Form DEFA14A Septerna, Inc.

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

SCHEDULE 14A

(Rule 14a-101)

Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934

(Amendment No. )

Filed by the Registrant ☒

Filed by a party other than the Registrant ☐

Check the appropriate box:

SEPTERNA, INC.

(Name of Registrant as Specified In Its Charter)

Not applicable.

(Name of Person(s) Filing Proxy Statement, if other than the Registrant)

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Logo SEPTERNA, INC. 250 EAST GRAND AVENUE SOUTH SAN FRANCISCO, CA 94080 Your Vote Counts! SEPTERNA, INC. 2026 Annual Meeting of Stockholders To be held Online on June 26, 2026 Vote by June 25, 2026 11:59 PM ET V96872-P48357 Important Notice Regarding the Availability of Proxy Materials for the Stockholder Meeting To Be Held on June 26, 2026. You invested in SEPTERNA, INC. and it’s time to vote! You have the right to vote on proposals being presented at the Annual Meeting. Get informed before you vote View the Notice, Proxy Statement and 2025 Annual Report online at www.ProxyVote.com OR you can receive a free paper or email copy of the material(s) by requesting prior to June 12, 2026. If you would like to request a copy of the material(s) for this and/or future stockholder meetings, you may (1) visit www.ProxyVote.com, (2) call 1-800-579-1639 (toll-free from the U.S., U.S. territories and Canada) or (3) send an email to [email protected]. If sending an email, please include your control number (indicated below) in the subject line. Unless requested, you will not otherwise receive a paper or email copy. For complete information and to vote, visit www.ProxyVote.com Control # Smartphone users Point your camera here and vote without entering a control number Vote Virtually at the Meeting* June 26, 2026 2:00 PM PST Virtually at: www.virtualshareholdermeeting.com/SEPN2026 *Please check the meeting materials for any special requirements for meeting attendance.

Vote at www.ProxyVote.com THIS IS NOT A VOTABLE BALLOT This is an overview of the proposals being presented at the upcoming 2026 Annual Meeting. Please follow the instructions on the reverse side to vote these important matters. Voting Items Board Recommends 1. Election of Directors Nominees: 1a. Shalini Sharp, M.B.A. Board Recommends For 1b. Jake Simson, Ph.D. 2. For Ratification of the appointment of Ernst & Young LLP as the Company’s independent registered public accounting firm for the fiscal year ending December 31, 2026. For NOTE: Such other business as may properly come before the meeting or any adjournment or postponement thereofPrefer to receive an email instead? While voting on www.ProxyVote.com, be sure to click “Delivery Settings”. V96873-P48357