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Feature|Videos|August 5, 2026

What Determines a Best-in-Class Antibody Drug Conjugate

Key Takeaways

  • Recognize why best-in-class ADC design depends on integrating multiple attributes rather than a single innovation.
  • Understand how real-time MS monitoring supports faster conjugation process decisions.
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Understand why a best-in-class antibody drug conjugate (ADC) depends on balancing antibody, linker, conjugation chemistry, and payload together.

Episodes in this series

Sponsored by Waters Corporation

Identifying what separates a best-in-class ADC from an adequate one is complicated by the fact that no single technique or innovation determines success. Zhengqi Zhang, Associate Principal Scientist at Merck & Co., explains that achieving a best-in-class molecule requires integrating the antibody, conjugation chemistry, linker, and payload as a coordinated system. He describes how his team uses real-time mass spectrometry (MS) based methods—high-throughput size exclusion mass spectrometry (SEC-MS) and hydrophobic interaction chromatography mass spectrometry (HIC-MS)—to monitor conjugation and reduction reactions as they happen, supporting faster decision-making during process development. Linker stability and payload potency must be balanced against each other; a linker that is too stable can create payload-release issues, while one that is too labile can raise off-target toxicity. Determining the drug-to-antibody ratio (DAR), or DAR distribution requires weighing potency, pharmacokinetics, and linker and payload stability together rather than applying a fixed rule.

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