Anti-Claudin 18.2 antibody YH005 ADC

YH005 is a recombinant humanized Claudin 18.2 monoclonal antibody generated by our Claudin 18.2 knock-out mice.

We have out-licensed Claudin 18.2 antibody YH005 to RemeGen to develop a YH005 ADC, which is also known as RC118.

The RC118 has obtained approval for Phase I clinical trials in Australia in August 2021, and has obtained approval for Phase I clinical trials in China in September 2021. The clinical studies are currently in smooth progress and ongoing dose escalation study demonstrates good safety and tolerability. The RC118 has been granted two orphan drug designations by the U.S. FDA for the treatment of gastric cancer, including gastroesophageal junction cancer, and pancreatic cancer.

Target Claudin 18.2

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.


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