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]

Core Insights - Disc Medicine, Inc. is a clinical-stage biopharmaceutical company focused on developing novel treatments for serious hematologic diseases [3] - The company will participate in a fireside chat at the H.C. Wainwright 3rd Annual BioConnect Investor Conference on May 20, 2025 [1] - A live webcast of the event will be available on the company's investor relations website, with an archived replay accessible afterward [2] Company Overview - Disc Medicine is committed to discovering and commercializing innovative treatments targeting red blood cell biology, specifically heme biosynthesis and iron homeostasis [3] - The company aims to build a portfolio of potentially first-in-class therapeutic candidates addressing a wide spectrum of hematologic diseases [3]

Summary of Disc Medicine Conference Call Company Overview - **Company**: Disc Medicine - **Focus**: Hematology, specifically targeting pathways of red blood cell biology and iron metabolism - **Lead Programs**: Bidipertin for erythropoietin protoporphyria and DISCO-nine 74 for anemia of myelofibrosis [3][6][8] Industry Context - **Disease Focus**: Myelofibrosis, a type of blood cancer characterized by anemia, splenomegaly, and constitutional symptoms [16][22] - **Current Treatment Landscape**: - Four JAK inhibitors approved for myelofibrosis, primarily targeting spleen size reduction and symptom improvement [46][49] - No approved therapies specifically for anemia of myelofibrosis, leading to significant unmet medical needs [19][45] Key Points from the Call Myelofibrosis and Anemia - **Prevalence**: Approximately 25,000 patients in the U.S. diagnosed with myelofibrosis, with a five-year survival rate around 50% [26][27] - **Anemia Statistics**: - 40% of patients present with significant anemia at diagnosis, increasing to 60% within one year [36] - Nearly all patients will develop anemia over the disease course, with transfusion dependency rising from 25% at diagnosis to 45% within a year [36][37] - **Prognostic Importance**: Anemia is a significant prognostic factor, with lower hemoglobin levels correlating with worse survival outcomes [30][38] Current Treatment Limitations - **JAK Inhibitors**: While effective for managing symptoms, they often exacerbate anemia, leading to treatment discontinuation in many patients [60][61] - **Existing Treatments for Anemia**: Use of erythropoietin, steroids, and androgens, but these are not specifically approved for myelofibrosis-related anemia [49][50] Emerging Therapies - **DISCO-nine 74**: - A monoclonal antibody targeting hepcidin suppression to mobilize iron for red blood cell production [8][10] - Phase 1b data shows promise in treating anemia of myelofibrosis [14][19] - **Luspatercept and Elitracept**: - Both are in development as potential treatments for anemia, with luspatercept already approved for MDS [79][80] - Phase 3 trials for luspatercept are ongoing, focusing on patients requiring transfusions while on stable doses of JAK inhibitors [80] Market Opportunity - **Anemia of Myelofibrosis**: Significant market opportunity exists for effective treatments targeting anemia, given the high prevalence and unmet needs [19][45] - **Potential Impact of New Therapies**: New treatments could improve patient quality of life, reduce healthcare costs associated with transfusions, and address the underlying pathophysiology of anemia in myelofibrosis [40][41][44] Conclusion - The call emphasized the critical need for new therapies specifically targeting anemia in myelofibrosis, highlighting the potential of DISCO-nine 74 and other emerging treatments to fill this gap in the current treatment landscape [19][45][76]

[Forward-Looking Statements](index=3&type=section&id=FORWARD-LOOKING%20STATEMENTS) This section outlines the report's forward-looking statements, which are subject to inherent risks and uncertainties, with no obligation for the company to update them except as required by law - The report contains forward-looking statements regarding the company's plans and expectations for its research and development programs, clinical trials (including for bitopertin, DISC-0974, and DISC-3405), potential for accelerated FDA approval, manufacturing capabilities, funding needs, and future financial performance[10](index=10&type=chunk) - These statements are based on current expectations and are not guarantees of future performance. The company cautions that actual results may differ materially due to various risks and uncertainties[11](index=11&type=chunk) - The company explicitly states it does not undertake any obligation to update forward-looking statements, except as required by law, and refers readers to the 'Risk Factors' section for a detailed discussion of these risks[11](index=11&type=chunk)[12](index=12&type=chunk) [Risk Factor Summary](index=5&type=section&id=RISK%20FACTOR%20SUMMARY) This section summarizes the principal risks, including limited operating history, significant losses, funding needs, clinical development uncertainties, third-party reliance, and internal control weaknesses - Financial Risks: The company has a limited