KY1070 mobilizes iron for erythropoiesis in 2 rodent models of chronic anemias and has a synergistic effect on anemia resolution when combined with Darbepoetin alfa. (A-C) ACD in female Lewis rats was induced by intraperitoneal administration of group A streptococcal peptidoglycan-polysaccharide. ACD rats were treated with IgG4 isotype control (ACD; n = 8), KY1070 (3 mg/kg; n = 9), EPO (10 µg/kg; n = 8), or both (n = 7). Hgb, RBC, MCV, MCH (A), plasma hepcidin levels (B), plasma iron levels and Tf-Sat (C) were determined in ACD rats at the end of treatment (week 4; see also supplemental Figure 4A). (D-G) CKD in male C57BL/6N mice was induced by a diet containing 0.2% adenine. CKD mice were either treated with IgG4 isotype control (CKD; n = 5), KY1070 (3 mg/kg; n = 6), Darbepoetin alfa (10 µg/kg; n = 6), or both (n = 6). (D) Hematological parameters (Hgb, RBC, MCH, and MCV) were determined in CKD mice at the end of treatment (week 4; see also supplemental Figure 7A). Plasma EPO levels (E), plasma iron levels, Tf-Sat (F), liver Hamp mRNA and plasma hepcidin levels (G) of indicated mice following treatment (week 4; see also supplemental Figure 7A). A naive control group was included in all experiments (n = 5 [rats], n = 7 [mice]). Two-way ANOVA with Tukey corrected post hoc Student t test for multiple comparisons between ACD and CKD animals was applied. Results are shown as means ± SEM. *P < .05; **P < .01; ***P < .001.