Bispecific antibody-drug conjugates (BsADCs) targeting dual tumor-associated antigens (TAAs) offer advantages in fighting against cancer. The advantages of bsADCs include:
- The ability to simultaneously target multiple tumor-driven proteins, potentially overcoming drug resistance.
- Recognition of cells co-expressing both targets to increase tumor specificity and reduce off-target toxicity.
- The combination of two selected targets increases internalization and thus tumor killing.
Overview of Biocytogen’s Bispecific ADC platform
The fully human antibodies produced by RenLite® mice have a complete human heavy chain variable region with a common kappa light chain, which can effectively eliminate chain mispairing issues during the drug development process.
RenLite® mice can produce fully human antibodies with diverse epitopes and high affinity. To assemble bispecific antibodies (bsAb), KIH (knobs-into-holes) technology is used to connect the heavy chains of the two parental monoclonal antibodies, ensuring the successful assembly of a BsAb molecule with a stable monoclonal antibody structure.
Advantages of Biocytogen’s BsADC Platform
- RenLite®-derived common light chain antibodies are assembled into a BsAb with a low mismatch rate and ideal physiochemical properties.
- Immunization of RenLite® target KO mice can generate antibodies with increased diversity that potentially recognize novel epitopes of a given target. These antibodies are more likely to exhibit cross-species reactivity.
- Our platform enables rapid generation of high-quality BsAbs/BsADCs for high-throughput in vitro and in vivo screening.
- Use of a novel proprietary linker-payload system, BLD1102, which is comprised of a novel topoisomerase 1 inhibitor with broad-spectrum and potent tumor killing ability, and a uniquely designed cleavable linker with hydrophilic properties that renders conjugated antibodies as hydrophilic as monoclonal antibodies. Preclinical studies indicate BLD1102-ADCs exhibit good stability and tolerability in vivo.
Discovery of Novel BsADCs: Project Integrum
As part of Biocytogen’s Project Integrum, combinations of TAA-targeting antibodies generated from RenLite® mice are subsequently assembled and evaluated in vivo for pharmacologic efficacy, and subjected to in vitro analyses. The company’s large animal translational platform will further screen out products with better translational properties: