Core Insights - Fulcrum Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing small molecules for genetically defined rare diseases [3] - The company will participate in a fireside chat at the 46th Annual Goldman Sachs Global Healthcare Conference on June 11, 2025 [1] - Fulcrum's lead clinical program is pociredir, aimed at increasing fetal hemoglobin expression for treating sickle cell disease [3] Company Overview - Fulcrum Therapeutics specializes in small molecule development to address high unmet medical needs in rare diseases [3] - The company employs proprietary technology to identify drug targets that modulate gene expression [3] - More information about the company can be found on their website and social media platforms [3]

Fulcrum Therapeutics Inc (FULC) 2025 Conference Summary Company Overview - Fulcrum Therapeutics is a SMIDGAP biotech company focused on rare benign hematological conditions, with its lead program, Posiridir, targeting sickle cell disease currently in Phase 1b studies [4][2] Market Opportunity in Sickle Cell Disease - Sickle cell disease affects approximately 100,000 people in the U.S. and 4.4 million globally, with a significantly decreased life expectancy of 20 to 25 years [6][6] - Recent drug approvals have not met expectations; Voxelotor was pulled from the market, and Crizanlizumab failed to show significant efficacy in reducing vaso-occlusive crises [7][8] - The unmet need in the sickle cell market remains extremely high, creating an opportunity for Posiridir [8][8] Mechanism of Action - Posiridir induces fetal hemoglobin (HBF) expression, which can mitigate the effects of sickle hemoglobin by diluting it and preventing sickling under hypoxic conditions [10][12] - The drug works by inhibiting the PRC2 enzyme complex, leading to an altered gene expression profile that upregulates the HBG gene responsible for fetal hemoglobin production [11][12] Clinical Development and Regulatory Updates - A clinical hold was placed by the FDA in early 2023 due to preclinical findings of hematological malignancies, but the hold was lifted after redefining the patient population to include more severely affected patients [14][16][18] - The new inclusion criteria restrict concomitant use of hydroxyurea, which is labeled as a carcinogen, to ensure patient safety during early development [19][21] Patient Population and Enrollment - Approximately 10% of the 100,000 U.S. sickle cell patients meet the new inclusion criteria, equating to about 10,000 potential participants for the study [22][22] - The company anticipates that demonstrating the drug's efficacy in increasing fetal hemoglobin levels could lead to a relaxation of these criteria in future studies [24][24] Efficacy and Clinical Meaningfulness - There is a strong correlation between increased fetal hemoglobin levels and reduced vaso-occlusive crises, with a target of achieving a clinically meaningful reduction of at least 25% in these crises [29][30] - Initial cohorts showed dose-dependent increases in fetal hemoglobin, with higher doses leading to more significant increases [26][27] Competitive Landscape - Renewed interest in fetal hemoglobin as a treatment mechanism has emerged, with several competitors entering the field, including BMS, Novartis, and GSK, although they are at earlier stages of development compared to Fulcrum [33][34] Financial Position and Future Aspirations - Fulcrum has a cash position of approximately $226 million, with an annual burn rate of $55 to $65 million, providing a runway until at least 2027 [40][41] - The company aims to expand beyond sickle cell disease and become a leader in benign hematological rare conditions [41][42]

Core Viewpoint - Fulcrum Therapeutics, Inc. is actively participating in upcoming conferences to engage with investors and stakeholders, highlighting its focus on developing treatments for genetically defined rare diseases [1][3]. Company Overview - Fulcrum Therapeutics is a clinical-stage biopharmaceutical company dedicated to developing small molecules aimed at improving the lives of patients with genetically defined rare diseases, particularly in areas with high unmet medical needs [2]. - The company's lead clinical program is pociredir, a small molecule designed to enhance fetal hemoglobin expression for treating sickle cell disease (SCD) [2]. - Fulcrum employs proprietary technology to identify drug targets that can modulate gene expression, addressing the root causes of gene mis-expression [2]. Upcoming Events - The company will participate in the H.C. Wainwright BioConnect Investor Conference on May 20, 2025, in New York, New York [3]. - Fulcrum will also take part in the RBC Capital Markets Global Healthcare Conference on May 21, 2025, with a fireside chat scheduled for 3:35 pm ET [3].

