BridgeBio's BBOT Begins Phase 1 Trial for BBO-10203 in Advanced Solid Tumors

SOUTH SAN FRANCISCO, CA, USA I October 30, 2024 I TheRas, Inc., operating as BridgeBio Oncology Therapeutics (BBOT), a clinical-stage biopharmaceutical company, has announced the initiation of the BREAKER-101 trial by dosing the first patient with BBO-10203. BBOT specializes in the treatment of RAS-pathway malignancies. BBO-10203 is a pioneering orally bioavailable RAS:PI3Ka breaker that interrupts the interaction between RAS and PI3Kα, thereby inhibiting the PI3Kα-AKT signaling pathway in tumors without directly affecting the catalytic activity of PI3Kα.

Dr. Minal Barve, Chief Medical Officer and Principal Investigator at Mary Crowley Cancer Research in Dallas, TX, expressed enthusiasm about collaborating with BBOT to introduce this promising new treatment in a clinical setting. Dr. Barve highlighted the potential of BBO-10203 to meet significant unmet medical needs and to revolutionize cancer care.

BBO-10203 is designed to bind covalently and selectively to the RAS-binding domain of PI3Kα. This selective inhibition is independent of the mutational status of PI3Kα and RAS. Preclinical models demonstrated that BBO-10203 completely inhibits RAS-driven pAKT signal at very low nanomolar concentrations. Moreover, no hyperglycemia was noted in preclinical tests. The discovery of BBO-10203 stemmed from a collaborative effort between the RAS Initiative at Frederick National Laboratory, Lawrence Livermore National Laboratory, and BBOT.

Pedro Beltran, PhD, Chief Scientific Officer of BBOT, emphasized that BBO-10203 is a groundbreaking program that blocks the interaction between the two most commonly mutated oncogenes in human cancer. This will enable the first-ever testing of the significance of RAS-coordinated activation of the MAPK and AKT signaling pathways. The achievement of discovering BBO-10203 was attributed to the collaborative efforts of academic, national laboratory, and industry experts dedicated to advancing cancer treatments.

The BREAKER-101 trial intends to enroll patients worldwide with locally advanced or metastatic HER2-positive breast cancer, HR-positive/HER2-negative breast cancer, KRAS mutant advanced colorectal cancer, and KRAS mutant advanced non-small cell lung cancer.

Yong (Ben) Ben, MD, Chief Medical and Development Officer of BBOT, remarked on the substantial opportunity to enhance the standard of care in oncology by inhibiting oncogenic pAKT signaling without the metabolic side effects commonly associated with kinase inhibitors. The initiation of the Phase 1 study of BBO-10203 is a crucial milestone. Dr. Ben noted that the second IND within six months of BBOT's establishment showcases the team's proficiency in advancing novel programs into clinical trials. The new mechanism and scientific rationale behind BBO-10203 promise significant combination opportunities to inhibit both pAKT and pERK optimally, potentially offering unprecedented benefits to patients with RAS-driven cancers.

BridgeBio Oncology Therapeutics (BBOT), originally formed as a subsidiary of BridgeBio, is a clinical-stage biopharmaceutical company developing innovative small molecule therapeutics targeting RAS and PI3K malignancies. In 2024, BBOT secured $200M in private financing from external investors, aiming to improve outcomes for patients with cancers driven by the most prevalent oncogenes in human tumors.