Fulcrum Therapeutics, Inc.
For the period ended Jun 30, 2025. Filed Jul 29, 2025.
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.
Jun 30, 2025 · Filed Jul 29, 2025
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 2025-03-31; filed 2025-05-01.
0000950170-25-061442
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of OperationsCurrent report: 10-Q
Period ended 2025-06-30; filed 2025-07-29.
0000950170-25-099407
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 115 previous paragraphs and 149 current paragraphs.
86 unchanged; 21 reworded; 34 added; 8 removed; 0 previous and 8 current paragraphs rearranged.
Tables are not compared: 5 previous and 8 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 (34)
Current report
In July 2025, we announced results from the 12 mg dose cohort of our Phase 1b trial, following conclusion of the 12-week treatment period (n=16). Results are as follows:
Current report
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 a recent analysis of real-world data we conducted, which has been accepted for publication at the 20th Annual Sickle Cell & Thalassaemia Conference (ASCAT), to be held in London, United Kingdom, October 1-4, 2025.
Current report
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 report
Markers of hemolysis and erythropoiesis improved with pociredir treatment at 12 weeks:
Current report
o
Current report
Decreased indirect bilirubin (mean decrease of 37%)
Current report
o
Current report
Decreased lactate dehydrogenase (mean decrease of 28%)
Current report
o
Current report
Decreased red cell distribution width (mean decrease of 27%), indicating a more uniform red blood cell population
Current report
o
Current report
Decreased reticulocyte counts (mean decrease of 30%), indicating healthier bone marrow function
Current 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.
Current 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.
Current report
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 report
o
Current report
103 healthy subjects, including 44 who received pociredir from 10 to 14 days treatment duration
Current report
o
Current report
32 SCD patients who received pociredir up to 12 weeks treatment duration
Current report
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 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.
Current report
The 12 mg data (n=16) discussed in this report relates to cohort 3b (incomplete prior 12 mg cohort (3a) conducted prior to study hold not included in this analysis).
Current report
Collaboration Revenue
Current report
Collaboration revenue decreased by $80.0 million from the three months ended June 30, 2024 to the three months ended June 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 Sanofi collaboration agreement.
Current report
$2.7 million of decreased employee compensation costs due to decreased headcount, including a $1.1 million decrease in stock-based compensation expense; and
Current report
partially offset increased laboratory supplies costs of $0.3 million and $0.2 million of increased other costs.
Current report
Other income, net decreased by $0.4 million from $2.9 million for the three months ended June 30, 2024 to $2.5 million for the three months ended June 30, 2025. The decrease was primarily due to decreased interest income.
Current report
Comparison of the Six Months ended June 30, 2025 and 2024
Current report
Collaboration Revenue
Current report
Collaboration revenue decreased by $80.0 million from the six months ended June 30, 2024 to the six months ended June 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 Sanofi collaboration agreement.
Current report
Research and development expense decreased by $10.6 million from $37.0 million for the six months ended June 30, 2024 to $26.4 million for the six months ended June 30, 2025. The decrease in research and development expense was primarily attributable to the following:
Current report
$4.3 million of decreased employee compensation costs due to decreased headcount, including a $1.5 million decrease in stock-based compensation expense;
Current report
General and administrative expenses decreased by $6.5 million from $20.3 million for the six months ended June 30, 2024 to $13.8 million for the six months ended June 30, 2025. The decrease in general and administrative expenses was primarily attributable to the following:
Current report
$2.7 million of decreased employee compensation costs due to decreased headcount, including a $0.8 million decrease in stock-based compensation expense;
Removed paragraphs (8)
Previous report
Research and Development Expenses
Previous report
General and Administrative Expenses
Previous report
Other Income, Net
Previous report
Research and Development Expenses
Previous report
$1.7 million of decreased employee compensation costs due to decreased headcount, including a $0.3 million decrease in stock-based compensation expense;
Previous report
General and Administrative Expenses
Previous report
Other Income, Net
Previous report
Net cash used in operating activities was $15.3 million during the three months ended March 31, 2025 compared to $25.3 million during the three months ended March 31, 2024. The decrease in net cash used in operating activities of $10.0 million was primarily due to a decrease in our net loss, including as a result of decreased external research and development costs due to the suspension of the losmapimod program as well as decreased employee compensation costs.
