Cancer

Cell culture and mouse studies suggest modulating SF3B1-mediated splicing alone or in combination with BCL-2 and Bcl-XL inhibitors could help treat MCL1-dependent NSCLC. In three human MCL1-dependent NSCLC cell lines, a tool compound that modulates SF3B1-mediated splicing decreased growth compared with no treatment. Also in the cell lines, the SF3B1 modulator plus a dual BCL-2/Bcl-XL inhibitor tool compound decreased growth compared with either agent alone. In two xenograft mouse models of MCL1-dependent NSCLC, the SF3B1 modulator decreased tumor volume compared with vehicle. Next steps by H3 Biomedicine Inc. include investigating the therapeutic window for SF3B1-mediated splicing modulation/Bcl-XL inhibitor combination in animal models of NSCLC.

H3 Biomedicine has H3B-8800, a small molecule modulator of SF3B1, in Phase I testing for acute myelogenous leukemia (AML), myelomonocytic leukemia and other hematologic malignancies...