Selective CD47 targeting to improve therapeutic windows
The ubiquitous expression of CD47 on normal cells, including red blood cells, presents a therapeutic challenge. Systemic targeting of CD47, by either anti-CD47 monoclonal antibodies or SIRPα-Fc fusion proteins, yielded only moderate clinical benefit due to severe adverse side effects, mainly anemia. QLSF has developed a tumor targeted CD47 bispecific antibody with reduced binding to red blood cells while retaining potent phagocytosis of tumor cells in vitro and delayed tumor growth in vivo. QL401 also blocked the PD-L1/PD-1 checkpoint, providing a secondary mechanism of immune reactivation. QL401 was well tolerated in a toxicology study without anemia. A phase 1 clinical trial is expected to start late Q4 2021.