BTK degradation and anti-CLL activity of NRX-0492 in PDX model. In vivo activity was tested in the PDX model of CLL. Ten NSG mice were inoculated with PBMCs from patient #5539 with CLL. (A) Schematic display of the experimental schedule. (B) Representative histogram of AF647-BTK staining in CLL cells from peripheral blood (pb) on day1 before drug treatment (left) and after 7 days of treatment with NRX-0492 (day 8, right). (C-E) Mean (± SEM) CLL AF647-BTK MFI in peripheral blood on day 8 (C), day 22 (D), and spleen on day 22 (E). Each symbol represents 1 mouse. (F, G) Mean (± SEM) percentage of Ki67 expression in CLL cells in peripheral blood on day 8 (F), day 22 (G), and spleen on day 22 (H). (I, J) The percentage of CD69 positive CLL cells in peripheral blood (I) and spleen (J) on day 22. (K) Mean total cell counts (± SEM) of human cells (CD45⁺), T cells, and CLL cells in spleen on day 22. Comparisons are by unpaired student t test; ns, not significant. Veh, vehicle; NRX, NRX-0492; pb, peripheral blood; sp, spleen.