SecProbe.io

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 Prelude Therapeutics Inc.
 175 Innovation Boulevard
 Wilmington, Delaware 19805

 December 15, 2025

 VIA EDGAR TRANSMISSION

 Securities and Exchange Commission
 Division of Corporation Finance
 100 F Street, N.E.
 Washington, D.C. 20549
 Attention: Alan Campbell, Esq.

 Re:

 Prelude Therapeutics Inc.
 Registration Statement on Form S-3
 Filed December 10, 2025
 File No. 333-292048

 Ladies and Gentlemen:

 Pursuant to Rule 461 under the Securities Act of 1933, as amended, Prelude
 Therapeutics Inc. hereby requests acceleration of the effective date of its Registration Statement on Form S-3 (File No. 333-292048), so that such registration statement may become effective at 4:00 p.m. (Washington, D.C. time) on December
 16, 2025 or as soon as practicable thereafter.

 PRELUDE THERAPEUTICS INC.

 By:

 /s/ Krishna Vaddi, Ph.D.

 Name:

 Krishna Vaddi, Ph.D.

 Title:

 Chief Executive Officer

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CORRESP

 June 6, 2024

VIA EDGAR

 Securities and Exchange Commission

 Division of Corporation Finance

 100 F Street, N.E.

Washington, D.C. 20549

 Attention:  Office of Life Sciences

Re:
 Prelude Therapeutics Incorporated

Registration Statement on Form S-3

Filed May 30, 2024

File No. 333-279829

Ladies and Gentlemen:

 Pursuant to Rule 461 under the Securities
Act of 1933, as amended, Prelude Therapeutics Incorporated (the “Company”) hereby requests acceleration of the effective date of the above referenced registration statement, as amended, so that such registration statement may become
effective at 4:30 p.m. (Washington, D.C. time) on June 10, 2024, or as soon as practicable thereafter.

PRELUDE THERAPEUTICS INCORPORATED

By:

 /s/ Bryant D. Lim

Name:

Bryant D. Lim

Title:

Chief Legal Officer, Secretary & Interim Chief Financial Officer

cc:
 Richard B. Aldridge, Morgan, Lewis & Bockius LLP

Bryan S. Keighery, Morgan, Lewis & Bockius LLP

United States securities and exchange commission logo
June 3, 2024
Krishna Vaddi
Chief Executive Officer
Prelude Therapeutics Incorporated
175 Innovation Boulevard
Wilmington, DE 19805
Re:Prelude Therapeutics Incorporated
Registration Statement on Form S-3
Filed May 30, 2024
File No. 333-279829
Dear Krishna Vaddi:
            This is to advise you that we have not reviewed and will not review your registration
statement.
            Please refer to Rules 460 and 461 regarding requests for acceleration. We remind you
that the company and its management are responsible for the accuracy and adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action by the staff.
            Please contact Jason Drory at 202-551-8342 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Bryan S. Keighery

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 PRELUDE THERAPEUTICS INCORPORATED

175 Innovation Boulevard

Wilmington, Delaware 19805

 May 6, 2024

VIA EDGAR

 United States Securities and Exchange
Commission

 Division of Corporation Finance

 100 F Street,
N.E.

 Washington, DC 20549

Attention:

Alan Campbell

Re:

Prelude Therapeutics Incorporated, Registration Statement on Form S-3 (File No. 333-277123), as amended (“Registration
Statement”).

 Requested Date: May 8, 2024

Requested Time: 4:30 PM Eastern Time

 Ladies and
Gentlemen:

 Prelude Therapeutics Incorporated (the “Registrant”) hereby requests that the Securities and Exchange
Commission (the “Commission”) take appropriate action to declare the above-captioned Registration Statement effective at the “Requested Date” and “Requested Time” set forth above or as soon thereafter as
practicable, or at such later time as the Registrant may orally request via telephone call to the staff of the Commission.

 The Registrant
hereby authorizes Robert Freedman or Julia Forbess, both of whom are attorneys with the Registrant’s outside legal counsel, Fenwick & West LLP, to orally modify or withdraw this request for acceleration.

The Registrant requests that it be notified of such effectiveness by a telephone call to Mr. Freedman at (206) 389-4524 or, in his absence, to Ms. Forbess at (415) 875-2420.

[REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]

Sincerely,

Prelude Therapeutics Incorporated

By:

/s/ Bryant Lim

Bryant Lim

Chief Legal Officer, Corporate Secretary, and Interim Chief Financial Officer

cc:
 Kris Vaddi, Chief Executive Officer

Prelude Therapeutics Incorporated

Robert Freedman, Esq.

 Julia
Forbess, Esq.

 Fenwick & West LLP

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 PRELUDE THERAPEUTICS INCORPORATED

175 Innovation Boulevard

Wilmington, Delaware 19805

 May 3, 2024

VIA EDGAR

 United States Securities and Exchange
Commission

 Division of Corporation Finance

 100 F Street,
N.E.

 Washington, DC 20549

 Attention: Alan Campbell

Re:
 Prelude Therapeutics Incorporated (the “Registrant”), Registration Statement on Form S-3 (File No. 333-277123) filed February 16, 2024.

Ladies and Gentlemen:

 Reference is made to our
letter, filed with the Securities and Exchange Commission (the “Commission”) as correspondence via EDGAR on May 1, 2024 in which we requested the effective date of the above-captioned Registration Statement on Form S-3 be accelerated so that it would be declared effective at 4:30 PM, Eastern Time, on May 3, 2024, or as soon as thereafter practicable.

The purpose of this letter is to memorialize our conversations with the Commission in which we advised that we are not seeking effectiveness
of the above-captioned Registration Statement on Form S-3 at the above requested time and that we intend to resubmit our request for acceleration of effectiveness at a later date.

