Disc Medicine, Inc. · NASDAQ:IRON
Disc Medicine — Merger or Acquisition (August 2022)
52 slides from Disc Medicine's merger presentation, Aug 10, 2022
Slide 1: Merger Announcement
Merger Announcement August 10, 2022
Slide 2: Disclaimer and FLS
Disclaimer and FLS Forward-Looking Statements Certain statements in this communication may constitute “forward-looking statements” for purposes of the federal securities laws concerning Gemini, Disc, the proposed transaction and other matters. These forward-looking statements include express or impl
Slide 3: Merger with Disc to be Transformative
Merger with Disc to be Transformative Transition into a clinical-stage company with multiple programs focused on hematology • Disc Medicine opportunity: Provides Gemini shareholders with opportunity to participate in the Disc Medicine growth story, at a pivotal time for Disc Medicine • Diversified a
Slide 4: Merger of Gemini and Disc
Merger of Gemini and Disc • Merger with Disc Medicine, a privately-held company focused on hematology • Strong balance sheet of approximately $175 MM expected to provide funding for operations Overview into 2025 • Upon close, company expected to be renamed “Disc Medicine” trading as NASDAQ: IRON • E
Slide 5: Disc is Building a Leading Company Dedicated to Treating Hematologic Diseases
Disc is Building a Leading Company Dedicated to Treating Hematologic Diseases Focus on Fundamental Clinical-Stage Multiple Hematologic & Validated Portfolio with Near-Term Disorders Pathways Broad Potential Catalysts Potential to address Fundamental to red blood Initiated Bitopertin Ph 2 in Data exp
Slide 6: Our Executive Team
Our Executive Team Deep experience building companies and bringing therapies to patients John Quisel, JD, PhD | CEO & President Joanne Bryce, CPA | Chief Financial Officer Former EVP & Chief Business Officer at Acceleron Pharma; 14 years through Former CFO of Arkuda Therapeutics, Dyne Therapeutics,
Slide 7: Our Investors & Advisors
Our Investors & Advisors Investors Board of Directors Scientific Advisory Board Donald Nicholson, PhD Kevin Bitterman, PhD Eric Snyder, PhD Mark Fleming, MD, DPhil Stefano Rivella, PhD Former CEO, Nimbus Therapeutics Partner Partner Professor, Pathology Professor, Pediatric Medicine Chairman of the
Slide 8: Targeting Fundamental Pathways that Impact the Biology of Red Blood Cells
Targeting Fundamental Pathways that Impact the Biology of Red Blood Cells Iron and heme Critical points of formation play a intervention across central role in multiple hematologic erythropoiesis diseases Wide Spectrum of Hematologic Diseases Addressable by Disc Portfolio Severe Rare (000s) Moderate
Slide 9: Our Hematology-Focused Pipeline
Our Hematology-Focused Pipeline Multiple programs in development, each with pipeline-in-a-product potential Portfolio Program Preclinical Phase 1 Phase 2 Near-Term Milestones EPP / XLP Erythropoietic Porphyrias (EPP and XLP) – Initiated July ‘22 Heme • Phase 2 BEACON Trial in EPP / XLP Bitopertin† (
Slide 10: Strong Growth Trajectory Towards Building a Leading Hematology Company
Strong Growth Trajectory Towards Building a Leading Hematology Company Initiate Phase 3 Studies and Expand Portfolio Demonstrate Phase 2 POC in Multiple 2023 and Beyond Build Portfolio Programs Positioned to enter potentially pivotal trials; expand range of indications and of Clinical pipeline Estab
Slide 11: Bitopertin
Bitopertin GlyT1 Inhibitor Heme Biosynthesis Modulation 11
Slide 12: Bitopertin: Oral, Selective GlyT1 Inhibitor
Bitopertin: 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 HMBS Glycine FECH ferrochelatase Critical and initiating UROS Iron precursor for heme biosynth
Slide 13: Dysregulated Hemoglobin Synthesis Drives Disease
Dysregulated Hemoglobin Synthesis Drives Disease Inhibiting heme synthesis with bitopertin has potential to address a wide range of hematologic diseases + Succinyl + Iron + Globin CoA Mature red blood Glycine Porphyrins Heme Hemoglobin cells (RBCs) Porphyrin Toxicity Heme Toxicity Globin Toxicity Ex
Slide 14: 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 EPP and XLP Prevalence: biosynthesis – deficient enzyme ferrochelatase Approximately 7-8k+ addressable patients in
Slide 15: EPP Impacts Multiple Aspects of Patients’ Lives
EPP Impacts Multiple Aspects of Patients’ Lives Attacks are easily triggered and result in excruciating pain that has neuropathic qualities and can last for days “I can only tolerate about 10 minutes “It’s like a chemical burn. It’s like a burn of direct sunlight before I get a from the inside out a
