Ultragenyx Pharmaceutical Inc. 10-K

Item 9A. Controls and Procedures Evaluation of Disclosure Controls and Procedures We carried out an evaluation, under the supervision and with the participation of our management, including our Chief Executive Officer and our Chief Financial Officer, of the effectiveness of our “disclosure controls and procedures” as of the end of the period covered by this Annual Report, pursuant to Rules 13a-15(b) and 15d-15(b) under the Exchange Act. In connection with that evaluation, our Chief Executive Officer and our Chief Financial Officer concluded that our disclosure controls and procedures were effective and designed to provide reasonable assurance that the information required to be disclosed is recorded, processed, summarized and reported within the time periods specified in the SEC rules and forms as of December 31, 2020. For the purpose of this review, disclosure controls and procedures means controls and procedures designed to ensure that information required to be disclosed by us in the reports that we file or submit is recorded, processed, summarized and reported within the time periods specified in the SEC’s rules and forms. These disclosure controls and procedures include, without limitation, controls and procedures designed to ensure that information required to be disclosed by us in the reports that we file or submit is accumulated and communicated to management, including our principal executive officer and principal financial officer, as appropriate to allow timely decisions regarding required disclosure. In designing and evaluating the disclosure controls and procedures, our management recognized that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving the desired control objectives, and our management necessarily was required to apply its judgment in evaluating the cost-benefit relationship of possible controls and procedures. Management’s Annual Report on Internal Control Over Financial Reporting Management is responsible for establishing and maintaining adequate internal control over financial reporting as defined in Rules 13a-15(f) and 15d-15(f) of the Exchange Act. Our management used the Committee of Sponsoring Organizations of the Treadway Commission Internal Control - Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework), or the COSO framework, to evaluate the effectiveness of internal control over financial reporting. Management believes that the COSO framework is a suitable framework for its evaluation of financial reporting because it is free from bias, permits reasonably consistent qualitative and quantitative measurements of our internal control over financial reporting, is sufficiently complete so that those relevant factors that would alter a conclusion about the effectiveness of our internal control over financial reporting are not omitted and is relevant to an evaluation of internal control over financial reporting. Management has assessed the effectiveness of our internal control over financial reporting as of December 31, 2020 and has concluded that such internal control over financial reporting is effective. Our independent registered public accounting firm, Ernst & Young LLP, has audited the financial statements included in this Annual Report and has issued a report on the effectiveness of our internal control over financial reporting. The report of Ernst & Young LLP is included below. Changes in Internal Control over Financial Reporting There have been 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 our fourth quarter ended December 31, 2020, that have materially affected, or are reasonably likely to materially affect our internal control over financial reporting. Report of Independent Registered Public Accounting Firm To the Stockholders and the Board of Directors of Ultragenyx Pharmaceutical Inc.: Opinion on Internal Control over Financial Reporting We have audited Ultragenyx Pharmaceutical Inc.’s internal control over financial reporting as of December 31, 2020, based on criteria established in Internal Control—Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework) (the COSO criteria). In our opinion, Ultragenyx Pharmaceutical Inc (the Company) maintained, in all material respects, effective internal control over financial reporting as of December 31, 2020, based on the COSO criteria. We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the consolidated balance sheets of Ultragenyx Pharmaceutical Inc. (the Company) as of December 31, 2020 and 2019, the related consolidated statements of operations, comprehensive loss, stockholders’ equity and cash flows for each of the three years in the period ended December 31, 2020, and our report dated February 11, 2021 expressed an unqualified opinion thereon. Basis for Opinion The Company’s management is responsible for maintaining effective internal control over financial reporting and for its assessment of the effectiveness of internal control over financial reporting included in the accompanying Management’s Annual Report on Internal Control over Financial Reporting. Our responsibility is to express an opinion on the Company’s internal control 77 over financial reporting based on our audit. We are a public accounting firm registered with the 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 audit in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether effective internal control over financial reporting was maintained in all material respects. Our audit included obtaining an understanding of internal control over financial reporting, assessing the risk that a material weakness exists, testing and evaluating the design and operating effectiveness of internal control based on the assessed risk, and performing such other procedures as we considered necessary in the circumstances. We believe that our audit provides a reasonable basis for our opinion. 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 (1) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the company; (2) 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 (3) 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. /s/ Ernst & Young LLP San Jose, California February 11, 2021 Item 9B. Other Information None. 78 PART III Item 10. Directors, Executive Officers and Corporate Governance The information required by this Item is incorporated herein by reference to information in the proxy statement for our 2021 Annual Meeting of Stockholders, which we will file with the SEC within 120 days of the end of the fiscal year to which this Annual Report relates (the “2021 Proxy Statement”), including under the headings “Proposal No. 1—Election of Class II Directors,” “Information About Our Executive Officers,” “Corporate Governance—Global Code of Conduct,” “Proposal No. 1—Election of Class II Directors—Nomination of Directors,” “Board of Directors and Committees,” and, as applicable, “Delinquent Section 16(a) Reports.” We have adopted a code of ethics that applies to all of our directors, officers and employees, including our principal executive, principal financial and principal accounting officers, or persons performing similar functions, or Code of Ethics. Our Code of Ethics is posted on our corporate governance website located at www.ultragenyx.com . We intend to disclose future amendments to certain provisions of the Code of Ethics, and waivers of the Code of Ethics granted to executive officers and directors, on the website within four business days following the date of the amendment or waiver. Item 11. Executive Compensation The information required by this Item is incorporated herein by reference to information in the 2021 Proxy Statement, including under the headings “Executive Compensation,” “Director Compensation,” “Board of Directors and Committees—Compensation Committee Interlocks and Insider Participation,” “Executive Compensation—Risk Management and Mitigation,” and “Executive Compensation—Compensation Committee Report.” Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters The information required by this Item is incorporated herein by reference to information in the 2021 Proxy Statement, including under the headings “Security Ownership of Certain Beneficial Owners and Management” and “Equity Compensation Plan Information.” Item 13. Certain Relationships and Related Transactions, and Director Independence The information required by this Item is incorporated herein by reference to information in the 2021 Proxy Statement, including under the headings “Certain Relationships and Related-Person Transactions,” “Corporate Governance,” and “Board of Directors and Committees.” Item 14. Principal Accountant Fees and Services The information required by this Item is incorporated herein by reference to information in the 2021 Proxy Statement, including under the heading “Proposal No. 2—Ratification of the Selection of Independent Registered Public Accounting Firm.” 79 PART IV Item 15. Exhibits and Financial Statement Schedules (a) The following documents are filed as part of this Annual Report. (1) Consolidated Financial Statements Consolidated Financial Statements—See Index to Consolidated Financial Statements at page F-1 of this Annual Report. (2) Consolidated Financial Statement Schedules Consolidated Financial statement schedules have been omitted in this Annual Report because they are not applicable, not required under the instructions, or the information requested is set forth in the consolidated financial statements or related notes thereto. (b) Exhibits Exhibit Number Exhibit Description Incorporated by Reference Filed Form Date Number Herewith 3.1 Amended and Restated Certificate of Incorporation 8-K 2/5/2014 3.1 3.2 Amended and Restated Bylaws 8-K 2/5/2014 3.2 4.1 Reference is made to Exhibits 3.1 and 3.2 4.2 Form of Common Stock Certificate S-1 11/8/2013 4.2 4.3 Description of Common Stock 10-K 2/14/2020 4.3 10.1† Collaboration and License Agreement, ef fective as of August 29, 2013, between Ultragenyx Pharmaceutical Inc. and Kyowa Hakko Kirin Co., Ltd. S-1/A 12/23/2013 10.1 10.2 Amendment No. 1 to Collaboration and License Agreement, e ffective as of August 24, 2015, between Ultragenyx Pharmaceutical Inc. and Kyowa Hakko Kirin Co., Ltd. 10-Q 11/10/2015 10.2 10.3 Amendment No. 2 to Collaboration and License Agreement, effective as of November 28, 2016, between Ultragenyx Pharmaceutical Inc. and Kyowa Hakko Kirin Co., Ltd. 10-K 2/21/2018 10.3 10.4† Amendment No. 3 to Collaboration and License Agreement, effective September 29, 2017, between Ultragenyx Pharmaceutical Inc. and Kyowa Hakko Kirin Co., Ltd. 10-K 2/21/2018 10.4 10.5† Amendment No. 4 to Collaboration and License Agreement, effective as of January 29, 2018, between Ultragenyx Pharmaceutical Inc. and Kyowa Hakko Kirin Co., Ltd. 10-K 2/21/2018 10.5 10.6† Amendment No. 5 to Collaboration and License Agreement, effective as of April 30, 2018, between Ultragenyx Pharmaceutical Inc. and Kyowa Hakko Kirin Co., Ltd. 10-Q 8/3/2018 10.1 10.7* Amendment No. 6 to Collaboration and License Agreement, effective as of February 1, 2019, between Ultragenyx Pharmaceutical Inc. and Kyowa Hakko Kirin Co., Ltd. 10-Q 5/7/2019 10.2 10.8* Amendment No. 7 to Collaboration and License Agreement, effective as of December 5, 2018, between Ultragenyx Pharmaceutical Inc. and Kyowa Hakko Kirin Co., Ltd . 