We hereby formally withdraw our request for acceleration of the effective date at 4:30 PM, Eastern Time, on May 3, 2024.

[REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]

Sincerely,

Prelude Therapeutics Incorporated

By:

 /s/ Bryant Lim

Bryant Lim

Chief Legal Officer, Corporate Secretary, and Interim Chief Financial Officer

cc:
 Kris Vaddi, Chief Executive Officer

Prelude Therapeutics Incorporated

Robert Freedman, Esq.

 Julia
Forbess, Esq.

 Fenwick & West LLP

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CORRESP

 PRELUDE THERAPEUTICS INCORPORATED

175 Innovation Boulevard

Wilmington, Delaware 19805

 May 1, 2024

VIA EDGAR

 United States Securities and Exchange
Commission

 Division of Corporation Finance

 100 F Street,
N.E.

 Washington, DC 20549

 Attention: Alan Campbell

Re:
 Prelude Therapeutics Incorporated, Registration Statement on Form S-3
(File No. 333-277123) filed February 16, 2024.

 Requested Date:
May 3, 2024

 Requested Time: 4:30 PM Eastern Time

Ladies and Gentlemen:

 Prelude Therapeutics
Incorporated (the “Registrant”) hereby requests that the Securities and Exchange Commission (the “Commission”) take appropriate action to declare the above-captioned Registration Statement on Form
S-3 effective at the “Requested Date” and “Requested Time” set forth above or as soon thereafter as practicable, or at such later time as the Registrant may orally request via telephone call to the staff of the Commission.

 The Registrant hereby authorizes Robert Freedman or Julia Forbess, both of whom are attorneys with the Registrant’s outside legal
counsel, Fenwick & West LLP, to orally modify or withdraw this request for acceleration.

 The Registrant requests that it be
notified of such effectiveness by a telephone call to Mr. Freedman at (206) 389-4524 or, in his absence, to Ms. Forbess at (415) 875-2420.

[REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]

Sincerely,

Prelude Therapeutics Incorporated

By:

 /s/ Bryant Lim

Bryant Lim

Chief Legal Officer, Corporate Secretary, and Interim Chief Financial Officer

cc:
 Kris Vaddi, Chief Executive Officer

Prelude Therapeutics Incorporated

Robert Freedman, Esq.

 Julia
Forbess, Esq.

 Fenwick & West LLP

United States securities and exchange commission logo
February 21, 2024
Krishna Vaddi, Ph.D.
Chief Executive Officer
Prelude Therapeutics Incorporated
175 Innovation Boulevard
Wilmington, Delaware 19805
Re:Prelude Therapeutics Incorporated
Registration Statement on Form S-3
Filed February 16, 2024
File No. 333-277123
Dear Krishna Vaddi:
            This is to advise you that we have not reviewed and will not review your registration
statement.
            Please refer to Rules 460 and 461 regarding requests for acceleration. We remind you
that the company and its management are responsible for the accuracy and adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action by the staff.
            Please contact Alan Campbell at 202-551-4224 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Robert Freedman

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 PRELUDE THERAPEUTICS INCORPORATED

200 Powder Mill Road

 Wilmington,
Delaware 19803

 November 22, 2021

 VIA EDGAR

 United States Securities and Exchange Commission

Division of Corporation Finance

 100 F Street, N.E.

Washington, DC 20549

Attention:

Michael Davis

Joe McCann

Re:

Prelude Therapeutics Incorporated, Registration Statement on Form S-3 (File No. 333-261019) filed November 12, 2021.

 Requested Date: November 24, 2021

Requested Time: 4:30 PM Eastern Time

 Ladies and
Gentlemen:

 Prelude Therapeutics Incorporated (the “Registrant”) hereby requests that the Securities and Exchange
Commission (the “Commission”) take appropriate action to declare the above-captioned Registration Statement on Form S-3 effective at the “Requested Date” and “Requested Time” set forth above or as
soon thereafter as practicable, or at such later time as the Registrant may orally request via telephone call to the staff of the Commission.

The Registrant hereby authorizes Robert Freedman or Julia Forbess, both of whom are attorneys with the Registrant’s outside legal
counsel, Fenwick & West LLP, to orally modify or withdraw this request for acceleration.

 The Registrant requests that it be
notified of such effectiveness by a telephone call to Mr. Freedman at (650) 335-7292 or, in his absence, to Ms. Forbess at (415) 875-2420.

[REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]

Sincerely,

Prelude Therapeutics Incorporated

By:

 /s/ Kris Vaddi

Kris Vaddi

Chief Executive Officer

cc:
 Kris Vaddi, Chief Executive Officer

Prelude Therapeutics Incorporated

Robert Freedman, Esq.

 Julia
Forbess, Esq.

 Fenwick & West LLP

United States securities and exchange commission logo
November 19, 2021
Kris Vaddi, Ph.D.
Chief Executive Officer
Prelude Therapeutics Inc
200 Powder Mill Road
Wilmington, Delaware 19803
Re:Prelude Therapeutics Inc
Registration Statement on Form S-3
Filed November 12, 2021
File No. 333-261019
Dear Kris Vaddi:
            This is to advise you that we have not reviewed and will not review your registration
statement.
            Please refer to Rules 460 and 461 regarding requests for acceleration.  We remind you
that the company and its management are responsible for the accuracy and adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action by the staff.
            Please contact Michael Davis at 202-551-4385 or Joe McCann at 202-551-6262 with any
questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Robert Freedman

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 Prelude Therapeutics Incorporated

200 Powder Mill Road

 Wilmington, Delaware 19803

January 4, 2021

 VIA EDGAR

United States Securities and Exchange Commission

 Division of
Corporation Finance

 100 F Street, NE

 Washington, DC 20549

 Attention:

 Deanna Virginio

Re:

Prelude Therapeutics Incorporated Registration Statement on Form S-1 (File No. 333-251874) originally filed January 4, 2021.

