KY1070 leads to an EPO-sparing effect. Female ACD rats were used to evaluate an EPO-sparing effect of KY1070 combination therapy (for further details on the study protocol, please see supplemental Figure 10A-C and supplemental “ACD rats EPO-sparing protocol”). (A) The weekly number of Darbepoetin alfa (EPO) applications needed for anemia correction in ACD rats with an EPO monotherapy (left panel; n = 10) and KY1070 + EPO combination (right panel; n = 11) is shown. (B) Percent of applied Darbepoetin alfa doses in total (week 1 to 4) and consequent reduction of EPO doses needed (in %) is indicated. (C) Number of possible vs indeed consumed EPO doses in total (week 1 to 4) is shown. (D) Differences (Δ) in hemoglobin (ΔHgb) for CKD mice treated with indicated combinations of KY1070 and Darbopoietin alfa. Pooled data from 5 separate experiments are plotted. Δ values refer to the difference in the parameter value between the given combination treatment group and IgG4 isotype control-treated CKD group in each experiment. Results are shown as means ± SEM, and n, numbers, are presented. Surface of plotted circles is proportional to the Δ value. Statistical significance was assessed using Fisher's exact test (C) and with a 2-sided Student t test with Benjamini-Hochberg correction for multiple testing. **P < .01. Colored circles indicate statistical significant Δ values (P < .05); gray circles indicate insignificant Δ values. Comb, combination; ns, not significant.