AGIOS PHARMACEUTICALS, INC. 10-K

Item 9A. Controls and Procedures Evaluation of Disclosure Controls and Procedures Our management, with the participation of our principal executive officer and our principal financial officer, evaluated, as of the end of the period covered by this Annual Report on Form 10-K, the effectiveness of our disclosure controls and procedures. Based on that evaluation of our disclosure controls and procedures as of December 31, 2020, our principal executive officer and principal financial officer concluded that our disclosure controls and procedures as of such date are effective at the reasonable assurance level. The term “disclosure controls and procedures,” as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act, means controls and other procedures of a company that are designed to ensure that information required to be disclosed by a company in the reports that it files or submits under the Exchange Act are recorded, processed, summarized and reported within the time periods specified in the SEC’s rules and forms. Disclosure controls and procedures include, without limitation, controls and procedures designed to ensure that information required to be disclosed by us in the reports we file or submit under the Exchange Act is accumulated and communicated to our management, including our principal executive officer and principal financial officer, as appropriate to allow timely decisions regarding required disclosure. Management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving their objectives and our management necessarily applies its judgment in evaluating the cost-benefit relationship of possible controls and procedures. Management’s Annual Report on Internal Control over Financial Reporting Our management is responsible for establishing and maintaining adequate internal control over our financial reporting. Internal control over financial reporting is defined in Rules 13a-15(f) and 15d-15(f) promulgated under the Exchange Act as a process designed by, or under the supervision of, our principal executive and principal financial officers and effected by our board of directors, management and other personnel to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with U.S. GAAP. Our internal control over financial reporting includes those policies and procedures that: • pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect our transactions and dispositions of our assets; • provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with U.S. GAAP, and that our receipts and expenditures are being made only in accordance with authorizations of our management and directors; and • provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use or disposition of our assets that could have a material effect on our financial statements. Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate. Our management assessed the effectiveness of our internal control over financial reporting as of December 31, 2020. In making this assessment, management used the criteria set forth by the Committee of Sponsoring Organizations of the Treadway Commission (COSO) in its 2013 Internal Control – Integrated Framework. Based on our assessment, our management has concluded that, as of December 31, 2020, our internal control over financial reporting is effective based on those criteria. The effectiveness of our internal control over financial reporting as of December 31, 2020, has been audited by PricewaterhouseCoopers LLP, an independent registered public accounting firm, as stated in their report, which is included herein. Changes in Internal Control over Financial Reporting There were no changes in our internal control over financial reporting (as defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act) during the fiscal quarter ended December 31, 2020 that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting. Item 9B. Other Information None. 90 Table of Contents PART III Item 10. Directors, Executive Officers and Corporate Governance The information required by this Item 10 will be included in our definitive proxy statement to be filed with the Securities and Exchange Commission, or SEC, with respect to our 2021 Annual Meeting of Stockholders and is incorporated herein by reference. Item 11. Executive Compensation The information required by this Item 11 will be included in our definitive proxy statement to be filed with the SEC with respect to our 2021 Annual Meeting of Stockholders and is incorporated herein by reference. Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters The information required by this Item 12 will be included in our definitive proxy statement to be filed with the SEC with respect to our 2021 Annual Meeting of Stockholders and is incorporated herein by reference. Item 13. Certain Relationships and Related Transactions, and Director Independence The information required by this Item 13 will be included in our definitive proxy statement to be filed with the SEC with respect to our 2021 Annual Meeting of Stockholders and is incorporated herein by reference. Item 14. Principal Accountant Fees and Services The information required by this Item 14 will be included in our definitive proxy statement to be filed with the SEC with respect to our 2021 Annual Meeting of Stockholders and is incorporated herein by reference. 91 Table of Contents PART IV Item 15. Exhibits and Financial Statement Schedules (1) Financial Statements The following documents are included on pages F-1 through F-39 attached hereto and are filed as part of this Annual Report on Form 10-K. Report of Independent Registered Public Accounting Firm 2 Consolidated Balance Sheets 4 Consolidated Statements of Operations 5 Consolidated Statements of Comprehensive Loss 6 Consolidated Statements of Stockholders’ Equity 7 Consolidated Statements of Cash Flows 8 Notes to Consolidated Financial Statements 9 (2) Financial Statement Schedules Schedules have been omitted since they are either not required or not applicable or the information is otherwise included herein. (3) Exhibits Exhibit Number Description of Exhibit Incorporated by Reference Filed Herewith Form File Number Date of Filing Exhibit Number 2.1+ Purchase and Sale Agreement, dated as of December 20, 2020, by and among the Registrant, Servier Pharmaceuticals, LLC, and, solely for purposes of guaranteeing certain obligations of the Purchaser, Servier S.A.S 8-K 001-36014 December 22, 2020 2.1 3.1 Restated Certificate of Incorporation of the Registrant 8-K 001-36014 July 30, 2013 3.1 3.2 Second Amended and Restated By-Laws 8-K 001-36014 December 19, 2018 3.1 4.1 Specimen Stock Certificate evidencing the shares of common stock S-1 333-189216 June 24, 2013 4.1 4.2 Description of Securities Registered Under Section 12 of the Securities Exchange Act of 1934 10-K 001-36014 February 19, 2020 4.3 10.1# 2007 Stock Incentive Plan S-1 333-189216 June 10, 2013 10.1 10.2# Form of Incentive Stock Option Agreement under 2007 Stock Incentive Plan S-1 333-189216 June 10, 2013 10.2 10.3# Form of Nonstatutory Stock Option Agreement under 2007 Stock Incentive Plan S-1 333-189216 June 10, 2013 10.3 10.4# 2013 Stock Incentive Plan S-1 333-189216 June 24, 2013 10.4 10.5# Form of Incentive Stock Option Agreement under 2013 Stock Incentive Plan S-1 333-189216 June 24, 2013 10.5 10.6# Form of Nonstatutory Stock Option Agreement under 2013 Stock Incentive Plan S-1 333-189216 June 24, 2013 10.6 10.7# 2013 Employee Stock Purchase Plan S-1 333-189216 June 24, 2013 10.7 92 Table of Contents Exhibit Number Description of Exhibit Incorporated by Reference Filed Herewith Form File Number Date of Filing Exhibit Number 10.8 Form of Indemnification Agreement between the Registrant and each of its Executive Officers and Directors S-1 333-189216 July 11, 2013 10.12 10.9# Letter Agreement, dated as of April 1, 2014, between the Registrant and Christopher Bowden, Ph.D. 10-K 001-36014 February 26, 2016 10.13 10.10† Discovery and Development Collaboration and License Agreement, dated as of April 14, 2010, as amended on October 3, 2011, between the Registrant and Celgene Corporation S-1 333-189216 July 16, 2013 10.14 10.11† Third Amendment to Discovery and Development Collaboration and License Agreement, dated July 14, 2014 between the Registrant and Celgene Corporation 10-K 001-36014 February 24, 2015 10.15 10.12 Common Stock Purchase Agreement, dated as of July 16, 2013, between the Registrant and Celgene Alpine Investment Co., LLC S-1 333-189216 July 16, 2013 10.15 10.13 Lease, dated as of September 15, 2014, between the Registrant and Forest City 88 Sidney, LLC 8-K 001-36014 September 19, 2014 10.1 10.14 First Amendment to Lease for 88 Sidney Street, dated as of November 21, 2014, between the Registrant and Forest City 88 Sidney, LLC 8-K 001-36014 November 26, 2014 10.1 10.15# Summary Description of Annual Cash Incentive Program 10-Q 001-36014 May 11, 2015 10.1 10.16 Second Amendment to Lease for 88 Sidney Street, dated July 20, 2015, by and between the Registrant and Forest City 88 Sidney Street, LLC 8-K 001-36014 July 23, 2015 10.1 10.17† Collaboration and License Agreement by and between the Registrant and Celgene Corporation Re: AGI-23088 for the US Territory, dated as of April 27, 2015 10-Q 001-36014 August 7, 2015 10.1 10.18† Collaboration and License Agreement by and between Agios International Sarl and Celgene International II Sarl Re: AGI-23088 for the ROW Territory, dated as of April 27, 2015 10-Q 001-36014 August 7, 2015 10.2 10.19# Form of Performance Share Unit Agreement under 2013 Stock Incentive Plan 10-K 001-36014 February 26, 2016 10.25 10.20# Severance Benefits Plan 8-K 001-36014 April 22, 2016 10.1 10.21† Master Research and Collaboration Agreement, dated May 17, 2016, by and among the Registrant, Celgene Corporation and Celgene RIVOT Ltd. 10-Q 001-36014 August 8, 2016 10.1 10.22# Letter Agreement between the Registrant and Andrew Hirsch, effective August 11, 2016 8-K 001-36014 August 16, 2016 99.2 10.23 Lease, dated as of November 17, 2017, between the Registrant and UP 64 Sidney Street, LLC 8-K 001-36014 November 22, 2017 10.1 93 Table of Contents Exhibit Number Description of Exhibit Incorporated by Reference Filed Herewith Form File Number Date of Filing Exhibit Number 10.24 Third Amendment to Lease for 88 Sidney Street, dated November 17, 2017, by and between the Registrant and Forest City 88 Sidney Street, LLC 8-K 001-36014 November 22, 2017 10.2 10.25 First Amendment of Lease, dated April 11, 2018, by and between UP 64 Sidney Street, LLC and Agios Pharmaceuticals. Inc. 8-K 001-36014 April 13, 2018 10.1 10.26# Form of Restricted Stock Unit Agreement under 2013 Stock Incentive Plan (for employees) 10-Q 001-36014 May 4, 2018 10.1 10.27† License Agreement, dated June 25, 2018, by and between Agios Pharmaceuticals, Inc. and CStone Pharmaceuticals 10-Q 001-36014 August 2, 2018 10.2 10.28# Amended and Restated Letter Agreement, dated as of August 30, 2018, between the Registrant and David P. Schenkein, M.D. 10-Q 001-36014 November 1, 2018 10.1 10.29# Letter Agreement, dated as of August 30, 2018, between the Registrant and Jacqualyn A. Fouse, Ph.D. 10-Q 001-36014 November 1, 2018 10.2 10.30# Form of Restricted Stock Unit Agreement under 2013 Stock Incentive Plan (for directors) 10-K 001-36014 February 14, 2019 10.32 10.31 Lease, dated as of April 11, 2019, by and between the Registrant and Thirty-Eight Sidney Street Limited LLC 10-Q 001-36014 August 1, 2019 10.1 10.32 Fourth Amendment to Lease, dated as of April 11, 2019, by and between the Registrant and Forest City 88 Sidney Street, LLC 10-Q 001-36014 August 1, 2019 10.2 10.33 Third Amendment of Lease, dated as of April 11, 2019, by and between the Registrant and UP 64 Sidney Street, LLC 10-Q 001-36014 August 1, 2019 10.3 10.34# Letter Agreement, dated as of September 17, 2019, between the Registrant and Jonathan Biller 10-K 001-36014 February 19, 2020 10.35 10.35# Letter Agreement, dated as of October 7, between the Registrant and Bruce Car 10-Q 001-36014 April 30, 2020 10.1 10.36† Amendment to Master Research and Collaboration Agreement, dated as of February 5, 2020, by and among the Registrant, Celgene Corporation and Celgene RIVOT Ltd 10-Q 001-36014 April 30, 2020 10.2 10.37† Amendment I to License Agreement, dated as of March 2, 2020, by and between the Registrant and CStone Pharmaceuticals 10-Q 001-36014 April 30, 2020 10.3 10.38† Amendment II to License Agreement, dated as of March 2, 2020, by and between the Registrant and CStone Pharmaceuticals 10-Q 001-36014 April 30, 2020 10.4 10.39 Sales Agreement, dated April 30, 2020, by and between the Registrant and Cowen and Company, LLC S-3ASR 333-237930 April 30, 2020 1.2 94 Table of Contents Exhibit Number Description of Exhibit Incorporated by Reference Filed Herewith Form File Number Date of Filing Exhibit Number 10.40† Royalty Purchase Agreement, dated as of June 11, 2020, by and between the Registrant and RPI 2019 Intermediate Finance Trust 10-Q 001-36014 July 30, 2020 10.2 21.1 Subsidiaries of the Registrant X 23.1 Consent of PricewaterhouseCoopers LLP, an Independent Registered Public Accounting Firm 31.1 Certification of principal executive officer pursuant to Rule 13a-14(a)/15d-14(a) of the Securities Exchange Act of 1934, as amended X 31.2 Certification of principal financial officer pursuant to Rule 13a-14(a)/15d-14(a) of the Securities Exchange Act of 1934, as amended. X 32.1* Certification of principal executive officer pursuant to 18 U.S.C. §1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002. X 32.2* Certification of principal financial officer pursuant to 18 U.S.C. §1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002. X 101.INS XBRL Instance Document X 101.SCH XBRL Taxonomy Extension Schema Document X 101.CAL XBRL Taxonomy Calculation Linkbase Document X 101.DEF XBRL Taxonomy Extension Definition Linkbase Document X 101.LAB XBRL Taxonomy Label Linkbase Document X 101.PRE XBRL Taxonomy Presentation Linkbase Document X 104 Cover Page Interactive Data File (formatted as Inline XBRL and contained in Exhibit 101) X # Indicates management contract or compensatory plan or arrangement. † Confidential treatment has been granted as to certain portions, which portions have been omitted and filed separately with the Securities and Exchange Commission. + Pursuant to Item 601(6)(2) of Regulation S-K, the disclosure schedules to the Purchase Agreement (identified therein) have been omitted from this Current Report on Form 8-K and will be furnished to the SEC supplementally upon request. * This certification will not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or the Exchange Act, or otherwise subject to the liability of that section. Such certification will not be deemed to be incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Exchange Act, except to the extent specifically incorporated by reference into such filing. Item 16. Form 10-K Summary None. 95 Table of Contents SIGNATURES Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized. AGIOS PHARMACEUTICALS, INC. February 25, 2021 By: /s/ Jacqualyn A. Fouse Jacqualyn A. Fouse, Ph.D. Chief Executive Officer Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf of the registrant and in the capacities and on the dates indicated. Signature Title Date /s/ Jacqualyn A. Fouse Chief Executive Officer and Director (Principal executive officer) February 25, 2021 Jacqualyn A. Fouse, Ph.D. /s/ Jonathan Biller Chief Financial Officer and Head of Legal and Corporate Affairs (Principal financial officer) February 25, 2021 Jonathan Biller /s/ Carman Alenson Vice President of Accounting, Treasury and Tax (Principal accounting officer) February 25, 2021 Carman Alenson /s/ Paul J. Clancy Director February 25, 2021 Paul J. Clancy /s/ Ian Clark Director February 25, 2021 Ian Clark /s/ Kaye Foster Director February 25, 2021 Kaye Foster /s/ Maykin Ho Director February 25, 2021 Maykin Ho, Ph.D. /s/ John M. Maraganore Director February 25, 2021 John M. Maraganore, Ph.D. /s/ David Scadden Director February 25, 2021 David Scadden, M.D. /s/ David P. Schenkein Director February 25, 2021 David P. Schenkein, M.D. 96 Table of Contents Agios Pharmaceuticals, Inc. Index to Consolidated Financial Statements Report of Independent Registered Public Accounting Firm 2 Consolidated Balance Sheets 4 Consolidated Statements of Operations 5 Consolidated Statements of Comprehensive Loss 6 Consolidated Statements of Stockholders’ Equity 7 Consolidated Statements of Cash Flows 8 Notes to Consolidated Financial Statements 9 F-1 Table of Contents Report of Independent Registered Public Accounting Firm To the Board of Directors and Stockholders of Agios Pharmaceuticals, Inc. Opinions on the Financial Statements and Internal Control over Financial Reporting We have audited the accompanying consolidated balance sheets of Agios Pharmaceuticals, Inc. and its subsidiaries (the “Company”) as of December 31, 2020 and 2019, and the related consolidated statements of operations, of comprehensive loss, of stockholders’ equity and of cash flows for each of the three years in the period ended December 31, 2020, including the related notes (collectively referred to as the “consolidated financial statements”). We also have audited the Company's internal control over financial reporting as of December 31, 2020, based on criteria established in Internal Control - Integrated Framework (2013) issued by the Committee of Sponsoring Organizations of the Treadway Commission (COSO). In our opinion, the consolidated financial statements referred to above present fairly, in all material respects, the financial position of the Company as of December 31, 2020 and 2019, and the results of its operations and its cash flows for each of the three years in the period ended December 31, 2020 in conformity with accounting principles generally accepted in the United States of America. Also in our opinion, the Company maintained, in all material respects, effective internal control over financial reporting as of December 31, 2020, based on criteria established in Internal Control - Integrated Framework (2013) issued by the COSO. Changes in Accounting Principles As discussed in Note 3 to the consolidated financial statements, the Company changed the manner in which it accounts for leases in 2019 and the manner in which it accounts for revenue from contracts with customers in 2018. Basis for Opinions The Company's management is responsible for these consolidated financial statements, for maintaining effective internal control over financial reporting, and for its assessment of the effectiveness of internal control over financial reporting, included in Management’s Annual Report on Internal Control over Financial Reporting appearing under Item 9A. Our responsibility is to express opinions on the Company’s consolidated financial statements and on the Company's internal control over financial reporting based on our audits. We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States) (PCAOB) and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB. We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audits to obtain reasonable assurance about whether the consolidated financial statements are free of material misstatement, whether due to error or fraud, and whether effective internal control over financial reporting was maintained in all material respects. Our audits of the consolidated financial statements included performing procedures to assess the risks of material misstatement of the consolidated financial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the consolidated financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the consolidated financial statements. Our audit of internal control over financial reporting included obtaining an understanding of internal control over financial reporting, assessing the risk that a material weakness exists, and testing and evaluating the design and operating effectiveness of internal control based on the assessed risk. Our audits also included performing such other procedures as we considered necessary in the circumstances. We believe that our audits provide a reasonable basis for our opinions. Definition and Limitations of Internal Control over Financial Reporting A company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles. A company’s internal control over financial reporting includes those policies and procedures that (i) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the company; (ii) provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the company are being made only in accordance with authorizations of management and directors of the company; and (iii) provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use, or disposition of the company’s assets that could have a material effect on the financial statements. Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate. F-2 Table of Contents Critical Audit Matters The critical audit matter communicated below is a matter arising from the current period audit of the consolidated financial statements that was communicated or required to be communicated to the audit committee and that (i) relates to accounts or disclosures that are material to the consolidated financial statements and (ii) involved our especially challenging, subjective, or complex judgments. The communication of critical audit matters does not alter in any way our opinion on the consolidated financial statements, taken as a whole, and we are not, by communicating the critical audit matter below, providing a separate opinion on the critical audit matter or on the accounts or disclosures to which it relates. Liability related to sale of future revenue As described in Notes 3 and 10 to the consolidated financial statements, on June 11, 2020 the Company sold its tiered, sales-based royalty rights on worldwide net sales of IDHIFA®, as well as rights to receive up to $55 million in regulatory milestone payments from Bristol Myers Squibb to Royalty Pharma (“RPI”) for $255 million. Management accounted for the sale of future revenue to RPI as a debt financing, as the Company continues to have significant continuing involvement in the generation of the cash flows. Management applied significant judgment in determining the appropriate accounting treatment for the transaction. The liability related to sale of future revenue and the related interest expense are based on Management’s current estimates of future royalties expected to be paid over the life of the arrangement. Management periodically assesses the expected royalty payments using forecasts from external sources. Th e Company recognized non-cash interest expense for the sale of future revenue of $17.8 million for the year ended December 31, 2020, and the liability related to the sale of future revenue was $261.3 million as of December 31, 2020. The principal considerations for our determination that performing procedures relating to the liability related to the sale of future revenue is a critical audit matter are the significant judgment by management in determining the appropriate accounting for the transaction and the valuation of the liability related to sale of future revenue. This in turn led to a high degree of auditor judgment, effort, and subjectivity in performing procedures and evaluating management’s determination of the accounting for the transaction and the assumption related to the current estimates of future royalties expected to be paid over the life of the arrangement. Addressing the matter involved performing procedures and evaluating audit evidence in connection with forming our overall opinion on the consolidated financial statements. These procedures included testing the effectiveness of controls relating to management’s determination of the accounting treatment for the transaction, as well as controls over the development of the assumption related to the current estimates of future royalties expected to be paid over the life of the arrangement. These procedures also included, among others, evaluating whether the transaction has been properly accounted for in accordance with the relevant accounting standards, testing management’s process for determining the valuation of the liability related to the sale of future revenue, testing the completeness and accuracy of underlying data used in determining the valuation of the liability, and evaluating the significant assumption used by management related to the current estimate of future royalties expected to be paid over the life of the arrangement. Evaluating management’s assumption related to the current estimate of future royalties expected to be paid over the life of the arrangement involved evaluating whether the assumption used by management was reasonable considering the terms of the agreement, consistency with external market and industry data, and consistency with evidence obtained in other areas of the audit. /s/ PricewaterhouseCoopers LLP Boston, Massachusetts February 25, 2021 We have served as the Company’s auditor since 2017. F-3 Table of Contents Agios Pharmaceuticals, Inc. Consolidated Balance Sheets (In thousands) December 31: 2020 2019 Assets Current assets: Cash and cash equivalents $ 127,436 $ 80,931 Marketable securities 445,493 483,946 Accounts receivable, net 21,328 8,952 Collaboration receivable – related party 2,123 1,539 Collaboration receivable – other 1,948 1,928 Royalty receivable – related party — 2,900 Inventory 14,698 7,331 Prepaid expenses and other current assets 23,651 24,177 Total current assets 636,677 611,704 Marketable securities 97,608 152,929 Operating lease assets 84,661 93,643 Property and equipment, net 32,291 31,472 Financing lease assets 590 993 Other non-current assets 1,125 — Total assets $ 852,952 $ 890,741 Liabilities and stockholders’ equity Current liabilities: Accounts payable $ 26,844 $ 21,896 Accrued expenses 60,140 53,142 Deferred revenue – related party — 10,933 Operating lease liabilities 7,093 6,642 Financing lease liabilities 317 273 Total current liabilities 94,394 92,886 Deferred revenue, net of current portion – related party — 50,580 Operating lease liabilities, net of current portion 97,458 106,074 Financing lease liabilities, net of current portion 331 673 Liability related to the sale of future revenue, net of debt issuance costs 261,269 — Total liabilities 453,452 250,213 Commitments and contingent liabilities (Note 11) Stockholders’ equity: Preferred stock, $ 0.001 par value; 25,000,000 shares authorized, no shares issued and outstanding at December 31, 2020 and 2019 — — Common stock, $ 0.001 par value; 125,000,000 shares authorized and 69,293,920 and 68,401,105 shares issued and outstanding at December 31, 2020 and 2019, respectively 69 68 Additional paid-in capital 2,242,801 2,156,363 Accumulated other comprehensive income 105 202 Accumulated deficit ( 1,843,475 ) ( 1,516,105 ) Total stockholders’ equity 399,500 640,528 Total liabilities and stockholders’ equity $ 852,952 $ 890,741 See accompanying Notes to Consolidated Financial Statements. F-4 Table of Contents Agios Pharmaceuticals, Inc. Consolidated Statements of Operations (In thousands, except share and per share data) Years Ended December 31: 2020 2019 2018 Revenues: Product revenue, net $ 121,089 $ 59,851 $ 13,841 Collaboration revenue – related party 68,274 39,257 60,661 Collaboration revenue – other 3,571 8,262 12,670 Royalty revenue – related party 10,262 10,542 7,215 Total revenue 203,196 117,912 94,387 Cost and expenses: Cost of sales 2,805 1,317 1,397 Research and development 367,470 410,894 341,324 Selling, general and administrative 149,070 132,034 114,145 Total cost and expenses 519,345 544,245 456,866 Loss from operations ( 316,149 ) ( 426,333 ) ( 362,479 ) Interest income, net 6,611 14,861 16,451 Non-cash interest expense for the sale of future revenue ( 17,832 ) — — Net loss $ ( 327,370 ) $ ( 411,472 ) $ ( 346,028 ) Net loss per share – basic and diluted $ ( 4.74 ) $ ( 6.86 ) $ ( 6.03 ) Weighted-average number of common shares used in computing net loss per share – basic and diluted 68,997,879 59,994,539 57,418,300 See accompanying Notes to Consolidated Financial Statements. F-5 Table of Contents Agios Pharmaceuticals, Inc. Consolidated Statements of Comprehensive Loss (In thousands) Years Ended December 31: 2020 2019 2018 Net loss $ ( 327,370 ) $ ( 411,472 ) $ ( 346,028 ) Other comprehensive (loss) income: Unrealized (loss) gain on available-for-sale securities ( 97 ) 2,373 ( 782 ) Comprehensive loss $ ( 327,467 ) $ ( 409,099 ) $ ( 346,810 ) See accompanying Notes to Consolidated Financial Statements. F-6 Table of Contents Agios Pharmaceuticals, Inc. Consolidated Statements of Stockholders’ Equity Common Stock Additional Paid-In Capital Accumulated Other Comprehensive Income (Loss) Accumulated Deficit Total Stockholders’ Equity (In thousands, except share amounts) Shares Amount Balance at December 31, 2017 48,826,153 $ 49 $ 1,174,904 $ ( 1,389 ) $ ( 798,061 ) $ 375,503 Unrealized loss on available-for-sale securities — — — ( 782 ) — ( 782 ) Net loss — — — — ( 346,028 ) ( 346,028 ) Adjustment to beginning accumulated deficit resulting from adoption of ASC 606 — — — — 39,456 39,456 Stock-based compensation expense — — 73,357 — — 73,357 Issuance of common stock under stock incentive and employee stock purchase plans 1,239,514 1 30,215 — — 30,216 Issuance of common stock for follow-on offering 8,152,986 8 516,198 — — 516,206 Other — — ( 391 ) — — ( 391 ) Balance at December 31, 2018 58,218,653 $ 58 $ 1,794,283 $ ( 2,171 ) $ ( 1,104,633 ) $ 687,537 Unrealized gain on available-for-sale securities — — — 2,373 — 2,373 Net loss — — — — ( 411,472 ) ( 411,472 ) Stock-based compensation expense — — 72,373 — — 72,373 Issuance of common stock under stock incentive and employee stock purchase plans 694,952 1 12,515 — — 12,516 Issuance of common stock for follow-on offering 9,487,500 9 277,192 — — 277,201 Other — — — — — — Balance at December 31, 2019 68,401,105 $ 68 $ 2,156,363 $ 202 $ ( 1,516,105 ) $ 640,528 Unrealized loss on available-for-sale securities — — — ( 97 ) — ( 97 ) Net loss — — — — ( 327,370 ) ( 327,370 ) Stock-based compensation expense — — 75,122 — — 75,122 Issuance of common stock under stock incentive and employee stock purchase plans 892,815 1 11,316 — — 11,317 Issuance of common stock for follow-on offering — — — — — — Other — — — — — — Balance at December 31, 2020 69,293,920 $ 69 $ 2,242,801 $ 105 $ ( 1,843,475 ) $ 399,500 See accompanying Notes to Consolidated Financial Statements. F-7 Table of Contents Agios Pharmaceuticals, Inc. Consolidated Statements of Cash Flows (In thousands) Years Ended December 31: 2020 2019 2018 Operating activities Net loss $ ( 327,370 ) $ ( 411,472 ) $ ( 346,028 ) Adjustments to reconcile net loss to net cash used in operating activities: Depreciation and amortization 9,984 8,087 7,172 Stock-based compensation expense 75,122 72,373 73,357 Net amortization of premium (accretion of discount) on marketable securities 3,022 ( 3,195 ) ( 3,837 ) Loss on disposal of property and equipment — 1,052 20 Non-cash operating lease expense 8,982 8,532 — Non-cash interest expense associated with the sale of future revenue 17,832 — — Non-cash royalty revenue ( 7,294 ) — — Changes in operating assets and liabilities: Accounts receivable, net ( 12,376 ) ( 3,876 ) ( 5,076 ) Collaboration receivable – related party ( 584 ) 923 ( 14 ) Collaboration receivable – other ( 20 ) ( 1,258 ) ( 670 ) Royalty receivable – related party 2,900 ( 666 ) ( 1,012 ) Inventory ( 7,367 ) ( 6,462 ) ( 869 ) Prepaid expenses and other current and non-current assets ( 599 ) ( 7,742 ) 1,148 Accounts payable 5,889 3,716 ( 5,488 ) Accrued expenses 10,760 7,233 8,623 Deferred revenue – related party ( 61,513 ) ( 31,006 ) ( 31,665 ) Operating lease liabilities ( 8,127 ) ( 6,861 ) — Deferred rent — — ( 82 ) Net cash used in operating activities ( 290,759 ) ( 370,622 ) ( 304,421 ) Investing activities Purchases of marketable securities ( 557,030 ) ( 488,566 ) ( 933,320 ) Proceeds from maturities and sales of marketable securities 647,685 592,177 666,481 Purchases of property and equipment ( 14,909 ) ( 12,171 ) ( 6,986 ) Net cash provided by (used in) investing activities 75,746 91,440 ( 273,825 ) Financing activities Payments on financing lease obligations ( 336 ) ( 113 ) — Proceeds from public offering of common stock, net of reimbursements — 277,201 516,206 Reimbursement (payment) of public offering costs — — ( 391 ) Proceeds from the sale of future revenue, net of issuance costs 250,537 — — Net proceeds from stock option exercises and employee stock purchase plan 11,317 12,523 30,209 Net cash provided by financing activities 261,518 289,611 546,024 Net change in cash and cash equivalents 46,505 10,429 ( 32,222 ) Cash and cash equivalents at beginning of the period 80,931 70,502 102,724 Cash and cash equivalents at end of the period $ 127,436 $ 80,931 $ 70,502 Supplemental disclosure of non-cash investing and financing transactions: Additions to property and equipment in accounts payable and accrued expenses $ 465 $ 5,168 $ 1,106 Proceeds from stock option exercises in other current assets $ — $ — $ 7 Operating lease liabilities arising from obtaining operating lease assets $ — $ 42,322 $ — Financing lease liabilities arising from obtaining financing lease assets $ — $ 1,052 $ — See accompanying Notes to Consolidated Financial Statements. F-8 Table of Contents Agios Pharmaceuticals, Inc. Notes to Consolidated Financial Statements Note 1. Nature of Business References to Agios Throughout this Annual Report on Form 10-K, “the Company,” “we,” “us,” and “our,” and similar expressions, except where the context requires otherwise, refer to Agios Pharmaceuticals, Inc. and its consolidated subsidiaries, and “our board of directors” refers to the board of directors of Agios Pharmaceuticals, Inc. Overview We are a biopharmaceutical company committed to transforming patients’ lives through scientific leadership in the field of cellular metabolism and adjacent areas of biology, with the goal of creating differentiated, small molecule medicines in the areas of genetically defined diseases, or GDDs, and, until the completion of the sale of our oncology business to Servier as described below, hematologic malignancies and solid tumors. To address our focus areas, we take a systems biology approach to deeply understand disease states, drive the discovery and validation of novel therapeutic targets, and define patient selection strategies, thereby increasing the probability that our experimental medicines will have the desired therapeutic effect. We are located in Cambridge, Massachusetts. Our wholly-owned product, TIBSOVO® (ivosidenib) is an oral targeted inhibitor of the mutated isocitrate dehydrogenase 1, or IDH1 enzyme. TIBSOVO® is the first and only U.S. Food and Drug Administration, or FDA-approved therapy for the treatment of adult patients with (i) relapsed or refractory acute myeloid leukemia, or R/R AML, with a susceptible IDH1 mutation as detected by an FDA-approved test (approved by the FDA in July 2018) and (ii) newly diagnosed AML with a susceptible IDH1 mutation as detected by an FDA-approved test who are at least 75 years old or who have comorbidities that preclude use of intensive induction chemotherapy (approved by the FDA in May 2019). In December 2018, we submitted a Marketing Authorization Application, or MAA, to the European Medicines Agency, or EMA, for TIBSOVO® for the treatment of adult patients with R/R AML with an IDH1 mutation. In October 2020, we announced the withdrawal of the MAA based on feedback from the EMA's Committee for Medicinal Products for Human Use (CHMP) that the available clinical data from our single arm, uncontrolled Phase 1 trial did not sufficiently support a positive benefit-risk balance for the proposed indication. Our other marketed product is IDHIFA® (enasidenib), an oral targeted inhibitor of the mutated isocitrate dehydrogenase 2, or IDH2 enzyme and the first and only FDA-approved therapy for patients with R/R AML and an IDH2 mutation. In August 2017, the FDA granted our collaboration partner Celgene approval of IDHIFA® for the treatment of adult patients with R/R AML and an IDH2, mutation as detected by an FDA-approved test. We were eligible to receive royalties at tiered low-double digit to mid-teen percentage rates on any net sales of IDHIFA® and have exercised our rights to provide up to one-third of the field-based commercialization efforts in the United States. In June 2018, Celgene submitted an MAA to the EMA for IDHIFA® for IDH2 mutant-positive AML which it subsequently withdrew in December 2019. On June 11, 2020 we sold our tiered, sales-based royalty rights on worldwide net sales of IDHIFA®, as well as our rights to receive up to $ 55.0 million in outstanding regulatory milestone payments from Bristol Myers Squibb, or BMS, to Royalty Pharma, or RPI, for $ 255.0 million. Our pre-commercial clinical cancer product candidates are vorasidenib and AG-270. Vorasidenib is an orally available, selective brain-penetrant pan-IDH mutant inhibitor. We are developing vorasidenib for the treatment of IDH mutant-positive low grade glioma and are currently evaluating vorasidenib in clinical trials. AG-270 is an orally available selective potent inhibitor of methionine adenosyltransferase 2a, or MAT2A. We are currently evaluating AG-270 in a phase 1 dose-escalation and expansion trial in multiple tumor types carrying a methylthioadenosine phosphorylase, or MTAP, deletion. AG-636 is an inhibitor of the metabolic enzyme dihydroorotate dehydrogenase, or DHODH. In the first quarter of 2020, we made the decision to halt internal development of AG-636, due to limited enrollment in this trial, and will continue to wind down the trial during 2021.We are currently evaluating AG-636 in the phase 1 dose-escalation trial in lymphoma. The lead product candidate in our GDD portfolio, mitapivat, is an activator of both wild-type and mutant pyruvate kinase-R for the potential treatment of hemolytic anemias. We are currently evaluating mitapivat for the treatment of pyruvate kinase, or PK, deficiency, thalassemia and sickle cell disease, or SCD, in clinical trials. We are also developing AG-946, a next-generation PKR activator, for the potential treatment of hemolytic anemias and other indications. In addition to the aforementioned development programs, we are seeking to advance a number of early-stage discovery programs in our focus areas of GDDs, malignant hematology and solid tumors based on our scientific leadership in the field of cellular metabolism and adjacent areas of biology. F-9 Table of Contents We are subject to risks common to companies in our industry including, but not limited to, uncertainties relating to conducting clinical research and development, the manufacture and supply of products for clinical and commercial use, obtaining and maintaining regulatory approvals and pricing and reimbursement for our products, market acceptance, managing global growth and operating expenses, availability of additional capital, competition, obtaining and enforcing patents, stock price volatility, dependence on collaborative relationships and third-party service providers, dependence on key personnel, potential litigation, product liability claims and government investigations. Liquidity On June 11, 2020, we sold our tiered, sales-based royalty rights on worldwide net sales of IDHIFA® (enasidenib), as well as our rights to receive up to $ 55.0 million in outstanding regulatory milestone payments from BMS, to RPI for $ 255.0 million. Under the 2010 Agreement, we remain eligible to receive