Topoisomerase 1 Inhibitor
Zymeworks camptothecin payload is specifically designed for antibody-drug conjugate (ADC) use, and is paired with established linker and conjugation technologies that provide a good balance of stability, safety, and anti-tumor activity.
Zymeworks Topoisomerase-1 inhibitor technology uses a novel fit-for-purpose camptothecin payload with moderate potency and strong bystander activity in conjunction with a traceless, plasma-stable, cleavable peptide linker. The properties of the drug-linker enable conjugation at a drug to antibody ratio of 8. Catabolism of the ADC following target engagement, internalization, and lysosomal trafficking releases the topoisomerase inhibitor payload ZD06519.
We keep the ADC in mind, from concept to pipeline.
Our lead payload was developed specifically for ADCs, with selection driven by moderate potency, limited hydrophobicity, and favorable ADME characteristics. We believe that ADCs must rely on more than a drug-linker platform; we pair our TOPO1i platform with antibodies selected for their superior PK, internalization and tumor penetration. Robust tolerability in non-human primate toxicology studies support clinical dosing in the range of >5mg/kg.