10-Q 5/7/2019 10.3 10.9* Amendment No. 8 to Collaboration and License Agreement, effective as of July 4, 2019, between Ultragenyx Pharmaceutical Inc. and Kyowa Kirin Co., Ltd. (formerly, Kyowa Hakko Kirin Co., Ltd.) 10-Q 8/2/2019 10.1 80 Exhibit Number Exhibit Description Incorporated by Reference Filed Form Date Number Herewith 10.10* Amendment No. 9 to Collaboration and License Agreement, effective December 23, 2019, between Ultragenyx Pharmaceutical Inc. and Kyowa Kirin Co., Ltd. 10-K 2/14/2020 10.10 10.11* Amendment No. 10 to Collaboration and License Agreement, effective as of April 1, 2020, between Ultragenyx Pharmaceutical Inc. and Kyowa Kirin Co., Ltd. 10-Q 5/7/2020 10.2 10.12* License Agreement, dated as of September 20, 2012, between Ultragenyx Pharmaceutical Inc. and Baylor Research Institute X 10.13* Amendment to the License Agreement, dated as of March 22, 2013, between Ultragenyx Pharmaceutical Inc. and Baylor Research Institute X 10.14† Exclusive License Agreement, dated as of November 22, 2010, between Ultragenyx Pharmaceutical Inc. and Saint Louis University S-1/A 12/23/2013 10.8 10.15† License Agreement, dated October 30, 2013, by and between Dimension Therapeutics, Inc. and REGENXBIO Inc. (f/k/a ReGenX Biosciences, LLC), as amended 10-K 2/21/2018 10.13 10.16† Option and License Agreement, dated March 10, 2015, by and between Dimension Therapeutics, Inc. and REGENXBIO Inc. 10-K 2/21/2018 10.14 10.17* First Amendment to Option and License Agreement, dated March 18, 2019, by and between REGENXBIO, Inc. and Ultragenyx Pharmaceutical Inc. (as assignee of Dimension Therapeutics, Inc.) 10-Q 5/7/2019 10.1 10.18* Amended and Restated Collaboration Agreement and License Agreement, dated June 3, 2019, between Ultragenyx Pharmaceutical Inc. and Bayer Healthcare LLC 10-Q 8/2/2019 10.2 10.19† Research, Collaboration and License Agreement, dated as of May 5, 2016, by and between Dimension Therapeutics, Inc. and The Trustees of the University of Pennsylvania, as amended 10-K 2/21/2018 10.16 10.20† 3 rd Amendment to Research, Collaboration and License Agreement, entered into as of October 30, 2017, by and between Dimension Therapeutics, Inc. and The Trustees of the University of Pennsylvania 10-K 2/21/2018 10.17 10.21† Commercial Supply and Services Agreement – Drug Substance, effective December 7, 2017, between Ultragenyx Europe GmbH and Rentschler Biopharma SE 10-K 2/21/2018 10.18 10.22† Commercial Supply and Services Agreement – Drug Product, effective January 31, 2018, between Ultragenyx Europe GmbH and Rentschler Biopharma SE 10-K 2/21/2018 10.19 10.23 Supply Agreement, dated as of November 19, 2012, between Ultragenyx Pharmaceutical Inc. and CREMER OLEO GmbH & Co KG 10-K 2/21/2018 10.11 81 Exhibit Number Exhibit Description Incorporated by Reference Filed Form Date Number Herewith 10.2 4 * M aster Services Agreement, dated April 8, 2019, between Ultragenyx Pharmaceutical Inc. and Aenova Haupt Pharma Wolfratshausen GmbH X 10.25* Royalty Purchase Agreement, dated as of December 17, 2019, between Ultragenyx Pharmaceutical Inc. and RPI Finance Trust 10-K 2/14/2020 10.25 10.26 Equity Purchase Agreement, dated as of June 18, 2019 by and among Ultragenyx Pharmaceutical Inc. and Arcturus Therapeutics Ltd. 10-Q 7/30/2020 10.1 10.27# 2011 Equity Incentive Plan (including forms of Stock Option Grant Notice and Stock Option Agreement thereunder) S-1 11/8/2013 10.11 10.28# Amendment to the 2011 Equity Incentive Plan S-1 11/8/2013 10.12 10.29# 2014 Incentive Plan (as amended) 10-K 2/17/2017 10.20 10.30# Form of Incentive Stock Option Agreement S-1/A 1/17/2014 10.14 10.31# Form of Non Statutory Stock Option Agreement (Employees) S-1/A 1/17/2014 10.15 10.32# Form of Non Statutory Stock Option Agreement (Employees)(ex-U.S.) 10-Q 5/10/2016 10.3 10.33# Form of Non-Statutory Stock Option Agreement (Directors) S-1/A 1/17/2014 10.16 10.34# Form of Restricted Stock Unit Agreement (Employees) 10-Q 5/10/2016 10.1 10.35# Form of Restricted Stock Unit Agreement (Employees)(ex-U.S.) 10-Q 5/10/2016 10.2 10.36# Form of Restricted Stock Unit Agreement (Directors) S-1/A 1/17/2014 10.18 10.37# Form of Performance Stock Unit Agreement (Current Employees) 10-K 2/21/2018 10.31 10.38# Form of Performance Stock Unit Agreement (New Employees) 10-K 2/21/2018 10.32 10.39# Form of Performance Stock Unit Agreement (2019) 10-Q 5/7/2019 10.4 10.40# Form of Performance Stock Unit Agreement (2020) 10-Q 5/7/2020 10.3 10.41# 2014 Employee Stock Purchase Plan (as amended) 10-K 2/17/2017 10.28 10.42# Corporate Bonus Plan S-1/A 1/17/2014 10.27 10.43# Employment Inducement Plan X 10.44# Form of Non Statutory Stock Option Agreement (Inducement Plan) X 10.45# Form of Non Statutory Stock Option Agreement (Inducement Plan) (ex-US) X 10.46# Form of Restricted Stock Unit Agreement (Inducement Plan) X 10.47# Form of Restricted Stock Unit Agreement (Inducement Plan)(ex-US) X 10.48# Executive Employment Agreement, dated as of June 15, 2011, between Ultragenyx Pharmaceutical Inc. and Emil D. Kakkis, M.D., Ph.D. S-1 11/8/2013 10.18 10.49# Amendment No. 1 to Executive Employment Agreement, dated August 8, 2014, by and between Ultragenyx Pharmaceutical Inc. and Emil D. Kakkis, M.D., Ph.D. 10-Q 8/11/2014 10.2 82 Exhibit Number Exhibit Description Incorporated by Reference Filed Form Date Number Herewith 10.50# Offer Letter, dated as of October 31, 2011, between Ultragenyx Pharmaceutical Inc. and Thomas Kassberg S-1 11/8/2013 10.19 10.51# Amendment No. 1 to Offer of Employment, dated as of August 8, 2014, by and between Ultragenyx Pharmaceutical Inc. and Thomas Kassberg 10-Q 8/11/2014 10.3 10.52# Transition Letter Agreement, dated as of March 5, 2020, between Ultragenyx Pharmaceutical Inc. and Shalini Sharp 8-K 3/6/2020 10.1 10.53# Amendment, dated as of August 28, 2020 to Transition Letter Agreement between Ultragenyx Pharmaceutical Inc. and Shalini Sharp dated as of March 5, 2020 8-K 9/2/2020 10.2 10.54# Amendment No. 2, dated as of October 8, 2020, to Transition Letter Agreement between Ultragenyx Pharmaceutical Inc. and Shalini Sharp dated as of March 5, 2020, as amended on August 28, 2020 8-K 10/13/2020 10.2 10.55# Offer Letter, dated as of August 28, 2020 between Ultragenyx Pharmaceutical Inc. and Mardi C. Dier . 8-K 9/2/2020 10.1 10.56# Amendment, dated as of, October 9, 2020 to the Offer Letter between Ultragenyx Pharmaceutical Inc. and Mardi C. Dier dated August 28, 2020 8-K 10/13/2020 10.1 10.57# Offer Letter, dated as of April 26, 2016, between Ultragenyx Pharmaceutical Inc. and Karah Parschauer 10-Q 8/9/2016 10.3 10.58# Offer Letter, dated as of February 20, 2015, between Ultragenyx Pharmaceutical Inc. and Dennis Huang 10-K 2/17/2017 10.36 10.59# Offer Letter, dated as of June 11, 2015, between Ultragenyx Pharmaceutical Inc. and John R. Pinion II 10-K 2/17/2017 10.37 10.60# Offer Letter, dated as of January 15, 2018, between Ultragenyx Pharmaceutical Inc. and Camille Bedrosian, M.D. 10-K 2/21/2018 10.46 10.61# Offer Letter, dated May 16, 2017, by and between Ultragenyx Pharmaceutical Inc. and Erik Harris 10-Q 8/2/2019 10.4 10.62# Addendum #1, dated August 8, 2017, to Offer Letter dated May 16, 2017 between Ultragenyx Pharmaceutical Inc. and Erik Harris 10-Q 8/2/2019 10.5 10.63# Addendum #2, dated June 19, 2019, to Offer Letter dated May 16, 2017 between Ultragenyx Pharmaceutical Inc. and Erik Harris 10-Q 8/2/2019 10.6 10.64# Form of Indemnification Agreement 10-K 3/24/2014 10.23 10.65 Standard Lease, dated as of July 5, 2011, between Ultragenyx Pharmaceutical Inc. and Condiotti Enterprises, Inc. S-1 11/8/2013 10.22 10.66 Addendum One to Standard Lease, dated as of July 5, 2011, between Ultragenyx Pharmaceutical Inc. and Condiotti Enterprises, Inc. 10-K 2/26/2016 10.34 83 Exhibit Number Exhibit Description Incorporated by Reference Filed Form Date Number Herewith 10. 6 7 Addendum Two to Standard Lease, dated as of March 7, 2012, between Ultragenyx Pharmaceutical Inc. and Condiotti Enterprises, Inc. 10-K 2/26/2016 10.35 10.68 Addendum #3 to Standard Lease, effective as of February 12, 2014, by and between Ultragenyx Pharmaceutical Inc. and Condiotti Enterprises, Inc. 8-K 2/25/2014 10.1 10.69 Addendum #4 to Standard Lease, effective as of March 9, 2015, by and between Ultragenyx Pharmaceutical Inc. and Condiotti Enterprises, Inc. 8-K 3/13/2015 10.1 10.70 Addendum #5 to Standard Lease, effective as of April 7, 2015, by and between Ultragenyx Pharmaceutical Inc. and Condiotti Enterprises, Inc. 10-K 2/26/2016 10.38 10.71 Addendum #6 to Standard Lease, effective as of April 29, 2019, by and between Ultragenyx Pharmaceutical Inc. and Condiotti Enterprises, Inc. 10-Q 8/2/2019 10.3 10.72 Lease Agreement between Marina Boulevard Property, LLC and Ultragenyx Pharmaceutical Inc., dated as of December 8, 2015 10-K 2/26/2016 10.43 10.73 Indenture of Lease between Dimension Therapeutics, Inc. and Rivertech Associates II, LLC, dated March 11, 2014, as amended 10-K 2/21/2018 10.64 10.74 Second Lease Amendment to the Lease between Dimension Therapeutics, Inc. and Rivertech Associates II, LLC, dated April 28, 2017 10-K 2/21/2018 10.65 10.75 Third Lease Amendment to the Lease between Ultragenyx Pharmaceutical Inc. and Rivertech Associates II, LLC, effective December 31, 2018 10-K 2/20/2019 10.66 10.76 Lease Agreement, by and between Dimension Therapeutics, Inc. and ARE-MA Region No. 20, LLC, dated November 2, 2015, and Consent to Assignment to Ultragenyx Pharmaceutical Inc. 10-K 2/21/2018 10.66 10.77 First Amendment to Lease Agreement, dated March 20, 2018, between Ultragenyx Pharmaceutical Inc. and ARE-MA Region No. 20, LLC 10-Q 5/8/2018 10.6 10.78 Second Amendment to Lease Agreement, made July 1, 2018, between Ultragenyx Pharmaceutical Inc. and ARE-MA Region No. 20, LLC 10-Q 8/3/2018 10.3 10.79 Third Amendment, dated July 29, 2019, to the Lease Agreement dated October 30, 2015 by and between Ultragenyx Pharmaceutical Inc. and ARE-MA Region No., LLC. 10-Q 7/30/2020 10.2 10.80 Amended and Restated Fourth Amendment, dated August 4, 2020, to the Lease Agreement dated October 30, 2015 by and between Ultragenyx Pharmaceutical Inc. and ARE-MA Region No., LLC. 10-Q 10/27/2020 10.5 84 Exhibit Number Exhibit Description Incorporated by Reference Filed Form Date Number Herewith 10. 81 Lease Agreement, dated December 15, 2019, between Ultragenyx Pharmaceutical Inc. and ARE-San Francisco No. 17, LLC. X 10.82 First Amendment, dated September 20, 2020, to the Lease Agreement dated December 15, 2019 between Ultragenyx Pharmaceutical Inc. and ARE-San Francisco No. 17, LLC. X 10.83 Second Amendment, dated October 21, 2020, to the Lease Agreement dated December 15, 2019 between Ultragenyx Pharmaceutical Inc. and ARE-San Francisco No. 17, LLC. X 10.84 Office Lease, dated April 19, 2019, between Ultragenyx Pharmaceutical Inc. and Woburn MCB II, LLC 10-K 2/14/2020 10.70 10.85 Commercial Lease, dated July 2, 2018, between Ultragenyx Pharmaceutical Inc. and 32 Leveroni LLC 10-K 2/14/2020 10.71 21.1 Subsidiaries of Ultragenyx Pharmaceutical Inc. X 23.1 Consent of Independent Registered Public Accounting Firm X 24.1 Power of Attorney (included on the signature page of this report) 31.1 Certification of Chief Executive Officer of Ultragenyx Pharmaceutical Inc., as required by Rule 13a-14(a) or Rule 15d-14(a) of the Exchange Act as adopted pursuant to Section 302 of the Sarbanes-Oxley Act of 2002 X 31.2 Certification of Chief Financial Officer of Ultragenyx Pharmaceutical Inc., as required by Rule 13a-14(a) or Rule 15d-14(a) of the Exchange Act as adopted pursuant to Section 302 of the Sarbanes-Oxley Act of 2002 X 32.1§ Certification by the Chief Executive Officer and Chief Financial Officer, as required by Rule 13a-14(b) or Rule 15d-14(b) and Section 1350 of Chapter 36 of Title 18 of the United States Code (18 U.S.C. §1350) X 101.INS XBRL Instance Document, formatted in Inline XBRL X 101.SCH Inline XBRL Taxonomy Extension Schema Document X 101.CAL Inline XBRL Taxonomy Extension Calculation Linkbase Document X 101.DEF Inline XBRL Taxonomy Extension Definition Linkbase Document X 101.LAB Inline XBRL Taxonomy Extension Labels Linkbase Document X 101.PRE Inline XBRL Taxonomy Extension Presentation Linkbase Document X 104 The cover page from this Annual Report on Form 10-K, formatted in Inline XBRL † Confidential treatment has been granted with respect to certain portions (indicated by asterisks) of this exhibit. Omitted portions have been filed separately