Boan Biotech announced today that its BA1202, a CEACAM5 (CEA)/CD3 bispecific antibody, has been approved for a clinical trial by the Center for Drug Evaluation of China's National Medical Products Administration (NMPA). BA1202 is the first CEA/CD3 bispecific antibody approved for a clinical trial in China.

BA1202 is intended for the treatment of solid tumors, including CEA-positive tumors such as advanced/metastatic colorectal cancer, non-small cell lung cancer (NSCLC), pancreatic cancer, and gastric cancer. The clinical trial approved for BA1202 is a multicenter, open-label, single-arm, and Phase 1 trial that evaluates the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of BA1202. The study consists of two phases: dose escalation and dose expansion.

CD3 bispecific antibodies are an important direction for the development of innovative cancer immunotherapies. They function by recruiting CD3+ T cells to target tumors. As a bispecific T-cell engager (BiTE), they can bind to both CD3 antigens on the T cell surface and tumor-associated antigens. This enables them to bring T cells to tumor cells and stimulate the release of granzymes and perforin from T cells, which in turn lead to the killing of tumor cells. In addition, 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 such as PD-L1 antibodies for enhanced efficacy. CEA is widely expressed on the cell surface of many epithelial tumors, such as colorectal cancer, NSCLC, pancreatic cancer, and gastric cancer, but is expressed less in normal tissues, making it a potential target for tumor-targeted therapy.

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.

BA1202 adopts a new butterfly-shaped antibody structure, 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 through activating endogenous T cells to eliminate CEA-positive tumor cells.

Pre-clinical studies showed that BA1202 exhibited excellent killing activity against CEA-positive tumor cells. In the colorectal cancer model in mouse, it completely eradicated tumors, and showed a good dose-effect relationship which demonstrated the anti-tumor effect even at a low dose of 0.1mg/kg. BA1202 also demonstrated good safety in a repeat-dose toxicity study in transgenic mice. Compared to other CEA/CD3 antibodies being developed abroad, BA1202 demonstrated more potent anti-tumor activity both in vivo and in vitro. Moreover, compared to single agent use, BA1202 demonstrated enhanced in vivo anti-tumor effects when used in combination with PD-L1 antibodies. The results of the study have been published in Antibody Therapeutics.¹

Dr. Dou Changlin, President of R&D and Chief Operating Office of Boan Biotech, said: "BA1202 was developed on the company's proprietary T-cell Engager Platform. The platform technology provides bispecific antibodies with a symmetrical structure that avoids light chain mispair and balanced and controllable affinities for the tumor target and T cells. These features make the product high on efficacy, low on toxicity, and low on immunogenicity. Compared to other similar products under development internationally, BA1202 has demonstrated enhanced efficacy in animal studies, and its mode of action is expected to reduce the risk of CRS, which commonly appears for the similar products in clinical use. In a word, BA1202 has demonstrated differentiation advantages as shown in pre-clinical data. We will step up the effort to accelerate its clinical development, fully explore its clinical advantages and value, and provide patients with relevant cancers more treatment options."