We’re excited to share further details on our upcoming presentations at the European Organisation for Research and Treatment of Cancer-National Cancer Institute-American Association for Cancer Research (EORTC-NCI-AACR) Conference taking place in Barcelona on October 23-25, 2024.

Oral Presentation:

Title: 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
Session Type: Plenary Session 6
Session Title: Proffered Papers: New drugs on the Horizon
Session Code: 110
Date/Time: Friday, October 25 / 12:00 – 12:12 pm Central European Summer Time (CEST).

About ZW220

ZW220 is an antibody-drug conjugate (ADC) that targets sodium-dependent phosphate transporter 2b (“NaPi2b”)-expressing NSCLC and ovarian cancer, is (like ZW191) built using our proprietary TOPO1i-based payload technology. The NaPi2b-targeting monospecific antibody incorporated in ZW220 was generated in-house and selected based on a favorable binding profile and enhanced internalization properties to enable targeting of both high- and low-expressing NaPi2b-expressing tumors. A drug-to-antibdy ratio (DAR) of four was selected to balance tolerability and efficacy, with the fragment crystallizable (“Fc”) gamma receptor being silenced with the goal to minimize potential toxicities associated with this target. NaPi2b is expressed in approximately 96% of ovarian and 87% of non-small cell lung cancer (NSCLC), with anti-tumor activity being demonstrated in patient-derived cell lines and growth inhibition in 3D spheroid NSCLC models (data generated using ZW220 that had a wildtype Fc region of the antibody). The bystander effect of the TOPO1i payload may help address NaPi2b heterogeneity across different cancers. We expect to submit an investigational new drug application (IND) and non-U.S. applications for ZW220 in 2025.

The abstract and presentation will be available to conference attendees on the virtual meeting platform on October 25, 2024 at 10:00 am CEST. The presentation will also be available on the Publications page of our website.

Poster Presentation:

Title: ZW251, a novel glypican-3-targeting antibody-drug conjugate bearing a topoisomerase I inhibitor payload demonstrates compelling preclinical activity in hepatocellular carcinoma models
Session Title: Antibody-Drug Conjugates
Catalog Number: 177
Poster Board Number: PB165
Date/Time: Thursday, October 24 / 9:00 am – 5:30 pm CEST

Abstract Highlights:

• ZW251 antibody backbone demonstrated strong binding to GPC3-expressing cancer cell lines.
• Rapid internalization of ZW251 antibody was observed in GPC3-expressing HCC cell lines.
• ZW251 exhibited potent and target-specific cytotoxicity in HCC cells cultured as 3D spheroids.
• ZW251 showed effective bystander-mediated killing of GPC3 negative cancer cells when in co-culture with GPC3 positive cancer cells.
• A single administration of ZW251 resulted in robust tumor growth inhibition of a panel of CDX and PDX models representing a range of GPC3-expression.
• A repeat-dose NHP toxicology study of ZW251 showed encouraging tolerability and dose-dependent antibody pharmacokinetics at 30, 60, and 120 mg/kg dose levels, with the 120 mg/kg level determined as the maximum tolerated dose (MTD).

About ZW251

ZW251, a potential first-in-class ADC molecule designed for the treatment of glypican 3 (“GPC3”)-expressing hepatocellular carcinoma (“HCC”), which incorporates the same Zymeworks proprietary bystander-active TOPO1i payload utilized in ZW191 (anti-FRα) and ZW220 (anti-NaPi2b). A DAR of four was selected to balance tolerability and efficacy, with ZW251 anti-tumor activity observed in multiple patient-derived xenograft models of HCC reflecting a range of GPC3 over-expression. GPC3, a glycosylphosphatidylinositol (“GPI”)-anchored cell surface oncofetal antigen, is over-expressed in most HCC patients (>75%), and displays minimal normal adult tissue expression, making it an appealing ADC target. We are encouraged by published research demonstrating the potential of GPC3-targeting antibody in HCC patients as evidenced by tumor localization of iodine radiolabeled condrituzumab, a prior clinical-stage anti-GPC3 mAb, and believe that ADC-based targeting of GPC3 could enable a novel and effective approach to treatment of HCC. We expect to submit an IND and non-U.S. applications for  ZW251 in 2025.

The poster will be available to conference attendees as a virtual e-poster on the virtual meeting platform on October 23, 2024, at 9:00 am CEST, as well as on the Publications page of our website.