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Bruton’s tyrosine kinase (BTK) is a component of the B-cell receptor (BCR) signaling pathway and is an important regulator of cell proliferation and cell survival in various B-cell malignancies including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Waldenström’s macroglobulinemia (WM), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL) and follicular lymphoma (FL).^U

BGB-16673 is an orally available BTK-targeting chimeric degradation activating compound (CDAC) with demonstrated preclinical degradation activity against both wildtype BTK and multiple mutant forms commonly identified in patients who have progressed on BTK inhibitors.^_ BGB-16673 triggers selective BTK degradation via the intracellular ubiquitin-proteasome system. By degrading BTK, BGB-16673 blocks BCR-induced BTK activation and its downstream signaling in a rapid and sustained manner, leading to growth inhibition and cell death in B-cells.

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BGB-16673 is currently being investigated as monotherapy in two phase 1 dose-escalation/expansion studies in adult patients with relapsed/refractory (R/R) B-cell malignancies.^\

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1. Wang, H., et al. Abstract P1219: BGB-16673, a BTK degrader, overcomes on-target resistance from BTK inhibitors and presents sustainable long-term tumor regression in lymphoma xenograft models. n+Y]?`C+M+ 2023; 7(Suppl):
2. Singh, S. P., Dammeijer, F. & Hendriks, R. W. Role of Bruton’s tyrosine kinase in B cells and malignancies. %~f Uq#Z?p 2018; 17(1):57.
3. Tam, C.S, et al. Abstract P686: A Phase 1 first-in-human study of BGB-16673, a Bruton’s tyrosine kinase protein degrader, in patients with B-cell malignancies (trial in progress). n+Y]?`C+M+ 2022; 6:582-583.