Calithera Biosciences, Inc. (Exact name of registrant as specified in its charter)

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1 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): January 4, 2021 Calithera Biosciences, Inc. (Exact name of registrant as specified in its charter) Delaware (State or other jurisdiction (Commission (I.R.S. Employer of incorporation) File Number) Identification No.) 343 Oyster Point Blvd., Suite 200 South San Francisco, California (Address of principal executive offices) (Zip Code) Registrant s telephone number, including area code: (650) (Former name or former address, if changed since last report) Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below): Written communications pursuant to Rule 425 under the Securities Act (17 CFR ) Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR a-12) Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR d-2(b)) Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR e-4(c)) Securities registered pursuant to Section 12(b) of the Act: Trading Name of Each Exchange Title of Each Class Symbol(s) on Which Registered Common Stock, par value $ per share CALA The Nasdaq Global Select Market Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 ( of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 ( b-2 of this chapter). Emerging Growth Company If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.

2 Item 2.02 Results of Operations and Financial Condition. On January 4, 2021, Calithera Biosciences, Inc. ( Calithera ) issued a press release titled Calithera Biosciences Reports CANTATA Study of Telaglenastat in Renal Cell Carcinoma Did Not Achieve Primary Endpoint a copy of which is filed as Exhibit 99.1 hereto. In the press release, the Company announced that based upon information currently available as of the date of this Current Report on Form 8-K (this Current Report ), Calithera anticipates cash, cash equivalents and investments of approximately $115 million at December 31, 2020, which management believes will be sufficient to meet its current operating plan through December 31, The information relating to cash, cash equivalents and investments is preliminary, has not been audited and is subject to change upon completion of the audit of Calithera s financial statements as of and for the year ended December 31, Item 2.05 Costs Associated with Exit or Disposal Activities. On January 4, 2021, Calithera also announced in the press release a reduction in force to extend its cash runway and ensure long-term sustainability. Calithera will reduce its workforce by approximately 35% to preserve cash resources. All employees affected by the workforce reduction will be eligible to receive, among other things, severance payments based on the applicable employee s level and years of service with Calithera and the continuation of group health insurance coverage for a specified time period post-termination. Each affected employee s eligibility for the severance benefits is contingent upon such employee s execution of a separation agreement, which includes a general release of claims against Calithera. Calithera anticipates the one-time severance-related charge associated with the workforce reduction to be approximately $1.3 million to $1.5 million, with the majority to be completed by the first quarter of The severance-related charge, which is expected to represent cash expenditures that the Company expects to incur in connection with the workforce reduction, are subject to a number of assumptions, and actual results may differ materially. The Company may also incur other charges or cash expenditures not currently contemplated due to events that may occur as a result of, or associated with, the workforce reduction. If the Company subsequently determines that it will incur additional significant costs and realignment charges, it will amend this Current Report to disclose such information. Item Other Events. The information contained in Item 2.02 above and the press release, dated January 4, 2021, titled Calithera Biosciences Reports CANTATA Study of Telaglenastat in Renal Cell Carcinoma Did Not Achieve Primary Endpoint are incorporated herein by reference. Cautionary Statement Regarding Forward-Looking Statements This Current Report contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, without limitation, statements regarding Calithera s expectations regarding our cash position as of December 31, 2020 and the estimated cash expenditures associated with termination benefits and severance-related charges. These risks and uncertainties may be amplified by the COVID-19 pandemic, which has caused significant economic uncertainty. If any of these risks materialize or underlying assumptions prove incorrect, actual results could differ materially from the results implied by these forward-looking statements. Additional risks and uncertainties that could cause actual outcomes and results to differ materially from those contemplated by the forwardlooking statements are included under the caption Risk Factors and elsewhere in Calithera s most recent filings with the SEC, including Calithera s Quarterly Report on Form 10-Q for the quarter ended September 30, 2020 and other documents Calithera has filed, or will file, with the SEC, including any subsequent reports on Form 10-K, Form 10-Q or Form 8-K filed with the SEC from time to time and available at These documents can be accessed on Calithera s Investor Relations page at by clicking on the link titled SEC Filings.

3 These forward-looking statements are based on management s beliefs and assumptions and on information currently available to management. The forward-looking statements included in this Current Report are made only as of the date hereof. We assume no obligation and do not intend to update these forward-looking statements, except as required by law or applicable regulation. Item (d) Exhibits. Financial Statements and Exhibits. Exhibit No. Description 99.1 Press Release, dated January 4, 2021, titled Calithera Biosciences Reports CANTATA Study of Telaglenastat in Renal Cell Carcinoma Did Not Achieve Primary Endpoint 104 Cover Page Interactive Data File (the cover page XBRL tags are embedded within the Inline XBRL document)

4 SIGNATURES Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized. Dated: January 4, 2021 Calithera Biosciences, Inc. By: /s/ Susan M. Molineaux Susan M. Molineaux President and Chief Executive Officer

