Fulcrum Therapeutics Inc美股招股说明书(2025-12-11版)

11,851,853 Shares of Common Stock Pre-Funded Warrants to Purchase 1,111,193 Shares of Common Stock We are offering 11,851,853 of shares of our common stock pursuant to this prospectus supplement and accompanying prospectus, and, in lieu ofcommon stock, pre-funded warrants to purchase 1,111,193 shares of our common stock, to certain investors. Our common stock is traded on The Nasdaq Global Market under the symbol “FULC.” On December9, 2025, the last reported sale price per share of our The purchase price of each pre-funded warrant will equal the price per share at which shares of our common stock are being sold to the public in thisoffering, minus $0.001, which is the exercise price of each pre-funded warrant. The pre-funded warrants do not expire, and each pre-funded warrant willbe exercisable at any time after the date of issuance, subject to an ownership limitation and in some cases clearance under the Hart-Scott- RodinoAntitrust Improvements Act of 1976, as amended, or the HSR Act. This prospectus supplement also relates to the offering of the shares of our commonstock issuable upon the exercise of such pre-funded warrants. There is no established public trading market for the pre-funded warrants, and we do not expect a market to develop. We do not intend to list the pre-funded warrants on The Nasdaq Global Market or any other national securities exchange or nationally recognized trading system. Investing in our securities involves a high degree of risk. You should carefully consider the risks and uncertainties described under theheading “RiskFactors” on pageS-10of this prospectus supplement and in the accompanying prospectus, as well as those contained in theother documents that are incorporated by reference into this prospectus supplement, the accompanying prospectus and any related freewriting prospectus. You should carefully read this entire prospectus supplement and the accompanying prospectus, including any informationincorporated by reference hereto and thereto, before deciding whether to purchase our securities. (1)See “Underwriting” beginning on page S-25 of this prospectus supplement for additional information regarding underwriting compensation. The underwriters may also exercise their option to purchase up to an additional 1,944,456 shares of common stock from us, at the public offering price,less the underwriting discounts and commissions, for 30 days after the date of this prospectus supplement. If the underwriters exercise the option in full,the total underwriting discounts and commissions payable by us will be $12.1million, and the total proceeds to us, before expenses, will be $189.2millionin each case, assuming no exercise of any pre-funded warrants offered or sold by us. See “Underwriting” for more information. Neither the U.S. Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securitiesor passed upon the adequacy or accuracy of this prospectus supplement or the accompanying prospectus. Any representation to the contraryis a criminal offense. The shares of common stock and the pre-funded warrants will be ready for delivery against payment therefor on or about December 11, 2025. Book-Running Managers J.P.Morgan LeerinkPartners Cantor Oppenheimer& Co. Truist Securities Prospectus Supplement dated December 10, 2025 Table of Contents TABLE OF CONTENTSPROSPECTUS SUPPLEMENT ABOUT THIS PROSPECTUS SUPPLEMENTS-1CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS AND INDUSTRY DATAS-2PROSPECTUS SUPPLEMENT SUMMARYS-4THE OFFERINGS-7RISK FACTORSS-10DESCRIPTION OF PRE-FUNDED WARRANTSS-13USE OF PROCEEDSS-15DILUTIONS-16MATERIAL U.S. FEDERAL INCOME AND ESTATE TAX CONSIDERATIONS FOR NON-U.S. HOLDERS OF COMMON STOCKAND PRE-FUNDED WARRANTSS-18UNDERWRITINGS-25LEGAL MATTERSS-36EXPERTSS-36WHERE YOU CAN FIND MORE INFORMATIONS-36INCORPORATION OF CERTAIN DOCUMENTS BY REFERENCES-37 PROSPECTUS ABOUT THIS PROSPECTUS1RISK FACTORS2WHERE YOU CAN FIND MORE INFORMATION3INCORPORATION OF CERTAIN DOCUMENTS BY REFERENCE3CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS AND INDUSTRY DATA4ABOUT FULCRUM THERAPEUTICS,INC.5USE OF PROCEEDS6DESCRIPTION OF DEBT SECURITIES7DESCRIPTION OF CAPITAL STOCK14DESCRIPTION OF DEPOSITARY SHARES21DESCRIPTION OF UNITS24DESCRIPTION OF WARRANTS25FORMS OF SECURITIES26PLAN OF DISTRIBUTION28LEGAL MATTERS31EXPERTS31 Table of Contents ABOUT THIS PROSPECTUS SUPPLEMENT This document is part of a registration statement that we filed with the Securities and Exchange Commission, or the SEC, utilizing a “shelf”registration process and consists of two parts. The first part is this prospectus supplement, which describes the specific terms of thissecurities offering and also adds to and updates information contained in the accompanying prospectus and the documents incorporatedby reference herein. The second part, the accompanying prospectus, provides more general information. Generally, when we refer to thisprospectus, we a