KTI-mAb2.0 / Keros Therap - LARVOL DELTA

COMBINING ALK2 INHIBITION WITH A MODIFIED ACTIVIN RECEPTOR IIA LIGAND TRAP PROVIDED ADDITIVE BENEFITS IN RESOLVING ANEMIA IN A MOUSE MODEL OF ANEMIA OF INFLAMMATION (EHA 2023) - "KTI-m216 at 3mg/kg reduced hepcidin for 72h, and liberated spleen iron from the recycling pathway to increase iron availability, resulting in improved iron-restricted erythropoiesis in CKD mice. Combining the iron mobilization properties of KTI-m216 with the stimulation of erythropoiesis from RKER-050 increased the potential to resolve anemia in this AI model. Erythropoieisis, Anemia, Hepcidin, Iron metabolism"

Preclinical • Anemia • Chronic Kidney Disease • Hematological Disorders • Inflammation • Nephrology • Renal Disease • IL6

ALK2 Inhibition and a Modified Activin Receptor Type Iia Ligand Trap Cotherapy Maximized Hematologic Improvements in a Mouse Model of Anemia of Inflammation (ASH 2022) - "These data illustrate that inhibition of ALK2 with KTI-m216 could potentially release sufficient iron from the recycling pathway to ameliorate anemia, but not restore RBC parameters to normal levels. Combined treatment with activin receptor ligand trap, RKER-050 and KTI-m216 normalized the RBC production in this preclinical model. These data support that increasing erythropoiesis with RKER-050 combined with iron mobilization with KTI-m216 has the potential to achieve the maximal amelioration of anemia in AI."

Preclinical • Anemia • Chronic Kidney Disease • Hematological Disorders • Immunology • Inflammation • Nephrology • Renal Disease • ACVR2A • IL6

ALK2 INHIBITION LOWERED HEPCIDIN AND LIBERATED SPLEEN IRON FOR ERYTHROPOIESIS IN ANEMIA OF INFLAMMATION (EHA 2022) - "We developed two investigational neutralizing antibodies against ALK2, KTI-m216 (m216) and KTI-m218 (m218), with unique variable regions but observed to have similar affinity for ALK2 and effect on hepcidin suppression in mice and monkeys. Conclusion These data suggest that IL-6-induced hepcidin is largely independent of ALK2, but ALK2 inhibition may be sufficient to result in a net hepcidin reduction and improved erythropoiesis. Data also suggest that, in AI with adequate iron stores, ALK2 inhibition potentially acts by liberating iron from the recycling pathway."

Anemia • Chronic Kidney Disease • Hematological Disorders • Immunology • Inflammation • Nephrology • Renal Disease • IL6