Prelude Therapeutics Inc美国招股说明书（2026年3月12日版）

PROSPECTUS SUPPLEMENT(to Prospectus dated June10, 2024) Up to $25,000,000Common Stock We have previously entered into an Open Market Sale AgreementSM,, or Sales Agreement, with Jefferies LLC, or Jefferies, relating to shares ofour common stock, par value $0.0001 per share, pursuant to which we may offer and sell up to $75.0million of our common stock. In accordance withthe terms of the Sales Agreement, pursuant to this prospectus supplement, we may offer and sell shares of our common stock having an aggregate Our common stock is traded on The Nasdaq Global Select Market under the symbol “PRLD.” The last reported sales price of our common stockon The Nasdaq Global Select Market on March10, 2026, was $3.60 per share. Sales of our common stock, if any, under this prospectus supplement may be made in sales deemed to be an “at the market offering” as defined inRule415(a)(4) promulgated under the Securities Act of 1933, as amended, or the Securities Act. Jefferies is not required to sell any specific number ordollar amount of securities, but will act as a sales agent using commercially reasonable efforts consistent with its normal trading and sales practices, on The compensation to Jefferies for sales of common stock sold pursuant to the Sales Agreement will be up to 3.0% of the aggregate gross proceedsof any shares of common stock sold under the Sales Agreement. In connection with the sale of the common stock on our behalf, Jefferies will be deemedto be an “underwriter” within the meaning of the Securities Act and the compensation of Jefferies will be deemed to be underwriting commissions or Investing in our securities involves a high degree of risk. You should review carefully the risks and uncertainties referenced under theheading “Risk Factors” on page S-7 of this prospectus supplement as well as those contained in the accompanying prospectus and any relatedfree writing prospectus or prospectus supplement we prepare or authorize in connection with this offering, and in the other documents that are Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities ordetermined if this prospectus supplement and the accompanying prospectus is truthful or complete. Any representation to the contrary is acriminal offense. Jefferies The date of this prospectus supplement is March12, 2026. Table of Contents TABLE OF CONTENTSPROSPECTUS SUPPLEMENT ABOUT THIS PROSPECTUS SUPPLEMENTWHERE YOU CAN FIND MORE INFORMATIONINCORPORATION OF INFORMATION BY REFERENCESUMMARYTHE OFFERINGRISK FACTORSCAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTSUSE OF PROCEEDSDILUTIONPLAN OF DISTRIBUTIONLEGAL MATTERSEXPERTS PROSPECTUS ABOUT THIS PROSPECTUSPROSPECTUS SUMMARYRISK FACTORSFORWARD-LOOKING STATEMENTS DESCRIPTION OF DEBT SECURITIES DESCRIPTION OF WARRANTS DESCRIPTION OF UNITS Table of Contents ABOUT THIS PROSPECTUS SUPPLEMENT This prospectus supplement and the accompanying prospectus are part of a registration statementonFormS-3(RegistrationNo.333-279829)thatwe filed with the Securities and Exchange Commission, or the SEC, using a “shelf” registration process.Under this prospectus supplement and the accompanying prospectus, we may from time to time sell shares of our common stock having an aggregate This document is in two parts. The first part is a prospectus supplement, which describes the specific terms of this offering and certain othermatters relating to us. The second part is the accompanying prospectus, which provides more general information, some of which may not apply to thisoffering. You should read both this prospectus supplement and the accompanying prospectus as well as the additional information described in this This prospectus supplement describes the terms of this offering of common stock and also adds to and updates information contained in theaccompanying prospectus and the documents incorporated by reference into this prospectus supplement and the accompanying prospectus. To the extentthat any statement that we make in this prospectus supplement is inconsistent with the statements made in the accompanying prospectus or in anydocument incorporated by reference that was filed with the SEC before the date of this prospectus supplement, the statements made in the You should rely only on the information contained or incorporated by reference in this prospectus supplement. We have not, and Jefferies has not,authorized anyone to provide you with any information other than that contained or incorporated by reference in this prospectus supplement, theaccompanying prospectus or any accompanying prospectus supplement or related free writing prospectus to which we have referred you. Neither we norJefferies take any responsibility for, and can provide no assurance as to the reliability of, any other information others may give you. We are not, andJefferies is not, making an offer to sell these securities in any jurisdiction where the offer o