― Pociredir Phase 1b PIONEER Trial Data in Sickle Cell Disease to be Presented and Published, Including 12 mg and 20 mg Cohorts ― ― Live and Webcast Investor Event with Fulcrum Leadership and Medical Experts will be Hosted Onsite on Sunday, December 7 ― CAMBRIDGE, Mass., Nov. 03, 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 di ...

Financial Data and Key Metrics Changes - Research and development expenses for Q3 2025 were $14.3 million, a decrease from $14.6 million in Q3 2024, primarily due to reduced employee compensation costs and decreased costs associated with a discontinued program [10] - General administrative expenses decreased to $7.6 million in Q3 2025 from $8.4 million in Q3 2024, mainly due to lower professional services costs [10] - The net loss for Q3 2025 was $19.6 million, compared to a net loss of $21.7 million in Q3 2024 [11] - Cash, cash equivalents, and marketable securities at the end of Q3 2025 totaled $200.6 million, down from $241 million at the end of 2024, primarily due to cash used for operating activities [11] - The company expects its existing cash resources to fund operations into 2028, allowing for substantial progress in clinical development [11] Business Line Data and Key Metrics Changes - The lead program, FTX-6058, for sickle cell disease showed promising results, including a dose-dependent increase in fetal hemoglobin and a reduction in vaso-occlusive crises [5][8] - Enrollment in the 20-milligram dose cohort was completed with 12 evaluable patients, and data will be presented at the upcoming ASH conference [6][7] - The company is also advancing programs for bone marrow failure syndromes and plans to submit an IND for these conditions in Q4 2025 [9] Market Data and Key Metrics Changes - Approximately 100,000 people in the U.S. and 7.7 million worldwide suffer from sickle cell disease, indicating a significant market need for effective treatments [4] - The company estimates that about 20% of the U.S. sickle cell disease population meets the inclusion-exclusion criteria for the Phase 1B Pioneer trial [35] Company Strategy and Development Direction - The company aims to position FTX-6058 as a best-in-class once-daily oral therapy for sickle cell disease, with plans for an open-label extension trial to evaluate long-term safety and efficacy [6][8] - The strategy includes engaging with the FDA for an end-of-Phase 1 meeting in Q1 2026 to discuss the next stages of clinical development [8] - The company is focused on expediting the drug's market entry to address the unmet needs of sickle cell disease patients globally [36] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the encouraging results from the 12-milligram cohort and the upcoming data readout at the ASH conference [12][13] - The management team highlighted the importance of generating additional safety data through the open-label extension study, which is expected to inform future discussions with the FDA [24][75] Other Important Information - The company has seen a high adherence rate of over 90% among patients in the study, indicating strong patient engagement with the treatment regimen [7] - The management team emphasized the need for a comprehensive approach to evaluating the drug's efficacy, considering multiple parameters such as fetal hemoglobin levels and reduction in vaso-occlusive crises [52] Q&A Session Summary Question: How does the company define a win in the context of the trial results? - Management believes they have already achieved a win with the 12-milligram cohort, showing robust increases in fetal hemoglobin and a favorable safety profile [16] Question: What are the expectations for the 20 mg dose cohort? - Management anticipates that the 20 mg cohort will outperform the 12 mg cohort based on previous healthy volunteer data [18] Question: What is the addressable market following the withdrawal of a competitor's product? - The company estimates that about 20% of the 100,000 U.S. patients with sickle cell disease currently meet the trial criteria, with plans to discuss potential market expansion with the FDA [35] Question: What metrics will be important for defining the activity of FTX-6058? - Management indicated that the totality of data, including fetal hemoglobin levels, pan-cellularity, and reduction in markers of hemolysis, will be crucial for evaluating the drug's efficacy [52] Question: What is the timeline for the final Pioneer data set? - The full data set is expected to be available in the first quarter of the following year [56]

Fulcrum Therapeutics (NasdaqGM:FULC) Q3 2025 Earnings Call October 29, 2025 08:00 AM ET Company ParticipantsAlan Musso - CFOIain Fraser - SVP of Clinical DevelopmentAlex Sapir - CEO and PresidentMatthew Biegler - Managing DirectorTazeen Ahmad - Managing DirectorConference Call ParticipantsCorinne Johnson - Equity Research AnalystAndres Maldonado - Senior Biotechology AnalystKristen Kluska - Equity Research AnalystEdward Tenthoff - Biotech Equity Research AnalystJoseph P. Schwartz - Senior Research AnalystLu ...

