• Assessing the role of linker architecture as a key element of ADC design
• Discussion of ThioBridge® as a Next-Generation, site-specific conjugation technology for modulation of DAR and production of homogeneous ADCs
• Reviewing the use of ThioBridge® conjugation for generating ADCs with improved efficacy

ThioBridge™ is a site-specific conjugation technology designed to offer homogenous drug–antibody ratios (DARs), improved stability and pharmacokinetic profiles by exploiting natural interchain disulfide bonds to generate stable, homogeneous ADCs.

A key advantage of ThioBridge™ is its ability to consistently achieve high conversion to a single DAR species, improving the uniformity of the ADC population. This precision in conjugation supports improved manufacturing reproducibility, superior control over biophysical properties, and the potential for enhanced biological performance. ThioBridge™ also offers versatility and can accommodate a broad variety of payloads, linker architectures as well as flexibility of DAR loading with the potential to generate DAR 2, DAR 4, and DAR 8 formats as well as dual-payloads with defined DARs in a one-step process.

Beyond homogeneity, ThioBridge™ provides improvements in stability. Maleimide derived linkages are prone to deconjugation or exchange reactions in serum, which can diminish efficacy or increase systemic toxicity. In contrast, ThioBridge™ conjugates exhibit resistance to deconjugation and maintain durable attachment under physiological conditions, as demonstrated in 96-hour serum incubation studies.

Overall, ThioBridge® offers a robust, versatile, and clinically validated platform that improves homogeneity, stability, solubility, and manufacturability, enabling next generation ADC designs.