Summary of Disc Medicine Management Call - December 07, 2025 Company Overview - **Company**: Disc Medicine (NasdaqGM:IRON) - **Focus**: Development of therapies for hematologic diseases, particularly myelofibrosis (MF) and related anemias Key Updates on Products and Trials Bitopertin - **Status**: NDA accepted for review by the FDA for accelerated approval for erythropoietic protoporphyria (EPP) with a potential launch by the end of January 2026 [3][6][8] - **Review Process**: Engaged in a rigorous review process with the FDA, characterized by increased communication and collaboration [6][41] - **Commercialization**: Accelerated efforts for launch readiness, including drug supply expected by the end of January 2026 [7][8] DISC-0974 - **Indication**: Treatment for anemia of myelofibrosis (MF) - **Trial Updates**: Phase II RALLI-MF study shows significant decreases in hepcidin, leading to improved hemoglobin levels and reduced transfusion burden [4][10][12] - **Response Rates**: - Non-transfusion-dependent (NTD) group: 63% overall response, 50% major response - Transfusion-dependent (TD) low group: 71% overall response, with consistent results across different JAK inhibitors [12][14] - **Safety Profile**: Well tolerated with no treatment-related serious adverse events reported [14] DISC-3405 - **Mechanism**: Increases endogenous hepcidin production to limit iron availability, targeting conditions like polycythemia vera and sickle cell disease [21][22] - **Trial Initiation**: Phase II trials for polycythemia vera and sickle cell disease initiated, with initial data expected in 2026 [26][27] Market Opportunity - **Anemia of MF**: Affects approximately 22,000 patients in the U.S., representing a significant unmet need [17][18] - **Potential for Blockbuster Status**: DISC-0974 is positioned to address this unmet need effectively, with high response rates and the ability to work alongside existing therapies [19][18] Future Plans - **Regulatory Engagement**: Plans for an end-of-phase II meeting with the FDA for DISC-0974 to align on registrational trial design [19] - **Expansion of Trials**: Plans to initiate a phase II study in anemia of inflammatory bowel disease (IBD) and explore other anemias of inflammation [19][55] Financial and Operational Updates - **Funding**: Completed two follow-on offerings, providing a runway into 2029 without relying on revenue from bitopertin [29] - **Sales Force Preparation**: Hiring 24 sales representatives in anticipation of bitopertin's launch [90] Additional Insights - **Patient Experience**: Anecdotal reports indicate patients feel significantly better on DISC-0974, with improvements in fatigue and overall well-being [70] - **Combination Therapy Potential**: Ongoing discussions about potential combination studies with other agents to enhance efficacy [49][50] Conclusion Disc Medicine is making significant strides in the development of therapies for hematologic conditions, with promising data from ongoing trials and a clear path toward commercialization of its lead products. The company is well-positioned to address significant unmet needs in the market, particularly in the treatment of anemia associated with myelofibrosis.

Summary of DISC Medicine Management Conference Call Company Overview - **Company**: DISC Medicine (NasdaqGM:IRON) - **Focus**: Development of therapies for anemia and related conditions, particularly in myelofibrosis (MF) and other hematological disorders Key Industry and Company Updates Bitopertin - **NDA Status**: The New Drug Application (NDA) for bitopertin has been accepted for review by the FDA, with a potential approval decision expected by the end of January 2026 [6][12][73] - **Commercialization Readiness**: The company is accelerating its commercialization efforts, with plans to hire 24 sales representatives across the U.S. [7][158] - **Regulatory Engagement**: The FDA is providing increased engagement and communication during the review process, which is part of the Commissioner's National Priority Voucher Program [11][73] DISC-0974 - **Rally MF Trial**: Initial data from the phase 2 Rally MF study shows significant decreases in hepcidin, leading to improved iron mobilization and clinically meaningful benefits in anemia measures such as hemoglobin levels and fatigue [8][22][27] - **Response Rates**: The overall response rate in the non-transfusion dependent (NTD) group is 63%, while the transfusion dependent low (TDLO) group shows a 50% major response rate [22][23] - **Market Opportunity**: Anemia of MF affects approximately 22,000 patients in the U.S., presenting a significant market opportunity for DISC-0974, which has shown high response rates and durability [35][37] DISC-3405 - **Mechanism of Action**: DISC-3405 aims to increase endogenous hepcidin production to limit iron availability, targeting conditions like polycythemia vera and sickle cell disease [43][45] - **Trial Updates**: The phase 2 trial for polycythemia vera has been expanded due to rapid enrollment, and initial data is expected in 2026 [9][48] Core Insights and Arguments - **Efficacy Across Background Therapies**: DISC-0974 shows consistent efficacy regardless of concomitant JAK inhibitors, indicating its potential as a versatile treatment option [26][70] - **Safety Profile**: The safety profile of DISC-0974 is consistent with background adverse events typical for the MF population, with no treatment-related serious adverse events reported [27] - **Future Development Plans**: The company plans to initiate a phase 2 study in anemia of inflammatory bowel disease (IBD) and is exploring the potential of a long-acting version of DISC-0974 [41][90] Additional Important Points - **Patient Experience**: Anecdotal reports suggest patients are experiencing significant improvements in quality of life and reduced fatigue while on DISC-0974 [118] - **Regulatory Landscape**: The acceptance of bitopertin's NDA under the accelerated approval pathway is a significant milestone, potentially paving the way for future therapies [73] - **Market Dynamics**: The company is positioning itself to address a serious unmet need in the anemia market, particularly for MF patients who currently have limited treatment options [40][41] This summary encapsulates the critical updates and insights from the DISC Medicine management conference call, highlighting the company's strategic direction and the potential impact of its therapies in the hematology space.

Core Insights - Disc Medicine, Inc. presented positive initial data from the RALLY-MF Phase 2 trial of DISC-0974 for treating anemia in myelofibrosis (MF) at the ASH Annual Meeting, showing significant reductions in hepcidin and increases in iron levels, leading to clinically meaningful improvements in anemia across various patient types [1][2]. Group 1: Trial Results - The ongoing Phase 2 trial enrolled 47 adult patients with MF and anemia, with 34 patients included in the responder analysis [2]. - DISC-0974 treatment resulted in over 75% reduction in hepcidin and significant increases in serum iron [6]. - 63% of non-transfusion dependent (nTD) patients achieved a hemoglobin increase of ≥1 g/dL for ≥12 weeks, while 50% had an increase of ≥1.5 g/dL for ≥12 weeks [6]. - 71% of low transfusion burden patients achieved transfusion independence over a 16-week period [6]. - 67% of high transfusion burden patients achieved a ≥50% reduction in transfusion requirement [6]. - 50% of patients receiving concomitant JAK inhibitor therapy achieved a major hematologic response [6]. Group 2: Treatment Administration and Tolerability - DISC-0974 was administered subcutaneously at a dose of 50 mg every 4 weeks for up to 6 treatments [2]. - The treatment was generally well-tolerated, with diarrhea and urinary tract infections being the only related adverse events reported in two or more subjects [6]. Group 3: Future Plans and Developments - The company plans to advance the DISC-0974 program to address the unmet need for anemia treatment in MF, as there are currently no approved therapies for this condition [2]. - Additional data from the trial is expected to be shared in the second half of 2026 [6].