Financial Data and Key Metrics Changes - Research and development expenses for Q3 2025 were $14.3 million, a slight decrease from $14.6 million in Q3 2024, primarily due to reduced employee compensation costs and discontinued programs [10] - General administrative expenses decreased to $7.6 million in Q3 2025 from $8.4 million in Q3 2024, mainly due to lower professional services costs [10] - The net loss for Q3 2025 was $19.6 million, compared to a net loss of $21.7 million in Q3 2024 [11] - Cash, cash equivalents, and marketable securities at the end of Q3 2025 totaled $200.6 million, down from $241 million at the end of 2024, primarily due to cash used for operating activities [11] - The company expects its existing cash resources to fund operations into 2028, allowing for substantial progress in clinical development [11] Business Line Data and Key Metrics Changes - The lead program, FTX-6058, for sickle cell disease showed promising results, with a dose-dependent increase in fetal hemoglobin and a reduction in vaso-occlusive crises [4][8] - Enrollment in the 20-milligram dose cohort was completed, with data to be presented at the upcoming ASH conference [5][6] - The company is also advancing programs for bone marrow failure syndromes and plans to submit an IND for these conditions in Q4 2025 [9] Market Data and Key Metrics Changes - Approximately 100,000 people in the U.S. and 7.7 million worldwide suffer from sickle cell disease, indicating a significant market need for effective treatments [3] - The company estimates that about 20% of the U.S. sickle cell population meets the inclusion-exclusion criteria for the Phase 1B Pioneer trial [30] Company Strategy and Development Direction - The company aims to position FTX-6058 as a best-in-class once-daily oral therapy for sickle cell disease, with plans for an open-label extension trial to evaluate long-term safety and efficacy [5][21] - The strategy includes engaging with the FDA for an end-of-Phase 1 meeting in Q1 2026 to discuss the next stages of clinical development [8] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the encouraging results from the FTX-6058 program and the potential to provide differentiated therapeutic options for sickle cell disease patients [8][12] - The company is focused on expediting the drug's market entry to address the unmet needs of patients, especially following the withdrawal of other treatment options [31] Other Important Information - The company presented preclinical data for FTX-6274, an oral EED inhibitor, showing efficacy in prostate cancer models, indicating potential expansion beyond hematology programs [9] Q&A Session Summary Question: Insights on baseline characteristics of the 20 mg cohort - Management noted that the baseline characteristics of the 20 mg cohort are similar to previous cohorts, and they are analyzing the data to determine the dose response [14][15] Question: Interest in the open-label extension study - The decision to initiate the open-label extension study was influenced by patient and investigator feedback, allowing continued treatment for patients post-trial [20][21] Question: Addressable market assumptions - The company estimates that about 20% of the 100,000 U.S. patients with sickle cell disease meet the trial criteria, and they aim to expand treatment access [30][31] Question: Safety follow-up requirements from the FDA - The FDA has not specified numerical criteria for safety follow-up, but ongoing favorable safety profiles will be crucial for future discussions [64] Question: Future clinical plans beyond Phase 1B - The next study design will depend on discussions with regulators and may include a registrational trial focused on VOC reduction as a primary endpoint [65][66]

