Disc Medicine, Inc. · NASDAQ:IRON
Disc Medicine — Investor Presentation (June 2023)
54 slides from Disc Medicine's investor presentation, Jun 9, 2023
Slide 1: Corporate Presentation June 2023
Corporate Presentation June 2023 Exhibit 99.2
Slide 2: Disclaimer and FLS
Disclaimer and FLS This presentation includes “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. These forward-looking statements include express or implied statements relating to Disc's management team's expectations, hopes, beliefs,
Slide 3: Disc is Building a Leading Company Dedicated to Treating Hematologic Diseases
Disc is Building a Leading Company Dedicated to Treating Hematologic Diseases Fundamental & Validated Pathways Multiple Clinical Programs with Broad Potential Multiple Near-Term Catalysts Focus on Hematologic Disorders Immense medical need across a wide spectrum of disorders Predictive, objective en
Slide 4: Our Executive Team
Former CFO of Arkuda Therapeutics, Dyne Therapeutics, and Quartet Medicine; previously at WiTricity, Speedy Packets, Narrative Communications; Arthur Andersen Joanne Bryce, CPA | Chief Financial Officer Magenta Therapeutics and Shire / Takeda; Trained in Pediatric Hematology & Transfusion Medicine;
Slide 5: Targeting Fundamental Pathways that Impact the Biology of Red Blood Cells
Targeting Fundamental Pathways that Impact the Biology of Red Blood Cells Erythropoietic Porphyrias ~7,500 CKD Anemia 6 Million+ (US) Sickle Cell Disease 200,000 Myelodysplastic Syndromes 200,000 Iron and heme formation play a central role in erythropoiesis Polycythemia Vera 200,000+ Critical points
Slide 6: Disc’s Portfolio Addresses Broad Spectrum of Hematologic Disorders
Disc’s Portfolio Addresses Broad Spectrum of Hematologic Disorders Hepcidin Suppression Increase Iron Hepcidin Induction Reduce Iron Heme Synthesis Modulation Bitopertin (GlyT1 Inhibition) EPP, DBA, other rare blood disorders Phase 2 studies in EPP Phase 2 in DBA – init. midyear ‘23 DISC-0974 (Anti-
Slide 7: 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 Near-Term Milestones DISC-0974‡ Anti-HJV monoclonal antibody Subcutaneous, once-monthly DISC-0998‡ Anti-HJV monoclonal ant
Slide 8: Projected Upcoming Milestones and Events
Projected Upcoming Milestones and Events Multiple catalysts expected beginning mid-year and through 2024 Program Indication H1 2023 H2 2023 2024 Erythropoietic Porphyrias (EPP and XLP) Initial Ph 2 BEACON presented at EHA Phase 2 BEACON data Phase 2 AURORA data (early 2024) End of Ph 2 Meeting Diamo
Slide 9: Strong Projected Growth Trajectory Towards Building a Leading Hematology Company
Strong Projected Growth Trajectory Towards Building a Leading Hematology Company Establish Company Build Portfolio of Clinical Programs Demonstrate Phase 2 POC in Multiple Programs 2021-2022 Licensed bitopertin and MWTX-003; DISC-0974 and bitopertin enter the clinic; Series B financing and transitio
Slide 10: Bitopertin GlyT1 Inhibitor Heme Biosynthesis Modulation
Bitopertin GlyT1 Inhibitor Heme Biosynthesis Modulation
Slide 11: 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 Glycine Critical and initiating precursor for heme biosynthesis and is supplied by GlyT1 transporter H
Slide 12: 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 of
Slide 13: PPIX is a Driver of Disease in EPP / XLP Patients
PPIX is a Driver of Disease in EPP / XLP Patients Toxic and photo-active metabolite accumulates in RBCs and is transported to skin and other organs, causing damage Skin Porphyrin ring absorbs light and emits energy and heat Oxidative damage to endothelial capillaries and surrounding tissue, perivasc
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 High PPIX Levels Bitopertin Treatment Designed to Reduce PPIX Levels Potential first disease-modifying treatment for EPP and XLP M
Slide 15: Bitopertin Reduced PPIX in Models of EPP / XLP