a $ 25.0 million potential milestone payment for the enasidenib program. The potential payment is a $ 25.0 million milestone payment upon achievement of a specified ex-U.S. commercial milestone event, as well as reimbursement for costs incurred for our co-commercialization efforts and development activities. On April 30, 2020, we entered into an at-the-market sales agreement, or the 2020 sales agreement, with Cowen & Company LLC, or Cowen, pursuant to which we may offer and sell shares of our common stock having an aggregate offering price of up to $ 250.0 million through Cowen pursuant to a universal shelf registration statement on Form S-3 filed with the SEC on April 30, 2020. As of December 31, 2020, $ 250.0 million in common stock remained available for future issuance under the 2020 sales agreement. In November 2019, we completed a public offering of 8,250,000 shares of common at an offering price of $ 31.00 per share. We received net proceeds from this offering of $ 241.0 million, after deducting underwriting discounts and commissions paid by us. In addition, we granted the underwriters the right to purchase up to an additional 1,237,500 shares of common stock, which was exercised in November 2019, resulting in additional net proceeds to us of $ 36.2 million, after underwriting discounts and commissions. After giving effect to the full exercise of the over-allotment option, the number of shares sold by us in the public offering totaled 9,487,500 shares, and net proceeds to us totaled $ 277.2 million, after underwriting discounts and commissions. As of December 31, 2020, we had cash, cash equivalents and marketable securities of $ 670.5 million. Although we have incurred recurring losses and expect to continue to incur losses for the foreseeable future, we expect our cash, cash equivalents and marketable securities to be sufficient to fund current operations for at least the next twelve months from the issuance of the financial statements. If the Company is unable to raise additional funds through equity or debt financings, the Company may be required to delay, limit, reduce or terminate product development or future commercialization efforts or grant rights to develop and market products or product candidates that the Company would otherwise prefer to develop and market itself. Note 2. Proposed Sale of Oncology Business to Servier Pharmaceuticals, LLC (Servier) On December 20, 2020, we entered into a Purchase and Sale Agreement, or the Purchase Agreement, with Servier. The Purchase Agreement provides for the sale of our commercial, clinical and research-stage oncology portfolio assets and pipeline, or oncology business, for a payment of $ 1.8 billion in cash at the closing, subject to certain adjustments for working capital of the oncology business at the closing and amounts for a representation and warranty insurance policy, and a payment of $ 200 million in cash, if, prior to January 1, 2027, vorasidenib is granted new drug application, or NDA, approval from the U.S. Food and Drug Administration, or FDA, with an approved label that permits vorasidenib’s use as a single agent for the adjuvant treatment of patients with Grade 2 glioma that have an isocitrate dehydrogenase 1 or 2, or IDH1 or IDH2, mutation (and, to the extent required by such approval, the vorasidenib companion diagnostic test is granted an FDA premarket approval), as well as a royalty of 5 % of U.S. net sales of TIBSOVO® from the close of the transaction through loss of exclusivity of TIBSOVO® and a royalty of 15 % of U.S. net sales of vorasidenib from the first commercial sale of vorasidenib through loss of exclusivity of vorasidenib. The transaction includes the proposed sale of our oncology business, including TIBSOVO®, our clinical-stage product candidates vorasidenib, AG-270 and AG-636, and our oncology research programs. Servier will also acquire our co-commercialization rights for Bristol Myers Squibb’s IDHIFA®, the $ 25.0 million potential milestone payment, and conduct certain clinical development activities within the IDHIFA® development program. The proposed sale has been approved by our Board of Directors. The parties’ obligations to consummate the proposed sale are subject to customary conditions, including the approval of the sale by the holders of at least a majority of our outstanding shares of common stock, the expiration or termination of the applicable waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended, and the receipt of required regulatory approvals in Germany. Subject to certain exceptions, we and Servier have agreed to use reasonable best efforts to cause the sale to be completed. The Purchase Agreement includes certain termination provisions for both Servier and us and provides that, in connection with a F-10 Table of Contents termination of the Purchase Agreement under specified circumstances, we may be required to pay Servier a termination fee of $ 45 million. We currently expect to complete the transaction at the end of the first quarter of or in the beginning of the second quarter of 2021. Note 3. Summary of Significant Accounting Policies Principles of consolidation The consolidated financial statements include our accounts and the accounts of our wholly owned subsidiaries, Agios Securities Corporation, Agios International Sarl, Agios Germany GmbH, Agios Netherlands B.V., Agios Italy S.R.L., Agios France SARL, and Agios Limited. All intercompany transactions have been eliminated in consolidation. The consolidated financial statements have been prepared in conformity with U.S. generally accepted accounting principles, or U.S. GAAP. Use of estimates The preparation of financial statements in conformity with U.S. GAAP requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities, disclosure of contingent assets and liabilities at the date of the financial statements and the reported amounts of revenue and expenses during the reporting period. On an ongoing basis we evaluate our estimates, judgments and methodologies. We base our estimates on historical experience and on various other assumptions that we believe are reasonable, the results of which form the basis for making judgments about the carrying values of assets, liabilities and equity and the amount of revenues and expenses. The full extent to which the COVID-19 pandemic will directly or indirectly impact our business, results of operations and financial condition, including sales, expenses, reserves and allowances, clinical trials, research and development costs and employee-related amounts, will depend on future developments that are highly uncertain, including as a result of new information that may emerge concerning COVID-19 and the actions taken to contain the pandemic or treat COVID-19, as well as the economic impact on local, regional, national and international customers and markets. We have made estimates of the impact of COVID-19 within our financial statements and there may be changes to those estimates in future periods. Actual results may differ from these estimates. Cash and cash equivalents We consider highly liquid investments with a maturity of three months or less when purchased to be cash equivalents. Cash equivalents are stated at fair value. Marketable securities Marketable securities at December 31, 2020 and 2019 consisted of investments in U.S. Treasuries, government securities and corporate debt securities. We determine the appropriate classification of the securities at the time they are acquired and evaluate the appropriateness of such classifications at each balance sheet date. We classify our marketable securities as available-for-sale pursuant to Accounting Standards Codification, or ASC, 320, Investments – Debt and Equity Securities . Marketable securities are recorded at fair value. Unrealized gains are included as a component of accumulated other comprehensive income in the consolidated balance sheets and statements of stockholders’ equity and a component of total comprehensive loss in the consolidated statements of comprehensive loss, until realized. Realized gains and losses are included in investment income on a specific-identification basis. At December 31, 2020 and 2019, we held both current and non-current investments. Investments classified as current have maturities of less than one year . Investments classified as non-current are those that: (i) have a maturity of one to two years , and (ii) we do not intend to liquidate within the next twelve months , although these funds are available for use and therefore classified as available-for-sale. We review marketable securities for impairment whenever the fair value of a marketable security is less than the amortized cost and evidence indicates that a marketable security’s carrying amount is not recoverable. Unrealized losses are evaluated for impairment under ASC 326, Financial Instruments - Credit Losses , to determine if the impairment is credit-related or noncredit-related. Credit-related impairment is recognized as an allowance on the balance sheet with a corresponding adjustment to earnings, and noncredit-related impairment is recognized in other comprehensive income, net of taxes. Evidence considered in this assessment includes reasons for the impairment, compliance with our investment policy, the severity of the impairment, collectibility of the security, and any adverse conditions specifically related to the security, an industry, or geographic area. F-11 Fair value measurements We record cash equivalents and marketable securities at fair value. ASC 820, Fair Value Measurements and Disclosures , establishes a fair value hierarchy for those instruments measured at fair value that distinguishes between assumptions based on market data (observable inputs) and our own assumptions (unobservable inputs). The hierarchy consists of three levels: Level 1 – Unadjusted quoted prices in active markets for identical assets or liabilities. Level 2 – Quoted prices for similar assets and liabilities in active markets, quoted prices in markets that are not active, or inputs which are observable, either directly or indirectly, for substantially the full term of the asset or liability. Level 3 – Unobservable inputs that reflect our own assumptions about the assumptions market participants would use in pricing the asset or liability in which there is little, if any, market activity for the asset or liability at the measurement date. Our financial assets, which include cash equivalents and marketable securities, have been initially valued at the transaction price, and subsequently revalued at the end of each reporting period, utilizing third-party pricing services or other observable market data. The pricing services utilize industry standard valuation models, including both income and market based approaches, and observable market inputs to determine value. After completing our validation procedures, we did not adjust or override any fair value measurements provided by the pricing services as of December 31, 2020 or 2019. Fair value information for these assets, including their classification in the fair value hierarchy is included in Note 4. Fair Value Measurements . There have been no changes to the valuation methods during the years ended December 31, 2020 and 2019. We evaluate transfers between levels at the end of each reporting period. The carrying amounts of collaboration receivable – related party, collaboration receivable – other, royalty receivable – related party, accounts receivable, prepaid expenses and other current assets, accounts payable, and accrued expenses approximate their fair values due to their short-term maturities. Accounts receivable, net Our trade accounts receivable arise from product sales and represent amounts due from specialty distributors and specialty pharmacy providers in the U.S. We monitor the financial performance and creditworthiness of our customers so that we can properly assess and respond to changes in their credit profile. We reserve against these receivables for estimated losses that may arise from a customer’s inability to pay. Amounts determined to be uncollectible are charged or written-off against the reserve. Concentrations of credit risk Financial instruments which potentially subject us to credit risk consist primarily of cash, cash equivalents, and marketable securities. We hold these investments in highly rated financial institutions, and, by policy, limit the amounts of credit exposure to any one financial institution. These amounts at times may exceed federally insured limits. We have not experienced any credit losses in such accounts and do not believe we are exposed to any significant credit risk on these funds. We have no off-balance sheet concentrations of credit risk, such as foreign currency exchange contracts, option contracts, or other hedging arrangements. We are also subject to credit risk on our receivables, including trade receivables from our customers and collaboration and royalty receivables from Celgene and CStone Pharmaceuticals, or CStone. Concentrations of credit risk with respect to receivables, which are typically unsecured, are somewhat mitigated due to the number of customers using our products. Our trade receivables arise from product sales and have standard payment terms that generally require payment within 30 to 60 days. We have evaluated the creditworthiness of our customers, including Celgene, and determined them to be creditworthy. To date we have not experienced any losses with respect to our receivables. Inventory Inventory is stated at the lower of cost or estimated net realizable value on a first-in, first-out basis. Prior to the regulatory approval of our product candidates, we incur expenses for the manufacture of drug product that could potentially be available to support the commercial launch of those products. Until the date at which regulatory approval has been received or is otherwise considered probable, we record all such costs as research and development expenses. Upon approval of our wholly owned product, TIBSOVO®, by the FDA on July 20, 2018 for the treatment of adult patients with R/R AML with susceptible IDH1 mutation as detected by an FDA-approved test, we began to capitalize inventories of TIBSOVO®. We perform an assessment of the recoverability of capitalized inventory during each reporting period and write down any excess and obsolete inventory to its estimated net realizable value in the period in which the impairment is first identified. Such impairment charges, should they occur, are recorded as a component of cost of sales in the consolidated statements of operations. The determination of whether inventory costs will be realizable requires the use of estimates by management. If F-12 actual market conditions are less favorable than projected by management, additional write-downs of inventory may be required. Property and equipment Property and equipment consist of laboratory equipment, computer equipment and software, leasehold improvements, furniture and fixtures, and office equipment. Costs of major additions and betterment are capitalized; maintenance and repairs, which do not improve or extend the life of the respective assets, are charged to expense as incurred. Upon retirement or sale, the cost of the disposed asset and the related accumulated depreciation are removed from the accounts and the resulting gain or loss is recognized. Property and equipment is stated at cost, and depreciated using the straight-line method over the estimated useful lives of the respective assets: Years Laboratory equipment 5 Computer equipment and software 3 Furniture and fixtures 5 Office equipment 5 Leasehold improvements are amortized over the lesser of the remaining lease term or the estimated useful life of the improvement. Impairment of long-lived assets We periodically evaluate our long-lived assets for potential impairment in accordance with ASC 360, Property, Plant and Equipment . Potential impairment is assessed when there is evidence that events or changes in circumstances indicate that the carrying amount of an asset may not be recovered. Recoverability of these assets is assessed based on the undiscounted expected future cash flows from the assets, considering a number of factors, including past operating results, budgets and economic projections, market trends and product development cycles. If impairments are identified, assets are written down to their estimated fair value. We did not recognize any impairment charges through December 31, 2020. Leases We determine if an arrangement is a lease at inception. An arrangement is determined to contain a lease if the contract conveys the right to control the use of an identified property or equipment for a period of time in exchange for consideration. If we can benefit from the various underlying assets of a lease on their own or together with other resources that are readily available, or if the various underlying assets are neither highly dependent on nor highly interrelated with other underlying assets in the arrangement, they are considered to be a separate lease component. In the event multiple underlying assets are identified, the lease consideration is allocated to the various components based on each of the component’s relative fair value. Operating lease assets represent our right to use an underlying asset for the lease term and operating lease liabilities represent our obligation to make lease payments arising from the leasing arrangement. Operating lease assets and operating lease liabilities are recognized at commencement date based on the present value of lease payments over the lease term. As most of our leases do not provide an implicit rate, in determining the operating lease liabilities, we use an estimate of our incremental borrowing rate. The incremental borrowing rate is determined using two alternative credit scoring models to estimate our credit rating, adjusted for collateralization. The calculation of the operating lease assets includes any lease payments made and excludes any lease incentives. Our lease terms may include options to extend or terminate the lease when it is reasonably certain that we will exercise that option. For operating leases, we record operating lease assets and lease liabilities in our consolidated balance sheets. Lease expense for lease payments is recognized on a straight-line basis over the lease term. Short-term leases, or leases that have a lease term of 12 months or less at commencement date, are excluded from this treatment and are recognized on a straight-line basis over the term of the lease. We have not entered into any material short-term leases or financing leases as of December 31, 2020. Liability related to sale of future revenue We treat the sale of future revenue to RPI as a debt financing, as we have significant continuing involvement in the generation of the cash flows. As result, we recorded the proceeds from this transaction as a liability related to the sale of future revenue to be amortized to interest expense using the effective interest rate method over the life of the arrangement. F-13 The liability related to sale of future revenue and the related interest expense are based on our current estimates of future royalties expected to be paid over the life of the arrangement. We will periodically assess the expected royalty payments using forecasts from external sources. To the extent our future estimates of royalty payments are greater or less than previous estimates or the estimated timing of such payments is materially different than its previous estimates, we will prospectively recognize related non-cash interest expense. For further discussion of the sale of future revenue, refer to Note 10, Sale of Future Revenue . Amortization of issuance costs We treated the