Cancers evolve, or mutate, to evade the effects of a drug. When confronted with kinase inhibitors, two types of mutations most commonly emerge: solvent-front mutations and gatekeeper mutations. Both are “acquired,” meaning they emerge only after a tumor is exposed to the drug.
Most of the currently approved or investigational ROS1, ALK and TRK kinase inhibitors have an extra chemical group that extends to the solvent-front area of the kinase. As a result, these drugs are vulnerable to solvent-front mutations.
We seek to overcome resistance by design.
Our therapies are designed differently. They are structurally compact, with a low molecular weight and a rigid three-dimensional structure that binds neatly inside an area of the cancer cell known as the “ATP” pocket. ATP is a critical molecule for cell energy and growth. By binding completely inside the ATP pocket, our TKIs can bind to solvent-front mutations that evade conventional TKIs.