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CORRESP
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CORRESP

 Goodwin Procter LLP

601 Marshall St.

 Redwood City, CA 94063

 goodwinlaw.com

+1 650 752 3100

 October 15, 2024

FOIA CONFIDENTIAL TREATMENT REQUESTED

 The entity
requesting confidential treatment is

 Septerna, Inc.

 250
East Grand Avenue

 South San Francisco, California 94080

Telephone: (650) 338-3533

CERTAIN PORTIONS OF THIS LETTER HAVE BEEN OMITTED FROM THE VERSION FILED VIA EDGAR. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT
TO THE OMITTED PORTIONS. INFORMATION THAT WAS OMITTED IN THE EDGAR VERSION HAS BEEN NOTED IN THIS LETTER WITH A PLACEHOLDER IDENTIFIED BY THE MARK “[***].”

VIA EDGAR

 U.S. Securities and Exchange Commission

 Division of Corporation Finance

 Office of Life Sciences

 100 F Street, N.E.

 Washington, D.C. 20549

Attention: Ibolya Ignat, Angela Connell, Tamika Sheppard and Suzanne Hayes

RE: Septerna, Inc.

 Registration Statement on Form S-1

 File No. 333-282469

CIK No. 0001984086

 Rule 83 Confidential
Treatment Request by Septerna, Inc.

 Dear Ladies and Gentlemen:

On behalf of Septerna, Inc. (the “Company”), in response to comments from the staff (the “Staff”) of the U.S. Securities and Exchange
Commission (the “Commission”) received by letter dated September 5, 2024 (the “Comment Letter”) relating to the Company’s Registration Statement on Form S-1, originally
confidentially submitted to the Commission on August 2, 2024 and resubmitted on September 12, 2024, and subsequently publicly filed by the Company with the Commission on October 2, 2024 (File
No. 333-282469) (the “Registration Statement”), we submit this supplemental letter to address comment 16 of the Comment Letter.

FOIA CONFIDENTIAL TREATMENT REQUESTED BY SEPTERNA, INC.

 Division of Corporation Finance

Office of Life Sciences

 U.S. Securities and Exchange Commission

 October 15, 2024

  Page
 2

 Because of the commercially sensitive nature of information contained herein, this submission is accompanied
by the Company’s request for confidential treatment for selected portions of this letter. The Company has concurrently filed a separate letter with the Office of Freedom of Information and Privacy Act Operations in connection with the
confidential treatment request, pursuant to Rule 83 of the Commission’s Rules on Information and Requests, 17 C.F.R. § 200.83. For the Staff’s reference, we have enclosed a copy of the Company’s letter to the Office of Freedom of
Information and Privacy Act Operations. A redacted version of this letter will be filed with the Commission on EDGAR, omitting the confidential information.

We confirm on behalf of the Company that, prior to circulating copies of the preliminary prospectus in connection with the offering, the Company will file a pre-effective amendment to the Registration Statement that will include all information other than information that may be excluded in reliance upon Rule 430A of Regulation C, and the final price range to be
included in such amendment which will comply with the Staff’s interpretation regarding the parameters of a bona fide price range.

 Prior to
the effectiveness of the Registration Statement, the Company intends to implement a reverse stock split of its Common Stock (as defined below) (the “Stock Split”). The Company expects to reflect the Stock Split in a pre-effective amendment to the Registration Statement that includes the actual price range. For purposes of this letter, we have presented all dollar and per share amounts without giving effect to the Stock Split to
be consistent with the current presentation in the Registration Statement.

 The Company respectfully requests that the bracketed information contained
in this letter be treated as confidential information pursuant to Rule 83 promulgated by the Commission, 17 C.F.R. §200.8, and that the Commission provide timely notice to Jeffrey Finer, M.D., Ph.D. before it permits any disclosure of the
bracketed information in this letter.

 For the convenience of the Staff, we have recited the prior comment from the Staff in the Comment Letter in
italicized type and have followed the comment with the Company’s response.

16.
 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 initial public offering and the estimated offering price. This information will help
facilitate our review of your accounting for equity issuances. Please discuss with the staff how to submit your response.

 The
Company respectfully submits the below additional information to assist the Staff in its review of the Company’s position with respect to its determination of the fair value of the Company’s common stock, par value $0.001 per share
(“Common Stock”), underlying its outstanding equity awards and the reasons for the differences between the recent valuation of its Common Stock and the estimated offering price for its initial public offering (“IPO”).

