Multi-specific Antibody Platform

The distinctive features of our multi-specific antibody platform are biology function driven and structurally designed with enhanced flexibility and efficiency. The platform enables us to construct multi-specific antibodies quickly which facilitates the efficient production of multi-specific antibodies. Our multi-specific antibody platform enables us to develop antibodies simultaneously binding to different targets to achieve synergistic therapeutic functions. The major types of multi-specific antibody structure we are developing are set forth as below.

• Bispecific antibodies targeting dual TAAs: In order to simultaneously bind to two different tumor-associated antigens or two different domains of the same tumor-associated antigen, a 1:1 bispecific antibody structure based on KIH structure is designed. This type of bispecific antibodies can increase binding affinity and specificity to tumor cells, and increase tumor suppression. We are currently developing a clinical-stage drug candidate using this platform, namely MBS301, which binds to dual epitopes of HER2 and displays superior anti-tumor efficacy in vitro and in vivo.

• T cell redirected bispecific antibody: In order to recruit T cells to specifically kill tumor cells, a 2:1 bispecific antibody structure is designed, which binds to TAA by two arms and CD3 molecule by one arm to increase affinity with tumor cells and decrease the off-target toxicity of T cells. Since this type of 2:1 bispecifc antibody contains a scFv structure targeting TAA, antibody aggregation is usually a major problem affecting the production process. To address this issue, we have optimized our platform using scFv stability enhancement technology to improve drug developability. We are currently developing two preclinical-stage drug candidates using this platform, namely MBS303 (CD3/CD20) and MBS304 (CD3/Claudin18.2).

• Immune stimulation multi-specific antibody: In order to simultaneously bind to two different immune checkpoint targets, a 2:2 multi-specific antibody structure based on scFv tandem structure is designed. This type of multi-specific antibodies can be designed to enhance cross-linking, achieve efficacy synergies and increase enrichment towards tumor. We are currently developing a preclinical multi-specific antibody using this platform, namely MBS307 (CD40/PD-L1). We have also developed antibody cytokine fusion technology, by linking the mutated cytokine to the C terminal of PD-1 antagonist antibody. Based on the principle of cis-action, the fusion protein can select activated effector T cells. MBS309 (PD-1 antibody/IL2 fusion protein) is developed based on this technology. We have also applied scFv stability enhancement technology to improve drug developability.