YH003 is a novel humanized antibody targeting CD40, a member of the tumor necrosis factor receptor superfamily on the surface of immune cells. This drug promotes the activation of innate immune cells, such as dendritic antigen presenting cells (DCs), and positively regulates the effector activity of anti-tumor T cells by specifically activating the CD40 receptor signaling pathway. To date, studies have shown that CD40 activation is a key regulatory point for tumor immunotherapy, effectively transforming cold tumors lacking immune cell infiltration into hot tumors that respond well to tumor immunotherapy. Considering the inevitable defects of the traditional in vitro drug screening process, the YH003 project adopted the screening strategy of high-throughput in vivo efficacy studies combined with the investigation of side effects and toxicity in vivo in the early stages of development. The syngeneic tumor model was constructed by inoculating a variety of tumor cells into CD40 humanized transgenic mice, and then injecting different lead antibody molecules to observe the effects on tumor growth, so as to scientifically evaluate the safety and tumor inhibition effectiveness of the drug candidates in animals. Clinical drug candidates identified in this way have shown superior safety and efficacy over controls. Combining data from preclinical studies, this novel antibody targeting CD40 also has great potential in combination with chemotherapy, radiotherapy, targeted therapy and immunomodulators.
In July 2020, the Phase I clinical trial of YH003 combined with anti-PD-1 MAb (Toripalimab Injection) of TopAlliance Biosciences Inc. was officially launched in Australia. In 2021, approval was granted to initiate Phase I trials in China. In June 2021, the FDA approved initiation of Phase II studies for YH003.