Company Overview - The company, Disc, focuses on controlling red blood cell biology by managing the metabolism of iron and heme, which are essential for red blood cell formation [2] - The lead program, Bitopertin, is in-licensed from Roche and aims to control heme biosynthesis in red blood cells [2] Key Programs - Bitopertin is being studied for a rare disease called erythropoietic protoporphyria (EPP), with approximately 14,000 diagnosed patients in the U.S. [2] - The company has completed a Phase II program for Bitopertin and is currently in an accelerated approval process with the FDA [2] - The approval process was further expedited by receiving a Commissioner's National Priority Voucher [2]

Summary of Disc Medicine Conference Call Company Overview - **Company**: Disc Medicine (NasdaqGM:IRON) - **Focus**: Controlling red blood cell biology through iron and heme metabolism - **Lead Program**: Bitopertin, licensed from Roche, targeting erythropoietic protoporphyria (EPP) with approximately 14,000 diagnosed patients in the US [4][15] Key Programs and Developments 1. **Bitopertin for EPP** - **Status**: Submitted NDA at the end of September 2025, in accelerated approval process with FDA [5][11] - **Timeline**: Potential approval and launch expected late 2025 to early 2026, accelerated by a commissioner’s national priority voucher [5][12] - **Sales Force**: Team of 24 prepared to engage with physicians treating the 6,000 highly engaged patients identified [17] 2. **DISC-0974 for Myelofibrosis** - **Phase**: Ongoing phase 2 trial (RALI-MF) with data expected at ASH 2025 [5][26] - **Data**: Previous data showed unprecedented positive response rates in treating anemia in myelofibrosis patients [5][27] - **Market Size**: Approximately 22,000 anemic myelofibrosis patients in the US could benefit from this therapy [34] 3. **Polycythemia Vera Program** - **Status**: Phase 2 trial initiated, focusing on restricting iron to manage excess red blood cell production [44] Financial Position - **Balance Sheet**: Approximately $825 million available, sufficient to fund operations until 2029 without revenue [46] Competitive Landscape - **Current Competitors**: JAK inhibitors like Jakafi exacerbate anemia, creating a market opportunity for anemia-specific therapies [27][42] - **Emerging Competitors**: Incyte's early clinical programs targeting calreticulin mutations, but efficacy in managing anemia remains uncertain [41][43] Important Considerations - **Patient Engagement**: Identified patient population is engaged, with a significant number already receiving treatment, facilitating quicker access to therapy post-approval [15][18] - **Reimbursement Pathways**: Initial reimbursement pathways may be less established at launch, requiring strategies like free drug programs [13][20] - **Regulatory Strategy**: Plans for a pivotal trial with broad enrollment criteria to support rapid patient recruitment [39][40] Upcoming Milestones - **ASH Presentation**: Expected data from the RALI-MF trial to be presented, with insights into response rates across different patient categories [28][29] - **Pivotal Trial Design**: Anticipated discussions with FDA post-phase 2 trial completion to outline pivotal trial strategy [39][40] This summary encapsulates the key points discussed during the conference call, highlighting the strategic direction, clinical programs, financial health, and competitive landscape of Disc Medicine.

Company Overview - Disc Medicine focuses on developing treatments for serious and debilitating hematologic diseases, with a name that reflects the shape of red blood cells [2] - The company's portfolio is constructed by targeting pathways fundamental to red blood cell biology, including programs that affect heme synthesis and regulate iron metabolism through the hormone Hepcidin [2] Lead Program - The lead program of the company is called Bitopertin, which is an oral treatment [3] Growth and Development - The company is currently experiencing significant growth, with ongoing developments in its portfolio that have been followed by Stifel for some time [1]

Summary of Disc Medicine Conference Call Company Overview - **Company**: Disc Medicine (NasdaqGM:IRON) - **Focus**: Developing treatments for serious hematologic diseases, particularly targeting pathways fundamental to red blood cell biology [2][3] Key Programs and Developments - **Lead Program**: Bidapertin - **Type**: Oral small molecule inhibitor targeting GLIT1 - **Indication**: Erythropoietic protoporphyria (EPP) - **NDA Submission**: Submitted at the end of September 2025 - **FDA Priority Voucher**: Received, which accelerates review time from 10-12 months to 1-2 months [3][7][10] - **Potential Approval Timeline**: Expected by December 2025 or January 2026 [9] - **Iron Portfolio**: - **Disco 974**: Antibody against hemojuvelin, in Phase 2, targeting anemia of myelofibrosis [4] - **Disc 3405**: Antibody targeting Tempor S6, also in Phase 2, aimed at inducing hepcidin production and restricting iron [5] Commercialization and Launch Readiness - **Commercial Infrastructure**: Currently building out capabilities, with a focus on market access [16][17] - **Salesforce**: Hiring ongoing, with a staged approach to launch [18] - **Patient Identification**: Utilizing existing ICD-10 codes and claims data to target accounts effectively [21] Market Dynamics and Competitive Landscape - **EPP Market**: Recognized unmet medical need, with a specific diagnostic code aiding in patient identification [19][21] - **Competitive Products**: Cinesse and Mitsubishi Tanabe products are in the market; Disc Medicine's approach targets the underlying disease mechanism [30][31] Financial Position - **Balance Sheet**: Approximately $820 million available, projected to support operations through 2029, including commercialization of Bidapertin and completion of ongoing studies [63][64] Future Directions - **Exploratory Studies**: Plans to explore Bidapertin in other indications, including Diamond Blackfan anemia and inflammatory bowel disease (IBD) anemia [34][53] - **Phase 3 Apollo Trial**: Ongoing recruitment, with no expected negative impact from Bidapertin's commercial availability [27][29] Conclusion - Disc Medicine is positioned for significant growth with its innovative therapies targeting hematologic diseases, backed by a strong financial position and strategic plans for commercialization and market entry. The company is focused on leveraging its unique drug profiles to address unmet medical needs in rare diseases.

