Iron-restricted Anemia
SRK-256 for iron-restricted anemia
We are discovering and developing novel selective inhibitors of RGMc/HJV for the treatment of iron-restricted anemia. Iron-restricted anemia is a consequence of insufficient iron being present in the bloodstream, despite sufficient iron being present within the patient cells. This condition occurs in patients with chronic inflammatory conditions, chronic kidney disease and myelofibrosis.
Our preclinical program for the treatment of iron-restricted anemia targets the BMP signaling pathway which controls the expression of hepcidin, a key controller of the body’s ability to regulate the availability of iron for use by the body. In iron-restricted anemia, aberrant elevation of hepcidin leads to the trapping of iron within cells, leaving insufficient iron available in the blood for the production of red blood cells. We believe that targeting this BMP signaling specifically in the liver gives us the potential to address iron-restricted anemias.
Within the liver, BMP signaling is regulated by a co-receptor molecule, RGMc, also known as hemojuvelin (HJV). HJV is a protein whose expression is largely restricted to the liver and has a specific role in iron homeostasis, demonstrated by people with mutations in the gene. By targeting RGMc/HJV instead of the more broadly expressed BMPs, we can selectively control iron homeostasis under conditions where BMP signaling and consequently hepcidin expression is aberrantly high.
We have leveraged our antibody discovery platform to target RGMc/HJV specifically over closely related family members RGMa and RGMb that act similarly to bind BMPs but modulate very different biological pathways. Our anti-RGMc antibody inhibits its interaction with BMPs and thus inhibits BMP signaling selectively in the liver and reduces the expression of hepcidin which in turn results in an increase in iron in the bloodstream. We are conducting preclinical research on this molecule, which has the potential to alleviate anemia in patients with iron restriction.
We are advancing our iron-restricted anemia program towards investigational new drug (IND)-enabling studies.
