Disc Medicine, Inc. · NASDAQ:IRON
Disc Medicine — Investor Presentation (October 2025)
61 slides from Disc Medicine's investor presentation, Oct 20, 2025
Slide 1: Corporate Presentation October 2025
Exhibit 99.2 Corporate Presentation October 2025
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: 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 3
Slide 4: Bitopertin selected for FDA's CNPV Pilot Program
Bitopertin selected for the FDA’s Commissioner’s National Priority Voucher (CNPV) Pilot Program New program announced June 2025 offering accelerated reviews for drug product applications that support US national interests FDA’s Stated Program Priorities Key Program Benefits • Addressing a US public
Slide 5: Targeting Fundamental Pathways of Red Blood Cell Biology
Targeting Fundamental Pathways of Red Blood Cell Biology using Validated Mechanisms Iron and heme metabolism Iron are critical pathways in hematology with genetically- validated targets Key points of intervention across a wide range of diseases Heme Spectrum of Hematologic Diseases Addressable by Di
Slide 6: 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 Increase Iron Restrict Iron Modulate Heme Hepcidin Hepcidin Synthesis Suppression Induction Bitopertin DISC-0974 DISC-3405 Lead Program (GlyT1 Inhibition) (Anti-HJV mAb) (Anti-TMPRSS6 mAb) (MOA) Diseases e
Slide 7: Disc's Hematology-Focused Pipeline
Disc’s Hematology-Focused Pipeline Multiple programs in development with pipeline-in-a-product potential Portfolio Program Preclinical Phase 1 Phase 2 Phase 3 / Confirmatory Erythropoietic Porphyrias (EPP and XLP) – NDA Submitted; CNPV Received; Potential for Accelerated Approval; APOLLO study under
Slide 8: 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 ü Feedback from Type C ü NDA Submission Erythropoietic Porphyrias Potential Approval Meeting with FDA ü CNPV Received (EPP and XLP) (late ’25 - early
Slide 9: Bitopertin GlyT1 Inhibitor Heme Biosynthesis Modulation
Bitopertin GlyT1 Inhibitor Heme Biosynthesis Modulation 9
Slide 10: 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 ALAS CoA ALAD HMBS FECH Glycine ferrochelatase UROS Iron Critical and initiating precursor f
Slide 11: Erythropoietic Protoporphyria (EPP)
Erythropoietic Protoporphyria (EPP) Rare, debilitating and lifelong condition characterized by extreme pain and damage to skin caused by light Genetic condition caused by defective heme biosynthesis – deficient enzyme ferrochelatase • Lifelong and presents in early childhood • Caused by accumulation
Slide 12: EPP patient population is well-defined
The EPP patient population is well-defined, enabling an efficient commercial model Prevalence of EPP Patients in the US Distribution of EPP Treatment Centers Expansion ~ 20K Predicted Genetic Misdiagnosed or have not Prevalence of EPP sought treatment for EPP Growth Diagnosed EPP patients with lower
Slide 13: Real world data confirm EPP impact on patients' lives
Real world data confirm EPP has a significant impact on patients’ lives across multiple domains Psychosocial Concomitant Medication 56% have anxiety Skin and/or depression 57% 30% 19% <30 min. receive steroid treated get prescription treatment with narcotics Vitamin D sun exposure before symptoms He
Slide 14: Bitopertin: Potential Disease-Modifying Treatment
Bitopertin: Potential Disease-Modifying Treatment Designed to reduce disease-causing PPIX by limiting uptake of glycine into developing erythrocytes EPP and XLP Patients Bitopertin Treatment High PPIX Levels Designed to Reduce PPIX Levels ↓ Glycine Glycine Heme Heme ALAS2 ALAS2 FECH FECH X X (+++) (
Slide 15: EPP Development Program
EPP Development Program BEACON, AURORA, HELIOS, and APOLLO Studies Phase 2 – Completed Confirmatory – Initiated EPP and XLP; N = 26 (22 adults, EPP and XLP; N = ~150 adults EPP; N = 75 adults 4 adolescents) and adolescents United States, Canada, Europe, Australia United States and Australia Open-lab
Slide 16: APOLLO Trial
APOLLO Trial Post marketing confirmatory trial required for US full approval N Size ~150* patients across sites in the US, Canada, Europe, and Australia Trial Duration 6-month treatment period; Expected to fully enroll within ~12 months Trial Design Randomized 1:1, double-blind, placebo-controlled E