with the SEC. 85 * Certain confidential portions of this exhibit were omitted by means of marking such portions with asterisks because the identified confidential portions ( i ) are not material and (ii) would be competitively harmful if publicly disclosed. # Indicates management contract or compensatory plan. § The certification attached as Exhibit 32.1 that accompanies this Annual Report is not deemed filed with the SEC and is not to be incorporated by reference into any filing of Ultragenyx Pharmaceutical Inc. under the Securities Act or the Exchange Act, whether made before or after the date of this Annual Report, irrespective of any general incorporation language contained in such filing. Item 16. Form 10-K Summary None. 86 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. U LTRAGENYX P HARMACEUTICAL I nc . By: /s/ Emil D. Kakkis Emil D. Kakkis, M.D., Ph.D. President and Chief Executive Officer Date: February 11, 2021 POWER OF ATTORNEY KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Emil D. Kakkis, M.D., Ph.D. and Mardi C. Dier, and each of them, as his or her true and lawful attorneys-in-fact and agents, with full power of substitution for him or her, and in his or her name in any and all capacities, to sign any and all amendments to this Annual Report, and to file the same, with exhibits thereto and other documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorneys-in-fact and agents, and each of them, full power and authority to do and perform each and every act and thing requisite and necessary to be done therewith, as fully to all intents and purposes as he or she might or could do in person, hereby ratifying and confirming all that said attorneys-in-fact and agents, and any of them, his or her substitute or substitutes, may lawfully do or cause to be done by virtue hereof. 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/ Emil D. Kakkis Emil D. Kakkis, M.D., Ph.D. President and Chief Executive Officer and Director (Principal Executive Officer) February 11, 2021 /s/ Mardi C. Dier Mardi C. Dier Executive Vice President and Chief Financial Officer (Principal Financial Officer) February 11, 2021 /s/ Theodore A. Huizenga Theodore A. Huizenga Senior Vice President, Corporate Controller (Principal Accounting Officer) February 11, 2021 /s/ Daniel G. Welch Daniel G. Welch Chairman of the Board February 11, 2021 /s/ William Aliski William Aliski Director February 11, 2021 /s/ Deborah Dunsire Deborah Dunsire, M.D. Director February 11, 2021 /s/ Lars Ekman Lars Ekman, M.D., Ph.D. Director February 11, 2021 /s/ Matthew K. Fust Matthew K. Fust Director February 11, 2021 /s/ Michael Narachi Michael Narachi Director February 11, 2021 /s/ Clay B. Siegall Clay B. Siegall, Ph.D. Director February 11, 2021 /s/ Shehnaaz Suliman Director February 11, 2021 Shehnaaz Suliman, M.D. 87 Ultragenyx Pharmaceutical Inc. INDEX TO FINANCIAL STATEMENTS Page Report of Independent Registered Public Accounting Firm F-2 Consolidated Financial Statements: Consolidated Balance Sheets F-4 Consolidated Statements of Operations F-5 Consolidated Statements of Comprehensive Loss F-6 Consolidated Statements of Stockholders’ Equity F-7 Consolidated Statements of Cash Flows F-8 Notes to Consolidated Financial Statements F-10 F-1 Report of Independent Registered Public Accounting Firm To the Stockholders and the Board of Directors of Ultragenyx Pharmaceutical Inc.: Opinion on the Financial Statements We have audited the accompanying consolidated balance sheets of Ultragenyx Pharmaceutical Inc. (the Company) as of December 31, 2020 and 2019, the related consolidated statements of operations, comprehensive loss, stockholders' equity and cash flows for each of the three years in the period ended December 31, 2020, and the related notes (collectively referred to as the “consolidated financial statements”). In our opinion, the consolidated financial statements present fairly, in all material respects, the financial position of the Company at 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 U.S. generally accepted accounting principles. We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the Company's internal control over financial reporting as of December 31, 2020, based on criteria established in Internal Control-Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework) and our report dated February 11, 2021 expressed an unqualified opinion thereon. Basis for Opinion These financial statements are the responsibility of the Company's management. Our responsibility is to express an opinion on the Company’s financial statements based on our audits. We are a public accounting firm registered with the 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 audit to obtain reasonable assurance about whether the financial statements are free of material misstatement, whether due to error or fraud. Our audits included performing procedures to assess the risks of material misstatement of the 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 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 financial statements. We believe that our audits provide a reasonable basis for our opinion. Critical Audit Matters The critical audit matters communicated below are matters arising from the current period audit of the financial statements that were communicated or required to be communicated to the audit committee and that: (1) relate to accounts or disclosures that are material to the financial statements and (2) 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 matters below, providing separate opinions on the critical audit matters or on the accounts or disclosures to which they relate. Net product sales Description of the Matter The Company sells approved products through a limited number of distributors. As discussed in Note 2, when recognizing revenue, the Company makes an estimate of the transaction price, including an assessment of whether to constrain any variable consideration. Product sales are recorded net of estimated government-mandated rebates and chargebacks, estimated product returns, and other deductions at the time revenue is recorded. Limited historical data is available for use in developing such estimates which are periodically reviewed and adjusted as necessary. Auditing the Company’s net product sales was complex due to the Company’s limited history of product sales and the growth of sales in international markets. The Company’s estimates of government mandated rebates, chargebacks and estimated product returns depend on the identification of key customer contract terms and conditions, as well as estimates of sales volumes to different classes of payors. The revenue recognition process can be complex and involves significant judgment to identify and assess the terms and conditions of customer agreements and related government regulations that could affect revenue recognition, as the Company’s revenue expands with new customers and new markets. How We Addressed the Matter in Our Audit We obtained an understanding, evaluated the design and tested the operating effectiveness of controls over the Company’s process of recording product sales and related rebates, chargebacks and returns. We also tested management’s controls related to the identification and assessment of the terms and conditions of customer agreements and the completeness and accuracy of data utilized in the controls, and the calculations supporting management’s estimates. To test net product sales, our audit procedures included, among others, tracing a sample of revenue transactions recognized during the year to source documentation. We also confirmed a sample of outstanding receivable balances directly with the Company’s customers. To test management’s estimates of rebates, chargebacks and returns, we obtained management’s calculations for the respective estimates and performed one or more of the following procedures: tested management’s estimation process to assess whether the recorded reserve balances are within a reasonable range of estimate, performed retrospective reviews, assessed subsequent events, and tested a sample of credits issued throughout the year. F-2 Liability related to the sale of future royalties Description of the Matter As discussed in Note 10, the Company entered into a royalty purchase agreement in 2019, in which the Company sold its right to receive royalty payments arising from the net sales of Crysvita in the European market in exchange for $320 million. The proceeds from the transaction were recorded as a liability that is being amortized using the effective interest method over the estimated life of the arrangement. In order to determine the amortization of the liability, the Company is required to estimate the total amount of future royalty payments to be paid to the counterparty, subject to the capped amount, over the life of the arrangement. The Company estimates an imputed interest on the unamortized portion of the liability and records interest expense relating to the transaction. Auditing the Company’s liability related to the sale of future royalties was complex due to the subjective judgments required to forecast the expected royalty payments subject to the agreement. Specifically, the forecasted revenues of Crysvita in the European market involved significant estimation uncertainty. How We Addressed the Matter in Our Audit We obtained an understanding, evaluated the design and tested the operating effectiveness of controls over the Company’s process of accounting for the liability related to the sale of future royalties, including controls over the Company’s estimates of projected sales of Crysvita in the European market . To test management’s estimates of the future royalties and the imputed effective interest rate, we performed audit procedures that included, among others, evaluating the reasonableness of management’s assumptions related to the treatable patient population, estimated pricing and reimbursement, and the rate of adoption. We compared the significant assumptions with historical trends of actual sales, analyst expectations and performed sensitivity analyses of estimated future royalties to evaluate the impact of the changes in the future royalties on the implied effective interest rate. /s/ Ernst & Young LLP We have served as the Company’s auditor since 2010. San Jose, California February 11, 2021 F-3 ULTRAGENYX PHARMACEUTICAL INC. CONSOLIDATED BALANCE SHEETS (In thousands, except share and per share amounts) December 31, 2020 2019 ASSETS Current assets: Cash and cash equivalents $ 713,526 $ 433,584 Marketable debt securities 488,007 321,646 Accounts receivable, net 23,093 32,844 Inventory 13,048 11,546 Prepaid expenses and other current assets 57,630 51,397 Total current assets 1,295,304 851,017 Property, plant, and equipment, net 73,515 44,348 Equity investments 155,375 27,752 Marketable debt securities 10,506 5,174 Right-of-use assets 40,524 30,328 Intangible assets, net 131,113 129,000 Goodwill 44,406 44,406 Other assets 8,812 3,471 Total assets $ 1,759,555 $ 1,135,496 LIABILITIES AND STOCKHOLDERS' EQUITY Current liabilities: Accounts payable $ 12,923 $ 12,871 Accrued liabilities 108,491 83,194 Contract liabilities 59,219 — Lease liabilities 8,976 7,235 Total current liabilities 189,609 103,300 Contract liabilities 7,349 — Lease liabilities 39,251 29,757 Deferred tax liabilities 33,306 33,306 Liability related to the sale of future royalties 335,665 315,369 Total liabilities 605,180 481,732 Commitments and contingencies (Notes 8 and 15) Stockholders’ equity: Preferred stock, par value of $ 0.001 per share— 25,000,000 shares authorized; nil outstanding as of December 31, 2020 and 2019 — — Common stock, par value of $ 0.001 per share— 250,000,000 shares authorized; 66,818,520 and 57,838,220 shares issued and outstanding as of December 31, 2020 and 2019, respectively 67 58 Additional paid-in