Financial Data and Key Metrics Changes - Research and development expenses decreased to $13.4 million in Q1 2025 from $19.8 million in Q1 2024, a reduction of $6.4 million attributed to the discontinuation of the losmapimod program and global development cost sharing reimbursement under the Sanofi collaboration [11] - General and administrative expenses fell to $7 million in Q1 2025 from $10.1 million in Q1 2024, a decrease of $3.1 million primarily due to reduced employee compensation costs following a workforce reduction [12] - Net loss improved to $17.7 million in Q1 2025 compared to a net loss of $26.9 million in Q1 2024 [12] - Cash, cash equivalents, and marketable securities decreased to $226.6 million as of March 31, 2025, from $241 million as of December 31, 2024, a decrease of $14.4 million mainly due to cash used for operating activities [12][13] Business Line Data and Key Metrics Changes - The lead program, coceridere, is currently enrolling in a phase 1b trial called PIONEER for sickle cell disease, with 16 patients enrolled in the 12 mg cohort [5][7] - The data monitoring committee recommended continuing the study and initiating the 20 mg cohort, which is now underway [7] Market Data and Key Metrics Changes - Approximately 100,000 people in the US and 4.4 million people worldwide are afflicted by sickle cell disease, indicating a significant market opportunity for treatments targeting this condition [5] Company Strategy and Development Direction - The company aims to induce fetal hemoglobin as a strategy for treating sickle cell disease, supported by data showing that even modest increases in fetal hemoglobin correlate with reduced disease severity [8] - The company plans to submit an IND for Diamond Blackfan anemia in Q4 2025, indicating a focus on expanding its treatment portfolio for inherited hematological conditions [9][10] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the progress made in 2025 and looks forward to delivering important data releases from the PIONEER trial [14] - The company believes that the current operating plans will allow existing cash reserves to fund operations into at least 2027 [13] Other Important Information - The company has two abstracts accepted for presentation at the upcoming European Hematology Association meeting, highlighting ongoing research efforts [9] Q&A Session Summary Question: Data expectations from the twelve milligram cohort of PIONEER - Management confirmed that data will include hematological parameters and that all 16 patients will have data from the three-month treatment phase, with a subset having four-week follow-up data [16][17] Question: Adherence data and dosing timing - Management explained that adherence is monitored using an AI tool, with over 90% adherence reported, and that they can track the timing of doses taken by patients [19][20][22] Question: Representativeness of the patient sample - Management acknowledged that while the sample size is small, the baseline fetal hemoglobin levels were higher than expected, and they do not believe baseline levels will determine response to treatment [25][28] Question: Expectations for the twelve-week data - Management indicated that any increase in fetal hemoglobin is beneficial, with clinically meaningful reductions in vaso-occlusive crises expected from the data [34][36] Question: Enrollment dynamics and site selection - Management attributed faster enrollment to having the right sites on board and the loss of other treatment options, which increased patient interest in the trial [42][44] Question: FDA interactions and endpoint selection - Management plans to interact with the FDA at the end of the 20 mg cohort to discuss future study plans and endpoint selection [54][56]

Fulcrum Therapeutics Inc (FULC) Q1 2025 Earnings Call May 01, 2025 08:00 AM ET Company Participants Alex Sapir - CEO, President, & Board MemberAlan Musso - Chief Financial OfficerJoseph Schwartz - Senior Managing DirectorIain Fraser - Senior Vice President of Early DevelopmentMatthew Biegler - Managing DirectorAnish Nikhanj - Senior Associate - Biotechnology Equity Research Conference Call Participants Edward Tenthoff - MD & Senior Research AnalystKristen Kluska - Equity Research Analyst Operator Good morni ...

