Financial Data and Key Metrics Changes - The company is preparing to file its New Drug Application (NDA) for bitopertin in October, with a potential PDUFA date between June and October of the following year, marking a significant milestone for the company [4][5] - The company reported a strong reduction in protoporphyrin-9 (PP9) levels with a P-value of less than 0.001, indicating clinically meaningful results from its phase 2 studies [9][10] Business Line Data and Key Metrics Changes - The lead program, bitopertin, is focused on treating erythropoietic protoporphyria, with the company ramping up efforts for its launch [4][5] - The second program is expected to present data on anemia of myelofibrosis and anemia of chronic kidney disease at upcoming conferences [5][6] Market Data and Key Metrics Changes - The company identified approximately 14,000 diagnosed patients in the U.S. for its lead indication, with enrollment in trials not being a problem due to strong patient advocacy [19][24] - The company plans to target the European and Japanese markets, with the genetic prevalence in Japan estimated to be four times higher than in the U.S. [39] Company Strategy and Development Direction - The company is focused on raising disease awareness and ensuring that patients and physicians are informed about available therapies, which is crucial given the historical lack of treatment options [23][24] - The company aims to build a self-sustaining entity driven by revenues from bitopertin to support its broader heme portfolio and explore larger indications [62] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the regulatory pathway for bitopertin, highlighting positive interactions with the FDA regarding the accelerated approval process [11][12] - The company is well-funded with $650 million on the balance sheet, providing a runway into 2028 to support ongoing trials and commercial preparations [62] Other Important Information - The company has orphan protection for bitopertin, which provides seven years of exclusivity in the U.S., along with method-of-use patents extending until 2042 [37] - The safety profile of bitopertin shows that dizziness occurs in over 50% of patients initially but resolves over time, indicating a manageable side effect [35] Q&A Session Summary Question: Can you recap the interactions with the FDA regarding the accelerated approval path for bitopertin? - The company had a series of meetings with the FDA, which were responsive to the rationale for using PP9 as a surrogate endpoint, leading to the decision to submit an NDA this fall [11][12] Question: What are the key differences between the Apollo and Aurora trials? - Apollo will focus on measuring the time patients can spend in light as a co-primary endpoint, while Aurora primarily assessed the reduction in PP9 levels [18][20] Question: How does the company plan to address the patient population for bitopertin? - The company segments the patient population based on engagement with healthcare providers, identifying about 6,000 engaged patients who regularly seek care [27][28] Question: What is the expected market opportunity for the anemia treatment in myelofibrosis? - The company estimates a market of about 22,000 patients for anemia in myelofibrosis, with potential pricing similar to other anemia treatments in related indications [45] Question: How does the company view its capital position and runway? - The company is well-funded and expects its current capital to support its operations and trials through 2028, aiming to become self-sustaining through revenues from bitopertin [62]

Financial Data and Key Metrics Changes - The company is preparing to file its New Drug Application (NDA) for bitopertin in October, with a potential PDUFA date between June and October of the following year, marking a significant milestone for the company [4][5][11] - The company reported a strong reduction in protoporphyrin-9 (PP9) levels with a P-value of less than 0.001, indicating clinically meaningful results from its phase 2 studies [9][10] Business Line Data and Key Metrics Changes - The lead program, bitopertin, is focused on treating erythropoietic protoporphyria, with plans for an accelerated approval pathway [4][5] - The second program is expected to present data on anemia of myelofibrosis and anemia of chronic kidney disease at upcoming conferences [5][6] Market Data and Key Metrics Changes - The company identified approximately 14,000 diagnosed patients in the U.S. for its lead indication, with expectations for rapid enrollment in clinical trials [19] - The market for bitopertin is expected to be significant, with pricing comparisons to existing therapies like Scenesse, which is priced at $300,000 to $350,000 per year [36] Company Strategy and Development Direction - The company is focused on increasing disease awareness and ensuring that healthcare providers are informed about available therapies for rare diseases [23][24] - The company plans to leverage claims data to identify and engage with physicians who treat diagnosed patients, enhancing its commercial strategy [24][25] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the regulatory pathway for bitopertin, citing positive interactions with the FDA regarding the use of PP9 as a surrogate endpoint [11][12] - The company is well-funded with $650 million on its balance sheet, providing a runway into 2028 to support ongoing trials and commercial preparations [62] Other Important Information - The company has orphan drug designation for bitopertin, providing seven years of market exclusivity in the U.S. [37] - The company is also exploring additional indications for its iron modulation programs, indicating a broad pipeline strategy [62] Q&A Session Summary Question: Can you recap the interactions with the FDA regarding the accelerated approval path for bitopertin? - Management detailed a series of meetings with the FDA that confirmed the rationale for an accelerated approval pathway based on phase 2 data and the use of PP9 as a surrogate endpoint [11][12] Question: What are the key differences between the Apollo and Aurora trials? - The Apollo trial will focus on measuring the time patients can spend in light as a co-primary endpoint, alongside the reduction of PP9 levels [19][20] Question: How does the company plan to address the patient population for bitopertin? - The company plans to segment the patient population based on engagement with healthcare providers, identifying approximately 6,000 engaged patients and 8,000 less engaged patients [27][28] Question: What is the expected pricing strategy for bitopertin? - The company anticipates pricing in line with existing therapies for rare diseases, potentially around $300,000 to $350,000 per year [36] Question: How does the company view the competitive landscape for its anemia treatments? - Management highlighted the significant unmet need in treating anemia in myelofibrosis, positioning their drug as the only one currently in development for this indication [43][44]

Summary of Disc Medicine Conference Call Company Overview - **Company**: Disc Medicine - **Focus**: Development of treatments for diseases related to red blood cell metabolism, specifically through manipulation of iron and heme metabolism [5][6] Key Programs 1. **Bidipertin** - **NDA Filing**: Scheduled for October 2025 with expected acceptance in December 2025, leading to a PDUFA date in 2026 [5] - **Patient Data**: Approximately 6,000 engaged patients identified from a claims database, with a total of 14,000 diagnosed patients [8][9] - **Market Strategy**: MSLs (Medical Science Liaisons) are engaging with physicians to confirm patient existence and raise disease awareness [10][13] - **Patient Education**: Emphasis on educating patients about the new therapy post-approval, with a focus on transitioning from clinical trials to commercial therapy [19][20] 2. **DISCO-974** - **Indication**: Targeting anemia of myelofibrosis (MF) with data cuts expected to be presented at ASH [6] - **Competitive Landscape**: Comparison with luspatercept, which failed in Phase 3 trials, highlighting the potential for DISCO-974 to address anemia more effectively across various patient subgroups [46][48] 3. **Chronic Kidney Disease (CKD) Anemia** - **Phase 1b SADMAD Program**: Data expected to be presented at ASN or ASH, focusing on iron mobilization and hemoglobin response [61][62] - **Future Trials**: Plans for a Phase 2 trial to confirm efficacy based on initial data, with a focus on identifying responding populations [63][64] Regulatory and Market Considerations - **Regulatory Alignment**: Confidence in the design of the Apollo confirmatory trial based on successful Phase 2 data, with a focus on minimizing placebo effects [38][41] - **Market Entry Strategy**: Anticipation of a gradual launch process, with emphasis on payer approval and physician engagement [22][24] - **Patient Population**: Targeting a significant unmet need in rare diseases, with a focus on educating both patients and physicians about new treatment options [19][57] Competitive Landscape - **Comparative Analysis**: Insights drawn from other rare disease launches, particularly Solano in rare obesity, and the challenges faced by luspatercept in treating anemia [33][46] - **Market Size**: Potential to address a population of approximately 22,000 anemic patients in the U.S. [56] Additional Insights - **Patient Advocacy**: Strong support from patient advocacy groups, which aids in raising awareness and sharing patient success stories [37] - **Data Presentation**: Upcoming data presentations at ASH are expected to provide further clarity on the efficacy and competitive positioning of DISCO-974 and other programs [56][65] This summary encapsulates the key points discussed during the conference call, highlighting the strategic direction and anticipated developments for Disc Medicine.