Reworded paragraphs (21)
Previous wording
In January 2023, we announced interim data from our Phase 1b clinical trial of pociredir in SCD. We completed enrollment in the 6 mg and 2 mg once daily dose cohorts, and do not plan to enroll additional subjects in these cohorts. Although we commenced enrollment in the 12 mg dose cohort, in February 2023 the FDA placed a full clinical hold on the investigational new drug, or IND, application for pociredir for SCD, which was lifted in August 2023. Following the clinical hold, we amended the protocol to revise the inclusion and exclusion criteria for the Phase 1b clinical trial to target subjects with higher disease severity. We reinitiated the Phase 1b clinical trial at the 12 mg once daily dose level in the fourth quarter of 2023. Subjects are evaluated over a 12-week treatment period. We completed enrollment in the 12 mg dose cohort (with 16 patients), and we have initiated the 20 mg once daily dose cohort. We expect to provide clinical data from the 12 mg dose cohort in early third quarter 2025 and from the 20 mg dose cohort by the end of 2025. The median and mean baseline fetal hemoglobin, or HbF, levels of the 16 patients enrolled in the 12 mg dose cohort is 7.7% and 7.6%, respectively. No discontinuations have occurred to date in the 12 mg dose cohort, and we have observed greater than 90% adherence rates (patients took the prescribed dose at the prescribed time) to study drug for the patients in this 12 mg dose cohort.
Current wording
In January 2023, we announced interim data from the 6 mg and 2 mg once daily dose cohorts of our Phase 1b clinical trial of pociredir in SCD. Although we commenced enrollment in the 12 mg dose cohort, in February 2023 the FDA placed a full clinical hold on the investigational new drug, or IND, application for pociredir for SCD, which was lifted in August 2023. Following the clinical hold, we amended the protocol to revise the inclusion and exclusion criteria for the Phase 1b clinical trial to target subjects with higher disease severity. We reinitiated the Phase 1b clinical trial at the 12 mg once daily dose level in the fourth quarter of 2023.
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 $17.7 million for the three months ended March 31, 2025. Our net loss was $26.9 million for the three months ended March 31, 2024. As of March 31, 2025, we had an accumulated deficit of $537.1 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 loss was $35.0 million for the six months ended June 30, 2025. Our net income was $28.5 million for the six months ended June 30, 2024, primarily due to the $80.0 million of collaboration revenue associated with our collaboration and license agreement with Sanofi that we recognized during the second quarter of 2024. As of June 30, 2025, we had an accumulated deficit of $554.3 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
As of March 31, 2025, we had $226.6 million in cash, cash equivalents, and marketable securities. We believe that our existing cash, cash equivalents, and marketable securities as of March 31, 2025 will enable us to fund our operating expenses and capital expenditure requirements into at least 2027. 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 June 30, 2025, we had $214.1 million in cash, cash equivalents, and marketable securities. We believe that our existing cash, cash equivalents, and marketable securities as of June 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.”
Previous wording
During the three months ended March 31, 2025, we recorded a $1.0 million reduction in research and development expenses in connection with global development activities for losmapimod. During the three months ended March 31, 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 do not expect to recognize additional revenues under the Sanofi collaboration agreement.
Current wording
During the three and six months ended June 30, 2025, we recorded a less than $0.1 million and $1.0 million reduction in research and development expenses, respectively, in connection with global development activities for losmapimod. During the three and six months ended June 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 wording
The following table summarizes our external research and development expenses by program for the three months ended March 31, 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 and six months ended June 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.
Previous wording
Research and development expense decreased by $6.4 million from $19.8 million for the three months ended March 31, 2024 to $13.4 million for the three months ended March 31, 2025. The decrease in research and development expense was primarily attributable to the following:
Current wording
Research and development expense decreased by $4.3 million from $17.3 million for the three months ended June 30, 2024 to $13.0 million for the three months ended June 30, 2025. The decrease in research and development expense was primarily attributable to the following:
Previous wording
General and administrative expenses decreased by $3.1 million from $10.1 million for the three months ended March 31, 2024 to $7.0 million for the three months ended March 31, 2025. The decrease in general and administrative expenses was primarily attributable to the following:
Current wording
General and administrative expenses decreased by $3.4 million from $10.2 million for the three months ended June 30, 2024 to $6.8 million for the three months ended June 30, 2025. The decrease in general and administrative expenses was primarily attributable to the following:
Previous wording
$1.1 million of decreased professional services costs, primarily due to decreased commercial and legal costs.
Current wording
$2.0 million of decreased professional services costs, primarily due to decreased commercial and legal costs;
Previous wording
$1.4 million of decreased employee compensation costs due to decreased headcount, including a $0.4 million decrease in stock-based compensation expense;
Current wording
$1.2 million of decreased employee compensation costs due to decreased headcount, including a $0.4 million decrease in stock-based compensation expense; and
Previous wording
$0.2 million of decreased other costs.
Current wording
$0.3 million of decreased other costs.
Previous wording
$4.9 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 collaboration with Sanofi for losmapimod, partially offset by increased development costs associated with the advancement of the Phase 1b PIONEER trial of pociredir;
Current wording
$7.0 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 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 wording
partially offset by $0.2 million of increased laboratory supplies costs.
Current wording
partially offset by $0.5 million of increased laboratory supplies costs and $0.2 million of increased other costs.
