Disc Medicine, Inc. announced positive additional data for bitopertin in erythropoietic protoporphyria (EPP), including additional analyses of AURORA data that further demonstrated the clinical activity of bitopertin and highlighted meaningful improvements in light tolerance, phototoxic reactions, and quality of life. Additionally, Disc shared updated data from a Phase 1b trial of DISC-0974 in MF anemia which demonstrated durable increases in hemoglobin and reduced transfusion burden in a majority of evaluable patients. Disc also shared initial SAD data from a Phase 1 healthy volunteer trial of DISC-3405 that provided proof of mechanism, showing that the drug has the potential to provide deep and sustained increases in hepcidin and reductions in iron. The data were presented at the European Hematology Association (EHA) 2024 Congress. The AURORA study is a randomized, double-blind, placebo-controlled Phase 2 clinical trial that enrolled 75 adult subjects with EPP. Subjects were randomized 1:1:1 to receive 20 mg of bitopertin (n=26), 60 mg of bitopertin (n=25), or placebo (n=24) once daily for 17 weeks. Key AURORA data presented include: Significant reductions in protoporphyrin IX (PPIX) (40% for the 60 mg group) compared to placebo. Meaningful improvements on key aspects of EPP. Time-dependent improvement in light tolerance that was nominally significant compared to placebo in both the 20 mg (p=0.026) and 60 mg (p=0.013) dose groups. ~2x improvement in light tolerance relative to baseline in both 20 mg and 60 mg dose groups as evaluated in a post-hoc longitudinal analysis. Substantial, dose-dependent reductions in rate of phototoxic reactions compared to placebo, reaching statistical significance in the 60 mg dose group (75.3% reduction, p=0.011). Dose-dependent improvements in Patient Global Impression of Change (PGIC), which were statistically significant for the 60 mg dose (p=0.022). Evaluation of the time course of phototoxic reactions and sunlight exposure showed greater treatment effect in the time period after PPIX nadir was reached, including elimination of observed phototoxic reactions in the 60 mg dose group. Greater PPIX reductions were associated with improvements in multiple light tolerance measures, including cumulative total time in light, average time in sunlight without pain, change from baseline in time to prodrome, as well as PGIC. Bitopertin was generally well-tolerated with no reported serious adverse events (SAEs) to date. Disc also presented the full adult data set from BEACON, which was consistent with previously-presented results and demonstrated similar clinical activity to that observed in AURORA. The Phase 1b/2a multi-center, open-label, ascending-dose clinical trial of DISC-0974 is enrolling patients with MF and severe anemia, including both transfusion and non-transfusion dependent patients. In the phase 1b dose-escalation phase, DISC-0974 is administered subcutaneously every 4 weeks for up to 6 treatments. Updated data from 34 patients with an April 29, 2024 cutoff include: Substantial and sustained reductions in hepcidin levels and increases in iron were observed in patients for several weeks after each dose
Strong hematologic response was observed across all patient types at 28-100 mg doses: 68.9% of non-transfusion dependent (nTD) participants demonstrated a hemoglobin response of =1.5 g/dL (n=29). 60% of nTD participants who have completed at least 16 weeks of treatment had a mean hemoglobin response of =1.5 g/dL above baseline sustained for at least 12 weeks (n=15). One of two evaluable transfusion dependent (TD) participants became transfusion independent (TI) by the end of the trial. Hemoglobin response of =1.5 g/dL above baseline was achieved in 6 of 10 participants with concomitant JAK inhibitor therapy. All evaluable participants with baseline transfusion requirements demonstrated at least a 50% reduction in transfusions over a rolling 8-week window on trial compared to baseline (n=8). DISC-0974 was generally well-tolerated at all evaluated dose levels. Initial data were also presented from the SAD portion of the Phase 1 clinical trial of DISC-3405 in healthy volunteers. In this trial, healthy males and females ages 18 to 65 were given a single dose of placebo (n=10) or DISC-3405 at 75 mg intravenously (IV) (n=6), 37.5 mg subcutaneously (SC) (n=6), 75 mg SC (n=6), 150 mg SC (n=6), or 300 mg SC (n=6). This initial data showed: A meaningful dose-dependent increase in hepcidin and corresponding reduction in serum iron across all dose levels. Mean serum iron reduction in excess of 50% from baseline was achieved in the150- and 300-mg dose groups. Mean serum iron reduction in excess of 50% was sustained for at least 4 weeks for the 300-mg dose group, with meaningful reduction observed in selective hematological parameters (CHr, hemoglobin, and hematocrit). PK/PD profile is supportive of monthly subcutaneous dosing. DISC-3405 was generally well-tolerated with no SAEs, AEs higher than Grade 2, or AEs leading to trial withdrawal reported to date.