Financial Performance - Collaboration revenue for the three months ended September 30, 2025, was $0, compared to $80,000,000 for the same period in 2024, indicating a significant drop[19] - Net loss for the three months ended September 30, 2025, was $19,595,000, compared to a net loss of $21,696,000 for the same period in 2024, showing an improvement of about 9.7%[19] - For the nine months ended September 30, 2025, the company reported a net loss of $54.546 million compared to a net income of $6.843 million in the same period of 2024[25] - The net loss for the nine months ended September 30, 2025, was $54.5 million, compared to a net income of $6.8 million for the same period in 2024, primarily due to $80.0 million of collaboration revenue recognized in 2024[101] - The company has incurred significant operating losses since inception and expects to continue incurring losses over the next several years[156] Assets and Liabilities - Total current assets decreased from $249,923,000 as of December 31, 2024, to $205,863,000 as of September 30, 2025, a decline of approximately 17.7%[16] - Cash and cash equivalents decreased from $58,212,000 as of December 31, 2024, to $47,078,000 as of September 30, 2025, a decrease of approximately 19.1%[16] - Total liabilities decreased from $17,684,000 as of December 31, 2024, to $16,492,000 as of September 30, 2025, a reduction of about 6.7%[16] - Stockholders' equity decreased from $243,034,000 as of December 31, 2024, to $198,366,000 as of September 30, 2025, a decline of approximately 18.4%[16] - As of September 30, 2025, total cash equivalents and marketable securities amounted to $200,404,000, a decrease from $241,021,000 as of December 31, 2024[43][44] Operating Expenses - Total operating expenses for the nine months ended September 30, 2025, were $62,076,000, down from $82,468,000 in the same period of 2024, representing a reduction of approximately 24.7%[19] - General and administrative expenses for the nine months ended September 30, 2025, were $21,389,000, down from $28,732,000 in the same period of 2024, a decrease of approximately 25.6%[19] - The company recorded total operating expenses of $21,858,000 for the three months ended September 30, 2025, down from $25,126,000 in the same period of 2024[94] - Total operating expenses decreased by $20.4 million from $82.5 million in the nine months ended September 30, 2024 to $62.1 million in the same period in 2025[127] Research and Development - Research and development expenses for the three months ended September 30, 2025, were $14,296,000, slightly down from $14,639,000 in the same period of 2024[19] - Research and development expenses fell by $11.0 million from $51.7 million in the nine months ended September 30, 2024 to $40.7 million in the same period in 2025, mainly due to decreased external research and employee compensation costs[131] - External research and development expenses for pociredir were $5.4 million for the three months ended September 30, 2025, compared to $2.2 million in the same period in 2024[113] Cash Flow - Net cash used in operating activities was $43.267 million for the nine months ended September 30, 2025, a significant decrease from $14.543 million provided in the same period of 2024[25] - The company expects its cash and marketable securities to be sufficient to fund operating expenses for at least 12 months from the date of the financial statements[32] - The company had $200.6 million in cash, cash equivalents, and marketable securities as of September 30, 2025, which is expected to fund operations into 2028[104] Stock and Equity - Weighted-average common shares outstanding, basic, increased from 62,409,000 for the three months ended September 30, 2024, to 62,597,000 for the same period in 2025[19] - The company has reserved 28,952,871 shares of common stock for future issuance as of September 30, 2025, an increase from 26,673,185 shares as of December 31, 2024[52] - The total number of outstanding stock options increased to 11,870,785 with a weighted average exercise price of $6.57[61] Collaboration Agreements - The Company entered into a collaboration and license agreement with Sanofi in May 2024, which included an upfront payment of $80.0 million, but was terminated in April 2025[69][70] - The Company recognized no revenue associated with the Sanofi Agreement during the nine months ended September 30, 2025[74] - Collaboration revenue dropped by $80.0 million from $80.0 million in the nine months ended September 30, 2024 to $0 in the same period in 2025, due to the termination of the Sanofi collaboration agreement[128] Clinical Development and Risks - The successful development of product candidates remains uncertain, with no revenue expected from product sales for several years[105] - The company is still in the early stages of product development and has not completed development of any product candidates[156] - The company may face limitations on utilizing its net operating losses and research and development tax credit carryforwards due to an ownership change deemed to have occurred on September 12, 2024[176] - The company is subject to risks related to the lengthy and expensive clinical drug development process, which may not yield successful outcomes[184] - The company may need to conduct additional clinical trials or testing if initial results are not positive, which could delay marketing approvals[189] Market and Competition - Competition in the pharmaceutical industry is substantial, with major companies potentially developing products more successfully or rapidly[212] - Recent FDA approvals for competitive products, such as CASGEVY and LYFGENIA, could impact the company's market position[214] - The company may need to price its products at a significant premium over generic alternatives, affecting market acceptance and sales[214]

Financial Performance - As of September 30, 2025, cash, cash equivalents, and marketable securities totaled $200.6 million, down from $241.0 million as of December 31, 2024, reflecting a decrease of $40.4 million primarily due to operating activities [10]. - The net loss for Q3 2025 was $19.6 million, compared to a net loss of $21.7 million in Q3 2024, indicating an improvement in financial performance [10]. - The company expects its current cash position to fund operations into 2028, ensuring financial stability for ongoing projects [6]. Research and Development - Research and development expenses for Q3 2025 were $14.3 million, slightly down from $14.6 million in Q3 2024, attributed to reduced costs from the discontinuation of the losmapimod program [10]. - Fulcrum plans to submit an investigational new drug application (IND) for the treatment of bone marrow failure syndromes in Q4 2025 [4]. - Fulcrum aims to present additional clinical data at the 67th American Society of Hematology Congress in December 2025 [4]. Clinical Trials - The Phase 1b PIONEER trial of pociredir showed a clinically meaningful increase in fetal hemoglobin (HbF) levels, with no drug-related serious adverse events reported [4]. - Enrollment in the 20 mg dose cohort of the PIONEER trial was completed, achieving over 90% adherence to the study drug [4]. Regulatory Designations - Pociredir has received FDA Fast Track designation and Orphan Drug Designation for the treatment of sickle cell disease [8]. Administrative Expenses - General and administrative expenses decreased to $7.6 million in Q3 2025 from $8.4 million in Q3 2024, primarily due to lower professional services costs [10].

