DISC-0974 / Disc Medicine, AbbVie - LARVOL DELTA

RALLY MF: A phase 2 Study of DISC-0974, an anti-hemojuvelin antibody, in patients with myelofibrosis and anemia (ASH 2025) - P1/2 | "A stable dose ofconcomitant hydroxyurea and/or Janus kinase (JAK) inhibitor (ruxolitinib and fedratinib for primarycohorts; momelotinib and pacritinib for exploratory cohort) was allowed. Based on these initial data, the protocol was amended to allowconcomitant momelotinib or pacritinib in all cohorts. Preliminary results, including baselinecharacteristics, PD, and hematologic responses across all cohorts, will be presented."

Clinical • P2 data • Anemia • Hematological Disorders • Immunology • Myelofibrosis

DISC-0974: “Hematologic responses achieved across transfusion cohorts and regardless of concomitant JAKi use“; Myelofibrosis (Disc Medicine) - ASH 2025

P2 data • Hematological Malignancies • Myelofibrosis • Oncology

Disc Medicine Presents Positive Initial Data from RALLY-MF Phase 2 Trial in Patients with Myelofibrosis (MF) and Anemia at the 67th American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - "Initial results demonstrated: Consistent, substantial decreases in hepcidin reaching >75% reduction from baseline and corresponding increases in serum iron; 63% of baseline nTD patients achieved a hemoglobin increase of ≥1 g/dL for ≥12 weeks (overall response) and 50% had an increase of ≥1.5 g/dL for ≥12 weeks (major response)....50% of patients receiving concomitant JAK inhibitor therapy achieved a major hematologic response; Dosing with DISC-0974 was associated with improvements in FACIT-Fatigue scores in nTD and TD Low participants....Additional data to be shared in H2 2026."

P2 data • Anemia • Myelofibrosis

Anti-Hemojuvelin Monoclonal Antibody Alleviated Anemia Induced By Ruxolitinib Treatment in Mice (ASH 2024) - P1, P1/2 | "DISC-0974 is a humanized anti-hemojuvelin (HJV) monoclonal antibody. These data highlight the therapeutic potential of anti-HJV monoclonal antibodies in the treatment of anemia in diseases such as MF, in which ruxolitinib is a commonly used therapy that may be a significant additional factor in the development of anemia. The combination therapy may enhance the benefits of JAK inhibitors, particularly in the patient population with MF and anemia."

Preclinical • Anemia • Chronic Kidney Disease • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Myelofibrosis • Nephrology • Oncology • Renal Disease

Molecular and Cytokine Correlates of Anemia Response to Treatment with DISC-0974 (An Anti-Hemojuvelin Antibody) in Non-Transfusion-Dependent Patients with Myelofibrosis (ASH 2024) - P1/2 | "Twelve (60%) patients were on DISC-0974 monotherapy while 9 (40%) received concomitant ruxolitinib (N=5), pacritinib (N=1), or hydroxyurea (N=3). Elevated inflammatory cytokines in MF are often associated with increased hepcidin levels (AJH 2013 : 88 : 312) and this might explain their association with a higher response rate to DISC-0974, observed in the current study. Regardless, it is important to note that these observations represent preliminary data from a subset of patients from an ongoing clinical trial."

Clinical • Anemia • Hematological Disorders • Myelofibrosis • ASXL1 • CALR • IL18 • IL2RA • IL6 • SF3B1 • SRSF2 • U2AF1

A Phase 1b Double-Blind, Placebo-Controlled Study of DISC-0974, an Anti-Hemojuvelin Antibody, in Patients with Non-Dialysis Dependent Chronic Kidney Disease and Anemia (ASH 2023) - P1 | "Secondary endpoints include changes in serum hepcidin-25, iron, TSAT, ferritin, Hgb, and other hematology biomarkers. Enrollment is currently ongoing, and available study results will be presented at the meeting."