Slide 17: Summary of AURORA Results
Diff vs Placebo in Pain-Free Sunlight Exposure (hr) Summary of AURORA Results Bitopertin 60 mg Significant reductions in PPIX PPIX Change: Bitopertin 60 mg Sunlight Exposure: Bitopertin 60 mg 40% reduction vs baseline 12 0 Time-dependent, improvements in pain- -10 8 free time in sunlight vs placebo
Slide 18: Summary of BEACON Results
Summary of BEACON Results Consistent with AURORA data, with similar results in adults and adolescents Tertiles of PPIX Change Adolescents (n=4) Adults (n=22) 0 PPIX Decreased PPIX Increased -20 Light Tolerance Tertile 3 Tertile 2 Tertile 1 Measure (-43% to (-53% to (-98% to (Mean ± SD) 25%) -43%) -5
Slide 19: Summary of HELIOS Initial Results
Summary of HELIOS Initial Results Favorable long-term efficacy and safety Sustained reductions in PPIX with continued bitopertin treatment All patients on bitopertin 40 End of AURORA Greater PPIX decreases in participants who received 60 mg bitopertin continuously 20 Continued treatment with 60 mg b
Slide 20: Bitopertin Next Steps
Bitopertin Next Steps Collaborate with FDA throughout their review Accelerate activities to support a potential US approval and launch in late 2025 or early 2026 Drive enrollment of ongoing APOLLO confirmatory trial ongoing in US and Europe Disc is committed to ensuring access to bitopertin for pati
Slide 21: Bitopertin in Diamond Blackfan Anemia
Bitopertin in Diamond Blackfan Anemia By slowing the influx of glycine, bitopertin lowers heme production, reducing the amount of excess heme and preventing cell death Less Heme Hemoglobin Slower Globin Production Glycine Critical and initiating precursor Complete for heme biosynthesis and is suppli
Slide 22: Multiple Additional Potential Applications of Bitopertin
Multiple Additional Potential Applications of Bitopertin Inhibiting heme synthesis with bitopertin has potential to address a wide range of hematologic diseases + Succinyl + Iron + Globin CoA Mature red blood Porphyrins Heme Hemoglobin Glycine cells (RBCs) Porphyrin Toxicity Heme Toxicity Globin Tox
Slide 23: Hepcidin Modulation Iron Homeostasis
Hepcidin Modulation Iron Homeostasis 23
Slide 24: 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 24
Slide 25: 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 Low Hepcidin Normal Hepcidin Regulated erythropoiesis Restricted Iron Iron Overload Anemias of Inflammatory Disease Iron Overload and Excess Red Blood Cell Disorders Regulate
Slide 26: DISC-0974 Anti-HJV mAb Hepcidin Suppression
DISC-0974 Anti-HJV mAb Hepcidin Suppression 26
Slide 27: 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 Enables Reduces Increases RBC Hepcidin Iron Production Inhibits endogenous Releases iron stores Potential to treat production of hepcidin Enables GI absorption wi
Slide 28: Significant Opportunity in Anemia of Inflammation
Significant Opportunity in Anemia of Inflammation Numerous chronic diseases associated with anemia from high hepcidin nd Est. % • Anemia of inflammation is the 2 Anemia Types US Prev. Anemic most common form of anemia Myelofibrosis (MF) 25K 87% • Estimated 40% of all anemias are Chronic Kidney Disea
Slide 29: 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-functi
Slide 30: Phase 1 SAD Trial in Healthy Volunteers
Phase 1 SAD Trial in Healthy Volunteers Established proof-of-mechanism based on hepcidin and iron parameters DISC-0974 Reduced Hepcidin DISC-0974 Increased TSAT Trial Design Production • Single-ascending dose in ≥32 healthy volunteers • Key outcome measures: • Safety and PK • Hepcidin level, serum i
Slide 31: DISC-0974 Development Strategy
DISC-0974 Development Strategy Ph 1b / 2 in MF or MDS Patients with Transfusion- Dependent and Non-Transfusion Dependent Anemia – Assessing safety, PK, Ongoing hepcidin, iron, Established initial POC in MF hemoglobin and Initiated POC study in CKD transfusion burden (MF Ph 1b / 2a in CKD Patients wi
Slide 32: Hepcidin is a Key Driver of Myelofibrosis Anemia
Hepcidin is a Key Driver of Myelofibrosis (MF) Anemia Anemia is severe and prevalent in MF and can limit treatment Hepcidin Levels are Elevated in MF Anemia of MF ~ 12× higher than control and associated with severity of anemia and transfusion burden 6.5 Est. # Patients • 25,000 patients (US) 6 • ~8
Slide 33: DISC-0974 Anemia of MF Phase 1b Study overview
DISC-0974 Anemia of MF Phase 1b Study overview – enrollment data as of October 17, 2024 Screening Treatment Period Optional Continuation (28 Days) (6 months) (Up to 2 years) Screen Baseline D1 D2 D8 D15 D22 D29 D43 D57 D71 85 D113 D141 D169/EOS Q28 Day/EOS 14 mg 28 mg 50 mg 75 mg 100 mg Overall Trea
Slide 34: DISC-0974 Anemia of MF Phase 1b Results: 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 35: Phase 1b Results: Hematologic response
DISC-0974 Anemia of MF Phase 1b Results Hematologic response: 14, 28, 50, 75, and 100 mg Substantial reductions in hepcidin and increases in iron levels translating to hematologic response Positive impact on clinically meaningful measures of anemia across a broad range of MF patients nTD Patients TD
Slide 36: Hematologic response with concomitant JAKi therapy
DISC-0974 Anemia of MF Phase 1b Results Hematologic response with concomitant JAKi therapy (n=13) nTD Response (n=9) TD High Response (n=4) Any Hgb ≥1.5 g/dL 78% Overall response 50% ≥50% reduction in During the treatment transfusion period requirement Major response 67% Major response 25% Mean Hgb
Slide 37: Biomarker analysis – major responders vs non-major responders
DISC-0974 Anemia of MF Phase 1b Results Biomarker analysis – major responders vs non-major responders Sustained hepcidin suppression and iron mobilization, consistent with mechanism and previous results Also showed sustained reduction in Zinc PPIX, a measure of iron restricted hemoglobin production
Slide 38: Durability of hematologic response
DISC-0974 Anemia of MF Phase 1b Results Durability of hematologic response – major responders vs non-major responders Anemia response is durable in continuation phase for major responders No nTD or TD Low major responders received a transfusion during continuation phase Hemoglobin Change from Baseli
Slide 39: Phase 1b Results: Safety
DISC-0974 Anemia of MF Phase 1b Results Safety 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 par
Slide 40: DISC-0974 in Combination Regimens
DISC-0974 in Combination Regimens Wild-type mouse models Mouse analog: Mouse analog: Mouse analog: DISC-0974 + ruxolitinib DISC-0974 + ESA DISC-0974 + luspatercept 80 60 80 *** *** Target *** *** 60 60 40 Engagement 40 40 ↓ Hepcidin 20 20 ↑ Serum Iron 20 0 0 0 160 200 200 *** *** 140 Hematologic Imp
Slide 41: RALLY-MF: Phase 2 Study Overview
RALLY-MF: Phase 2 Study Overview Study Population Design • N = ~90 (30 per cohort) Screening Treatment Period Follow-Up Continuation Treatment (28 Days) (6 Cycles q28 Days) (28 Days) (q28 Days – optional) – 12 patients carried over from Phase 1b* nTD: N=30* • Adult patients with MF Key endpoints: an
Slide 42: MF Anemia Opportunity
MF Anemia Opportunity Anemia remains a high unmet need within an established field ~22K US addressable MF patients with anemia Clear Unmet Well- Differentiated Severe Need Characterized Product Condition Market HCPs and patients Progressive in Aiming to address recognize importance MF expert network
Slide 43: Hepcidin is a Key Driver of CKD Anemia
Hepcidin is a Key Driver of CKD Anemia Pervasive issue that is currently highly under-treated Hepcidin Levels Elevated in CKD Patients Anemia of CKD ~20x higher than healthy subjects and increases with disease severity Est. # Patients • 5 to 6 million anemic NDD-CKD patients in the US alone Etiology
Slide 44: DISC-0974 Improved Anemia in Model of CKD
DISC-0974 Improved Anemia in Model of CKD Rat Model of Adenine Diet-Induced CKD DISC-0974 Reduced DISC-0974 Increased DISC-0974 Increased Hepcidin Expression Serum Iron Hemoglobin Levels Serum Iron HGB 80 80 14 14 2.0 2.0 1.7 g/dL vs. Vehicle 13 13 60 60 1. 1.5 5 12 12 40 40 11 11 1. 1.0 0 10 10 20
Slide 45: 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 (ASN 2024) Substantial, durable, dose-dependent reduction in hepcidin and sustained increase in TSAT from baseline Serum Hepcidin Serum TSAT Reticulocyte Hemoglobin Hemoglobin Maximal Change in Hemoglobin +0.7 g