Pipeline and Product Development - The company has a pipeline including bitopertin for treating erythropoietic porphyrias and Diamond-Blackfan Anemia, DISC-0974 for anemia of myelofibrosis and chronic kidney disease, and DISC-3405 for polycythemia vera [100][101][104]. - Bitopertin has shown significant reduction in the toxic metabolite protoporphyrin IX (PPIX) and improvements in quality of life in clinical trials, with plans to submit a New Drug Application (NDA) in October 2025 [101]. - DISC-0974 has completed Phase 1 trials and is currently in Phase 1b/2 trials for anemia of myelofibrosis and chronic kidney disease, with interim data expected in the second half of 2025 [102][103]. - The company is developing DISC-0998, a preclinical anti-hemojuvelin monoclonal antibody, targeting hepcidin suppression for inflammatory disease-related anemia [103]. - The company initiated the APOLLO trial for bitopertin in May 2025, which will serve as a post-marketing confirmatory clinical trial under the FDA's Accelerated Approval Program [101]. - The company has entered into a collaborative agreement with the National Institutes of Health to conduct a clinical trial of bitopertin in Diamond-Blackfan Anemia, which began in July 2023 [101]. Financial Performance and Position - The company has not generated any revenue since inception and does not expect to do so in the near future, relying on successful commercialization of product candidates for future revenue [106]. - The net loss for the three months ended June 30, 2025, was $55.2 million, compared to a net loss of $26.4 million in 2024, reflecting a 109.5% increase [116]. - The company incurred an accumulated deficit of $387.3 million as of June 30, 2025 [126]. - The company expects to continue incurring significant operating losses and may require additional capital to fund operations [124]. - Cash, cash equivalents, and marketable securities totaled $650.0 million as of June 30, 2025, up from $489.9 million as of December 31, 2024 [144]. - Net cash used in operating activities for the six months ended June 30, 2025, was $89.3 million, compared to $49.0 million in 2024, indicating an increase of 82.2% [130]. - Net cash provided by financing activities for the six months ended June 30, 2025, was $245.1 million, primarily from an underwritten offering, compared to $189.1 million in the same period of 2024 [133]. Expenses and Cost Management - Research and development expenses are expected to increase substantially as the company advances its clinical programs, with no accurate estimates available for future costs [110]. - Selling, general and administrative expenses are anticipated to rise significantly as the company expands its workforce to support research and potential commercialization activities [112]. - Research and development expenses increased to $46.3 million for the three months ended June 30, 2025, up from $23.5 million in the same period of 2024, representing a 97.1% increase [117]. - The increase in research and development expenses for the six months ended June 30, 2025, was $26.9 million, totaling $74.1 million compared to $47.2 million in 2024, a 57.0% increase [118]. - Selling, general and administrative expenses rose to $15.1 million for the three months ended June 30, 2025, compared to $7.4 million in 2024, marking a 104.8% increase [120]. - For the six months ended June 30, 2025, selling, general and administrative expenses were $27.3 million, up from $15.1 million in 2024, an increase of 80.0% [121]. Market and Economic Factors - Other income (expense), net was $6.2 million for the three months ended June 30, 2025, compared to $4.6 million in 2024, a 34.8% increase [122]. - If market interest rates increase by one percentage point, the net fair value of marketable securities would decrease by approximately $3.0 million [144]. - The company has minimal exposure to foreign currency exchange rate fluctuations due to short transaction durations [145]. - Inflation has not materially affected the company's business or financial condition during the six months ended June 30, 2025, and 2024 [146]. Obligations and Future Funding - The total contractual obligations as of June 30, 2025, amount to $3.54 million, with $794,000 due within one year [137]. - The company expects substantial increases in expenses as it advances product candidates through clinical development and continues public operations [134]. - The company may require substantial additional funds to achieve business objectives, as product candidates may take longer to become commercially available [135].

