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Bexobrutideg + venetoclax (NX-5948 + venetoclax) is an investigational combination therapy being evaluated for the treatment of B-cell malignancies, specifically chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). The combination pairs bexobrutideg (NX-5948), an orally bioavailable, brain-penetrant, highly selective small-molecule degrader of Bruton's tyrosine kinase (BTK), with venetoclax, an FDA-approved small-molecule inhibitor of B-cell lymphoma 2 (BCL2). Bexobrutideg functions as a proteolysis-targeting chimera (PROTAC) that recruits the cereblon (CRBN) E3 ligase complex to ubiquitinate and degrade both wild-type and mutant forms of BTK, thereby overcoming resistance associated with traditional BTK inhibitors. Venetoclax selectively binds and inhibits BCL2, an anti-apoptotic protein, restoring the apoptotic pathway in cancer cells. By combining targeted BTK degradation with BCL2 inhibition, this regimen aims to achieve synergistic anti-tumor activity and deeper, more durable responses in patients with relapsed/refractory or treatment-naïve CLL/SLL. The combination is being co-developed by Nurix Therapeutics and Roche.
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