BridgeBio Pharma, Inc. has announced that the United States Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for BBO-8520, a first-in-class orally bioavailable and highly potent small molecule direct inhibitor of KRASG12C (ON) state. BBO-8520 binds covalently to the Switch II pocket in both the GTP-bound (ON) and GDP-bound (OFF) state conformations of KRASG12C, leading to rapid and robust inhibition of KRASG12C activity. BBO-8520 drives substantial tumor growth inhibition in multiple preclinical models, even after emergence of resistance to sotorasib, an FDA approved (OFF) state inhibitor of KRASG 12C.