Fulcrum Therapeutics, Inc.
For the period ended Mar 31, 2026. Filed Apr 27, 2026.
View on SEC.govAbout this filing
A company's report for each of its first three quarters. The financial statements are not audited. It shows how the business has moved since the last annual report, and what management says changed.
Mar 31, 2026 · Filed Apr 27, 2026
FULC$3.70+0.5%Stored close · as of Nov 6, 2026
What changed in Management’s Discussion and Analysis?
Read the current filingPrevious report: 10-Q
Period ended 2025-09-30; filed 2025-10-29.
0001193125-25-254633
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of OperationsCurrent report: 10-Q
Period ended 2026-03-31; filed 2026-04-27.
0001193125-26-178814
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of OperationsThe baseline is this issuer’s latest earlier reporting period of the same form that was filed before the current report. A previous 10-Q is a different quarter, not a year-over-year comparison. Amendments are excluded.
Compared 146 previous paragraphs and 131 current paragraphs.
82 unchanged; 29 reworded; 20 added; 31 removed; 4 previous and 0 current paragraphs rearranged.
Tables are not compared: 8 previous and 5 current tables excluded. Dates, whitespace, punctuation and numbering changes are ignored; changes to financial figures remain significant.
A changed paragraph is not evidence that risk increased or decreased. An unchanged paragraph does not establish that risk stayed the same.
Added paragraphs (20)
Current report
In February 2026, we announced updated 20 mg cohort results from the PIONEER trial as of the December 23, 2025 data cut off date showing:
Current report
Indirect bilirubin decreased by 40% (vs. 37% at Week 12 in the 12 mg cohort)
Current report
Lactate dehydrogenase decreased by 34% (vs. 28% at Week 12 in the 12 mg cohort)
Current report
RBC distribution width decreased by 26% (vs. 27% at Week 12 in the 12 mg cohort)
Current report
Reticulocyte counts decreased by 42% (vs. 31% at Week 12 in the 12 mg cohort)
Current report
Mean hemoglobin increased by 1.1 g/dL at Week 12 (vs. 0.9 g/dL at Week 12 in the 12 mg cohort), increasing from a baseline of 7.3 g/dL to 8.4 g/dL.
Current report
Based on treating physician-documented medical records from the 6-12 months prior to enrollment, approximately 16 VOCs would have been expected during the 12-week treatment period. During the 12-week treatment period, six VOCs were reported. Seven of 12 patients (58%) reported no VOCs during the treatment period.
Current report
We are currently activating sites in an open-label, long-term dosing trial to evaluate longer-term safety and PD durability in patients who completed the PIONEER trial. We plan to provide details regarding the design of the next trial in the second quarter of 2026 following receipt of meeting minutes from our End-of-Phase meeting with the FDA. Pending feedback from the FDA, we plan to initiate a potential registration-enabling trial in the second half of 2026. We also plan to engage with the EMA in mid-2026 to obtain protocol assistance and feedback on the design of the next trial.
Current report
Based on results from IND-enabling studies, we have decided not to advance our program for bone marrow failure syndromes into clinical development and will focus our resources on advancing pociredir and our core benign hematology programs. In April 2026, we provided notice to terminate our license agreement with CAMP4.
Current report
Research and Development Expenses
Current report
General and Administrative Expenses
Current report
Other Income, Net
Current report
Research and Development Expenses
Current report
General and Administrative Expenses
Current report
$0.5 million of increased employee compensation costs due to increased headcount, including a $0.3 million increase in stock-based compensation expense;
Current report
Other Income, Net
Current report
Net cash used in operating activities was $18.8 million during the three months ended March 31, 2026 compared to $15.3 million during the three months ended March 31, 2025. The increase in net cash used in operating activities of $3.5 million was primarily due to an increase in net loss.
Current report
Net Cash Used in Investing Activities
Current report
Net Cash Used in Financing Activities
Current report
Net cash used in financing activities was $0.3 million during the three months ended March 31, 2026, which primarily consisted of offering costs paid in connection with the December 2025 public offering of our common stock and pre-funded warrants.