liability related to sale of future revenue as a debt financing. As such, the long-term liability is initially recorded at its proceeds, net of deferred costs. Issuance costs, fees directly related to the sale of future revenue, are offset against initial carrying value of the long-term liability and are amortized on a straight-line basis over the remaining patent life of the product to an operating expense. Revenue from contracts with customers On January 1, 2018 we adopted ASC 606, Revenue from Contracts with Customers , under the modified retrospective method. Prior to January 1, 2018 we accounted for the consideration received under the Collaboration Agreements under ASC 605-25, Multiple Element Arrangements. In adopting ASC 606, we applied the practical expedient that permits aggregating the effect of all contract modifications that occurred prior to January 1, 2018. No other practical expedients were used. Similar to the accounting under ASC 605-25, the 2016 Agreement was determined to be a modification of the 2010 Agreement and the AG-881 Agreements with Celgene. Revenue is recognized when the customer obtains control of promised goods or services, in an amount that reflects the consideration that we expect to receive in exchange for those goods or services. To determine revenue recognition for arrangements that we determined to be within the scope of ASC 606, we perform the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) we satisfy a performance obligation. We only apply the five-step model to contracts when it is probable that we will collect the consideration we are entitled to in exchange for the goods or services we transfer to the customer. At contract inception, once the contract is determined to be within the scope of ASC 606, we assess the goods or services promised within each contract and determine those that are performance obligations, and assess whether each promised good or service is distinct. We will then recognize as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) the performance obligation is satisfied. Product revenue We sell TIBSOVO®, our wholly owned product, to a limited number of specialty distributors and specialty pharmacy providers, or collectively, the Customers. The Customers subsequently resell TIBSOVO® to pharmacies or dispense directly to patients. In addition to distribution agreements with Customers, we enter into arrangements with healthcare providers and payors that provide for government-mandated and/or privately-negotiated rebates, chargebacks and discounts with respect to the purchase of TIBSOVO®. The performance obligation related to the sale of TIBSOVO® is satisfied and revenue is recognized when the Customer obtains control of the product, which occurs at a point in time, typically upon delivery to the Customer. Revenues from product sales are recorded at the net sales price, or transaction price, which includes estimates of variable consideration for which reserves are established and result from contractual adjustments, government rebates, returns and other allowances that are offered within the contracts with our Customers, healthcare providers, payors and other indirect customers relating to the sale of our products. Contractual adjustments. We generally provide Customers with discounts, including prompt pay discounts, and allowances that are explicitly stated in the contracts and are recorded as a reduction of revenue in the period the related product revenue is recognized. In addition, we receive sales order management, data and distribution services from certain Customers. Chargebacks for fees and discounts represent the estimated obligations resulting from contractual commitments to sell products to qualified healthcare providers at prices lower than the list prices charged to Customers who directly purchase the product from us. Customers charge us for the difference between what they pay for the product and the ultimate selling price to the qualified healthcare providers. These reserves are estimated using the expected value method, based upon a range of possible outcomes that are probability-weighted for the estimated channel mix and are established in the same period that the related revenue is recognized, resulting in a reduction of product revenue. F-14 Government rebates. Government rebates include Medicare, TriCare, and Medicaid rebates, which we estimate using the expected value method, based upon a range of possible outcomes that are probability-weighted for the estimated payor mix. These reserves are recorded in the same period the related revenue is recognized, resulting in a reduction of product revenue. For Medicare, we also estimate the number of patients in the prescription drug coverage gap for whom we will owe an additional liability under the Medicare Part D program. Returns. We estimate the amount of product sales that may be returned by Customers and record this estimate as a reduction of revenue in the period the related product revenue is recognized. We currently estimate product return liabilities using the expected value method, based on available industry data, including our visibility into the inventory remaining in the distribution channel. Collaboration revenue We apply the provisions of ASC 808, Collaborative Arrangements, when accounting for our collaboration agreements. We evaluate the presentation of amounts due from our collaborative partners associated with activities in the collaborative arrangement based on the nature of each activity. For transactions with customers, we have reported revenues and costs in accordance with ASC 606 and ASC 606-10-55-36 through 55-40, Principal versus Agent Considerations . We recognize revenue when the customer obtains control of promised goods or services, in an amount that reflects the consideration that we expect to receive in exchange for those goods or services. To determine revenue recognition for arrangements that have been determined to be within the scope of ASC 606, we perform the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract based on the relative standalone selling prices of the goods or services provided; (iii) determine the transaction price; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) we satisfy a performance obligation. We only apply the five-step model to contracts when it is probable that we will collect the consideration we are entitled to in exchange for the goods or services we transfer to the customer. Once the contract is determined to be within the scope of ASC 606, we assess the goods or services promised within each contract and determine those that are performance obligations, and assess whether each promised good or service is distinct. We will then recognize as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) the performance obligation is satisfied. The transaction price for each collaboration agreement is determined based on the amount of consideration we expect to be entitled to for satisfying all performance obligations within the agreement. Significant judgment may be required in determining the amount of variable consideration to be included in the transaction price. We use the expected value methods to determine variable consideration and will re-evaluate the transaction price in each reporting period and as uncertain events are resolved or other changes in circumstances occur. As part of the initial accounting for these arrangements, we must develop assumptions that require judgment to determine the standalone selling price, or SSP, for each performance obligation identified in the contract. We use these key assumptions to determine the SSP, which include forecast of revenues, development timelines, reimbursement rates for personnel costs, discount rates and probabilities of technical and regulatory success. We recognize the transaction price allocated to upfront license payments as revenue upon delivery of the license to the customer and resulting ability of the customer to use and benefit from the license, if the license is determined to be distinct from the other performance obligations identified in the contract. If the license is considered to not be distinct from other performance obligations, we exercise judgment to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied (i) at a point in time, but only for licenses determined to be distinct from other performance obligations in the contract, or (ii) over time; and, if over time, the appropriate method of measuring progress for purposes of recognizing revenue from license payments. We evaluate the measure of progress each reporting period and, if necessary, adjust the measure of performance and related revenue recognition. A significant portion of revenue generated from our collaboration agreements with Celgene relates to the provision of research and development services whereby revenue is recognized under an input method using the ratio of effort incurred to date compared to the total estimated effort required to complete the performance obligation. The calculation of the total estimated effort includes the total amount of forecasted costs associated with the completion of discovery, pre-clinical or clinical trials, as well as the assumed timing of these activities and estimated patient populations. Such cost estimates include forecasted direct labor and material costs, subcontractor costs, and external contract research organization, or CRO, costs. Milestone revenue Many of our collaboration agreements also entitle us to additional payments upon the achievement of performance-based milestones. These milestones are generally categorized into three types: development milestones, which are generally based on F-15 the initiation of clinical trials; regulatory milestones, which are generally based on the submission, filing or approval of regulatory applications such as a new drug application, or NDA, in the U.S.; and sales-based milestones, which are generally based on meeting specific thresholds of sales in certain geographic areas during a specified period. Upfront and ongoing development milestones per our collaboration agreements are not subject to refund if the development activities are not successful. For each collaboration that includes development milestone payments, we evaluate whether it is probable that the consideration associated with each milestone will not be subject to a significant reversal in the cumulative amount of revenue recognized. Amounts that meet this threshold are included in the transaction price using the most likely amount method, whereas amounts that do not meet this threshold are considered constrained and excluded from the transaction price until they meet this threshold. Milestones tied to regulatory approval, and therefore not within our control, are considered constrained until such approval is received. At the end of each subsequent reporting period, we re-evaluate the probability of a significant reversal of the cumulative revenue recognized for our milestones, and, if necessary, adjust our estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis, which would affect revenues from collaborators and loss in the period of adjustment. For arrangements that include sales-based milestone or royalty payments based on the level of sales, and in which the license is deemed to be the predominant item to which the sales-based milestone or royalties relate to, we recognize revenue in the period in which the sales-based milestone is achieved and in the period in which the sales associated with the royalty occur. Adoption of ASC 606 We adopted ASC 606 using the modified retrospective method. Under this method, we recognized the cumulative effect of the change in the opening balance of accumulated deficit in the January 1, 2018 consolidated balance sheet. In adopting ASC 606, we applied the practical expedient that permits aggregating the effect of all contract modifications that occurred prior to January 1, 2018. No other practical expedients were used. The impact of the cumulative effect of the accounting changes upon the adoption of the standard is as follows: (In thousands) December 31, 2017 Cumulative Effect January 1, 2018 Deferred revenue – related party, current and net of current portions $ 163,640 $ ( 39,456 ) $ 124,184 Accumulated deficit ( 798,061 ) 39,456 ( 758,605 ) The following tables summarize the effects of adopting ASC 606 on our consolidated financial statements: Consolidated Balance Sheets December 31, 2018 (In thousands) Under Topic 606 Under Topic 605 Effect of Change Accounts receivable, net $ 5,076 $ 5,076 $ — Collaboration receivable – related party 2,462 2,462 — Collaboration receivable – other 670 230 440 Total current assets 613,780 613,340 440 Total assets 858,457 858,017 440 Deferred revenue – related party 32,710 29,133 3,577 Total current liabilities 93,503 89,926 3,577 Deferred revenue, net of current portion – related party 59,809 101,180 ( 41,371 ) Total liabilities 170,920 208,714 ( 37,794 ) Accumulated deficit ( 1,104,633 ) ( 1,142,867 ) 38,234 Total stockholders’ equity 687,537 649,303 38,234 Total liabilities and stockholders’ equity 858,457 858,017 440 F-16 Consolidated Statements of Operations Year ended December 31, 2018 (In thousands, except per share data) Under Topic 606 Under Topic 605 Effect of Change Product revenue, net $ 13,841 $ 13,841 $ — Collaboration revenue – related party 60,661 58,994 1,667 Collaboration revenue – other 12,670 12,230 440 Total revenue 94,387 92,280 2,107 Research and development expense 341,324 337,995 3,329 Total cost and expenses 456,866 453,537 3,329 Loss from operations ( 362,479 ) ( 361,257 ) ( 1,222 ) Net loss ( 346,028 ) ( 344,806 ) ( 1,222 ) Net loss per share – basic and diluted ( 6.03 ) ( 6.01 ) ( 0.02 ) Consolidated Statements of Comprehensive Loss Year ended December 31, 2018 (In thousands) Under Topic 606 Under Topic 605 Effect of Change Net loss $ ( 346,028 ) $ ( 344,806 ) $ ( 1,222 ) Comprehensive loss ( 346,810 ) ( 345,588 ) ( 1,222 ) Consolidated Statements of Cash Flows Year ended December 31, 2018 (In thousands) Under Topic 606 Under Topic 605 Effect of Change Net loss $ ( 346,028 ) $ ( 344,806 ) $ ( 1,222 ) Adjustments to reconcile net loss to net cash used in operating activities: Accounts receivable, net ( 5,076 ) ( 5,076 ) — Collaboration receivable – related party ( 14 ) ( 14 ) — Collaboration receivable – other ( 670 ) ( 230 ) ( 440 ) Deferred revenue – related party ( 31,665 ) ( 33,327 ) 1,662 Cost of Sales Cost of sales consists primarily of manufacturing costs of TIBSOVO®. Based on our policy to expense costs associated with the manufacturing of our products prior to regulatory approval, certain of the manufacturing costs associated with product shipments of TIBSOVO® r ecorded during the years ended December 31, 2020, 2019, and 2018 were expensed prior to July 20, 2018 and, therefore, are not included in costs of sales during the years ended December 31, 2020, 2019 or 2018. Research and development costs Research and development costs, including those accrued as of each balance sheet date, are expensed as incurred. These costs include salaries and personnel-related costs, consulting fees, fees paid for contract research services, fees paid to contract CROs, and other third parties in connection with clinical trials and preclinical development activities, fees paid to investigative sites in connection with clinical studies, the costs associated with the product manufacturing, development, and distribution of clinical supplies, the costs of laboratory equipment and facilities, and other external costs. Nonrefundable advance payments for goods or services to be received in the future for use in research and development activities are deferred and capitalized. Additionally, there may be instances in which payments made to our vendors will exceed the level of services provided, and result in a prepayment of the research and development expense. The capitalized amounts are expensed as the related goods are delivered or the services are performed. We estimate the time period over which services will be performed and the level of effort to be expended in each period. If the actual timing of the performance of services or the level of effort varies from our estimate, we adjust the accrual or prepaid accordingly. F-17 Stock-based compensation We account for stock-based compensation awards in accordance with ASC 718, Compensation –Stock Compensation , or ASC 718. For stock-based awards granted to employees and to members of the board of directors for their services and for participation in our employee stock purchase plan, we primarily estimate the grant date fair value of each option award using the Black-Scholes option-pricing model. The use of the Black-Scholes option-pricing model requires us to make assumptions with respect to the expected term of the option, the expected volatility of the common stock consistent with the expected life of the option, risk-free interest rates and expected dividend yields of the common stock. For awards subject to service-based vesting conditions, we recognize stock-based compensation expense equal to the grant date fair value of stock options on a straight-line basis over the requisite service period. For awards subject to both performance and service-based vesting conditions, we recognize stock-based compensation expense over the remaining service period if the performance condition is considered probable of achievement using management’s best estimates. Income taxes Income taxes are recorded in accordance with ASC 740, Accounting for Income Taxes , or ASC 740, which provides for deferred taxes using an asset and liability approach. We recognize deferred tax assets and liabilities for the expected future tax consequences of events that have been included in our financial statements or tax returns. We determine our deferred tax assets and liabilities based on differences between the financial reporting and tax bases of assets and liabilities, which are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse. Valuation allowances are provided, if based upon the weight of available evidence, it is more likely than not that some or all of the deferred tax assets will not be realized. We also account for uncertain tax positions in accordance with the provisions of ASC 740. When uncertain tax positions exist, we recognize the tax benefit of tax positions to the extent that the benefit will more likely than not be realized. The determination as to whether the tax benefit will more likely than not be realized is based upon the technical merits of the tax position as well as consideration of the available facts and circumstances. Comprehensive income (loss) Comprehensive income (loss) is defined as the change in equity of a business enterprise during a period from transactions, and other events and circumstances, and currently consists of net loss and unrealized gains and losses on available-for-sale securities. Accumulated other comprehensive loss consists entirely of unrealized gains and losses from available-for-sale securities as of December 31, 2020 and 2019. Net loss per share Basic net loss per share is calculated by dividing net loss by the weighted-average shares outstanding during the period, without consideration for common stock equivalents. Diluted net loss per share is calculated by adjusting weighted-average shares outstanding for the dilutive effect of common stock equivalents outstanding for the period, determined using the treasury-stock method. For purposes of the dilutive net loss per share calculation, stock options, restricted stock units, or RSUs, performance-based stock units, or PSUs, and market-based stock units, or MSUs, for which the performance vesting conditions have been met, and employee stock purchase plan