2024 ASH Management Call Clinical Data Updates: Bitopertin, DISC-0974, and DISC-3405 December 8, 2024 Exhibit 99.1
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Bitopertin, DISC-0974, and DISC-3405 are investigational agents and are not approved for use as therapies in any jurisdiction worldwide CONFIDENTIAL
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-0974 Updated Data in Anemia of MF and Phase 2 Study Plan Will Savage, MD, PhD, Chief Medical Officer Preclinical Data in Anemia of IBD Will Savage, MD, PhD, Chief Medical Officer Closing Remarks John Quisel, JD, PhD, Chief Executive Officer 05 Q&A Session 06 04 DISC-3405 Phase 1b MAD and Preclinical SCD Data Will Savage, MD, PhD, Chief Medical Officer
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 antibody Extended half-life Erythropoietic Porphyrias (EPP and XLP) – Potential for Accelerated Approval; study to start mid-2025 Diamond-Blackfan Anemia – Initiated July 2023** Anemia of Myelofibrosis (MF) Anemia of Non-Dialysis-Dependent Chronic Kidney Disease (CKD) Anemia Associated with Inflammatory Diseases Heme Biosynthesis Modulator Iron Modulation Hepcidin Suppression Increase Iron Hepcidin Induction Restrict Iron Portfolio Program † Bitopertin in-licensed from Roche; ‡ DISC-0974 and DISC-0998 in-licensed from AbbVie; *DISC-3405 in-licensed from Mabwell (formerly MWTX-003); **IIT with the NIH DISC-3405* Anti-TMPRSS6 Monoclonal antibody Healthy Volunteers – Initiated October 2023
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 patient and KOL community; commercial readiness activities well underway Patient survey highlights the burden of EPP and its impacts on multiple aspects of daily life Positive feedback from EOP2 meeting with the FDA setting up a path to accelerated approval
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 anemias of inflammatory disease Substantial reductions in hepcidin and increases in iron levels translating to hematologic response Final results from the Phase 1b study in MF anemia demonstrate efficacy across patient types; clinical data in CKD and preclinical data in IBD provide evidence of broad potential in anemias of inflammation. Key findings:
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 markers of inflammation and hemolysis Substantial, dose-dependent increase in hepcidin levels Multiple-ascending dose portion of the DISC-3405 healthy volunteer study confirmed proof of mechanism, and preclinical data demonstrated potential for use in sickle cell disease. Key findings:
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-0974 Updated Data in Anemia of MF and Phase 2 Study Plan Will Savage, MD, PhD, Chief Medical Officer Preclinical Data in Anemia of IBD Will Savage, MD, PhD, Chief Medical Officer Closing Remarks John Quisel, JD, PhD, Chief Executive Officer 05 Q&A Session 06 04 DISC-3405 Phase 1b MAD and Preclinical SCD Data Will Savage, MD, PhD, Chief Medical Officer
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, randomized, 24-week study EPP; N = 75 adults United States Double-blind, randomized, placebo-controlled, 17-week study EPP and XLP; adults and adolescents US and Australia Open-label extension study (>80% rollover from BEACON and AURORA)
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 vs placebo 86% reported EPP was ‘much better’ Clear association between PPIX reduction and clinical endpoints Summary of AURORA Results Bitopertin 60 mg Placebo Bitopertin 60 mg Phototoxic Reactions = Phototoxic Reaction = 2 Phototoxic Reactions
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 sunlight without pain (hr) 145.6 ± 99.5 190.5 ± 111.6 262.1 ± 160.6 Average time in sunlight without pain (hr) 0.86 ± 0.6 1.1 ± 0.7 1.6 ± 1.0 Change from baseline in time to prodrome (min) 85.3 ± 78.8 96.0 ± 109.0 165.5 ± 128.8 PPIX Decreased PPIX Increased Significant reductions in PPIX, improvements in pain-free time in sunlight, reductions in rate of phototoxic reactions, and improvement in QoL with clear association between PPIX reduction and clinical endpoints Compared to 16 reactions in the 4-week baseline period (92% reduction)
