SL-172154 + azacitidine

**SL-172154 + azacitidine** is a combination therapy under investigation for the treatment of acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (MDS). SL-172154 is a hexameric, bi-functional fusion protein comprising extracellular SIRPα domains linked to extracellular CD40L domains via an inert IgG4-derived Fc domain. Its design enables dual action: blockade of CD47–SIRPα (a "don't eat me" signal from cancer cells to macrophages) and agonism of CD40 (activating APCs and B cells), enhancing both innate and adaptive antitumor immunity. Azacitidine is a hypomethylating agent that alters DNA methylation, restoring the function of tumor suppressor genes and promoting cell death in malignant cells. Preclinical and early clinical results suggest this combination enhances pro-phagocytic signaling and immunomodulation, potentially improving outcomes for patients with AML and higher-risk MDS, including those with TP53 mutations[1][3][5].

Other names

SIRPα-Fc-CD40L + azacitidine