Statement of Changes in Beneficial Ownership (Form 4)

FORM 4 Check this box if no longer subject to Section 16. Form 4 or Form 5 obligations may continue. See Instruction 1(b). Check this box to indicate that a transaction was made pursuant to a contract, instruction or written plan that is intended to satisfy the affirmative defense conditions of Rule 10b5-1(c). See Instruction 10.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 STATEMENT OF CHANGES IN BENEFICIAL OWNERSHIP OF SECURITIES Filed pursuant to Section 16(a) of the Securities Exchange Act of 1934 or Section 30(h) of the Investment Company Act of 1940

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(Print or Type Responses)

1. Name and Address of Reporting Person * Shaikhly Samira 2. Issuer Name and Ticker or Trading Symbol Septerna, Inc. [SEPN] 5. Relationship of Reporting Person(s) to Issuer (Check all applicable) _____ Director _____ 10% Owner __X__ Officer (give title below) _____ Other (specify below) Chief People Officer (Last) (First) (Middle) C/O SEPTERNA, INC., 250 EAST GRAND AVENUE 3. Date of Earliest Transaction (Month/Day/Year) 03/02/2026 (Street) SOUTH SAN FRANCISCO, CA 94080 4. If Amendment, Date Original Filed (Month/Day/Year) 6. Individual or Joint/Group Filing (Check Applicable Line) _X_ Form filed by One Reporting Person ___ Form filed by More than One Reporting Person (City) (State) (Zip) Table I - Non-Derivative Securities Acquired, Disposed of, or Beneficially Owned

1.Title of Security (Instr. 3) 2. Transaction Date (Month/Day/Year) 2A. Deemed Execution Date, if any (Month/Day/Year) 3. Transaction Code (Instr. 8) 4. Securities Acquired (A) or Disposed of (D) (Instr. 3, 4 and 5) 5. Amount of Securities Beneficially Owned Following Reported Transaction(s) (Instr. 3 and 4) 6. Ownership Form: Direct (D) or Indirect (I) (Instr. 4) 7. Nature of Indirect Beneficial Ownership (Instr. 4) Code V Amount (A) or (D) Price Common Stock 03/02/2026 M 53,714 A $1.55 54,507(1) D Common Stock 03/02/2026 M 11,638 A $2.76 66,145 D Common Stock 03/02/2026 M 5,101 A $2.76 71,246 D Common Stock 03/02/2026 S(2) 4,090 D $27.5052(3) 67,156 D Common Stock 03/02/2026 S(2) 66,363 D $28.1383(4) 793 D

Reminder: Report on a separate line for each class of securities beneficially owned directly or indirectly.
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Table II - Derivative Securities Acquired, Disposed of, or Beneficially Owned
(e.g., puts, calls, warrants, options, convertible securities)

1. Title of Derivative Security (Instr. 3)

2. Conversion or Exercise Price of Derivative Security

3. Transaction Date (Month/Day/Year)

3A. Deemed Execution Date, if any (Month/Day/Year)

4. Transaction Code (Instr. 8)

5. Number of Derivative Securities Acquired (A) or Disposed of (D) (Instr. 3, 4, and 5)

6. Date Exercisable and Expiration Date (Month/Day/Year)

7. Title and Amount of Underlying Securities (Instr. 3 and 4)

8. Price of Derivative Security (Instr. 5)

9. Number of Derivative Securities Beneficially Owned Following Reported Transaction(s) (Instr. 4)

10. Ownership Form of Derivative Security: Direct (D) or Indirect (I) (Instr. 4)

11. Nature of Indirect Beneficial Ownership (Instr. 4)

Code

V

(A)

(D)

Date Exercisable

Expiration Date

Title

Amount or Number of Shares

Stock Option (Right to Buy)

$1.55

03/02/2026

M

53,714

(5)

03/30/2033

Common Stock

53,714

$ 0

15,969

D

Stock Option (Right to Buy)

$2.76

03/02/2026

M

11,638

(5)

11/11/2033

Common Stock

11,638

$ 0

3,460

D

Stock Option (Right to Buy)

$2.76

03/02/2026

M

5,101

(6)

03/19/2034

Common Stock

5,101

$ 0

5,101

D

Reporting Owners

Reporting Owner Name / Address	Relationships
	Director	10% Owner	Officer	Other
Shaikhly Samira C/O SEPTERNA, INC. 250 EAST GRAND AVENUE SOUTH SAN FRANCISCO, CA 94080			Chief People Officer

Signatures

/s/ Mark A. Wilson, Attorney-in-Fact		03/04/2026
**Signature of Reporting Person		Date

Explanation of Responses:

*	If the form is filed by more than one reporting person, see Instruction 4(b)(v).
**	Intentional misstatements or omissions of facts constitute Federal Criminal Violations. See 18 U.S.C. 1001 and 15 U.S.C. 78ff(a).
(1)	Includes 793 shares acquired under the Septerna, Inc. 2024 Employee Stock Purchase Plan on October 31, 2025 in a transaction that was exempt under Rule 16b-3(c).
(2)	This transaction was effected pursuant to a Rule 10b5-1 sales plan adopted by the Reporting Person on October 31, 2025.
(3)	The price reported in Column 4 is a weighted average price. The shares were purchased in multiple transactions at prices ranging from $26.90 to $27.89. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the range.
(4)	The price reported in Column 4 is a weighted average price. The shares were purchased in multiple transactions at prices ranging from $27.90 to $28.70. The Reporting Person undertakes to provide to the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares purchased at each separate price within the range.
(5)	25% of the shares underlying this option vested on February 1, 2024, with the remainder vesting in thirty-six substantially equal monthly installments thereafter, subject to the Reporting Person's continuous service the Issuer on each such vesting date.
(6)	1/48th of the shares subject to such option vest and become exercisable in substantially equal monthly installments on each monthly anniversary of March 1, 2024, subject to the Reporting Person's continuous service to the Issuer on each such date.

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