Removed paragraphs (31)
Previous report
In July 2025, we announced results from the 12 mg dose cohort of our Phase 1b trial of pociredir in SCD, following conclusion of the 12-week treatment period (n=16). Results are as follows:
Previous report
Decreased indirect bilirubin (mean decrease of 37%)
Previous report
Decreased lactate dehydrogenase (mean decrease of 28%)
Previous report
Decreased red cell distribution width (mean decrease of 27%), indicating a more uniform red blood cell population
Previous report
Decreased reticulocyte counts (mean decrease of 30%), indicating healthier bone marrow function
Previous report
Mean hemoglobin concentration increased by 0.9 g/dL at 12 weeks of treatment with pociredir, from a baseline of 7.8 g/dL to 8.7 g/dL. Together with the observed decrease in reticulocyte counts, the increase in total hemoglobin indicates that pociredir decreased red blood cell destruction and showed reductions in anemia.
Previous report
A trend of reduced VOC rates was observed during the study period (as assessed by VOCs reported as adverse events, or AEs), compared to cohort patients’ VOC frequency over the 6–12 months prior to enrollment. Eight of 16 patients (50%) reported no VOCs during the treatment period (12 weeks); three VOCs occurred during the follow-up period as of the June 26, 2025 data cut-off date.
Previous report
Additional observations after completion of the 4-week follow-up period for 12 mg dose cohort (ongoing) will be shared at a future medical meeting.
Previous report
This 12 mg data (n=16) relates to cohort 3b (incomplete prior 12 mg cohort (3a) conducted prior to clinical study hold not included in this analysis).
Previous report
We have completed enrollment in the 20 mg dose cohort with 12 patients (excluding 1 discontinuation that was previously disclosed), with greater than 90% rates of adherence to study drug to date, and we expect to provide clinical data from this cohort by the end of 2025. The mean and median baseline HbF levels of the 12 patients enrolled in the 20 mg dose cohort is 7.1% and 7.3%, respectively. We are also initiating an open label extension trial to allow patients to continue receiving pociredir after completing the PIONEER trial, enabling longer-term evaluation of safety and durability of response.
Previous report
advance clinical-stage product candidates into later stage trials;
Previous report
make any milestone payments to CAMP4 under our license agreement;
Previous report
In May 2024, we entered into a collaboration and license agreement with Sanofi, pursuant to which we granted Sanofi an exclusive license under certain intellectual property rights to commercialize losmapimod, an oral small molecule for the treatment of facioscapulohumeral muscular dystrophy, or FSHD, outside of the United States and received an upfront payment of $80.0 million.
Previous report
During the three and nine months ended September 30, 2025, we recorded zero and $1.0 million reduction in research and development expenses, respectively, in connection with global development activities for losmapimod. During the three and nine months ended September 30, 2025, we recognized no revenue associated with the Sanofi territory-specific manufacturing activities for losmapimod. As a result of the suspension of future development of losmapimod following our September 2024 announcement that there was no statistically significant difference between losmapimod and placebo on the primary endpoint in the Phase 3 REACH trial, Sanofi terminated the license. Accordingly, we will not recognize additional revenues under the Sanofi collaboration agreement.
Previous report
$0.6 million of decreased employee compensation costs due to decreased headcount, including a $0.5 million decrease in stock-based compensation expense;
Previous report
$0.8 million of decreased professional services costs, primarily due to decreased commercial costs; and
Previous report
$0.1 million of decreased other costs;
Previous report
Comparison of the Nine Months ended September 30, 2025 and 2024
Previous report
Collaboration Revenue
Previous report
Collaboration revenue decreased by $80.0 million from the nine months ended September 30, 2024 to the nine months ended September 30, 2025. The decrease was attributable to the recognition of $80.0 million of revenue associated with the upfront license payment received during the second quarter of 2024 under the now terminated Sanofi collaboration agreement.
