Disc Medicine, Inc. · NASDAQ:IRON
Disc Medicine — Investor Presentation (September 2026)
63 slides from Disc Medicine's investor presentation, September 2026
Slide 1: Corporate Presentation
Corporate Presentation September 2026
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 its preclinical studies, clinical trials a
Slide 3: Bitopertin, selcodebart, and DISC-3405 are investigational agents
Bitopertin, selcodebart (DISC-0974), and DISC-3405 are investigational agents and are not approved for use as therapies in any jurisdiction worldwide 3
Slide 4: Targeting fundamental pathways of red blood cell biology using validated mechanisms
Targeting fundamental pathways of red blood cell biology using validated mechanisms Iron and heme metabolism Iron are critical pathways with genetically validated targets Key points of intervention across a broad range of diseases Heme Spectrum of Hematologic Diseases Addressable by Disc Portfolio V
Slide 5: By targeting heme and iron, Disc's portfolio can address a wide range of hematologic disorders
By targeting heme and iron, Disc’s portfolio can address a wide range of hematologic disorders Modulate Heme Increase Iron Restrict Iron Synthesis Hepcidin Suppression Hepcidin Induction Selcodebart Clinical Program Bitopertin DISC-3405 (MOA) (GlyT1 Inhibitor) (DISC-0974) (Anti-TMPRSS6 mAb) (Anti-HJ
Slide 6: Disc's hematology-focused pipeline
Disc’s hematology-focused pipeline Key programs driving upcoming catalysts PROGRAM Preclinical Phase 1 Phase 2 Phase 3 Heme Bitopertin HEME Synthesis GlyT1 Inhibitor Erythropoietic porphyrias (EPP and XLP) Modulation Oral, once daily Anemia of myelofibrosis (MF) Selcodebart Anti-HJV monoclonal antib
Slide 7: Bitopertin
Bitopertin GlyT1 inhibitor | Heme biosynthesis modulation
Slide 8: Bitopertin: Investigational oral, selective GlyT1 inhibitor
Bitopertin: Investigational oral, selective GlyT1 inhibitor In multiple clinical trials by Roche, bitopertin was observed to modulate heme biosynthesis by blocking uptake of glycine in erythrocytes +Succinyl CoA ALAS ALAD Glycine HMBS FECH Critical and initiating ferrochelatase UROS Iron precursor f
Slide 9: Erythropoietic Protoporphyria (EPP)
Erythropoietic Protoporphyria (EPP) Rare, debilitating and lifelong condition characterized by extreme pain and damage to the skin caused by light, as well as potential hepatobiliary complications and psychosocial impacts Genetic condition caused by defective heme biosynthesis – deficient enzyme fer
Slide 10: EPP: Well-defined rare disease population
EPP: Well-defined rare disease population Patient population defined by claims analysis and validated by real-world evidence Prevalence of EPP Patients in the US Epidemiology Real world prevalence of hepatobiliary complications in EPP match evidence of ~ 20K PREDICTED GENETIC liver/biliary issues in
Slide 11: Real world data confirm EPP has a significant impact on patients' lives
Real world data confirm EPP has a significant impact on patients’ lives across multiple domains Concomitant Medication 56% Psychosocial have anxiety and/or depression Skin 57% 30% 19% receive steroid treated get prescription treatment with narcotics Vitamin D <30 min. sun exposure before symptoms He
Slide 12: Bitopertin: Potential disease-modifying treatment
Bitopertin: Potential disease-modifying treatment Designed to reduce disease-causing PPIX by limiting update of glycine into developing erythrocytes EPP and XLP Patients Bitopertin Treatment High PPIX Levels Designed to Reduce PPIX Levels Glycine Heme ↓ Glycine Heme ALAS2 (+++) X FECH ALAS2 (+++) X
Slide 13: EPP development program
EPP development program BEACON, AURORA, HELIOS, and APOLLO studies Phase 2 – Completed Phase 3 – Enrollment Complete EPP and XLP; N=26 (22 EPP; N=75 adults EPP and XLP; N=183 adults and adults, 4 adolescents United States adolescents Australia Double-blind, United States, Canada, Europe, Australia O
Slide 14: Summary of AURORA results
