GM-DM1

GM-DM1 is a preclinical, long-acting **GM-CSF protein-drug conjugate** being developed for acute myeloid leukemia. It consists of recombinant human granulocyte-macrophage colony-stimulating factor fused to a human serum albumin-binding nanobody and covalently linked through a Sulfo-SMCC linker to DM1, a maytansinoid microtubule inhibitor. GM-CSF mediates selective uptake through the granulocyte-macrophage colony-stimulating factor receptor on AML blasts and leukemia stem cell-enriched populations, while also promoting cell-cycle entry; intracellular DM1 then disrupts microtubules, causing G2/M arrest and apoptosis. Preclinical studies reported selective activity in GM-CSF receptor-high AML models, including patient-derived xenografts, with reduced functional leukemia stem-cell frequency and limited toxicity to normal hematopoietic progenitors.