Previous report
Research and development expense decreased by $11.0 million from $51.7 million for the nine months ended September 30, 2024 to $40.7 million for the nine months ended September 30, 2025. The decrease in research and development expense was primarily attributable to the following:
Previous report
$4.9 million of decreased employee compensation costs due to decreased headcount, including a $1.9 million decrease in stock-based compensation expense;
Previous report
General and administrative expenses decreased by $7.3 million from $28.7 million for the nine months ended September 30, 2024 to $21.4 million for the nine months ended September 30, 2025. The decrease in general and administrative expenses was primarily attributable to the following:
Previous report
$2.6 million of decreased employee compensation costs due to decreased headcount, including a $0.8 million decrease in stock-based compensation expense;
Previous report
$0.3 million of decreased facility costs as a result of the expiration of our lease agreement for office space at 125 Sidney Street; and
Previous report
$0.7 million of decreased other costs.
Previous report
Other income, net decreased by $1.8 million from $9.3 million for the nine months ended September 30, 2024 to $7.5 million for the nine months ended September 30, 2025. The decrease was primarily attributable to the expiration of our sublease agreement for office space at 125 Sidney Street as well as a decrease in our average cash, cash equivalents, and marketable securities balance.
Previous report
Net Cash (Used in) Provided by Operating Activities
Previous report
Net Cash Provided by Investing Activities
Previous report
Net Cash Provided by Financing Activities
Previous report
Net cash provided by financing activities was $0.4 million during the nine months ended September 30, 2025 compared to net cash provided by financing activities of $2.7 million during the nine months ended September 30, 2024. Net cash provided by financing activities during the nine months ended September 30, 2025 primarily consisted of net proceeds of $0.2 million from the issuance of common stock under our benefit plans. Net cash provided by financing activities during the nine months ended September 30, 2024 primarily consisted of net proceeds of $2.4 million from the issuance of common stock under our benefit plans.
Reworded paragraphs (29)
Previous wording
We are a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with genetically defined rare diseases in areas of high unmet medical need. Our clinical-stage product candidate, pociredir, is being developed for the potential treatment of sickle cell disease, or SCD.
Current wording
We are a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with genetically defined rare diseases in areas of high unmet medical need. Our lead product candidate, pociredir, is in clinical development for the potential treatment of SCD.
Previous wording
Mean absolute fetal hemoglobin, or HbF, increased by 8.6% at 12 weeks of treatment with pociredir, representing an increase from a baseline of 7.6% to 16.2%. Seven of 16 patients achieved absolute HbF levels greater than 20% after 12 weeks of treatment with pociredir. HbF levels of 20% are associated with approximately 90% of individual patients experiencing zero vaso-occlusive crises, or VOCs, per year, based on an analysis of real-world data we conducted that was presented at the 20th Annual Sickle Cell & Thalassaemia Conference (ASCAT) in October 2025.
Current wording
Mean absolute HbF increased by 12.2% at 12 weeks of treatment with pociredir (vs. 8.6% at Week 12 in the 12 mg cohort), increasing from a baseline of 7.1% to 19.3%. Seven of 12 patients (58%) achieved absolute HbF levels ≥20% at Week 12, and all patients demonstrated a clinically relevant HbF increase. HbF levels of 20% are associated with ~90% of patients experiencing zero VOCs per year, based on real-world data that we presented at the 20th Annual Sickle Cell & Thalassemia Conference in October 2025.
Previous wording
Proportion of F-cells (HbF-containing red blood cells) increased from a mean of 34% at baseline to 67% at 12 weeks of treatment (n=8), consistent with pan-cellular HbF induction (evenly distributed across red blood cells). F-cells are resistant to red blood cell sickling and hemolysis because of HbF-mediated inhibition of sickle hemoglobin polymerization. Consequently, a higher proportion of F-cells is associated with improved red blood cell health.
Current wording
The proportion of HbF-containing red blood cells, or F-cells, increased from a mean of 31% at baseline to 63% at Week 12 (n=10), indicating progression toward pan-cellular HbF induction (HbF distributed across a substantial proportion of RBCs). F-cells are more resistant to sickling and hemolysis because of HbF-mediated inhibition of HbS polymerization. Higher proportions of F-cells are associated with improved RBC health.
