Zymeworks Presents New Preclinical Data on a PD-1 x VEGF x IL-7 Multispecific Antibody at the Society for Immunotherapy of Cancer Conference

We are pleased to present preclinical data on our novel IL-7 immunocytokine in a poster presentation at the annual Society for Immunotherapy of Cancer (SITC) Conference, taking place November 4-8 in Pheonix, Arizona.

Presentation Highlights

Engineering targeted IL-7 delivery to enhance anti-tumor T cell fitness and persistence
Abstract Number: 810

PD-1 blockade is the standard of care across multiple cancer indications, but benefit is not always durable, and many patients do not respond. By simultaneously neutralizing tumor angiogenesis, PD-1 x VEGF bispecific antibodies offer an opportunity to increase clinical responses, but benefit to patients could be further enhanced by increasing the durability of anti-tumor immune response.

In this poster, we describe a PD-1 x VEGF multispecific antibody carrying an engineered IL-7 that is attenuated and masked so that IL-7 signals mainly on PD-1-positive T cells, with minimal activity on bystander T cells. The product candidate builds on our protein engineering and immunology expertise, including our experience engineering attenuated, conditionally active, targeted cytokines, and on an AI-driven, high-throughput multispecific workflow that lets us screen and refine designs rapidly. The transition from PD-1 bispecific antibodies to trispecific antibodies aims to address the clinical limitations of current checkpoint approaches.

Key Highlights:

  • Combining a selected IL-7 mutation with masking strategies in the IL-7mut x PD-1 x VEGF multispecific provides approximately 200- to 1000-fold selectivity for PD-1+ T cells
  • The VEGF-binding domain acts as a mask for IL-7 in addition to full-strength VEGF blockade equipotent to clinical benchmarks
  • PD-1 blocking domain provides sustained, complete PD-1 inhibition equivalent to clinical antibody benchmark
  • Format-dependent properties allow complexing with VEGF for enhanced PD-1 blockade and IL-7 potency
  • IL-7mut x PD-1 x VEGF enhances T cell survival, function and fitness, and can restore function to exhausted T cells in patient tumor samples
  • An automated, AI-driven workflow using Azymetric™ solutions for proper chain pairing enabled rapid development of 3- and 4-chain IL-7 immunocytokine constructs

 

The poster is available to conference attendees as a virtual e-poster on the SITC website, as well as on Zymeworks’ website at https://www.zymeworks.com/publications/.