Disc Medicine Initiates Phase 1b/2 Clinical Study of DISC-0974 in Myelofibrosis Patients with Severe Anemia

• Open-label study will evaluate the potential for DISC-0974, a first-in-class, anti-HJV (hemojuvelin) monoclonal antibody to improve anemia in myelofibrosis patients
• DISC-0974 is administered as a once-monthly, subcutaneous injection and is designed to suppress hepcidin, a critical driver of anemia in myelofibrosis and other disease of inflammation
• DISC-0974 was previously shown to decrease hepcidin levels, increase serum iron, and improve markers of erythropoiesis including hemoglobin in a phase 1 study of healthy volunteers

CAMBRIDGE, Mass., June 23, 2022 /PRNewswire/ -- Disc Medicine, a clinical-stage biotechnology company dedicated to the discovery and development of novel therapeutic candidates for serious and debilitating hematologic diseases, announced today the initiation of a Phase 1b/2 study to evaluate the efficacy and safety of DISC-0974 in myelofibrosis (MF) patients with anemia. DISC-0974 is a monoclonal antibody designed to suppress hepcidin by inhibiting the hemojuvelin (HJV) co-receptor, thereby addressing anemia by enhancing the availability of iron for erythropoiesis.

"The initiation of this study in MF patients with anemia is an important milestone in the clinical development of DISC-0974 and builds on the encouraging findings that we observed in our healthy volunteer study," said John Quisel, JD, PhD, Chief Executive Officer at Disc Medicine. "This also marks the first of several patient studies that we plan to initiate this year across our portfolio, and I'm proud of our team for this achievement."

The study will be an open-label, multi-center, Phase 1b/2 trial and will evaluate the safety, tolerability, and efficacy of DISC-0974 in myelofibrosis patients with anemia. The study endpoints will include hepcidin levels, serum iron and markers of iron mobilization and measures of anemia benefit such as hemoglobin, reductions in transfusion burden and transfusion independence (TI) rate. The study allows enrollment of patients receiving stable background therapy, including Janus Kinase (JAK) inhibitors. The study will be conducted in two parts:

• Phase 1b (Dose-Escalation): Ascending, monthly doses of DISC-0974 administered for six months to MF patients with anemia (Hb levels < 10 g/dL), where a dose level will be selected based on optimal increases in hemoglobin and serum iron;
• Phase 2 (Expansion Stage): Multiple doses of DISC-0974 administered once-a-month at the dose level selected from the phase 1b portion of the study to MF patients with anemia who are transfusion dependent (TD) according IWG-MRT criteria, defined as receiving >6 units of RBC in a 12-week period.

"There is a tremendous need for novel therapies that specifically address anemia in MF patients, which is severe and progressively worsens over time, such that nearly all patients eventually require chronic RBC transfusions," said Srdan Verstovsek, MD, PhD, Professor of Medicine at The University of Texas MD Anderson Cancer Center. "Moreover, current treatments tend to exacerbate anemia, which limits optimal therapy or is a cause of treatment failure. We are excited to participate in this clinical trial, as there is growing evidence indicating that hepcidin is a key driver of anemia in myelofibrosis."

DISC-0974 is an investigational, first-in-class monoclonal antibody designed to suppress hepcidin production by inhibiting the hemojuvelin (HJV) co-receptor, a highly selective and critical target of the hepcidin pathway with biological activity that has been validated by human genetic evidence. Hepcidin is the primary regulatory hormone of iron homeostasis and plays a central role by restricting iron absorption and preventing deployment from internal iron stores. DISC-0974 is designed to suppress hepcidin production and increase iron availability for erythropoiesis and is being developed as a potential treatment for multiple forms of anemia of inflammation. DISC-0974 is currently being studied in a phase 1 clinical study of DISC-0974 in healthy volunteers and a phase 1b/2 study in myelofibrosis (MF) patients with severe anemia.

DISC-0974 is an investigational therapy that is not approved for any use in any country. Disc obtained global rights to DISC-0974 and related molecules under a license agreement from AbbVie in October 2019.

Myelofibrosis (MF) is a rare, chronic blood cancer that currently affects an estimated 16,000 to 18,500 patients in the United States alone. Severe, progressive, and treatment resistant anemia is the primary clinical manifestation of MF and at diagnosis, over 80% of MF patients have anemia, which progressively worsens and ultimately renders the majority of patients dependent on chronic red blood cell transfusions. There are currently no approved therapies to address anemia of MF. Recent studies have shown hepcidin to be a key molecular driver of anemia in myelofibrosis. Hepcidin is elevated by approximately 12-fold in MF patients, and is correlated with disease severity, anemia, and the need for red blood cell transfusions.

Disc Medicine is a clinical-stage biopharmaceutical company that is dedicated to transforming the lives of patients with hematologic disorders. We are building a portfolio of innovative, first-in-class therapeutic candidates that affect fundamental pathways of red blood cell biology. Disc Medicine is committed to developing treatments that empower and bring hope to the many patients who suffer from hematologic disease. For more information, please visit www.discmedicine.com. 

SOURCE Disc Medicine