Previous wording
Markers of hemolysis and erythropoiesis improved with pociredir treatment at 12 weeks:
Current wording
Mean changes in markers of hemolysis and erythropoiesis improved during the 12-week treatment period:
Previous wording
Through the completion of the 12 mg dose cohort, pociredir has been dosed in 135 adults, including 76 subjects in multiple dose cohorts up to 12 weeks.
Current wording
Through the completion of the 20 mg dose cohort, pociredir has been dosed in 148 adults, including 89 subjects in multiple dose cohorts up to 12 weeks.
Previous wording
103 healthy subjects, including 44 who received pociredir from 10 to 14 days treatment duration
Current wording
103 healthy subjects, including 44 who received pociredir for 10 to 14 days treatment duration
Previous wording
32 SCD patients who received pociredir up to 12 weeks treatment duration
Current wording
45 SCD patients who received pociredir for up to 12 weeks treatment duration
Previous wording
The safety profile for pociredir observed in the 12 mg dose cohort was consistent with previously reported safety data. Pociredir was generally well-tolerated, with no drug-related serious adverse events and no discontinuations due to treatment-emergent adverse events through the completion of the 12 mg dose cohort. In addition, all treatment-related adverse events were Grade 1.
Current wording
The safety profile observed in the 20 mg dose cohort as of the December 23, 2025 data cut off date remained consistent with previously reported safety data. Pociredir was generally well-tolerated, with no treatment-related serious adverse events and no discontinuations due to treatment-related adverse events through the December 23, 2025 data cut off date.
Previous wording
In addition to our product candidates, we developed a discovery approach that we employ to systematically identify and validate cellular drug targets that can potentially modulate gene expression to treat known root causes of genetically defined rare diseases. Our discovery approach led to the identification of pociredir for SCD, as well as other drug candidates. We continue to advance our program for the potential treatment of bone marrow failure syndromes, such as DBA, 5q deletion syndrome, Shwachman-Diamond syndrome, and Fanconi anemia, and we plan to submit an IND during the fourth quarter of 2025. We also presented preclinical data for FTX-6274, an oral embryonic ectoderm development, or EED, inhibitor candidate, at the European Society for Medical Oncology (ESMO) Congress 2025, demonstrating robust efficacy in castration resistant prostate cancer models.
Current wording
In addition to our product candidates, we developed a discovery approach that we employ to systematically identify and validate cellular drug targets that can potentially modulate gene expression to treat known root causes of genetically defined rare diseases. Our discovery approach led to the identification of pociredir for SCD, as well as other drug candidates. We are applying our discovery capabilities to explore additional mechanisms that may complement pociredir’s mechanism of action to induce HbF for the potential treatment of SCD. We also presented preclinical data for FTX-6274, an oral EED inhibitor candidate, at the European Society for Medical Oncology (ESMO) Congress 2025, demonstrating tumor growth inhibition in castration resistant prostate cancer models.
Previous wording
We have incurred significant operating losses since our inception and we expect to continue to incur significant operating losses for the foreseeable future. Our ability to generate product revenue sufficient to achieve profitability, if ever, will depend heavily on the successful development and eventual commercialization of one or more of our product candidates. Our net loss was $54.5 million for the nine months ended September 30, 2025. Our net income was $6.8 million for the nine months ended September 30, 2024, primarily due to the $80.0 million of collaboration revenue associated with our now terminated collaboration and license agreement with Sanofi that we recognized during the second quarter of 2024. As of September 30, 2025, we had an accumulated deficit of $573.9 million. We expect our expenses and operating losses will increase over the next several years in connection with our ongoing activities, as we:
Current wording
We have incurred significant operating losses since our inception and we expect to continue to incur significant operating losses for the foreseeable future. Our ability to generate product revenue sufficient to achieve profitability, if ever, will depend heavily on the successful development and eventual commercialization of one or more of our product candidates. Our net losses were $18.9 million and $17.7 million for the three months ended March 31, 2026 and 2025, respectively. As of March 31, 2026, we had an accumulated deficit of $613.2 million. We expect our expenses and operating losses will increase over the next several years in connection with our ongoing activities, as we:
Previous wording
continue our clinical development of pociredir;
Current wording
continue our clinical development of pociredir and advance the program into a later stage trial;
Previous wording
pursue the discovery of drug targets for other genetically-defined rare diseases and the subsequent development of any resulting product candidates, including for the potential treatment of bone marrow failure syndromes, such as DBA, 5q deletion syndrome, Shwachman-Diamond syndrome, and Fanconi anemia under our license agreement with CAMP4;
Current wording
pursue the discovery of drug targets for other genetically-defined rare diseases and the subsequent development of any resulting product candidates;
Previous wording
acquire or in-license products, product candidates, technologies and/or data referencing rights, such as our agreement with CAMP4;
Current wording
acquire or in-license products, product candidates, technologies and/or data referencing rights and make any milestone payments thereunder;
Previous wording
As of September 30, 2025, we had $200.6 million in cash, cash equivalents, and marketable securities. We believe that our existing cash, cash equivalents, and marketable securities as of September 30, 2025 will enable us to fund our operating expenses and capital expenditure requirements into 2028. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. See “—Liquidity and Capital Resources.”
