Boan Biotech announced today that its BA1202, a CEACAM5 (CEA)/CD3 bispecific antibody, has been administered to the first subject in a Phase I clinical trial. This makes BA1202 the first CEA/CD3 bispecific antibody to undergo a clinical trial in China.
With a novel format, BA1202 has the potential to be used alone or in combination with other drugs
BA1202 is a CEA/CD3 bispecific antibody that binds to both CD3 on T cells and CEA on tumor cells, enabling the linking of T cells with tumor cells to facilitate tumor killing. CEA is widely expressed on the cell surface of many epithelial tumors, such as colorectal cancer, non-small cell lung cancer (NSCLC), pancreatic cancer, and gastric cancer, but is expressed less in normal tissues, making it a potential target for tumor-targeted therapy. As a transmembrane protein on the surface of T cells, CD3 can bind to the T-cell receptor (TCR) to form a receptor complex, activate T cells, and stimulate the release of granzymes and perforin from T cells, so as to effectively kill cancer cells. In addition, anti-CD3 bispecific antibodies can enhance the sensitivity of immunotherapy as they can help turn cold tumors into hot ones by increasing immune cells infiltration into tumor tissues. This characteristic indicates their potential for use in combination with immune checkpoint inhibitors for enhanced efficacy.
BA1202 adopts a new butterfly-shaped antibody format, with one end binding bivalently with high affinity to CEA on tumor cells, and the other end binding monovalently with relatively low affinity to CD3 on T cells, while retaining the Fc region. Such a design enables it to reduce the risk of cytokine release syndrome (CRS) while retaining good efficacy.
BA1202 is faster than other CEA/CD3 bispecific antibodies in development with various indications
As the first CEA/CD3 bispecific antibody to undergo a clinical trial in China, BA1202 demonstrated strong therapeutic potential in the pre-clinical studies. BA1202 exhibited excellent killing activity against CEA-positive tumor cells. In the colorectal cancer model in mouse, it completely eradicated tumors, and demonstrated the anti-tumor effect even at a low dose of 0.1mg/kg, showing a good dose-effect relationship. Compared to single agent use, BA1202 demonstrated enhanced in vivo anti-tumor effects when used in combination with anti-PD-L1 antibodies et al. Moreover, BA1202 also demonstrated good safety in the repeat-dose toxicity study in transgenic mice. The results of these studies have been published in Antibody Therapeutics.
Dr. Dou Changlin, President of R&D and Chief Operating Office of Boan Biotech, said: "BA1202 is the first CEA/CD3 bispecific antibody candidate developed with our T-cell Engager platform. It has an innovative format and mechanism of action, we are fast in developing it, and its clinical development is also very promising. We will spare no effort to advance its clinical development, to provide a breakthrough therapy for patients with CEA-positive malignancies such as gastric cancer, lung cancer, and colorectal cancer."