Financial Data and Key Metrics Changes - Research and development expenses decreased to $13.4 million in Q1 2025 from $19.8 million in Q1 2024, a reduction of $6.4 million attributed to the discontinuation of the losmapimod program and reimbursement under the Sanofi collaboration [10] - General and administrative expenses fell to $7 million in Q1 2025 from $10.1 million in Q1 2024, a decrease of $3.1 million primarily due to reduced employee compensation costs following workforce reductions [11] - Net loss improved to $17.7 million in Q1 2025 compared to a net loss of $26.9 million in Q1 2024 [11] - Cash, cash equivalents, and marketable securities decreased to $226.6 million as of March 31, 2025, from $241 million at the end of 2024, a decrease of $14.4 million mainly due to cash used for operating activities [11][12] Business Line Data and Key Metrics Changes - The lead program, coceridere, is currently enrolling in a phase 1b trial called PIONEER for sickle cell disease, with 16 patients enrolled in the 12 mg cohort [4][5] - The data monitoring committee recommended continuing the study and initiating the 20 mg cohort, which is now underway [5] - The company plans to report data from the 20 mg cohort by the end of 2025 [5] Market Data and Key Metrics Changes - Approximately 100,000 people in the US and 4.4 million people worldwide are affected by sickle cell disease [4] - Evidence suggests that even modest increases in fetal hemoglobin correlate with reduced disease severity, with a 1% increase in fetal hemoglobin leading to a 4% to 8% reduction in vaso-occlusive crises [7] Company Strategy and Development Direction - The company believes inducing fetal hemoglobin is the optimal strategy for treating sickle cell disease, supported by recent data analysis and approved gene therapies [6] - Plans to submit an IND for Diamond Blackfan anemia in Q4 2025, indicating a focus on expanding treatment options for inherited hematological conditions [8] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the progress made in 2025 and the upcoming data releases from the PIONEER trial [13] - The company expects existing cash reserves to fund operations into at least 2027, indicating a stable financial outlook [12] Other Important Information - The company has two abstracts accepted for presentation at the upcoming European Hematology Association meeting, highlighting ongoing research efforts [8] Q&A Session Summary Question: Data expectations from the twelve milligram cohort of PIONEER - Management confirmed that they will provide hematological parameters, including markers of hemolysis, and data for all 16 patients after a three-month treatment phase [15][16] Question: Observed dosing data and adherence - The company utilizes an AI tool to track adherence, reporting over 90% adherence to the once-daily oral regimen [19][21] Question: Baseline fetal hemoglobin levels and patient demographics - Management acknowledged that the baseline fetal hemoglobin levels were higher than expected, indicating a representative sample of the broader demographic [25][26] Question: Win criteria from the twelve-week data - Any increase in fetal hemoglobin is considered beneficial, with a clinically meaningful reduction in vaso-occlusive crises expected from increases in fetal hemoglobin [34][35] Question: Impact of FDA shifts on development - The company plans to interact with the FDA at the end of the phase 1b study to gauge regulatory perspectives on endpoint selection and development timelines [53][55]

[PART I. FINANCIAL INFORMATION](index=7&type=section&id=PART%20I.%20FINANCIAL%20INFORMATION) [Financial Statements](index=7&type=section&id=Item%201.%20Financial%20Statements) This section presents unaudited consolidated financial statements for Q1 2025, reporting a net loss of **$17.7 million** and an accumulated deficit of **$537.1 million** Consolidated Balance Sheet Highlights (Unaudited, in thousands) | Account | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash and cash equivalents | $42,178 | $58,212 | | Marketable securities | $184,425 | $182,809 | | **Total Assets** | **$242,649** | **$260,718** | | Total current liabilities | $8,100 | $11,044 | | **Total Liabilities** | **$14,163** | **$17,684** | | Accumulated deficit | $(537,053) | $(519,398) | | **Total Stockholders' Equity** | **$228,486** | **$243,034** | Consolidated Statements of Operations (Unaudited, in thousands, except per share data) | Metric | Three Months Ended Mar 31, 2025 | Three Months Ended Mar 31, 2024 | | :--- | :--- | :--- | | Research and development | $13,404 | $19,773 | | General and administrative | $6,999 | $10,061 | | **Loss from