 Requested Date: January 6, 2021

Requested Time: 4:30 PM Eastern Time

 Ladies and Gentlemen:

Prelude Therapeutics Incorporated (the “Registrant”) hereby requests that the Securities and Exchange Commission take
appropriate action to declare the above-captioned Registration Statements on Form S-1 effective at the “Requested Date” and “Requested Time” set forth above or as soon thereafter as practicable.

The Registrant hereby authorizes Robert A. Freedman or Julia Forbess, both of whom are attorneys with the Registrant’s outside legal
counsel, Fenwick & West LLP, to orally modify or withdraw this request for acceleration.

 The Registrant requests that it be
notified of such effectiveness by a telephone call to Mr. Freedman at (650) 335-7292 or, in his absence, Ms. Forbess at (415) 875-2420.

* * *

Sincerely,

PRELUDE THERAPEUTICS INCORPORATED

By:

 /s/ Krishna Vaddi

Krishna Vaddi, Ph.D.

Chief Executive Officer

cc:
 Brian Piper, Chief Financial Officer

Prelude Therapeutics Incorporated

Effie Toshav, Esq.

 Robert A.
Freedman, Esq.

 Fenwick & West LLP

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CORRESP

 January 4, 2021

U.S. Securities and Exchange Commission

 Division of Corporation
Finance

 100 F Street, N.E.

 Washington, D.C. 20549

Attention: Deanna Virginio

Re:
 Prelude Therapeutics Incorporated

 Registration Statement on Form S-1 (File No. 333-251874)

 Request for Acceleration

Ladies and Gentlemen:

 Pursuant to Rule 460 of the General Rules
and Regulations under the Securities Act of 1933, as amended, please be advised that we will take reasonable steps to secure adequate distribution of the preliminary prospectus to underwriters, dealers, institutions and others, prior to the
requested effective time of the Registration Statement.

 We wish to advise you that the participating underwriters have informed us that they have
complied and will continue to comply with the requirements of Rule 15c2-8 under the Securities Exchange Act of 1934, as amended.

We hereby join in the request of the registrant that the effectiveness of the above-captioned Registration Statement, as amended, be accelerated to 4:30 p.m.
Eastern Time, on Wednesday, January 6, 2020 or as soon thereafter as practicable.

 [Signature page follows]

 Very truly yours,

Morgan Stanley & Co. LLC

 Goldman Sachs & Co.
LLC

 BofA Securities, Inc.

 As representatives of the
Underwriters

 By:

 Morgan Stanley & Co. LLC

By:

/s/ Chris Rigoli

Name:

Chris Rigoli

Title:

Vice President

 By:

 Goldman Sachs & Co. LLC

By:

/s/ Elizabeth Wood

Name:

Elizabeth Wood

Title:

Managing Director

 By:

 BofA Securities, Inc.

By:

/s/ Greg Butz

Name:

Greg Butz

Title:

Managing Director

 [Signature Page to Prelude Therapeutics Incorporated Acceleration Request]

United States securities and exchange commission logo
December 23, 2020
Krishna Vaddi, Ph.D.
Chief Executive Officer
Prelude Therapeutics Incorporated
200 Powder Mill Road
Wilmington, DE 19803
Re:Prelude Therapeutics Incorporated
Draft Registration Statement on Form S-1
Submitted December 21, 2020
CIK No. 0001678660
Dear Dr. Vaddi:
            This is to advise you that we do not intend to review your registration statement.
            We request that you publicly file your registration statement no later than 48 hours prior
to the requested effective date and time. Please refer to Rules 460 and 461 regarding requests for
acceleration. We remind you that the company and its management are responsible for the
accuracy and adequacy of their disclosures, notwithstanding any review, comments, action or
absence of action by the staff.
            Please contact Deanna Virginio at 202-551-4530 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Julia Forbess, Esq.

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 Prelude Therapeutics Incorporated

200 Powder Mill Road

 Wilmington, Delaware 19803

September 22, 2020

 VIA EDGAR

United States Securities and Exchange Commission

 Division of
Corporation Finance

 100 F Street, NE

 Washington, DC 20549

Attention:
 Jeffrey Gabor

Laura Crotty

 Rolf Sundwall

 Jeanne Baker

Re:
 Prelude Therapeutics Incorporated Registration Statement on Form S-1
(File No. 333-248628) originally filed September 4, 2020, as amended, and corresponding Registration Statement on Form 8-A (File
No. 001-39527) filed September 16, 2020.

 Requested Date: September 24, 2020

Requested Time: 4:00 PM Eastern Time

 Ladies and Gentlemen:

Prelude Therapeutics Incorporated (the “Registrant”) hereby requests that the Securities and Exchange Commission take
appropriate action to declare the above-captioned Registration Statements on Form S-1 and Form 8-A effective at the “Requested Date” and “Requested Time” set forth above or as soon thereafter as practicable.

The Registrant hereby authorizes Robert A. Freedman or Julia Forbess, both of whom are attorneys with the Registrant’s outside legal
counsel, Fenwick & West LLP, to orally modify or withdraw this request for acceleration.

 The Registrant requests that it be
notified of such effectiveness by a telephone call to Mr. Freedman at (650) 335-7292 or, in his absence, Ms. Forbess at (415) 875-2420.