shares are considered to be common stock equivalents but are excluded from the calculation of diluted net loss per share as their effect would be anti-dilutive. Segment and geographic information Operating segments are identified as components of an enterprise about which separate discrete financial information is available for evaluation by the chief operating decision maker, or decision-making group, in making decisions on how to allocate resources and assess performance. Our chief operating decision maker is the chief executive officer. Our chief operating decision maker and we view our operations and manage our business as one operating segment. Recent accounting pronouncements Leases In February 2016, the Financial Accounting Standard Board, or FASB issued Accounting Standards Update, or ASU, No. 2016-02, Leases (Topic 842) , which was codified as ASC 842, Leases , and amended through subsequent ASUs. We adopted ASC 842 effective January 1, 2019 using the optional transition method provided for under ASU 2018-11, Leases (Topic 842): Targeted Improvements , whereby we applied the new lease requirements through a cumulative-effect adjustment, which after completing our implementation analysis, resulted in no material adjustment to our January 1, 2019 beginning accumulated deficit balance. We also elected the package of practical expedients provided for under ASU 2018-11, which allows us not to reassess whether contracts are or contain leases, lease classification, and whether initial direct costs qualify for capitalization. F-18 Additionally, as an accounting policy, for our building leases, we chose not to separate the non-lease components from the lease components and, instead, accounted for each non-lease component and lease component as a single component. We completed our assessment over the impact of the standard and determined that the only material leases that we hold are our building leases. Upon adoption of the standard on January 1, 2019, we recorded operating right of use assets of $ 59.9 million and operating lease liabilities of $ 77.3 million on our consolidated balance sheets. Prior periods are presented in accordance with ASC 840, Leases . Other recent accounting pronouncements In June 2018, the FASB issued ASU 2018-07 – Compensation-Stock Compensation (Topic 718)-Improvements to Nonemployee Share-Based Payment Accounting . ASU 2018-07 simplifies the accounting for share-based payments to nonemployees by aligning it with the accounting for share-based payments to employees, with certain exceptions. ASU 2018-07 is effective for fiscal years beginning after December 15, 2018. The Company adopted the new standard as of January 1, 2019. There was no material impact to the Company’s consolidated financial position, results of operation, or cash flows. In December 2019, the FASB issued ASU 2019-12 – Income Taxes (Topic 740) Simplifying the Accounting for Income Taxes, as part of its initiative to reduce complexity in the accounting standards. The amendments in ASU 2019-12 eliminate certain exceptions related to the approach for intraperiod tax allocation, the methodology for calculating income taxes in an interim period and the recognition of deferred tax liabilities for outside basis differences. ASU 2019-12 also clarifies and simplifies other aspects of the accounting for income taxes. The amendments in ASU 2019-12 are effective for the fiscal years beginning after December 15, 2020. Early adoption is permitted, including adoption in any interim period. The Company has early adopted this amendment as of January 1, 2019. There was no material impact to the Company’s consolidated financial position, results of operation, or cash flows. In June 2016, the FASB issued ASU 2016-13, Financial Instruments - Credit Losses (Topic 326) , which introduces new guidance for the accounting for credit losses on instruments within its scope. The new guidance introduces an approach based on expected losses to estimate credit losses on certain types of financial instruments. Credit losses relating to available-for-sale debt securities will also be recorded through an allowance for credit losses rather than as a reduction in the amortized cost basis of the securities. The guidance is effective for fiscal years beginning after December 31, 2019, including interim periods within those years. The Company adopted this amendment as of January 1, 2020, which eliminated the concept of other-than-temporary impairments and required credit losses on debt securities to be recorded through an allowance for credit losses instead of as a reduction in the amortized cost basis of the securities. Application of the amendments is through a cumulative-effect adjustment to retained earnings as of the effective date. There was no material impact to the Company’s consolidated financial position, results of operation, or cash flows. Other accounting standards that have been issued by the FASB or other standards-setting bodies that do not require adoption until a future date are not expected to have a material impact on our financial statements upon adoption. Subsequent events We considered events or transactions occurring after the balance sheet date, but prior to the issuance of the consolidated financial statements, for potential recognition or disclosure in our consolidated financial statements. All significant subsequent events have been properly disclosed in the consolidated financial statements. F-19 Note 4. Fair Value Measurements The following table summarizes our cash equivalents and marketable securities measured at fair value and by level (as described in Note 3. Summary of Significant Accounting Policies ) on a recurring basis as of December 31, 2020: (In thousands) Level 1 Level 2 Level 3 Total Cash equivalents $ 69,424 $ — $ — $ 69,424 Total cash equivalents 69,424 — — 69,424 Marketable securities: U.S. Treasuries — 128,809 — 128,809 Government securities — 135,131 — 135,131 Corporate debt securities — 279,161 — 279,161 Total marketable securities — 543,101 — 543,101 Total cash equivalents and marketable securities $ 69,424 $ 543,101 $ — $ 612,525 There were no transfers between Level 1 and Level 2 and we had no financial assets or liabilities that were classified as Level 3, except for the liability related to the sale of future revenue as discussed in Note 10, Sale of Future Revenue , at any point during the year ended December 31, 2020. Note 5. Marketable Securities Marketable securities at December 31, 2020 consisted of the following: (In thousands) Amortized Cost Unrealized Gains Unrealized Losses Fair Value Current: U.S. Treasuries $ 113,559 $ 134 $ ( 21 ) $ 113,672 Government securities 108,263 37 ( 8 ) 108,292 Corporate debt securities 223,461 140 ( 72 ) 223,529 Total Current 445,283 311 ( 101 ) 445,493 Non-current: U.S. Treasuries 15,147 — ( 10 ) 15,137 Government securities 26,831 8 — 26,839 Corporate debt securities 55,735 2 ( 105 ) 55,632 Total Non-current 97,713 10 ( 115 ) 97,608 Total marketable securities $ 542,996 $ 321 $ ( 216 ) $ 543,101 F-20 Marketable securities at December 31, 2019 consisted of the following: (In thousands) Amortized Cost Unrealized Gains Unrealized Losses Fair Value Current: U.S. Treasuries $ 178,721 $ 58 $ ( 38 ) $ 178,741 Government securities 80,228 17 ( 16 ) 80,229 Corporate debt securities 224,928 139 ( 91 ) 224,976 Total Current 483,877 214 ( 145 ) 483,946 Non-current: U.S. Treasuries 35,296 3 ( 13 ) 35,286 Government securities 17,587 14 ( 10 ) 17,591 Corporate debt securities 99,913 239 ( 100 ) 100,052 Total Non-current 152,796 256 ( 123 ) 152,929 Total marketable securities $ 636,673 $ 470 $ ( 268 ) $ 636,875 There were no material realized gains or losses on marketable securities for the years ended December 31, 2020 and 2019. At December 31, 2020 and 2019, we held 87 and 113 debt securities, respectfully, that were in an unrealized loss position for less than one year. We did no t record an allowance for credit losses as of December 31, 2020 and December 31, 2019 related to these securities. The aggregate fair value of debt securities in an unrealized loss position at December 31, 2020 and 2019 was $ 299.0 million and $ 345.7 million, respectively. There were no individual securities that were in a significant unrealized loss position as of December 31, 2020 and 2019. We regularly review the securities in an unrealized loss position and evaluate the current expected credit loss by considering factors such as historical experience, market data, issuer-specific factors, and current economic conditions. We do not consider these marketable securities to be impaired as of December 31, 2020 and 2019. Note 6. Property and Equipment, net Property and equipment, net consisted of the following at December 31: (In thousands) 2020 2019 Laboratory equipment $ 25,334 $ 23,418 Computer equipment and software 6,945 6,415 Leasehold improvements 32,568 23,879 Furniture and fixtures 3,035 2,101 Office equipment 1,651 589 Construction in progress 4,111 7,182 Total property and equipment 73,644 63,584 Less: accumulated depreciation ( 41,353 ) ( 32,112 ) Total property and equipment, net $ 32,291 $ 31,472 Depreciation expense for the years ended December 31, 2020, 2019 and 2018 was $ 9.4 million, $ 8.0 million and $ 7.2 million, respectively. Note 7. Inventory Inventory consisted of the following at December 31: (In thousands) 2020 2019 Raw materials $ 294 $ 180 Work-in-process 13,039 6,808 Finished goods 1,365 343 Total Inventory $ 14,698 $ 7,331 F-21 Inventory is related to our approved product, TIBSOVO®. There were no write downs for excess and obsolete inventory during the years ended December 31, 2020, 2019 or 2018. Note 8. Leases Our building leases are comprised of office and laboratory space under non-cancelable operating leases. These lease agreements have remaining lease terms of seven years and contain various clauses for renewal at our option. The renewal options were not included in the calculation of the operating lease assets and the operating lease liabilities as the renewal option is not reasonably certain of being exercised. The lease agreements do not contain residual value guarantees. On April 11, 2019, we entered into an agreement to lease approximately 13,000 square feet of office space located at 38 Sidney Street, Cambridge, Massachusetts, or the 38 Sidney Lease, with Thirty-Eight Sidney Street, LLC. The initial term of the 38 Sidney Lease commenced on May 1, 2019 and expires on February 29, 2028. At the end of the lease term, we have the option to extend the 38 Sidney Lease for two consecutive terms of five years at fair market rent at the time of the extension. The 38 Sidney Lease provides us with the right to lease additional space within the 38 Sidney Street building and also includes rent escalation clauses and a tenant improvement allowance of $ 1.0 million. In connection with the 38 Sidney Lease, we also amended our existing building leases at 88 Sidney Street, Cambridge, Massachusetts and at 64 Sidney Street, Cambridge, Massachusetts to extend the initial terms of those leases by approximately three years through February 29, 2028. The amendments also provide us with the right to lease additional space at the 64 Sidney Street building. Our existing extension options for the 88 Sidney Street building and 64 Sidney Street building continue as set forth in the existing leases for those buildings. The components of lease expense and other information related to leases were as follows: (In millions) 2020 2019 Operating Lease Costs $ 15.2 $ 15.1 Cash paid for amounts included in the measurement of operating lease liabilities 14.4 12.8 Rental expense under these leases, net of tenant improvement reimbursements, amounted to $ 11.4 million, for the year ended December 31, 2018. In addition to rent, the leases may require us to pay additional amounts for taxes, insurance, maintenance and other operating expenses. We have not entered into any material short-term leases or financing leases as of December 31, 2020. In arriving at the operating lease liabilities as of December 31, 2020, we applied the weighted-average incremental borrowing rate of 5.7 % over a weighted-average remaining lease term of 7.2 years. In arriving at the operating lease liabilities as of December 31, 2019, we applied the weighted-average incremental borrowing rate of 5.7 % over a weighted-average remaining lease term of 8.2 years. As of December 31, 2020, undiscounted minimum rental commitments under non-cancelable leases, for each of the next five years and total thereafter, were as follows: (In thousands) 2021 $ 13,198 2022 16,773 2023 18,126 2024 18,660 2025 19,507 Thereafter 44,385 Undiscounted minimum rental commitments 130,649 Interest ( 26,098 ) Total operating lease liabilities $ 104,551 We provided our landlord a standby letter of credit of $ 2.9 million as security for our leases. We are not required to maintain any cash collateral for the standby letter of credit. F-22 Note 9. Accrued Expenses Accrued expenses consisted of the following at December 31: (In thousands) 2020 2019 Accrued compensation $ 26,286 $ 18,982 Accrued research and development costs 14,904 21,777 Accrued professional fees 3,366 8,335 Accrued revenue-related reserves and other 15,584 4,048 Total accrued expenses $ 60,140 $ 53,142 Note 10. Sale of Future Revenue On June 11, 2020, we sold our tiered, sales-based royalty rights on worldwide net sales of IDHIFA®, as well as our rights to receive up to $ 55.0 million in outstanding regulatory milestone payments from BMS, to RPI for $ 255.0 million. The gross proceeds of $ 255.0 million approximate the fair value of the liability related to the sale of future revenue based on a discounted cash flow model. The fair value for the liability related to the sale of future revenue at December 31, 2020 was based on our current estimates of future royalties expected to be paid to RPI over the remaining patent life of the product, which are considered level 3 inputs. Under the terms of the purchase agreement with RPI, although we sold all of our rights to receive royalties on worldwide net sales of IDHIFA® and future regulatory milestone payments, we continue to co-promote IDHIFA® and are therefore involved in the generation of these royalties. Due to our continuing involvement, we will continue to account for any royalties earned as revenue. We recorded the net proceeds from this transaction as a liability related to sale of future revenue, or the Royalty Obligation, that will be amortized using the effective interest method over the remaining patent life. Significant judgment was applied in determining the appropriate accounting treatment for the transaction. As royalties are remitted to RPI from BMS, the balance of the Royalty Obligation will be effectively repaid over the life of the BMS license agreement. In order to determine the amortization of the Royalty Obligation, we are required to estimate the total amount of future royalty payments to RPI over the life of the BMS license agreement. The $ 255.0 million recorded will be accreted to the total of these royalty payments as interest expense over the life of the Royalty Obligation. At December 31, 2020, our estimate of this total interest expense resulted in an effective annual interest rate of approximately 9.5 %. This estimate contains significant assumptions that impact both the amount recorded at execution and the interest expense that will be recognized over the royalty period. We will periodically assess the estimated royalty payments to RPI from BMS and to the extent the amount or timing of such payments is materially different than the original estimates, an adjustment will be recorded prospectively to increase or decrease interest expense. There are a number of factors that could materially affect the amount and timing of royalty payments to RPI from BMS, and correspondingly, the amount of interest expense recorded by us, most of which are not within our control. Such factors include, but are not limited to, delays or discontinuation of development of enasidenib, regulatory approval, changing standards of care, the introduction of competing products, manufacturing or other delays, generic competition, intellectual property matters, adverse events that result in governmental health authority imposed restrictions on the use of the drug products, significant changes in foreign exchange rates as the royalties remitted to RPI are made in U.S. dollars (USD) while the underlying sales of enasidenib will be made in currencies other than USD, and other events or circumstances that are not currently foreseen. Changes to any of these factors could result in increases or decreases to both royalty revenues and interest expense. The following table shows the activity of the Royalty Obligation since the transaction inception through December 31, 2020: (in thousands) December 31, 2020 Proceeds from the sale of future revenue $ 255,000 Issuance costs ( 4,463 ) Non-cash royalty related to the sale of future revenue ( 7,294 ) Non-cash interest expense associated with the sale of future revenue 17,832 Amortization of issuance costs 194 Liability related to the sale of future revenue $ 261,269 During the year ended December 31, 2020, $ 7.3 million of non-cash royalty revenue from net sales of IDHIFA® were recognized. F-23 Note 11. Commitments and Contingent Liabilities Manufacturing Commitments We are party to various agreements with contract manufacturing organizations that we are not contractually able to terminate for convenience and avoid any and all future obligations to the vendors. Under such agreements, we are obligated to make certain minimum payments, with the exact amounts in the event of termination to be based on the timing of the termination and the exact terms of the agreement. Legal Contingencies From time to time, we may be involved in disputes and legal proceedings in the ordinary course of business. These proceedings may include allegations of infringement of intellectual property, employment or other matters. We do no t have any ongoing legal proceedings that, based on our estimates, could have a material effect on our consolidated financial statements. Note 12. Product Revenue Upon FDA approval of TIBSOVO® in the U.S., on July 20, 2018, we began generating product revenue from sales of TIBSOVO®. (In thousands) 2020 2019 2018 Product revenue, net $ 121,089 $ 59,851 $ 13,841 The following table summarizes balances and activity in each of the product revenue allowance and reserve categories for the year ended December 31, 2020: (In thousands) Contractual Adjustments Government Rebates Returns Total Balance at December 31, 2019 $ 874 $ 1,124 $ 1,798 $ 3,796 Current provisions relating to sales in the current year 14,410 13,627 1,252 29,289 Adjustments relating to prior years ( 3 ) 122 ( 1,404 ) ( 1,285 ) Payments/returns relating to sales in the current year ( 13,112 ) ( 2,987 ) — ( 16,099 ) Payments/returns relating to sales in the prior years ( 653 ) ( 677 ) — ( 1,330 ) Balance at December 31, 2020 $ 1,516 $ 11,209 $ 1,646 $ 14,371 The following table summarizes balances and activity in each of the product revenue allowance and reserve categories for the year ended December 31, 2019: (In thousands) Contractual Adjustments Government Rebates Returns Total Balance at December 31, 2018 $ 592 $ 325 $ 334 $ 1,251 Current provisions relating to sales in the current year 7,899 2,387 1,464 11,750 Adjustments relating to prior years 8 ( 41 ) — ( 33 ) Payments/returns relating to sales in the current year ( 7,027 ) ( 1,286 ) — ( 8,313 ) Payments/returns relating to sales in the prior years ( 598 ) ( 261 ) — ( 859 ) Balance at December 31, 2019 $ 874 $ 1,124 $ 1,798 $ 3,796 Total revenue-related reserves for the years ended December 31, 2020 and 2019 