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FOIA CONFIDENTIAL TREATMENT REQUESTED BY SEPTERNA, INC.

 Division of Corporation Finance

Office of Life Sciences

 U.S. Securities and Exchange Commission

 October 15, 2024

  Page
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 Preliminary IPO Price Range

The Company advises the Staff that it estimates a preliminary price range of approximately $[***] to $[***] per share (the “Preliminary Price Range”)
for its IPO, before giving effect to the Stock Split, resulting in a midpoint of the Preliminary Price Range of $[***] per share. The actual price range to be included in a subsequent amendment to the Registration Statement (which will comply with
the Staff’s interpretation regarding the parameters of a bona fide price range) has not yet been determined and remains subject to adjustment based on factors outside of the Company’s control. However, the Company believes that the
foregoing Preliminary Price Range will not be subject to significant change.

 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, performance of recent initial public offerings of other comparable biotechnology companies
and input received from the lead underwriters of the IPO, including discussions that took place during a meeting of the Company’s board of directors (the “Board”) on September 30, 2024, that included representatives of the
underwriters. 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.

 Determining the Fair Value of Common Stock Prior to the IPO

As there has been no public market for the Common Stock to date, the estimated fair value of its Common Stock has historically been determined by the Board as
of the date of each equity award, with input from management, considering the Company’s most recently available third-party valuations of its Common Stock, and the Board’s assessment of additional objective and subjective factors that it
believed were relevant and which may have changed from the date of the most recent valuation through the date of the grant. Subsequent to the Board-approved third-party valuations, the fair values of the Common Stock as of the date of certain equity
awards were adjusted in connection with a retrospective fair value assessment for accounting purposes, as described below. These retrospective third-party valuations were performed in accordance with the guidance outlined in the American Institute
of Certified Public Accountants’ Accounting and Valuation Guide, Valuation of Privately-Held-Company Equity Securities Issued as Compensation (the “Practice Aid”).

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FOIA CONFIDENTIAL TREATMENT REQUESTED BY SEPTERNA, INC.

 Division of Corporation Finance

Office of Life Sciences

 U.S. Securities and Exchange Commission

 October 15, 2024

  Page
 4

 The Company’s most recent third-party valuations of its Common Stock utilized by the Board in
determining exercise prices at the time of each equity award were as follows:

 Date of

Third-Party Valuation

Estimated Fair Market
Value of Common
Stock per Share

Estimated Fair Market
Value of Common
Stock Per Share as
of Date of Grant

 November 7, 2022

$
0.18

$
0.18

 June 28, 2023

$
0.40

N/A
(1)

 September 30, 2023

$
0.32

$
0.36
(2)

 May 31, 2024

$
0.69

N/A
(1)

 July 15, 2024

$
0.79

$
0.79

(1)
 No awards were granted based on this third-party valuation.

(2)
 Reflects the results of retrospective valuations of the Company’s September 30, 2023 valuation in
connection with a fair value assessment for accounting purposes.

 Equity Awards Between January 1, 2023 and October 15, 2024

 The following table summarizes by grant date the number of shares subject to awards granted between January 1, 2023 and October 15,
2024, the per share exercise price of the awards and the fair value of Common Stock underlying the equity awards on each grant date:

 Grant Date

Type of
Award

Number of
Shares Subject
to Awards
Granted

Per Share
Exercise Price
of Award

Per Share Fair
Market Value of
Common Stock
on Grant Date(1)

Per Share
Estimated Fair
Value of Award
on Grant Date(3)

 March 31, 2023

Option

750,000

$
0.18

$
0.18

$
0.32

 November 12, 2023

Option

8,102,202

$
0.32

$
0.32

$
0.34-0.35

 December 8, 2023

Option

435,000

$
0.32

$
0.32

$
0.40

 January 24, 2024

Option

700,000

$
0.32

$
0.32

$
0.41

 March 20, 2024

Option

5,290,855

$
0.32

$
0.32

$
0.30-0.31

 August 30, 2024

Option

881,000

$
0.79

$
0.79

N/A
(2)

 September 23, 2024

Option

7,836,500

$
0.79

$
0.79

N/A
(2)

 September 26, 2024

Option

1,975,000

$
0.79

$
0.79

N/A
(2)

(1)
 The per share fair market value of Common Stock on grant date is based on the most recent third-party valuation
in effect at each grant date.

(2)
 Subject to adjustment based on the future reassessment as described below.

(3)
 The per share estimated fair value of options reflects the fair value of options granted on each grant date
determined using the Black-Scholes option-pricing model.

