Model BBP-454 -KRAS Inhibitor for KRAS Cancers

RAS is one of the most well-known oncogenic drivers, with approximately 30% of all cancers being driven by RAS mutations, including large proportions of lung, colorectal and pancreatic tumors. BridgeBio’s approach to RAS cancers encompasses multiple “shots on goal” that target both KRAS mutant tumors and those in which RAS activates PI3Ka. We believe two of our approaches have the potential to be first-in-class. In one approach, we have discovered multiple series of direct KRAS G12C dual inhibitors that block both the active and inactive states of KRAS G12C and have shown differentiation from KRAS G12C inactive state inhibitors such as sotorasib and adagrasib. Another approach has led to the discovery of multiple PI3Ka:RAS breakers that are able to block RAS activation of the key oncogenic effector PI3Ka. PI3Ka is the second most altered oncogene in human tumors.