capital 2,773,195 2,086,863 Accumulated other comprehensive income (loss) 689 ( 147 ) Accumulated deficit ( 1,619,576 ) ( 1,433,010 ) Total stockholders’ equity 1,154,375 653,764 Total liabilities and stockholders’ equity $ 1,759,555 $ 1,135,496 See accompanying notes. F-4 ULTRAGENYX PHARMACEUTICAL INC. CONSOLIDATED STATEMENTS OF OPERATIONS (In thousands, except share and per share amounts) Year Ended December 31, 2020 2019 2018 Revenues: Collaboration and license $ 219,315 $ 83,493 $ 41,693 Product sales 38,720 20,221 9,802 Non-cash collaboration royalty revenue 12,995 — — Total revenues 271,030 103,714 51,495 Operating expenses: Cost of sales 6,129 9,008 1,146 Research and development 412,084 357,355 293,998 Selling, general and administrative 182,933 161,524 127,724 Total operating expenses 601,146 527,887 422,868 Loss from operations ( 330,116 ) ( 424,173 ) ( 371,373 ) Interest income 7,038 13,238 9,542 Gain from sale of priority review vouchers — — 170,322 Change in fair value of equity investments 170,403 13,413 — Non-cash interest expense on liability related to the sale of future royalties ( 33,291 ) ( 1,135 ) — Other income (expense) 607 ( 787 ) ( 5,588 ) Loss before income taxes ( 185,359 ) ( 399,444 ) ( 197,097 ) Provision for income taxes ( 1,207 ) ( 3,283 ) ( 514 ) Net loss $ ( 186,566 ) $ ( 402,727 ) $ ( 197,611 ) Net loss per share, basic and diluted $ ( 3.07 ) $ ( 7.12 ) $ ( 3.97 ) Shares used in computing net loss per share, basic and diluted 60,845,550 56,576,885 49,775,223 See accompanying notes. F-5 ULTRAGENYX PHARMACEUTICAL INC. CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS (In thousands) Year Ended December 31, 2020 2019 2018 Net loss $ ( 186,566 ) $ ( 402,727 ) $ ( 197,611 ) Other comprehensive income: Foreign currency translation adjustments 735 23 ( 303 ) Transfer of currency translation adjustments balance to other income related to the liquidation of foreign subsidiaries — — 5,272 Unrealized gain on available-for-sale securities 101 463 78 Other comprehensive income: 836 486 5,047 Total comprehensive loss $ ( 185,730 ) $ ( 402,241 ) $ ( 192,564 ) See accompanying notes. F-6 ULTRAGENYX PHARMACEUTICAL INC. CONSOLIDATED STATEMENTS OF STOCKHOLDERS’ EQUITY (In thousands, except share amounts) Common Stock Additional Paid-In Accumulated Other Comprehensive Accumulated Total Stockholders' Shares Amount Capital Income (Loss) Deficit Equity Balance as of December 31, 2017 44,167,071 $ 44 $ 1,221,762 $ ( 5,680 ) $ ( 832,672 ) $ 383,454 Issuance of common stock in connection with underwritten public offering, net of issuance costs 5,043,860 5 270,964 — — 270,969 Issuance of common stock in connection with at-the-market offering, net of issuance costs 640,257 1 38,055 — — 38,056 Stock-based compensation expense — — 81,165 — — 81,165 Issuance of common stock under equity plan awards, net of tax 1,009,400 1 27,827 — — 27,828 Other comprehensive income — — — 5,047 — 5,047 Net loss — — — — ( 197,611 ) ( 197,611 ) Balance as of December 31, 2018 50,860,588 51 1,639,773 ( 633 ) ( 1,030,283 ) 608,908 Issuance of common stock in connection with underwritten public offering, net of issuance costs 5,833,333 6 330,409 — — 330,415 Issuance of common stock in connection with at-the-market offering, net of issuance costs 468,685 — 24,828 — — 24,828 Stock-based compensation expense — — 82,025 — — 82,025 Issuance of common stock under equity plan awards, net of tax 675,614 1 9,828 — — 9,829 Other comprehensive income — — — 486 — 486 Net loss — — — — ( 402,727 ) ( 402,727 ) Balance as of December 31, 2019 57,838,220 58 2,086,863 ( 147 ) ( 1,433,010 ) 653,764 Issuance of common stock in connection with underwritten public offering, net of issuance costs 5,111,110 5 435,551 — — 435,556 Issuance of common stock in connection with license agreement, net of issuance costs 1,243,913 1 55,267 — — 55,268 Issuance of common stock in connection with at-the-market offering, net of issuance costs 283,333 — 20,391 — — 20,391 Stock-based compensation expense — — 85,833 — — 85,833 Issuance of common stock upon exercise of warrants and under equity plan awards, net of tax 2,341,944 3 89,290 — — 89,293 Other comprehensive income — — — 836 — 836 Net loss — — — — ( 186,566 ) ( 186,566 ) Balance as of December 31, 2020 66,818,520 $ 67 $ 2,773,195 $ 689 $ ( 1,619,576 ) $ 1,154,375 See accompanying notes. F-7 ULTRAGENYX PHARMACEUTICAL INC. CONSOLIDATED STATEMENTS OF CASH FLOWS (In thousands) Year Ended December 31, 2020 2019 2018 Operating activities: Net loss $ ( 186,566 ) $ ( 402,727 ) $ ( 197,611 ) Adjustments to reconcile net loss to net cash used in operating activities: Stock-based compensation 85,735 81,995 80,107 Amortization of premium (discount) on marketable debt securities, net 848 ( 6,214 ) ( 2,641 ) Depreciation and amortization 12,261 8,539 19,538 Foreign currency remeasurement (gain) loss ( 221 ) 688 5,309 Change in fair value of equity investments ( 170,403 ) ( 13,413 ) — Non-cash collaboration royalty revenue ( 12,995 ) — — Non-cash interest expense on liability related to the sale of future royalties 33,291 1,135 — Gain from sale of priority review vouchers — — ( 170,322 ) Other 1,167 1,933 ( 156 ) Changes in operating assets and liabilities: Accounts receivable 9,840 ( 20,104 ) ( 7,583 ) Inventory ( 1,346 ) ( 4,451 ) ( 5,283 ) Prepaid expenses and other assets 2,748 ( 8,216 ) ( 14,285 ) Accounts payable, accrued, and other liabilities 26,853 13,312 2,361 Contract liabilities, net 66,568 — — Deferred tax liabilities — 2,140 — Net cash used in operating activities ( 132,220 ) ( 345,383 ) ( 290,566 ) Investing activities: Purchase of property, plant, and equipment ( 43,905 ) ( 24,832 ) ( 4,076 ) Purchase of marketable debt securities ( 813,237 ) ( 692,824 ) ( 509,796 ) Purchase of equity investments ( 37,062 ) ( 14,339 ) — Proceeds from sale of marketable debt securities 50,990 42,718 7,655 Proceeds from sale of equity investment 79,842 — — Proceeds from maturities of marketable debt securities 589,806 676,238 302,564 Proceeds from sale of priority review vouchers — — 170,322 Other ( 5,555 ) — — Net cash used in investing activities ( 179,121 ) ( 13,039 ) ( 33,331 ) Financing activities: Proceeds from the sale of future royalties, net — 314,234 — Proceeds from the issuance of common stock in connection with underwritten public offerings, net 435,556 330,415 270,969 Proceeds from the issuance of common stock in connection with the license agreement, net 55,268 — — Proceeds from the issuance of common stock in connection with at-the-market offering, net 20,391 24,828 38,056 Proceeds from the issuance of common stock from exercise of warrants and equity plan awards, net 89,293 9,829 27,828 Other ( 236 ) — — Net cash provided by financing activities 600,272 679,306 336,853 Effect of exchange rate changes on cash 1,119 ( 165 ) ( 472 ) Net increase in cash, cash equivalents, and restricted cash 290,050 320,719 12,484 Cash, cash equivalents, and restricted cash at beginning of year 436,244 115,525 103,041 Cash, cash equivalents, and restricted cash at end of year $ 726,294 $ 436,244 $ 115,525 See accompanying notes. F-8 ULTRAGENYX PHARMACEUTICAL INC. CONSOLIDATED STATEMENTS OF CASH FLOWS (In thousands) Year Ended December 31, 2020 2019 2018 Supplemental disclosures of non-cash investing and financing information: Acquired lease liabilities arising from obtaining right-of-use assets $ 18,775 $ 21,861 $ — Stock-based compensation capitalized into ending inventory $ 1,304 $ 1,206 $ 1,058 Costs of property and equipment included in accounts payable, accrued, and other liabilities $ 8,515 $ 10,367 $ 1,192 See accompanying notes. F-9 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements 1. Organization and Basis of Presentation Ultragenyx Pharmaceutical Inc. (the Company) is a biopharmaceutical company incorporated in California on April 22, 2010. The Company subsequently reincorporated in the state of Delaware in June 2011. The Company is focused on the identification, acquisition, development, and commercialization of novel products for the treatment of serious rare and ultra-rare genetic diseases. The Company has three commercially approved products. Crysvita ® (burosumab) is approved in the United States by the U.S. Food and Drug Administration (FDA) and in Canada for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients one year of age and older, and is approved in the European Union (EU) and the United Kingdom, for the treatment of XLH with radiographic evidence of bone disease in children one year of age and older, adolescents, and adults. In Brazil and Mexico, Crysvita is approved for treatment of XLH in adult and pediatric patients one year of age and older. Crysvita was approved by the FDA on June 18, 2020 for the treatment of fibroblast growth factor 23 (FGF23)-related hypophosphatemia in tumor-induced osteomalacia (TIO), associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adults and pediatric patients 2 years of age and older. The Company has also received FDA approval for Mepsevii™ (vestronidase alfa), the first medicine approved for the treatment of children and adults with mucopolysaccharidosis VII (MPS VII), also known as Sly syndrome. In the European Union and the United Kingdom, Mepsevii is approved under exceptional circumstances for patients of all ages for the treatment of non-neurological manifestations of MPS VII. In Brazil, Mepsevii is approved for the treatment of MPS VII for patients of all ages. Dojolvi, formerly known as UX007, was approved by FDA on June 30, 2020 for the treatment of pediatric and adult patients severely affected by long-chain fatty acid oxidation disorders (LC-FAOD). In addition to the approved products, the Company has the following ongoing clinical development programs: DTX401 is an adeno-associated virus 8 (AAV8) gene therapy product candidate for the treatment of patients with glycogen storage disease type Ia (GSDIa); and DTX301 is an AAV8 gene therapy product candidate in development for the treatment of patients with ornithine transcarbamylase (OTC) deficiency, the most common urea cycle disorder. UX143 (setrusumab) which the Company began collaborating on the development with Mereo BioPharma 3 Limited (Mereo) beginning in January 2021, is a fully human monoclonal antibody that inhibits sclerostin, a protein that acts on a key bone-signaling pathway and inhibits the activity of bone-forming cells for the treatment of patients with osteogenesis imperfect (OI). GTX-102 is an antisense oligonucleotide, or ASO, which the Company is collaborating on the development with GeneTx Biotherapeutics LLC (GeneTx) for the treatment of Angelman syndrome, a debilitating and rare neurogenetic disorder caused by loss-of-function of the maternally inherited allele of the UBE3A gene. UX701 is an AAV type 9 gene therapy designed to deliver stable expression of a truncated version of the ATP7B copper transporter following a single intravenous infusion to improve copper distribution and excretion from the body and reverse pathological findings of Wilson liver disease. The Company operates as one reportable segment. The Company has sustained operating losses and expects such annual losses to continue over the next several years. The Company’s ultimate success depends on the outcome of its research and development and commercialization activities, for which it expects to incur additional losses in the future. Management recognizes that the Company will likely need to raise additional capital to fully implement its business plans. Through December 31, 2020, the Company has relied primarily on its sale of equity securities, its sale of future royalties, and strategic collaboration arrangements, to finance its operations. The Company will likely raise additional capital through the issuance of equity, borrowings, or strategic alliances with partner companies. However, if such financing is not available at adequate levels, the Company would need to reevaluate its operating plans. 