SITC 2022 Poster 491

HX009, A Novel BsAb Dual Targeting PD-1xCD47, Demonstrates Potent Anti-Lymphoma Activity

Hang Ke, Faming Zhang, Jingjing Wang, Lingxin Xiong, Annie An, Xiaolong Tu, Cunxiang Ju, Yueying Wang, Binchen Mao, Xiangfei He, Ruiling Sun, Lei Zhang, Henry Li

PD-1/PD-L1 blockade has demonstrated limited activity in most subtypes of Non-Hodgkin Lymphoma (NHL) save for NK/T-cell lymphoma. Strategies to block CD47, the ‘Do Not Eat Me’ receptor, have also demonstrated marginal activity in select NHL subtypes. The development of thrombocytopenia and anemia with select anti-CD47 agents in the clinic has been speculated to account for some of the limitations with these drugs.

Herein we describe a first-in-class bispecific (BsAb) anti-PD-1 x SIRPα, HX009, targeting both PD-1 and CD47 but with weakened CD47 binding, which selectively hones the antibody for the tumor microenvironment (TME) through the PD-1 interaction, potentially reducing off-tumor CD47 interactions, while augmenting anti-lymphoma activity.

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• In vitro characterization of HX009
  
  
• Preclinical in vivo pharmacology modeling
  
  
• Genomic biomarker analysis

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