Prelude Therapeutics Inc

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

SCHEDULE 14A

Proxy Statement Pursuant to Section 14(a) of the

Securities Exchange Act of 1934

(Amendment No. )

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NOTICE OF ANNUAL MEETING OF STOCKHOLDERS

To Be Held June 9, 2026

To Our Stockholders:

NOTICE IS HEREBY GIVEN that the 2026 Annual Meeting of Stockholders of Prelude Therapeutics Incorporated (the "Company") will be held via live audiocast on Tuesday, June 9, 2026 at 8:30 a.m. (Eastern Time). You will be able to participate in the 2026 Annual Meeting and vote during the 2026 Annual Meeting by visiting www.virtualshareholdermeeting.com/PRLD2026 and following the instructions contained in the accompanying proxy statement. It is important that you retain a copy of the control number found on the proxy card or voting instruction form, or included in the e-mail to you if you received the proxy materials by e-mail, as such number will be required in order for stockholders to gain access to the virtual meeting.

We are holding the meeting for the following purposes, which are more fully described in the accompanying proxy statement:

To elect three Class III directors, each to serve a three-year term through the 2029 annual meeting of stockholders following this meeting and until a successor has been elected and qualified or until earlier resignation or removal.

To ratify the appointment of Ernst & Young LLP as our independent registered public accounting firm for the fiscal year ending December 31, 2026.

To approve, on a non-binding advisory basis, the compensation of the Company’s named executive officers, as described in this proxy statement.

To approve, on a non-binding advisory basis, the frequency of the approval, on a non-binding advisory basis, of the compensation of the Company’s named executive officers.

In addition, stockholders may be asked to consider and vote upon such other business as may properly come before the meeting or any adjournment or postponement thereof.

Only stockholders of record at the close of business on April 16, 2026 are entitled to receive notice of, and to vote at, the meeting and any adjournments thereof.

Your vote as a stockholder of the Company is very important. Each share of voting common stock that you own represents one vote.

For questions regarding your stock ownership, you may contact our Investor Relations department at https://investors.preludetx.com/investor-relations or, if you are a registered holder, our transfer agent, Computershare Trust Company, N.A. by email at shareholder@computershare.com or through their website at www.computershare.com. Whether or not you expect to attend the meeting, we encourage you to read the proxy statement and vote through the internet or by telephone, or to request, sign and return your proxy card as soon as possible, so that your shares may be represented at the meeting. For specific instructions on how to vote your shares, please refer to the section entitled “General Proxy Information” in the proxy statement.

By Order of the Board of Directors,

Krishna Vaddi, Ph.D.

Chief Executive Officer

Wilmington, Delaware

April 29, 2026

Important Notice Regarding the Availability of Proxy Materials for the virtual Annual Meeting of Stockholders to be held on June 9, 2026: the Proxy Statement and our Annual Report on Form 10-K are available athttps://investors.preludetx.com/investor-relations.

PROXY STATEMENT FOR 2026 ANNUAL MEETING OF STOCKHOLDERS

TABLE OF CONTENTS

WEBSITE ADDRESSES

Website addresses referenced in this Proxy Statement are inactive textual references only, and the content on the referenced websites specifically does not constitute a part of this Proxy Statement.

CAUTIONARY STATEMENTS REGARDING FORWARD-LOOKING INFORMATION

This Proxy Statement contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). Forward-looking statements may be identified by words like “anticipate,” “expect,” “project,” “believe,” “plan,” “may,” “estimate,” “intend,” and other similar words. We base these forward-looking statements on our beliefs, assumptions, and estimates using information available to us at the time. They are not intended to be guarantees of future events or performance. Factors that may cause actual results to differ materially from forward-looking statements in this Proxy Statement can be found in our most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission ("SEC") on March 10, 2026 and in our subsequent filings with the SEC, including under the headings “Risk Factors” and “Forward-Looking Statements.”

We caution you not to unduly rely on any of our forward-looking statements. We disclaim any intention or obligation to publicly update or revise any forward-looking statements, except as required by law. This cautionary statement applies to all forward-looking statements contained in this document.

PROXY STATEMENT FOR THE 2026 ANNUAL MEETING OF STOCKHOLDERS

To Be Held on June 9, 2026