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(Mark One)☒ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year endedDecember 31,2024OR☐TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934FOR THE TRANSITION PERIOD FROMTOCommission File Number001-38978 FULCRUM THERAPEUTICS, INC. (Exact name of registrant as specified in its Charter) Delaware(State or other jurisdiction ofincorporation or organization)26 Landsdowne StreetCambridge,Massachusetts(Address of principal executive offices) Registrant’s telephone number, including area code:(617)651-8851 Securities registered pursuant to Section 12(b) of the Act: Securities registered pursuant to Section 12(g) of the Act: None Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. YES☐NO☒ Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or 15(d) of the Act. YES☐NO☒ Indicate by check mark whether the registrant: (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filingrequirements for the past 90 days.YES☒NO☐ Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 ofRegulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files).YES☒NO☐ Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, smaller reporting company, or anemerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growthcompany” in Rule 12b-2 of the Exchange Act. Large accelerated filer☐Non-accelerated filer☒Emerging growth company☐ Accelerated filer Smaller reporting company If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any newor revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.☐ Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internalcontrol over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm thatprepared or issued its audit report.☐If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements.☐Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b).☐ Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). YES☐NO☒ As of June 30, 2024, the last business day of the registrant’s most recently completed second fiscal quarter, the aggregate market value of the registrant’scommon stock held by non-affiliates of the registrant, based on the closing price of the shares of common stock on the Nasdaq Global Market on June 28,2024, was approximately $308,714,932. The number of shares of registrant’s common stock outstanding as of February 18, 2025 was53,979,306.DOCUMENTS INCORPORATED BY REFERENCE The registrant intends to file a definitive proxy statement pursuant to Regulation 14A relating to the 2024 Annual Meeting of Stockholders within 120 days of the end of the registrant’s fiscal year ended December 31, 2024. Portions of such definitive proxy statement are incorporated by reference into Part IIIof this Annual Report on Form 10-K to the extent stated herein. Table of Contents PART I Item 1.BusinessItem 1A.Risk FactorsItem 1B.Unresolved Staff CommentsItem 1C.CybersecurityItem 2.PropertiesItem 3.Legal ProceedingsItem 4.Mine Safety Disclosures PART II Item 5.Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of EquitySecurities79Item 6.Reserved79Item 7.Management’s Discussion and Analysis of Financial Condition and Results of Operations80Item 7A.Quantitative and Qualitative Disclosures About Market Risk91Item 8.Financial Statements and Supplementary Data91Item 9.Changes in and Disagreements With Accountants on Accounting and Financial Disclosure91Item 9A.Controls and Procedures91Item 9B.Other Information92Item 9C.Disclosure Regarding Foreign Jurisdictions that Prevent Inspections92 PART III Item 10.Directors, Executiv