operating history, has incurred significant net losses since inception, has no revenue from product sales, and may need to raise substantial additional funding[15](index=15&type=chunk) - Developmental Risks: No product candidates have progressed through a Phase 3 trial, the company's approach is novel and may not succeed, and early-stage clinical data may not predict later results. There is also a risk of significant adverse events in trials[15](index=15&type=chunk) - Operational and Competitive Risks: The company relies on third parties for clinical trials and manufacturing, faces substantial competition, and its intellectual property protection may not be sufficient[15](index=15&type=chunk)[17](index=17&type=chunk) - Governance and Market Risks: A material weakness in internal controls over financial reporting has been identified. The stock price is expected to be volatile, and the company faces increased costs associated with being a public company[17](index=17&type=chunk) [PART I. FINANCIAL INFORMATION](index=8&type=section&id=PART%20I.%20FINANCIAL%20INFORMATION) [Financial Statements (Unaudited)](index=8&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) This section presents the unaudited condensed consolidated financial statements for Q1 2025, reflecting increased assets and stockholders' equity from a stock offering, alongside a wider net loss due to higher operating expenses [Condensed Consolidated Balance Sheets](index=8&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) Total assets increased to **$709.3 million** by March 31, 2025, from **$496.8 million** at year-end 2024, driven by marketable securities and a **$216.8 million** rise in stockholders' equity from an equity offering Condensed Consolidated Balance Sheet Highlights (in thousands) | | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $122,675 | $192,434 | | Marketable securities | $571,987 | $297,447 | | Total current assets | $705,600 | $493,615 | | **Total assets** | **$709,266** | **$496,773** | | **Liabilities & Stockholders' Equity** | | | | Total current liabilities | $18,741 | $23,316 | | Total liabilities | $48,904 | $53,186 | | Total stockholders' equity | $660,362 | $443,587 | | **Total liabilities and stockholders' equity** | **$709,266** | **$496,773** | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) Net loss for Q1 2025 widened to **$34.1 million** from **$26.9 million** in Q1 2024, primarily due to increased R&D and SG&A expenses, partially offset by higher interest income Statement of Operations Highlights (in thousands, except per share data) | | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Research and development | $27,763 | $23,704 | | Selling, general and administrative | $12,183 | $7,758 | | **Loss from operations** | **($39,946)** | **($31,462)** | | Interest income | $6,880 | $4,519 | | **Net loss** | **($34,085)** | **($26,949)** | | **Net loss per share, basic and diluted** | **($1.02)** | **($1.09)** | [Condensed Consolidated Statements of Stockholders' Equity](index=10&type=section&id=Condensed%20Consolidated%20Statements%20of%20Stockholders%27%20Equity) Stockholders' equity increased to **$660.4 million** by March 31, 2025, primarily due to **$234.0 million** from common stock and **$9.4 million** from pre-funded warrants in a January 2025 offering, offset by the **$34.1 million** net loss - In Q1 2025, the company completed an underwritten offering, issuing 4,533,182 shares of common stock for net proceeds of **$234.0 million** and pre-funded warrants for net proceeds of **$9.4 million**[25](index=25&type=chunk) Changes in Stockholders' Equity (in thousands) | | Amount | | :--- | :--- | | **Balance at December 31, 2024** | **$443,587** | | Sale of common stock in underwritten offering, net | $234,003 | | Sale of pre-funded warrants in underwritten offering, net | $9,386 | | Stock-based compensation expense | $6,363 | | Net loss | ($34,085) | | **Balance at March 31, 2025** | **$660,362** | [Condensed Consolidated Statements of Cash Flows](index=11&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operations increased to **$41.4 million** in Q1 2025, while investing activities used **$272.6 million**, largely offset by **$244.3 million** from financing activities, resulting in a **$69.8 million** net decrease in cash Cash Flow Summary (in thousands) | | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | ($41,376) | ($33,599) | | Net cash used in investing activities | ($272,633) | ($67) | | Net cash provided by financing activities | $244,251 | $15,900 | | **Net decrease in cash, cash equivalents and restricted cash** | **($69,758)** | **($17,766)** | [Notes to Unaudited Condensed Consolidated Financial Statements](index=12&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) These notes detail the company's focus on hematologic diseases, its **$694.7 million** capital position sufficient for 12 months, key license and loan agreements, and the **$243.4 million** net proceeds from the January 2025 equity offering - The company is a clinical-stage biopharmaceutical firm focused on hematologic diseases, with key product candidates including bitopertin, DISC-0974, DISC-3405, and