Tegavivint with PARP inhibitor talazoparib is an effective combination against MCL in vitro and in vivo. (A) MCL cell killing activity of the combination of tegavivint plus talazoparib in vitro in MCL cell lines, JeKo-1, UPN-1, and Maver. Matrices display calculated Loewe additivity scores ± standard deviation from dose concentration combinations of tegavivint and talazoparib viability studies. Matrices are color-coded; blue indicates synergistic cell killing; red, antagonism; and green represents dose combinations for which additive effect was found. Cells were treated with the indicated concentrations of talazoparib, tegavivint, and/or DMSO control, and cell viability was determined by acridine orange (AO) and propidium iodide (PI) staining and Nexcelom Cellaca cell counter. Combenefit was used to generate isobologram analyses and determine synergism (Loewe additivity model).³⁴ (B) Kaplan-Meier plot showing OS in an MCL PDX mouse model treated with tegavivint (30 mg/kg, IV via tail vein, twice weekly) and/or talazoparib (0.33 mg/kg, oral gavage, once daily for 5 days per week), or the relevant VC. Note: because of tail edema, all treatments were discontinued on day 63 (indicated on plot with black dotted line). Mean OS was 73 days for the tegavivint VC cohort (n = 7), 68 days for talazoparib VC (n = 7), 70 days for combination VC (n = 7), 79 days for tegavivint (n = 8), 96 days talazoparib (n = 8), and 108 days for combination (n = 6). P values were calculated by the log-rank Mantel-Cox test. Tala, talazoparib; Teg, tegavivint; Veh, vehicle control. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001.