ORM-6151 + azacitidine

ORM-6151 + azacitidine is an investigational combination therapy consisting of ORM-6151 (BMS-986497), a first-in-class degrader-antibody conjugate (DAC), and azacitidine, an established hypomethylating agent. ORM-6151 comprises a CD33-targeting monoclonal antibody conjugated to a GSPT1 (G1 to S phase transition 1) protein degrader payload (SMol006). By targeting CD33, ORM-6151 selectively delivers the GSPT1 degrader to myeloid leukemia cells, inducing GSPT1 protein degradation and subsequent cell death. Azacitidine is a nucleoside metabolic inhibitor that incorporates into DNA and RNA, leading to DNA hypomethylation and cytotoxicity. The combination was developed by Bristol Myers Squibb (which acquired the asset from Orum Therapeutics in 2023) and was evaluated in a Phase 1 clinical trial (NCT06419634) for the treatment of relapsed or refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In September 2026, Bristol Myers Squibb discontinued the development of ORM-6151, terminating the Phase 1 trial due to strategic and clinical data reviews.