[Introduction](index=1&type=section&id=Introduction) This section provides an overview of Disc Medicine, its recent financial performance, and strategic pipeline advancements [Company Overview and CEO Statement](index=1&type=section&id=Company%20Overview%20and%20CEO%20Statement) Disc Medicine reported Q2 2025 results, advancing bitopertin NDA and other pipeline programs, with cash runway into 2028 - Disc Medicine is a clinical-stage biopharmaceutical company focused on discovering, developing, and commercializing novel treatments for patients suffering from serious hematologic diseases [2](index=2&type=chunk)[11](index=11&type=chunk) - On track to submit an NDA for bitopertin in EPP under the accelerated approval pathway in **October 2025**, following positive feedback from a pre-NDA meeting [3](index=3&type=chunk)[6](index=6&type=chunk) - Initiated a Phase 2 study of DISC-3405 in polycythemia vera and expects data from the Phase 2 trial of DISC-0974 in MF anemia and Phase 1b trial in NDD-CKD anemia in the **second half of the year** [3](index=3&type=chunk)[6](index=6&type=chunk) - Maintains a **strong balance sheet** that provides cash runway into **2028**, positioning the company for potential commercialization of bitopertin and pipeline advancement [3](index=3&type=chunk)[6](index=6&type=chunk) [Recent Highlights and Anticipated Milestones](index=1&type=section&id=Recent%20Highlights%20and%20Anticipated%20Milestones) This section details Disc Medicine's progress across its key clinical programs and corporate developments, outlining significant achievements and upcoming milestones [Bitopertin Program Update](index=1&type=section&id=Bitopertin%20Program%20Update) Bitopertin is on track for EPP NDA submission in October 2025, supported by positive pre-NDA feedback and favorable HELIOS data - Company on track to submit NDA for bitopertin in erythropoietic protoporphyria (EPP) under accelerated approval pathway in **October 2025**, supported by successful pre-NDA meeting [6](index=6&type=chunk)[7](index=7&type=chunk) - Presented data from HELIOS, an ongoing open-label extension study, showing **favorable long-term efficacy and safety** with sustained protoporphyrin IX (PPIX) reductions, improvement in quality of life, and improved liver biomarkers [6](index=6&type=chunk)[7](index=7&type=chunk) - Progressing confirmatory Phase 3 APOLLO clinical trial of bitopertin in adults and adolescents with EPP [7](index=7&type=chunk) - Publication of preclinical study results showing bitopertin may help **prevent liver disease in EPP**, in addition to ameliorating blood PPIX levels [7](index=7&type=chunk) [DISC-0974 Program Update](index=1&type=section&id=DISC-0974%20Program%20Update) DISC-0974 is progressing with initial data expected in Q4 2025 from Phase 2 MF anemia and Phase 1b NDD-CKD - Expect initial data from Phase 2 study of DISC-0974 in patients with anemia of myelofibrosis (MF) and multiple dose data from Phase 1b study in NDD-CKD in **Q4 2025** [6](index=6&type=chunk)[13](index=13&type=chunk) - Presented clinical data from the continuation phase of the Phase 1b trial of DISC-0974 in MF anemia demonstrating **durable hematologic response** at EHA 2025 [6](index=6&type=chunk)[13](index=13&type=chunk) - RALLY-MF Phase 2 study's exploratory cohort for patients on concomitant momelotinib or pacritinib is fully enrolled, and the trial protocol was updated to allow these patients into main study cohorts [13](index=13&type=chunk) [DISC-3405 Program Update](index=2&type=section&id=DISC-3405%20Program%20Update) DISC-3405 initiated a Phase 2 study in PV with initial data expected in 2026, backed by Phase 1 proof-of-mechanism data - Initiated a Phase 2 study of DISC-3405 in patients with PV with initial data expected in **2026** [6](index=6&type=chunk)[13](index=13&type=chunk) - Presented updated SAD/MAD data from the Phase 1 trial of DISC-3405 in healthy volunteers providing **proof of mechanism** to support advancement of the program at EHA 2025 [6](index=6&type=chunk)[13](index=13&type=chunk) [Corporate Developments](index=2&type=section&id=Corporate%20Developments) Nadim Ahmed joined Disc Medicine's Board in July 2025, bringing extensive hematology development and commercial leadership - Appointed Nadim Ahmed, President and CEO of Cullinan Therapeutics, to the Company's Board of Directors in **July**, bringing over **25 years of development and commercial leadership experience** including