Fulcrum Therapeutics, Inc.
For the period ended Sep 30, 2025. Filed Oct 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.
Sep 30, 2025 · Filed Oct 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 2025-06-30; filed 2025-07-29.
0000950170-25-099407
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of OperationsCurrent 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 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 149 previous paragraphs and 146 current paragraphs.
107 unchanged; 35 reworded; 4 added; 6 removed; 1 previous and 0 current paragraphs rearranged.
Tables are not compared: 8 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 (4)
Current report
$0.6 million of decreased employee compensation costs due to decreased headcount, including a $0.5 million decrease in stock-based compensation expense;
Current report
partially offset by $0.1 million of increased employee compensation costs.
Current report
Comparison of the Nine Months ended September 30, 2025 and 2024
Current report
$4.9 million of decreased employee compensation costs due to decreased headcount, including a $1.9 million decrease in stock-based compensation expense;
Removed paragraphs (6)
Previous report
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 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
Previous report
$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 report
Comparison of the Six Months ended June 30, 2025 and 2024
Previous report
Collaboration Revenue
Previous report
$4.3 million of decreased employee compensation costs due to decreased headcount, including a $1.5 million decrease in stock-based compensation expense;
Reworded paragraphs (35)
Previous wording
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 wording
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 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 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 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.
Previous wording
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 wording
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 wording
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 wording
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 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 inherited aplastic anemias, such as DBA, Shwachman-Diamond syndrome, and Fanconi anemia, and we plan to submit an IND for DBA during the fourth quarter of 2025.
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 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.
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 $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:
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 $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:
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 inherited aplastic anemias, such as DBA, 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, 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;
Previous 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.”
Current 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.”
Previous 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.
Current wording
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 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.
Current 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.
Previous 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:
Current 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:
Previous wording
$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 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
Previous wording
partially offset increased laboratory supplies costs of $0.3 million and $0.2 million of increased other costs.
Current wording
increased laboratory supplies costs of $0.1 million.
Previous 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:
Current 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:
Previous wording
$3.1 million of decreased professional services costs, primarily due to decreased commercial and legal costs;
Current wording
$0.8 million of decreased professional services costs, primarily due to decreased commercial costs; and
Previous wording
$0.3 million of decreased other costs.
Current wording
$0.1 million of decreased other costs;
Previous wording
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 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.
Previous wording
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 wording
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 wording
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 wording
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 wording
The following table summarizes our research and development expenses for the six months ended June 30, 2025 and 2024:
Current wording
The following table summarizes our research and development expenses for the nine months ended September 30, 2025 and 2024:
Previous wording
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 wording
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 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
Current wording
$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 wording
partially offset by $0.5 million of increased laboratory supplies costs and $0.2 million of increased other costs.
Current wording
partially offset by $0.6 million of increased laboratory supplies costs and $0.2 million of increased other costs.
Previous wording
The following table summarizes our general and administrative expenses for the six months ended June 30, 2025 and 2024:
Current wording
The following table summarizes our general and administrative expenses for the nine months ended September 30, 2025 and 2024:
Previous wording
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 wording
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 wording
$2.0 million of decreased professional services costs, primarily due to decreased commercial and legal costs;
Current wording
$3.8 million of decreased professional services costs, primarily due to decreased commercial and legal costs;
Previous wording
$2.7 million of decreased employee compensation costs due to decreased headcount, including a $0.8 million decrease in stock-based compensation expense;
Current wording
$2.6 million of decreased employee compensation costs due to decreased headcount, including a $0.8 million decrease in stock-based compensation expense;
Previous 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
Current 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
Previous wording
$0.6 million of decreased other costs.
Current wording
$0.7 million of decreased other costs.
Previous 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.
Current wording
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 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.
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 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.
Previous wording
The following table provides information regarding our cash flows for the six months ended June 30, 2025:
Current wording
The following table provides information regarding our cash flows for the nine months ended September 30, 2025:
Previous 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.
Current 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.
Previous 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.
Current 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.
Previous 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.
Current wording
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.
Rearranged previous paragraphs (1)
Previous report — wording carried elsewhere
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.