operations** | **$(20,403)** | **$(29,834)** | | **Net loss** | **$(17,655)** | **$(26,870)** | | Net loss per share, basic and diluted | $(0.28) | $(0.43) | Consolidated Statements of Cash Flows (Unaudited, in thousands) | Cash Flow Activity | Three Months Ended Mar 31, 2025 | Three Months Ended Mar 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(15,257) | $(25,284) | | Net cash (used in) provided by investing activities | $(777) | $38,128 | | Net cash provided by financing activities | $0 | $1,651 | - The company expects its existing cash, cash equivalents, and marketable securities to be sufficient to fund operating expenses and capital expenditure requirements for at least 12 months from the date of the financial statements[33](index=33&type=chunk) - The collaboration agreement with Sanofi for losmapimod was terminated for convenience by Sanofi, effective April 17, 2025, following the discontinuation of the drug's development. The company is not entitled to any further payments[66](index=66&type=chunk)[67](index=67&type=chunk) - MyoKardia elected to terminate its collaboration and license agreement for convenience, with the termination becoming effective on June 26, 2025. The company will not be entitled to further milestone or royalty payments[76](index=76&type=chunk)[77](index=77&type=chunk) - In September 2024, the company implemented a restructuring plan to focus on pociredir and DBA, reducing its workforce from 80 to 51 full-time employees[94](index=94&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=31&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the company's focus on developing pociredir for SCD, with Q1 2025 net loss decreasing to **$17.7 million** due to reduced R&D expenses - The company is a clinical-stage biopharmaceutical company focused on developing small molecules for genetically defined rare diseases, with its lead candidate, pociredir, being developed for Sickle Cell Disease (SCD)[101](index=101&type=chunk) - Clinical trial updates for pociredir: The Phase 1b trial was reinitiated in Q4 2023. The 12 mg dose cohort is fully enrolled, with data expected in early Q3 2025. The 20 mg dose cohort has been initiated, with data expected by the end of 2025[102](index=102&type=chunk) - The company plans to submit an Investigational New Drug (IND) application for Diamond-Blackfan Anemia (DBA) during the fourth quarter of 2025[103](index=103&type=chunk) Comparison of Operating Results (in thousands) | Item | Three Months Ended Mar 31, 2025 | Three Months Ended Mar 31, 2024 | Change ($) | | :--- | :--- | :--- | :--- | | Research and development | $13,404 | $19,773 | $(6,369) | | General and administrative | $6,999 | $10,061 | $(3,062) | | **Total operating expenses** | **$20,403** | **$29,834** | **$(9,431)** | | **Net loss** | **$(17,655)** | **$(26,870)** | **$9,215** | - R&D expenses decreased by **$6.4 million**, primarily due to a **$4.9 million** decrease in external costs from the suspension of the losmapimod program and a **$1.7 million** decrease in employee compensation costs from lower headcount[127](index=127&type=chunk)[129](index=129&type=chunk) - G&A expenses decreased by **$3.1 million**, mainly due to a **$1.4 million** decrease in employee compensation costs and a **$1.1 million** decrease in professional services costs[130](index=130&type=chunk)[135](index=135&type=chunk) - As of March 31, 2025, the company had **$226.6 million** in cash, cash equivalents, and marketable securities, which is expected to fund operations into at least 2027[108](index=108&type=chunk)[131](index=131&type=chunk)[139](index=139&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=41&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a smaller reporting company, the company is not required to provide quantitative and qualitative disclosures about market risk - As a smaller reporting company, Fulcrum Therapeutics is not required to provide quantitative and qualitative disclosures about market risk[146](index=146&type=chunk) [Controls and Procedures](index=42&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded disclosure controls and procedures were effective as of March 31, 2025, with no material changes in internal control - The CEO and CFO concluded that the company's disclosure controls and procedures were effective as of March 31, 2025[147](index=147&type=chunk) - No changes in internal control over financial reporting occurred during the quarter that materially affected, or are reasonably likely to materially affect, the company's internal controls[148](index=148&type=chunk) [PART II. OTHER INFORMATION](index=43&type=section&id=PART%20II.%20OTHER%20INFORMATION) [Legal Proceedings](index=43&type=section&id=Item%201.