Disc Medicine, Inc. · NASDAQ:IRON
Disc Medicine — 2024 ASH Management Call
45 slides from Disc Medicine's conference presentation, Dec 9, 2024
Slide 1: 2024 ASH Management Call Clinical Data Updates
2024 ASH Management Call Clinical Data Updates: Bitopertin, DISC-0974, and DISC-3405 December 8, 2024 Exhibit 99.1
Slide 2: Disclaimer and FLS
Disclaimer and FLS This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, express or implied statements regarding Disc’s expectations with respect to: (i) the timing, progress and results of p
Slide 3: Investigational agents not approved for use
Bitopertin, DISC-0974, and DISC-3405 are investigational agents and are not approved for use as therapies in any jurisdiction worldwide CONFIDENTIAL
Slide 4: Agenda
Agenda 01 Introduction and Summary John Quisel, JD, PhD, Chief Executive Officer 02 Bitopertin in EPP Review of Updated Data and Regulatory Path Will Savage, MD, PhD, Chief Medical Officer EPP Market Opportunity and Commercialization Approach Pamela Stephenson, MPH, Chief Commercial Officer 03 DISC-
Slide 5: Disc's Hematology-Focused Pipeline
Disc’s Hematology-Focused Pipeline Multiple programs in development with pipeline-in-a-product potential Preclinical Phase 1 Bitopertin† GlyT1 Inhibitor Oral, once-daily Phase 2 Phase 3 / Confirmatory DISC-0974‡ Anti-HJV monoclonal antibody Subcutaneous, once-monthly DISC-0998‡ Anti-HJV monoclonal a
Slide 6: Bitopertin: Summary of Updates
Bitopertin: Summary of Updates Strong data package and high unmet need in EPP support a potential path to accelerated approval BEACON data show similar results between adults and adolescents with clear correlation between PPIX reduction and clinical outcomes Strong market potential due to engaged pa
Slide 7: DISC-0974: Summary of Updates for Multiple Indications
DISC-0974: Summary of Updates for Multiple Indications Positive impact on clinically meaningful measures of anemia across a broad range of MF patients Development path aligned on with regulators; Phase 2 study initiated Initial proof of concept in anemia of CKD and preclinical evidence in broader an
Slide 8: DISC-3405: Summary of ASH Data
DISC-3405: Summary of ASH Data Deep, sustained reductions in serum iron (50-80% from baseline) supportive of SC monthly dosing Meaningful changes in hematologic parameters, supporting initiation of a Phase 2 study in PV in 2025 Preclinical SCD data showing decreased HbS concentration and improved ma
Slide 9: Agenda
Agenda 01 Introduction and Summary John Quisel, JD, PhD, Chief Executive Officer 02 Bitopertin in EPP Review of Updated Data and Regulatory Path Will Savage, MD, PhD, Chief Medical Officer EPP Market Opportunity and Commercialization Approach Pamela Stephenson, MPH, Chief Commercial Officer 03 DISC-
Slide 10: EPP Phase Development Program
EPP Phase 2 Development Program BEACON, AURORA, and HELIOS Studies Successful End of Phase 2 meeting with the FDA puts bitopertin on a path to potential accelerated approval, with the confirmatory APOLLO study starting by mid-2025 EPP and XLP; N = 26 (22 adults, 4 adolescents) Australia Open-label,
Slide 11: Summary of AURORA Results
Significant reductions in PPIX 40% reduction vs baseline Time-dependent improvements in pain-free time in sunlight vs placebo 2x more light time vs baseline Significant 75% reduction in rate of phototoxic reactions vs placebo Phototoxic reaction-free in last 60 days Significant improvement in PGIC v
Slide 12: Summary of BEACON Results
Summary of BEACON Results Consistent with AURORA data, with similar results in adults and adolescents Phototoxic Reactions Bitopertin 60 mg Tertiles of PPIX Change Light Tolerance Measure (Mean ± SD) Tertile 3 (-43% to 25%) Tertile 2 (-53% to -43%) Tertile 1 (-98% to -53%) Cumulative total time in s
