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NEBULA is a combination therapy regimen consisting of nemtabrutinib, bortezomib, and rituximab. It is primarily being investigated for the treatment of Waldenström's Macroglobulinemia (WM). Nemtabrutinib is a reversible, non-covalent inhibitor of Bruton's tyrosine kinase (BTK), designed to overcome resistance associated with the C481S mutation. Bortezomib is a proteasome inhibitor that induces apoptosis in plasma cells, and rituximab is a monoclonal antibody targeting CD20 on B-cells. The combination aims to provide a synergistic effect by targeting multiple pathways in B-cell malignancies. This regimen is currently being evaluated in a Phase II clinical trial (NCT05814107) sponsored by Seoul National University Hospital.
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