GSK’s $300M Acquisition of Chimagen’s CMG1A46: A Deep Dive into B Cell-Targeted Trispecific T Cell Engagers

On October 29, GSK made headlines with a $300 million upfront payment to acquire Chimagen Biosciences’ clinical-stage asset, CMG1A46, a dual-target CD19/CD20 trispecific T cell engager (TCE). This acquisition signals GSK’s commitment to advancing therapies for B-cell-driven autoimmune diseases, such as systemic lupus erythematosus and lupus nephritis, with possible applications in other autoimmune conditions.

B Cell Depletion Therapy in Autoimmune Diseases

B cell therapies are capturing growing interest as a promising approach to treating autoimmune diseases. B cells play a central role in these conditions, producing antibodies that mistakenly attack the body’s own tissues. B cell depletion therapy (BCDT) offers promising treatment options for conditions such as systemic lupus erythematosus, rheumatoid arthritis, and lupus nephritis. This approach involves selectively depleting, clearing, or inhibiting B cells at various stages of their lifecycle—development, maturation, and activation. Throughout their lifecycle, B cells express different surface antigens, such as CD19, CD20, CD38, CD138, BCMA, and BAFF. CD19, for example, appears across multiple stages, from Pro-B cells to plasma cells, while CD20 is found from Pre-B to memory B cells, making both ideal targets for B cell depletion therapies in autoimmune disease treatment.

CMG1A46 is a trispecific antibody targeting CD19 and CD20 on B cells with high affinity and CD3 with low affinity. Preclinical studies show it effectively depletes B cells in blood and tissue while minimizing TCE toxicity, overcoming resistance issues in single-target therapies and showcasing strong therapeutic potential.

B Cell-Related Drug-Targeted Humanized Models

Biocytogen has pioneered the development of drug-targeted humanized mice carrying human CD3E and CD3EDG genes, along with B-cell-specific dual and multi-targets, creating powerful in vivo models for assessing TCE bispecific, trispecific, and multispecific antibodies in autoimmune disease research within a human biological context. Our portfolio also includes humanized mice targeting additional B cell-related proteins, such as CD40/CD40L and BAFF/BAFFR.

Are Trispecific Antibodies the Next Frontier in Disease Treatment?

By inhibiting multiple signaling pathways or targeting multiple cell types, bispecific and multispecific antibodies significantly enhance therapeutic efficacy. However, developing these antibodies presents challenges, particularly with chain mispairing during production. Our proprietary RenLite® mice, designed to generate antibodies with a common light chain, greatly reduce heavy and light chain mismatching during bispecific and multispecific antibody assembly. Paired with knobs-into-holes (KIH) technology, RenLite® achieves an assembly success rate of over 95%, simplifying the CMC process. The resulting bispecific antibodies from RenLite® mice retain structures similar to monoclonal antibodies and exhibit strong physicochemical properties. Using RenLite® KO mice, Biocytogen has developed an OX40 bispecific antibody, BCG028, for autoimmune disease therapy, demonstrating superior in vivo efficacy compared to traditional OX40 monoclonal antibodies.

Expanding on these advancements, Biocytogen, with its RenTCR-mimic™ platform, and CtM Bio, with its T-cell Engager platform, have jointly developed a WT1/HLA-A02-specific T cell engager (WT1xCD3x4-1BB tri-specific antibody). This project has achieved significant milestones, demonstrating impressive preclinical anti-tumor activity against both hematological malignancies and solid tumors.

Looking Forward

Development of bi- or tri-specific TCEs marks an exciting new chapter in the fight against various diseases, offering hope for more targeted, effective therapies. At Biocytogen, we’re committed to supporting this progress by equipping researchers with the advanced tools needed to accelerate discoveries and innovations.

To explore how our drug-targeted humanized mouse models and antibody platforms can elevate your research, request a demo and connect with our team today!