Slide 13: EPP LIGHT Survey
EPP LIGHT Survey Highlights the significant burden of illness and unmet need in EPP Quantitative survey conducted with 197 EPP patients (164 adults, 33 adolescents) from May to July 2024 reinforces the severity of phototoxic reactions, the high rate of comorbidities, and the overall impact EPP has o
Slide 14: Key Takeaways from Positive End of Phase 2 Meeting
Alignment with the FDA on all proposed study parameters FDA acknowledged that EPP is a serious and potentially life-threatening disease with significant unmet medical need FDA agreed that average monthly time in sunlight without pain at the end of a 6-month treatment period can be used as a primary
Slide 15: EPP Opportunity
EPP Opportunity Engaged, concentrated patient and KOL community eager for a disease-modifying therapy Focused HCP Network EPP experts Rare Disease 6K engaged US patients Differentiated Product Disease-modifying effects High Unmet Need Significant impact to health and QoL EPP Opportunity
Slide 16: EPP patient population is well-defined and concentrated
The EPP patient population is well-defined and relatively concentrated, enabling an efficient commercial model Source: Trinity Life Sciences; Komodo Claims Data (2016-2022) Distribution of EPP Treatment Centers Concentration of patients in key accounts enables a targeted and efficient field force ~
Slide 17: Relationships with patient advocacy groups and physician organizations
Building strong relationships with patient advocacy groups and physician organizations worldwide
Slide 18: Commercial Readiness Activities Well Underway
Commercial Readiness Activities Well Underway Patient Identification and Account Mapping Payer Engagement and Pricing Assessments Evidence Generation, including HEOR and Burden of Illness Disease State Education and Brand Proposition Operational Readiness Commercial Manufacturing and Suppl
Slide 19: Bitopertin Summary and Next Steps
Discussion of confirmatory study design with FDA, with updates provided in Q1 2025 APOLLO study initiation by mid-2025 European protocol assistance and confirmation of regulatory path with EMA Continued commercialization and launch preparation Next Steps Positive EOP2 meeting sets up the path toward
Slide 20: Agenda
Agenda 01 Introduction and Summary John Quisel, JD, PhD, Chief Executive Officer 02 Bitopertin in EPP Review of Updated Data and Regulatory Path Will Savage, MD, PhD, Chief Medical Officer EPP Market Opportunity and Commercialization Approach Pamela Stephenson, MPH, Chief Commercial Officer 03 DISC-
Slide 21: DISC-0974: Novel Anti-HJV mAb to Suppress Hepcidin
DISC-0974: Novel Anti-HJV mAb to Suppress Hepcidin Designed to enhance iron availability to address a wide range of hematologic disorders Releases iron stores Enables GI absorption Increases Iron Reduces Hepcidin Inhibits endogenous production of hepcidin Potential to treat wide range of anemias Ena
Slide 22: DISC-0974 Phase 1b Study Design and Baseline Characteristics
Screening (28 Days) Treatment Period (6 months) Optional Continuation (Up to 2 years) Study Endpoints Primary: Safety and tolerability; Secondary: Hematologic response, pharmacodynamic markers of mechanism engagement Screen Baseline D15 D29 D43 D71 D113 D141 D169/EOS 14 mg 28 mg 50 mg 75 mg 100 mg O
Slide 23: DISC-0974 Anemia of MF Phase 1b Patient Segmentation
DISC-0974 Anemia of MF Phase 1b Overview of patient segmentation Shift informed by FDA feedback on clinically meaningful measures for MF anemia patient types and new clinical response criteria1 Previous Data Readouts Today Source: 1Tefferi A, et al. Blood. 2024. Hgb <10 and 0 units transfused / 12 w
Slide 24: DISC-0974 Anemia of MF Phase 1b Pharmacodynamics