multiple product launches in the hematology space [9](index=9&type=chunk) [Second Quarter 2025 Financial Results](index=2&type=section&id=Second%20Quarter%202025%20Financial%20Results) This section presents Disc Medicine's financial performance for the second quarter of 2025, detailing key income statement and balance sheet figures [Financial Summary](index=2&type=section&id=Financial%20Summary) Disc Medicine reported a **$55.2 million net loss** in Q2 2025, driven by higher operating costs, maintaining **$650.0 million cash** into 2028 Financial Metric (Q2 2025) | Financial Metric (Q2 2025) | 2025 (in millions) | 2024 (in millions) | YoY Change | | :------------------------- | :----------------- | :----------------- | :--------- | | Research and Development | $46.3 | $23.5 | +97.0% | | Selling, General & Admin | $15.1 | $7.4 | +104.1% | | Net Loss | $(55.2) | $(26.4) | +109.1% | - Cash, cash equivalents, and marketable securities were **$650.0 million** as of June 30, 2025, which are expected to fund operational plans into **2028** [6](index=6&type=chunk)[13](index=13&type=chunk) - The increase in R&D expenses was primarily driven by the progression of Disc's portfolio, including bitopertin's clinical studies and drug manufacturing, the advancement of the DISC-0974 program, increased headcount, and a **$10 million milestone payment** upon initiation of the APOLLO study [13](index=13&type=chunk) - The increase in SG&A expenses was primarily due to increased headcount including establishing infrastructure to support potential commercialization [13](index=13&type=chunk) [Condensed Consolidated Statements of Operations](index=4&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) The company reported a **net loss of $55.2 million** for Q2 2025, up from **$26.4 million** in Q2 2024, due to higher R&D and SG&A Statements of Operations (in thousands) | Metric (in thousands) | Three months ended June 30, 2025 | Three months ended June 30, 2024 | Six months ended June 30, 2025 | Six months ended June 30, 2024 | | :-------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development | $46,319 | $23,485 | $74,082 | $47,189 | | Selling, general and administrative | $15,091 | $7,367 | $27,274 | $15,125 | | Total operating expenses | $61,410 | $30,852 | $101,356 | $62,314 | | Loss from operations | $(61,410) | $(30,852) | $(101,356) | $(62,314) | | Other income (expense), net | $6,215 | $4,560 | $12,195 | $9,078 | | Income tax expense | $(52) | $(60) | $(171) | $(65) | | Net loss | $(55,247) | $(26,352) | $(89,332) | $(53,301) | | Net loss per share, basic and diluted | $(1.58) | $(1.03) | $(2.61) | $(2.11) | | Weighted-average common shares outstanding, basic and diluted | 35,024,592 | 25,649,043 | 34,179,364 | 25,229,456 | [Condensed Consolidated Balance Sheets](index=4&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) Total assets increased to **$665.1 million** as of June 30, 2025, driven by **$650.0 million cash**, with equity rising to **$614.2 million** Balance Sheets (in thousands) | Metric (in thousands) | June 30, 2025 (Unaudited) | December 31, 2024 | | :-------------------- | :------------------------ | :---------------- | | Cash, cash equivalents, and marketable securities | $649,973 | $489,881 | | Total current assets | $661,592 | $493,615 | | Total assets | $665,061 | $496,773 | | Total liabilities | $50,896 | $53,186 | | Total stockholders' equity

Core Viewpoint - Disc Medicine, Inc. received positive feedback from the FDA regarding its planned New Drug Application (NDA) submission for bitopertin, aimed at treating Erythropoietic Protoporphyria (EPP) [1][2] Group 1: NDA Submission Details - The pre-NDA meeting confirmed alignment with the FDA on the timing and content of the NDA submission, which is scheduled for October 2025 [2] - The NDA will be submitted under the FDA's accelerated approval pathway based on existing data [2] Group 2: About Bitopertin - Bitopertin is an investigational, orally administered inhibitor of glycine transporter 1 (GlyT1), designed to modulate heme biosynthesis [3] - It has potential as a first disease-modifying therapy for various hematologic diseases, including EPP [3] - Bitopertin has undergone multiple clinical trials, including the Phase 2 BEACON trial and the Phase 2 AURORA trial [3] Group 3: About Erythropoietic Protoporphyria (EPP) - EPP is a rare and potentially life-threatening disease caused by mutations affecting heme biosynthesis, leading to the accumulation of protoporphyrin IX (PPIX) [5] - Symptoms include severe pain and complications such as gallstones and liver damage, with current treatment options being limited [5] - There is currently only one FDA-approved therapy for EPP, Scenesse® (afamelanotide) [5] Group 4: About Disc Medicine - Disc Medicine is focused on discovering and developing novel treatments for serious hematologic diseases, targeting heme biosynthesis and iron homeostasis [6] - The company aims to build a portfolio of innovative therapeutic candidates to address a wide spectrum of hematologic diseases [6]