2. Summary of Significant Accounting Policies Basis of Consolidation The consolidated financial statements include the accounts of Ultragenyx Pharmaceutical Inc. and its wholly-owned subsidiaries. All intercompany balances and transactions have been eliminated. Use of Estimates The accompanying consolidated financial statements have been prepared in accordance with U.S. generally accepted accounting principles (GAAP). The preparation of the consolidated financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities, disclosure of contingent liabilities and the reported amounts of expenses in the consolidated financial statements and the accompanying notes. On an ongoing basis, management evaluates its estimates, including those related to clinical trial accruals, fair value of assets and liabilities, income taxes, stock-based compensation, and the liability related to the sale of future royalties. Management bases its estimates on historical experience and on various other market-specific and relevant assumptions that management believes to be reasonable under the circumstances. Actual results could differ from those estimates. F-10 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) Cash, Cash Equivalents, and Restricted Cash The Company considers all highly liquid investments with original maturities of three months or less from the date of purchase to be cash equivalents. Cash equivalents consist primarily of amounts invested in money market accounts. Restricted cash primarily consists of money market accounts used as collateral for the Company’s obligations under its facility leases and the gene therapy building construction project. The following table provides a reconciliation of cash, cash equivalents, and restricted cash reported within the consolidated balance sheets that sum to the total of the amounts shown in the consolidated statement of cash flows (in thousands): December 31, 2020 2019 2018 Cash and cash equivalents $ 713,526 $ 433,584 $ 113,432 Restricted cash included in prepaid expenses and other current assets 10,847 161 271 Restricted cash included in other assets 1,921 2,499 1,822 Total cash, cash equivalents, and restricted cash shown in the statements of cash flows $ 726,294 $ 436,244 $ 115,525 Marketable Debt Securities All marketable debt securities have been classified as “available-for-sale” and are carried at estimated fair value as determined based upon quoted market prices or pricing models for similar securities. Management determines the appropriate classification of its investments at the time of purchase and reevaluates such designation as of each balance sheet date. Investments with a maturity of one year or less from the balance sheet date are reported as current marketable debt securities and investments with a maturity of greater than one year from the balance sheet date are reported as non-current marketable debt securities. Unrealized gains and losses are excluded from earnings and are reported as a component of comprehensive loss. Realized gains and losses and declines in fair value judged to be other than temporary, if any, on available-for-sale securities are included in other income (expense). The cost of securities sold is based on the specific-identification method. Interest on investments is included in interest income. Equity Investments In June 2019, the Company entered into an amendment to the Research Collaboration and License Agreement and an Equity Purchase Agreement with Arcturus Therapeutics Holdings Inc. (Arcturus). Pursuant to the Equity Purchase Agreement, the Company purchased 2,400,000 shares of common stock and received an option to purchase an additional 600,000 shares of common stock, which was exercised in May 2020. In December 2020, the Company sold 800,000 shares . The Company elected to apply the fair value option to account for the equity investment in Arcturus. The option to purchase additional Arcturus stock was accounted for at fair value using the Black-Scholes option pricing method prior to the exercise of options. In October 2020, the Company entered into a Research Collaboration and License Agreement, Stock Purchase Agreement and Investor Agreement, with Solid Biosciences Inc. (Solid). Pursuant to the Stock Purchase Agreement, the Company purchased 7,825,797 shares of Solid’s common stock. The investment is being accounted at fair value based on quoted market prices. The changes in fair value of the equity investments and an option to purchase additional stock are included in the Consolidated Statements of Operations. See “Note 7. License and Research Agreements” for additional details on the transaction. Concentration of Credit Risk, Credit Losses, and Other Risks and Uncertainties Financial instruments that potentially subject the Company to a concentration of credit risk consist of cash, cash equivalents, and investments. The Company’s cash, cash equivalents, and investments are held by financial institutions that management believes are of high credit quality. The Company’s investment policy limits investments to fixed income securities denominated and payable in U.S. dollars such as U.S. government obligations, money market instruments and funds, corporate bonds, commercial paper, and asset-backed securities and places restrictions on maturities and concentrations by type and issuer. Such deposits may, at times, exceed federally insured limits. The Company has not experienced any losses on its deposits of cash and cash equivalents and its accounts are monitored by management to mitigate risk. The Company is exposed to credit risk in the event of default by the financial institutions holding its cash and cash equivalents, corporate issuers, and other financial instruments, to the extent recorded in the balance sheets . Effective January 1, 2020, the Company adopted Accounting Standards Update (ASU) 2016-13, Financial Instruments — Credit Losses, (Topic 326): Measurement of Credit Losses on Financial Instruments, which changed the impairment model for most financial assets and certain other instruments. For trade receivables and other instruments, the Company uses a new forward-looking F-11 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) expected loss model that generally results in the earlier recognition of allowances for losses. For available-for-sale debt securities with unrealized losses, the losses are recognized as allowances rather than as reductions in the amortized cost of the securities. The Company is exposed to credit losses primarily through receivables from customers and collaborators and through its available-for-sale debt securities. The Company’s expected loss allowance methodology for the receivables is developed using historical collection experience, current and future economic market conditions, a review of the current aging status and financial condition of the entities. Specific allowance amounts are established to record the appropriate allowance for customers that have a higher probability of default. Balances are written off when determined to be uncollectible. The Company’s expected loss allowance methodology for the debt securities is developed by reviewing the extent of the unrealized loss, the size, term, geographical location, and industry of the issuer, the issuers’ credit ratings and any changes in those ratings, as well as reviewing current and future economic market conditions and the issuers’ current status and financial condition. The Company considered the current and expected future economic and market conditions surrounding the novel coronavirus (COVID-19) pandemic and determined that the estimate of credit losses was not significantly impacted. The adoption of the guidance did not have a material impact on the Condensed Consolidated Financial Statements and related disclosures and there was no allowance for losses on available-for-sale debt securities which were attributable to credit risk for the year ended December 31, 2020. The Company is dependent on third-party manufacturers to supply products for research and development activities in its programs. In particular, the Company relies and expects to continue to rely on a small number of manufacturers to supply it with its requirements for the active pharmaceutical ingredients and formulated drugs related to these programs. These programs could be adversely affected by a significant interruption in the supply of active pharmaceutical ingredients and formulated drugs. Inventory The Company values inventory at the lower of cost and net realizable value and determines the cost of inventory using the average-cost method. The Company expenses costs associated with the manufacture of product candidates prior to regulatory approval. Inventories consist of currently approved products. The Company periodically reviews its inventories for excess amounts or obsolescence and writes down obsolete or otherwise unmarketable inventory to its estimated net realizable value. Management determines excess inventory based on expected future demand. Estimates related to future demand are sensitive to significant inputs and assumptions such as acceptance by patients and physicians and the availability of formulary coverage and adequate reimbursement from private third-party payers for the product. Property, Plant, and Equipment Property, plant, and equipment are stated at cost, less accumulated depreciation and amortization. Depreciation and amortization is computed using the straight-line method over the estimated useful lives of the respective assets. Depreciation and amortization begins at the time the asset is placed in service. Maintenance and repairs are charged to operations as incurred. Upon sale or retirement of assets, the cost and related accumulated depreciation or amortization are removed from the balance sheet and the resulting gain or loss, if any, is reflected in operations. The useful lives of property, plant, and equipment are as follows: Research and development equipment 5 years Furniture and office equipment 5 years Computer equipment 3 years Software 3-5 years Land Not applicable Leasehold improvements Shorter of lease term or estimated useful life Intangible Assets The Company’s intangible assets consist of acquired in-process research and development (IPR&D) and contractual payments made for certain milestones achieved with collaboration partners. IPR&D assets represent capitalized incomplete research projects that the Company acquired through business combinations. Such assets are initially measured at their acquisition date fair values and are tested for impairment, until the completion or abandonment of the associated research and development efforts. If and when development is complete, which generally occurs when regulatory approval to market a product is obtained, the associated assets will be deemed finite-lived and will be amortized over a period that best reflects the economic benefits provided by these assets. The contractual payments made for certain milestones achieved was recorded as an intangible and are amortized over its estimated useful life. F-12 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) The Company tests its definite and indefinite-lived intangible assets for impairment annually during the fourth quarter and more frequently if events or changes in circumstances indicate that it is more likely than not that the asset is impaired. If it is determined that the asset becomes impaired, the carrying value is written down to its fair value with the related impairment charge recognized in consolidated statements of operations in the period in which the impairment occurs. The Company has not recorded any impairments of intangible assets. Goodwill Goodwill represents the excess of purchase price