* * *

Sincerely,

PRELUDE THERAPEUTICS INCORPORATED

By:

 /s/ Krishna Vaddi, Ph.D.

Krishna Vaddi, Ph.D.

Chief Executive Officer

cc:
 Krishna Vaddi, Ph.D., Chief Executive Officer

Prelude Therapeutics Incorporated

Effie Toshav, Esq.

 Robert A.
Freedman, Esq.

 Fenwick & West LLP

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CORRESP

 September 22, 2020

U.S. Securities and Exchange Commission

 Division of Corporation
Finance

 100 F Street, N.E.

 Washington, D.C. 20549

 Attention:

 Jeffrey Gabor

 Laura Crotty

 Rolf Sundwall

 Jeanne Baker

Re:
 Prelude Therapeutics Incorporated

Registration Statement on Form S-1 (File
No. 333-248628)

 Request for Acceleration

Ladies and Gentlemen:

 Pursuant to Rule 460 of the General
Rules and Regulations under the Securities Act of 1933, as amended, we wish to advise that as of the date hereof, approximately 3,016 copies of the Preliminary Prospectus dated September 21, 2020 were distributed to prospective underwriters,
institutional investors and prospective dealers in connection with the above-captioned Registration Statement.

 We wish to advise you that the
participating underwriters have informed us that they have complied and will continue to comply with the requirements of Rule 15c2-8 under the Securities Exchange Act of 1934, as amended.

We hereby join in the request of the registrant that the effectiveness of the above-captioned Registration Statement, as amended, be accelerated to
4:00 p.m. Eastern Time, on September 24, 2020 or as soon thereafter as practicable.

 [Signature page follows]

 Very truly yours,

MORGAN STANLEY & CO. LLC

 GOLDMAN SACHS & CO.
LLC

 BOFA SECURITIES, INC.

 As representatives of the
Underwriters

 MORGAN STANLEY & CO. LLC

By:

 /s/ Chris Rigoli

Name:

Chris Rigoli

Title:

Vice President

 GOLDMAN SACHS & CO. LLC

By:

 /s/ Elizabeth Wood

Name:

Elizabeth Wood

Title:

Managing Director, Goldman Sachs Investment Banking Division

 BOFA SECURITIES, INC.

By:

 /s/ Greg Butz

Name:

Greg Butz

Title:

Managing Director

 [Signature Page to Prelude Therapeutics Incorporated Acceleration Request]

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CORRESP

 ROBERT A. FREEDMAN

September 16, 2020

 EMAIL:
RFREEDMAN@FENWICK.COM

 Direct Dial: +1 (650)
335-7292

 VIA EDGAR AND OVERNIGHT DELIVERY

 U.S. Securities and Exchange Commission

Division of Corporation Finance

100 F Street, NE

Washington, DC 20549

Attention:

 Jeffrey Gabor

 Laura Crotty

Rolf Sundwall

 Jeanne Baker

Re:

 Prelude Therapeutics Incorporated

Registration Statement on Form S-1

Filed September 4, 2020

 File No. 333-248628

 Ladies and Gentlemen:

We are submitting this letter on behalf of Prelude Therapeutics Incorporated (the “Company”) in response to the
comments of the staff (the “Staff”) of the U.S. Securities and Exchange Commission (the “Commission”) in its letter dated September 4, 2020 (the “Letter”) regarding the
Company’s Registration Statement on Form S-1 (File No. 333-248628) initially filed with the Commission on September 4, 2020 (“Registration
Statement”). The Company advises the Staff that it has filed Amendment No. 1 (“Amendment No. 1”) to the Registration Statement on September 16, 2020. The numbered paragraphs below
correspond to the numbered comments in the Letter and the Staff’s comments are presented in bold italics.

 In addition to addressing
the comments raised by the Staff in the Letter, the Company has revised Amendment No. 1 to update certain other disclosures.

 Draft
Registration Statement on Form S-1

 Description of Capital Stock, page 171

1.
 We note that you have revised the prospectus to reflect dual classes of common stock and state on page
171 that holders of non-voting common stock have the right to convert each share of non-voting common stock into one share of voting common stock at such holder’s
election. In addition, we note that the 9.99% ownership limitation related to any conversion may be “increased (not to exceed 19.99%) or decreased to any other percentage designated by such holder of
non-voting common stock upon 61 days’ notice”. Please add a risk factor addressing the potential dilutive effective of such conversion rights and the impact of the potential increase in the 9.99%
ownership limitation.

 U.S. Securities and Exchange Commission

September 16, 2020

 Page 2

 The Company respectfully acknowledges the Staff’s comment and has revised its disclosure on page 65
of Amendment No. 1 to address the potential dilutive effect to the voting power of the existing investors of the Company. The Company respectfully advises that the conversion of the non-voting common
stock into voting common stock will not be dilutive to the share ownership percentage of the investors of the Company as it converts on a one-to-one basis and is
included in the total outstanding shares as disclosed.

 Audited Financial Statements as of December 31, 2018 and 2019 and for the Years then
Ended

 Note 3. Summary of Significant Accounting Policies

Net Loss Per Share and Unaudited Pro Forma Net Loss Per Share, page F-11

2.
 Refer to your response to our prior comment eleven. Please explain to us your consideration of your
Series C Convertible Preferred Stock, issued in August 2020, in your presentation of pro forma net loss per share, or revise accordingly.