Summary of AURORA results Bitopertin 60mg Significant reductions in PPIX 40% reduction vs baseline PPIX Change: Bitopertin 60 mg Sunlight Exposure: Bitopertin 60 mg Pain-Free Sunlight Exposure (hr) 0 12 Time-dependent, improvements in % Change in WB PPIX -10 pain-free time in sunlight vs placebo Dif
Slide 15: Summary of BEACON results
Summary of BEACON results Consistent with AURORA data, with similar results in adults and adolescents Tertiles of PPIX Change Mean Change in PPIX (%) 0 Adolescents (n=4) Adults (n=22) PPIX Increased PPIX Decreased -20 Light Tolerance Measure Tertile 3 Tertile 2 Tertile 1 (Mean ± SD) (-43% to (-53% t
Slide 16: Summary of HELIOS results
Summary of HELIOS results Favorable long-term efficacy and safety Sustained reductions in PPIX with continued bitopertin treatment All patients on bitopertin 40 Greater PPIX decreases in participants % Change WB Metal-Free PPIX End of AURORA who received 60 mg bitopertin 20 continuously 0 Continued
Slide 17: APOLLO trial overview
APOLLO trial overview Enrollment completed in March 2026; topline data expected Q4 2026 183 patients across sites in the US, Canada, N Size Europe, and Australia Robust Endpoint Trial Longitudinal analysis leverages robust model that 6-month treatment period; Fully enrolled March 2026 Duration demon
Slide 18: Phase 2 Experience Supports Confidence in APOLLO Design
Phase 2 Experience Supports Confidence in APOLLO Design Co-primary Endpoints: Average Monthly Time in Light without Pain and PPIX Change from Baseline 28 AURORA:28Sunlight Tolerance Over Time† AURORA: PPIX Over Time Daily Sunlight Exposure, Daily Sunlight Exposure, p=0.03 vs PBO* 24 28 24 Mean ± SE
Slide 19: APOLLO Baseline Characteristics
APOLLO Baseline Characteristics Adolescent (n=34) Adult (n=149) Overall (n=183) Age (years), Mean 14 42 37 Adolescent, n (%) 34 0 34 (19%) Sex (female), n (%) 20 (59%) 87 (58%) 107 (59%) Diagnosis EPP 31 (91%) 140 (94%) 171 (93%) XLP 3 (9%) 9 (6%) 12 (7%) Prior EPP Treatment Afamelanotide 2 (6%) 50
Slide 20: Bitopertin: Potential to be the first approved medicine targeting the underlying cause of EPP
Bitopertin: Potential to be the first approved medicine that targets the underlying cause of EPP Shown in clinical trials to reduce PPIX and improve multiple clinically meaningful measures of EPP Functional benefit by Targets underlying Meaningful improvement Significantly improved reducing debilita
Slide 21: Bitopertin in EPP: Progressing toward CRL response by end of 2026
Bitopertin in EPP: Progressing toward CRL response by end of 2026 In Type A meeting, aligned with the FDA that the Phase 3 APOLLO study can serve as the basis for CRL response and, if successful, support a traditional approval APOLLO trial fully enrolled in March 2026 and topline data expected in Q4
Slide 22: Hepcidin Modulation
Hepcidin Modulation Iron homeostasis
Slide 23: Iron is fundamental to RBC biology
Iron is fundamental to RBC biology Hepcidin is a regulatory hormone that plays a central role in iron metabolism and homeostasis Induced by Inflammation Hepcidin Gatekeeper Function: Blocks iron absorption and recycling GI Tract Spleen Iron Intake Iron Storage RBC Production in Bone Marrow 23
Slide 24: Hepcidin is a therapeutic target for diseases
Hepcidin is a therapeutic target for diseases Dysregulated hepcidin drives a wide range of hematologic diseases High Hepcidin Normal Hepcidin Low Hepcidin Regulated erythropoiesis Restricted Iron Overload Iron Anemias of Inflammatory Disease Iron Overload and Excess Red Blood Cell Disorders Regulate
Slide 25: Selcodebart
Selcodebart Anti-HJV mAb | Hepcidin suppression
Slide 26: Selcodebart (DISC-0974): Novel anti-HJV mAb to suppress hepcidin
Selcodebart (DISC-0974): Novel anti-HJV mAb to suppress hepcidin Designed to enhance iron availability to address a wide range of hematologic disorders Enables Reduces Increases RBC Hepcidin Iron Production Inhibits endogenous Releases iron stores Potential to treat production of hepcidin Enables GI
Slide 27: Significant opportunity in anemia of inflammation
Significant opportunity in anemia of inflammation Numerous chronic diseases associated with anemia from high hepcidin Anemia Types US Prev. Est. % Anemic Anemia of inflammation is the 2nd Myelofibrosis (MF) 25K 87% most common form of anemia Inflammatory Bowel Estimated 40% of all anemias are 1.6 MM
Slide 28: Targeting hemojuvelin (HJV) to suppress hepcidin
Targeting hemojuvelin (HJV) to suppress hepcidin Critical and specific target for hepcidin expression Inhibiting Hemojuvelin (HJV) Prevents Hepcidin Expression and Increases Iron Genetic validation in patients with Juvenile Hemochromatosis (lower hepcidin and elevated iron levels) • Loss-of-function
Slide 29: Phase 1 SAD trial in healthy volunteers
Phase 1 SAD trial in healthy volunteers Established proof-of-mechanism based on hepcidin and iron parameters Selcodebart Reduced Hepcidin Trial Design Selcodebart Increased TSAT Production • Single-ascending dose in ≥32 healthy volunteers • Key outcome measures: • Safety and PK • Hepcidin level, ser
Slide 30: Selcodebart development strategy
Selcodebart development strategy Ph 1b / 2 in MF or MDS Patients with Transfusion- Dependent and Non-Transfusion Dependent Anemia – Ongoing POC established in MF Initiated POC study in IBD Phase 2 in IBD Patients with Anemia – Initiated Q1 2026 Established POM in Healthy Volunteers Expansion in Othe
Slide 31: Hepcidin is a key driver of myelofibrosis anemia
Hepcidin is a key driver of myelofibrosis (MF) anemia Anemia of MF Hepcidin Levels are Elevated in MF ~ 12× higher than control and associated with Est. # Patients severity of anemia and transfusion burden • 25,000 patients (US) 6.5 • ~87% are anemic; severe and require transfusion 6 Etiology of Ane
Slide 32: RALLY-MF: Study overview and baseline characteristics
RALLY-MF: Study overview and baseline characteristics Data as of April 27, 2026 Screening Treatment Period Follow-Up Optional Continuation (28 Days) (6 cycles, q28 days) (28 Days) (Up to 2 years) Key Study Endpoints Anemia response defined by cohort (TI, transfusion burden reduction, Hgb change); Ir
Slide 33: Updated RALLY-MF phase 2 data
Updated RALLY-MF phase 2 data Positive, durable benefits on hemoglobin and transfusion burden in anemia of MF across a broad range of patients Hepcidin by Transfusion Cohort Iron by Transfusion Cohort Hematologic Response 150 300 nTD Serum Hepcidin, ng/mL 125 TD Low 250 Serum Iron, ng/mL TD High Mea
Slide 34: Updated RALLY-MF data: nTD cohort
Updated RALLY-MF phase 2 data nTD (n=31): Early-acting, meaningful, and durable hemoglobin increases with 55% of patients achieving major response and 68% achieving overall response nTD Hematologic Response nTD Hemoglobin Increase from Baseline Evaluable participants (n=31) Treatment period Optional
Slide 35: Updated RALLY-MF data: TD Low cohort
Updated RALLY-MF phase 2 data TD Low (n=11): Meaningful, and durable hemoglobin increases translating to transfusion reduction, with 64% of patients achieving major response and 73% achieving overall response TD Low Hematologic Response TD Low Hemoglobin Increase from Baseline Evaluable participants
Slide 36: Updated RALLY-MF data: TD High cohort
Updated RALLY-MF phase 2 data TD High (n=8): Meaningful transfusion reduction, with 50% of patients achieving major response and 88% achieving overall response TD High (n=8) Overall response 88 ≥50% reduction in transfusion requirement Major response 50 TI ≥12 weeks 0 20 40 60 80 100 % of Responders
Slide 37: Updated RALLY-MF data: FACIT-Fatigue improvement
Updated RALLY-MF phase 2 data nTD and TD Low patients experienced clinically significant improvement in FACIT-Fatigue FACIT-Fatigue (nTD patients) FACIT Fatigue (TD Low patients) 12 nTD - Major responders 12 TD Low - Major responders FACIT-Fatigue improvement 9 and Hgb change were Δ FACIT-Fatigue Δ
Slide 38: Efficacy regardless of concomitant JAK inhibitor use
RALLY-MF phase 2 data update Selcodebart has demonstrated efficacy regardless of concomitant JAK inhibitor use, setting up for utilization across all anemic MF patients Hepcidin by JAKi Cohort Iron by JAKi Cohort Hemoglobin by JAKi Cohort Response by JAKi Cohort Evaluable participants (n=50) Evaluab
