BridgeBio doses first patient in Ph. 1 trial for KRASG12C NSCLC therapy BBO-8520

BridgeBio Oncology Therapeutics (BBOT), a clinical-stage biopharmaceutical company specializing in RAS-pathway malignancies, has dosed the first patient in its ONKORAS-101 trial. This trial focuses on the efficacy of their lead compound, BBO-8520, in treating KRASG12C non-small cell lung cancer. BBO-8520 is a pioneering small molecule that inhibits KRASG12C by binding to its Switch II pocket in both its active (GTP-bound) and inactive (GDP-bound) states, thereby hindering KRASG12C activity.

Professor Benjamin Solomon, head of lung medical oncology at the Peter MacCallum Cancer Center, shared his enthusiasm for this collaboration with BBOT. He highlighted the critical need for innovative precision oncology treatments in non-small cell lung cancer, one of the most prevalent cancers globally. Solomon emphasized that BBO-8520 has the potential to significantly improve outcomes for patients with metastatic disease by offering a novel therapeutic approach.

BBO-8520 was specifically designed to target the active state of KRASG12C, which optimizes target coverage and counters resistance mechanisms, such as KRASG12C amplification and receptor tyrosine kinase activation. These mechanisms often limit the efficacy of existing inhibitors that target only the inactive state. Preclinical studies have shown that BBO-8520 can substantially inhibit tumor growth, even in cases where resistance to FDA-approved KRASG12C (inactive state) inhibitors like sotorasib has developed.

This compound’s development is the result of a collaborative effort between the National Cancer Institute RAS Initiative at Frederick National Laboratory for Cancer Research, Lawrence Livermore National Laboratory, and BridgeBio Oncology Therapeutics. The ONKORAS-101 study aims to enroll patients who have previously been treated with first-generation KRASG12C inhibitors and those who have not undergone any KRASG12C-targeted therapies. The trial will take place across multiple regions, including the US, Australia, Canada, and the EU.

BBOT’s CEO, Eli Wallace, PhD, remarked on the significance of this Phase 1 clinical trial, marking BBOT's transition into a clinical-stage organization. He expressed gratitude for the opportunity to provide a more effective targeted therapy for patients suffering from KRASG12C-driven lung cancer, potentially improving current standards of care.

BridgeBio Oncology Therapeutics is dedicated to advancing a next-generation pipeline of small molecule therapeutics targeting RAS and PI3K malignancies. Originally a subsidiary of BridgeBio, the company secured a $200M private financing deal in 2024 to further its mission of enhancing treatment outcomes for patients with cancers driven by two of the most common oncogenes in human tumors.