The Company respectfully acknowledges the Staff’s comment and has revised its disclosure on pages 9, 81, F-4,
F-11, F-12, F-22 and F-28 of Amendment No. 1 to assume that all shares of its convertible preferred stock, including the
Series C Convertible Preferred Stock issued in August 2020, converted into shares of voting and non-voting common stock at the beginning of period after consideration of the guidance contained in Regulation
S-X 11-02(b)(7). It is the Company’s understanding that the Staff believes that this is an appropriate approach to calculating pro forma net loss per share in these
circumstances. In addition, the Company has presented this information consistently in the unaudited interim financial statements for the six months ended June 30, 2020 included in Amendment No. 1.

* * * * * * *

 U.S. Securities and Exchange Commission

September 16, 2020

 Page 3

 Should the Staff have additional questions or comments regarding the foregoing, please do not
hesitate to contact the undersigned at (650) 335-7292, or, in his absence, Julia Forbess at (415) 875-2420.

Sincerely,

FENWICK & WEST LLP

/s/ Robert A. Freedman

Robert A. Freedman

Partner

cc:

Kris Vaddi, Ph.D., Chief Executive Officer

Brian Piper, M.B.A., Chief Financial Officer

Prelude Therapeutics Incorporated

Effie Toshav, Esq.

Julia Forbess, Esq.

Fenwick & West LLP

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CORRESP

 September 9, 2020

CERTAIN PORTIONS OF THIS LETTER AS FILED VIA EDGAR HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED FOR THE OMITTED PORTIONS, WHICH HAVE BEEN REPLACED WITH THE FOLLOWING PLACEHOLDER: “[*].”

VIA EDGAR AND OVERNIGHT DELIVERY

 U.S. Securities and
Exchange Commission

 Division of Corporation Finance

 Office
of Healthcare & Insurance

 100 F Street, NE

Washington, DC 20549

Attention:      Jeffrey Gabor

Laura Crotty

 Rolf Sundwall

Jeanne Baker

Re:
 Prelude Therapeutics Incorporated

 Registration Statement on Form S-1

 Filed September 4, 2020

 File No. 333-248628

Ladies and Gentlemen:

 On behalf of Prelude
Therapeutics Incorporated (the “Company”), we submit this letter to assist the staff (the “Staff”) of the Securities and Exchange Commission (the “Commission”) in its review of
the Company’s Registration Statement on Form S-1 (File No. 333-248628) (the “Registration Statement”), to further address comment #5 of
the Staff set forth in its letter to the Company dated August 19, 2020, concerning valuation considerations related to the Company’s equity awards.

Because of the commercially sensitive nature of information contained herein, this submission is accompanied by the Company’s request for
confidential treatment of selected portions of this letter pursuant to Rule 83 of the Commission’s Rules on Information and Requests, 17 C.F.R. § 200.83 and the Freedom of Information Act.

 CONFIDENTIAL TREATMENT
REQUESTED BY PRELUDE THERAPEUTICS INCORPORATED

 Securities and Exchange Commission

Division of Corporation Finance

 September 9, 2020

 Page
 2

 Preliminary IPO Price Range

The Company advises the Staff that the Company currently anticipates that it will include an expected price range in its preliminary prospectus
(the “Preliminary Prospectus”) for the proposed initial public offering (the “IPO”) that will be between approximately $[*] and $[*] per share (the “Price Range”). The Company
plans to effect a reverse stock split (the “Stock Split”) in connection with its IPO pursuant to a future amendment of the Company’s certificate of incorporation that will be filed with the Secretary of State of the
State of Delaware before filing the Preliminary Prospectus with the Commission. The share numbers and stock prices set forth in this letter do not reflect the Stock Split and are all set forth on a pre-split
basis.

 The Preliminary Price Range has been determined based, in part, upon current market conditions, the Company’s current
financial condition and prospects, the Company’s progress in developing its pipeline of product candidates, recent public offerings of other comparable companies and input received from representatives of Morgan Stanley, Goldman
Sachs & Co. LLC and BofA Securities (the “Lead Underwriters”), the lead underwriters of the proposed offering, including discussions that took place on September 2, 2020 among senior management of the Company, the
Board of Directors of the Company (the “Board”) and the Lead Underwriters. Prior to September 2, 2020, the Company had not held formal discussions with the Lead Underwriters regarding a price range for the IPO. The
Preliminary Price Range does not take into account the current lack of liquidity for the Common Stock and assumes a successful IPO with no weighting attributed to any other outcome for the Company’s business, such as remaining a privately held
company.

 The Company expects to include a bona fide price range in an amendment to the Registration Statement (which will comply with the
Staff’s interpretation regarding the parameters of a bona fide price range and which the Company expects to be a two-dollar range within the Price Range) that would shortly precede the commencement of the
Company’s public marketing process, which it anticipates could commence as soon as [*]. Such price range could differ from the Price Range based on then-current market conditions, continuing discussions with the Lead Underwriters and further
business developments impacting the Company.

 Fair Value Determinations

Given the absence of an active market for the Common Stock, the Board was required to estimate the fair value of the Common Stock at the time
of each equity-based award based upon several factors, including the Board’s consideration of input from management and third-party valuations.

We supplementally advise the Staff that, as described on pages 92 through 93 of the Registration Statement, for all periods prior to the IPO,
the fair values of the shares of common stock underlying the Company’s share-based awards were estimated on each grant date by the Board. To determine the fair value of the Common Stock underlying option grants, the Board considered a variety
of factors including, among other things, timely valuations of the Common Stock prepared by an independent third-party valuation firm in accordance with the guidance provided by the American Institute of Certified Public Accountants Practice
Guide, Valuation of Privately-Held-Company Equity Securities Issued as Compensation. Given the absence of a public trading market for the Common Stock , the Board exercised reasonable judgment and considered a number of objective and
subjective factors to determine the best estimate of the fair value of the Common Stock, including important developments in the Company’s operations, such as progress on initial new drug (“IND”) submissions and clinical
data read-outs, its stage of development, valuations performed by an independent third party valuation firm, sales of the Company’s preferred stock, actual operating results and financial performance, the conditions in the life sciences and
biotechnology industry sectors and the economy in general, the stock price performance and volatility of comparable public companies, the lack of liquidity of the Common Stock, and the likelihood of achieving a liquidity event, such as an initial
public offering or sale.