Clinical • P1 data • Anemia • Chronic Kidney Disease • Hematological Disorders • Immunology • Nephrology • Renal Disease

Anti-Hemojuvelin Monoclonal Antibody DISC-0974 Elicits a Durable and Consistent Response with Repeated Dosing in Cynomolgus Monkeys (ASH 2023) - "Increases in serum iron (up to approximately 3-fold baseline) (Figure 1) and TSAT (>90%), representative of PD activity, correlated with systemic exposures of DISC-0974, with similar activity maintained after each of the 7 monthly doses. ConclusionOverall, these data demonstrate that DISC-0974 is well tolerated after repeated monthly exposure in cynomolgus monkeys, and an appropriate and durable PK/PD profile was observed, supporting clinical development of chronic once-monthly dosing."

Anemia • Chronic Kidney Disease • Hematological Disorders • Myelofibrosis • Nephrology • Renal Disease

A Phase 1b Trial of DISC-0974, an Anti-Hemojuvelin Antibody, in Patients with Myelofibrosis and Anemia (ASH 2023) - P1/2 | "A stable dose of hydroxyurea and/or Janus kinase (JAK) inhibitor is allowed on trial. As of August 1, 2023, enrollment and dose escalation are ongoing. Safety, PK, and PD data from at least the first two cohorts will be presented."

Clinical • P1 data • Anemia • Hematological Disorders • Immunology • Myelofibrosis

A Phase 1b, Double-Blind, Placebo-Controlled Study of DISC-0974, an Anti-Hemojuvelin Antibody, in Patients with Nondialysis-Dependent CKD and Anemia (KIDNEY WEEK 2025) - P1 | "Multiple-dose cohort enrollment is ongoing to evaluate optimal regimen for sustained Hgb increase. Complete SAD and available multiple-dose cohort data are forthcoming."

Clinical • P1 data • Anemia • Chronic Kidney Disease • Hematological Disorders

Disc Medicine Announces Presentation of Initial Data from RALLY-MF Phase 2 Trial in Patients with Myelofibrosis (MF) and Anemia at the 67th American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - "We will also present a poster on the design of our ongoing Phase 2 trial of DISC-3405 in polycythemia vera. We expect to share an initial readout for this trial, as well as for the Phase 1b trial of DISC-3405 in sickle cell disease, in 2026."

Clinical data • Clinical protocol • Anemia • Myelofibrosis • Polycythemia Vera • Sickle Cell Disease

Anti-Hemojuvelin Monoclonal Antibody Reverses Anemia and Exerts Disease-Modifying Effects in a Mouse Model of Inflammatory Bowel Disease (ASH 2024) - P1, P1/2 | "Of note, while some beneficial effects of DBIO-100 were equivalent to those of mesalamine, others showed superiority. The findings highlight the therapeutic potential of DISC-0974 in the treatment of anemia of chronic inflammatory disease such as IBD."

Preclinical • Anemia • Chronic Kidney Disease • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • Myelofibrosis • Nephrology • Renal Disease • IL6 • TNFA

A Phase 1b Study of DISC-0974, an Anti-Hemojuvelin Antibody, in Patients with Myelofibrosis and Anemia (ASH 2024) - P1/2 | "A stable dose of concomitant hydroxyurea and/or Janus kinase (JAK) inhibitor was allowed. Sustained hepcidin reduction with DISC-0974 led to increased serum iron that preceded hematological response. Additional Phase 1b data, including longer follow-up, will be presented."

Clinical • P1 data • Anemia • Hematological Disorders • Immunology • Musculoskeletal Pain • Myelofibrosis • Pain

Initial data from Phase 2 RALLY-MF trial of DISC-0974 in patients with anemia of myelofibrosis (MF) to be presented…with topline data expected in 2026 (GlobeNewswire)

P2 data • Anemia • Myelofibrosis

DISC-0974: Anti-Hemojuvelin Antibody (Hepcidin Suppression) (GlobeNewswire) - "Phase 2 study in patients with inflammatory bowel disease (IBD) and anemia anticipated to begin in Q1 2026."

