PANCREATIC CANCER

KRAS G12D AND TARGETING THE ‘UNTARGETABLE’ BY PCC TECHNOLOGY

This therapeutic program focuses on KRAS(G12D), the most common driver mutation in pancreatic, colorectal and other cancers. The target represents a significant challenge for small molecule therapeutics given the relatively featureless attributes of KRAS. This program deploys PCC technology to discover potent inhibitors of KRAS G12D by targeting subtle differences in the protein’s switch region between wild-type vs. mutant KRAS.

KRAS is membrane anchored.  Therefore, we pursued a strategy of intracellular targeting to facilitate the co-localization of discovered cyclic peptide inhibitor leads within proximity of its KRAS G12D target.  To achieve this result, we utilize PCC technology to have the discovered cyclic peptides deploy a lipid component designed to insert the cyclic peptide inhibitor into the plasma membrane. The resulting membrane associated properties facilitate the cyclic peptide’s KRAS G12D inhibitory activity by concentrating the inhibitor where KRAS G12D exerts its biologic function.  

Our discovered KRAS G12D lead therapeutic molecules have several encouraging pharmacokinetic properties, including excellent tolerability and once-a-day dosing.

Our CEO Presents:

Click through the slides below or watch our CEO, Albert A. Luderer, Ph.D., present them in the video above.