 Valuation Methodologies

The third-party valuations were performed in accordance with the guidance outlined in the Practice Aid. As disclosed in the Registration Statement, the
Company’s enterprise value valuations were prepared using either an option pricing method (“OPM”) market-adjusted back-solve approach based on a recent arms-length transaction, a market-adjusted equity, or a hybrid method
(“Hybrid”), which is a combination of an OPM scenario and one or more scenarios using a probability-weighted expected return method (“PWERM”), with an IPO scenario and a continued operation as a private company scenario.

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FOIA CONFIDENTIAL TREATMENT REQUESTED BY SEPTERNA, INC.

 Division of Corporation Finance

Office of Life Sciences

 U.S. Securities and Exchange Commission

 October 15, 2024

  Page
 5

 The OPM treats common stock and preferred stock as call options on the total equity value of a company, with
exercise prices based on the value thresholds at which the allocation among the various holders of a company’s securities changes. Under this method, the common stock has value only if the funds available for distribution to stockholders
exceeded the value of the preferred stock liquidation preferences at the time of the liquidity event, such as a strategic sale or a merger.

 The PWERM is
a scenario-based methodology that estimates the fair value of common stock based upon an analysis of future values for the company, assuming various outcomes. The common stock value is based on the probability-weighted present value of expected
future investment returns considering each of the possible outcomes available as well as the rights of each class of stock. The future value of the common stock under each outcome is discounted back to the date of the applicable valuation (each, a
“Valuation Date”) at an appropriate risk-adjusted discount rate and probability weighted to arrive at an indication of value for the common stock. A discount for lack of marketability (“DLOM”) of the common stock is then applied
to arrive at an indication of value for the common stock.

 The hybrid method is a hybrid between the PWERM and OPM, estimating the probability-weighted
value across multiple scenarios, but using the OPM to estimate the allocation of value within one or more of those scenarios. When using the hybrid method, the third-party valuations considered two future-event scenarios: an IPO scenario and a
continued operation as a private company scenario. The equity value of the Company in the IPO scenario was determined using a market approach. The IPO scenario assumed that all shares of convertible preferred stock would convert into shares of
Common Stock and would no longer have the liquidation preferences and preferential rights attributable to the convertible preferred stock as compared to the Common Stock prior to the IPO. The guideline initial public offering transactions in the IPO
scenario consist of biotechnology companies with recent initial public offerings. The valuation converted the Company’s estimated future value in an IPO to present value using a risk-adjusted discount rate. The equity value for the continued
operation as a private company scenario was estimated using the price of a recently issued preferred security or a market-adjusted equity approach. At certain Valuation Dates, a preferred tranche model was used (time-based call option or
milestone-based model) as appropriate at each respective Valuation Date. The valuation utilized an OPM to quantify or attribute value to these economic rights of convertible preferred stock as compared to the Common Stock, such as liquidation
preferences, dividend provisions, and participation rights after liquidation preferences.

 November 7, 2022 Valuation

The fair value of the Common Stock of $0.18 per share at November 7, 2022 was determined with the assistance of an independent third-party valuation firm
and approved by the Board. This valuation was used to support the fair market value of the Common Stock in accordance with Section 409A of the Internal Revenue Service’s Internal Revenue Code (the “IRC”) with respect to
March 31, 2023, along with other factors determined by the Board to be relevant at the time of such grant of options. Between November 7, 2022 and March 31, 2023, the Company continued to operate its business in the ordinary course
and there were no significant developments impacting the valuation of the Company.

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FOIA CONFIDENTIAL TREATMENT REQUESTED BY SEPTERNA, INC.

 Division of Corporation Finance

Office of Life Sciences

 U.S. Securities and Exchange Commission

 October 15, 2024

  Page
 6

 The November 7, 2022 valuation applied the OPM to allocate the fair value of the Company’s equity
to various securities within the Company’s capital structure. Under this method, the OPM model was built based on the Company’s capital structure and reasonable option model inputs. The total equity value of the Company was determined
based on a market-adjusted approach. Under this approach, the Company’s equity value from the prior valuation of November 2, 2021 was adjusted based on consideration given to the performance of the biotechnology indices as well as the
Company’s entity-specific factors. The equity value of the Company was determined such that the implied value per share of Series A convertible preferred stock (the “Series A Preferred Stock”), is equal to its original issue price,
which included the initial closing and first subsequent closing of the Series A Preferred Stock financing in November 2022 plus the future call option right of Series A Preferred Stock in