%20Legal%20Proceedings) A securities class action lawsuit related to the pociredir clinical hold was dismissed in full by the court on March 27, 2025 - A securities class action lawsuit filed against the company and its officers, related to the clinical hold on pociredir, was dismissed in full by the court on March 27, 2025[151](index=151&type=chunk)[90](index=90&type=chunk) [Risk Factors](index=43&type=page&id=Item%201A.%20Risk%20Factors) This section details significant risks including financial losses, funding needs, reliance on pociredir, clinical development uncertainties, competition, and intellectual property challenges [Risks Related to Financial Position and Need for Additional Capital](index=43&type=section&id=Risks%20Related%20to%20our%20Financial%20Position%20and%20Need%20for%20Additional%20Capital) The company faces significant historical losses and requires substantial additional funding to advance product candidates, with current cash expected to fund operations into at least 2027 - The company has incurred significant losses since inception, with a net loss of **$17.7 million** for Q1 2025 and an accumulated deficit of **$537.1 million** as of March 31, 2025[153](index=153&type=chunk) - Substantial additional funding is required to continue clinical development of pociredir and other candidates. Failure to raise capital could force delays, reductions, or elimination of programs[156](index=156&type=chunk) - The company's cash, cash equivalents, and marketable securities of **$226.6 million** are expected to fund operations into at least 2027, but this estimate is based on assumptions that could prove wrong[160](index=160&type=chunk) [Risks Related to Discovery and Development of Product Candidates](index=51&type=section&id=Risks%20Related%20to%20the%20Discovery%20and%20Development%20of%20our%20Product%20Candidates) The company is early in development with one clinical candidate, pociredir, facing lengthy, expensive, and uncertain clinical processes and enrollment challenges - The company is early in its development efforts with only one product candidate, pociredir, in active clinical development after suspending the losmapimod program[178](index=178&type=chunk) - Clinical drug development is a lengthy, expensive process with an uncertain outcome. The Phase 3 trial for losmapimod did not meet its primary endpoint, leading to its discontinuation[183](index=183&type=chunk)[185](index=185&type=chunk) - In February 2023, the FDA placed a clinical hold on the IND for pociredir due to hematological malignancies in nonclinical studies. Although the hold was lifted in August 2023, future adverse events could halt or delay development[196](index=196&type=chunk) - The company may experience difficulties enrolling patients in clinical trials for rare diseases, which could delay regulatory approvals. The revised protocol for the pociredir trial has more stringent criteria, making enrollment challenging[190](index=190&type=chunk) [Risks Related to Commercialization of Product Candidates](index=62&type=section&id=Risks%20Related%20to%20the%20Commercialization%20of%20our%20Product%20Candidates) Product candidates may not achieve market acceptance due to substantial competition, lack of sales infrastructure, reliance on CMOs, and small patient populations - The company faces substantial competition from major pharmaceutical companies and recently approved gene therapies for SCD, such as CASGEVY and LYFGENIA[211](index=211&type=chunk)[213](index=213&type=chunk) - The company has no sales, marketing, or distribution infrastructure and establishing these capabilities is expensive and risky[206](index=206&type=chunk)[207](index=207&type=chunk) - The company relies on contract manufacturing organizations (CMOs) for clinical and potential commercial supply, which creates risks related to supply delays, quality issues, and regulatory compliance[218](index=218&type=chunk)[219](index=219&type=chunk) - The addressable patient populations for the company's target rare diseases are small, requiring it to capture a significant market share to achieve profitability[216](index=216&type=chunk) [Risks Related to Dependence on Third Parties](index=68&type=section&id=Risks%20Related%20to%20our%20Dependence%20on%20Third%20Parties) The company relies on third-party CROs and collaborators, which reduces control and introduces risks of performance failures, delays, and potential conflicts of interest - The company relies on third-party contract research organizations (CROs) to conduct its clinical trials, which reduces control over these activities and may lead to delays if these parties do not perform