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NX-5948 + obinutuzumab is an investigational drug combination consisting of bexobrutideg (NX-5948), an oral, brain-penetrant, highly selective small-molecule degrader of Bruton's tyrosine kinase (BTK), and obinutuzumab (Gazyva), an approved glycoengineered, type II anti-CD20 monoclonal antibody. Bexobrutideg functions as a proteolysis-targeting chimera (PROTAC) that recruits the cereblon (CRBN) E3 ubiquitin ligase complex to induce the ubiquitination and subsequent proteasomal degradation of both wild-type and mutated forms of BTK, thereby overcoming resistance to conventional BTK inhibitors. Obinutuzumab targets CD20 on B cells, inducing direct cell death and enhancing antibody-dependent cellular cytotoxicity (ADCC). The combination is being co-developed by Nurix Therapeutics and Roche and is currently in Phase 1b/2 clinical trials for the treatment of B-cell malignancies, including chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).
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