above, included in our consolidated balance sheets, are summarized as follows: (In thousands) December 31, 2020 December 31, 2019 Reduction of accounts receivable $ 902 $ 540 Component of accrued expenses 13,469 3,256 Total revenue-related reserves $ 14,371 $ 3,796 F-24 The following table presents changes in our contract assets during the year ended December 31, 2020: (In thousands) December 31, 2019 Additions Deductions December 31, 2020 Contract assets Accounts receivable, net (1) $ 8,952 $ 149,207 $ ( 136,831 ) $ 21,328 (1) Additions to accounts receivable, net relate to amounts billed to Customers for product sales and deductions primarily relate to collection of receivables during the reporting period. The following table presents changes in our contract assets during the year ended December 31, 2019: (In thousands) December 31, 2018 Additions Deductions December 31, 2019 Contract assets Accounts receivable, net (1) $ 5,076 $ 71,542 $ ( 67,666 ) $ 8,952 (1) Additions to accounts receivable, net relate to amounts billed to Customers for product sales and deductions primarily relate to collection of receivables during the reporting period. Note 13. Collaboration and License Agreements Celgene Corporation To date, our revenue has primarily been generated from our collaboration agreements with Celgene, or collectively, the Collaboration Agreements. Celgene is a related party through ownership of our common stock. In April 2010, we entered into a discovery and development collaboration and license agreement focused on cancer metabolism, or the 2010 Agreement. The 2010 Agreement was amended in October 2011 and July 2014. On June 11, 2020, we sold our tiered, sales-based royalty rights on worldwide net sales of IDHIFA®, as well as our rights to receive up to $ 55.0 million in outstanding regulatory milestone payments from BMS, to RPI for $ 255.0 million. Under the 2010 Agreement, we are eligible to receive a $ 25.0 million potential milestone payment for the enasidenib program upon achievement of a specified ex-U.S. commercial milestone event, as well as reimbursement for costs incurred for our co-commercialization efforts and development activities. In April 2015, we entered into a joint worldwide development and profit share collaboration and license agreement with Celgene, and our wholly owned subsidiary, Agios International Sarl, entered into a collaboration and license agreement with Celgene International II Sarl, or collectively, the AG-881 Agreements, to establish a worldwide collaboration focused on the development and commercialization of vorasidenib products. The AG-881 Agreements were terminated effective September 4, 2018. In May 2016, we entered into a master research and collaboration agreement with Celgene, or the 2016 Agreement. The initial four-year research term for the 2016 Agreement expired on May 17, 2020. On March 25, 2020 Celgene declined the option to extend the research agreement. Further, on April 10, 2020 Celgene notified us that they declined to elect any program as a continuation program under the 2016 agreement. Celgene had designated AG-270, our inhibitor MAT2A, as a development candidate under the 2016 Agreement. On March 25, 2020, Celgene notified us of their decision to decline their option to enter into a development & commercialization agreement with respect to the MAT2A program under the 2016 Agreement. 2016 Agreement The 2016 Agreement focused on metabolic immuno-oncology, a developing field which aims to modulate the activity of relevant immune cells by targeting critical metabolic nodes, thereby enhancing the immune mediated anti-tumor response. In addition to new programs identified under the 2016 Agreement, both parties also agreed that all future development and commercialization of two remaining cancer metabolism programs discovered under the 2010 Agreement, including AG-270, would be governed by the 2016 Agreement. The initial four-year research term expired on May 17, 2020. On March 25, 2020 Celgene declined the option to extend the research agreement for up to two , or in specified cases, up to four additional one-year terms which would have required the payment of a $ 40.0 million extension fee. Further, on April 10, 2020 Celgene notified us that they declined to elect any program as a continuation program under the 2016 agreement. Celgene had designated AG-270, our inhibitor of methionine adenosyltransferase 2a, or MAT2A, as a development candidate under the 2016 Agreement. On March 25, 2020, Celgene notified us of their decision to decline their option to enter into a development & commercialization agreement with respect to the MAT2A program under the 2016 Agreement which would have required the payment of a $ 30.0 million fee. As a result of the decisions, the research services were fully satisfied as of May 17, 2020, no additional performance obligations remain under the 2016 Agreement and we are no longer eligible for any milestone payments for the 2016 Agreement. F-25 During the research term of the 2016 Agreement, we conducted research programs focused on discovering compounds that are active against metabolic targets in the immuno-oncology, or IO, field. For each program under the 2016 Agreement, we could have nominated compounds that meet specified criteria as development candidates and, in limited circumstances, Celgene could also nominate compounds as development candidates for each such program. Celgene could designate the applicable program for further development following any such nomination, after which we could conduct, at our expense, additional preclinical and clinical development for such program through the completion of an initial phase 1 dose escalation study. At the end of the research term, Celgene could designate for continued development up to three research programs for which development candidates have yet to be nominated, which are referred to as continuation programs. We could conduct further research and preclinical and clinical development activities on any continuation program, at our expense, through the completion of an initial phase 1 dose escalation study. We granted Celgene the right to obtain exclusive options for development and commercialization rights for each program that Celgene designated for further development, and for each continuation program. Celgene could have exercised each such option beginning on the designation of a development candidate for such program (or on the designation of such program as a continuation program) which ended on the earlier of: (i) the end of a specified period after we have furnished Celgene with specified information about the initial phase 1 dose escalation study for such program, or (ii) January 1, 2030. Research programs that have applications in the inflammation or autoimmune, or I&I, field that may result from the 2016 Agreement would also subject to the exclusive options described above. We retain rights to all program that Celgene did not designate for further development or as to which it did not exercise its option. Under the terms of the 2016 Agreement, if Celgene had exercised their option, the parties would enter into either a co-development and co-commercialization agreement if such program is in the IO field, or a license agreement if such program is in the I&I field. Under each co-development and co-commercialization agreement, the two parties would co-develop and co-commercialize licensed products worldwide. Either we or Celgene would lead development and commercialization of licensed products for the United States, and Celgene would lead development and commercialization of licensed products outside of the United States. Depending on the country, the parties would each have the right to provide a portion of field-based marketing activities. Under each license agreement, Celgene would have the sole right to develop and commercialize licensed products worldwide. Co-development and co-commercialization agreements Under each co-development and co-commercialization agreement entered into under the 2016 Agreement, if Celgene had exercised their option, the parties would have split all post-option exercise worldwide development costs, subject to specified exceptions, as well as any profits from any net sales of, or commercialization losses related to, licensed products in the IO field. Celgene had the option to designate one program in the IO field as the 65/35 program, for which Celgene would be the lead party for the United States and would have a 65 % profit or loss share. For programs in the IO field other than the 65/35 program, we and Celgene would alternate, on a program-by-program basis, being the lead party for the United States, with us having the right to be the lead party for the first such program, and each party will have a 50 % profit or loss share. The lead party for the United States would book commercial sales of licensed products, if any, in the United States, and Celgene would book commercial sales of licensed products, if any, outside of the United States. License agreements Under each license agreement under the 2016 Agreement, Celgene would be responsible for all post-option exercise worldwide development and associated costs, subject to specified exceptions, as well as worldwide commercialization and associated costs, for licensed products in the I&I field. Financial terms Under the terms of the 2016 Agreement, we received an initial upfront payment in the amount of $ 200.0 million. The 2016 Agreement provided specified rights to extend the research term for up to two , or in specified cases, up to four , additional years by paying a $ 40.0 million per-year extension fee. On March 25, 2020, Celgene declined the option to extend the research agreement for up to two, or in specified cases, up to four additional one-year terms. Celgene was also required to pay an $ 8.0 million designation fee for each program that Celgene designated for further development and for each continuation program. On April 10, 2020, Celgene notified us that they declined to elect any program as a continuation program under the 2016 agreement. During the year ended December 31, 2017, we received $ 8.0 million from Celgene upon the designation of AG-270 as a development candidate. For each program as to which Celgene exercised its option to develop and commercialize, subject to antitrust clearance, Celgene would be required to pay an option exercise fee of at least $ 30.0 million for any designated development program and at least $ 35.0 million for any continuation programs. On March 25, 2020, Celgene notified us of their decision to decline their option to enter into a Development & Commercialization Agreement with respect to the MAT2A F-26 program under the 2016 Agreement. In certain cases, Celgene could exercise its option to develop and commercialize two early-stage I&I programs, prior to Celgene designating the program for further development, by paying an option exercise fee of $ 10.0 million, which was not exercised during the year ended December 31, 2020. As a result of the decisions, the research services were fully satisfied as of May 17, 2020, no additional performance obligations remain under the 2016 Agreement and we are no longer eligible for any milestone payments for the 2016 Agreement. We were eligible to receive the following milestone-based payments associated with the 2016 Agreement: Program Milestone Amount 65/35 program in IO field Specified clinical development event $ 25.0 million 65/35 program in IO field Specified regulatory milestone events Up to $ 183.8 million 50/50 program in IO field Specified clinical development event $ 20.0 million 50/50 program in IO field Specified regulatory milestone events Up to $ 148.8 million I&I field Specified clinical development event $ 25.0 million I&I field Specified regulatory milestone events Up to $ 236.3 million I&I field Specified commercial milestone events Up to $ 125.0 million Additionally, for each licensed program in the I&I field, we were eligible to receive royalties at tiered, low double-digit percentage rates on Celgene’s net sales, if any, of the applicable licensed products. Opt-out right Under the 2016 Agreement, we could elect to opt out of the cost and profit share under any co-development and co-commercialization agreement, subject to specified exceptions. Upon opting out, Celgene would have the sole right to develop, manufacture and commercialize the applicable licensed products throughout the world, at its cost, and we would undertake transitional activities reasonably necessary to transfer the development, manufacture and commercialization of such licensed products to Celgene, at our expense. Further, in lieu of the profit or loss sharing described above, we would be eligible to receive royalties at tiered, low double-digit percentage rates on Celgene’s net sales, if any, of the applicable licensed products. However, we would continue to be eligible to receive the developmental and regulatory milestone-based payments described above. Termination The term of the 2016 Agreement commenced on May 17, 2016 and expired on May 17, 2020 in its entirety. The research services were fully satisfied as of May 17, 2020, no additional performance obligations remain under the 2016 Agreement and we are no longer eligible for any milestone payments for the 2016 Agreement. Exclusivity While any of Celgene’s options remained available under the 2016 Agreement, subject to specified exceptions, we could not directly or indirectly develop, manufacture or commercialize, outside of the 2016 Agreement, any therapeutic modality in the IO or I&I field with specified activity against a metabolic target. During the term of each co-development and co-commercialization agreement and license agreement, subject to specified exceptions, neither we nor Celgene could directly or indirectly develop, manufacture or commercialize outside of such agreement any therapeutic modality in any field with specified activity against the metabolic target that is the focus of the program licensed under such agreement. Ivosidenib Letter Agreement On May 17, 2016, we entered into a letter agreement with Celgene regarding ivosidenib, or the Ivosidenib Letter Agreement. Under the Ivosidenib Letter Agreement, the parties agreed to terminate the 2010 Agreement, effective as of August 15, 2016, as to the program directed to the IDH1 target, for which ivosidenib is the lead development candidate. Under the 2010 Agreement, Celgene had held development and commercialization rights to the IDH1 program outside of the United States, and we held such rights inside the United States. As a result of the Ivosidenib Letter Agreement, we obtained global rights to ivosidenib and the IDH1 program. Neither party will have any further financial obligation, including royalties or milestone payments, to the other concerning ivosidenib or the IDH1 program. Under the terms of the Ivosidenib Letter Agreement, the parties also agreed to conduct specified transitional activities in connection with the termination. In addition, pursuant to the Ivosidenib Letter Agreement, the parties are released from their exclusivity obligations under the 2010 Agreement with respect to the IDH1 program. The Ivosidenib Letter Agreement does not affect the AG-881 Agreements, which were directed to both the IDH1 target and the IDH2 target, and were subsequently terminated in September 2018 as discussed below. F-27 Termination of AG-881 Agreements We and Celgene terminated the AG-881 Agreements, effective as of September 4, 2018. From and after September 4, 2018, we obtained sole global rights to vorasidenib. Neither we nor Celgene will have any further financial obligation under the AG-881 Agreements, including milestones, royalties or other payments, except that (a) Celgene is eligible to receive royalties from us at a low single-digit percentage rate on worldwide net sales of products containing vorasidenib and (b) we and Celgene agreed to split certain agreed-upon worldwide development costs for vorasidenib until December 31, 2018. In addition, for a specified period and subject to specified exceptions, Celgene and its affiliates are prohibited from developing, manufacturing or commercializing any product that inhibits IDH1 at specified levels of binding for any indication and we are prohibited from developing, manufacturing or commercializing vorasidenib in hematologic indications. 2010 Agreement The 2010 Agreement, which was entered into in April 2010, was amended in October 2011 and July 2014. The goal of the collaboration was to discover, develop and commercialize disease-altering therapies in oncology based on our cancer metabolism research platform. We initially led discovery, preclinical and early clinical development for all cancer metabolism programs under the collaboration. The discovery phase of the 2010 Agreement expired in April 2016. Upon agreement to terminate the 2010 Agreement, effective as of August 15, 2016, as to the program directed to the IDH1 target, for which ivosidenib is the lead development candidate, the sole program remaining under the 2010 Agreement is IDHIFA®, a co-commercialized licensed program for which Celgene leads and funds global development and commercialization activities. We have exercised our right to participate in a portion of commercialization activities in the United States for IDHIFA® in accordance with the applicable commercialization plan. On August 1, 2017, the FDA granted Celgene approval of IDHIFA® for the treatment of adult patients with R/R AML with an IDH2 mutation as detected by an FDA-approved test. Under the 2010 Agreement, we received royalties at tiered, low-double digit to mid-teen percentage rates on net sales of IDHIFA®. On June 11, 2020, we sold our tiered, sales-based royalty rights on worldwide net sales of IDHIFA®, as well as our rights to receive up to $ 55.0 million in outstanding regulatory milestone payments from BMS, to RPI for $ 255.0 million. Under the 2010 Agreement, we were eligible to receive a $ 25.0 million potential milestone payment for the enasidenib program upon achievement of a specified ex-U.S. commercial milestone event, as well as reimbursement for costs incurred for our co-commercialization efforts and development activities. Unless terminated earlier by either party, the term of the 2010 Agreement will continue until the expiration of all royalty terms with respect to IDHIFA®. Celgene may terminate this agreement for convenience in its entirety upon ninety days written notice to us. If either party is in material breach and fails to cure such breach within the specified cure period, the other party may terminate the 2010 Agreement in its entirety. Either party may terminate the agreement in the event of specified insolvency events involving the other party. Collaboration revenue Performance obligations identified Upon the adoption of ASC 606 on January 1, 2018, we applied the practical expedient that permits aggregating the effect of all contract modifications that occurred prior to January 1, 2018. No other practical expedients were used. Similar to the accounting under ASC 605-25, the 2016 Agreement was determined to be a modification of the 2010 Agreement and the AG-881 Agreements. In determining the appropriate amount of revenue to be recognized under ASC 606, we perform the following steps: (i) identified the promised goods or services in the contract; (ii) determined whether the promised goods or services are performance obligations including whether they are distinct in the context of the contract; (iii) measured the transaction price, including the constraint on variable consideration; (iv) allocated the transaction price to the performance obligations; and (v) recognized revenue when (or as) we satisfied each