Bitopertin Reduced PPIX in Models of EPP / XLP Effects on PPIX have the potential to be disease-modifying EC50 3.8 nM Free PPIX (pmol / 1x106 cells) Bitopertin log[M] Data presented at the 63rd ASH Annual Meeting (December 2021); Studies performed in collaboration with Boston Children’s Hospital (PI
Slide 16: Bitopertin Robust Data Package
Bitopertin Robust Data Package Extensive non-clinical, CMC and clinical development has already been completed Non-Clinical CMC Clinical Genetic toxicity and Safety pharmacology Long-term GLP toxicology Juvenile GLP toxicology studies supporting patients ≥2 y/o Carcinogenicity studies Full reproduct
Slide 17: BEACON Trial: Open-Label Ph 2 Trial in EPP / XLP
BEACON Trial: Open-Label Ph 2 Trial in EPP / XLP Open-label, parallel-dose trial to establish POC and assess efficacy, safety in patients (N~22) Trial Design Trial endpoints: Changes in blood PPIX levels, light tolerance, time to prodromal symptom (TTPS), QOL, safety, tolerability, and PK Data avail
Slide 18: Initial BEACON Data: % Change in Whole-Blood PPIX
Initial BEACON Data: % Change in Whole-Blood PPIX PPIX data as of 7 April 2023 PPIX Changes Over Time Individual PPIX Data Whole-blood (WB) metal-free PPIX reduction was observed in trial participants Dose-dependent reductions were observed across broad range of baseline WB PPIX levels (140-3,410 µg
Slide 19: Light Tolerance: Time to First Prodromal Symptom (20 mg QD)
Light Tolerance: Time to First Prodromal Symptom Individual Patient Sunlight Challenges (20 mg QD) Additional data not visible due to y-axis scale include prodrome (*) after 2 minutes of sunlight and prodrome-free (*) challenge with 4 minutes of sunlight Sunlight challenge time for individual partic
Slide 20: Light Tolerance: Time to First Prodromal Symptom (60 mg QD)
Light Tolerance: Time to First Prodromal Symptom Individual Patient Sunlight Challenges (60 mg QD) Sunlight challenge time for individual participant while receiving 60 mg of bitopertin. Participants could complete more than 1 sunlight exposure challenge per week and if a patient was unable to elici
Slide 21: Initial BEACON Data: Light Tolerance Days without Symptoms or Prodromes
Initial BEACON Data: Light Tolerance Days without Symptoms or Prodromes *as assessed with a daily diary; **as assessed with a weekly sunlight challenge; ***summed across all patients Percentages calculated relative to total number of days with sunlight exposure (left) or total number of weekly sunli
Slide 22: Initial BEACON Data: Aggregated Light Tolerance Data
Initial BEACON Data: Aggregated Light Tolerance Data Time to Prodrome and Weekly Total Time in Sunlight Time to prodrome during weekly sun exposure challenges averaged over a two-week period, including cumulative time in sunlight challenges where the patient did not report a prodrome (left); if a pa
Slide 23: Initial BEACON Data: Measures of Quality of Life
Initial BEACON Data: Measures of Quality of Life QOL data may be entered at Day 43 ± 3 days and includes data from 1 participant who had not completed Day 43 visit; Responses at baseline or most recent visit while receiving bitopertin (combined 20/60 mg doses, n=10), subjects with data beyond Day 43
Slide 24: Initial BEACON Data: Safety and Tolerability
Initial BEACON Data: Safety and Tolerability Data as of 8 May 2023. Summaries include uncoded TEAEs categorized by verbatim terms; hgb = hemoglobin. Bitopertin 20 mg (n=8) Bitopertin 60 mg (n=7) Total (n=15) Total Number of TEAEs (all Grade 1) 8 8 16 Subjects with any TEAE (all Grade 1) 6 (75%) 6 (8
Slide 25: AURORA Trial: Ph 2 Trial in EPP
AURORA Trial: Ph 2 Trial in EPP Randomized, Double-Blind, Placebo Controlled trial to assess efficacy, safety in patients (N~75) Trial Design Trial endpoints: Changes in blood PPIX levels, time in daylight without pain, light tolerance, time to prodromal symptom (TTPS), QOL, safety / tolerability Da
Slide 26: Multiple Additional Potential Applications of Bitopertin
Glycine Hemoglobin Heme Porphyrins + Globin + Iron + Succinyl CoA Porphyrin Toxicity Erythropoietic Protoporphyria X-Linked Protoporphyria Congenital Erythropoietic Porphyria Hepatic Porphyrias Heme Toxicity Diamond-Blackfan Anemia Myelodysplastic Syndromes Globin Toxicity Beta-Thalassemia Sickle Ce