Summary of Disc Medicine Conference Call Company Overview - **Company**: Disc Medicine - **Ticker Symbol**: IRON - **Public Trading Since**: End of 2022 - **Focus**: Development of therapies for blood disorders, particularly related to iron and heme metabolism [4][3] Key Programs and Developments Bitopertin - **Indication**: Erythropoietic protoporphyria (EPP) - **Regulatory Status**: Received a Commissioner's National Priority Voucher (CNPV), projecting potential approval by end of 2023 or early 2024 [2][5] - **Clinical Trials**: Completed a Phase 2 program with 100 participants; FDA aligned on an accelerated approval pathway using the toxic metabolite PPIX as a surrogate endpoint [5][6] - **Sales Force**: Planning to hire 24 sales representatives targeting 6,000 engaged patients identified through claims data [9][11] - **Market Size**: Estimated 14,000 diagnosed patients in the US, with a potential market size of $800 million to $1.4 billion [50] Competitive Landscape - **Existing Treatment**: Scenesse, which requires surgical implantation every two months, limiting its accessibility to about 3% of patients [12][14] - **Pricing Comparison**: Scenesse costs approximately $300,000 annually, while another treatment, Givlaari, is priced at $575,000 [18] Apollo Study - **Confirmatory Trial**: Enrolling 150 patients across the US, Europe, Canada, and Australia, expected to complete enrollment in about one year [21] - **Endpoints**: Co-primary endpoints include PPIX reduction and a measure of time in light at the end of the six-month trial [21] Other Assets 0974 - **Mechanism**: Monoclonal antibody targeting hemojuvelin to release iron for red blood cell production, primarily for myelofibrosis [22][23] - **Phase 1b Results**: Showed response rates of 50% in non-transfused patients, 80% in low transfusion burden patients, and 40% in high transfusion burden patients [26] - **Next Steps**: Interim results expected at ASH; aiming for a pivotal trial post-data analysis [37] Polycythemia Vera Program - **Goal**: Achieve iron restriction with a patient-friendly administration schedule [43] - **Phase 2 Study**: Aiming for a target hematocrit of 45% without phlebotomy, with a benchmark set against Rusfertide's 75% achievement [44][46] Financial Overview - **Cash Position**: Approximately $826 million post-stock offering, providing a runway until early 2029 without revenue from bitopertin [49] - **Investment Outlook**: Strong financial backing supports ongoing clinical trials and potential market entry [49] Additional Considerations - **Patient Engagement**: Focus on engaging the 6,000 identified patients initially, with broader outreach planned for the remaining diagnosed population [11] - **Regulatory Strategy**: Discussions with the FDA regarding the use of existing drug batches for potential early launch [6][8] This summary encapsulates the critical aspects of Disc Medicine's current status, focusing on their lead program, competitive landscape, financial health, and future plans.

