Zymeworks reports new preclinical data from ADC candidates ZW220 and ZW251

Zymeworks (ZYME) announced new preclinical data for Zymeworks’ antibody-drug conjugate, or ADC, candidates ZW220 and ZW251 in presentations at the European Organisation for Research and Treatment of Cancer-National Cancer Institute-American Association for Cancer Research, or EORTC-NCI-AACR, Conference taking place in Barcelona on October 23-25. An oral presentation titled “ZW220, a NaPi2b-directed topoisomerase I inhibitor Antibody-Drug Conjugate, demonstrates compelling preclinical activity in NSCLC, ovarian and uterine cancer models, with a favorable toxicology profile in non-human primate” highlights preclinical data that continue to support an IND submission in the first half of 2025. Results demonstrate that ZW220 has the potential for improvement over previous NaPi2b ADCs and on the basis of efficacy, tolerability and payload mechanism. ZW220 features a novel, moderate potency TOPO1i payload with strong bystander activity, beneficial for tumors with low and heterogeneous NaPi2b expression. We believe it offers a differentiated safety profile compared to other ADCs currently in the clinic, demonstrating high tolerability in animal studies with MTD greater than or equal to90 mg/kg in non-human primates and greater than or equal to200 mg/kg in rats, suggesting potential for high doses in humans. A poster titled “ZW251, a novel glypican-3-targeting antibody-drug conjugate bearing a topoisomerase I inhibitor payload, demonstrates compelling preclinical activity in hepatocellular carcinoma models” highlights preclinical data that continue to support an IND submission in the second half of 2025. Results demonstrate that ZW251 shows promise as a new treatment option for patients, potentially improving upon the current standard of care. Demonstrating strong anti-tumor activity across a wide range of hepatocellular carcinoma models, including those with lower and heterogenous GPC3 expression, ZW251 was designed with a DAR of four, striking a balance between tolerability and broad anti-tumor effectiveness.