SCHEDULE 13D/A 0001688327 XXXXXXXX LIVE 2 Common Stock 11/12/2025 false 0001819133 87583X109 Tango Therapeutics, Inc.

201 Brookline Avenue Suite 901 Boston MA 02215

Third Rock Ventures, LLC 617-585-2000 201 Brookline Avenue Suite 1401 Boston MA 02215 0001688327 N Third Rock Ventures IV, L.P. b WC N DE 0 9374574 0 9374574 9374574 N 6.97 PN The percent of class was calculated based on 134,593,998 shares of common stock issued and outstanding as of October 28, 2025, as disclosed in the Issuer's 10-Q filed with the Securities and Exchange Commission on November 4, 2025. 0001688326 N Third Rock Ventures GP IV, L.P. b AF N DE 0 9374574 0 9374574 9374574 N 6.97 PN The percent of class was calculated based on 134,593,998 shares of common stock issued and outstanding as of October 28, 2025, as disclosed in the Issuer's 10-Q filed with the Securities and Exchange Commission on November 4, 2025. 0001688325 N TRV GP IV, LLC b AF N DE 0 9374574 0 9374574 9374574 N 6.97 OO The percent of class was calculated based on 134,593,998 shares of common stock issued and outstanding as of October 28, 2025, as disclosed in the Issuer's 10-Q filed with the Securities and Exchange Commission on November 4, 2025. Common Stock Tango Therapeutics, Inc. 201 Brookline Avenue Suite 901 Boston MA 02215 This Amendment No. 2 (this "Amendment") amends and supplements the Schedule 13D (the "Schedule 13D") filed by the Reporting Persons with respect to the shares of common stock, $0.001 par value per share ("Common Stock"), of Tango Therapeutics, Inc. (the "Company" or the "Issuer"). The transactions described in Item 5(c) resulted in a decrease of over one percent (1%) in the aggregate percentage ownership reported by the Reporting Persons in the Schedule 13D. Except as specifically provided herein, this Amendment does not modify any of the information previously reported in the Schedule 13D. As of November 11, 2025, TRV IV had shared voting and dispositive power with respect to 9,374,574 shares of the Issuer's Common Stock, constituting approximately 6.97% of the Issuer's outstanding Common Stock. As of November 11, 2025, Third Rock Ventures GP IV, L.P. ("TRV GP IV"), as the general partner of TRV IV may be deemed to have shared voting and dispositive power with respect to all 9,374,574 shares of the Issuer's Common Stock owned by TRV IV, constituting approximately of the Issuer's outstanding Common Stock. As of November 11, 2025, TRV GP IV, LLC ("TRV GP IV LLC," and collectively with TRV IV and TRV GP IV, the "Reporting Persons"), as the general partner of TRV GP IV may be deemed to have shared voting and dispositive power with respect to all 9,374,574 shares of the Issuer's Common Stock owned by TRV IV, constituting approximately 6.97% of the Issuer's outstanding Common Stock. The percent of class was calculated based on 134,593,998 shares of common stock issued and outstanding as of October 28, 2025, as disclosed in the Issuer's 10-Q filed with the Securities and Exchange Commission on Novemebr 4, 2025. Regarding the number of shares as to which such person has: (i) sole power to vote or to direct the vote: See line 7 of cover sheets (ii) shared power to vote or to direct the vote: See line 8 of cover sheets (iii) sole power to dispose or to direct the disposition: See line 9 of cover sheets. (iv) shared power to dispose or to direct the disposition: See line 10 of cover sheets Except as set forth in the table below, no transactions in the Common Stock were effected by the Reporting Persons during the 60-day period ended November 11, 2025. Date Amount of Securities Price per Share Where and How Effected TRV IV 9/16/2025 363,541 $7.04* Disposed in the Open Market TRV IV 9/25/2025 500,000 $8.02* Disposed in the Open Market TRV IV 10/23/2025 477,401 $10.15* Disposed in the Open Market TRV IV 11/6/2025 1,500,000 $8.00* Disposed in the Open Market TRV IV 11/10/2025 278,956 $8.00* Disposed in the Open Market TRV IV 11/11/2025 721,044 $8.20* Disposed in the Open Market TRV IV 11/12/2025 1,512,000 $8.20* Disposed in the Open Market * The price reported is a weighted average price. These shares were sold in multiple transactions. Third Rock Ventures IV, L.P. /s/ Kevin Gillis 11/14/2025 Third Rock Ventures GP IV, L.P. /s/ Kevin Gillis 11/14/2025 TRV GP IV, LLC /s/ Kevin Gillis 11/14/2025