ALX90

ALX90 is an engineered recombinant fusion protein designed as a high-affinity inhibitor of CD47, a myeloid checkpoint protein often overexpressed by cancer cells to evade immune destruction. Developed by ALX Oncology, ALX90 serves as a preclinical tool compound for the clinical-stage therapeutic evorpacept (ALX148). The molecule is composed of the N-terminal D1 domain of SIRPα genetically linked to an inactive human IgG Fc domain. This design allows for potent blockade of the "don't eat me" signal (CD47-SIRPα interaction) while minimizing hematological toxicities, such as anemia and hemagglutination, typically caused by CD47-binding agents with active Fc regions. Research has demonstrated that ALX90 can enhance the efficacy of standard-of-care regimens like venetoclax and azacitidine in acute myeloid leukemia (AML) models, particularly when combined with agents that activate medullary macrophages.