BridgeBio Oncology Therapeutics, Inc. ("BBOT") (NASDAQ:BBOT), a clinical-stage biopharmaceutical company focused on RAS-pathway malignancies, today presented new preclinical data in an oral presentation for BBO-10203, a first-in-class covalent small molecule RAS:PI3Kα breaker that selectively blocks the physical interaction between RAS and PI3Kα resulting in the inhibition of RAS-driven PI3Kα-AKT signaling in tumors with no observed hyperglycemia. The data were presented at the American Association for Cancer Research (AACR) Annual Meeting 2026.

"The interaction between RAS and PI3Kα plays a critical role in malignant cells," said Pedro J. Beltran, PhD, Chief Scientific Officer of BBOT. "BBO-10203 physically disrupts the interaction between RAS and PI3Kα, leading to signaling inhibition and tumor regressions. Importantly, unlike competing approaches, no hyperglycemia has been observed to date. In addition, BBO-10203's ability to block RAS-mediated activation of PI3Kα is independent of the mutational status of either RAS or PI3Kα, which may enable treatment of a broader patient population. These data suggest that non-canonical RAS proteins play a key role in PI3Kα activation in HER2AMP cell lines. Furthermore, BBO-10203 demonstrates strong in vivo combination activity with HER2-targeted therapies, including tucatinib and trastuzumab, in HER2 AMP models."

Highlights from the oral presentation include:

  • BBO-10203 physically and allosterically disrupts the interaction between RAS and PI3Kα, leading to signaling inhibition without inhibiting the kinase activity of PI3Kα 
  • BBO-10203 induces tumor regressions at 30 mg/kg QD and no hyperglycemia observed at 100 mg/kg QD
  • BBO-10203 shows that PI3Kα activity in HER2AMP cells is RAS-dependent
  • RAS RBD mutations recapitulate the pAKT and viability effects of breaker activity in HER2AMP cell lines
  • Non-canonical RAS signaling appears to be the dominant driver of pAKT in HER2AMP cell lines
  • BBO-10203 displays strong in vivo combination effects with HER2 inhibitors tucatinib or trastuzumab in HER2AMP models