Previous wording
$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
Current wording
$0.2 million of decreased facility costs as a result of the expiration of our lease agreement for office space at 125 Sidney Street; and
Previous wording
Other income, net decreased by $0.3 million from $3.0 million for the three months ended March 31, 2024 to $2.7 million for the three months ended March 31, 2025. The decrease was primarily attributable to the expiration of our sublease agreement for office space at 125 Sidney Street.
Current wording
Other income, net decreased by $0.6 million from $5.9 million for the six months ended June 30, 2024 to $5.3 million for the six months ended June 30, 2025. The decrease was primarily attributable to the expiration of our sublease agreement for office space at 125 Sidney Street as well as due to decreased interest income.
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 March 31, 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 March 31, 2025, we had cash, cash equivalents, and marketable securities of $226.6 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 June 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 June 30, 2025, we had cash, cash equivalents, and marketable securities of $214.1 million.
Previous wording
The following table provides information regarding our cash flows for the three months ended March 31, 2025:
Current wording
The following table provides information regarding our cash flows for the six months ended June 30, 2025:
Previous wording
Net Cash (Used in) Provided by Investing Activities
Current wording
Net Cash (Used in) Provided by Operating Activities
Previous wording
Net Cash Used in Operating Activities
Current wording
Net cash used in operating activities was $29.1 million during the six months ended June 30, 2025 compared to net cash provided by operating activities of $33.6 million during the six months ended June 30, 2024. Net cash used in operating activities during the six months ended June 30, 2025 was primarily due to our net loss of $35.0 for the six months ended June 30, 2025. Net cash provided by operating activities during the six months ended June 30, 2024 primarily consisted of the $80.0 million upfront license payment during the second quarter of 2024 under the Sanofi collaboration agreement.
Previous wording
Net cash used in investing activities was $0.8 million during the three months ended March 31, 2025 compared to net cash provided by investing activities of $38.1 million during the three months ended March 31, 2024. The increase in net cash used in investing activities of $38.9 million was primarily due to net purchases of marketable securities during the three months ended March 31, 2025, as compared to net maturities of marketable securities during the three months ended March 31, 2024.
Current wording
Net cash provided by investing activities was $13.2 million during the six months ended June 30, 2025 compared to net cash provided by investing activities of $25.6 million during the six months ended June 30, 2024. The decrease in net cash provided by investing activities of $12.4 million was primarily due a decrease in net maturities of marketable securities during the six months ended June 30, 2025, as compared to the six months ended June 30, 2024.
Previous wording
Net cash provided by financing activities was zero during the three months ended March 31, 2025 compared to net cash provided by financing activities of $1.7 million during the three months ended March 31, 2024. Net cash provided by financing activities during the three months ended March 31, 2024 primarily consisted of net proceeds of $1.7 million from the issuance of common stock under our benefit plans.
Current wording
Net cash provided by financing activities was $0.3 million during the six months ended June 30, 2025 compared to net cash provided by financing activities of $2.0 million during the six months ended June 30, 2024. Net cash provided by financing activities during the six months ended June 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 six months ended June 30, 2024 primarily consisted of net proceeds of $1.8 million from the issuance of common stock under our benefit plans.
Previous wording
Based on our current operating plan, we believe that our existing cash, cash equivalents, and marketable securities as of March 31, 2025 will enable us to fund our operating expenses and capital expenditure requirements into at least 2027. However, we have based this estimate on assumptions that may prove to be wrong and we could exhaust our capital resources sooner than we expect.
Current wording
Based on our current operating plan, we believe that our existing cash, cash equivalents, and marketable securities as of June 30, 2025 will enable us to fund our operating expenses and capital expenditure requirements into 2028. However, we have based this estimate on assumptions that may prove to be wrong and we could exhaust our capital resources sooner than we expect.
Rearranged current paragraphs (8)
Current report — wording carried from elsewhere
The 20 mg once daily dose cohort is ongoing, and we expect to provide clinical data from this cohort by the end of 2025.
Current report — wording carried from elsewhere
$2.1 million of decreased external research and development costs, primarily due to the suspension of the losmapimod program, partially offset by increased development costs associated with the advancement of the Phase 1b PIONEER trial of pociredir;
Current report — wording carried from elsewhere
The following summarizes our results of operations for the six months ended June 30, 2025 and 2024 along with the changes in those items in dollars:
Current report — wording carried from elsewhere
The following table summarizes our research and development expenses for the six months ended June 30, 2025 and 2024:
Current report — wording carried from elsewhere
The following table summarizes our general and administrative expenses for the six months ended June 30, 2025 and 2024:
Current report — wording carried from elsewhere
$3.1 million of decreased professional services costs, primarily due to decreased commercial and legal costs;
Current report — wording carried from elsewhere
$0.6 million of decreased other costs.
Current report — wording carried from elsewhere
Net Cash Provided by Investing Activities