Current wording
As of March 31, 2026, we had $333.3 million in cash, cash equivalents, and marketable securities. We believe that our existing cash, cash equivalents, and marketable securities as of March 31, 2026 will enable us to fund our operating expenses and capital expenditure requirements into 2029. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. See “—Liquidity and Capital Resources.”
Previous wording
The following table summarizes our external research and development expenses by program for the three and nine months ended September 30, 2025 and 2024. Pre-development candidate expenses, unallocated expenses and internal research and development expenses are classified separately. Payments to or reimbursements from Sanofi related to global development activities are accounted for as an increase to or reduction of losmapimod external expenses.
Current wording
The following table summarizes our external research and development expenses by program for the three months ended March 31, 2026 and 2025. Pre-development candidate expenses, unallocated expenses and internal research and development expenses are classified separately.
Previous wording
the availability of raw materials and active pharmaceutical ingredient, or API, for use in production of our product candidates;
Current wording
the availability of raw materials and API for use in production of our product candidates;
Previous wording
Research and development expense decreased by $0.3 million from $14.6 million for the three months ended September 30, 2024 to $14.3 million for the three months ended September 30, 2025. The decrease in research and development expense was primarily attributable to the following:
Current wording
Research and development expense increased by $0.7 million from $13.4 million for the three months ended March 31, 2025 to $14.1 million for the three months ended March 31, 2026. The increase in research and development expense was primarily attributable to the following:
Previous wording
partially offset by $0.1 million of increased employee compensation costs.
Current wording
$1.3 million of increased employee compensation costs due to increased headcount, including a $0.4 million increase in stock-based compensation expense;
Previous wording
partially offset by $0.2 million of increased external research and development costs, primarily due to increased development costs associated with the advancement of the Phase 1b PIONEER trial of pociredir, partially offset by decreased costs due to the suspension of the losmapimod program; and
Current wording
$0.3 million of decreased external research and development costs, primarily due to the termination of the losmapimod program, partially offset by increased development costs associated with the advancement of the Phase 1b PIONEER trial of pociredir; and
Previous wording
increased laboratory supplies costs of $0.1 million.
Current wording
decreased laboratory supplies costs of $0.4 million.
Previous wording
General and administrative expenses decreased by $0.8 million from $8.4 million for the three months ended September 30, 2024 to $7.6 million for the three months ended September 30, 2025. The decrease in general and administrative expenses was primarily attributable to the following:
Current wording
General and administrative expenses increased by $1.1 million from $7.0 million for the three months ended March 31, 2025 to $8.1 million for the three months ended March 31, 2026. The increase in general and administrative expenses was primarily attributable to the following:
Previous wording
$3.8 million of decreased professional services costs, primarily due to decreased commercial and legal costs;
Current wording
$0.5 million of increased professional services costs, primarily due to higher legal costs; and
Previous wording
partially offset by $0.6 million of increased laboratory supplies costs and $0.2 million of increased other costs.
Current wording
$0.1 million of increased other costs.
