Enhancing Erythropoiesis: The Impact of KER-050 on Red Blood Cell Production in Cynomolgus Monkeys

KER-050 is an innovative therapy designed to enhance red blood cell (RBC) production by targeting specific ligands in the TGFβ superfamily, which act as checkpoints in the hematopoiesis process. By inhibiting these ligands, KER-050 allows more hematopoietic precursor cells to mature into RBCs. This therapy is a fusion of a modified ActRIIA extracellular domain with the Fc region of a human IgG, capable of binding activin A, activin B, and myostatin with high affinity.

Preclinical studies have shown that KER-050 significantly raises RBC count and hemoglobin levels in mice. Encouraging results from a Phase 1 clinical study also indicated increases in RBCs, hemoglobin, and platelets following KER-050 administration.

To further evaluate KER-050's efficacy, a study was conducted on cynomolgus monkeys, a preclinical model considered highly representative of humans. Monkeys were administered subcutaneous doses of KER-050 at varying concentrations every other week for three months. Blood samples were collected to measure RBC count, hemoglobin levels, hematocrit (Hct), and absolute reticulocyte number (RET).

The results demonstrated that KER-050 significantly increased RBC count, Hgb, Hct, and RET in both male and female monkeys in a dose-dependent manner. Notably, female monkeys exhibited an increase in RBC numbers of up to 42.6% and Hct up to 36.1% at the highest dose. Similarly, male monkeys showed increases in RBC numbers of up to 62.1% and Hct up to 53.6%. Hemoglobin levels and RET also increased substantially in both genders.

These findings indicate that KER-050 is effective in enhancing erythropoiesis in higher order species. The collective results from preclinical studies and Phase 1 clinical trials suggest that KER-050 has the potential to be an efficacious treatment for anemias caused by ineffective hematopoiesis, such as myelodysplastic syndrome and myelofibrosis. The therapy's impact on stimulating hematopoiesis and RBC production offers a promising avenue for addressing these conditions.