Slide 39: Updated RALLY-MF phase 2 data: Safety
Updated RALLY-MF phase 2 data Safety Preferred Term nTD (n=35) TD Low (n=13) TD High (n=13) Overall (n=61) Any TEAE, n (%) 33 (94.3) 12 (92.3) 11 (84.6) 56 (91.8) Related TEAE, n (%) 6 (17.1) 4 (30.8) 5 (38.5) 15 (24.6) SAE, n (%) 8 (22.9) 1 (7.7) 3 (23.1) 12 (19.7) AESIs, n (%) 2 (5.7) 0 0 2 (3.3)
Slide 40: Myelofibrosis opportunity
Myelofibrosis opportunity Positioned for use across all anemia MF patients, regardless of background MF-directed therapy, setting up for a potential blockbuster opportunity Significant Unmet Need for Anemia-Focused Therapy ~$2.0B Total Est. 2024 JAK Inhibitor US Sales (MF) Anemia is associated with
Slide 41: Selcodebart: Emerging product profile for MF anemia therapy
Selcodebart: Emerging product profile aiming to address key needs for MF anemia therapy Key Needs for Anemia Therapy Selcodebart Emerging Product Profile ✓ Achieved POC in NTD, TD Low, and TD High patients 1 Works across anemia severity levels • Recruiting greater N for each cohort in ongoing Phase
Slide 42: Selcodebart in other anemias of inflammation
Selcodebart in other anemias of inflammation Inflammatory bowel disease mouse model Mouse analog of selcodebart supressed hepcidin, increased serum iron, and increased hemoglobin in anemic IBD mice Treatment also demonstrated disease-modifying and anti-inflammatory effects Target Engagement Hematolo
Slide 43: RALLY IBD: Phase 2 trial design
RALLY IBD: Phase 2 trial design Initiated Q1 2026 Study Population Study Schema • N=21 • ≥18 years of age with IBD Selcodebart 60 mg Screen D1 D8 D15 D29 D43 D57 D85/EOS D92 D99 D113 D127 D141 EOS (sc) • Mild disease assessed by baseline R endoscopy at screening Scr Treatment Period Optional OLE for
Slide 44: Anti-HJV franchise: Next steps and future development
Anti-HJV franchise: Next steps and future development Anemia of Myelofibrosis • Additional RALLY-MF data expected Q4 2026 • End of Phase 2 Meeting with FDA expected by end of year • Phase 3 Pivotal trial initiation expected H1 2027 Other Anemias of Inflammation • RALLY-IBD signal-seeking Phase 2 stu
Slide 45: DISC-3405
DISC-3405 Anti-TMPRSS6 mAb | Hepcidin induction
Slide 46: 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 Limits Modulates Increases Iron RBC Hepcidin Availability Production Enables Endogenous Promotes Iron Restriction Erythrocytosis (PV) Production of Hepcidin Decreases GI Ab
Slide 47: Targeting TMPRSS6 to increase hepcidin
Targeting TMPRSS6 to increase hepcidin Potent, specific target controls endogenous hepcidin production TMPRSS6 Inhibiting TMPRSS6 with an Antibody Enables Hepcidin Production to Suppress Iron Genetic validation in patients with IRIDA (Iron-Refractory Iron Deficiency Anemia) TMPRSS6 selectively degra
Slide 48: DISC-3405 in beta thalassemia and polycythemia vera
DISC-3405 in beta thalassemia and polycythemia vera Significant effects on hallmarks of disease HbbTh3/+ Model of Beta-Thalassemia Jak2V617F model of Polycythemia Vera ↑ Hepcidin ↓ Spleen ↑ Hepcidin ↓ RBC ↓ Iron ↓ Hematocrit Production Weight Production Production Chen B. et al Blood (2021) 138 (Sup
Slide 49: DISC-3405 development strategy
DISC-3405 development strategy Phase 2 Proof-of-Concept Study in Polycythemia Vera -- Ongoing • Strong proof of therapeutic hypothesis; clarity on regulatory development path • Assess safety, PK, hepcidin, iron, hematologic parameters; % HCT and requirement for phlebotomy Phase 1 SAD/MAD in HV Phase
Slide 50: DISC-3405 Phase 1 study in healthy volunteers
DISC-3405 Phase 1 study in healthy volunteers Established proof-of-mechanism based on hepcidin, iron, and hematologic parameters Single-Ascending Dose Multiple-Ascending Dose 300 mg SC 150 mg SC 150 mg SC (Q4W) 75 mg SC 75 mg SC (Q4W) 37.5 mg SC 75 mg IV N=8 per Cohort (6 Active, 2 Placebo); Assessm
Slide 51: DISC-3405: Iron pulse study in healthy volunteers
