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Bispecific antibody (BsAb) refers to an antibody molecule that can specifically bind two antigens or two epitopes at the same time. In theory, it can exert synergistic effect of two monoclonal antibodies, which is one of the most popular new drug research and development investment direction in the industry.

On February 5 this year, Merck and GSK of Germany announced that they have reached a global strategic cooperation alliance to jointly develop a dual-function fusion protein tumor immunotherapy M7824 targeting PD-L1/TGF-β with a protocol of 3.7 billion euros.

Bispecific antibodies are not found in nature and require manual preparation by recombinant DNA or cell fusion techniques. BsAbs constructed by means of DNA recombination and protein engineering techniques have also become one of the new research directions of antibody drugs.
There are many BsAb technology platforms in the industry, and the bispecific antibody structures developed based on these platforms are generally classified into IgG-like bispecific antibodies and non-IgG-like bispecific antibodies depending on whether or not the FC region is contained.
For example, the BsAb prepared by the platform such as Triomabs, DVD-Ig, CrossMAb and the like has an Fc region which is an IgG-like bispecific antibody, and an antibody prepared by BiTE, DART or the like lacks an Fc region, that is, non-IgG-like. Currently, three bispecific antibody drugs have been approved worldwide. Only Amgen’s Blincyto belongs to non-IgG-like bispecific antibodies, and the other two belong to IgG-like bispecific antibodies.

The mechanism of action of bispecific antibodies mainly includes three types of mediating immune cell killing, blocking of dual-target signaling pathways, and promoting protein formation of functional complexes. The mechanism of action of Removab and Blincyto mediates the killing effect of immune cells. Removab contains two antigen-binding arms that bind to the CD3 site of cytotoxic T cells and the EpCAM site of tumor cells, respectively; Blincyto binds to the CD3 site of cytotoxic T cells and the CD19 target of tumor cells, respectively, to guide T cell killing target cells.

Unlike the two, Hemlibra is a targeted antibody targeting factor X and factor IXa, allowing factor IXa and factor X to aggregate together to restore the clotting process in patients with hemophilia A.

From the post-marketing market performance, Removab is only approved by the European Commission for sale in Europe. Blincyto’s global sales in 2018 is $230 million, and Hemlibra’s global sales in 2018 is 234 million Swiss francs.

According to public information, investment and cooperative development in the field of “bispecific antibodies” has been significantly active since the second half of 2018.

After entering 2019, the “BsAb tide” swept the world. In addition to the 3.7 billion euros that Merck and GSK mentioned at the beginning of this article, there are other pharmaceutical giants that have added BsAb layout. On February 11, AbbVie and Teneobio and its subsidiary TeneoOne announced that they have signed a global development strategy cooperation on the bispecific antibody TNB-383B (BCMA|CD3) and plans to launch the Human clinical trials project in the first half of 2019.


Overview of the global “BsAb” project development

The global BsAb program is mainly concentrated in the early stage of preclinical-I stage (154), accounting for 81%; the target to be developed is mainly tumor and autoimmune diseases; the target is mainly concentrated in CD3 (69), PD1/PD -L1 (41), EGFR, 4-1BB, HER2 above.

From the perspective of enterprises, the companies with the most global BsAb projects include Amgen, Roche, Abpro, and Xencor.

In addition to the three BsAb drugs already on the market, there are currently only two Phase III projects in the global BsAb new drug pipeline, namely ABL Bio’s DLL4-VEGF project ABL001, intended for development of chronic myeloid leukemia; and Roche’s The VEGFA-Ang2 project faricimab is used to treat diabetic macular edema.



BsAb is a technology that has gradually begun to commercialize in the past decade. Its business prospects are worth looking forward to, but it should also be noted that BsAb’s current industrialization still faces some challenges, such as mismatch problems, BsAb stability and even balance of two antibodies. The amount of expression, etc. When investment cooperation tends to be frenetic, we have to be more calm and look at all kinds of data. More and more BsAb projects are expected to be commercially successful, bringing real therapeutic benefits to patients.

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