Financial Position - As of September 30, 2025, the company had cash, cash equivalents, and marketable securities totaling $615.9 million[107] - Cash, cash equivalents, and marketable securities as of September 30, 2025, totaled $615.9 million, up from $489.9 million as of December 31, 2024[150] - The accumulated deficit as of September 30, 2025, was $449.7 million, reflecting ongoing operational losses since inception[132] - The company has contractual lease commitments totaling $3.34 million, with payments due over the next five years[143] - Interest income primarily consists of earnings from cash equivalents and marketable securities, contributing to the company's financial operations[117] Revenue and Losses - The company has not generated any revenue since inception and does not expect to do so in the near future[108] - Net loss for Q3 2025 was $62.3 million, compared to a net loss of $26.6 million in Q3 2024, reflecting a 134% increase in losses year-over-year[119] - Total operating expenses for Q3 2025 reached $67.7 million, up 106% from $32.9 million in Q3 2024, leading to a loss from operations of $67.7 million compared to a loss of $32.9 million in the same period last year[119] - The company expects to continue incurring significant operating losses and may require additional capital to fund operations, potentially through equity or debt financing[128][129] Expenses - Research and development expenses for Q3 2025 were $50.3 million, a 103% increase from $24.7 million in Q3 2024, primarily due to increased costs in clinical trials and personnel-related expenses[120][122] - Selling, general and administrative expenses for Q3 2025 were $17.4 million, a 113% increase from $8.2 million in Q3 2024, driven by higher personnel-related costs and professional fees[123][124] - Selling, general and administrative expenses are expected to increase significantly as the company expands its workforce and infrastructure for potential commercialization[116] - The company anticipates substantial increases in research and development expenses as clinical programs advance[112] Clinical Development - Bitopertin, the lead product candidate, has shown significant reduction in protoporphyrin IX (PPIX) levels and improvements in quality of life in clinical trials[103] - The FDA agreed that PPIX reduction could serve as a surrogate endpoint for accelerated approval of bitopertin in EPP and XLP[103] - DISC-0974 demonstrated substantial decreases in hepcidin and increases in iron levels in a Phase 1b study for anemia of myelofibrosis[105] - The company plans to initiate a Phase 2 clinical trial of DISC-0974 in patients with inflammatory bowel disease and anemia in Q1 2026[105] - The company expects substantial increases in expenses as it advances product candidates through clinical development, necessitating additional funding[140] Financing Activities - In October 2025, the company completed a public offering for net proceeds of approximately $210.9 million, which will fund operations into 2029[107] - In October 2025, the company completed a public offering that generated net proceeds of approximately $210.9 million, enhancing its capital resources[131] - Net cash provided by financing activities increased to $256.7 million in the nine months ended September 30, 2025, from $189.5 million in the same period of 2024[138][139] - Future funding may come from equity offerings, debt financings, collaborations, and licensing arrangements, but there is a risk of dilution for existing stockholders[141] Cash Flow - Net cash used in operating activities for the nine months ended September 30, 2025, was $137.1 million, significantly higher than $66.4 million for the same period in 2024, indicating increased operational expenditures[133][135] - Net cash used in investing activities for the nine months ended September 30, 2025, was $491.3 million, compared to $313.9 million for the same period in 2024[137][138] Market and Economic Factors - If market interest rates increase by one percentage point, the net fair value of marketable securities would decrease by approximately $2.6 million[150] - Inflation has not had a material effect on the company's financial condition or results of operations during the nine months ended September 30, 2025[152] - The company has minimal exposure to foreign currency risk due to the short duration of transactions[151] - There are no material changes to critical accounting estimates from the previous year, indicating stability in financial reporting[147]

