DISC-0974 (anti-HJV mAb)
for Anemia of Inflammation
DISC-0974 is a first-in-class monoclonal antibody against
hemojuvelin (HJV) to suppress the production of hepcidin
and enhance iron levels to treat anemia of inflammation.
Biological Role of Hemojuvelin
Hemojuvelin (HJV) serves a critical function in iron metabolism and is required for hepcidin production. HJV is unique that its role is specific to iron regulation and is selectively expressed in the liver, where hepcidin is produced. DISC-0974 binds to and prevents signaling through the HJV pathway, resulting in suppression of hepcidin expression which improves availability of iron for erythropoiesis. This mechanism has been validated by human genetics, where patients with mutations in HJV have constitutively reduced hepcidin and elevated levels of iron.
Anemia of Inflammation and Chronic Disease
Anemia of inflammation (AI, also known as anemia of chronic disease or ACD) is one of the most common forms of anemia, comprising up to 40% of all anemias and affecting millions of patients, including those with cancer, chronic kidney disease, and autoimmune diseases. Hepcidin is a key driver of the disease as inflammation induces excessive hepcidin production and restricts iron absorption and utilization. These forms of anemia are refractory to current treatments, but exploratory clinical studies with modest inhibitors of the hepcidin pathway have demonstrated promising effects on anemia. We believe that targeting HJV provides a uniquely selective and potent approach to suppress hepcidin and normalize iron metabolism.
DISC-0974 was in-licensed from Abbvie and is in advanced preclinical development. We have completed IND-enabling studies and initiated a phase 1 clinical study in healthy volunteers in 2021. Our plan is to develop DISC-0974 to treat multiple forms of anemias of inflammation: we have initiated a phase 1b / 2 study in patients with anemia of myelofibrosis (MF) and are planning additional studies in patients with anemia of chronic kidney disease (CKD) and other indications.