AMDC Innovative Points
1. Linker
A completely new linker concept, distinct from cleavable or non-cleavable linkers, known as a 'cleavage-controlled linker.' This linker provides high blood stability while enabling specific and efficient payload release into tumor cells.
2. Conjugation
Unlike existing ADCs, conjugation of the payload with antibody mimetics does not require a complex and time-consuming process for optimizing binding and manufacturing conditions. Instead, simple mixing utilizing the high-affinity Avidin-Biotin complex enables stable complex formation of DAR2.
3. Antibody mimetics
Computationally engineered VHH tetramers bind to tumor cell target molecules with high selectivity and affinity, facilitating rapid internalization and reducing extracellular clearance.
4. Payload
Duocarmycin, a fully synthetic drug, exhibits strong antitumor activity as a payload due to its DNA alkylation mechanism and is expected to have synergistic effects with DDR inhibitors.
AMDC's Ingenious Technology
AMDC redefines the construction of all ADC formulations.
・Binding of the payload to the antigen recognition site is non-covalent
・No need to mutate the antibody structure to bind the payload
・The number of payload binding sites can be easily adjusted.
Compared to the ADC preparation method, the AMDC method is faster and simpler to implement.
・Cupid protein is easily purified in its insoluble fraction in *E. coli*.
・After solubilization with urea, the tetramer is formed by refolding.
・Psyche is a chemically synthesized compound comprising iminobiotin and a linker-attached payload.
・The final product is a complex of Cupid and Psyche, which remains stable through simple mixing.
AMDC vs. ADC
Solving ADC Formulation Issues with AMDC Formulations
How to introduce Payload (anticancer drug) into the formulation
•In ADC formulations, covalently bonded to amino acid residues through organic chemical reactions with antibodies
•In the AMDC formulation, Cupid-Psyche is introduced by non-covalent bonding through simple mixing of Cupid-Psyche
Control design for linker disconnection is no longer required.
•ADC formulations require a unique linker sequence that allows cleavage in the target cell
•The AMDC formulation does not require a special linker sequence and takes advantage of the difference between the structure of the Cupid-Psyche complex in blood and the structure of the Cupid-Psyche complex after it is taken up into the cell, which changes the environment for linker cleavage.