Drug Development and Regulatory Approvals - Bitopertin has been selected for the FDA's Commissioner's National Priority Voucher (CNPV) Pilot Program, which offers accelerated reviews for drug applications, with an anticipated review period of 1-2 months[7]. - The NDA for Bitopertin was submitted on September 29, 2025, with FDA acceptance expected on or before November 28, 2025[7]. - The company is advancing commercial readiness activities to support the potential launch of Bitopertin on an accelerated timeline, if approved[7]. - The ongoing APOLLO confirmatory trial aims to support potential US approval and launch of Bitopertin in late 2025 or early 2026[57]. - Positive data across two Phase 2 studies support the durability of efficacy, with potential approval anticipated late 2025 to early 2026[175]. - NDA submitted on September 29, 2025, with a designed review time of 1-2 months[175]. - Initial data from the RALLY-MF Phase 2 study in MF anemia is expected soon, alongside the initiation of a Phase 2 study in IBD anemia anticipated in Q1 2026[175]. Clinical Trials and Study Results - The APOLLO study for EPP is currently underway, with a confirmatory trial required for full approval in the US[44]. - The anticipated initiation of the Phase 2 study for Anemia of Inflammatory Bowel Disease (IBD) is expected in Q1 2026[20]. - The Phase 2 trial for Bitopertin in Diamond Blackfan Anemia is currently underway, sponsored by NIH[61]. - The study enrolled a total of 35 participants, with 32 (91%) completing the study[95]. - 54% of participants receiving concomitant JAK inhibitor therapy achieved a major hematologic response[105]. - A significant 66% of patients experienced an increase in hemoglobin of at least 1.5 g/dL during the treatment period[101]. - The overall response rate for any hemoglobin increase of ≥1.5 g/dL was 68%[101]. - The study demonstrated a 43% reduction in erythropoietin levels and a 29% reduction in ferritin levels from baseline among major responders[108]. - Safety profile indicated that 94.1% of participants experienced any treatment-emergent adverse events (TEAEs), with most being Grade 1 or 2[112]. - The ongoing RALLY-MF Phase 2 study is assessing options for the NDD-CKD anemia program[175]. - A Phase 1b study for Sickle Cell Disease is expected to be initiated by the end of the year[172]. - The study design includes dose escalation and safety follow-up for Sickle Cell Disease participants[173]. Patient Populations and Disease Impact - The Erythropoietic Protoporphyria (EPP) patient population is estimated at approximately 20,000 in the US, with around 6,000 diagnosed patients actively seeking treatment[32]. - Real-world data indicates that 56% of EPP patients experience anxiety and/or depression, highlighting the significant impact of the disease on quality of life[35]. - Anemia remains a high unmet need within the myelofibrosis patient population, with approximately 22,000 addressable patients in the US[120]. - Approximately 5 to 6 million anemic non-dialysis dependent chronic kidney disease (NDD-CKD) patients in the US, with hepcidin levels ~20 times higher than healthy subjects[122]. - The estimated number of myelofibrosis patients in the US is 25,000, with around 87% experiencing anemia[94]. Pipeline and Future Studies - The pipeline includes multiple programs targeting hematologic diseases, with significant potential for addressing severe and moderate prevalence conditions[18]. - The company plans to initiate a Phase 2 study in IBD patients with anemia in Q1 2026[90]. - The company plans to initiate a Phase 2 study in patients with inflammatory bowel disease (IBD) and anemia in 2026[134]. - Phase 1 studies for DISC-3405 in healthy volunteers began in October 2023, assessing safety, pharmacokinetics, and hematologic parameters[154]. - The company is exploring other indications for DISC-3405, including hereditary hemochromatosis and beta-thalassemia[154]. Treatment Efficacy and Safety - Bitopertin 60 mg demonstrated a significant 40% reduction in PPIX levels compared to baseline after 6 months of treatment[48]. - Patients experienced a 75% reduction in the rate of phototoxic reactions versus placebo, with 86% reporting that their condition was 'much better'[48]. - The average cumulative total time in sunlight without pain increased significantly, with patients in the highest tertile experiencing 262.1 hours[52]. - Nearly all participants in the HELIOS study reported substantial improvements in quality of life measures through week 24[56]. - DISC-0974, an anti-HJV mAb, is designed to enhance iron availability and address a wide range of hematologic disorders[75]. - Hepcidin levels in myelofibrosis patients are approximately 12 times higher than controls, correlating with anemia severity[93]. - DISC-0974 demonstrated a 1.7 g/dL increase in hemoglobin levels compared to the vehicle control in a rat model of CKD[127]. - DISC-0974 resulted in a substantial, durable, dose-dependent reduction in hepcidin and sustained increase in transferrin saturation (TSAT) from baseline[129]. - DISC-3405 achieved ~70% suppression of serum iron levels lasting for 3 weeks in non-human primates[145]. - DISC-3405 produced dose-related increases in serum hepcidin, with corresponding reductions in serum iron ranging from 50-80% from baseline[161]. - The study showed consistent decreases in hepcidin and increases in serum iron across patients[99]. - DISC-3405 demonstrated meaningful reductions in hematologic parameters, including reticulocyte hemoglobin and hematocrit, in healthy volunteers[162]. - DISC-3405 resulted in an average 94% reduction in iron absorption at Day 2 and 68% at Day 15, confirming its mechanism to block dietary iron absorption[171].