Core Insights - Disc Medicine, Inc. has appointed Nadim Ahmed to its Board of Directors, which is seen as a pivotal moment for the company as it advances its drug bitopertin towards commercialization in EPP [1][2] - Mr. Ahmed brings over 25 years of leadership experience in drug development and commercialization, having held significant roles at Cullinan Therapeutics, Bristol Myers Squibb, and Celgene [2] - The company is focused on developing novel treatments for serious hematologic diseases and aims to address various conditions through innovative therapeutic candidates [3] Company Developments - The appointment of Mr. Ahmed is expected to enhance Disc Medicine's capabilities in drug launches and development, particularly in hematological diseases [2] - The company anticipates multiple meaningful catalysts in the coming months, including a potential NDA filing and launch for bitopertin in EPP [2] - Disc Medicine is committed to building a portfolio of first-in-class therapeutic candidates targeting red blood cell biology, specifically heme biosynthesis and iron homeostasis [3]

Bitopertin in EPP - NDA preparation is on track with planned submission in H2 2025 under accelerated approval path[11] - HELIOS extension study data showed sustained PPIX reductions and improvements in QoL with favorable long-term efficacy and safety[8, 21, 25] - HELIOS data suggests potential for bitopertin to improve liver function, with continued treatment of 60 mg reducing ALT[8, 24] - The prevalence of EPP patients in the US is estimated to be around 20,000, with ~6,000 diagnosed and ~14,000 misdiagnosed or not seeking treatment[31] DISC-0974 - Phase 1b results in MF anemia showed durable anemia response through the continuation phase among major responders[8, 57] - Phase 1b data showed sustained activity on key biomarkers, supporting target engagement and iron mobilization[8, 53] - In MF Phase 1b study, major responders treated with DISC-0974 experienced a 43% and 29% reduction from baseline at Day 113 in erythropoietin and ferritin, respectively[53] - RALLY-MF Phase 2 enrollment is ongoing, with the momelotinib exploratory cohort fully enrolled[8, 62] DISC-3405 - Phase 1 data from healthy volunteers showed deep, sustained reductions in serum iron and meaningful changes in hematologic parameters[9, 78, 80] - Iron pulse study in healthy volunteers showed a 94% reduction in iron absorption at Day 2 and 68% at Day 15, confirming MOA and potential in diseases of iron overload[9, 86] - A Phase 2 study in polycythemia vera has been initiated[9, 87]

Summary of DISC Medicine Corporate Call Company Overview - **Company**: DISC Medicine - **Focus**: Development of therapies for rare hematologic diseases, particularly Erythropoietic Protoporphyria (EPP) and Myelofibrosis (MF) anemia Key Points Industry and Product Pipeline - **Bidapertin**: - NDA submission planned for the second half of the year for EPP [11] - Positive data from HELIOS study showing long-term efficacy and safety, with significant PP9 reduction and quality of life improvement [7][20] - Evidence of liver function improvement indicated by sustained ALT level reduction [7][20] - **DISCO-974**: - Monoclonal antibody targeting anemia of inflammation, with ongoing Phase II RALEY MF trial [28][50] - Durable efficacy observed in Phase 1b study, with sustained activity on key biomarkers [29][50] - Initial data from the RALEY MF trial expected later this year [50] - **DISC-3405**: - Monoclonal antibody for polycythemia vera, Phase II trial initiated [44][48] - Demonstrated ability to suppress iron absorption, with significant reductions in dietary iron uptake [47][48] Clinical Data and Efficacy - **Bidapertin**: - 86 patients in HELIOS study showed approximately 40% reduction in PP9 levels [17][19] - Patients on the 60 mg dose