TRANSCENTA HOLDING - A Global Fully Integrated Biotherapeutics Company

Transcenta, Biologics, Antibody, Claudin 18.2

TRANSCENTA HOLDING - A Global Fully Integrated Biotherapeutics Company

Careers Contact
Project Status:
Phase II

TST002 (Blosozumab) is a humanized anti-sclerostin monoclonal antibody as a drug candidate for severe osteoporosis. It has a dual effect possessing both anabolic and anti-resorptive effects, which stimulates bone formation and inhibits bone absorption, resulting in fast increase in bone density and bone strength. 

Blocking sclerostin activity in human treated with anti-sclerostin antibody or with naturally occurring genetic deletion has been shown to be an effective approach in increasing bone mineral density (BMD) and reducing bone fracture. Currently there is no approved anti-sclerostin antibody therapy in China yet although Romosozumab from Amgen has been approved in the United States, Europe and Japan.

Mechanism of Action

The balance between bone resorption and bone deposition is determined by the activities of two principal cell types, namely, osteoclasts and osteoblasts. Therefore, the bone rebuilding cycle needs to start from the two aspects of inhibiting osteoclasts or promoting osteoblasts. The loss of gonadotropin with aging reduces the conversion of bone marrow stromal stem cells into adipocytes and decreases the differentiation of osteoblast precursor cells. The increased activity of osteoclasts results in osteocyte death and at the same time enhances bone resorption.

Sclerostin is a glycoprotein encoded by the SOST gene and produced in osteocytes. Sclerostin is an inhibitor of the WNT/-catenin signaling pathway, which stimulates osteoblast differentiation and bone formation. By inhibiting the activity of sclerostin, sclerostin mAbs can promote bone formation, reduce bone absorption and increase bone mineral density and bone strength, thus reverse the symptoms of osteoporosis.