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]

Summary of Disc Medicine (IRON) FY Conference Call Company Overview - **Company**: Disc Medicine - **Focus**: Non-malignant hematology, specifically manipulating red blood cell biology - **Lead Program**: Vitapertin targeting erythropoietic protoporphyria (EPP) with a projected NDA filing in the second half of 2025 [4][12][26] Core Points and Arguments Erythropoietic Protoporphyria (EPP) - **Disease Description**: Genetic condition caused by mutations in the heme biosynthetic pathway leading to excessive buildup of protoporphyrin IX (PP9), which causes severe pain and potential liver failure [6][8] - **Patient Impact**: Patients experience excruciating pain from light exposure, leading to significant lifestyle restrictions [7][8] - **Current Treatment Landscape**: Many patients resort to ineffective opioid therapy [7] Clinical Trials and Data - **Phase II Studies**: Completed two studies (AURORA and BEACON) with approximately 100 patients showing a significant reduction in PP9 levels (50-60% at the 60 mg dose) [10][11] - **Clinical Significance**: Reduction in PP9 correlates with improved quality of life and reduced phototoxic reactions [10][11] - **FDA Interaction**: Positive discussions with the FDA regarding the use of PP9 as a surrogate endpoint for accelerated approval [13][16] Upcoming Trials - **APOLLO Trial**: Designed as a confirmatory trial to support full approval, incorporating learnings from Phase II studies [18][21] - **Endpoints**: Co-primary endpoints include PP9 reduction and clinically meaningful measures of light exposure [21][22] Market Opportunity - **Patient Population**: Approximately 14,000 diagnosed EPP patients in the U.S., with 6,000 engaged patients based on claims analysis [27][28] - **Commercial Potential**: High motivation among patients to improve quality of life, leading to expected rapid uptake of the drug [28][29] Payer and Reimbursement Landscape - **Initial Interactions with Payers**: Payers recognize the severe nature of EPP and the potential value of effective treatments [31] - **Pricing Context**: Existing treatments for related conditions priced at $300,000 to $575,000 annually, indicating a willingness to pay for effective therapies [32] Second Asset: Nine Seven Four - **Indication**: Treatment for anemia associated with myelofibrosis, addressing a significant unmet need as no approved therapies exist for this condition [37][38] - **Phase II Study**: Ongoing with initial data expected in the second half of 2025 [41] Third Asset: Nine Thousand Nine Hundred Fourteen - **Indication**: Anemia in non-dialysis dependent chronic kidney disease (CKD) patients, with a significant unmet need in this population [48][49] Future Outlook - **Pipeline Development**: Disc Medicine aims to remain capital efficient while exploring new opportunities for pipeline expansion [59][60] - **Exciting Year Ahead**: Anticipation of NDA filing for Vitapertin and further data releases from ongoing studies [62] Important but Overlooked Content - **Patient Engagement**: High patient motivation and engagement in clinical trials, which may facilitate faster enrollment and data collection [26][27] - **Regulatory Environment**: Positive momentum from the FDA regarding accelerated approval pathways for rare diseases, which may benefit Disc Medicine's programs [16][46]

Summary of the Conference Call for Disc Medicine (IRON) Company Overview - **Company**: Disc Medicine (Ticker: IRON) - **Event**: 2025 Jefferies Global Healthcare Conference - **Date**: June 05, 2025 Key Points Discussed Industry and Regulatory Environment - **FDA Interactions**: Positive and consistent interactions with the FDA regarding the NDA submission for Erythropoietic Protoporphyria (EPP) treatment, with alignment on using Protoporphyrin IX (PP9) as a surrogate endpoint for accelerated approval [4][11] - **NDA Timeline**: Projected NDA filing in the second half of 2025, with a pre-NDA meeting scheduled without issues [8][12] Market Opportunity for EPP Treatment - **Patient Population**: Estimated 20,000 patients in the U.S. with EPP, with 14,000 patients seeking treatment based on claims data [16][17] - **Engagement with Healthcare**: Approximately 6,000 patients show a higher degree of engagement with the medical system, indicating a target population for the launch [18] - **Commercial Strategy**: Plans to utilize advocacy groups and marketing strategies to activate the full patient opportunity [18][19] Launch Trajectory and Market Dynamics - **Launch Expectations**: Anticipated launch curve similar to other successful rare disease therapies, with high patient engagement and awareness [21] - **Disease Modifying Therapy**: The treatment is positioned as a disease-modifying therapy, addressing the underlying cause of EPP rather than just symptoms [23][24] Clinical Data and Efficacy - **PP9 Reduction**: Significant reduction in PP9 levels is expected to be a key indicator of treatment efficacy, with a robust response anticipated from KOLs [24][28] - **Phototoxic Reactions**: Previous trials showed a 75% reduction in phototoxic reactions at the highest dose, which would be impactful if replicated in larger trials [28][29] Competitive Landscape - **Other Treatments**: Awareness of competitors like Dursomelagon and other early-stage assets targeting EPP, but limited activity in the space [31][32] - **Anemia Program (974)**: Focus on anemia associated with chronic inflammation, particularly in myelofibrosis (MF) and chronic kidney disease (CKD) [35][36] Upcoming Data and Regulatory Path - **Data Readouts**: Anticipated data from EHA and ASH conferences, with a focus on long-term efficacy and safety [42][45] - **Regulatory Path for Anemia**: Clearer regulatory path established with the FDA for different patient groups in myelofibrosis, including non-transfusion dependent and lightly transfused patients [67][72] Patient Stratification and Efficacy - **Identifying Responders**: Potential to identify high responders based on baseline ferritin and EPO levels, which may guide treatment decisions [82][84] Additional Insights - **Market Dynamics**: The treatment landscape for anemia in myelofibrosis is evolving, with a focus on addressing unmet needs in patient care [39][60] - **Long-term Vision**: The company aims to position its therapies as first-line treatments for anemia in myelofibrosis, differentiating from competitors that target more niche populations [64][66] This summary encapsulates the critical discussions and insights from the conference call, highlighting the company's strategic direction, market opportunities, and clinical developments.