over fair value of net assets acquired in a business combination and is not amortized. Goodwill is subject to impairment testing at least annually during the fourth quarter or when a triggering event occurs that could indicate a potential impairment. If it is determined that the goodwill becomes impaired, the carrying value is written down to its fair value with the related impairment charge recognized in consolidated statements of operations in the period in which the impairment occurs. The Company has not recorded any impairments of goodwill. Impairment of Long-Lived Assets The Company evaluates its long-lived assets, including property and equipment, for impairment whenever events or changes in circumstances indicate that the carrying value of these assets may not be recoverable. Recoverability of these assets is measured by comparison of the carrying amount of each asset to the future undiscounted cash flows expected to result from the use of the asset and its eventual disposition. If the asset is considered to be impaired, the amount of any impairment is measured as the difference between the carrying value and the fair value of the impaired asset. The Company has not recorded impairment of any long-lived assets. Accruals of Research and Development Costs The Company records accruals for estimated costs of research, preclinical and clinical studies and manufacturing development. These costs are a significant component of the Company’s research and development expenses. A substantial portion of the Company’s ongoing research and development activities are conducted by third-party service providers, including contract research organizations. The Company accrues the costs incurred under its agreements with these third parties based on actual work completed in accordance with agreements established with these third parties. The Company determines the actual costs through obtaining information from external service providers as to the progress or stage of completion of the services and the agreed-upon fee to be paid for such services. Revenue Recognition Collaboration and license revenue The Company has certain license and collaboration agreements that are within the scope of Accounting Standards Codification (ASC) 808, Collaborative Agreements , which provides guidance on the presentation and disclosure of collaborative arrangements. Generally, the classification of the transactions under the collaborative arrangements is determined based on the nature of contractual terms of the arrangement, along with the nature of the operations of the participants. The Company records its share of collaboration revenue, net of transfer pricing related to net sales in the period in which such sales occur, if the Company is considered as an agent in the arrangement. The Company is considered an agent when the collaboration partner controls the product before transfer to the customers and has the ability to direct the use of and obtain substantially all of the remaining benefits from the product. Funding received related to research and development services and commercialization costs is generally classified as a reduction of research and development expenses and selling, general and administrative expenses, respectively, in the consolidated statement of operations, because the provision of such services for collaborative partners are not considered to be part of the Company’s ongoing major or central operations. The Company also records royalty revenues under certain of the Company’s license or collaboration agreements in exchange for license of intellectual property. If the Company does not have any future performance obligations for these license or collaboration agreements, royalty revenue is recorded as the underlying sales occur. In order to record collaboration revenue, the Company utilizes certain information from its collaboration partners , including revenue from the sale of the product, associated reserves on revenue, and costs incurred for development and sales activities. For the periods covered in the financial statements presented, there have been no material changes to prior period estimates of revenues and expenses. The terms of the Company’s collaboration and license agreements may contain multiple performance obligations, which may include licenses and research and development activities. The Company evaluates these agreements under ASC 606, Revenue from Contracts with Customers (ASC 606), to determine the distinct performance obligations. The Company analogizes to ASC 606 for the accounting for distinct performance obligations for which there is a customer relationship. Prior to recognizing revenue, the Company makes estimates of the transaction price, including variable consideration that is subject to a constraint. Amounts of variable consideration are included in the transaction price to the extent that it is probable that a significant reversal in the amount of F-13 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) cumulative revenue recognized will not occur and when the uncertainty associated with the variable consideration is subsequently resolved. Total consideration may include nonrefundable upfront license fees, payments for research and development activities, reimbursement of certain third-party costs, payments based upon the achievement of specified milestones, and royalty payments based on product sales derived from the collaboration. If there are multiple distinct performance obligations, the Company allocates the transaction price to each distinct performance obligation based on its relative standalone selling price. The standalone selling price is generally determined based on the prices charged to customers or using expected cost-plus margin. The Company estimates the efforts needed to complete the performance obligations and recognizes revenue by measuring the progress towards complete satisfaction of the performance obligations using input measures. Product sales The Company sells its approved products through a limited number of distributors. Under ASC 606, revenue from product sales is recognized at the point in time when the delivery is made and when title and risk of loss transfers to these distributors. The Company also recognizes revenue from sales of certain products on a “named patient” basis, which are allowed in certain countries prior to the commercial approval of the product. Prior to recognizing revenue, the Company makes estimates of the transaction price, including any variable consideration that is subject to a constraint. Amounts of variable consideration are included in the transaction price to the extent that it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur and when the uncertainty associated with the variable consideration is subsequently resolved. Product sales are recorded net of estimated government-mandated rebates and chargebacks, estimated product returns, and other deductions. Provisions for returns and other adjustments are provided for in the period the related revenue is recorded, as estimated by management. These reserves are based on estimates of the amounts earned or to be claimed on the related sales and are reviewed periodically and adjusted as necessary. The Company’s estimates of government mandated rebates, chargebacks, estimated product returns, and other deductions depends on the identification of key customer contract terms and conditions, as well as estimates of sales volumes to different classes of payors. If actual results vary, the Company may need to adjust these estimates, which could have an effect on earnings in the period of the adjustment. Non-cash collaboration royalty revenue Effective January 1, 2020, the Company sold the right to receive certain royalty payments from net sales of Crysvita in the European territories to RPI Finance Trust (RPI), an affiliate of Royalty Pharma, as further described in “Note 10. Liability Related to the Sale of Future Royalties”. The Company records the royalty revenue from the net sales of Crysvita in the applicable European territories on a prospective basis as non-cash royalty revenue in the Consolidated Statements of Operations over the term of the arrangement. Leases The Company adopted Accounting Standards Update (ASU) No. 2016-02, Leases (Topic 842) as of January 1, 2019 using the modified retrospective method. The results for years ended December 31, 2019 and 2020 are presented under ASC 842. The results for the year ended December 31, 2018 were not adjusted and continue to be reported in accordance with historical accounting under prior lease guidance, ASC 840, Leases (Topic 840) . The Company also elected the package of practical expedients under the transition guidance that will retain the historical lease classification and initial direct costs for any leases that existed prior to adoption of the new guidance and the practical expedient to not separate lease and non-lease components. The Company determines if an arrangement includes a lease at inception. Right-of-use lease assets and lease liabilities are recognized based on the present value of the future minimum lease payments over the lease term at the commencement date. The right-of-use lease asset includes any lease payments made and excludes lease incentives. Incremental borrowing rate is used in determining the present value of future payments. The Company applies a portfolio approach to the property leases to apply an incremental borrowing rate to leases with similar lease terms. The lease terms may include options to extend or terminate the lease. The Company recognizes the options to extend the lease as part of the right-of-use lease assets and lease liabilities only if it is reasonably certain that the option would be exercised. Lease expense for minimum lease payments is recognized on a straight-line basis over the non-cancelable lease term. As a result of the adoption of the new guidance, effective January 1, 2019, the Company recorded a right-of-use lease asset of $ 16.2 million, a current lease liability of $ 4.5 million, and a non-current lease liability of $ 17.0 million and no cumulative effect adjustment was made to the retained earnings as of the adoption date. In addition, as of the adoption date, the Company derecognized a net deferred rent obligation of $ 5.2 million. See “Note 8. Leases” for further disclosure. F-14 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) Comprehensive Loss Comprehensive loss is the change in stockholders’ equity from transactions and other events and circumstances other than those resulting from investments by stockholders and distributions to stockholders. The Company’s other comprehensive loss is comprised of unrealized gains and losses on investments in available-for-sale securities and foreign currency translation adjustments. Research and Development Research and development costs are expensed as incurred and consist of salaries and benefits, stock-based compensation expense, lab supplies and facility costs, as well as fees paid to other nonemployees and entities that conduct certain research and development activities on the Company’s behalf. Amounts incurred in connection with license agreements are also included in research and development expense. Nonrefundable advance payments for goods or services to be received in the future for use in research and development activities are deferred. The deferred amounts are expensed as the related goods are delivered or the services are performed. Stock-Based Compensation Stock-based awards issued to employees, including stock options, restricted stock units (RSUs), and performance stock units (PSUs) are recorded at fair value as of the grant date and recognized as expense on a straight-line basis over the employee’s requisite service period (generally the vesting period). PSUs vest only if certain specified criteria