Slide 27: Hepcidin Modulation Iron Homeostasis
Hepcidin Modulation Iron Homeostasis
Slide 28: 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 GI Tract Iron Intake Spleen Iron Storage Hepcidin Gatekeeper Function: Blocks iron absorption and recycling RBC Production in Bone Marrow Induced by Inflammation
Slide 29: Hepcidin is a Therapeutic Target for Diseases
Hepcidin is a Therapeutic Target for Diseases Dysregulated hepcidin drives a wide range of hematologic diseases Anemias of Inflammatory Disease Myelofibrosis Chronic Kidney Disease Autoimmune / Inflammatory Disorders Iron Overload and Excess Red Blood Cell Disorders Polycythemia Vera Hereditary Hemo
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Slide 31: 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 32: Anemia of Inflammation or Chronic Disease
Anemia of Inflammation or Chronic Disease Inflammation caused by a wide range of conditions results in anemia due to elevated hepcidin Anemia of inflammation (also called Anemia of Chronic Disease or ACD) is the 2nd most common form of anemia Estimated 40% of all anemias are driven by or have an inf
Slide 33: Targeting Hemojuvelin (HJV) to Suppress Hepcidin
Genetic validation in patients with Juvenile Hemochromatosis (lower hepcidin and elevated iron levels) Loss-of-function mutations in HJV are phenotypically indistinguishable from mutations in HAMP (hepcidin) gene Functionally specific to hepcidin / iron Tissue specific expression primarily in the li
Slide 34: DISC-0974 Mechanism of Action
DISC-0974 Mechanism of Action Designed to reduce hepcidin and increase serum iron levels Potent and rapid effects on hepcidin and iron with single 5 mg / kg dose (NHP) Days DISC-0974 mAb binds to and prevents signaling through hemojuvelin (HJV) co-receptor x
Slide 35: Phase 1 SAD Trial in Healthy Volunteers
Phase 1 SAD Trial in Healthy Volunteers Established proof-of-mechanism based on hepcidin and iron parameters Dose Level 7 mg IV 6 Treated / 2 Placebo Dose Level 14 mg SC 6 Treated / 2 Placebo Dose Level 28 mg SC 6 Treated / 2 Placebo Assessment of safety, PK, hepcidin and iron after each dose level
Slide 36: DISC-0974 Phase 1 SAD Data
DISC-0974 Phase 1 SAD Data Dosing of DISC-0974 demonstrated a reduction of hepcidin and iron mobilization DISC-0974 Increased TSAT DISC-0974 Reduced Hepcidin Production TSAT = transferrin saturation; SAD = single ascending dose
Slide 37: DISC-0974 Phase 1 SAD Data (cont.)
DISC-0974 Phase 1 SAD Data (cont.) Top dose (56 mg) pharmacodynamic activity improved key clinical parameters (> 1g/dL Hgb) 56 mg SC Placebo Hgb = hemoglobin; SAD = single ascending dose
Slide 38: DISC-0974 Phase 1 SAD Safety
DISC-0974 Phase 1 SAD Safety Safety profile was consistent with selective target biology and preclinical studies; no serious or AEs > Grade 1 Total n=42 Pooled Placebo n=10 7 mg IV n=8 14 mg SC n=6 28 mg SC n=6 28 mg IV n=6 56 mg SC n=6 Diarrhea 1 (2.4) 1 (10.0) 0 0 0 0 0 Dizziness 2 (4.8) 0 0 0 0 1
Slide 39: DISC-0974 Development Strategy
DISC-0974 Development Strategy Aim to demonstrate POC in anemia of MF and CKD Establish POM in Healthy Volunteers Ph 1b / 2a in MF Patients with Transfusion-Dependent Anemia – Ongoing Ph 1b / 2a in CKD Patients with Anemia (Non-Dialysis Dependent) – Ongoing Expansion in Other Forms of Anemia of Infl
Slide 40: DISC-0974: Anemia of Inflammation
DISC-0974: Anemia of Inflammation Initiate development in parallel in anemias of MF and NDD-CKD Anemia of Myelofibrosis (MF) Anemia of CKD (NDD and DD) Est. # Patients 16,000 to 18,500 patients (US alone) 5 to 6 million patients (US alone) Etiology of Anemia High hepcidin from inflammation JAKi’s wo
Slide 41: Hepcidin is a Key Driver of MF Anemia
Hepcidin is a Key Driver of MF Anemia Clinical POC* that inhibiting hepcidin axis can impact Hb Levels Source: Pardanani et al (2013) Am. J. Hematol; Oh et al., (2020) Blood Adv: TI-R: Transfusion-Independent for > 12 weeks by week 24; TI-NR: Transfusion Independent Non-Response; *from third party H