satisfactorily[237](index=237&type=chunk)[239](index=239&type=chunk) - Future collaborations with third parties for development or commercialization are subject to risks, including collaborators not performing as expected, delaying trials, or terminating agreements for convenience[241](index=241&type=chunk)[244](index=244&type=chunk) - If the company cannot establish or maintain successful collaborations, it may have to alter its development plans, which could require additional capital and expertise that may not be available[247](index=247&type=chunk)[249](index=249&type=chunk) [Risks Related to Intellectual Property](index=71&type=section&id=Risks%20Related%20to%20our%20Intellectual%20Property) Success depends on obtaining and enforcing patent protection, an uncertain and expensive process, with risks of litigation, license non-compliance, and trade secret breaches - The company's success depends on its ability to obtain and maintain patent protection for its technology and product candidates, which is an expensive and uncertain process[250](index=250&type=chunk)[251](index=251&type=chunk) - The company may be subject to litigation or other proceedings challenging its patent rights, which could result in invalidation or narrowing of its patents[254](index=254&type=chunk)[268](index=268&type=chunk) - Failure to comply with obligations in license agreements could lead to the loss of important intellectual property rights[282](index=282&type=chunk) - The company relies on trade secrets and confidentiality agreements, which may be breached, and protecting them can be difficult and costly[295](index=295&type=chunk) [Risks Related to Regulatory Approval and Legal Compliance](index=87&type=section&id=Risks%20Related%20to%20Regulatory%20Approval%20of%20our%20Product%20Candidates%20and%20Other%20Legal%20Compliance%20Matters) Marketing approval is expensive and uncertain, with ongoing regulatory oversight and complex healthcare laws posing risks of delays, rejections, and significant penalties - The marketing approval process is expensive, time-consuming, and uncertain, and the company may not obtain approvals for its product candidates[298](index=298&type=chunk)[301](index=301&type=chunk) - Even if orphan drug designation is obtained, it may not prevent competitors from getting approval for different drugs for the same condition or for the same drug if it is proven clinically superior[308](index=308&type=chunk)[311](index=311&type=chunk) - The company's relationships with healthcare providers and payors are subject to fraud and abuse, false claims, and other healthcare laws, with violations potentially leading to criminal sanctions and civil penalties[328](index=328&type=chunk)[330](index=330&type=chunk) - Compliance with global privacy and data security laws (e.g., GDPR, CCPA) is costly and complex, and failure to comply could result in significant fines and penalties[331](index=331&type=chunk)[336](index=336&type=chunk) [Risks Related to Employee Matters and Managing Growth](index=100&type=section&id=Risks%20Related%20to%20Employee%20Matters%20and%20Managing%20Growth) Success depends on retaining key personnel amid intense competition and recent transitions, with future growth requiring significant managerial and financial resources - The company is highly dependent on its key executives and scientific teams and has experienced recent transitions in several leadership roles, including CEO, CFO, and CSO[353](index=353&type=chunk)[354](index=354&type=chunk) - Competition for qualified personnel is intense, and the company's recent workforce reductions may make it a less attractive employer[354](index=354&type=chunk) - Future growth in operations would require significant expansion of managerial, operational, and financial systems, which may be difficult to manage effectively[356](index=356&type=chunk) [Risks Related to Common Stock](index=102&type=section&id=Risks%20Related%20to%20our%20Common%20Stock) The company's stock price is volatile, with significant control by principal stockholders, anti-takeover provisions, and no anticipated cash dividends - As of April 24, 2025, executive officers, directors, and principal stockholders beneficially owned approximately **72.6%** of the company's capital stock, giving them significant control[357](index=357&type=chunk) - The company's stock price has been and is likely to continue to be volatile due to factors such as clinical trial results, regulatory developments, and market conditions[363](index=363&type=chunk) - The company is a "smaller reporting company" and can rely on scaled disclosure requirements, which may make its common stock less attractive to some investors[369](index=369&type=chunk) - The