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 on daily life *of those who work (n=114) / are in school (n=45); **of adults, compared to the general population. Source: EPP LIGHT Survey, ASH 2024 Abstract #3631 Significant Impacts of EPP Phototoxic Reactions 5 days for reaction to improve 7.5 / 10 pain level from a reaction Comorbidities 33% with liver or gallbladder issues >70% depressed or anxious due to EPP Daily Life 22% missed work due to EPP* 33% missed school due to EPP* 63% experience greater social isolation**
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 endpoint Key Takeaways from Positive End of Phase 2 Meeting Proceeding to APOLLO, a 6-month study with a 60 mg dose of bitopertin in EPP and XLP patients ages 12+ by mid-2025 PPIX reduction may be sufficient as a surrogate endpoint supportive of accelerated approval
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
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 ~ 3.2K ~ 6.1K ~ 14K Growth Patients with lower degree of engagement with HC system ~ 20K Predicted Genetic Prevalence of EPP Expansion Misdiagnosed or have not sought treatment for EPP Prevalence of EPP Patients in the US Focus Engaged EPP patients recent or recurring claims
Building strong relationships with patient advocacy groups and physician organizations worldwide
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 Supply
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 potential accelerated approval Additional data from BEACON supportive of drug activity and use of bitopertin in adolescents Robust market opportunity with a clearly defined population of 3-6K patients with the opportunity to expand to 14K DBA Study: 14 patients have been enrolled; bitopertin has been well-tolerated with safety consistent with prior studies; efficacy evaluation is ongoing Bitopertin Summary and Next Steps Bitopertin Summary
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-0974 Updated Data in Anemia of MF and Phase 2 Study Plan Will Savage, MD, PhD, Chief Medical Officer Preclinical Data in Anemia of IBD Will Savage, MD, PhD, Chief Medical Officer Closing Remarks John Quisel, JD, PhD, Chief Executive Officer 05 Q&A Session 06 04 DISC-3405 Phase 1b MAD and Preclinical SCD Data Will Savage, MD, PhD, Chief Medical Officer
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 Enables RBC Production HJV = hemojuvelin
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 Overall Treated, N 1 7 12 9 6 35 Completed study, N (%) 1 (100) 6 (86) 12 (100) 8 (89) 5 (83) 32 (91) Subjects with early withdrawal (N)* 0 1 0 0 1 2 Participating in continuation, N (%) 0 2 (29) 10 (83) 8 (89) 4 (67) 24 (69) Concomitant JAK inhibitor, N (%) 0 4 (57) 6 (50) 2 (22) 1 (17) 13 (37) Baseline hepcidin, median (min, max), ng/mL 48 93 (21, 171) 90 (9, 156) 47 (23, 188) 64 (12, 375) 69 (9, 375) Baseline hemoglobin, median (min, max), g/dL 8.2 8.4 (6.7, 9.3) 8.4 (5.5, 10) 8.8 (6.7, 9.9) 8.3 (5.5, 9) 8.4 (5.5, 10) Q28 Day/EOS D2 D8 D22 85 D57 *Reason for early withdrawal: Physician decision due to inadequate response (n=2) D1 DISC-0974 Anemia of MF Phase 1b Study overview – enrollment data as of October 17, 2024
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 weeks nTD 1-2 units transfused / 12 weeks TD Low 3-12 units transfused / 12 weeks TD High Hgb <10 and not TD Non-Transfusion Dependent (NTD) ≥6 units transfused / 12 weeks Transfusion Dependent (TD)
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 Hemoglobin Hemoglobin 28 mg 50 mg 75 mg 100 mg
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 received continuation treatment with median response not reached. Follow-up ongoing (maximum 14.7 months). 1nTD participants: Baseline Hgb <10 with 0 units PRBC in the 84 days prior to screening. * Participants dosed at 28-100 mg dose levels. 67% of participants (n=9) receiving concomitant JAKi therapy achieved durable response Mean Hgb ↑ ≥1 g/dL for ≥12 weeks Mean Hgb ↑ ≥1.5 g/dL for ≥12 weeks During the treatment period DISC-0974 Anemia of MF Phase 1b Results Hematologic response: nTD participants* (n=22)
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 during treatment period. No TD Low participants were receiving concomitant JAKi therapy ≥50% reduction in transfusion requirement TI ≥16 weeks DISC-0974 Anemia of MF Phase 1b Results Hematologic response: TD Low participants (n=5) 100% of TD Low1 participants achieved a ≥50% reduction in transfusion requirement; 80% of participants achieved TI-16 weeks^ 1TD Low: Participants receiving 1-2 units PRBC in the 84 days prior to screening. ^ with a minimum Hgb of 7 g/dL.
