 kinases in the kinome so the commercial potential of the approach is significant. Furthermore, its broader impact is to provide a general method for identifying conformation-specific drugs across all target classes.

This Small Business Innovation Research (SBIR) Phase II project will build a real-time detection instrument for conformational change. Conformational change is a change in the structure of a biomolecule such as a protein. For a given protein, different structural changes produce different functionals effect in a biological cell, for example turning biochemical networks on or off. Virtually all biological processes, and all diseases, are mediated by a particular conformational change or the lack of one. Conformational change is thus a topic of enormous scientific and medical importance. In this Phase II project, multiple improvements will be made to the existing in-house prototype instrument, in software, mechanical and optical design, and fluidics handling, to produce an instrument with high precision and robustness. The research objective of this Phase II project is to create an instrument that can be used by scientists, an important milestone in the development of the technology. The broader impact and commercial potential of this project is to create an instrument that will significantly increase scientists? basic understanding of how conformational changes work, and also enable scientists to discover better or new medicines for diseases. In particular, three-quarters of all proteins known to cause or contribute to disease, due to some mutation, cannot be addressed using conventional techniques. Thus, no effective medicines exist for many diseases. Cancer is one such example. The instrument will enable scientists to find better and new medicines for these diseases. Thus this innovation has great societal and scientific potential. Commercially, this Phase II project will play a critical role in the development of the innovation. It will enable to transition the technology funded by NSF from the current lab prototype to an instrument that will be robust, reproducible and comprehensive enough in its capabilities to enable scientists to use it independently. This important and necessary step is the first on the path to commercialize the innovation