Previous wording
Other income, net decreased by $1.1 million from $3.4 million for the three months ended September 30, 2024 to $2.3 million for the three months ended September 30, 2025. The decrease was primarily due to a decrease in our average cash, cash equivalents, and marketable securities balance.
Current wording
Other income, net increased by $0.6 million from $2.7 million for the three months ended March 31, 2025 to $3.3 million for the three months ended March 31, 2026. The increase was primarily due to an increase in our average cash, cash equivalents, and marketable securities balance.
Previous wording
We have incurred significant operating losses since our inception and expect to continue to incur significant operating losses for the foreseeable future and may never become profitable. We have not yet commercialized any of our product candidates, which are in various phases of preclinical and clinical development, and we do not expect to generate revenue from sales of any products for several years, if at all. As of September 30, 2025, we have funded our operations primarily with aggregate gross proceeds of $792.5 million from the sale of shares of our capital stock and from upfront payments received under our collaboration and license agreements. As of September 30, 2025, we had cash, cash equivalents, and marketable securities of $200.6 million.
Current wording
We have incurred significant operating losses since our inception and expect to continue to incur significant operating losses for the foreseeable future and may never become profitable. We have not yet commercialized any of our product candidates, which are in various phases of preclinical and clinical development, and we do not expect to generate revenue from sales of any products for several years, if at all. As of March 31, 2026, we have funded our operations primarily with aggregate gross proceeds of $967.5 million from the sale of shares of our capital stock and from upfront payments received under our collaboration and license agreements. As of March 31, 2026, we had cash, cash equivalents, and marketable securities of $333.3 million.
Previous wording
The following table provides information regarding our cash flows for the nine months ended September 30, 2025:
Current wording
The following table provides information regarding our cash flows for the three months ended March 31, 2026:
Previous wording
Net cash used in operating activities was $43.3 million during the nine months ended September 30, 2025 compared to net cash provided by operating activities of $14.5 million during the nine months ended September 30, 2024. Net cash used in operating activities during the nine months ended September 30, 2025 was primarily due to our net loss of $54.5 million for the nine months ended September 30, 2025. Net cash provided by operating activities during the nine months ended September 30, 2024 primarily consisted of the $80.0 million upfront license payment during the second quarter of 2024 under our former Sanofi collaboration agreement.
Current wording
Net Cash Used in Operating Activities
Previous wording
Net cash provided by investing activities was $31.8 million during the nine months ended September 30, 2025 compared to net cash provided by investing activities of $30.0 million during the nine months ended September 30, 2024. The decrease in net cash provided by investing activities of $1.8 million was primarily due a decrease in net maturities of marketable securities during the nine months ended September 30, 2025, as compared to the nine months ended September 30, 2024.
Current wording
Net cash used in investing activities was $128.2 million during the three months ended March 31, 2026 compared to $0.8 million during the three months ended March 31, 2025. The increase in net cash used in investing activities of $127.4 million was primarily due an increase in net purchases of marketable securities during the three months ended March 31, 2026, as compared to the three months ended March 31, 2025.
Previous wording
the scope, progress, costs and results of discovery research, preclinical development, laboratory testing and clinical trials for our current product candidates in additional indications or for any future product candidates that we may pursue, including under our license agreement with CAMP4;
Current wording
the scope, progress, costs and results of discovery research, preclinical development, laboratory testing and clinical trials for our current product candidates in additional indications or for any future product candidates that we may pursue;
Rearranged previous paragraphs (4)
Previous report — wording carried elsewhere
The following summarizes our results of operations for the nine months ended September 30, 2025 and 2024 along with the changes in those items in dollars:
Previous report — wording carried elsewhere
The following table summarizes our research and development expenses for the nine months ended September 30, 2025 and 2024:
Previous report — wording carried elsewhere
$6.8 million of decreased external research and development costs, primarily due to the suspension of the losmapimod program as well as $1.0 million of reimbursement from the global development cost sharing under our former collaboration with Sanofi for losmapimod, partially offset by increased development costs associated with the advancement of the Phase 1b PIONEER trial of pociredir; and
Previous report — wording carried elsewhere
The following table summarizes our general and administrative expenses for the nine months ended September 30, 2025 and 2024: