Shanghai, China—InxMed (Shanghai) Co., Ltd. (“InxMed” or “Company”), a clinical stage biotech company dedicated to developing innovative, individualized medicines with international impact, announced today one study in collaboration with Ruijin Hospital, Shanghai Jiaotong University School of Medicine made an online publication on Advanced Science titled “Focal Adhesion Kinase (FAK) Inhibition Synergizes with KRAS G12C Inhibitors in Treating Cancer through the Regulation of the FAK–YAP Signaling”. This study demonstrated that cancer cells under the effect of KRAS G12C inhibition induce sustained activation of focal adhesive kinase (FAK) leading to its drug resistance and showed that a combination therapy comprising KRAS G12C inhibition and a FAK inhibitor (IN10018) achieves synergistic anticancer effects with multiple in vitro and in vivo models. It can simultaneously reduce the extent of drug resistance to improve treatment outcomes of KRAS G12C inhibitors.

 (Article link: https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202100250 ) 

FAK is one of the downstream targets of KRAS. Its inhibition is effective against KRAS mutant cancers preclinically. FAK activation is closely related to drug resistance of chemotherapies and targeted therapies. This study elucidated that the sustained hyperactivity of FAK signaling induces the drug resistance KRAS G12C inhibition. Diverse CDX and PDX models of KRAS G12C mutant cancers were tested and synergistic benefits from the combination therapy of KRAS G12C inhibitors (AMG510 or MRTX849) and FAK inhibitor (IN10018) were consistently observed. Mechanistically, it is found that aberrant FAK–YAP signaling leading to the development of KRAS G12C inhibitor resistance. This study provides an innovative combination therapy strategy to improve treatment outcomes for KRAS G12C mutant cancers.

Dr. Zaiqi Wang, InxMed’s Chairman and CEO, said “This study showed that FAK inhibitor (IN10018) overcomes drug resistance of KRAS G12C inhibitors and provides a potential innovative combination therapy to improve treatment outcomes for KRAS G12C mutant cancers. FAK inhibitor (IN10018) has performed three clinical trials in United States, Australia and China which showed IN10018 with good safety tolerance and antitumor effects. InxMed will fully develop on translational medicine research and global clinical trial organization capabilities to resolve the problem of unmet needs from clinics and eventually benefit patients by providing efficient treatment options.”

About IN10018

IN10018, formerly known as BI853520, is a potent and selective ATP-competitive focal adhesion kinase (FAK) small molecule inhibitor under clinical development stage in United States, Australia, and China. InxMed owns the exclusive global rights for development and commercialization. Early clinical data of IN10018 has demonstrated a favorable safety profile and promising efficacy signals against a number of tumor types. Emerging science also showed that FAK inhibitors, like IN10018, potentially overcomes fibrotic barrier and immune tolerance, boosting multi-modalities including targeted therapy, chemotherapy, immune-therapy and radiation therapy.

About InxMed

InxMed is a clinical-stage biotech company established in the end of 2018. Our innovations are inspired by patients and driven by in-depth understanding of disease biology. InxMed is committed to building an efficient engine for clinical translational science and proof of concept platform and being a China based biotech company with global impact. InxMed has built translational medicine and clinical development team across Shanghai, Beijing, United States, Canada and Australia focusing on tumor resistance and metastasis especially new drug development on anti PD-1/PD-L1 treatment drug resistance. We have built a highly differentiated pipeline driven by “Best-in-Disease Combination” and owned the patent right globally and established licensing or co-development partnership with various multinational pharmaceutical companies including Merck, Roche and Boehringer Ingelheim.