DISC-0998[30](index=30&type=chunk) - As of March 31, 2025, the company had **$694.7 million** in cash, cash equivalents, and marketable securities, which is expected to fund planned operations for at least the next twelve months[32](index=32&type=chunk) - The company has a loan agreement for up to **$200.0 million**, with an initial **$30.0 million** borrowed in November 2024. The loan matures in December 2029[61](index=61&type=chunk) - In January 2025, the company raised net proceeds of **$243.4 million** from an underwritten offering of common stock and pre-funded warrants[70](index=70&type=chunk)[71](index=71&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=25&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses Q1 2025 financial results, highlighting a **$34.1 million** net loss driven by increased R&D and SG&A, significant clinical pipeline progress, and a strong **$694.7 million** liquidity position expected to fund operations into 2028 [Overview](index=25&type=section&id=Overview) This overview highlights the company's clinical pipeline progress, including planned NDA submission for bitopertin and Phase 2 trials for DISC-0974 and DISC-3405, supported by **$694.7 million** in cash expected to fund operations into 2028 - The company plans to submit a New Drug Application (NDA) for accelerated approval of bitopertin for EPP and XLP in the second half of 2025[98](index=98&type=chunk) - Key data readouts are expected in the second half of 2025 for the Phase 2 trial of DISC-0974 in anemia of MF and the MAD portion of the Phase 1b trial in non-dialysis dependent CKD[99](index=99&type=chunk)[100](index=100&type=chunk) - A Phase 2 clinical trial of DISC-3405 for polycythemia vera (PV) is planned to be initiated in the first half of 2025[101](index=101&type=chunk) - As of March 31, 2025, the company had **$694.7 million** in cash, cash equivalents, and marketable securities, which it believes is sufficient to fund operations into 2028[102](index=102&type=chunk) [Results of Operations](index=30&type=section&id=Results%20of%20Operations) Net loss increased by **$7.1 million** to **$34.1 million** in Q1 2025, driven by a **$4.1 million** rise in R&D and a **$4.4 million** increase in SG&A expenses, partially offset by higher interest income Comparison of Results of Operations (in thousands) | | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | Change | | :--- | :--- | :--- | :--- | | Research and development | $27,763 | $23,704 | $4,059 | | Selling, general and administrative | $12,183 | $7,758 | $4,425 | | **Loss from operations** | **($39,946)** | **($31,462)** | **($8,484)** | | **Net loss** | **($34,085)** | **($26,949)** | **($7,136)** | - R&D expenses increased by **$4.1 million**, primarily due to a **$2.4 million** increase in DISC-0974 development and a **$2.1 million** increase for bitopertin, related to advancing clinical trials and manufacturing. This was partially offset by a **$3.0 million** decrease in DISC-3405 expenses[114](index=114&type=chunk) - SG&A expenses increased by **$4.4 million**, mainly from a **$2.0 million** increase in personnel-related costs due to higher headcount and a **$2.1 million** increase in legal and professional fees for commercialization readiness[115](index=115&type=chunk)[116](index=116&type=chunk) [Liquidity and Capital Resources](index=31&type=section&id=Liquidity%20and%20Capital%20Resources) The company maintains a strong liquidity position with **$694.7 million** in cash and marketable securities as of March 31, 2025, expected to fund operations into 2028, primarily bolstered by **$244.3 million** from the January 2025 equity offering - The company has funded operations primarily through sales of preferred and common stock and debt borrowings, with **$694.7 million** in cash, cash equivalents, and marketable securities as of March 31, 2025[120](index=120&type=chunk) - Management believes current cash reserves are sufficient to fund operating plans and debt service obligations into 2028[121](index=121&type=chunk) Cash Flow Summary (in thousands) | | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | ($41,376) | ($33,599) | | Net cash used in investing activities | ($272,633) | ($67) | | Net cash provided by financing activities | $244,251 | $15,900 | [Quantitative and Qualitative Disclosures About Market Risk](index=35&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The primary market risk is interest rate sensitivity, where a 1% increase could decrease the fair value of **$694.7 million** in investments by **$3.6 million**, while foreign currency and inflation risks are minimal - The company's main market risk is interest rate sensitivity. A hypothetical 1% increase in interest rates would decrease the fair value of its marketable securities by approximately **$3.6 million**[140](index=140&type=chunk) - Exposure to foreign currency risk is considered minimal as operations are primarily in the U.S. and contracts in foreign currencies are short-term[141](index=141&type=chunk) - Inflation is not believed to have had a material effect on the business during the reported periods[142](index=142&type=chunk) [Controls and Procedures](index=35&type=section&id=Item%204.