YH005 is a recombinant humanized Claudin 18.2 monoclonal antibody. We have out-licensed YH005 to RemeGen for the development RC118, a potentially first-in-class ADC for the treatment of solid tumors. RC118 has obtained TGA approval for clinical trials in Australia and is currently under IND application process in China.

Claudin 18.2 (CLDN18.2) is an intercellular tight-junction protein and a member of the CLDN family, which comprises 24 members. Normally, this protein is selectively expressed only in differentiated gastric mucosal epithelial cells, but in cancer, it is expressed in primary gastric tumors and their metastatic lesions. It is also frequently ectopically activated in pancreatic, esophageal, ovarian, and pulmonary tumors.

Claudin 18.2 has prognostic value in gastric cancer and is a promising molecular target for anti-tumor drugs. Antibodies targeting Claudin 18.2 can activate ADCC and CDC effects and induce tumor cell apoptosis.

However, multi-transmembrane proteins like Claudin 18.2 are challenging as antigens due to their multiple transmembrane structures, small exposed extracellular regions, and the low success rate of antibody discovery. Current strategies to prepare Claudin 18.2 antigens include ECL1 polypeptide, VLP displaying ECL1, cell antigen expressing Claudin 18.2, and mimic membrane protein.

YH005 is a monoclonal antibody produced by Claudin 18.2 knockout mice immunized with different antigens. It specifically binds to Claudin 18.2 and shows promise as a therapeutic option for solid tumors.