The Evolving Bioconjugate Landscape

As the diversity of conjugated therapeutics has grown, the field has moved beyond early lysine-based conjugation methods that produced unpredictable drug loading. Zhengqi Zhang, Associate Principal Scientist at Merck & Co., traces how this challenge has been addressed since 2016, when most antibody-drug conjugate (ADC) programs relied on lysine conjugation and basic measurement of drug-to-antibody ratio (DAR). The industry’s shift toward site-specific cysteine and glycan conjugation has improved control over where and how many drug molecules attach to an antibody. The discussion also covers how payload classes have expanded from microtubule inhibitors to topoisomerase-1 inhibitors and DNA- or RNA-damaging agents. The average DAR has also risen from three or four toward ten or higher. These advances have extended bioconjugation beyond oncology into new therapeutic areas, while regulators increasingly ask not just whether an attribute can be measured, but why it matters for patients.