5 Exhibit 99.1 Calithera Biosciences Reports CANTATA Study of Telaglenastat in Renal Cell Carcinoma Did Not Achieve Primary Endpoint Company will continue to advance telaglenastat KEAPSAKE trial in non-small cell lung cancer, arginase inhibitor CB-280 trial in cystic fibrosis and emerging pipeline Company to host webcast and conference call today at 8:30 a.m. ET / 5:30 a.m. PT SOUTH SAN FRANCISCO, Calif., January 4, 2021 (GLOBE NEWSWIRE) Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage biotechnology company focused on discovering and developing novel small-molecule drugs for the treatment of cancer and other life-threatening diseases, today announced topline results from the CANTATA clinical study of the company s glutaminase inhibitor telaglenastat in patients with advanced or metastatic renal cell carcinoma (RCC). As compared to treatment with cabozantinib, the combination of telaglenastat and cabozantinib did not meet the primary endpoint of improving progression free survival (PFS) in the study population. The primary study endpoint is PFS by blinded independent review. The hazard ratio was 0.94 (p=0.65). Median PFS was 9.2 months among patients treated with telaglenastat and cabozantinib as compared to 9.3 months with cabozantinib and placebo. Sixty-two percent of patients were treated with prior PD(L)-1-containing therapy, and the arms were well balanced. The frequency and severity of adverse events in the telaglenastat-treated population were comparable to that of cabozantinib alone. We are disappointed that the CANTATA trial did not achieve its primary endpoint, particularly on behalf of the people living with advanced RCC, many of whom could benefit from additional treatment options with novel mechanisms of action to address this difficult-to-treat disease, said Susan Molineaux, PhD, president and chief executive officer of Calithera. Based on the strong scientific rationale for telaglenastat in KEAP1/NRF2 mutant non-small cell lung cancer patients, and the safety profile observed in CANTATA, we remain dedicated to advancing our randomized KEAPSAKE trial. Calithera will focus its financial resources on the ongoing KEAPSAKE trial, the ongoing trial of the arginase inhibitor CB-280 in cystic fibrosis patients and pipeline programs. As a result of the outcome of CANTATA, the company will reduce its workforce by approximately 35 percent to allow the company to focus on ongoing programs. Calithera expects cash, cash equivalents and investments to be approximately $115 million at December 31, 2020 based on preliminary estimates, which management believes will be sufficient to meet its current operating plan through 2022, including the release of interim results of the KEAPSAKE trial and completion of the current cystic fibrosis study in Calithera anticipates the one-time severance-related charge associated with the workforce reduction to be approximately $1.3 million - $1.5 million, with the majority to be completed by the first quarter of More financial details will be provided by the company in its fourth quarter 2020 financial report in March 2021.

6 The information relating to cash, cash equivalents and investments is preliminary, has not been audited and is subject to change upon completion of the audit of Calithera s financial statements as of and for the year ended December 31, The CANTATA trial (NCT ) is a global, randomized, double-blind trial designed to evaluate the efficacy and safety of telaglenastat in combination with cabozantinib versus placebo with cabozantinib in patients with advanced or metastatic RCC who have been treated with one or two prior lines of systemic therapy, including at least one vascular endothelial growth factor (VEGF)-pathway targeted anti-angiogenic therapy or the combination of nivolumab and ipilimumab. The CANTATA trial enrolled 444 patients at multiple centers globally. Exelixis, Inc. provided cabozantinib for the trial through a material supply agreement with Calithera. Calithera will submit the CANTATA results for presentation at a medical meeting. Webcast and Conference Call Information Calithera will hold a webcast today, Monday, January 4, at 8:30 a.m. Eastern Time / 5:30 a.m. Pacific Time. To access the link to the webcast, which will be broadcast live in listen-only mode, or the subsequent archived recording, visit the Investors section of the Calithera website at Alternatively, the call may be accessed by dialing (855) (domestic) or (631) (international) and referring to conference ID The webcast will be recorded and available for replay on Calithera s website for 30 days. About Telaglenastat Telaglenastat (CB-839) is an investigational, first-in-class, novel glutaminase inhibitor specifically designed to block glutamine consumption in tumor cells. While normal cells use glucose to meet cellular energy demands, tumor cells have a unique oncometabolism that increases their dependence on glutamine to fuel growth and survival. Calithera is conducting the randomized Phase 2 KEAPSAKE trial to evaluate telaglenastat in patients with advanced non-small cell lung cancer harboring KEAP1/NRF2 mutations. About Calithera Calithera Biosciences is a clinical-stage biopharmaceutical company pioneering the discovery and development of targeted therapies that disrupt cellular metabolic pathways to preferentially block tumor cells and enhance immune-cell activity. Driven by a commitment to rigorous science and a passion for improving the lives of people impacted by cancer and other life-threatening diseases, Calithera is advancing a pipeline of first-in-clinic, oral therapeutics to meaningfully expand treatment options available to patients. Calithera is headquartered in South San Francisco, California. For more information about Calithera, please visit Forward Looking Statements Statements contained in this press release regarding matters that are not historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of Words such as may, will, expect, anticipate, estimate, intend, poised and similar expressions (as

7 well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. These statements include those related to the overall advancement and timing of telaglenastat in clinical trials, including the randomized Phase 2 KEAPSAKE trial in patients with KEAP1/NRF2 mutations; the ongoing trial of the arginase inhibitor CB-280; the timing of regulatory submissions; our expectations regarding our cash position as of December 31, 2020; and our estimated cash expenditures associated with termination benefits and severance-related charges. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. The product candidates that Calithera develops may not progress through clinical development or receive required regulatory approvals within expected timelines or at all. In addition, clinical trials may not confirm any safety, potency or other product characteristics described or assumed in this press release. Such product candidates may not be beneficial to patients or successfully commercialized. The failure to meet expectations with respect to any of the foregoing matters may have a negative effect on Calithera s stock price. Additional information concerning these and other risk factors affecting Calithera s business can be found in Calithera s most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission, and other periodic filings with the Securities and Exchange Commission at These forward-looking statements are not guarantees of future performance and speak only as of the date hereof, and, except as required by law, Calithera disclaims any obligation to update these forward-looking statements to reflect future events or circumstances. SOURCE: Calithera Biosciences, Inc. CONTACTS: Investor Relations Jennifer McNealey Calithera ir@calithera.com Media Michele Parisi Sam Brown, Inc. micheleparisi@sambrown.com

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