Tango Therapeutics, Inc.

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

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Securities Exchange Act of 1934

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TANGO THERAPEUTICS, INC.

(Name of Registrant as Specified In Its Charter)

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

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☐ Fee computed on table in exhibit required by Item 25(b) per Exchange Act Rules 14a-6(i)(1) and 0-11.

Dear Fellow Stockholder:

Tango Therapeutics was founded with a clear mission: to discover the next generation of targeted therapies in oncology by addressing the specific genetic alterations that drive cancer. We develop new drugs directed at tumor suppressor gene loss in defined patient populations with high unmet medical need. We made significant progress across our research and clinical development programs in 2024 and early 2025:

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In November 2024, we reported positive early data from the ongoing Phase 1/2 clinical trial of TNG462, our lead PRMT5 inhibitor, demonstrating durable clinical activity across multiple cancer types, with a strong safety and tolerability profile. We have initiated a robust clinical development program for TNG462.

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In November 2024, we also announced data from the Phase 1/2 clinical trial of TNG908, our first brain-penetrant PRMT5 inhibitor. TNG908 demonstrated clinical activity and was well-tolerated in non-CNS solid tumors. However, TNG908 did not meet the pharmacokinetic exposure threshold for clinical efficacy in glioblastoma and, therefore, we decided to discontinue further development in TNG908 to focus our resources on TNG462 and TNG456, our next generation brain-penetrant PRMT5 inhibitor being developed for glioblastoma.

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In January 2025, the U.S. Food and Drug Administration, or FDA, cleared the Investigational New Drug, or IND, application for TNG45.

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TNG260, our first-in-class CoREST inhibitor, demonstrated a favorable safety, tolerability, and pharmacokinetic profile in dose escalation, and we have established clinical proof-of-mechanism based on pharmacodynamic data from on-treatment patient biopsies. We are now enrolling lung cancer patients in the dose expansion portion of our Phase 1 study.

The board of directors and I are pleased to invite you to attend the 2025 Annual Meeting of Stockholders, or the Annual Meeting, of Tango Therapeutics, Inc., or Tango, or the Company, to be held virtually on Wednesday, June 5, 2025 at 9:00 a.m. Eastern Time. Stockholders will have the ability to participate in the Annual Meeting, vote their shares and ask questions by accessing the virtual meeting.

At the Annual Meeting, our stockholders will be asked to: (1) elect one nominee who is named in the Proxy Statement as a Class I Director; (2) ratify the appointment of PricewaterhouseCoopers LLP as our independent registered public accounting firm for the fiscal year ending December 31, 2025; (3) approve an amendment to our amended and restated certificate of incorporation, as amended to date, to increase to the number of shares of authorized common stock from 200,000,000 to 400,000,000; (3) hold a non-binding, advisory vote to approve the compensation of our named executive officers; (4) hold a non-binding, advisory vote on the frequency of further non-binding, advisory votes on the compensation of our named executive officers; and (5) transact any other business that properly comes before the Annual Meeting (including adjournments, continuations and postponements thereof). Our board of directors recommends that you vote “FOR” the election of the director nominee, “FOR” the ratification of the appointment of PricewaterhouseCoopers LLP, “FOR” the amendment to our amended and restated certificate of incorporation, as amended to date, to increase the number of shares of authorized common stock, “FOR” the compensation of our named executive officers and “FOR” the option of once every "one year" as the preferred frequency of future non-binding, advisory votes on the compensation of our named executive officers. You should carefully read our proxy materials, which contain detailed information concerning each of these proposals.

Under the Securities and Exchange Commission rules, the Company is providing access to the proxy materials for the Annual Meeting to stockholders via the Internet. Accordingly, you can access the proxy materials and vote at www.proxyvote.com. Instructions for accessing the proxy materials and voting are described below and in the Notice of Internet Availability of Proxy Materials that you received in the mail (unless you have previously requested a paper copy of our proxy materials). The Notice of Internet Availability of Proxy Materials also contains instructions on how to request a paper copy of our proxy materials and our Annual Report on Form 10-K for the year ended December 31, 2024. This process allows us to provide our stockholders with the information they need on a more timely basis, while reducing the environmental impact and lowering the costs of printing and distributing our proxy materials.

