Rethinking ADC Design: Lessons from NBE-002 and the Potency of PNU-159682

Antibody-drug conjugates (ADCs) have emerged as a transformative class of targeted cancer therapeutics, combining the specificity of monoclonal antibodies with the cytotoxicity of potent payloads. The development of NBE-002*, an ROR1-targeted ADC using the highly potent anthracycline derivative PNU-159682, provides valuable insights into the opportunities and challenges of ADC chemical design. By examining the story of NBE-002, we can better understand how payload potency, linker chemistry, and conjugation strategy determine both preclinical promise and clinical limitations.