are achieved and the employees’ continued service requirements are met; therefore, the expense recognition occurs when the likelihood of the PSUs being earned is deemed probable. Stock compensation expense on awards expected to vest are recognized net of estimated forfeitures. Income Taxes The Company uses the liability method of accounting for income taxes. Under this method, deferred tax assets and liabilities are determined based on the differences between the financial reporting and the tax bases of assets and liabilities and are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse. The Company must then assess the likelihood that the resulting deferred tax assets will be realized. A valuation allowance is provided when it is more likely than not that some portion or all of a deferred tax asset will not be realized. Due to the Company’s lack of earnings history, the net deferred tax assets have been fully offset by a valuation allowance. In conjunction with Dimension acquisition, a deferred tax liability was recorded reflecting the tax impact of the difference between the book basis and tax basis of acquired IPR&D. Such deferred income tax liability is not used to offset deferred tax assets when analyzing the Company’s valuation allowance as the acquired IPR&D is considered to have an indefinite life until the Company completes or abandons development of the acquired IPR&D. The Company recognizes benefits of uncertain tax positions if it is more likely than not that such positions will be sustained upon examination based solely on their technical merits, as the largest amount of benefit that is more likely than not to be realized upon the ultimate settlement. The Company’s policy is to recognize interest and penalties related to the underpayment of income taxes as a component of income tax expense or benefit. To date, there have been no interest or penalties charged in relation to the unrecognized tax benefits. Foreign Currency Assets and liabilities of non-U.S. subsidiaries that operate in a local currency environment, where the local currency is the functional currency, are translated to U.S. dollars at exchange rates in effect at the balance sheet date, with the resulting translation adjustments directly recorded to a separate component of accumulated other comprehensive loss. Income and expense accounts are translated at average exchange rates for the period. Transactions which are not in the functional currency of the entity are remeasured into the functional currency and gains or losses resulting from the remeasurement recorded in other income (expense). Net Loss per Share Basic net loss per share is calculated by dividing the net loss by the weighted-average number of shares of common stock outstanding during the period, without consideration for common stock equivalents. Diluted net loss per share is the same as basic net loss per share, since the effects of potentially dilutive securities are antidilutive. In periods when we have incurred a net loss, options and warrants to purchase common stock are considered common stock equivalents, but have been excluded from the calculation of diluted net loss per share, as their effect is antidilutive. F-15 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) 3. Fair Value Measurements Financial assets and liabilities are recorded at fair value. The carrying amount of certain financial instruments, including cash and cash equivalents, accounts receivable, accounts payable and accrued liabilities approximate fair value due to their relatively short maturities. Assets and liabilities recorded at fair value on a recurring basis in the balance sheets are categorized based upon the level of judgment associated with the inputs used to measure their fair values. Fair value is defined as the exchange price that would be received for an asset or an exit price that would be paid to transfer a liability in the principal or most advantageous market for the asset or liability in an orderly transaction between market participants on the measurement date. The authoritative guidance on fair value measurements establishes a three-tier fair value hierarchy for disclosure of fair value measurements as follows: Level 1 —Inputs are unadjusted, quoted prices in active markets for identical assets or liabilities at the measurement date; Level 2 —Inputs are observable, unadjusted quoted prices in active markets for similar assets or liabilities, unadjusted quoted prices for identical or similar assets or liabilities in markets that are not active, or other inputs that are observable or can be corroborated by observable market data for substantially the full term of the related assets or liabilities; and Level 3 —Unobservable inputs that are significant to the measurement of the fair value of the assets or liabilities that are supported by little or no market data. The Company’s financial instruments consist of Level 1, Level 2, and Level 3 assets. Where quoted prices are available in an active market, securities are classified as Level 1. Money market funds and U.S. Government treasury bills are classified as Level 1. Level 2 assets consist primarily of corporate bonds, asset backed securities, commercial paper and U.S. Government agency securities based upon quoted market prices for similar movements in active markets, quoted prices for identical or similar instruments in markets that are not active and model-based valuation techniques for which all significant inputs are observable in the market or can be corroborated by observable market data for substantially the full term of the assets. Where applicable these models project future cash flows and discount the future amounts to a present value using market-based observable inputs obtained from various third party data providers, including but not limited to, benchmark yields, interest rate curves, reported trades, broker/dealer quotes and reference data. The Company determines the fair value of its equity investments in Arcturus and Solid by using the quoted market prices, which are Level 1 fair value measurements. T he fair value of the option to purchase additional shares of Arcturus common stock was based on unobservable inputs that are significant to the measurement of the fair value of the asset and is supported by little or no market data; accordingly, the fair value of the option is considered a Level 3 financial asset. The Company measures the Level 3 financial asset by applying the Black-Scholes option pricing method and utilizes the following inputs: stock price, strike price, volatility, risk free interest rate, and expected term. The expected term is the Company’s estimated period to purchase additional stock. The option was exercised in May 2020 and converted to Arcturus common stock. The following table sets forth the fair value of the Company’s financial assets and liabilities remeasured on a recurring basis based on the three-tier fair value hierarchy (in thousands): December 31, 2020 Level 1 Level 2 Level 3 Total Financial Assets: Money market funds $ 598,392 $ — $ — $ 598,392 Time deposits — 10,000 — 10,000 Corporate bonds — 193,802 — 193,802 Commercial paper — 173,859 — 173,859 Asset-backed securities — 11,225 — 11,225 U.S. Government Treasury and agency securities 167,967 17,661 — 185,628 Investments in Arcturus and Solid common stock 154,756 — — 154,756 Total $ 921,115 $ 406,547 $ — $ 1,327,662 F-16 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) December 31, 2019 Level 1 Level 2 Level 3 Total Financial Assets: Money market funds $ 293,309 $ — $ — $ 293,309 Repurchase agreements — 100,000 — 100,000 Time deposits — 10,000 — 10,000 Corporate bonds — 77,026 — 77,026 Commercial paper — 80,119 — 80,119 Asset-backed securities — 30,406 — 30,406 U.S. Government Treasury and agency securities 96,329 53,979 — 150,308 Equity investment in Arcturus 26,088 — 1,664 27,752 Total $ 415,726 $ 351,530 $ 1,664 $ 768,920 In July 2020, the Company invested $ 2.5 million in a private diagnostic company in the form of a convertible promissory note that matures in two years , if not converted earlier. The Company was also issued a warrant to purchase up to $ 1.0 million of the entity’s preferred stock. The fair value of the warrant to purchase shares of the entity was based on unobservable inputs that are significant to the measurement of the fair value of the asset and is supported by little or no market data; accordingly, the warrant is considered a Level 3 financial asset and is remeasured on a nonrecurring basis. The Company measured the fair value of the warrant by applying the Black-Scholes option pricing method and utilizing the following inputs: stock price, strike price, volatility, risk-free interest rate, and expected term. The Company will recognize interest income on the convertible promissory note based on the effective interest rate method over the life of the note. As of December 31, 2020, the balance of the convertible promissory note was $ 2.1 million, including $ 0.2 million in interest receivable, and was recorded in other assets, and the allocated fair value of the warrant was $ 0.6 million and was recorded in equity investments. In December 2020, the Company invested $ 1.4 million in Mazi Therapeutics, Inc. (Mazi), a private pharmaceutical company founded by a current employee of the Company, in the form of a convertible promissory note that matures in two years , if not converted earlier. 4. Balance Sheet Components Cash Equivalents and Marketable Debt Securities The fair values of cash equivalents and marketable debt securities classified as available-for-sale securities consisted of the following (in thousands): December 31, 2020 Gross Unrealized Amortized Cost Gains Losses Estimated Fair Value Money market funds $ 598,392 $ — $ — $ 598,392 Time deposits 10,000 — — 10,000 Corporate bonds 193,610 209 ( 17 ) 193,802 Commercial paper 173,859 — — 173,859 Asset-backed securities 11,224 1 — 11,225 U.S. Government Treasury and agency securities 185,561 67 — 185,628 Total $ 1,172,646 $ 277 $ ( 17 ) $ 1,172,906 F-17 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) December 31, 2019 Gross Unrealized Amortized Cost Gains Losses Estimated Fair Value Money market funds $ 293,309 $ — $ — $ 293,309 Repurchase agreements 100,000 — — 100,000 Time deposits 10,000 — — 10,000 Corporate bonds 77,022 17 ( 13 ) 77,026 Commercial paper 80,119 — — 80,119 Asset-backed securities 30,375 31 — 30,406 U.S. Government Treasury and agency securities 150,184 124 — 150,308 Total $ 741,009 $ 172 $ ( 13 ) $ 741,168 At December 31, 2020, the remaining contractual maturities of available-for-sale securities were less than two years . There have been no significant realized gains or losses on available-for-sale securities for the periods presented. All marketable securities with unrealized losses at December 31, 2020 have been in a loss position for less than twelve months or the loss is not material and were temporary in nature. We do not intend to sell the investments that are in an unrealized loss position before recovery of their amortized cost basis. Inventory Inventory consists of the following (in thousands): December 31, 2020 2019 Work-in-process $ 7,184 $ 8,191 Finished goods 5,864 3,355 Total $ 13,048 $ 11,546 Property, Plant, and Equipment, net Property, plant, and equipment, net consists of the following (in thousands): December 31, 2020 2019 Leasehold improvements $ 39,356 $ 16,871 Research and development equipment 28,394 17,881 Furniture and office equipment 5,051 3,496 Computer equipment and software 8,181 7,817 Land 11,722 — Construction-in-progress 17,649 24,271 Other 554 — Property, plant, and equipment, gross 110,907 70,336 Less accumulated depreciation ( 37,392 ) ( 25,988 ) Property, plant, and equipment, net $ 73,515 $ 44,348 Depreciation expense for the years ended December 31, 2020, 2019 and 2018 