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) 60% of TD High1 participants achieved a ≥50% reduction in transfusion requirement; 40% of participants achieved TI-12 weeks^ 1TD High: Participants receiving 3-12 units PRBC in the 84 days prior to screening. ^ with a minimum Hgb of 7 g/dL; 2 TD-high participants were considered not evaluable due to incomplete data entry at time of data cut. TI ≥12 weeks ≥50% reduction in transfusion requirement
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 concomitant JAKi therapy achieved a major hematologic response
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 Engagement Hematologic Improvement Serum Hepcidin Serum Iron 0 20 Serum Hepcidin (ng/mL) 40 60 80 Vehicle Ruxolitinib (90 mg/kg)-BID DBIO-100 (20 mg/kg)-QW Ruxolitinib (90 mg/kg)-BID +DBIO-100 (20 mg/kg)-QW 0 20 Serum Iron (μmol/L) 40 60 80 Hemoglobin Ruxolitinib alone reduced Hgb by ~1.1 g/dL Adding DISC-0974 analog increased Hgb by ~0.9 g/dL HGB (g/L) 100 120 140 160 Vehicle Ruxolitinib (90 mg/kg)-BID DBIO-100 (20 mg/kg)-QW Ruxolitinib (90 mg/kg)-BID +DBIO-100 (20 mg/kg)-QW
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 (16.7) 14 (41.2) Nausea 2 (28.6) 2 (16.7) 2 (22.2) 2 (33.3) 8 (23.5) Vomiting 1 (14.3) 2 (16.7) 0 3 (50.0) 6 (17.6) Constipation 0 4 (33.3) 1 (11.1) 0 5 (14.7) Fatigue 3 (42.9) 3 (25.0) 1 (11.1) 3 (50.0) 10 (29.4) Lymphocyte count decreased 1 (14.3) 2 (16.7) 2 (22.2) 1 (16.7) 6 (17.6) Dizziness 0 2 (16.7) 2 (22.2) 3 (50.0) 7 (20.6) Headache 1 (14.3) 1 (8.3) 1 (11.1) 2 (33.3) 5 (14.7) Dyspnea 0 1 (8.3) 2 (22.2) 2 (33.3) 5 (14.7) Hyperhidrosis 1 (14.3) 1 (8.3) 1 (11.1) 2 (33.3) 5 (14.7) Anemia 5 (71.4) 4 (33.3) 0 0 9 (26.5) Hypertension 0 3 (25.0) 3 (33.3) 0 6 (17.6) No TEAEs were reported at the 14 mg dose level. Related AEs occurring in ≥2 participants: diarrhea (n=6); SAEs: arthralgia, cellulitis related to cat scratch, cellulitis related to cat bite, and kidney infection; ≥Grade 3 AEs: anemia, lymphocyte count decreased, platelets decreased, cellulitis, kidney infection (same as SAE), muscular weakness, and headache. DISC-0974 Anemia of MF Phase 1b Results Safety
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 disease-directed treatment Any transfusion status Source: 1Elena C, et al, Haematologica, 2010. JAKi can worsen anemia Anemia can drive JAK discontinuation or suboptimal treatment choice / dose Treating anemia separately may allow JAKi regimen to be optimized Anemia and transfusions are associated with high burden and poor survival, regardless of other risk factors1 87% of MF patients develop anemia; most MF patients become more transfusion dependent over time Anemia symptoms worsen QoL regardless of transfusions >20K MF patients with anemia DISC-0974 Efficacy Unmet Need
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, Hgb change) Iron, hepcidin, hematologic parameters FACIT fatigue score N= ~90 (30 per cohort) 12 patients carried over from Phase 1b* Adult patients with MF and anemia Hgb <10 g/dL on ≥3 assessments over 12 weeks, or 1 or more PRBC units transfused in 12 weeks Severity: DIPSS INT-1/High +/- JAK inhibitor permitted nTD: N=30* TD Low: N=30* TD High: N=30* momelotinib / pacritinib nTD, TD Low, or TD High; N=10 Open-Label, 3 cohorts Exploratory cohort Flexibility to add exploratory cohorts *Patients carried over from Phase 1b: nTD n=8, TD (Low + High) n=4
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 majority of adverse events were deemed not related to DISC-0974, and all adverse events assessed as treatment-related were Grade 1 or 2 Early and sustained increase in mean reticulocyte hemoglobin across dose groups Increase in mean hemoglobin from baseline across dose groups, with maximal observed individual increases in hemoglobin up to +0.95 g/dL at 28 mg, +1.5 g/dL at 40 mg, and +1.8 g/dL at 60 mg Serum Hepcidin Serum TSAT Reticulocyte Hemoglobin Hemoglobin
