BGB-16673 is an investigational chimeric degradation activating compound (CDAC) targeting Bruton’s tyrosine kinase (BTK), with demonstrated preclinical degradation activity against both wildtype BTK and multiple mutant forms commonly identified in patients who have progressed on BTK inhibitors.¹

Preliminary data from the first-in-human study in patients with relapsed/refractory B-cell malignancies showed meaningful clinical responses and generally tolerable safety.^2,3 Expansion cohorts in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) and R/R mantle cell lymphoma (MCL) are currently enrolling. BGB-16673 has been granted Fast Track Designation by FDA for R/R CLL.

References

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. Hemasphere 2023; 7(Suppl): e24358c2.
2. Parrondo, R., et al. Preliminary efficacy and safety of the Bruton tyrosine kinase (BTK) degrader BGB-16673 in patients with relapsed or refractory (R/R) CLL/SLL: Results from the phase 1 BGB-16673-101 study. Oral presentation at EHA 2024; abstract S157.
3. Cheah, C. Y., et al. Preliminary efficacy and safety of the Bruton tyrosine kinase (BTK) degrader BGB-16673 in patients with relapsed or refractory (R/R) indolent NHL: results from the phase 1 BGB-16673-101 study. Poster presentation at EHA 2024; abstract P1119.

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).¹

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. Targeting BTK via an alternative mechanism may overcome the current challenges of BTK inhibitors and may allow continued targeting of a critical pathway in B-cell malignancies.^2,3

References

1. Singh, S. P., Dammeijer, F. and Hendriks, R. W. Role of Bruton’s tyrosine kinase in B cells and malignancies. Mol Cancer2018; 17(1):57.
2. 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. Hemasphere2023; 7(Suppl): e24358c2.
3. An, S. and Fu, L. Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs. EBioMedicine 2018; 36:553-562.

BGB-16673 is an investigational compound for which safety and efficacy have not been established. Because of the uncertainty of clinical trials, there is no guarantee that BGB-16673 will receive regulatory approval and become commercially available for the uses being investigated.

For a complete list of BGB-16673 clinical trials, view the pipeline.