Disc presents clinical, translational data across portfolio at ASH meeting

DISC-0974: DISC-0974+Ruxolitinib Mouse Model: Wild-type mice were randomized to receive doses of placebo, ruxolitinib, DBIO-100, or a combination of ruxolitinib and DBIO-100. Results showed: Ruxolitinib treatment alone reduced hemoglobin by 1.2 g/dL in wild-type mice, inducing anemia; Adding treatment with DBIO-100 had a positive impact on anemia, increasing hemoglobin by 0.8 g/dL and further enhancing serum iron availability; These results highlight the potential for DISC-0974 to treat anemia of myelofibrosis in patients where disease-directed therapies such as ruxolitinib can significantly contribute to the development of anemia. DISC-0974 in a Mouse Model of Inflammatory Bowel Disease: The effect of DISC-0974 on improving anemia in a dextran sodium sulfate-induced colitis mouse model was evaluated. Results showed: Treatment with DBIO-100 suppressed hepcidin, increased serum iron, increased hemoglobin by up to 6 g/dL, and effectively alleviated anemia in IBD mice; Treated mice also experienced protective effects against IBD, evidenced by attenuated weight loss, decreased disease activity index score, preserved colon length, improved colon histopathology, and reduced markers of inflammation; These results highlight the potential value of DISC-0974 in treating anemia of chronic inflammatory diseases, such as IBD, and add to the body of evidence supporting the application of DISC-0974 to broadly address anemia of inflammation. DISC-3405: Healthy Volunteer Study: Complete SAD/MAD data from the Phase 1 trial of DISC-3405 in healthy volunteers were presented. In the SAD portion of this trial, healthy males and females ages 18 to 65 were given a single dose of placebo or DISC-3405 at 75 mg intravenously, 37.5 mg subcutaneously, 75 mg SC, 150 mg SC, or 300 mg SC. The MAD portion included placebo, 75 mg SC, and 150 mg SC cohorts dosed every 4 weeks for a total of 2 doses. Results showed: DISC-3405 produced dose-related increases in serum hepcidin with corresponding reductions in serum iron across all dose levels; DISC-3405 resulted in deep reductions in serum iron that were sustained and support a once-monthly SC dosing regimen; Single and repeat dosing of DISC-3405 demonstrated meaningful reductions in hematologic parameters, including reticulocyte hemoglobin, hemoglobin, and hematocrit; DISC-3405 was generally well-tolerated at all evaluated dose levels, with no serious adverse events, greater than Grade 2 AEs, or AEs leading to study withdrawal; These results support Disc’s plans to advance the DISC-3405 program into a Phase 2 study in polycythemia vera in 2025. SCD Mouse Model: The effect of DISC-3405 in the Townes mouse model of SCD was evaluated. Results showed: Treatment with 10 mg/kg dose of a mouse analog of DISC-3405 resulted in iron restriction and a significant decrease in hemoglobin S concentration without affecting red blood cell counts; Also observed a significant decrease in lactate dehydrogenase, suggesting decreased hemolysis, and decrease in white blood cells, suggesting reduced inflammation; These results highlight the potential value of DISC-3405 in providing therapeutic benefits to SCD patients by reducing HbS concentration within red blood cells.