KTI-mAb2.1 / Keros Therap - LARVOL DELTA

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

A Monoclonal Antibody Targeting ALK2 As a Potential Therapeutic Agent for Anemia of Inflammation (ASH 2021) - "We further described that administration of a selective small molecule ALK2 kinase inhibitor (KTI-2338) reversed changes in hepcidin and iron in a mouse model of CKD, supporting the potential benefit of ALK2 inhibition in AI...The treatment group received twice weekly intraperitoneal treatment with KTI-018 (CKD-KTI-018), and the control group received tris-buffered saline (CKD-TBS)... After 42 days of adenine or vehicle administration, serum hepcidin, serum iron, and hematologic parameters were assessed in representative cohorts of CKD-TBS and healthy mice. The CKD-TBS cohort experienced changes associated with anemia of inflammation as compared to the healthy mice, including increased hepcidin, decreased serum iron, and decreased hematologic parameters. The differences between the healthy and CKD-TBS groups were maintained through the duration of the study."

Anemia • Chronic Kidney Disease • Fibrosis • Hematological Disorders • Immunology • Inflammation • Nephrology • Renal Disease • IL6 • TGFB1