Zymeworks Presents Preclinical Data on ZW171 at the Society for Immunotherapy of Cancer (SITC) Conference

We are pleased to present preclinical data on ZW171 in a poster presentation at the annual SITC Conference, taking place November 6-10 in Houston, TX.

The poster presentation titled “Mechanistic QSP modeling and translational strategy for determining an FIH dose for ZW171, a bispecific 2+1 T-cell engager molecule targeting mesothelin and CD3” (Abstract #: 1062) demonstrates how a Quantitative System Pharmacology (QSP) model was developed for ZW171 using in vitro data, pharmacokinetics (PK) data from cynomolgus monkey, and literature data (e.g., CD3 receptors per T cells, number of T cells in central and peripheral compartments, and clinical PK data of MSLN-targeting TCE) to facilitate the selection of ZW171 starting dose for Phase 1 clinical study.

Key Highlights:

  • A MABEL approach is commonly used to select the starting dose for bispecific CD3 T-cell engagers in first-in-human (FIH) studies based on the most sensitive in vitro assay, potentially leading to selection of a sub-optimal dose.
  • The fit-for-purpose QSP model for ZW171 was established to integrate physiological information (e.g., T cells, MSLN+ cells, CD3/MSLN expression, receptor dynamics), in vitro cytotoxicity data, and preclinical PK data.
  • Unlike traditional MABEL, which relies solely on in vitro data, the QSP-based MABEL approach characterizes the complex interplay between ZW171 and its target antigens.
  • The QSP-based MABEL approach was used to determine the starting dose for the ZW171 Phase 1 clinical study.

 

The Phase 1 clinical trial (NCT06523803) evaluating the safety and tolerability of the investigational therapy ZW171 in the treatment of advanced or metastatic ovarian cancer, non-small cell lung cancer (NSCLC), and other cancers that express mesothelin is now actively recruiting.