Your vote is very important. Whether or not you plan to virtually attend the meeting, please carefully review the proxy materials and then cast your vote. If you are a stockholder of record and have received our Notice of Internet Availability of Proxy Materials, then instructions regarding how you can vote are contained in that notice. If you requested to receive a printed set of the proxy materials, please vote by completing, signing, dating and mailing the accompanying proxy card in the return envelope or voting by telephone or the Internet, in accordance with the instructions set forth on the proxy card. Submitting your vote via the Internet or by telephone or proxy card will not affect your right to attend and to vote at the Annual Meeting if you decide to virtually attend the Annual Meeting. If your shares are held in street name (held for your account by a broker or other nominee), you will receive instructions from your broker or other nominee explaining how to vote your shares, and you will have the option to cast your vote by telephone or over the Internet if your voting instruction form from your broker or nominee includes instructions and a toll-free telephone number or Internet website to do so. In any event, to be sure that your vote will be received in time, please cast your vote by your choice of available means at your earliest convenience.

On behalf of our board of directors, team members, and patients, thank you for your ongoing support of, and continued interest in, Tango.

Sincerely,

Barbara Weber, M.D.

President and Chief Executive Officer

201 Brookline Avenue, Suite 901

Boston, MA 02215

NOTICE OF 2025 ANNUAL MEETING OF STOCKHOLDERS

To be held on June 5, 2025

Notice is hereby given that the 2025 Annual Meeting of Stockholders, or Annual Meeting, of Tango Therapeutics, Inc., will be held online on Thursday, June 5, 2025. You may attend the meeting virtually via the Internet, where you will be able to participate in the meeting, vote electronically and submit questions that are germane to the matters under consideration at the Annual Meeting. You will need the 16-digit control number included with the Notice of Internet Availability of Proxy Materials, your proxy card (if you received a printed copy of the proxy materials) or in the instructions that accompanied your proxy materials in order to attend the Annual Meeting.

The purpose of the Annual Meeting is the following:

1. To elect one Class I Director, Lesley Ann Calhoun, to our board of directors, to serve until the 2028 annual meeting of stockholders and until her successor has been duly elected and qualified, or until her earlier death, resignation or removal;

2. To ratify the appointment of PricewaterhouseCoopers LLP as the independent registered public accounting firm for the fiscal year ending December 31, 2025;

3. To approve an amendment to our Second Amended and Restated Certificate of Incorporation, as amended to date, to increase the number of authorized shares of common stock from 200,000,000 to 400,000,000;

4. To approve, on a non-binding, advisory basis, the compensation of our named executive officers;

5. To vote on a non-binding, advisory basis, on the frequency of future non-binding, advisory votes on executive compensation; and

6. To transact any other business properly brought before the Annual Meeting or any adjournment or postponement of the Annual Meeting.

The Annual Meeting will begin promptly at 9:00 a.m. Eastern Time. Only stockholders of record at the close of business on April 8, 2025 will be entitled to vote at the Annual Meeting and any adjournment or postponement thereof.

We are pleased to adhere to the Securities and Exchange Commission’s “Notice and Access” rule that allows companies to furnish their proxy materials by posting them on the Internet. As a result, we are mailing to our stockholders a Notice of Internet Availability of Proxy Materials, or the Notice, instead of a paper copy of the accompanying proxy statement and our Annual Report on Form 10-K for the fiscal year ended December 31, 2024, or 2024 Annual Report. We plan to mail the Notice on or about April 21, 2025, and it contains instructions on how to access both the 2024 Annual Report and accompanying proxy statement over the Internet. This method provides our stockholders with expedited access to proxy materials and not only lowers the cost of printing and distribution but also reduces the environmental impact of the Annual Meeting. If you would like to receive a print version of the proxy materials, free of charge, please follow the instructions in this Notice.

To be virtually admitted to the Annual Meeting and vote your shares, you must provide the 16-digit control number as provided in the Notice, your proxy card (if you received a printed copy of the proxy materials) or in the instructions that accompanied your proxy materials. Please see the “General Information Regarding the Meeting”

section of the proxy statement that accompanies this notice for more details regarding the logistics of the virtual Annual Meeting, including the ability of stockholders to submit questions that are germane to the topics under consideration at the Annual Meeting during the Annual Meeting, and technical details and support related to accessing the virtual platform.

Your vote is important. Whether or not you expect to attend the Annual Meeting virtually, it is important that your shares be represented. To ensure that your vote is recorded promptly, please vote as soon as possible, even if you plan to attend the meeting, by submitting your proxy via the Internet at the address listed on the proxy card, via the telephone number listed on the proxy card or by signing, dating and returning the proxy card. Even if you have voted by proxy, you may still vote at the Annual Meeting. Please note, however, that if your shares are held through a broker, bank or other nominee and you wish to vote at the Annual Meeting, you must obtain a proxy issued in your name from that record holder.

By order of the Board of Directors,

Douglas Barry

Chief Legal Officer, Chief Compliance Officer and Corporate Secretary

Boston, MA

April 21, 2025

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