B1655 is a fully humanized mAb targeting proprotein convertase subtilisin/kexin type 9 (“PCSK9”) intended to treat hypercholesterolemia. B1655 was originally developed by Mab-Science (Hong Kong) Co. Ltd. (“Mab-Science”). In September 2016, we entered into a technology transfer agreement with Mab-Science under which Mab-Science agreed to transfer to us all intellectual property and research data with respect to the fully humanized anti-PCSK9 mAb in Greater China, including all intellectual property associated with B1655 and generated during the performance of the agreement. We paid a portion of the technology transfer fees upon transfer of the technology data to us, and then initiated independent drug research & development.
Mechanism of Action
Hypercholesterolemia is caused by excessive LDL-C in the serum. Excessive LDL-C in serum is also an important factor leading to dyslipidemia. Low-density lipoprotein receptor (“LDL-R”) acts as a receptor for LDL-C to determine the uptake and degradation of LDL-C cells. The binding of PCSK9 to LDL-R inhibits the degradation of LDL-C. B1655 can specifically bind to PCSK9 and block the interaction between PCSK9 and LDL-R, which results in the uptake and degradation of LDL-C, improves the liver’s ability to clear LDL-C and lowers the amount of LDL-C in the blood, thereby achieving the purpose of treating hypercholesterolemia.
The diagram below illustrates the mechanism of action of B1655:
PCSK9-mediated degradation of low-density lipoprotein (LDL). The compound of LDL-C, LDL-R, and PCSK9 is internalized into the hepatocytes to form clathrin-coated vesicles, which are then degraded by the lysosome.
B1655 specifically binds to PCSK9 to block the binding between PCSK9 and LDL-R. LDL-R binds to LDL-C and is internalized, LDL-C is degraded by the lysosome, and LDL-R is released for re-cycling back to the hepatocyte surface.
B1655 clinical phase I trial enrollment was completed