DISC-0974 Anemia of MF Phase 1b Results Pharmacodynamics DISC-0974 demonstrated consistent decreases in hepcidin and increases in serum iron across patients Iron mobilization translated to increased reticulocyte hemoglobin and hemoglobin from baseline Serum Hepcidin Serum Iron Reticulocyte Hemoglobi
Slide 25: Hematologic response: nTD participants
68% of nTD1 participants achieved a Hgb Increase of ≥1.5 g/dL during study period; 50% achieved a sustained Hgb response for ≥12 weeks Response Mean ± SD (days) Time to first Hgb increase for major response 36 ± 18 Duration of response during treatment period 150 ± 27 17 of 22 nTD participants have
Slide 26: Hematologic response: TD Low participants
Response Mean ± SD (days) TD Low duration of major response during treatment period 171 ± 4 5 of 5 TD Low participants have received continuation treatment with median response not reached. Follow-up ongoing (maximum 16.6 months). *Indicates transfusion; #Indicates patient receiving transfusion duri
Slide 27: Hematologic response: TD High participants
Response Mean ± SD (days) TD High duration of major response during treatment period 127 ± 60 50% of participants (n=4) receiving concomitant JAKi therapy achieved ≥50% transfusion reduction; 25% achieved TI-12 DISC-0974 Anemia of MF Phase 1b Results Hematologic response: TD High participants (n=5)
Slide 28: Hematologic response with concomitant JAKi therapy
nTD Response (n=9) TD High Response (n=4) During the treatment period Mean Hgb ↑ ≥1.5 g/dL for ≥12 weeks ≥50% reduction in transfusion requirement TI ≥12 weeks DISC-0974 Anemia of MF Phase 1b Results Hematologic response with concomitant JAKi therapy (n=13) Overall, 54% of participants receiving con
Slide 29: DISC-0974 Alleviated Ruxolitinib-Induced Anemia in Mice
Treating wild-type mice with ruxolitinib reduced hemoglobin and induced anemia Adding a mouse analog of DISC-0974 reversed these effects, further decreasing hepcidin, increasing serum iron, and increasing hemoglobin DISC-0974 Alleviated Ruxolitinib-Induced Anemia in Mice Wild-type mouse model Target
Slide 30: DISC-0974 Safety: Treatment-Emergent Adverse Events
Preferred Term 28 mg (n=7) 50 mg (n=12) 75 mg (n=9) 100 mg (n=6) Overall (n=35) Any TEAE 6 (85.7) 12 (100) 8 (88.9) 6 (100) 32 (94.1) Related AE 4 (57.1) 6 (50) 5 (55.6) 1 (16.7) 16 (47.1) SAE 1 (14.3) 2 (16.7) 0 1 (16.7) 4 (11.8) Common TEAEs in ≥5 participants Diarrhea 3 (42.9) 5 (41.7) 5 (55.6) 1
Slide 31: Overview of MF Anemia Market
Overview of MF Anemia Market DISC-0974 positioned to address all clinically significant patient types Transfusion Status JAK Inhibitor Experience On JAKi Not on JAKi nTD TD Low TD High 50% Major response 80% Major response 40% Major response 54% Major response 53% Major response With or without dise
Slide 32: Phase 2 MF Anemia Study Overview
Phase 2 MF Anemia Study Overview Phase 2 Dosing: 50 mg, SC, q28 days Study Population Screening (28 Days) Treatment Period (6 Cycles q28 Days) Continuation Treatment (q28 Days – optional) Follow-Up (28 Days) Design Key endpoints: Anemia response defined by cohort (TI, transfusion burden reduction, H
Slide 33: DISC-0974 Anemia of NDD-CKD: Hepcidin, Iron, and Hgb
DISC-0974 Anemia of NDD-CKD: Hepcidin, Iron, and Hgb 28 mg, 40 mg, and 60 mg SAD cohorts Substantial, durable, dose-dependent reduction in hepcidin and sustained increase in TSAT from baseline Safety: DISC-0974 demonstrated acceptable safety and tolerability at all evaluated dose levels; the majorit
Slide 34: DISC-0974 in Other Anemias of Inflammation
Mouse analog of DISC-0974 supressed hepcidin, increased serum iron, and increased hemoglobin in anemic IBD mice Treatment also demonstrated disease-modifying and anti-inflammatory effects DISC-0974 in Other Anemias of Inflammation Inflammatory bowel disease mouse model Target Engagement Hematologic