Slide 16: 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 Hepatobiliary • Porphyrin ring absorbs light and emits • PPIX accumulation in bile canaliculae, energy and heat causing oxidative d
Slide 17: 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 Heme ↓ Glycine Heme ALAS2 X FECH ALAS2 X FECH ↑↑↑↑ (+
Slide 18: 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 In vitro – EPP Model (K562 Cell) In vivo - EPP Model (Mouse) In vivo - XLP Model (Mouse) FECHIVS3-48C/KO Mutation FECHm1pas Missense Mutation ALAS2Q548X Gain-of-Function Mutation 25 / 1x1066cell
Slide 19: 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 Commercial-scale production Healthy volunteer studies pharmacology Optimized oral formulation Drug-drug interaction studies
Slide 20: 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~20) Study Design Treatment Arms • Open-label, randomized 20 mg QD Bitopertin • EPP and XLP; 18 years + • Two dose levels, parallel • Not receiving afamelanotid
Slide 21: 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) Study Design Treatment Arms Placebo • Double-blind, placebo-controlled (1:1:1) • EPP; 18 years + • Stratified by light tolerance 20 mg QD Bitopertin • Not receiving afamel
Slide 22: Development Status and Upcoming Milestones
Development Status and Upcoming Milestones Phase 2 BEACON trial initiated, data expected by 1H’23 Operational activities to enable initiation of patient studies completed • Roche license signed May 2021 • GMP clinical supply completed June 2022 • BEACON trial - Open-label, parallel-dose trial in EPP
Slide 23: Hepcidin Modulation
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 Normal Hepcidin Low Hepcidin Regulated erythropoiesis Restricted Iron Iron Overload Anemias of Inflammatory Disease Iron Overload and Excess Red Blood Cell Disorders Regulate
Slide 26: DISC-0974
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: 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 Types Est. % Anemic • Anemia of inflammation (also called Anemia of Myelofibrosis (MF) 87% Chronic Disease or ACD) is the 2nd most common form of anemia Chron
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: DISC-0974 Mechanism of Action
DISC-0974 Mechanism of Action Designed to reduce hepcidin and increase serum iron levels DISC-0974 mAb binds to and prevents signaling Potent and rapid effects on hepcidin and iron with through hemojuvelin (HJV) co-receptor single 5 mg / kg dose (NHP) 150 10 6 10 5 DISC-0974 / hepcidin Serum conc (n
Slide 31: Phase 1 SAD Trial in Healthy Volunteers
Phase 1 SAD Trial in Healthy Volunteers Establish proof-of-mechanism based on hepcidin and iron parameters (dosing completed) Final Escalation Cohort - Dosing Complete Study Design Dose Level 56 mg SC 6 Treated / 2 Placebo • Single-ascending dose in ≥32 healthy volunteers Dose Level 28 mg SC • Key o
Slide 32: DISC-0974 Phase 1 SAD Preliminary Data
DISC-0974 Phase 1 SAD Preliminary Data Dosing of DISC-0974 resulted in reduction of hepcidin and iron mobilization ↓ DISC-0974 Reduced Hepcidin Production ↑ DISC-0974 Increased TSAT 32
Slide 33: DISC-0974 Phase 1 SAD Preliminary Data (cont.)
DISC-0974 Phase 1 SAD Preliminary Data (cont.) Top dose (56 mg) pharmacodynamic activity improves key clinical parameters (> 1g/dL Hgb) 56 mg SC o Placebo 56 mg SC o Placebo 33
Slide 34: DISC-0974 Phase 1 SAD Preliminary Safety
DISC-0974 Phase 1 SAD Preliminary Safety Safety profile is consistent with selective target biology and preclinical studies; no serious or AEs > Grade 1 Total Pooled Placebo 7 mg IV 14 mg SC 28 mg SC 28 mg IV 56 mg SC n=42 n=10 n=8 n=6 n=6 n=6 n=6 Diarrhea 1 (2.4) 1 (10.0) 0 0 0 0 0 Dizziness 2 (4.8
Slide 35: DISC-0974 Development Strategy
DISC-0974 Development Strategy Demonstrate POC in anemia of MF and CKD Ph 1b / 2a in MF Patients with Transfusion- Plan to assess safety, Dependent Anemia - Initiated PK, hepcidin, iron, hemoglobin and Initiate studies transfusion burden 2H 2022 (MF) and others Ph 1b / 2a in CKD Patients with Anemia
Slide 36: DISC-0974: Anemia of Inflammation
DISC-0974: Anemia of Inflammation Initiate development in parallel in anemias of MF and 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 High hepcidin from inflammation High hepcidin from i
Slide 37: 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 Hepcidin Levels are Elevated in MF Clinical Proof-of-Principle ~ 12x higher than control and associated with severity of Hepcidin suppression increased Hb and reduced anemia and transfusion burden t