New P2 trial • Inflammatory Bowel Disease

Disc Medicine to Present Data from Phase 1b Trial of DISC-0974 in Patients with Chronic Kidney Disease (CKD) and Anemia at 2025 American Society of Nephrology (ASN) Kidney Week (Disc Medicine Press Release) - "The poster presentation will provide a data update from the Phase 1b, randomized, placebo-controlled study of DISC-0974 in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) and anemia. This study was designed to assess the safety, tolerability and pharmacokinetics of single ascending and multiple doses of DISC-0974, as well as measures of pharmacodynamic activity, including changes to hepcidin, iron, and hematologic parameters."

P1 data • Chronic Kidney Disease

Individualizing Treatment Selection in MF (SOHO 2025) - P3 | "These include the activin receptor ligand trap luspatercept, the telomerase inhibitor imetelstat, the selective inhibitor of nuclear export selinexor, the human double minute 2 inhibitor navtemadlin, and the bromodomain and extra-terminal protein inhibitor pelabresib...Elritercept — another activin receptor ligand trap — and the anti-hemojuvelin antibody DISC-0974 are being developed for anemia of MF...Currently, these patients are observed or managed for thrombotic risk similarly to those with essential thrombocythemia (ET) — receiving hydroxyurea for control of cytoses, ruxolitinib for symptoms, or interferon for long-term disease modification. Encouraging data on ruxolitinib in patients with intermediate-1-risk MF, along with analyses from the COMFORT trials demonstrating the benefits of early initiation of ruxolitinib in patients with intermediate-2/high-risk MF and intriguing evidence of event-free survival (EFS) improvement with both ruxolitinib and..."

Clinical • Essential Thrombocythemia • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Myeloproliferative Neoplasm • Non-melanoma Skin Cancer • Oncology • Polycythemia Vera • Skin Cancer • Solid Tumor • ACVR1 • IRAK1

A Phase 1b Trial of DISC-0974, an Anti-Hemojuvelin Antibody, in Patients With Myelofibrosis and Anemia (SOHO 2025) - P1/2 | "DISC-0974 demonstrated safety and tolerability at evaluated dose levels. Anemia responses were achieved in non-TD and TD participants. Sustained hepcidin reduction with DISC-0974 led to increased serum iron preceding hematologic responses."

Clinical • P1 data • Myelofibrosis • Oncology

DISC-0974-103: Study of DISC-0974 to Assess the Safety, Tolerability, PK and PD of DISC-0974 in Participants With CKD and Anemia (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: Disc Medicine, Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Recent Highlights and Anticipated Milestones: (GlobeNewswire) - "Progressing RALLY-MF Phase 2 study of DISC-0974 in patients with anemia of MF with initial data expected in Q4 2025: Exploratory cohort for patients on concomitant momelotinib or pacritinib fully enrolled, and trial protocol updated to allow patients on these therapies into the main study cohorts....Initiated a Phase 2 study of DISC-3405 in patients with PV with initial data expected in 2026."

P2 data • Trial status • Anemia • Myelofibrosis • Polycythemia Vera

DISC-0974 (AN ANTI-HEMOJUVELIN ANTIBODY) IN NON-TRANSFUSION-DEPENDENT PATIENTS WITH MYELOFIBROSIS: LABORATORY CORRELATES OF MAJOR ANEMIA RESPONSE (EHA 2025) - P1/2 | "Twelve (60%) patients were on DISC-0974 monotherapy while 9 (40%) received concomitant ruxolitinib (N=5), pacritinib (N=1), or hydroxyurea (N=3). The current study suggests a robust (MR >50%) and durable (median 13+ months) anemia response in MF treated with DISC-0974 and the possibility of using biomarkers for predicting MR."