DISC-3405: Iron pulse study in healthy volunteers Strong inhibition of iron absorption with DISC-3405 DISC-3405 Increased DISC-3405 Reduced Iron Trial Design Hepcidin Production Absorption at D2 and D15 • N=8 healthy volunteers received oral Average Hepcidin** Average Serum Iron** ferrous sulfate ta
Slide 52: DISC-3405: Polycythemia vera opportunity
DISC-3405: Polycythemia vera opportunity Multi-billion-dollar market with significant unmet need for an effective, safe, and convenient treatment to maintain HCT <45% Polycythemia Vera DISC-3405 Positioning ~150,000 US Patients Attractive Market Current Treatment Options ~75k treated patients; signi
Slide 53: RESTORE-PV: Polycythemia vera phase 2 trial design
RESTORE-PV: Polycythemia vera phase 2 trial design Data as of July 13, 2026: All 20 participants in Cohort A were dosed, with n=13 completing 26 weeks of the study, and 18 of 20 participants in Cohort B were dosed Design Dose escalation Maintenance 1 Maintenance 2 (12 weeks) (20 weeks) (20 weeks) 15
Slide 54: RESTORE-PV: Baseline characteristics
RESTORE-PV: Baseline characteristics Data as of July 13, 2026 Cohort A (N=20) Cohort B (N=20) Age, years; mean (SD) 58.6 (13.3) 60.1 (11.4) Sex, male; n (%) 16 (80.0) 8 (40.0) 95% White 95% White Race 5% Black 5% Asian Disease duration, years; mean (SD) 5.8 (5.7) 5.6 (3.7) Risk High 65% 60% Low 35%
Slide 55: Initial RESTORE-PV phase 2 data
Initial RESTORE-PV phase 2 data In participants from Cohort A, DISC-3405 administration increased hepcidin levels, leading to reduced serum iron and increased ferritin Hepcidin Serum Iron Ferritin 55
Slide 56: Initial RESTORE-PV phase 2 data: hematocrit and phlebotomy
Initial RESTORE-PV phase 2 data Restricting iron availability with DISC-3405 translated to controlled mean HCT <45%, reduced PHL burden, and improved symptoms in Cohort A participants who completed weeks 0-26 of therapy (n=13) Hematocrit Total PHL Events: 26 Weeks Pre- vs Post-Treatment Initiation (
Slide 57: Initial RESTORE-PV phase 2 data: Maintenance 1
Initial RESTORE-PV phase 2 data Of the n=9 participants who completed Maintenance 1, 77.8% (7/9) remained PHL-free during the Maintenance 1 period DISC-3405 Reduced PHL Events in Cohort A Participants N=2 patients voluntarily withdrew, not due to adverse events. N=2 patients met PHL eligibility at 1
Slide 58: Initial RESTORE-PV phase 2 data: Safety
Initial RESTORE-PV phase 2 data Safety Adverse Event Cohort A (N=20) Cohort B (N=18) Total (N=38) Any TEAE, n (%)* 16 (80.0) 11 (61.1) 27 (71.1) Serious AE* 1 (5.0) 1 (5.6) 2 (5.3) Related TEAE∆ 4 (20.0) 6 (33.3) 10 (26.3) Abdominal pain 6 (30) 1 (5.6) 7 (18.4) Injection site reaction† 3 (15.0) 2 (1
Slide 59: 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 Growing Body of Evidence for Iron Restriction DISC-3405 in a Townes Model for Disease Modification in Sickle Cell Disease 3 and 10 mg/kg IP weekly for 8 w
Slide 60: Sickle cell disease phase 1b trial design
Sickle cell disease phase 1b trial design Initiated October 2025; initial data expected Q4 2026 Design Dose escalation Optional Maintenance 4 weeks 8 weeks 8 weeks 12 weeks Cohort A 75 mg 150 mg 300 mg 300 mg HbSC or HbSS X1 dose X1 dose X1 dose Q4W (n=12) 4-week Screening safety follow-up Optional
Slide 61: Corporate Outlook
Corporate Outlook
Slide 62: Projected Upcoming Milestones and Events
Projected Upcoming Milestones and Events Multiple data catalysts anticipated through 2026-2027 Program Indication 2H 2026 2027 • APOLLO topline – Q4 2026 • FDA decision mid-2027 Bitopertin Erythropoietic Porphyrias (EPP & XLP) • Submit response to CRL – late 2026 • Ex-US regulatory submissions Heme
Slide 63: Disc Medicine: Built for Sustainable Growth
Disc Medicine: Built for Sustainable Growth Three programs addressing blockbuster markets with significant potential for expansion Bitopertin Selcodebart DISC-3405 Phase 3 Ongoing POC Established Initial POC Established CRL response expected to be Additional MF data and Phase 3 RESTORE-PV update and
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