SCHEDULE 13G/A 0000950170-25-019900 0001778071 XXXXXXXX LIVE 1 Common Stock, $0.001 par value per share 03/31/2025 0001984086 Septerna, Inc. 81734D104 250 East Grand Avenue Suite 65 South San Francisco CA 94080 Rule 13d-1(d) Third Rock Ventures V, L.P. b DE 0 6215591 0 6215591 6215591 N 14.0 PN Third Rock Ventures GP V, L.P. b DE 0 6215591 0 6215591 6215591 N 14.0 PN TRV GP V, LLC b 0 6215591 0 6215591 6215591 N 14.0 OO Third Rock Ventures VI, L.P. b DE 0 4211659 0 4211659 4211659 N 9.5 PN Third Rock Ventures GP VI, L.P. b DE 0 4211659 0 4211659 4211659 N 9.5 PN TRV GP VI, LLC b DE 0 4211659 0 4211659 4211659 N 9.5 OO Septerna, Inc. 250 East Grand Avenue, South San Francisco, CA 94080 (i) Third Rock Ventures V, L.P. ("TRV V"); (ii) Third Rock Ventures GP V, L.P. ("TRV GP V"), which is the sole general partner of TRV V; (iii) TRV GP V, LLC ("TRV GP V LLC"), which is the sole general partner of TRV GP V; (iv) Third Rock Ventures VI, L.P. ("TRV VI"); (v) Third Rock Ventures GP VI, L.P. ("TRV GP VI"), which is the sole general partner of TRV VI; and (vi) TRV GP VI, LLC ("TRV GP VI LLC"), which is the sole general partner of TRV GP VI. The address of the principal business office of each of the Reporting Persons is Third Rock Ventures, LLC, 201 Brookline Ave, Suite 1401, Boston, MA 02215. Each of TRV V, TRV GP V, TRV VI and TRV GP VI is a Delaware limited partnership. Each of TRV GP V LLC and TRV GP VI LLC is a Delaware limited liability company. Y (i) TRV V directly owns 6,215,591 shares of Common Stock (the "V Shares") (ii) TRV GP V is the general partner of TRV V and may be deemed to beneficially own the V Shares. (iii) TRV GP V LLC is the general partner of TRV GP V and may be deemed to beneficially own the V Shares. (iv) TRV VI directly owns 4,211,659 shares of Common Stock (the "VI Shares"). (v) TRV GP VI is the general partner of TRV VI and may be deemed to beneficially own the VI Shares. (vi) TRV GP VI LLC is the general partner of TRV GP VI and may be deemed to beneficially own the VI Shares. Each of TRV V, TRV GP V, and TRV GP V LLC, on the one hand, and TRV VI, TRV GP VI and TRV GP VI LLC, on the other hand, disclaim the existence of a "group" for purposes of Rule 13d-5 of the Securities Exchange Act of 1934, as amended, and nothing contained in this report shall be deemed an admission that any such group exists or may exist. The V shares represent approximately 14.0% of the outstanding shares of Common Stock. The VI shares represent approximately 9.5% of the outstanding shares of Common Stock. The percent of class was calculated based on 44,442,496 shares of common stock issued and outstanding as of March 17, 2025, as disclosed in the Issuer's 10-K filed with the Securities and Exchange Commission on March 27, 2025. TRV V - 0 TRV GP V - 0 TRV GP V LLC - 0 TRV VI - 0 TRV GP VI - 0 TRV GP VI LLC - 0 TRV V - 6,215,591 shares TRV GP V - 6,215,591 shares TRV GP V LLC - 6,215,591 shares TRV VI - 4,211,659 shares TRV GP VI - 4,211,659 shares TRV GP VI LLC - 4,211,659 shares TRV V - 0 TRV GP V - 0 TRV GP V LLC - 0 TRV VI - 0 TRV GP VI - 0 TRV GP VI LLC - 0 TRV V - 6,215,591 shares TRV GP V - 6,215,591 shares TRV GP V LLC - 6,215,591 shares TRV VI - 4,211,659 shares TRV GP VI - 4,211,659 shares TRV GP VI LLC - 4,211,659 shares Y Y Y Y Y Y Third Rock Ventures V, L.P. /s/ Kevin Gillis 05/09/2025 Third Rock Ventures GP V, L.P. /s/ Kevin Gillis 05/09/2025 TRV GP V, LLC /s/ Kevin Gillis 05/09/2025 Third Rock Ventures VI, L.P. /s/ Kevin Gillis 05/09/2025 Third Rock Ventures GP VI, L.P. /s/ Kevin Gillis 05/09/2025 TRV GP VI, LLC /s/ Kevin Gillis 05/09/2025