Slide 42: DISC-0974 Lowered Hepcidin in Inflammation Model
DISC-0974 Lowered Hepcidin in Inflammation Model NHP: IL6-induced hepcidin and hypoferremia Similar effects in animal models of infection-induced hypoferremia, IRIDA and anemia of inflammation D-0 D-1 D-10 D-1 D-10 D-1 D-10 IL-6 Vehicle IL-6+‘974 0.6mpk IL-6+’974 6mpk D-0 D-1 D-10 D-1 D-10 D-1 D-10
Slide 43: Phase 1b / 2 Trial in MF Anemia
Phase 1b / 2 Trial in MF Anemia Aim to evaluate efficacy and safety and position program for pivotal trial; Ph 1b data expected by year-end 2023 N ~ 26 Severity: DIPSS INT-2/High Transfusion Dependent +/- JAK inhibitor permitted DISC-0974 in TD MF Patient Population Design Study Arms Open-label Flex
Slide 44: Hepcidin is a Key Driver of CKD Anemia
Hepcidin is a Key Driver of CKD Anemia Clinical POC* that inhibiting hepcidin axis can impact Hb levels Sources: Troutt et al. (2013), J Clin Lab Analy; Sheetz et al. (2019) Br J Clin Pharmacol. (2019); *from third party Clinical Proof-of-Principle* Hepcidin inhibition via single dose of mechanistic
Slide 45: DISC-0974 Improved Anemia in Model of CKD
DISC-0974 Improved Anemia in Model of CKD Rat Model of Adenine Diet-Induced CKD 1.7 g/dL vs. Vehicle DISC-0974 Reduced Hepcidin Expression DISC-0974 Increased Serum Iron DISC-0974 Increased Hemoglobin Levels Red:0.75% Adenine + DISC-0974 (20 mg/kg) Blue:0.75% Adenine + Vehicle Red:0.75% Adenine + DI
Slide 46: Phase 1b / 2a POC Trial in NDD-CKD Anemia
Phase 1b / 2a POC Trial in NDD-CKD Anemia Aim to evaluate efficacy and safety in non-dialysis dependent patients 28 mg 40 mg 60 mg Dose TBD x 3 (Once-monthly) Phase 1b Single-Ascending Dose Treatment Duration: 3 months (q28d) Stage II-V CKD; Adult Not receiving dialysis Hb (g/dL) < 10.5 (F), 11 (M)
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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 Promotes Iron Restriction Decreases GI Absorption Limits Iron Availability Increases Hepcidin Enables Endogenous Production of Hepcidin Erythrocytosis (PV) Ineffective Eryt
Slide 49: Targeting TMPRSS6 to Increase Hepcidin
Genetic validation in patients with IRIDA (Iron-Refractory Iron Deficiency Anemia) LOF TMPRSS6 mutation increases hepcidin and reduces iron availability Functionally specific to hepcidin / iron Tissue specific expression primarily in the liver Targeting TMPRSS6 to Increase Hepcidin Potent, specific
Slide 50: MWTX-003 Effects in Non-Human Primates
Potent PD effects observed across multiple preclinical studies consistent with TMPRSS6 inhibition Hepcidin: 3-4 fold induction Serum iron: ~ 60-70% suppression MWTX-003 demonstrated excellent safety profile in non-clinical GLP safety studies MWTX-003 Effects in Non-Human Primates Resulted in deep an
Slide 51: Effects in HbbTh3/+ Model of Beta-Thalassemia
Effects in HbbTh3/+ Model of Beta-Thalassemia Significant effects on hallmarks of disease including iron overload, ineffective erythropoiesis and splenomegaly were observed HbbTh3/+ mice were treated with the lead anti-TMPRSS6 antibody at 10 mg/kg IP for 4 weeks ↓ Serum and Liver Iron 60-65% Reducti
Slide 52: MWTX-003 Development Plans
MTWX-003 Development Plans Aim to establish phase 1 proof-of-mechanism and advance program into POC studies with focus on Polycythemia Vera Phase 1 SAD / MAD in HV Plan to Initiate 2H’23 Phase 2 Proof-of-Concept Trial in Polycythemia Vera Additional POC Studies in a Range of Indications Demonstrate
Slide 53: Disc is Building a Leading Company Dedicated to Treating Hematologic Diseases
Disc is Building a Leading Company Dedicated to Treating Hematologic Diseases Focused on fundamental and well-validated pathways that affect heme biosynthesis and iron homeostasis Initial data DISC-0974 Phase 1b/2 trials in anemias of NDD-CKD and MF; data from bitopertin Phase 2 trials in EPP / XLP
Slide 54: Thank You
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