performance obligation. The transaction price is calculated as the total amount of consideration to which the Company expects to be entitled to in exchange of transferring the promised goods and services to Celgene, and excludes any amounts of variable consideration that have been constrained (being contingency based development, regulatory and sales based milestones for which the Company cannot assert it is probable that a significant reversal of cumulative revenue recognized will not occur when the uncertainty associated with the milestone is subsequently resolved). The transaction price upon the adoption of ASC 606 was comprised of all consideration received to date under the agreements, as well as the estimated amount of research and development cost reimbursements that will be received under the agreement. F-28 The transaction price was subsequently allocated to the individual performance obligations based on their relative standalone selling prices. We developed assumptions that require judgment to determine the SSP for each performance obligation identified in the contract. We use key assumptions to determine the SSP, which include forecast of revenues, development timelines, reimbursement rates for personnel costs, discount rates and probabilities of technical and regulatory success. The satisfied and unsatisfied performance obligations at the time of the adoption of ASC 606, each of which are considered by us to be distinct within the context of the contract, their SSP, the method of recognizing the allocated consideration, and the period through which they are expected to be recognized were as follows: Performance Obligations SSP No. of Performance Obligations Recognition Method Fully satisfied at time of adoption Licenses (1) $ 86.7 million 4 Fully satisfied; recognized upon adoption of ASC 606 Research and development services (2) $ 350.7 million 10 Fully satisfied; recognized upon adoption of ASC 606 Partially satisfied at time of adoption Research and development services (2) $ 266.6 million 6 Proportionally as services are delivered over the performance period, expected to be through September 2023 (3) (1) The SSP was developed by probability weighting multiple cash flow scenarios using the income approach. Our management estimates within the models include the expected, probability-weighted net profits from estimated future sales, an estimate of the direct cost incurred to generate future cash flows, a discount rate and other business forecast factors. There are significant judgments and estimates inherent in the determination of the SSP of these performance obligations. These judgments and estimates include assumptions regarding future operating performance, the timelines of the clinical trials and regulatory approvals, and other factors. If different reasonable assumptions are utilized, the SSP and revenue recognized would vary. (2) The SSP was developed using our management’s best estimate of the cost of obtaining these services at arm’s length from a third-party provider and using internal full time equivalent costs to support the development services. (3) We determined that recognizing revenue on a proportional basis using the ratio of effort incurred to date compared to the total estimated effort required to complete the performance obligation best depicts the satisfaction of our obligations under the Collaboration Agreements. Remaining performance obligations As of December 31, 2020, there are no remaining performance obligations under the 2016 Agreement. The research services were fully satisfied as of May 17, 2020, no additional performance obligations remain under the 2016 Agreement and we are no longer eligible for any milestone payments for the 2016 Agreement. As of December 31, 2020, the aggregate amount of the transaction price allocated to performance obligations under the 2010 Agreement that are remaining was $ 3.9 million. This amount is expected to be recognized as performance obligations are satisfied through September 2023. Revenue recognition During the years ended December 31, we recognized the following collaboration revenue: (In thousands) 2020 2019 2018 Services performed that were considered performance obligations upon the adoption of ASC 606 Licenses $ — $ — $ 15,000 On-going research and development services 64,347 35,954 40,575 Committee participation — — — Services performed that were not considered performance obligations as of the adoption of ASC 606 Development activities — — 1,342 Commercialization Activities 3,927 3,303 3,744 Total collaboration revenue - related party $ 68,274 $ 39,257 $ 60,661 F-29 The following table presents changes in our contract assets and liabilities during the year ended December 31, 2020: (In thousands) December 31, 2019 Additions Deductions December 31, 2020 Contract assets Collaboration receivable – related party (1) $ 1,539 $ 5,610 $ ( 6,141 ) $ 1,008 Unbilled receivable – related party (2) — 1,821 ( 706 ) 1,115 Royalty receivable – related party (3) 2,900 5,015 ( 7,915 ) — Contract liabilities Deferred revenue – related party, current and non-current portions (4) 61,513 2,421 ( 63,934 ) — (1) Additions to collaboration receivables - related party relate to amounts billed to Celgene for reimbursable costs incurred by us during the reporting period. Deductions to receivables relate to collection of receivables during the reporting period. (2) Unbilled receivables - related party amounts relate to future reimbursable costs to Celgene. (3) Additions to royalty receivables - related party relate to amounts billed to Celgene during the reporting period. Deductions to receivables relate to collection of receivables during the reporting period. (4) Additions to deferred revenue - related party relate to consideration from Celgene during the reporting period. Deductions relate to deferred revenue recognized as revenue during the reporting period. The following table presents changes in our contract assets and liabilities during the year ended December 31, 2019: (In thousands) December 31, 2018 Additions Deductions December 31, 2019 Contract assets Collaboration receivable – related party (1) $ 2,462 $ 8,253 $ ( 9,176 ) $ 1,539 Royalty receivable – related party (2) 2,234 10,542 ( 9,876 ) 2,900 Contract liabilities Deferred revenue – related party, current and non-current portions (3) 92,519 4,948 ( 35,954 ) 61,513 (1) Additions to collaboration receivables - related party relate to amounts billed to Celgene for reimbursable costs incurred by us during the reporting period. Deductions to receivables relate to collection of receivables during the reporting period. (2) Additions to receivables relate to amounts billed to Celgene during the reporting period. Deductions to receivables relate to collection of receivables during the reporting period. (3) Additions to deferred revenue relate to consideration from Celgene during the reporting period. Deductions relate to deferred revenue recognized as revenue during the reporting period. During the years ended December 31, 2020, 2019 and 2018, we recognized the following as revenue due to changes in the contract liability balances: (In thousands) 2020 2019 2018 Amounts included in the contract liability at the beginning of the period $ 61,513 $ 31,605 $ 37,590 Performance obligations satisfied in previous periods — — 469 Royalty revenue During the years ended December 31, 2020, 2019 and 2018, we recognized the following as royalty revenue: (In thousands) 2020 2019 2018 Royalty revenue – related party $ 10,262 $ 10,542 $ 7,215 As the underlying performance obligation, or delivery of the enasidenib license, had been satisfied as of June 2014, royalty revenue is recognized as the related sales occur. On June 11, 2020, we sold our tiered, sales-based royalty rights on worldwide net sales of IDHIFA®, as well as our rights to receive up to $ 55.0 million in outstanding regulatory milestone payments from BMS, to RPI for $ 255.0 million. For further discussion of the sale of future revenue, refer to Note 10, Sale of Future Revenue . F-30 Milestone revenue (variable consideration) At each reporting period we evaluate whether milestones are considered probable of being reached and, to the extent that a significant reversal would not occur in future periods, estimate the amount to be included in the transaction price using the most likely amount method. Milestone payments that are not within our control, such as regulatory approvals, are not considered probable of being achieved and are excluded from the transaction price until those approvals are received. During the years ended December 31, 2020, and 2019 we did no t receive any milestone payments related to our Collaboration Agreements, and all variable consideration relating to the remaining development, regulatory and sales-based milestones that can be earned under the terms of the 2010 Agreement remain fully constrained. On June 11, 2020, we sold our tiered, sales-based royalty rights on worldwide net sales of IDHIFA®, as well as our rights to receive up to $ 55.0 million in outstanding regulatory milestone payments from BMS, to RPI for $ 255.0 million. For further discussion of the sale of future revenue, refer to Note 10, Sale of Future Revenue . During the year ended December 31, 2018, Celgene submitted an MAA to the EMA for IDHIFA® for IDH2 mutant-positive R/R AML. As a result of the filing, we determined that a $ 15.0 million milestone payment for the filing of a first new drug application equivalent in an ex-U.S. country was considered probable of being reached and that a significant reversal of revenue would not occur in future periods. As the underlying performance obligation, or delivery of the license to IDHIFA®, had been satisfied as of June 2014, the milestone payment was recognized in full as collaboration revenue. The next potential milestone expected to be achieved under our 2010 Agreement is the achievement of a specified ex-U.S. commercial milestone event. Achievement of this event will result in a milestone payment of $ 25.0 million under the 2010 Agreement. We remain eligible to receive this milestone payment under our purchase agreement with RPI. CStone Pharmaceuticals In June 2018, we entered into an exclusive license agreement with CStone, or the CStone Agreement, to grant CStone specified intellectual property licenses to enable CStone to develop and commercialize certain products containing ivosidenib in mainland China, Hong Kong, Macau, Singapore, and Taiwan, or the CStone Territory. We retain development and commercialization rights for the rest of the world. On March 2, 2020, we amended the CStone Agreement to include Singapore as part of the CStone Territory. Pursuant to the CStone Agreement, CStone will initially be responsible for the development and commercialization of ivosidenib in AML, cholangiocarcinoma, and, at our discretion, brain cancer indications. Pursuant to the CStone Agreement, we received an initial upfront payment in the amount of $ 12.0 million and are entitled to receive up to an additional $ 407.0 million in milestone payments upon the achievement of certain development, regulatory and sales milestone events. Approximately one third of the milestone payments are related to development and regulatory milestones, half of which are related to ivosidenib in AML and cholangiocarcinoma and the other half are related to brain cancer indications, including glioma. We will also be entitled to receive tiered royalties, ranging from 15 % to 19 % percent, on annual net sales, if any, of ivosidenib. CStone is responsible for all costs it incurs in developing, obtaining regulatory approval of, and commercializing ivosidenib in the CStone Territory, as well as certain costs incurred by us. During the term of the CStone Agreement, each party and its affiliates are prohibited from developing or commercializing any other compound or product that inhibits IDH1 mutations at specified levels of binding, in the case of CStone, anywhere in the world, and in our case, in the CStone Territory. Termination Unless earlier terminated, the CStone Agreement will expire upon the expiration of the last royalty term for the last licensed product within the scope of the CStone Agreement. At any time after CStone has obtained regulatory approval in mainland China in R/R AML and the last patient has been enrolled in a specified clinical trial (or, if earlier, at any time that CStone acquires or is acquired by an entity with a competing or restricted product), CStone may terminate the CStone Agreement in its entirety by providing us with prior written notice. Either party may, subject to specified cure periods, terminate the CStone Agreement in the event of the other party’s uncured material breach. Either party may terminate the CStone Agreement under specified circumstances relating to the other party’s insolvency. We have the right to terminate the CStone Agreement immediately if CStone or its affiliates or sublicensees or subcontractors challenges the validity, patentability, or enforceability of certain patent rights that relate to ivosidenib and are owned by or licensed to us or our affiliates. F-31 Collaboration revenue Performance obligations identified We developed assumptions that require judgment to determine the SSP for each performance obligation identified in the contract. We use key assumptions to determine the SSP, which include forecast of revenues, development timelines, reimbursement rates, discount rates and probabilities of technical and regulatory success. The satisfied and unsatisfied performance obligations, each of which are considered by us to be distinct within the context of the contract, their SSP, the method of recognizing the allocated consideration, and the period through which they are expected to be recognized are as follows: Performance Obligations SSP No. of Performance Obligation(s) Recognition Method Licenses (1) $ 16.4 million 1 Fully satisfied; recognized upon delivery of license Other services (2) $ 1.7 million 1 As services are delivered, expected to be through September 2021 (1) The SSP was developed by probability weighting multiple cash flow scenarios using the income approach. Our management estimates within the models include the expected, probability-weighted net profits from estimated future sales, an estimate of the direct costs incurred to generate future cash flows, a discount rate and other business forecast factors. There are significant judgments and estimates inherent in the determination of the SSP of this performance obligation. These judgments and estimates include assumptions regarding future operating performance, the timelines of the clinical trials and regulatory approvals, and other factors. If different reasonable assumptions are utilized, the SSP and revenue recognized would vary. (2) The SSP was developed using our management’s best estimate of the cost of obtaining these services at arm’s length from a third-party provider. As of December 31, 2020, the aggregate amount of the transaction price allocated to performance obligations that are partially unsatisfied was $ 0.5 million. This amount is expected to be recognized as performance obligations are satisfied through September 2021. Revenue recognition During the years ended December 31, we recognized the following collaboration revenue: (In thousands) 2020 2019 2018 Services performed that were considered performance obligations upon contract inception Licenses $ — $ 5,000 $ 12,440 Other services 192 235 — Services performed that were not considered performance obligations upon contract inception Other services 3,379 3,027 230 Total collaboration revenue – other $ 3,571 $ 8,262 $ 12,670 The following table presents changes in our contract assets during the year ended December 31, 2020: (In thousands) December 31, 2019 Additions Deductions December 31 2020 Contract assets Collaboration receivable – other (1) $ 1,928 $ 3,571 $ ( 3,551 ) $ 1,948 (1) Additions to contract assets relate to receivables from CStone and deductions to contract assets relate to collection of receivables during the reporting period. The following table presents changes in our contract assets during the year ended December 31, 2019: (In thousands) December 31 2018 Additions Deductions December 31, 2019 Contract assets Collaboration receivable – other (1) $ 670 $ 8,262 $ ( 7,004 ) $ 1,928 (1) Additions to contract assets relate to receivables from CStone and deductions to contract assets relate to collection of receivables during the reporting period. Royalty revenue F-32 The license was determined to be the predominant item to which sales-based royalties and sales-based milestones relate. As the license was delivered in June 2018, we will recognize royalty revenue when the related sales occur. To date, no royalties have been received under the CStone Agreement. Milestone revenue (variable consideration) During the year ended December 31, 2020, no milestone payments were received. During the year ended December 31, 2019, upon the dosing of the first patient in a local study in a hematological indication in mainland China, we earned and received a milestone payment of $ 5.0 million, which was recognized as collaboration revenue. Aurigene Discovery Technologies Limited In April 2017, we entered into a global license agreement with Aurigene Discovery Technologies Limited, or Aurigene, to research, develop and commercialize small molecule inhibitors for DHODH, or the Aurigene Agreement. Under the terms of the Aurigene Agreement, Aurigene will provide us exclusive rights to its portfolio of novel small molecules for DHODH. Financial terms of the Aurigene Agreement include a $ 3.0 million upfront payment and potential future milestone payments of up to $ 15.0 million if we achieve certain development and regulatory milestones. Aurigene is also eligible to receive low single-digit royalties on net product sales, if any. We will conduct preclinical studies and, if successful, fund further global research and development, as well as regulatory and commercial activities. The term of the Aurigene Agreement will continue until the earlier of: (a) termination for convenience at our sole discretion upon 90 days prior written notice, (b) termination by either party for material breach, or (c) the expiration of the last-to-expire of all payment obligations hereunder with respect to all licensed products under the Aurigene Agreement. Initial payment The $ 3.0 million upfront payment was incurred in the year ended December 31, 2017 and recorded as research and development expense. Costs incurred and milestone payments due to Aurigene prior to regulatory approval are recognized as expenses in the period incurred. Payments due to Aurigene upon or subsequent to regulatory approval will be capitalized and amortized over the shorter of the remaining license or product patent life. Milestone payments During the year ended December 31, 2020, no milestone payments were made. During the year ended December 31, 2019, we achieved the milestone relating to the initiation of the first phase 1 clinical trial for DHODH, and we made a payment of $ 2.0 million. During the year ended December 31, 2018, no milestone payments were made. Note 14. Common Stock We are authorized to issue 125,000,000 shares of our common stock. Holders of common stock are entitled to one vote per share. Additionally, holders of common stock are entitled to receive dividends, if and when declared by our board of directors, and to share ratably in our assets legally available for distribution to our shareholders in the event of liquidation. Note 15. Share-Based Payments Stock incentive plans In June 2013, our Board of Directors adopted and, in July 2013 our stockholders approved, the 2013 Stock Incentive Plan, or the 2013 Plan. The 