BBOT Announces Late-Breaking Preclinical Data on BBO-10203, a First-in-Class RAS:PI3Kα Breaker, at the San Antonio Breast Cancer Symposium (SABCS)

• Preclinical data demonstrate BBO-10203 blocks RAS-mediated activation of PI3Kα, strongly inhibits pAKT signaling in tumor cells without inducing hyperglycemia, and shows robust anti-tumor activity both as monotherapy and in combination with standard of care therapies in mutant or wild-type PIK3CA breast cancer models

• BBOT will also present a trial in progress poster on BREAKER-101, a Phase 1 clinical trial evaluating BBO-10203 in patients with locally advanced or metastatic HER2+ breast cancer, HR+/HER2- breast cancer, KRAS mutant colorectal cancer, and KRAS mutant non-small cell lung cancer with initial Phase 1 data expected in the first half of 2026

Excerpt from the Press Release:

SOUTH SAN FRANCISCO, Calif., Dec. 10, 2025 (GLOBE NEWSWIRE) — BridgeBio Oncology Therapeutics, Inc. (“BBOT”) (Nasdaq: BBOT), a clinical-stage biopharmaceutical company focused on RAS-pathway malignancies, today announced late-breaking preclinical data on BBO-10203, a first-in-class covalent small molecule RAS:PI3Kα breaker that selectively and specifically blocks the physical interaction between RAS and PI3Kα resulting in the inhibition of RAS-driven PI3Kα-AKT signaling in tumors without inducing hyperglycemia. The data is being presented today at the San Antonio Breast Cancer Symposium (SABCS). BBOT will also present a trial in progress poster on the Phase 1 BREAKER-101 trial in patients with locally advanced or metastatic HER2+ breast cancer, HR+/HER2- breast cancer, KRAS mutant colorectal cancer, and KRAS mutant non-small cell lung cancer on Friday, December 12.

“PIK3CA mutations are common, particularly in HR+/HER2- and HER2+ advanced breast cancer,” said Andreas Varkaris, MD, PhD, Attending Physician and Investigator at Massachusetts General Hospital and an investigator in the BREAKER-101 study. “Historically, we have treated these patients with successive generations of PI3K inhibitors, which have their limitations. We now look forward to a new generation of inhibitors, such as BBO-10203, that can more selectively target the mutant enzyme without affecting normal cells, potentially enabling us to treat more patients. Importantly, by improving selectivity and tolerability, these next-generation agents may also allow for combinations with other targeted therapies, something that was challenging in the past due to toxicity.”

“Although PI3Kα inhibitors have provided an important treatment option for HR+/HER2- and HER2+ breast cancer with PI3Kα mutations, their use is often limited by dose-dependent hyperglycemia and reduced treatment duration,” said Pedro Beltran, PhD, Chief Scientific Officer of BBOT. “Our preclinical work shows that BBO-10203 offers a differentiated mechanism by disrupting the RAS–PI3Kα interaction rather than inhibiting PI3Kα’s kinase activity. Because RAS-dependent activation drives tumor growth but not glucose regulation, this approach enables broad pathway inhibition without the risk of hyperglycemia.

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