Antibody-drug conjugates (ADCs) are designed to combine the specificity of antibodies directed against tumor-associated targets with potent cytotoxicity. Upon internalization of the ADC, the antibody-bound cytotoxic payload is released intracellularly, leading to programmed tumor cell death.
While the cytotoxic payloads used in the majority of advanced programs in the field prevent tubulin polymerization during cell division, Synthon's differentiated linker-drug technology - applying valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA) - is based on synthetic duocarmycin analogs, which bind to the minor groove of DNA and subsequently cause irreversible alkylation of the DNA. This disrupts the nucleic acid architecture, which subsequently leads to tumor cell death.
Duocarmycins are able to exert their mode of action at any phase in the cell cycle, whereas tubulin binders will only attack tumor cells when they are in the mitotic phase. Growing evidence demonstrates that DNA damaging agents, such as duocarmycins, are more efficacious in tumor cell killing than tubulin binders, particularly in solid tumors.
Although based on natural products, Synthon's proprietary ADC linker-drug technology uses fully synthetic duocarmycin analogs. The unique design of the selectively cleavable linker connecting the antibody to the duocarmycin drug leads to high stability in circulation and induces efficient release of the cytotoxin in the tumor.
Synthon's ADC technology aims to create ADCs having an optimal therapeutic window, balancing the effect of potent cell-killing agents on tumor cells versus healthy cells.