Slide 46: DISC-0974 in Other Anemias of Inflammation
DISC-0974 in Other Anemias of Inflammation Inflammatory bowel disease mouse model 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 Target Engagement Hematologic
Slide 47: DISC-3405 Anti-TMPRSS6 mAb Hepcidin Induction
DISC-3405 Anti-TMPRSS6 mAb Hepcidin Induction 47
Slide 48: 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 49: Targeting TMPRSS6 to Increase Hepcidin
Targeting TMPRSS6 to Increase Hepcidin Potent, specific target controls endogenous hepcidin production Inhibiting TMPRSS6 with an Antibody Enables TMPRSS6 Hepcidin Production to Suppress Iron • Genetic validation in patients with IRIDA (Iron- Refractory Iron Deficiency Anemia) TMPRSS6 selectively de
Slide 50: DISC-3405 Effects in Non-Human Primates
DISC-3405 Effects in Non-Human Primates Resulted in deep and sustained suppression of serum iron levels Single dose of DISC-3405 resulted in ~ 70% suppression of serum iron lasting 3 weeks • Potent PD effects observed across multiple preclinical studies consistent with TMPRSS6 inhibition • Hepcidin:
Slide 51: DISC-3405 in Beta Thalassemia and Polycythemia Vera
DISC-3405 in Beta Thalassemia and Polycythemia Vera Significant effects on hallmarks of disease Th3/+ V617F Hbb Model of Beta-Thalassemia Jak2 model of Polycythemia Vera ↑ Hepcidin ↓ Spleen ↑ Hepcidin ↓ RBC ↓ Iron ↓ Hematocrit Production Weight Production Production Chen B. et al Blood (2021) 138 (S
Slide 52: 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
Slide 53: DISC-3405 Development Plans
DISC-3405 Development Plans Advancing program into POC studies with Phase 2 polycythemia vera and planned Phase 1b sickle cell disease initiation anticipated by year end Phase 2 Proof-of-Concept Study in Polycythemia Vera • Strong proof of therapeutic hypothesis; clarity on regulatory development pa
Slide 54: DISC-3405 Phase 1 Healthy Volunteer Study Overview
DISC-3405 Phase 1 Healthy Volunteer Study Overview Single-Ascending Dose Multiple-Ascending Dose 300 mg SC 150 mg SC 150 mg SC (Q4W) 75 mg SC (Q4W) 75 mg SC 37.5 mg SC 75 mg IV N=8 per Cohort (6 Active, 2 Placebo) Assessment of safety, PK, hepcidin, and iron after each dose level Key Endpoints/Measu
Slide 55: Updated DISC-3405 HV Data: Hepcidin, Iron, and PK
% Change from Baseline % Change from Baseline Updated DISC-3405 HV Data: Hepcidin, Iron, and PK DISC-3405 produced dose-related increases in serum hepcidin, with corresponding reductions in serum iron across all dose levels DISC-3405 resulted in deep reductions in serum iron (ranging from 50-80% fro
Slide 56: Updated DISC-3405 HV Data: Hematologic Response
Updated DISC-3405 HV Data: Hematologic Response Single and repeat dosing of DISC-3405 demonstrated meaningful reductions in hematologic parameters (reticulocyte hemoglobin, hemoglobin, and hematocrit) Reticulocyte Hemoglobin Hemoglobin Hematocrit 5 5 5 0 0 0 -5 -5 -5 -10 -10 -10 -15 -15 -15 0 28 56
Slide 57: DISC-3405: Iron Pulse Study in Healthy Volunteers
DISC-3405: Iron Pulse Study in Healthy Volunteers Evaluating the effectiveness of DISC-3405 in inhibiting dietary iron uptake Study Design Conducted an iron pulse study to evaluate the effectiveness of DISC-3405 in inhibiting dietary iron uptake: • N=8 healthy volunteers received oral ferrous sulfat
Slide 58: DISC-3405: Iron Pulse Study Results
DISC-3405: Iron Pulse Study in Healthy Volunteers Strong inhibition of iron absorption with DISC-3405 DISC-3405 resulted in an average 94% reduction in iron absorption at Day 2 and 68% at Day 15 Data confirms the mechanism of DISC-3405 and its ability to block dietary iron absorption, supporting the
Slide 59: Sickle Cell Disease Phase 1b Study
Sickle Cell Disease Phase 1b Study Initiation anticipated by year end 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 Cohort B (n≤12, HbSC or Hb
Slide 60: Summary and Upcoming Objectives and Catalysts
Summary and Upcoming Objectives and Catalysts Summary Objectives and Catalysts • Positive data across two Phase 2 studies and HELIOS data supports the durability of efficacy • Potential approval late 2025-early 2026 Bitopertin Heme Synthesis • Confirmatory APOLLO study initiated in May 2025 • Accele
Slide 61: Thank You
Thank You disc)