company does not anticipate paying cash dividends in the foreseeable future; capital appreciation will be the sole source of gain for stockholders[374](index=374&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=106&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) This item is not applicable for the reporting period - Not applicable[377](index=377&type=chunk) [Defaults Upon Senior Securities](index=106&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) This item is not applicable for the reporting period - Not applicable[378](index=378&type=chunk) [Mine Safety Disclosures](index=106&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable for the reporting period - Not applicable[379](index=379&type=chunk) [Other Information](index=106&type=section&id=Item%205.%20Other%20Information) There is no other information to report for this period - None[380](index=380&type=chunk) [Exhibits](index=108&type=section&id=Item%206.%20Exhibits) This section lists exhibits filed with the Form 10-Q, including CEO and CFO certifications and Inline XBRL documents - Exhibits filed include CEO and CFO certifications pursuant to Sarbanes-Oxley Act Sections 302 and 906[382](index=382&type=chunk) - Inline XBRL documents are included as exhibits for interactive data filing[382](index=382&type=chunk)

Clinical Trials - Enrollment in the 12 mg dose cohort of the Phase 1b PIONEER trial for pociredir in sickle cell disease (SCD) is complete with 16 patients, and the 20 mg dose cohort has been initiated[2]. - Two abstracts accepted for presentation at the 2025 European Hematology Association Congress will highlight preclinical and clinical data related to pociredir[5]. - Pociredir has received FDA Fast Track designation and Orphan Drug Designation for the treatment of SCD[10]. Financial Performance - Cash, cash equivalents, and marketable securities as of March 31, 2025, were $226.6 million, down from $241.0 million as of December 31, 2024, reflecting a decrease of $14.4 million[12]. - Research and development expenses for Q1 2025 were $13.4 million, a decrease of 32.4% compared to $19.8 million in Q1 2024[12]. - General and administrative expenses for Q1 2025 were $7.0 million, down 30.9% from $10.1 million in Q1 2024[12]. - Net loss for Q1 2025 was $17.7 million, compared to a net loss of $26.9 million in Q1 2024, representing a 34.2% improvement[12]. - The total stockholders' equity as of March 31, 2025, was $228.5 million, down from $243.0 million as of December 31, 2024[15]. Future Plans - The company expects its current cash position to fund operations into at least 2027[7]. - The company plans to submit an investigational new drug application (IND) for Diamond-Blackfan anemia during Q4 2025[5].

Core Insights - Fulcrum Therapeutics has completed enrollment in the 12 mg dose cohort of the Phase 1b PIONEER trial for pociredir in sickle cell disease (SCD) and has initiated the 20 mg dose cohort [1][6] - The company plans to share data from the 12 mg dose cohort in early Q3 2025 and from the 20 mg dose cohort by the end of 2025 [2][5] Recent Business Highlights - The PIONEER trial shows strong engagement with 16 patients enrolled in the 12 mg cohort and adherence rates exceeding 90% [6] - Two abstracts related to pociredir have been accepted for presentation at the 2025 European Hematology Association Congress [6] - The company is advancing its program for inherited aplastic anemias and plans to submit an IND for Diamond-Blackfan anemia in Q4 2025 [6] Financial Results - As of March 31, 2025, Fulcrum had $226.6 million in cash, cash equivalents, and marketable securities, down from $241.0 million at the end of 2024 [5][14] - Research and development expenses for Q1 2025 were $13.4 million, a decrease from $19.8 million in Q1 2024, primarily due to the discontinuation of the losmapimod program [5][15] - General and administrative expenses decreased to $7.0 million in Q1 2025 from $10.1 million in Q1 2024, attributed to reduced employee compensation costs [5][15] - The net loss for Q1 2025 was $17.7 million, compared to a net loss of $26.9 million in Q1 2024 [5][15] Cash Position and Guidance - Fulcrum expects its current cash position to fund operations into at least 2027 [7]

Contact: CAMBRIDGE, Mass., April 24, 2025 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc. (the "Company") (Nasdaq: FULC), a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with genetically defined rare diseases, today announced that its first quarter 2025 financial results will be released on Thursday, May 1, 2025, before the U.S. financial markets open. Management will host a conference call and webcast at 8:00 a.m. ET to discuss the results an ...