Disc Medicine, Inc. · NASDAQ:IRON
Disc Medicine — ASH 2023
15 slides from Disc Medicine's conference presentation, December 2023
Slide 1: Interim Analyses from the BEACON trial: Bitopertin in Erythropoietic Protoporphyria
Interim Analyses from the BEACON trial: A Phase 2, Randomized, Open-Label Trial of Bitopertin in Erythropoietic Protoporphyria Gayle Ross, MD1; Peter Stewart, MD2; George Mensing, MPH3; Melanie Chin, PhD3; Haley Howell3; Heidi Mangus3; and William Savage, MD, PhD3 1 Royal Melbourne Hospital, Melbour
Slide 2: Bitopertin is an investigational agent and not approved
Bitopertin is an investigational agent and is not approved for use as a therapy in any jurisdiction worldwide. 2
Slide 3: Erythropoietic Protoporphyria (EPP)
Erythropoietic Protoporphyria (EPP) Rare condition affecting 7,000 to 8,000 individuals in the US and EU Debilitating condition characterized by extreme pain and damage to skin due to light exposure Deficient ferrochelatase enzyme causes pathologic accumulation of toxic metabolite, protoporphyrin IX
Slide 4: Protoporphyrin IX (PPIX) is a Driver of Disease in EPP
Protoporphyrin IX (PPIX) is a Driver of Disease in EPP Accumulation of toxic, photoactive metabolite results in complications Skin Hepatobiliary • Porphyrin ring absorbs light and emits energy • ~25% of patients develop cholelithiasis causing cellular injury and inflammation requiring surgery or imp
Slide 5: Bitopertin: Investigational, Oral, Selective GlyT1 Inhibitor
Bitopertin: Investigational, Oral, Selective GlyT1 Inhibitor Designed to reduce disease-causing PPIX by limiting uptake of glycine into developing erythrocytes Heme Synthesis Bitopertin Designed to block glycine uptake in red blood cells ALA Synthase by inhibiting GlyT1 PPIX Heme Succinyl-CoA Mutate
Slide 6: BEACON Trial Overview
BEACON Trial Overview Enrollment data as of 20 Oct 2023 Screening Randomized, Treatment Period (6 months) OLE (28 Days) 1:1 Bitopertin 20 mg (N=11) and Bitopertin 60 mg (N=11) (Up to 6 Months) Screen D1 D2 D15 D29 D43 D71 D113 D155 D169/EOS Q8 Weeks Trial Endpoints: Changes in blood PPIX levels, lig
Slide 7: Primary Endpoint: Percent Change in Whole-Blood PPIX
Primary Endpoint: Percent Change in Whole-Blood PPIX Bitopertin significantly reduced whole-blood (WB) metal-free PPIX levels by >40% Dose-dependent reductions observed across broad range of baseline WB PPIX levels (144-3,410 µg/dL) PPIX Changes Over Time 0 % Change in WB PPIX Overall 20 mg 60 mg >4
Slide 8: Key Secondary Endpoint: Total Time in Light Without Pain
Key Secondary Endpoint: Total Time in Light Without Pain Cumulative total time in light observed over 6-month treatment period with bitopertin represents >3x increase relative to historical control Time-dependent improvements in average daily light tolerance with bitopertin Cumulative 6-month Total
Slide 9: Association Between PPIX and Light Tolerance
Association Between PPIX and Light Tolerance Greatest improvements in light tolerance seen in participants with PPIX reductions ≥30% PPIX Reduction PPIX Reduction in Total Weekly Time in Sunlight (min) ≥30% Mean Max Change from Baseline <30% 1000 800 600 400 N=11 200 898 ± 419 170 ± 113 0 0 Mean Max
Slide 10: Secondary Endpoint: Time to Prodrome
Secondary Endpoint: Time to Prodrome Significant, time-dependent improvements in light tolerance during sunlight-exposure challenges Time to Prodrome 150 Mean Change in Time to Prodrome (min) 100 >3x 50 (p<0.001 vs baseline) 0 0 4 8 12 16 20 24 Week No. of Participantsa 22 19 21 20 19 18 21 15 15 17
Slide 11: Light Tolerance: Days Without Symptoms or Prodromes
Light Tolerance: Days Without Symptoms or Prodromes 92% reduction in patient-reported full phototoxic reactionsa An increase in the proportion of total symptom-free days (no prodrome / early warning symptoms or full phototoxic reactions) with sunlight exposure was observed 100% Screening Bitopertin
Slide 12: Measures of Quality of Life
Measures of Quality of Life Nearly all participants reported improvements in multiple quality-of-life measures at end of study “Since the start of the study, how would you rate the change in your EPP?” Patient Global Impression of Change No change A little better Much better “Overall, how severe was
Slide 13: Safety and Tolerability
Safety and Tolerability Mean ± SD Hgb (g/dL) Overall 20 mg 60 mg • No serious adverse events 16 • Stable mean Hgb levels; no anemia AEs reported 14 • Favorable safety profile consistent with prior studies enrolling 12 >4000 participants 10 • Safety profile supports enrollment of adolescents 0 15 43
Slide 14: Conclusions
Conclusions Proof of Functional Quality of Life Safety Concept Outcomes Impact Significant Significant Patients reported No meaningful reduction in PPIX improvement in an improved change in at low and high sunlight tolerance quality of life hemoglobin doses observed with bitopertin 14
Slide 15: Thank You
Thank You