Clinical • Anemia • Hematological Disorders • Myelofibrosis • ASXL1 • CALR • IL18 • IL6 • JAK2 • SF3B1 • SRSF2 • U2AF1

ANTI-HEMOJUVELIN MONOCLONAL ANTIBODY FURTHER ENHANCES HEMATOLOGIC RESPONSE TO ESA AND/OR LUSPATERCEPT IN MICE (EHA 2025) - P1, P1/2 | "DISC-0974 is currently in clinical studies to treat anemia in patients with MF (NCT05320198) and chronic kidney disease (NCT05745883)...In the DBIO-100/ESA combo study, wild-type C57BL/6J male mice were randomized to receive vehicle, darbepoetin alfa (DPO, an example of ESA; 1 or 3 ug/kg via subcutaneous route), DBIO-100 (20 mg/kg via intravenous route), or a combination of DBIO-100/DPO... These studies confirmed that DPO (an ESA) and DBIO-147 can increase hematological parameters in wild-type mice. Adding DBIO-100, a mouse anti-HJV monoclonal antibody, to either DPO or DBIO-147 led to further hematological improvements in vivo. Moreover, DBIO-100 enhanced serum iron availability for erythropoiesis in wild-type mice."

Preclinical • Anemia • Chronic Kidney Disease • Hematological Disorders • Hematological Malignancies • Myelofibrosis • Nephrology • Oncology • Renal Disease

A PHASE 1B/2 STUDY OF DISC-0974, AN ANTI-HEMOJUVELIN ANTIBODY, IN PATIENTS WITH MYELOFIBROSIS AND ANEMIA (EHA 2025) - P1/2 | "DISC-0974 demonstrated acceptable safety and tolerability at evaluated dose levels. Hematologic responses were achieved in all participants regardless of concomitant JAK-inhibitor use. Sustained hepcidin reduction with DISC-0974 increased serum iron that preceded hematological response."

Clinical • P1/2 data • Anemia • Dermatology • Fatigue • Hematological Disorders • Infectious Disease • Musculoskeletal Pain • Myelofibrosis • Pain

DISC-0974 in combination with luspatercept and ESA (mouse model) (GlobeNewswire) - "Results showed: Treatment with DBIO-100 (a mouse analog of DISC-0974) suppressed hepcidin, enhanced iron availability, and boosted erythropoiesis in wild-type mice; Combining with DPO (ESA) or RAP-536 (mouse analog of luspatercept) led to additional hematological benefits beyond those agents alone; These results demonstrate that DISC-0974 has a distinct mechanism of action among anemia-targeted agents and highlight the potential for synergistic anemia benefits when combining DISC-0974 with other anemia-targeted agents."

Preclinical • Anemia

DISC-0974 Phase 1b in MF anemia (GlobeNewswire) - P1b/2a | N=150 | NCT05320198 | Sponsor: Disc Medicine, Inc | "Sustained hepcidin suppression, iron mobilization, and reduction in Zinc PPIX, a measure of iron restricted hemoglobin production; nTD patients: 50% of evaluable patients achieved major response of sustained mean hemoglobin increase of ≥1.5 g/dL; TD Low patients: 80% of evaluable patients achieved major response of transfusion independence over 16 weeks. Hematologic improvement was durable, and all major responders remained transfusion independent during the continuation phase; DISC-0974 was safe and well-tolerated at all evaluated dose levels."

P1 data • Anemia • Myelofibrosis

Emerging Therapeutic Approaches for Anemia in Myelofibrosis. (PubMed, Curr Hematol Malig Rep) - "The pathobiology of anemia is multifactorial, including progressive bone marrow fibrosis, decreased erythropoiesis due to high hepcidin levels leading to iron sequestration in the reticuloendothelial system, hypersplenism, erythropoiesis inhibition by myelosuppressive JAK inhibitors (ruxolitinib, fedratinib), and others...Conventional agents to manage anemia include erythropoiesis-stimulating agents, danazol, corticosteroids, and immunomodulatory agents, but responses are infrequent and lack durability...Momelotinib and pacritinib (ACVR1/JAK2 inhibitor) are the preferred JAK inhibitors for patients with cytopenias (anemia, thrombocytopenia). Luspatercept and elritercept are activin receptor ligand traps, promoting erythroid maturation and late-stage erythropoiesis...DISC-0974 is a first-in-class anti-hemojuvelin (positive hepcidin regulator) monoclonal antibody that decreased hepcidin expression, increased serum iron, and enhanced erythropoiesis in anemic patients with..."

Journal • Review • Anemia • Fibrosis • Hematological Disorders • Immunology • Myelofibrosis • Thrombocytopenia • ACVR1