LAM-003

LAM-003 is an orally active, first-in-class small molecule immunomodulatory drug developed for the treatment of acute myeloid leukemia (AML), particularly in patients with relapsed or refractory disease and those harboring FLT3 internal tandem duplication (ITD) mutations. It acts as a prodrug of the heat shock protein 90 (HSP90) inhibitor LAM-003A. By inhibiting HSP90, LAM-003 destabilizes mutant FLT3 proteins—including those resistant to existing tyrosine kinase inhibitors—leading to their degradation and subsequent antileukemic effects. Preclinical studies demonstrated that LAM-003 has potent cytotoxic activity against AML cell lines and primary samples with FLT3 mutations, regresses tumors in xenograft models, extends survival in systemic mouse models, and retains efficacy against cells resistant to other FLT3 inhibitors due to secondary mutations or stromal signaling. The drug also shows synergistic activity when combined with venetoclax (a BCL-2 inhibitor) or EZH2 inhibitors. Clinical development included a Phase 1 trial in AML; however, further development for this indication has been discontinued[1][2][4][5][6][7][8].