exhibited the greatest benefits [8][19] - Positive patient-reported outcomes with nearly universal positive responses regarding disease severity and quality of life [20][21] - **DISCO-974**: - Strong responses across various anemia patient categories, with major responders maintaining hemoglobin increases [31][32] - Evidence of synergistic effects when combined with other anemia-targeted agents [33][34] - **DISC-3405**: - Phase I study showed significant reductions in iron levels and hematologic responses in healthy volunteers [46][48] Commercialization and Market Opportunity - **EPP Market**: - Approximately 6,000 engaged EPP patients in the U.S. with a total of 14,000 diagnosed patients [24][25] - Focused commercial model targeting key treatment centers and healthcare professionals [25][26] - Disease state education campaign launched to raise awareness among patients and physicians [27] - **MF Anemia Market**: - Estimated 22,000 addressable patients in the U.S. with a significant unmet need for anemia treatment [39][40] - DISCO-974 aims to address anemia across all levels of transfusion dependence [41] Regulatory and Future Outlook - **Regulatory Progress**: - Pre-NDA meeting with the FDA scheduled to align on NDA package [12][49] - Enrollment for the APOLLO trial expected to be completed by Q2 next year [83] - **Future Milestones**: - Initial data from the RALEY MF trial and multiple dose portion of the Phase 1b study in chronic kidney disease expected later this year [50] - Initial results from the Phase II study in polycythemia vera anticipated in 2026 [48] Additional Insights - **Physician Engagement**: - Physicians are optimistic about the potential liver health benefits of bidapertin, which may influence prescription decisions [63] - Market research indicates that many EPP patients have been disengaged from healthcare due to a lack of treatment options, but awareness campaigns may drive re-engagement [84] - **Combination Therapies**: - Potential for combination therapies with existing anemia treatments like luspatercept, which may enhance patient outcomes [75][78] This summary encapsulates the key points discussed during the DISC Medicine corporate call, highlighting the company's pipeline, clinical data, market opportunities, and future regulatory steps.

Core Insights - Disc Medicine, Inc. is advancing its clinical programs for bitopertin, DISC-0974, and DISC-3405, with positive data presented at the EHA 2025 annual meeting, indicating favorable long-term efficacy and safety profiles for these investigational therapies [1][5][6] Bitopertin - The HELIOS study demonstrated sustained reductions in protoporphyrin IX (PPIX) and improvements in quality of life for patients with erythropoietic protoporphyria (EPP) [1][6] - Continuous treatment with 60 mg of bitopertin resulted in significant reductions in ALT and other hepatobiliary biomarkers, with nearly all participants reporting substantial quality of life improvements [6][4] - The company plans to submit a New Drug Application (NDA) for bitopertin in the second half of 2025 and has initiated a confirmatory clinical trial, APOLLO, for EPP [1][3] DISC-0974 - Data from the Phase 1b trial in myelofibrosis (MF) anemia showed sustained activity on key biomarkers and durable anemia responses among major responders [2][7] - The trial included various patient cohorts, with long-term results indicating that 50% of non-transfusion dependent patients achieved a major response with a sustained mean hemoglobin increase of ≥1.5 g/dL [10][17] - Enrollment for the Phase 2 RALLY-MF trial is ongoing, with initial data expected in the second half of 2025 [2][5] DISC-3405 - The Phase 1 trial in healthy volunteers demonstrated deep, sustained reductions in serum iron and significant changes in hematologic parameters, supporting its mechanism of action [2][9] - An iron pulse study showed that DISC-3405 inhibited dietary iron uptake, resulting in an average 94% reduction in iron absorption at Day 2 and 68% at Day 15 [12][13] - A Phase 2 trial of DISC-3405 in polycythemia vera (PV) has been initiated, with initial results anticipated in 2026 [11][17] Overall Company Strategy - The data presented at EHA supports the advancement of all three clinical candidates and highlights potential expansion opportunities into new indications [3][5] - Management will host a corporate update call on June 16, 2025, to discuss these developments further [5][3]