Antibody-drug conjugates (ADCs) offer significant advantages in antibody-based drug research and development, combining accurate antibody targeting with efficient small molecule killing. Despite significant progress in ADC technologies, including linker and payload technologies, the currently approved ADC targets are limited. The identification of safe and effective innovative targets remains a key challenge in ADC field.
Bispecific antibodies represent a new drug mechanism that has the potential to offer significant benefits in the treatment of cancer. Bispecific antibody-drug conjugates (ADCs) targeting dual tumor-associated antigens (TAAs) offer a range of advantages in the fight against cancer. These include the ability to simultaneously target multiple tumor-driven signaling pathways, potentially overcoming drug resistance. Moreover, bispecific ADCs can efficiently bind to and kill tumor cells that co-express dual TAAs, thereby increasing tumor targeting specificity and reducing off-target toxicity. The dynamic mechanism of dual-target binding and endocytosis exhibited by bispecific ADCs also leads to a more efficient tumor-killing synergy, offering new hope for cancer patients.
The Bispecific ADC platform based on the RenLite® mouse offers significant advantages in the development of fully human bispecific antibody-drug conjugates (ADCs).
1. RenLite® mouse produces fully human antibodies with a common light chain, which effectively addresses the challenge of mismatch between heavy and light chains in the development of bispecific antibodies, thereby improving the success rate of assembly.
2. RenLite® mouse produces highly diverse antibodies with high affinity. The use of knobs-into-holes (KIH) technology to connect the heavy chains of two parent monoclonal antibodies ensures the successful assembly of a stable monoclonal antibody structure, which is essential for the development of bispecific ADC molecules.
3. With the support of Project Integrum and our integrated antibody discovery, conjugation technology, pharmacology and efficacy evaluation platform, we are conducting high-throughput antibody discovery and screening for hundreds of TAA targets. We will screen all potential bispecific ADC combinations for efficacy both in vivo and in vitro. Furthermore, we will validate these combinations using our own large-animal translational medicine platform, which will provide valuable translation data and improve the clinical success rate."
Bispecific ADCs Under Development
AACR 2022: YH012, a Novel Bispecific Anti-HER2 and TROP2 Antibody-Drug Conjugate, Exhibits Potent Antitumor Efficacy
World ADC San Diego2022：YH013, a fully-human EGFR x MET bispecific ADC exhibits outstanding specificity and anti-tumor efficacy
PEGS-EU 2022:YH013, a fully-human EGFR x MET bispecific ADC exhibits outstanding specificity and anti-tumor efficacy
AACR 2023: A First-In-Class Anti-HER2/TROP2 Bispecific Antibody-Drug Conjugate (YH012) Exhibits Potent Anti-Tumor Efficacy
AACR 2023: YH013, a Novel Bispecific EGFR x MET Antibody-Drug Conjugate, Exhibits Potent Anti-Tumor Efficacy
AACR 2023: A Novel EGFR x MUC1 Bispecific Antibody-Drug Conjugate, BSA01, Targets MUC1 Transmembrane Cleavage Products and Improves Tumor Selectivity
AACR 2023: BCG022: A Novel Bispecific Antibody-Drug Conjugate Targeting HER3 and MET
AACR 2023: Discovery of BCG033, A Novel Anti-PTK7 x TROP2 Bispecific Antibody-Drug Conjugate with Promising Efficacy Against Triple-Negative Breast Cancer
AACR 2023: A First-In-Class Anti-TROP2/EGFR Bispecific Antibody-Drug Conjugate, DM001, Exhibits Potent Anti-Tumor Efficacy
AACR 2023: A First-In-Class Bispecific Antibody-Drug Conjugate (DM002) Targeting HER3 and the Juxtamembrane Domain of MUC1
AACR 2023: Identification of DM004, A First-In-Class Anti-5T4/MET Bispecific Antibody-Drug Conjugate