8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): March 12, 2026

Prelude Therapeutics Incorporated

(Exact Name of Registrant as Specified in its Charter)

Registrant’s telephone number, including area code: (302) 467-1280

Not Applicable

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

Securities registered pursuant to Section 12(b) of the Act:

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth 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 new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

As previously disclosed in the Current Report on Form 8-K filed with the Securities and Exchange Commission (the “SEC”) on March 15, 2023, Prelude Therapeutics Incorporated (the “Company”) entered into an Open Market Sale AgreementSM (the “Sales Agreement”) with Jefferies LLC, as sales agent (“Jefferies”), relating to shares of the Company’s common stock, par value $0.0001 per share (the “Common Stock”), pursuant to which the Company may offer and sell up to $75.0 million of its Common Stock.

In accordance with the terms of the Sales Agreement, on March 12, 2026, the Company filed a prospectus supplement (the “Prospectus Supplement”) to the base prospectus under its existing Shelf Registration Statement on Form S-3 (File No. 333-279829) initially filed with the SEC on May 30, 2024 and declared effective on June 10, 2024. Pursuant to the Prospectus Supplement, the Company may offer and sell shares of its Common Stock having an aggregate offering price of up to $25.0 million from time to time through Jefferies acting as sales agent.

The legal opinion of Morgan, Lewis & Bockius LLP relating to the shares of Common Stock being offered pursuant to the Prospectus Supplement is filed as Exhibit 5.1 to this Current Report on Form 8-K.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy any shares under the Sales Agreement, nor shall there be any sale of such shares in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

(d) Exhibits

SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

EX-5.1

Exhibit 5.1

March 12, 2026

Prelude Therapeutics Incorporated

175 Innovation Boulevard

Wilmington, Delaware 19805

Ladies and Gentlemen:

We have acted as counsel to Prelude Therapeutics Incorporated, a Delaware corporation (the “Company”), in connection with the offer and sale by the Company, to or through Jefferies LLC, as the sales agent (the “Sales Agent”), from time to time, of shares of the Company’s common stock (“Common Stock”), par value $0.0001 per share, having an aggregate maximum offering price of up to $25.0 million (the “Placement Shares”) in accordance with the terms of the Sales Agreement (as defined herein). The Company has previously entered into an Open Market Sale Agreement^SM^, dated as of March 15, 2023 (the “Sales Agreement”), by and between the Company and the Sales Agent, pursuant to which the Company may offer and sell up to $75.0 million of its Common Stock.

The Placement Shares were registered pursuant to the Registration Statement on Form S-3 (File No. 333-279829) filed by the Company with the Securities and Exchange Commission (the “Commission”) on May 30, 2024 (the “Registration Statement”) under the Securities Act of 1933, as amended (the “Securities Act”), declared effective on June 10, 2024, including the prospectus dated May 30, 2024 included therein (the “Base Prospectus”). The Company has filed with the Commission pursuant to Rule 424(b) under the Securities Act a prospectus supplement dated March 12, 2026 (the “Prospectus Supplement” and, together with the Base Prospectus, the “Prospectus”), pursuant to which the Company may offer and sell the Placement Shares.

In connection with our opinion expressed below we have examined originals or copies of the Sales Agreement, the Company’s Amended and Restated Certificate of Incorporation, as amended, filed with, and certified by, the Delaware Secretary of State (the “Certificate”), the Company’s Amended and Restated Bylaws (the “Bylaws”), the Registration Statement, together with the exhibits filed as a part thereof and all other documents incorporated therein by reference, the Prospectus, certain corporate proceedings of the Company’s board of directors (the “Board”) or a committee or committees of the Board and the Company’s stockholders relating to the Registration Statement, the Company’s Certificate and Bylaws, and such other agreements, documents, certificates and statements of the Company, its transfer agent and public or government officials, as we have deemed advisable, and have examined such questions of law as we have considered necessary.

We have assumed, and express no opinion as to, the genuineness of all signatures on documents submitted to us, the authenticity and completeness of all documents submitted to us as originals, the conformity to originals and completeness of all documents submitted to us as copies, the legal capacity of all persons or entities executing the same, the absence of any undisclosed termination, modification, waiver or amendment to any document reviewed by

Morgan, Lewis & Bockius LLP
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us, the absence of any other extrinsic agreements or documents that might change or affect the interpretation or terms of documents we have reviewed, and the due authorization, execution and delivery of all such documents where due authorization, execution and delivery are prerequisites to the effectiveness thereof. In giving our opinion, we have also relied upon a good standing certificate regarding the Company issued by the Delaware Secretary of State dated March 12, 2026, and a management certificate addressed to us and dated of even date herewith executed by the Company containing certain factual representations by the Company.

We render this opinion only with respect to, and express no opinion herein concerning the application or effect of any laws other than the existing Delaware General Corporation Law.

In connection with our opinions expressed below, we have assumed that, (i) at or prior to the time of the issuance and delivery of any of the Placement Shares, there will not have occurred any change in the law or the facts affecting the validity of the Placement Shares, any change in actions of the Board or the Company’s stockholders, or any amendments to the Certificate or Bylaws, (ii) at the time of the offer, issuance and sale of any Placement Shares, the Company will have a sufficient number of authorized and unissued and unreserved shares of Common Stock to be able to issue all such Placement Shares and (iii) at the time of the offer, issuance and sale of any Placement Shares, no stop order suspending the Registration Statement’s effectiveness will have been issued and remain in effect, and that the Registration Statement will not have been modified or rescinded. We also have assumed that the issuance and delivery of the Placement Shares subsequent to the date hereof and the compliance by the Company with the terms of such Placement Shares will not result in a violation of the Certificate or any provision of any instrument or agreement then binding upon the Company or any restriction imposed by any court or governmental body then having jurisdiction over the Company.

Based upon, and subject to, the foregoing, it is our opinion that the Placement Shares, when issued, sold and delivered in the manner and for the consideration stated in the Registration Statement and the Prospectus, in a manner consistent with the Sales Agreement, and in accordance with the resolutions adopted by the Board or a committee thereof, will be validly issued, fully paid and non-assessable.

We consent to the use of this opinion as an exhibit to the Current Report on Form 8-K to be filed by the Company with the Commission in connection with the offering of the Placement Shares and further consent to all references to us, if any, in the Registration Statement, the Prospectus and any amendments or supplements thereto. We do not thereby admit that we are within the category of persons whose consent is required under Section 7 of the Securities Act or the rules and regulations of the Commission promulgated thereunder.

This opinion is intended solely for use in connection with the issuance and sale of the Placement Shares subject to the Registration Statement and is not to be relied upon for any other purpose. In providing this opinion, we are opining only as to the specific legal issues expressly set forth above and no opinion shall be inferred as to any other matter or matters. This opinion is rendered on, and speaks, only as of the date of this letter first written above, is based solely on our understanding of facts in existence as of such date after the date of this opinion letter and does not address any potential change in facts or law that may occur after the date of this opinion letter. We assume no obligation to advise you of any fact, circumstance, event or change in the law or the facts that may hereafter be brought to our attention, whether or not such occurrence would affect or modify the opinion expressed herein.

Very truly yours,

/s/ Morgan, Lewis & Bockius LLP