Slide 35: DISC-0974 Summary and Next Steps
MF Anemia Phase 2 study has been initiated with initial data expected H2 2025 CKD Anemia Phase 1b multiple-dose portion initiation by end of year, with data expected by end of 2025 Next Steps MF Phase 1b data demonstrate proof of concept for DISC-0974 across all clinically meaningful patient segment
Slide 36: Agenda
Agenda 01 Introduction and Summary John Quisel, JD, PhD, Chief Executive Officer 02 Bitopertin in EPP Review of Updated Data and Regulatory Path Will Savage, MD, PhD, Chief Medical Officer EPP Market Opportunity and Commercialization Approach Pamela Stephenson, MPH, Chief Commercial Officer 03 DISC-
Slide 37: Anti-TMPRSS6 mAb Induces Hepcidin
Anti-TMPRSS6 mAb Induces Hepcidin Designed to limit iron levels with potential to address a wide range of hematologic disorders Promotes Iron Restriction Decreases GI Absorption Limits Iron Availability Increases Hepcidin Enables Endogenous Production of Hepcidin Erythrocytosis (PV) Ineffective Eryt
Slide 38: DISC-3405 Healthy Volunteer Study Overview
DISC-3405 Phase 1 Healthy Volunteer Study Overview CONFIDENTIAL Single-Ascending Dose 75 mg IV 75 mg SC 150 mg SC 300 mg SC Multiple-Ascending Dose 150 mg SC (Q4W) 75 mg SC (Q4W) Key Endpoints/Measures: Iron, hepcidin, and other hematologic parameters, safety/tolerability N=8 per Cohort (6 Active, 2
Slide 39: DISC-3405 Healthy Volunteer Study Summary
DISC-3405 Phase 1 Healthy Volunteer Study Summary Dose-dependent increases in hepcidin and corresponding reductions in serum iron levels across all dose levels Deep and sustained reductions in serum iron (50-80% from baseline) Meaningful reductions in reticulocyte hemoglobin, hemoglobin, and hematoc
Slide 40: Iron Restriction in Sickle Cell Disease
Iron Restriction in Sickle Cell Disease Potential for iron restriction through inhibition of TMPRSS6 to benefit SCD by reducing HbS concentration DISC-3405 in a Townes Model 3 and 10 mg/kg IP weekly for 8 weeks Reduced HbS concentration Improved markers of inflammation Improved markers of hemolysis
Slide 41: DISC-3405 Summary and Next Steps
DISC-3405 Summary and Next Steps Polycythemia Vera Iron Overload Disorders Sickle Cell Disease Potential Development Opportunities for TMPRSS6 Inhibition Phase 2 study initiation in polycythemia vera in 1H 2025 Proof of mechanism in HVOL with reductions in hepcidin and increases in serum iron suppor
Slide 42: Agenda
Agenda 01 Introduction and Summary John Quisel, JD, PhD, Chief Executive Officer 02 Bitopertin in EPP Review of Updated Data and Regulatory Path Will Savage, MD, PhD, Chief Medical Officer EPP Market Opportunity and Commercialization Approach Pamela Stephenson, MPH, Chief Commercial Officer 03 DISC-
Slide 43: Summary of ASH Updates
Positive, durable benefits on hemoglobin and transfusion burden in anemia of MF across all meaningful patient types Preclinical data demonstrate potential to reverse the Hgb-lowering effects of ruxolitinib Demonstrated potential to treat additional anemias of inflammation with efficacy in a mouse mo
Slide 44: Projected Upcoming Milestones and Events
Projected Upcoming Milestones and Events Multiple additional data catalysts anticipated in the next 18 months Program Indication H1 2025 H2 2025 2026 Erythropoietic Porphyrias (EPP and XLP) Feedback from Type C Meeting with FDA APOLLO Study Initiation Diamond-Blackfan Anemia (DBA) IIT ongoing Anemia
Slide 45: Agenda
Agenda 01 Introduction and Summary John Quisel, JD, PhD, Chief Executive Officer 02 Bitopertin in EPP Review of Updated Data and Regulatory Path Will Savage, MD, PhD, Chief Medical Officer EPP Market Opportunity and Commercialization Approach Pamela Stephenson, MPH, Chief Commercial Officer 03 DISC-