Financial Data and Key Metrics Changes - The company is on an accelerated approval path for bitapertin, with strong scientific rationale supporting the use of protoporphyrin nine (PP9) as a surrogate endpoint for approval [4][5] - The data package provided to the FDA showed clear PP9 reduction and outperformance of the placebo group across multiple endpoints, which was persuasive in obtaining approval [5] Business Line Data and Key Metrics Changes - The target population for bitapertin is estimated to be around 20,000 individuals in the US with the genotype for EPP, with approximately 14,000 patients having received therapy under the EPP code [14][15] - The company aims to launch bitapertin targeting the 6,000 more recently treated patients while also reaching out to the full 14,000 patient population through advocacy campaigns [15] Market Data and Key Metrics Changes - The company acknowledges that many patients do not utilize the existing therapy, Senesse, due to access issues and the requirement for surgical procedures [7][8] - The competitive landscape includes the need for an oral therapy like bitapertin, which addresses the unmet needs of EPP patients [8] Company Strategy and Development Direction - The company is focusing on the EPP regulatory process and launch preparation, with plans to file an NDA in the second half of the year [34] - The company is also developing DISC 974, a monoclonal antibody aimed at treating anemia in myelofibrosis, with the goal of becoming the drug of choice for anemic patients [35][37] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the likelihood of success in the upcoming Apollo confirmatory trial, emphasizing the importance of both PP9 reduction and time in light as key endpoints [24] - The company is navigating the challenges of an accelerated launch timeline, having already built a commercial infrastructure and engaged with key opinion leaders [32][34] Other Important Information - The company is also exploring treatment options for anemia in chronic kidney disease (CKD) patients, with early data showing promising responses [45][47] - Management highlighted the importance of addressing anemia in myelofibrosis, noting that nearly 90% of patients are anemic and that there is currently no approved therapy for this condition [37][38] Q&A Session Summary Question: How did the FDA respond to the accelerated approval pathway for bitapertin? - The FDA required only one meeting to agree that PP9 could serve as a surrogate endpoint for accelerated approval, indicating a strong scientific rationale [5] Question: What is the estimated patient population for EPP? - The estimated patient population is around 20,000 individuals in the US, with 14,000 having received therapy under the EPP code [14][15] Question: How does the company plan to address the anemia in myelofibrosis? - The company aims to provide a drug that can be used from day one of diagnosis to manage anemia, which is a significant issue for myelofibrosis patients [37][38]

Core Insights - Disc Medicine, Inc. is set to present data from its hematology portfolio at the European Hematology Association (EHA) 2025 Congress in Milan from June 12-15, 2025, highlighting progress in its clinical programs [1][2] Company Developments - The company will showcase data from the HELIOS long-term extension trial, supporting bitopertin as a potential first disease-modifying treatment for erythropoietic protoporphyria (EPP) [2] - Additional data will be presented from the Phase 1b study of DISC-0974 in patients with myelofibrosis (MF) anemia, along with new findings from DISC-3405 in healthy volunteers, which supports its progression into a Phase 2 study in polycythemia vera [2][5] Presentation Details - The HELIOS study results will be presented on June 14, 2025, by Melanie Chin, while multiple presentations on DISC-0974 and DISC-3405 will occur on June 13 and 14, 2025, featuring various authors [4][6] - Management will host a corporate update call on June 16, 2025, to review the presented data [5]

About Disc Medicine Disc Medicine (NASDAQ:IRON) is a clinical-stage biopharmaceutical company committed to discovering, developing, and commercializing novel treatments for patients who suffer from serious hematologic diseases. We are building a portfolio of innovative, potentially first-in-class therapeutic candidates that aim to address a wide spectrum of hematologic diseases by targeting fundamental biological pathways of red blood cell biology, specifically heme biosynthesis and iron homeostasis. For mo ...