 CONFIDENTIAL TREATMENT
REQUESTED BY PRELUDE THERAPEUTICS INCORPORATED

 2

 Securities and Exchange Commission

Division of Corporation Finance

 September 9, 2020

 Page
 3

 The following table summarizes the grant of options by the Company since January 1,
2019:

 Date of Grant

Number of
Shares Subject to
Stock
Options Granted

Exercise Price
Per Share

Fair Value
Per Share

Valuation Date

 February 13, 2019

198,000

$
1.23

$
1.23

November 1, 2018

 June 17, 2019

1,114,500

$
1.63

$
1.63

May 15, 2019

 August 7, 2019

565,000

$
1.63

$
1.63

May 15, 2019

 November 13, 2019

93,000

$
1.63

$
1.63

May 15, 2019

 March 27, 2020*

1,375,500

$
1.63

$
2.82

March 27, 2020

 May 13, 2020*

310,000

$
1.63

$
2.82

March 27, 2020

 September 2, 2020

3,620,131

$
11.11

$
11.11

August 25, 2020

*
 Based on certain corporate development events described below, the Company adjusted the fair value of the
Company’s common stock for financial reporting purposes, for the grant dates of March 27, 2020 and May 13, 2020 to $2.82 per share respectively utilizing a linear interpolation from its May 15, 2019 valuation.

 Summary of Methods Used

For the November 2018 and May 2019 valuations, the Company employed attributes from the income and market approaches by way of an option
pricing method (“OPM”) framework. Given the very wide range of possible future exit events, the Company utilized an OPM, through a process known as the back-solve method for inferring and allocating the equity value
predicated on the most recent financing. Furthermore, for the November 2018 and May 2019 valuation dates, the Company was at an early stage of development and future liquidity events were difficult to forecast. Application of the OPM back-solve
method involves making assumptions for the expected time to liquidity, volatility and risk-free rate and then solving for the value of equity such that the value for the referenced financing equals the amount paid which is then discounted for a lack
of marketability (“DLOM”).

 Given certain progress made towards completing an IPO, the Company used a
probability-weighted expected return method (“PWERM”) in combination with the OPM as a hybrid method (“Hybrid Method”) to value the common stock of the Company for the March 2020 and August 2020
valuations.

 The Hybrid Method is appropriate for a company expecting a near term liquidity event, but where, due to market or other
factors, the likelihood of completing the liquidity event is uncertain. The Hybrid Method considers a company’s going concern nature, stage of development and the company’s ability to forecast near and long-term future liquidity scenarios.
The PWERM is a scenario-based analysis that estimates the value per share of common

 CONFIDENTIAL TREATMENT
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 Securities and Exchange Commission

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 4

stock based on the probability-weighted present value of expected future equity values for the common stock, under various possible future liquidity event scenarios, in light of the rights and
preferences of each class and series of stock, discounted for a lack of marketability.

 Summary of Valuations

For the November 2018 valuation, the Company employed an OPM method implied by the terms of the Company’s Series A convertible preferred
stock financing that initially closed in October 2017 (the “Series A Financing”) with a follow-on financing in August 2018. For the November 2018 valuation and for purposes of the OPM
allocation of total equity value determined with reference to the Series A Financing, the Company assumed a 65% volatility rate and a 2.5-year estimated term. The Company then reflected a DLOM of 35% to arrive
at a $1.23 per share valuation.

 For the May 2019 valuation, the Company employed an OPM method implied by the terms of the Series B
convertible preferred stock financing that closed in May 2019 (the “Series B Financing”) with a follow-on financing in March 2020. For the May 2019 valuation and for purposes of the OPM
allocation of total equity value determined with reference to the Series B Financing, the Company assumed a 70% volatility rate and a 2-year estimated term. The Company then reflected a DLOM of 30% to arrive
at a $1.63 per share valuation.

 For the March 2020 valuation, the Company employed a Hybrid Method implied by the terms of the
Company’s Series B financing. The Company was valued under two scenarios: (1) an initial public offering in September 2020 ([*]% probability) (the “March IPO scenario”); and (2) a forward sale
scenario at a later date ([*]% probability) (the “March forward sale scenario”). As of the March 2020 valuation, the Company had entered into initial discussions with investment banks regarding an initial public offering, but
had not yet held an organizational meeting or hired any investment banks. For the March 2020 valuation and for purposes of the OPM allocation of total equity value determined with reference to the Series B Financing, for the March IPO scenario the
Company assumed a 115% volatility rate, a 0.5-year estimated term and a DLOM of 22.6%, and for the March forward sale scenario, the Company assumed a 130% volatility rate, a
1.5-year estimated term and a DLOM of 30%. The Company then applied a probability weighted average to arrive at a $2.82 per share valuation.