%20Controls%20and%20Procedures) Disclosure controls were deemed ineffective as of March 31, 2025, due to a material weakness in IT General Controls, though no material misstatements occurred, and remediation efforts are underway - Management concluded that as of March 31, 2025, the company's disclosure controls and procedures were not effective at a reasonable assurance level[144](index=144&type=chunk) - The ineffectiveness is due to a material weakness identified in the design and maintenance of Information Technology General Controls (ITGCs) over certain key financial IT systems[145](index=145&type=chunk) - The company has begun remediation efforts, including developing training programs, engaging third-party consultants, expanding internal resources, and enhancing reporting to the Audit Committee[147](index=147&type=chunk) [PART II. OTHER INFORMATION](index=38&type=section&id=PART%20II.%20OTHER%20INFORMATION) [Legal Proceedings](index=38&type=section&id=Item%201.%20Legal%20Proceedings) The company reports no material legal proceedings or claims that would significantly adversely affect its business or financial condition - The company is not currently aware of any material legal proceedings or claims against it[151](index=151&type=chunk) [Risk Factors](index=38&type=section&id=Item%201A.%20Risk%20Factors) This section details numerous risks, including limited operating history, substantial funding needs, clinical development uncertainties, reliance on third parties, intellectual property protection, regulatory hurdles, and internal control weaknesses - Financial Risks: The company has a limited operating history, has incurred significant net losses (**$34.1 million** for Q1 2025), and anticipates needing substantial additional funding to continue its development and potential commercialization efforts[153](index=153&type=chunk)[155](index=155&type=chunk)[166](index=166&type=chunk) - Clinical Development Risks: The company has no products approved for sale and has not yet progressed any candidate through a Phase 3 trial. The success of its clinical trials is uncertain, and early positive results are not predictive of final outcomes[158](index=158&type=chunk)[174](index=174&type=chunk)[196](index=196&type=chunk) - Third-Party Reliance: The business is highly dependent on third parties for conducting clinical trials (CROs, NIH) and for the manufacturing of its product candidates, which increases risks related to supply, quality, and regulatory compliance[236](index=236&type=chunk)[253](index=253&type=chunk) - Intellectual Property Risks: The company's success depends on obtaining and maintaining robust patent protection for its technology and product candidates, much of which is in-licensed from partners like Roche, AbbVie, and Mabwell[268](index=268&type=chunk)[270](index=270&type=chunk) - Regulatory and Commercialization Risks: The company may seek accelerated approval for bitopertin, but this pathway is not guaranteed and carries post-marketing requirements. The company also faces risks from healthcare reform, pricing pressures, and competition from potential generics or biosimilars[335](index=335&type=chunk)[343](index=343&type=chunk)[352](index=352&type=chunk) - Internal Control Risks: The company has identified a material weakness in its internal controls over financial reporting related to Information Technology General Controls (ITGCs), which could impact the accuracy of financial reporting[414](index=414&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=122&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) There were no unregistered sales of the company's equity securities during the quarter ended March 31, 2025 - There were no unregistered sales of equity securities during the reported quarter[430](index=430&type=chunk) [Defaults Upon Senior Securities](index=122&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) The company reports no defaults upon its senior securities - No defaults upon senior securities occurred[433](index=433&type=chunk) [Mine Safety Disclosures](index=122&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company's business - This section is not applicable[434](index=434&type=chunk) [Other Information](index=122&type=section&id=Item%205.%20Other%20Information) This section discloses that three executive officers adopted Rule 10b5-1 trading plans during the first quarter of 2025 Adoption of Rule 10b5-1 Trading Plans (Q1 2025) | Name and Title | Date of Adoption | Aggregate Securities to be Sold | | :--- | :--- | :--- | | William Savage, M.D., Ph.D. (CMO) | January 23, 2025 | Up to 2,996 | | John Quisel, J.D., Ph.D. (CEO) | February 13, 2025 | Up to 80,000 | | Jean Franchi (CFO) | March 10, 2025 | Up to 6,031 | [Exhibits](index=123&type=section&id=Item%206.%20Exhibits) This section provides an index of exhibits filed with the Quarterly Report on Form 10-Q, including required officer certifications and an employment agreement - The exhibit index lists all documents filed with the report, including required officer certifications under Sarbanes-Oxley Sections 302 and 906[438](index=438&type=chunk)