Core Insights - Fulcrum Therapeutics announced positive results from the 12 mg dose cohort of the Phase 1b PIONEER trial for pociredir in sickle cell disease (SCD), indicating potential improvements in patient outcomes [1][2][5] - The company completed enrollment in the 20 mg dose cohort and expects to provide data by the end of 2025 [1][2] - As of Q3 2025, Fulcrum reported $200.6 million in cash and equivalents, ensuring operational funding into 2028 [1][7] Recent Business Highlights - The 12 mg dose cohort results showed a dose-dependent increase in fetal hemoglobin (HbF), improvements in hemolysis markers, and trends in reducing vaso-occlusive crises (VOC) [5] - Pociredir was well-tolerated with no serious adverse events reported during the 12-week treatment period [5][9] - An open-label extension trial for pociredir is being initiated to evaluate long-term safety and response durability [5] - Fulcrum presented real-world data correlating increased HbF levels with reduced VOC rates at the ASCAT Conference [5] Financial Results for Q3 2025 - Cash, cash equivalents, and marketable securities decreased from $241.0 million at the end of 2024 to $200.6 million [6][15] - Research and development expenses were $14.3 million, slightly down from $14.6 million in Q3 2024 [6][12] - General and administrative expenses decreased to $7.6 million from $8.4 million in the same period last year [12] - The net loss for Q3 2025 was $19.6 million, an improvement from a net loss of $21.7 million in Q3 2024 [12][17]

Core Viewpoint - Fulcrum Therapeutics, Inc. is set to release its third quarter 2025 financial results on October 29, 2025, and will host a conference call to discuss these results and recent corporate developments [1]. Company Overview - Fulcrum Therapeutics is a clinical-stage biopharmaceutical company focused on developing small molecules aimed at improving the lives of patients with genetically defined rare diseases [3]. - The company's lead clinical program is pociredir, a small molecule designed to increase fetal hemoglobin (HbF) expression for treating sickle cell disease (SCD) [3]. - Fulcrum employs proprietary technology to identify drug targets that can modulate gene expression, addressing the root cause of gene mis-expression [3]. Conference Call Details - Individuals interested in the conference call can register online to receive dial-in details and a unique PIN for access [2]. - An audio webcast will be available through the Investor Relations section of the company's website, with an archived replay accessible after the live event [2].

Core Insights - Fulcrum Therapeutics is presenting preclinical data for FTX-6274, an EED inhibitor, which shows potential for treating castration-resistant prostate cancer at the ESMO Congress 2025 [1][2] - The company is exploring strategic partnerships to advance FTX-6274 for oncology indications, given its focus on non-malignant hematologic diseases [2] 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 [3] - The company's lead clinical program is pociredir, designed to increase fetal hemoglobin expression for treating sickle cell disease [3] - Fulcrum employs proprietary technology to identify drug targets that can modulate gene expression to address the root causes of gene mis-expression [3]

Core Viewpoint - Fulcrum Therapeutics, a clinical-stage biopharmaceutical company, has granted stock options to new employees as part of its 2022 Inducement Stock Incentive Plan to attract talent in the field of genetically defined rare diseases [1][2]. Group 1: Stock Options Grant - Fulcrum granted a total of 47,450 stock options to new employees at an exercise price of $9.50 per share, which is the closing price on the grant effective date of October 6, 2025 [2]. - Each stock option has a ten-year term and vests over four years, with 25% vesting on the first anniversary of the employee's start date and an additional 6.25% vesting quarterly over the following twelve quarters [2]. Group 2: Company Overview - Fulcrum Therapeutics focuses on developing small molecules aimed at improving the lives of patients with genetically defined rare diseases, particularly in areas with high unmet medical needs [3]. - The company's lead clinical program is pociredir, designed to increase fetal hemoglobin expression for treating sickle cell disease, utilizing proprietary technology to target gene expression [3].