Disc Medicine, Inc. · NASDAQ:IRON
Disc Medicine — Gemini Therapeutics — 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 Exhibit 99.2
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: Disc Medicine opportunity
Disc Medicine opportunity: Provides Gemini shareholders with opportunity to participate in the Disc Medicine growth story, at a pivotal time for Disc Medicine Diversified and clinical-stage portfolio: Two programs currently in clinical trials (DISC-0974 and bitopertin); provides multiple shots on go
Slide 4: Merger of Gemini and Disc Overview
Merger of Gemini and Disc Overview Merger with Disc Medicine, a privately-held company focused on hematology Strong balance sheet of approximately $175 MM expected to provide funding for operations into 2025 Upon close, company expected to be renamed “Disc Medicine” trading as NASDAQ: IRON Transacti
Slide 5: 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 Clinical-Stage Portfolio with Broad Potential Multiple Near-Term Catalysts Focus on Hematologic Disorders Potential to address immense need spanning a wide spectrum of disorders Predictive,
Slide 6: 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 7: Our Investors & Advisors
Our Investors & Advisors Investors Board of Directors Donald Nicholson, PhD Former CEO, Nimbus Therapeutics Chairman of the Board Mona Ashiya, PhD Partner OrbiMed Jay Backstrom, MD, MPH Former EVP and CMO Acceleron Pharma Kevin Bitterman, PhD Partner Atlas Venture Mark Chin, MS, MBA Managing Directo
Slide 8: Targeting Fundamental Pathways that Impact the Biology of Red Blood Cells
Targeting Fundamental Pathways that Impact the Biology of Red Blood Cells Erythropoietic Porphyrias CKD Anemia Sickle Cell Disease Myelodysplastic Syndromes Iron and heme formation play a central role in erythropoiesis Polycythemia Vera Critical points of intervention across multiple hematologic dis
Slide 9: Our Hematology-Focused Pipeline
Our Hematology-Focused Pipeline Multiple programs in development, each 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 Mat-2 Inhibitor Oral small mole
Slide 10: Strong Growth Trajectory Towards Building a Leading Hematology Company
Strong Growth Trajectory Towards Building a Leading Hematology Company Establish Company Build Portfolio of Clinical Programs Demonstrate Phase 2 POC in Multiple Programs 2021 DISC-0974 enters the clinic, licensed bitopertin, Series B financing 2023 and Beyond Positioned to enter potentially pivotal
Slide 11: Bitopertin: GlyT1 Inhibitor Heme Biosynthesis Modulation
Bitopertin GlyT1 Inhibitor Heme Biosynthesis Modulation
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 Glycine Critical and initiating precursor for heme biosynthesis and is supplied by GlyT1 transporter Hemoglobin Protop
Slide 13: Dysregulated Hemoglobin Synthesis Drives Disease
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 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 biosynthesis – deficient enzyme ferrochelatase Lifelong and presents in early childhood Caused by accumulation of
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 Madelyn 11-Year Old Patient Kristin Mother of boy with EPP “I can only tolerate about 10 minutes of direct sunlight before I get a reactio
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 Porphyrin ring absorbs light and emits energy and heat Oxidative damage to endothelial capillaries and surrounding tissue, perivasc
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 High PPIX Levels Bitopertin Treatment Designed to Reduce PPIX Levels Potential first disease-modifying treatment for EPP and XLP M
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 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 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 pharmacology Long-term GLP toxicology Juvenile GLP toxicology studies supporting patients ≥2 y/o Carcinogenicity studies Full reproduct
Slide 20: BEACON Trial: Open-Label Phase 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 Study measures: Changes in blood PPIX levels, light tolerance, time to prodromal symptom (TTPS), hepatobiliary markers, QOL, safety / PK Data
Slide 21: AURORA Trial: Phase 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 Study measures: Changes in blood PPIX levels, time in daylight without pain, light tolerance, time to prodromal symptom (TTPS), hepatobiliary markers, QOL, sa
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 and X
Slide 23: Hepcidin Modulation Iron Homeostasis
Hepcidin Modulation Iron Homeostasis
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 GI Tract Iron Intake Spleen Iron Storage Hepcidin Gatekeeper Function: Blocks iron absorption and recycling RBC Production in Bone Marrow Induced by Inflammation
