CALITHERA BIOSCIENCES, INC. (Name of Registrant As Specified in Its Charter)

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A INFORMATION 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: ☐ Preliminary Proxy Statement ☐ Confidential, for Use of the Commission Only (as permitted by Rule 14a-6(e)(2)) ☑ Definitive Proxy Statement ☐ Definitive Additional Materials ☐ Soliciting Material Pursuant to § 240.14a-12 CALITHERA BIOSCIENCES, INC. (Name of Registrant as Specified In Its Charter) (Name of Person(s) Filing Proxy Statement if Other Than the Registrant) Payment of Filing Fee (Check the appropriate box) ☑ No fee required. ☐ Fee computed on table below per Exchange Act Rules 14a-6(i)(1) and 0-11. 1. Title of each class of securities to which transaction applies: 2. Aggregate number of securities to which transaction applies: 3. Per unit price or other underlying value of transaction computed pursuant to Exchange Act Rule 0-11 (Set forth the amount on which the filing fee is calculated and state how it was determined): 4. Proposed maximum aggregate value of transaction: 5. Total fee paid: ☐ Fee paid previously with preliminary materials. ☐ Check box if any part of the fee is offset as provided by Exchange Act Rule 0-11(a)(2) and identify the filing for which the offsetting fee was paid previously. Identify the previous filing by registration statement number, or the Form or Schedule and the date of its filing. 6. Amount Previously Paid: 7. Form, Schedule or Registration Statement No.: 8. Filing Party: 9. Date Filed: CALITHERA BIOSCIENCES, INC. 343 Oyster Point Blvd., Suite 200 South San Francisco, California 94080 (650) 870-1000 NOTICE OF ANNUAL MEETING OF STOCKHOLDERS To Be Held On June 11, 2021 Dear Stockholder: You are cordially invited to attend the Annual Meeting of Stockholders of Calithera Biosciences, Inc., a Delaware corporation (the “Company”). The meeting will be held virtually, via live webcast at https://web.lumiagm.com/282387153 originating from San Francisco, California on Friday, June 11, 2021 at 9:00 a.m. local time due to the continuing public health impact of the COVID-19 pandemic and to support the health and well-being of our partners, employees, and stockholders. You will not be able to attend the Annual Meeting in person. The meeting will be held for the following purposes, as more fully described in the accompanying proxy statement: 1. To elect the Board of Directors’ (the “Board”) three nominees for director to serve until the 2024 Annual Meeting of stockholders or until their successors are selected. 2. To ratify the selection by the Audit Committee of the Board (the “Audit Committee”) of Ernst & Young LLP as the independent registered public accounting firm of the Company for the year ending December 31, 2021. 3. To approve, on an advisory basis, the compensation of the Company’s named executive officers, as disclosed in the proxy statement accompanying this notice. 4. To conduct any other business properly brought before the meeting. These items of business are more fully described in the Proxy Statement accompanying this Notice. The record date for the Annual Meeting is April 12, 2021. Only stockholders of record at the close of business on that date may vote at the meeting or any adjournment thereof. Important notice regarding the availability of proxy materials for the Annual Meeting of Stockholders to be held on June 11, 2021. This notice, the proxy statement accompanying this notice and our Annual Report on Form 10-K may be found at http://ir.calithera.com/financial- information/annual-reports. By Order of the Board, /s/ Stephanie Wong Secretary South San Francisco, California April 23, 2021 You are cordially invited to attend the virtual annual meeting. Whether or not you expect to attend the virtual meeting, you are urged to vote and submit your proxy by following the voting procedures described in the proxy card. Even if you have voted by proxy, you may still vote during the virtual meeting. Please note, however, that if your shares are held of record by a broker, bank or other agent and you wish to vote during the meeting, you must follow the instructions from your broker, bank or other agent. CALITHERA BIOSCIENCES, INC. 343 Oyster Point Blvd., Suite 200 South San Francisco, California 94080 (650) 870-1000 PROXY STATEMENT FOR THE 2021 ANNUAL MEETING OF STOCKHOLDERS June 11, 2021 QUESTIONS AND ANSWERS ABOUT THESE PROXY MATERIALS AND VOTING Why did I receive a notice regarding the availability of proxy materials on the internet? Pursuant to rules adopted by the Securities and Exchange Commission (the “SEC”), we have elected to provide access to our proxy materials over the internet. Accordingly, we have sent you a Notice of Internet Availability of Proxy Materials (the “Notice”) because the Board of Calithera