Slide 38: DISC-0974 Lowered Hepcidin in Inflammation Model
DISC-0974 Lowered Hepcidin in Inflammation Model NHP: IL6-induced hepcidin and hypoferremia ↓ DISC-0974 Reduced Hepcidin Production ↑ DISC-0974 Increased Serum Iron Levels Serum Iron AUC0-24h (ugxh/dL) Hepcidin AUC0-24h (ng h/mL) 3000 10000 6000 2000 4000 1000 2000 0 0 D-0 D-1 D-10 D-1 D-10 D-1 D-10
Slide 39: Phase 1b / 2 Study in MF Anemia
Phase 1b / 2 Study in MF Anemia Evaluate efficacy and safety and position program for pivotal study; Ph 1b data expected 2023 Phase 1b Dose Phase 2 Study Focused on Transfusion-Dependent (TD) Patients Escalation in Pts Patient Design Design Study Arms Population • N =1-9 per cohort†, initial • N ~ 2
Slide 40: 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 Hepcidin Levels Elevated in CKD Patients Clinical Proof-of-Principle ~ 20x higher than healthy subjects and increases with Hepcidin inhibition via single dose of mechanistically disease severity si
Slide 41: 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 80 80 Serum Iron 14 HGB 2.0 2.0 14 ) 1.7 g/dL vs. Vehicle 13 13 (normalized to vehicle control) 60 60 1.5 1
Slide 42: Phase 1b / 2a POC Study in CKD Anemia
Phase 1b / 2a POC Study in CKD Anemia Evaluate efficacy and safety in non-dialysis dependent patients Study Phase 1b Phase 2a Population Single-Ascending Dose Open-Label, Multiple-Dose • Stage II-V CKD; Adult Dose Level C Dose TBD x 3 (Once-monthly) • Not receiving dialysis DISC-0974 (n=12); Placebo
Slide 43: Development Status and Upcoming Milestones
Development Status and Upcoming Milestones Ongoing phase 1b/2 study in MF and plans to initiate phase 1b/2 study in NDD-CKD by year-end 2022 Operational activities to enable initiation of patient studies completed • Ph 1 SAD study – completed; excellent safety profile and proof of mechanism for hepc
Slide 44: Matriptase-2 Inhibitor
Matriptase-2 Inhibitor Hepcidin Induction 44
Slide 45: Mat-2 Inhibitor to Induce Hepcidin Production
Mat-2 Inhibitor to Induce Hepcidin Production Designed to modulate RBC development by limiting iron availability to address a wide range of hematologic disorders Limits Modulates Increases Iron RBC Hepcidin Availability Production Enables Endogenous Promotes Iron Restriction Erythrocytosis (PV) Prod
Slide 46: Targeting Matriptase-2 to Increase Hepcidin
Targeting Matriptase-2 to Increase Hepcidin Potent and specific target normally limits endogenous hepcidin Inhibiting Matriptase-2 Promotes Hepcidin Expression through HJV • Genetic validation in patients with IRIDA (Iron- Mat-2 selectively Refractory Iron Deficiency Anemia) degrades HJV • LOF mutat
Slide 47: Mat-2 Inhibition Has Potent Effects on Hepcidin
Mat-2 Inhibition Has Potent Effects on Hepcidin Effects with a single dose in non-human primates ↑ Hepcidin ↓ Serum Iron ↓ % TSAT Hepcidin-25 AUC0-24h Serum iron AUC0-24h TSAT - 50mg/kg Serum iron AUC0-24h (ug h/mL) Hepcidin AUC0-24h (ng h/mL) 2500 5000 60 2000 4000 40 TSAT (%) 1500 3000 1000 20 200
Slide 48: Mat-2 Inhibitor Planned Development Strategy
Mat-2 Inhibitor Planned Development Strategy Erythrocytosis and Disorders of Iron Overload / Ineffective Erythropoiesis Myelodysplastic Polycythemia Vera Syndromes • Proof of therapeutic hypothesis • Majority of patients anemic and in patients require transfusion • Clarity on development path • Spec
Slide 49: Disc is Building a Leading Company Dedicated to Treating Hematologic Diseases
Disc is Building a Leading Company Dedicated to Treating Hematologic Diseases Clinical-stage biopharmaceutical company developing therapies for hematologic diseases • Focused on fundamental and well-validated pathways that affect heme biosynthesis and iron homeostasis Portfolio of 3 distinct “pipeli
Slide 50: Risk Factors
Risk Factors The list below of risk factors has been prepared solely for purposes of the proposed private placement transaction (the “Private Placement”) as part of the proposed merger transaction (the “Merger”) between Gemini Therapeutics, Inc. (“Gem”), Gemstone Merger Sub, Inc. (“Merger Sub”) and
Slide 51: Risk Factors
Risk Factors Risks Related to the Private Placement • Disc may be unable to raise sufficient capital in the Private Placement or otherwise obtain additional financing to fund the operations and growth of the combined company (the “Combined Company”) following the Merger. • The issuance of shares in
Slide 52: Merger Announcement
Merger Announcement August 10, 2022