LP-108 + azacitidine

LP-108 + azacitidine is a combination therapy under investigation for the treatment of relapsed or refractory myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). LP-108 is an oral, highly potent, and selective small molecule inhibitor of BCL-2, a protein that helps cancer cells evade apoptosis. Its mechanism is similar to that of venetoclax but with potentially greater potency. Azacitidine is a nucleoside analog classified as a DNA methyltransferase inhibitor; it works by causing hypomethylation of DNA at low doses and direct cytotoxicity at higher doses through incorporation into RNA and DNA. The combination aims to enhance antileukemic activity by targeting both apoptotic pathways (via BCL-2 inhibition) and epigenetic regulation/cytotoxicity (via azacitidine). This regimen has shown acceptable safety profiles and encouraging efficacy in early-phase clinical trials for patients with r/r MDS, CMML, or AML[2][3][5].