SALT LAKE CITY--(BUSINESS WIRE)--Tolero Pharmaceuticals, Inc., a clinical-stage company developing treatments for serious hematological diseases, today announced that it presented positive preclinical data on TP-0184 as a new approach to treating anemia associated with chronic disease at the 20th Congress of European Hematology Association (EHA) on June 13, 2015, in Vienna, Austria. TP-0184 acts to reverse increases in hepcidin, the master regulator of iron homeostasis, caused by chronic inflammatory conditions in animal models. In humans, increased hepcidin levels are present in diseases such as chronic kidney disease, rheumatoid arthritis, colitis and some forms of cancer, and the increased expression of hepcidin leads to anemia.
“Hepcidin is an attractive target for the treatment of chronic anemia in patients with chronic inflammatory diseases, as current therapies for anemia are either not well-tolerated by patients with comorbidities or ineffective at treating anemia caused by functional iron deficiency,” said David J. Bearss, PhD, CEO of Tolero. “Based on the data presented at EHA and other preclinical data, we are actively advancing TP-0184 towards clinical studies.”
Hepcidin is regulated, in part, by pro-inflammatory cytokines through activin-like receptor (ALK2) signaling. TP-0184 directly inhibits ALK2, and research presented at EHA demonstrated that by inhibiting ALK2, TP-0184 was able to reverse the increase in hepcidin in two separate disease models, acute turpentine oil induced inflammatory response and lung cancer. In addition, TP-0184 demonstrated favorable pharmacokinetic properties and drug-like characteristics, which make it a viable candidate to advance for the treatment of anemia associated with chronic inflammatory diseases.
TP-0184 is a small molecule inhibitor of activin-like kinase 2 (ALK2), also known as a bone morphogenic protein (BMP) receptor. ALK2 activation leads to high levels of hepcidin, a peptide liver hormone that functions as a master regulator of serum iron levels, particularly in response to inflammation. Anemia of chronic disease (ACD) is a condition where chronic infection, immune activation or cancer lead to high levels of hepcidin via Interleukin-6 production, which reduces iron levels in the blood to low levels. Inhibiting ALK2 with TP-0184 is a unique approach to treating ACD by reducing hepcidin expression and restoring blood iron levels to normal.
Tolero Pharmaceuticals is a clinical stage biopharmaceutical company developing treatments to improve and extend the lives of patients with serious oncological and hematological diseases. Our diverse pipeline targets important biological drivers of blood disorders to treat leukemias and anemia as well as important targets of drug resistance and transcriptional control. www.toleropharma.com