Activity of NRX-0492 against IBR-resistant CLL with BTK C481S mutation. (A) PBMCs from 2 patients with CLL with clinical progression on IBR and BTK C481S mutations were treated with NRX-0492 for 24 hours at the indicated concentrations and analyzed for BTK expression by Western blotting. (B) Estimates of DC₅₀ and DC₉₀ concentrations based on data shown in A. The fraction of residual BTK and the cancer cell fractions of C481S mutations for the samples tested is indicated (C-F) PBMCs from patient with CLL #12803 who progressed on IBR with BTK C481S were used to establish the PDX model. (C) BTK and (D) Ki67 expression by flow cytometry in peripheral blood CLL cells of vehicle (Veh) and NRX-0492 treated mice on day 8; (E) Western blotting for BTK in CLL cells, selected by CD3 negative selection, from spleens on day 20.