The Company advises the Staff that the Board determined the fair value of the underlying shares of common stock for option awards granted on
March 2020 and May 2020 was $2.82 per share. At the time of these grants, the Company’s Board carefully considered all relevant information available to it, including the most recent valuation report from its third-party valuation firm, which
concluded that, as of May 15, 2019, the fair value of shares of the Company’s common stock was $1.63 per share. A retroactive valuation analysis for financial reporting purposes concluded that as of March 27, 2020, the fair value of
the shares of the Company’s common stock was $2.82 per share. The retroactive analysis took into account events in 2020, including:

•

 Initiation of clinical programs and first patient enrolled for both PRT543 and PRT811 programs

•

 Filing of PRT1419 IND

•

 Hiring of CMO & CFO, and build out of Clinical development team (significant effort)

•

 Advancement of preclinical pipeline

For the August 2020 valuation, the Company employed a Hybrid Method implied by the terms of the Company’s Series C financing that
occurred in August 2020. The Company was valued under two scenarios: (1) an initial public offering in September 2020 ([*]% probability) (the “August IPO scenario”); and (2) a forward sale scenario at a later date
([*]% probability) (the “August forward sale scenario”). As of the August 2020 valuation,

 CONFIDENTIAL TREATMENT
REQUESTED BY PRELUDE THERAPEUTICS INCORPORATED

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the Company had completed an amendment to the initial confidential submission of the Registration Statement. For the August 2020 valuation and for purposes of the OPM allocation of total equity
value determined with reference to the Series C Financing, for the August IPO scenario the Company assumed a 80% volatility rate, a 0.08-year estimated term and a DLOM of 14%, and for the August forward sale
scenario, the Company assumed a 100% volatility rate, a 1.0-year estimated term and a DLOM of 25%. The Company then applied a probability weighted average to arrive at a $11.11 per share valuation.

The Board plans to grant, effective the effective date of the Registration Statement, an aggregate of 8,000 shares subject to stock options on
a pre-split basis to two directors with an exercise price per share equal to the IPO price per share. The Company has not granted any options since September 2, 2020, and does not currently intend to
grant any other options prior to the IPO.

 Comparison to Preliminary Assumed IPO Price

We are supplementally providing the Staff the following discussion regarding the significant factors contributing to the difference between the
Price Range and the estimated fair values of the Company’s common stock reflected in the table above.

 We note that, as is typical in
IPOs, the Price Range for the Offering was not derived using a formal determination of fair value, but was determined by negotiation between the Company and the underwriters. Among the factors that were considered in setting this range were the
following:

•

 an analysis of the typical valuation ranges seen in recent IPOs in the Company’s industry;

•

 the general condition of the public capital markets and the recent market prices of, and the demand for, publicly
traded common stock of generally comparable biopharma companies; and

•

 an assumption that there would be a receptive public trading market for the Company’s common stock.

 The Company submits that the primary reason for the difference between the fair value per share used for the stock
options granted since January 2019 and the midpoint of the Price Range are:

•

 Differences in the valuation methodologies, assumptions and inputs used by the underwriters in their valuation
analysis discussed with the Company and used to determine the Price Range, which assume a successful IPO as of today’s date with no weighting attributed to any other outcome for the Company’s business, such as remaining a privately held
company, compared to the valuation methodologies, assumptions and inputs used in the valuations determined by the Board as described above in connection with the description of methodologies used.

•

 The Price Range necessarily assumes that the IPO has occurred and a public market for the Company’s common
stock has been created and, therefore, excludes any marketability or liquidity discount

United States securities and exchange commission logo
September 4, 2020
Kris Vaddi, Ph.D.
Chief Executive Officer
Prelude Therapeutics Incorporated
200 Powder Mill Road
Wilmington, DE 19803
Re:Prelude Therapeutics Incorporated
Amendment No. 1 to Draft Registration Statement on Form S-1
Submitted August 26, 2020
CIK No. 0001678660
Dear Dr. Vaddi:
            We have reviewed your amended draft registration statement and have the following
comments.  In some of our comments, we may ask you to provide us with information so we
may better understand your disclosure.
            Please respond to this letter by providing the requested information and either submitting
an amended draft registration statement or publicly filing your registration statement on
EDGAR.  If you do not believe our comments apply to your facts and circumstances or do not
believe an amendment is appropriate, please tell us why in your response.
            After reviewing the information you provide in response to these comments and your
amended draft registration statement or filed registration statement, we may have additional
comments.
Amendment No. 1 to Draft Registration Statement on Form S-1
Description of Capital Stock, page 171
1.We note that you have revised the prospectus to reflect dual classes of common stock and
state on page 171 that holders of non-voting common stock have the right to convert each
share of non-voting common stock into one share of voting common stock at such
holder’s election. In addition, we note that the 9.99% ownership limitation related to
any conversion may be "increased (not to exceed 19.99%) or decreased to any other
percentage designated by such holder of non-voting common stock upon 61 days' notice".
Please add a risk factor addressing the potential dilutive effective of such conversion
rights and the impact of the potential increase in the 9.99% ownership limitation.

 FirstName LastNameKris Vaddi, Ph.D.
 Comapany NamePrelude Therapeutics Incorporated
 September 4, 2020 Page 2
 FirstName LastName
Kris Vaddi, Ph.D.
Prelude Therapeutics Incorporated
September 4, 2020
Page 2
Audited Financial Statements as of December 31, 2018 and 2019 and for the Years then Ended
Note 3. Summary of Significant Accounting Policies
Net Loss Per Share and Unaudited Pro Forma Net Loss Per Share, page F-11
2.Refer to your response to our prior comment eleven.  Please explain to us your
consideration of your Series C Convertible Preferred Stock, issued in August 2020, in
your presentation of pro forma net loss per share, or revise accordingly.
            You may contact Rolf Sundwall at 202-551-3105 or Jeanne Baker at 202-551-3691 if you
have questions regarding comments on the financial statements and related matters.  Please
contact Jeffrey Gabor at 202-551-2544 or Laura Crotty at 202-551-7614 with any other
questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Rob Freedman, Esq.