Biosciences, Inc. (sometimes referred to as the “Company” or “Calithera”) is soliciting your proxy to vote at the 2021 Annual Meeting of Stockholders (the “Annual Meeting”), including at any adjournments or postponements of the meeting. All stockholders will have the ability to access the proxy materials on the website referred to in the Notice or request to receive a printed set of the proxy materials. Instructions on how to access the proxy materials over the internet or to request a printed copy may be found in the Notice. We expect to mail the Notice on or about April 30, 2021 to all stockholders of record entitled to vote at the Annual Meeting. Will I receive any other proxy materials by mail? No, you will not receive any other proxy materials by mail unless you request a paper copy of proxy materials. To request that a full set of the proxy materials be sent to your specified postal address, please go to www.voteproxy.com or call 1-800-776-9962. Please have your proxy card in hand when you access the website or call and follow the instructions provided. How do I attend and participate in the Annual Meeting online? This year’s Annual Meeting will be a completely virtual meeting of stockholders and will be webcast live over the Internet. Any stockholder can attend the virtual meeting live online at https://web.lumiagm.com/282387153. The webcast will start at 9 a.m. Pacific Time. Stockholders as of the Record Date may vote and submit questions while attending the meeting online. We encourage you to access the meeting prior to the start time. If you encounter any difficulties accessing the virtual meeting during the check-in or meeting time, please refer to the technical support information located at https://go.lumiglobal.com/faq. In order to enter the meeting, you will need the control number and the password: cala2021. The control number will be included in the Notice or on your proxy card if you are a stockholder of record of shares of common stock (as defined below). If your shares are held in “street name” through a broker, bank or other nominee, in order to participate in the virtual annual meeting, you must first obtain a legal proxy from your broker, bank or other nominee reflecting the number of shares of CALA held as of the record date, your name and email address. You must then submit a request for registration to American Stock Transfer & Trust Company, LLC: (1) by email to [email protected]; (2) by facsimile to 718-765-8730; or (3) by mail to American Stock Transfer & Trust Company, LLC, Attn: Proxy Tabulation Department, 6201 15th Avenue, Brooklyn, NY 11219. Requests for registration must be labeled as “Legal Proxy” and be received by American Stock Transfer & Trust Company, LLC no later than 5:00 p.m. Eastern time on June 2, 2021. Instructions on how to attend and participate online are available at https://web.lumiagm.com/282387153. You will not be able to attend the Annual Meeting in person. 1 Why a Virtual-Only Online Meeting? Conducting the annual meeting virtually allows for remote participation in light of the COVID-19 pandemic and increases the opportunity for all stockholders to participate and communicate their views to a much wider audience. In addition, holding the meeting virtually allows us to make much more efficient use of the time of our independent directors. Stockholder rights are not affected. Additionally, we use software that verifies the identity of each participating stockholder and ensures during the question and answer portion of the meeting that they are granted the same rights they would have at an in-person meeting. We may consider a change in our virtual-only meeting practice in the future. Given the above listed factors, we feel a virtual- only meeting is the right choice for Calithera and its stockholders at this time. Our virtual Annual Meeting allows stockholders to submit questions and comments before and during the Annual Meeting. To the extent time doesn’t allow us to answer all of the appropriately submitted questions, we will answer them in writing on our investor relations website, at http://ir.calithera.com/investor-overview, soon after the meeting. If we receive substantially similar questions, we will group such questions together and provide a single response to avoid repetition. What happens if there are technical difficulties during the Annual Meeting? We will have technicians ready to assist you with any technical difficulties you may have accessing the virtual Annual Meeting, voting at the Annual Meeting or submitting questions at the Annual Meeting. If you encounter any difficulties accessing the virtual Annual Meeting during the check-in or meeting time, please refer to the technical support information located at https://go.lumiglobal.com/faq.

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