Grant: Proof of Principle Program - Phase II

The INDEL platform was the recipient of a Proof of Principle I grant in 2004, which successfully validated the science and allowed the creation of a University of British Columbia start-up company, INDEL Therapeutics Inc. The platform technology enables the discovery of new therapeutics for the treatment of infectious diseases. INDEL views the continued exchange between scientific advancement and microbial resistance in a revolutionary way. Bioinformatics and molecular modeling have grown in sophistication and predictive power, allowing INDEL to identify and target discreet differences in essential pathogen proteins that have a common counterpart in human cells. These differences between almost identical pathogen and human proteins are called indel-differentiated regions. The similarity observed between these pathogenic proteins and their human counterparts illustrates a shared essential function within the cell, conserved through strong evolutionary pressure. Pathogenic indel-differentiated targets do not readily permit mutation since they are critical cellular hubs and are absolutely essential for pathogen survival. As a result, when INDEL develops a novel therapeutic, its indel-differentiated target will be less likely to mutate and allow the organism to become resistant, since mutations will mean loss of function and pathogen death. INDEL has demonstrated its ability to discover small molecule compounds against its pathogenic indel-differentiated targets. Using unique expertise in computer (in silico) rational drug design, we have identified therapeutics that can bind to specific indel-differentiated targets and inhibit their function, while showing no interaction, and thus toxicology concerns with the human counterpart protein. Proceeds from the Proof of Principle II grant will be used to creates small molecule leads against several Indel Platform targets for the treatment of infectious disease.