United States securities and exchange commission logo
August 19, 2020
Kris Vaddi, Ph.D.
Chief Executive Officer
Prelude Therapeutics Incorporated
200 Powder Mill Road
Wilmington, DE 19803
Re:Prelude Therapeutics Incorporated
Draft Registration Statement on Form S-1
Submitted July 23, 2020
CIK No. 0001678660
Dear Dr. Vaddi:
            We have reviewed your draft registration statement and have the following comments.  In
some of our comments, we may ask you to provide us with information so we may better
understand your disclosure.
            Please respond to this letter by providing the requested information and either submitting
an amended draft registration statement or publicly filing your registration statement on
EDGAR.  If you do not believe our comments apply to your facts and circumstances or do not
believe an amendment is appropriate, please tell us why in your response.
            After reviewing the information you provide in response to these comments and your
amended draft registration statement or filed registration statement, we may have additional
comments.
Draft Registration Statement on Form S-1
Overview, page 2
1.Given the status of your development of your product candidates, please tell us the basis
for your claims on page 1 and throughout the registration statement that your product
candidates are potent and selective.
2.Please revise your pipeline tables on pages 2 and 93 to include columns depicting each of
Phase 1, Phase 2, and Phase 3 to ensure that all stages in the clinical trial process prior to
seeking FDA approval are shown. In addition, please remove the "Pivotal" label, as it is
premature to suggest that the completion of the Phase 1/2 clinical trials will lead to a

 FirstName LastNameKris Vaddi, Ph.D.
 Comapany NamePrelude Therapeutics Incorporated
 August 19, 2020 Page 2
 FirstName LastNameKris Vaddi, Ph.D.
Prelude Therapeutics Incorporated
August 19, 2020
Page 2
pivotal Phase 3 trial for the products listed. Note that the arrows for each listed program
should be accurately drawn to show the precise phase of development after the table has
been revised.
Implications of Being an Emerging Growth Company and a Smaller Reporting Company, page 5
3.Please provide us with copies of all written communications, as defined in Rule 405 under
the Securities Act, that you, or anyone authorized to do so on your behalf, present to
potential investors in reliance on Section 5(d) of the Securities Act, whether or not they
retain copies of the communications.
Use of Proceeds, page 72
4.Please revise the discussion to identify the stage of clinical development you expect to
achieve with the proceeds of the offering for PRT543, PRT811, and PRT1419.  To the
extent you expect to begin a particular stage of development but do not expect to complete
it, please indicate that you will need to raise additional funding to complete that stage of
development.
Management's Discussion and Analysis of Financial Condition and Results of Operations
Critical Accounting Policies
Stock-Based Compensation, page 88
5.Once you have an estimated offering price or range, please explain to us how you
determined the fair value of the common stock underlying your equity issuances and the
reasons for any differences between the recent valuations of your common stock leading
up to the IPO and the estimated offering price. This information will help facilitate our
review of your accounting for equity issuances including stock compensation and
beneficial conversion features.
Target Selection, page 99
6.We note your statements regarding your framework for optimizing your drug discovery
and development efforts that you believe "increases the probability of clinical and
regulatory success...."  We also note your statements that you believe your approach "will
result in better targeted and more effective cancer therapies" and that you have observed
"promising clinical activity" to date. Please revise the prospectus to remove any
statements, such as these, that imply forthcoming regulatory approval of you product
candidates or the safety and efficacy of your candidates, as these determinations are the
exclusive authority of the FDA or other regulators.
Our Product Candidates, page 101
7.Revise to explain briefly key measures you cite throughout your Business section,
including terms such as “complete response” and “stable disease.”  Also, please ensure
that you provide a balanced presentation of clinical results.  In this regard, we note that

 FirstName LastNameKris Vaddi, Ph.D.
 Comapany NamePrelude Therapeutics Incorporated
 August 19, 2020 Page 3
 FirstName LastName
Kris Vaddi, Ph.D.
Prelude Therapeutics Incorporated
August 19, 2020
Page 3
your discussion of the interim and preliminary efficacy data for your PRT543 Phase 1 trial
where you highlight a patient with a confirmed complete response but you do not provide
interim data for the other 25 patients.  Please revise or advise.
8.Please revise the discussion that accompanies Tables 2, 3, and 5 to clarify how these
results demonstrate the relative inhibitory potency of your product candidates and also
discuss why the levels achieved support continued clinical development.
Group A (Solid Tumors), page 111
9.Please revise your disclosure to briefly explain the parameters "Tmax" and "AUC0-T"
listed in the tables on pages 111, 112 and 119.
Employment Arrangements with our Named Executive Officers, page 153
10.Please file your employment agreements with each of your executive officers as exhibits
to the registration statement, as required by Item 601(b)(10) of Regulation S-K.
Audited Financial Statemetns as of December 31, 2018 and 2019 and for the Years then Ended
Note 1 Net Loss Per Share and Unaudited Pro Forma Net Loss Per Share, page F-11
11.Your pro forma net loss per share calculation appears to assume that the 8,823,529 shares
of Series B convertible preferred stock issued in May 2019 converted at the beginning of
the period rather than at their date of issuance.  Please refer to ASC 260-10-45-40(c) and
advise or revise your pro forma information accordingly.  Also, once you update your
financial statements for the six months ended June 30, 2020, please address this comment
as it relates to the 8,823,529 shares of Series B convertible preferred stock issued in
March 2020.
            You may contact Rolf Sundwall at 202-551-3105 or Jeanne Baker at 202-551-3691 if you
have questions regarding comments on the financial statements and related matters.  Please
contact Jeffrey Gabor at 202-551-2544 or Laura Crotty at 202-551-7614 with any other
questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Rob Freedman, Esq.