KRAS belongs to the RAS family of small GTPases and is one of the most frequently mutated oncogenes in human cancers. Under normal physiological conditions, KRAS cycles between an inactive, GDP-bound state (“OFF”) and an active, GTP-bound state (“ON”), regulating cellular growth, proliferation and survival.

Oncogenic KRAS alterations disrupt this normal regulatory cycle and promote sustained activation of downstream signaling pathways, including the RAF–MEK–ERK pathway, thereby supporting tumor-cell proliferation and survival.

Unlike inhibitors designed to target a single KRAS mutation subtype, pan-KRAS inhibitors are intended to address a broader range of KRAS-driven tumors. JAB-23E73 inhibits both the ON and OFF states of KRAS, providing the potential to suppress KRAS signaling across different functional states while sparing HRAS and NRAS.

Preclinical studies demonstrated that JAB-23E73 inhibited intratumoral p-ERK signaling and produced antitumor activity in multiple models harboring KRAS mutations or KRAS amplification.

KRAS alterations are found across a broad range of solid tumors. Approximately 23%–25% of patients with cancer harbor KRAS mutations, with particularly high prevalence in pancreatic cancer, colorectal cancer and non-small cell lung cancer.

JAB-23E73 is being evaluated in patients with advanced solid tumors harboring KRAS mutations or amplification. Tumor types under investigation include: PDAC, CRC, NSCLC, and other solid tumors.

In addition to monotherapy development, JAB-23E73 is being evaluated in combination with standard chemotherapy to address additional treatment settings and patient populations.

AstraZeneca holds exclusive development and commercialisation rights for JAB-23E73 outside mainland China. In mainland China, Jacobio and AstraZeneca will jointly develop and co-commercialise JAB-23E73.

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