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 Improvement IBD Disease Modification RBC Count HGB (g/L) 0 50 100 200 150 Hgb RBC (10^12/L) 0 5 10 15 WBC Count Disease Activity Serum Iron WBC (10^9/L) 0 5 10 15 DAI Score Days 2 4 6 8 Serum Hepcidin Hepcidin (ng/mL 0 100 200 300 Serum Iron (μmol/L) 0 20 40 60 DAI Score = Disease Activity Index
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 segments CKD Phase 1b SAD data demonstrate sustained pharmacologic activity and initial hematologic response with a single dose Multiple-dose portion will further explore optimal dose regimen to inform Phase 2a Preclinical IBD data provide further support for DISC-0974’s potential in anemias of inflammation DISC-0974 Summary and Next Steps DISC-0974 Summary
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-0974 Updated Data in Anemia of MF and Phase 2 Study Plan Will Savage, MD, PhD, Chief Medical Officer Preclinical Data in Anemia of IBD Will Savage, MD, PhD, Chief Medical Officer Closing Remarks John Quisel, JD, PhD, Chief Executive Officer 05 Q&A Session 06 04 DISC-3405 Phase 1b MAD and Preclinical SCD Data Will Savage, MD, PhD, Chief Medical Officer
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 Erythropoiesis Iron Overload Modulates RBC Production
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 Placebo) Assessment of safety, PK, hepcidin, and iron after each dose level 37.5 mg SC
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 hematocrit in both SAD and MAD cohorts Data set supportive of a once-monthly subcutaneous dosing regimen in polycythemia vera and iron-overload conditions DISC-3405 was well tolerated with no injection-site reactions
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 Growing Body of Evidence for Iron Restriction for Disease Modification in Sickle Cell Disease
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 supportive of monthly dosing Preclinical SCD data showing decreased HbS concentration and improved markers of inflammation and hemolysis ASH Data Summary Next Steps
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-0974 Updated Data in Anemia of MF and Phase 2 Study Plan Will Savage, MD, PhD, Chief Medical Officer Preclinical Data in Anemia of IBD Will Savage, MD, PhD, Chief Medical Officer Closing Remarks John Quisel, JD, PhD, Chief Executive Officer 05 Q&A Session 06 04 DISC-3405 Phase 1b MAD and Preclinical SCD Data Will Savage, MD, PhD, Chief Medical Officer
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 model of IBD anemia Phase 2 study in MF initiated DISC-0974 Hepcidin Suppression Consistent, strong efficacy across BEACON and AURORA in adults and adolescents Patient survey highlights high burden of disease in EPP Defined path to registration with potential for accelerated approval Commercial readiness activities are well underway Summary of ASH Updates Bitopertin Heme Synthesis Modulator Increased hepcidin and reduced serum iron across all dose levels supportive of subcutaneous monthly dosing Meaningful changes in hematologic parameters with multiple doses Positive preclinical data in SCD demonstrating potential for disease modification Phase 2 study in PV to start in 2025 DISC-3405 Hepcidin Induction
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 of Myelofibrosis (MF) Initial Phase 2 Data Final Phase 2 Data Anemia of Chronic Kidney Disease (CKD) Phase 1b Multiple-Dose Data Phase 2a Initiation Initial Phase 2a Data Polycythemia Vera Phase 2a Study Initiation Phase 2a Data DISC-3405 Hepcidin Induction Bitopertin Heme Synthesis Modulator DISC-0974 Hepcidin Suppression Supported by a strong cash position with runway well into 2027 Guidance on NDA timing to be provided in Q1 2025
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-0974 Updated Data in Anemia of MF and Phase 2 Study Plan Will Savage, MD, PhD, Chief Medical Officer Preclinical Data in Anemia of IBD Will Savage, MD, PhD, Chief Medical Officer Closing Remarks John Quisel, JD, PhD, Chief Executive Officer 05 Q&A Session 06 04 DISC-3405 Phase 1b MAD and Preclinical SCD Data Will Savage, MD, PhD, Chief Medical Officer