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 Anemias of Inflammatory Disease Myelofibrosis Chronic Kidney Disease Autoimmune / Inflammatory Disorders Iron Overload and Excess Red Blood Cell Disorders Polycythemia Vera Hereditary Hemo
Slide 26: DISC-0974 Anti-HJV mAb Hepcidin Suppression
DISC-0974 Anti-HJV mAb Hepcidin Suppression
Slide 27: DISC-0974: Novel Anti-HJV mAb to Suppress Hepcidin
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 DISC-0974: Novel Anti-HJV mAb to Suppress Hepcidin Designed to enhance iron availability to address a wide range of he
Slide 28: Anemia of Inflammation or Chronic Disease
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 inflammatory component Hepcidin is up-regulated and correlates with anemia, driven by inflammation Anemia Types Est. % Anemic Myelofibrosi
Slide 29: 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 30: DISC-0974 Mechanism of Action
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 DISC-0974 Mechanism of Action Designed to reduce hepcidin and increase serum iron levels
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) 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
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 Increased TSAT ↓ DISC-0974 Reduced Hepcidin Production
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 Placebo 56 mg SC Placebo
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 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
Slide 35: DISC-0974 Development Strategy
DISC-0974 Development Strategy Demonstrate POC in anemia of MF and CKD Establish POM in Healthy Volunteers Ph 1b / 2a in MF Patients with Transfusion-Dependent Anemia - Initiated Ph 1b / 2a in CKD Patients with Anemia (Non-Dialysis Dependent) Expansion in Other Forms of Anemia of Inflammation Initia
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 Anemia High hepcidin from inflammation JAKi’s worsen
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 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 Hepcidin Levels are E
Slide 38: DISC-0974 Effects in Animal Models of Inflammation
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 IL-6 Vehicle IL-6+‘974 0.6mpk IL-6+’974 6mpk DISC-0974 Lowered Hepcidin in Inflammation Mode
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 N ~ 26 Severity: DIPSS INT-2/High Transfusion Dependent +/- JAK inhibitor permitted DISC-0974 in TD MF Patient Population Design Study Arms Open-label Flexibility to add addi
Slide 40: Hepcidin is a Key Driver of CKD Anemia
Sources: Troutt et al. (2013), J Clin Lab Analy; Sheetz et al. (2019) Br J Clin Pharmacol. (2019) Hepcidin is a Key Driver of CKD Anemia Clinical POC that inhibiting hepcidin axis can impact Hb Levels Clinical Proof-of-Principle Hepcidin inhibition via single dose of mechanistically similar BMP-6 mA
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 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% Adenin
Slide 42: Phase 1b / 2a POC Study in CKD Anemia
Dose Level A Dose Level B Dose Level C 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), 11.5 (M) Hepcidin > median of healthy controls Exclude iron-deficient anemia by ferritin and TSAT K
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 hepcid
Slide 44: Matriptase-2 Inhibitor Hepcidin Induction
Matriptase-2 Inhibitor Hepcidin Induction
Slide 45: Mat-2 Inhibitor to Induce Hepcidin Production
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 Mat-2 Inhibitor to Induce Hepcidin Production Designed to modulate RBC develop
Slide 46: Targeting Matriptase-2 to Increase Hepcidin
Genetic validation in patients with IRIDA (Iron-Refractory Iron Deficiency Anemia) LOF mutation increases hepcidin levels Reduces iron availability Functionally specific to hepcidin / iron Tissue specific expression primarily in the liver Targeting Matriptase-2 to Increase Hepcidin Potent and specif
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 Time (hrs.)
Slide 48: Mat-2 Inhibitor Planned Development Strategy
Mat-2 Inhibitor Planned Development Strategy Erythrocytosis and Disorders of Iron Overload / Ineffective Erythropoiesis Polycythemia Vera Hereditary Hemochromatosis Myelodysplastic Syndromes Proof of therapeutic hypothesis in patients Clarity on development path Convenient, oral presentation Strong
Slide 49: 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 Interim data DISC-0974 Phase 1b/2 trials in anemias of CKD and MF; interim data bitopertin Phase 2 trial in EPP / XLP Bi
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: Private Placement and Transactions
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 conn
Slide 52: Merger Announcement
Merger Announcement August 10, 2022
Gemini Therapeutics — Merger or Acquisition (August 2022) on 6ix