Tolero Pharmaceuticals Presents Positive Preclinical Data on Hepcidin Inhibition for the Treatment of Anemia Associated with Chronic Disease
Data Presented in Oral Presentation at the 57th ASH Annual Meeting and Exposition
SALT LAKE CITY, UT - December 7, 2015 - Tolero Pharmaceuticals, Inc., a clinical-stage pharmaceutical company developing treatments for serious hematological diseases, today announced that it presented positive preclinical data on its hepcidin lowering agent, TP-0184
, in an oral presentation at the 57th American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida. TP-0184 inhibits activin-like kinase-2 (ALK2) activity leading to lowering of hepcidin levels, which is a master regulator of iron homeostasis caused by chronic inflammation. In patients with certain chronic inflammatory diseases such as chronic kidney disease, rheumatoid arthritis, colitis as well as in some forms of cancer, increased hepcidin levels lead to anemia which can be severely debilitating.
"TP-0184 is uniquely positioned as an orally available ALK2 inhibitor that lowers circulating hepcidin levels, increases bioavailable iron and reverses anemia in multiple models of chronic inflammation. Hepcidin signaling represents an attractive target for the treatment of anemia in individuals with chronic inflammatory diseases," said Steven L. Warner, Ph.D., Vice President of Discovery and Development at Tolero. "We are actively advancing this promising drug candidate towards clinical studies."
Current therapies for anemia are often either not well-tolerated or ineffective at treating anemia caused by functional iron deficiency. TP-0184 utilizes a novel approach to address current clinical challenges. TP-0184 reversed symptoms of anemia in three separate disease models, acute turpentine oil induced inflammatory response, lung cancer, and heat-inactivated Brucella abortus induced infectious response. Additionally, TP-0184 has favorable pharmacokinetic properties and drug-like characteristics, making 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 morphogenetic 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.
Tolero Pharmaceuticals, Inc.
Click here to open a PDF version