KRASG12C dual inhibitor for KRAS cancers
BBO-8520 is a small molecule that directly binds and inhibits KRASG12C in both its active (GTP bound) and inactive (GDP bound) conformations. In binding the active state, BBO-8520 disrupts effector protein binding and downstream oncogenic signaling. To date, BridgeBio has shown this molecule with its novel dual reactivity to be effective in vitro against several resistant mutants that have evolved in response to GDP-inhibitor treatment. In vivo, BBO-8520 demonstrated the potential to have strong efficacy and showed differentiated activity in some PDX models driving tumor regressions. BridgeBio believes this could lead to differentiated activity in cancer patients with KRASG12C driven cancer and plans to enter the clinic with its KRASG12C dual inhibitor in 2023.