2013 Plan became effective upon the closing of our initial public offering and provides for the grant of incentive stock options, non-qualified stock options, stock appreciation rights, restricted stock awards, RSUs, PSUs, and other stock-based awards to employees, non-employees and non-employee directors. Following the adoption of the 2013 Plan, we granted no further stock options or other awards under the 2007 Stock Incentive Plan, or the 2007 Plan. Any options or awards outstanding under the 2007 Plan at the time of adoption of the 2013 Plan remain outstanding and effective. As of December 31, 2020, the total number of shares reserved under the 2007 Plan and the 2013 Plan are 10,584,232 , and we had 2,971,884 shares available for future issuance under the 2013 Plan. The 2013 Plan provides for an annual increase, to be added on the first day of each fiscal year, beginning with the fiscal year ending December 31, 2014 and continuing until the expiration of the 2013 Plan, equal to the lesser of (i) 2,000,000 shares of common stock, (ii) 4 % of the outstanding shares of common stock on such date or (iii) an amount determined by our Board of Directors. On January 1, 2021, the annual increase for the 2013 Plan resulted in an additional 2,000,000 shares authorized for issuance. F-33 Stock options The following table summarizes the stock option activity of all stock incentive plans for the year ended December 31, 2020: Number of Stock Options Weighted- Average Exercise Price Weighted- Average Remaining Contractual Term (in years) Aggregate Intrinsic Value (in thousands) Outstanding at December 31, 2019 6,201,485 $ 58.61 7.09 $ 28,528 Granted 1,004,145 49.42 Exercised ( 360,822 ) 20.19 Forfeited/Expired ( 701,762 ) 66.48 Outstanding at December 31, 2020 6,143,046 $ 58.46 6.68 $ 13,714 Exercisable at December 31, 2020 4,117,900 $ 60.62 5.78 $ 11,791 Vested and expected to vest at December 31, 2020 6,143,046 $ 58.46 6.68 $ 13,714 The weighted-average grant date fair value of options granted was $ 32.10 , $ 36.44 and $ 53.22 during the years ended December 31, 2020, 2019 and 2018, respectively. The total intrinsic value of options exercised was $ 10.4 million, $ 6.4 million and $ 65.1 million during the years ended December 31, 2020, 2019 and 2018, respectively. At December 31, 2020, the total unrecognized compensation expense related to unvested stock option awards was $ 65.3 million, which we expect to recognize over a weighted-average period of approximately 2.26 years. Restricted stock units Upon vesting, each RSU entitles the holder to receive a specified number of shares of our common stock. The following table presents RSU activity for the year ended December 31, 2020: Number of Stock Units Weighted-Average Grant Date Fair Value Unvested shares at December 31, 2019 766,953 $ 63.44 Granted 1,040,515 48.39 Vested ( 332,780 ) 68.91 Forfeited ( 190,310 ) 57.04 Unvested shares at December 31, 2020 1,284,378 $ 50.78 As of December 31, 2020, there was approximately $ 41.1 million of total unrecognized compensation expense related to RSUs, which we expect to be recognized over a weighted-average period of 1.80 years. Performance-based stock units At the achievement of the performance-based and service-based vesting criteria, each PSU entitles the holder to receive a specified number of shares of our common stock. The following table presents PSU activity for the year ended December 31, 2020: Number of Stock Units Weighted-Average Grant Date Fair Value Unvested shares at December 31, 2019 218,143 $ 55.64 Granted 20,622 48.49 Vested ( 78,920 ) 54.82 Forfeited ( 17,616 ) 61.93 Unvested shares at December 31, 2020 142,229 $ 54.28 Stock-based compensation expense associated with these PSUs is recognized if the underlying performance condition is considered probable of achievement using our management’s best estimates. As of December 31, 2020, there was no unrecognized compensation expense related to PSUs with performance-based vesting criteria that are considered probable of achievement that we expect to recognize. There is $ 5.9 million of total unrecognized compensation expense related to PSUs F-34 with performance-based vesting criteria that are considered not probable of achievement. Market-based stock units The Company has issued certain equity awards that contain market based vesting conditions, in which shares of stock are earned at vesting based on stock price performance. The fair value of MSUs are estimated using a Monte Carlo simulation model. Assumptions and estimates utilized in the model include the risk-free interest rate, dividend yield, expected stock volatility and the estimated period to achievement of the market condition. The following table presents MSU activity for the year ended December 31, 2020: Number of Stock Units Weighted-Average Grant Date Fair Value Unvested shares at December 31, 2019 42,695 $ 41.50 Granted — — Unvested shares at December 31, 2020 42,695 $ 41.50 As of December 31, 2020, there was no remaining unrecognized compensation expense related to MSUs. 2013 Employee Stock Purchase Plan In June 2013, our Board of Directors adopted, and in July 2013 our stockholders approved, the 2013 Employee Stock Purchase Plan, or the 2013 ESPP. We issued 120,293 shares and 77,981 shares during the years ended December 31, 2020 and 2019, respectively, under the 2013 ESPP. The 2013 ESPP provides participating employees with the opportunity to purchase up to an aggregate of 836,363 shares of our common stock. As of December 31, 2020, we had 471,353 shares available for future issuance under the 2013 ESPP. On January 1, 2021, the annual increase for the 2013 ESPP resulted in an additional 509,091 shares authorized for issuance. Stock-based compensation expense During the years ended December 31, 2020, 2019 and 2018, we recorded stock-based compensation expense for employee and non-employee stock options, RSUs, PSUs, ESPP shares and other stock-based awards. Stock-based compensation expense by award type included within the consolidated statements of operations is as follows: (In thousands) 2020 2019 2018 Stock options $ 44,942 $ 48,219 $ 51,460 Restricted stock units 26,070 19,079 12,032 Performance-based stock units 1,866 2,647 8,717 Employee Stock Purchase Plan 1,463 1,437 1,148 Other stock awards 781 991 — Total stock-based compensation expense $ 75,122 $ 72,373 $ 73,357 Expenses related to equity-based awards were allocated as follows in the consolidated statements of operations: (In thousands) 2020 2019 2018 Research and development expense $ 37,147 $ 39,029 $ 41,982 Selling, general and administrative expense 37,975 33,344 31,375 Total stock-based compensation expense $ 75,122 $ 72,373 $ 73,357 No related tax benefits were recognized for the years ended December 31, 2020, 2019 and 2018. F-35 The fair value of each stock option granted to employees and nonemployees is estimated on the date of grant using the Black-Scholes option-pricing model. The following table summarizes the weighted average assumptions used in calculating the grant date fair value of the awards: 2020 2019 2018 Risk-free interest rate 1.24 % 2.32 % 2.71 % Expected dividend yield — — — Expected term (in years) 6.05 6.06 6.06 Expected volatility 73.80 % 76.19 % 76.62 % Expected term We use the “simplified method” as prescribed by the Securities and Exchange Commission Staff Accounting Bulletin No. 107, Share Based Payments , to estimate the expected term of stock option grants. Under this approach, the weighted-average expected life is presumed to be the average of the contractual term of ten years and the weighted-average vesting term of the stock options, taking into consideration multiple vesting tranches. We utilize this method due to lack of historical data and the plain-vanilla nature of our share-based awards. Volatility We use a weighted-average of expected volatility based on the volatilities of a representative group of publicly traded biopharmaceutical companies, including ourselves. The expected volatility has been determined using a weighted-average of the historical volatilities of the representative group of companies for a period equal to the expected term of the option grant. Risk-free rate The risk-free rate is based on the yield curve of U.S. Treasury securities with periods commensurate with the expected term of the options being valued. Dividends We have never paid, and do not anticipate paying, any cash dividends in the foreseeable future, and, therefore, use an expected dividend yield of zero in the option-pricing model. Forfeitures We account for forfeitures as they occur and, therefore, do not estimate forfeitures. Note 16. Income Taxes The domestic and foreign components of loss before income taxes are as follows: (In thousands) 2020 2019 2018 Domestic $ ( 328,813 ) $ ( 432,535 ) $ ( 311,159 ) Foreign 1,364 21,063 ( 34,869 ) Total $ ( 327,449 ) $ ( 411,472 ) $ ( 346,028 ) We did not have any material provision for income taxes for the years ended December 31, 2020, 2019 and 2018. F-36 A reconciliation of the expected income tax benefit (expense) computed using the federal statutory income tax rate to our effective income tax rate is as follows for the years ended December 31, 2020, 2019 and 2018: 2020 2019 2018 Income tax benefit computed at federal statutory tax rate 21.0 % 21.0 % 21.0 % State taxes, net of federal benefit 2.5 % 2.8 % 0.8 % Change in valuation allowance ( 28.3 ) % ( 27.2 ) % ( 28.4 ) % General business credits and other credits 7.0 % 5.0 % 5.7 % Permanent differences and other adjustments ( 1.6 ) % ( 1.3 ) % ( 0.7 ) % Stock based compensation ( 0.6 ) % ( 0.6 ) % 2.2 % Foreign rate differential — % 0.3 % ( 0.6 ) % Total — % — % — % Deferred income taxes reflect the net tax effects of temporary differences between the carrying amount of assets and liabilities for financial reporting purposes and the amounts used for income tax purposes. Significant components of our deferred tax assets and liabilities for the years ended December 31, 2020 and 2019 are as follows: (In thousands) 2020 2019 Deferred tax assets: Net operating loss carryforwards $ 310,841 $ 294,614 Deferred revenue — 14,372 Tax credit carryforwards 163,589 141,219 Purchased intangible assets 13,543 14,479 Stock-based compensation 34,284 30,861 Operating lease liability 25,085 27,173 Non-deductible accruals and reserves, including inventory 12,730 4,729 RPI Royalty Sale 58,048 — Other 1,230 — Total deferred tax assets 619,350 527,447 Depreciation and amortization ( 4,002 ) ( 2,613 ) Operating lease right of use asset ( 20,596 ) ( 22,625 ) Less: valuation allowance ( 594,752 ) ( 502,209 ) Net deferred taxes $ — $ — On March 27, 2020, the Coronavirus Aid, Relief, and Economic Security (CARES) Act was signed into law making several changes to the Internal Revenue Code. The changes include, but are not limited to: increasing the limitation on the amount of deductible interest expense, allowing companies to carryback certain net operating losses, and increasing the amount of net operating loss carryforwards that corporations can use to offset taxable income. The tax law changes in the Act did not have a material impact on the Company’s income tax provision. As of December 31, 2020, we had net operating loss carryforwards, or NOLs, available to reduce federal, state and foreign income taxes of approximately $ 1,201.6 million, $ 906.0 million and $ 67.0 million, respectively. If not utilized, these NOLs begin to expire in 2033 (for pre-2018 NOLs), 2032 and 2024, respectively. Approximately $ 738.2 million of federal NOLs can be carried forward indefinitely. At December 31, 2020, we also had available research and development tax credits for federal and state income tax purposes of approximately $ 36.9 million and $ 18.4 million, respectively. If not utilized, the credits begin to expire in 2027 for both federal and state income tax purposes, respectively. We engaged in clinical testing activities and incurred expenses that qualify for the federal orphan drug tax credit. At December 31, 2020, we had available orphan drug tax credits for federal purposes only of approximately $ 111.5 million. If not utilized, the orphan drug credits begin to expire in 2035. As provided by Section 382 of the Internal Revenue Code of 1986, or Section 382, and similar state provisions, utilization of NOLs and tax credit carryforwards may be subject to substantial annual limitations due to ownership change limitations that have previously occurred or that could occur in the future. Ownership changes may limit the amount of NOLs and tax credit F-37 carryforwards that can be utilized annually to offset future taxable income and tax, respectively. In general, an ownership change, as defined by Section 382, results from transactions that increase the ownership of five percent stockholders in the stock of a corporation by more than 50 percent in the aggregate over a three year period. We completed a review of our changes in ownership through December 31, 2020 and determined that transactions have resulted in no ownership changes during the year ended December 31, 2020, as defined by Section 382. The impact of the historical ownership changes has been reflected in our deferred tax assets in the table above. As required by ASC 740, we have evaluated the positive and negative evidence bearing upon the realizability of our deferred tax assets. Based on the weight of available evidence, both positive and negative, we recorded a valuation allowance of $ 594.8 million and $ 502.2 million as of December 31, 2020 and December 31, 2019, respectively, because we have determined that it is more likely than not that these assets will not be fully realized. The following table presents our change in valuation allowance for the years ended December 31, 2020 and, 2019: (in thousands) 2020 2019 Valuation allowance at the beginning of the year $ 502,209 $ 390,753 Increase for the current period 92,543 111,456 Valuation allowance at the end of the year $ 594,752 $ 502,209 As of December 31, 2020, the unremitted earnings of our foreign subsidiaries are not material. We have not provided for U.S. income taxes or foreign withholding taxes on these earnings as it is our current intention to permanently reinvest these earnings outside the U.S. The tax liability on these earnings is also not material. Events that could trigger a tax liability include, but are not limited to, distributions, reorganizations or restructurings and/or tax law changes. We apply the accounting guidance in ASC 740 related to accounting for uncertainty in income taxes. Our reserves related to taxes are based on a determination of whether, and how much of, a tax benefit taken by us in our tax filings or positions is more likely than not to be realized following resolution of any potential contingencies present related to the tax benefit. The following table presents our unrecognized tax benefits activity for the years ended December 31, 2020 and 2019: (In thousands) 2020 2019 Unrecognized tax benefits at the beginning of the year $ 17,460 $ 14,288 Gross increases - current period tax positions 3,671 3,172 Unrecognized tax benefits at the end of the year $ 21,131 $ 17,460 We will recognize interest and penalties related to uncertain tax positions above the line as an expense to continuing operations. As of December 31, 2020 and 2019, we had no accrued interest or penalties related to uncertain tax positions and no such amounts have been recognized. If all of the Company’s unrecognized tax benefits as of December 31, 2020 were to become recognizable in the future, we would record a $ 21.1 million of unrecognized tax benefits. Upon close of the proposed sale to Servier, we will evaluate the tax impact of the transaction. The uncertain tax position does not impact our effective income tax rate due to the full valuation allowance. We are subject to taxation in the United States, Switzerland, Netherlands, Germany, Italy and France. The statute of limitations for assessment by the IRS and state tax authorities is open for tax years ending December 31, 2020, 2019, 2018, and 2017, although carryforward attributes that were generated for tax years prior to 2017 may still be adjusted upon examination by the IRS or state tax authorities if they either have been, or will be, used in a future period. The statute of limitations for assessment in Switzerland remains open for tax year ending December 31, 2020, 2019, 2018, and 2017. The Company’s subsidiaries in the Netherlands and Germany were incorporated in 2019 and therefore the statute of limitations for assessment that remain open in these jurisdictions are for the tax year ending December 31, 2020 and 2019. The Company’s subsidiaries in the Italy and France were incorporated in 2020 and therefore the statute of limitations for assessment that remain open in these jurisdictions are for the tax year ending December 31, 2020. There are currently no federal, state or foreign audits in progress. Note 17. Defined Contribution Benefit Plan We sponsor a 401(k) retirement plan, in which substantially all of our full-time employees are eligible to participate. Participants may contribute a percentage of their annual compensation to this plan, subject to statutory limitations. We will make matching contributions equal to 100 % of the employee’s contributions, subject to a maximum of 4 % of eligible compensation. F-38 Note 18. Net Loss per Share Basic net loss per share is calculated by dividing net loss by the weighted-average shares outstanding during the period, without consideration for common stock equivalents. Diluted net loss per share is calculated by adjusting the weighted average shares outstanding for the dilutive effect of common stock equivalents outstanding for the period, determined using the treasury stock method. For purposes of the dilutive net loss per share calculation, stock options, RSUs, PSUs and MSUs for which the performance and market vesting conditions, respectively, have been deemed probable, and 2013 ESPP shares are considered to be common stock equivalents, while PSUs and MSUs with performance and market vesting conditions, respectively, that were not deemed probable as of December 31, 2020 are not considered to be common stock equivalents. Since we had a net loss for all periods presented, the effect of all potentially dilutive securities is anti-dilutive. Accordingly, basic and diluted net loss per share was the same for the years ended December 31, 2020, 2019 and 2018. The following common stock equivalents were excluded from the calculation of diluted net loss per share applicable to common stockholders for the periods indicated because including them would have had an anti-dilutive effect: Years ended December 31, 2020 2019 2018 Stock options 6,143,046 6,201,485 5,416,069 Restricted stock units 1,284,378 766,953 532,144 Performance-based stock units — 72,046 169,031 Employee Stock Purchase Plan shares 46,439 49,418 32,304 Total 7,473,863 7,089,902 6,149,548 Note 19. Selected Quarterly Financial Data (Unaudited) The following table contains quarterly financial information for 2020 and 2019: 2020 (in thousands, except per share data) First Quarter Second Quarter Third Quarter Fourth Quarter Total revenue $ 87,098 $ 37,347 $ 34,706 $ 44,045 Loss from operations ( 43,192 ) ( 90,196 ) ( 90,327 ) ( 92,434 ) Net loss ( 40,256 ) ( 90,478 ) ( 98,979 ) ( 97,657 ) Net loss per share – basic and diluted ( 0.59 ) ( 1.31 ) ( 1.43 ) ( 1.41 ) 2019 (in thousands, except per share data) First Quarter Second Quarter Third Quarter Fourth Quarter Total revenue $ 30,227 $ 26,221 $ 26,024 $ 35,440 Loss from operations ( 97,483 ) ( 113,861 ) ( 109,060 ) ( 105,929 ) Net loss ( 93,078 ) ( 109,871 ) ( 106,173 ) ( 102,350 ) Net loss per share – basic and diluted ( 1.59 ) ( 1.87 ) ( 1.81 ) ( 1.60 ) F-39