was $ 12.1 million, $ 8.3 million and $ 7.2 million respectively. Amortization of leasehold improvements and software is included in depreciation expense. The construction-in-progress balance primarily relates to the construction costs for the gene therapy manufacturing plant in Bedford, Massachusetts. F-18 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) Accrued Liabilities Accrued liabilities consists of the following (in thousands): December 31, 2020 2019 Research, clinical study, and manufacturing expenses $ 25,875 $ 22,894 Payroll and related expenses 58,176 41,324 Other 24,440 18,976 Total $ 108,491 $ 83,194 5. Intangible Assets, net Subsequent to the acquisition of Dimension Therapeutics, Inc. (Dimension) in November 2017, the Company recognized IPR&D assets of $ 129.0 million and a contract asset of $ 13.5 million. The estimated fair value of these intangible assets was measured using Level 3 inputs as of the acquisition date. IPR&D assets represent the fair value of acquired programs to develop an AAV gene therapy for OTC deficiency and to develop an AAV gene therapy for glycogen storage disease type Ia. The fair value of IPR&D assets acquired was determined based on the discounted present value of each research project’s projected cash flows using an income approach, including the application of probability factors related to the likelihood of success of the program reaching final development and commercialization. Additionally, the projections consider the relevant market sizes and growth factors, estimated future cash flows from product sales resulting from completed products and in-process projects and timing and costs to complete the in-process projects. The rates utilized to discount the net cash flows to their present value are commensurate with the stage of development of the projects and uncertainties in the economic estimates used in the projections. IPR&D assets are considered to be indefinite-life until the completion or abandonment of the associated research and development efforts. The contract asset represented the fair value of the agreement with Bayer HealthCare LLC to research, develop, and commercialize AAV gene therapy products for treatment of hemophilia A. The fair value of the contract asset was determined based on the discounted present value of the estimated net future income and was amortized to research and development expense over the research term which was completed in 2019. Subsequent to the FDA approval of Dojolvi for the treatment of LC-FAOD in June 2020, the Company recorded $ 2.3 million from contractual payments for the achievement of regulatory milestones to certain collaboration partners as intangible assets, which is being amortized over its useful life of seven years . The Company recorded research and development expense of $ 0.2 million, $ 0.2 million, and $ 12.3 million for the years ended December 31, 2020, 2019, and 2018, respectively, related to the amortization of the intangible assets. The Company tests the intangible assets for impairment annually during its fourth quarter. No impairment charges have been recognized on intangible assets. 6. Revenue The following table disaggregates total revenues from external customers by collaboration and license revenue and product sales (in thousands): Year Ended December 31, 2020 2019 2018 Collaboration and license revenue: Crysvita collaboration revenue in profit-share territory $ 128,597 $ 74,869 $ 15,334 Crysvita royalty revenue in European territory 1,498 8,120 2,892 Daiichi Sankyo 89,220 — — Bayer — 504 23,467 Total collaboration and license revenue 219,315 83,493 41,693 Product sales: Crysvita 10,350 4,286 644 Mepsevii 15,342 12,634 7,903 Dojolvi 13,028 3,301 1,255 Total product sales 38,720 20,221 9,802 Crysvita non-cash collaboration royalty revenue 12,995 — — Total revenues $ 271,030 $ 103,714 $ 51,495 F-19 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) The following table disaggregates total revenues based on geographic location (in thousands): Year Ended December 31, 2020 2019 2018 North America $ 237,666 $ 86,442 $ 45,339 Europe 21,318 12,085 5,293 All other 12,046 5,187 863 Total revenues $ 271,030 $ 103,714 $ 51,495 The following table presents the activity and ending balances for sales-related accruals and allowances (in thousands): December 31, 2020 2019 2018 Balance of product sales reserve at beginning of year $ 1,818 $ 1,240 $ 41 Provisions 5,763 3,846 2,148 Payments ( 2,785 ) ( 2,739 ) ( 949 ) Adjustments ( 883 ) ( 529 ) — Balance of product sales reserve at end of year $ 3,913 $ 1,818 $ 1,240 The following table presents changes in the contract assets (liabilities) for the years ended December 31, 2020 and 2019 (in thousands): December 31, 2020 2019 Balance of contract assets at beginning of period $ — $ 2,979 Additions ( 155,788 ) 504 Deductions 89,220 ( 3,483 ) Balance of contract liabilities at end of period, net $ ( 66,568 ) $ — See Note 7 for additional details on contract assets (liabilities) activities. The Company’s largest accounts receivable balance was from a collaboration partner and was 71 % and 87 % of the total accounts receivable balance as of December 31, 2020 and 2019, respectively. 7. License and Research Agreements Kyowa Kirin Co., Ltd. Collaboration and License Agreement In August 2013, the Company entered into a collaboration and license agreement with Kyowa Kirin Co., Ltd. (KKC or formerly Kyowa Hakko Kirin Co., Ltd. or KHK). Under the terms of this collaboration and license agreement, as amended, the Company and KKC collaborate on the development and commercialization of Crysvita in the field of orphan diseases in the United States and Canada, or the profit-share territory, and in the European Union, United Kingdom, and Switzerland, or the European territory, and the Company has the right to develop and commercialize such products in the field of orphan diseases in Mexico and Central and South America, or Latin America. Development Activities In the field of orphan diseases, and except for ongoing studies being conducted by KKC, the Company is the lead party for development activities in the profit-share territory and in the European territory until the applicable transition date; the Company is also the lead party for core development activities conducted in Japan and Korea, for which the core development plan is limited to clinical trials mutually agreed to by the Company and KKC. The Company shares the costs for development activities in the profit-share territory and the European territory conducted pursuant to the development plan before the applicable transition date equally with KKC. KKC is responsible for 100 % of the costs for development activities in Japan and Korea. In April 2023, which is the transition date for the profit-share territory, and on the applicable transition date for the European territory, KKC will become the lead party and be responsible for the costs of the development activities. However, the Company will continue to share the costs of the studies commenced prior to the applicable transition date equally with KKC. Crysvita was approved in the European Union and United Kingdom in February 2018 and was approved by the FDA in April 2018. The collaboration and license agreements are within the scope of ASC 808, which provides guidance on the presentation and disclosure of collaborative arrangements. F-20 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) Collaboration revenue related to sales in profit-share territory The Company and KKC share commercial responsibilities and profits in the profit-share territory until April 2023. Under the collaboration agreement, KKC manufactures and supplies Crysvita for commercial use in the profit-share territory and charges the Company the transfer price of 35 % of net sales through December 31, 2022, and 30 % thereafter. The remaining profit or loss after supply costs from commercializing products in the profit-share territory are shared between the Company and KKC on a 50 / 50 basis until April 2023. Thereafter, the Company will be entitled to receive a tiered double-digit revenue share in the mid-to-high 20 % range. As KKC is the principal in the sale transaction with the customer, the Company recognizes a pro-rata share of collaboration revenue, net of transfer pricing, in the period the sale occurs. The Company concluded that its portion of KKC’s sales in the profit-share territory is analogous to a royalty and therefore recorded its share as collaboration revenue, similar to a royalty. Royalty revenue related to sales in European territory KKC has the commercial responsibility for Crysvita in the European territory. In December 2019, the Company sold its right to receive royalty payments based on sales in the European territory to Royalty Pharma, effective January 1, 2020, as further described in “Note 10. Liability Related to the Sale of Future Royalties.” Prior to the Company’s sale of the royalty, the Company received a royalty of up to 10 % on net sales in the European territory, which was recognized as the underlying sales occur. Beginning in 2020, the Company records the royalty revenue as non-cash royalty revenues. During the year ended December 31 , 2020, there was a change in estimate of the revenue reserves related to sales made prior to January 1, 2020, as a result of which, the Company recorded $ 1.5 million as royalty revenue in European territory. The Company’s share of collaboration and royalty revenue related to Crysvita was as follows (in thousands): Year Ended December 31, 2020 2019 2018 Company's share of revenue in profit-share territory $ 128,597 $ 74,869 $ 15,334 Royalty revenue in European territory 1,498 8,120 2,892 Non-cash royalty revenue in European territory 12,995 — — Total $ 143,090 $ 82,989 $ 18,226 Product revenue related to sales in other territories The Company is responsible for commercializing Crysvita in Latin America and Turkey. The Company is considered the principal in these territories as the Company controls the product before it is transferred to the customer. Accordingly, the Company records revenue on a gross basis related to the sale of Crysvita once the product is delivered and the risk and title of the product is transferred to the distributor. The Company recorded product sales of $ 10.4 million, $ 4.3 million, and $ 0.6 million for the years ended December 31, 2020, 2019, and 2018, respectively, net of estimated product returns and other deductions. KKC has the option to assume responsibility for commercialization efforts in Turkey from the Company, after a certain minimum period. Under the collaboration agreement, KKC manufactures and supplies Crysvita, which is purchased by the Company for sales in the above territories, and is based on 35 % of the net sales through December 31, 2022 and 30 % thereafter. The Company also pays to KKC a low single-digit royalty on net sales in Latin America. Cost sharing payments Under the collaboration agreement, KKC and the Company share certain development and commercialization costs. As a result, the Company was reimbursed for these costs and operating expenses were reduced as follows (in thousands): Year Ended December 31, 2020 2019 2018 Research and development $ 21,476 $ 27,309 $ 32,240 Selling, general and administrative 25,186 21,828 14,228 Total $ 46,662 $ 49,137 $ 46,468 Collaboration receivable and payable The Company had accounts receivable from KKC in the amount of $ 16.4 million and $ 28.5 million from profit-share revenue and royalties and other receivables recorded in prepaid and other current assets of $ 9.6 million and $ 17.8 million and accrued liabilities of $ 2.4 million and $ 0.9 million from commercial and development activity reimbursements, as of December 31, 2020 and 2019, respectively. F-21 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) Saint Louis University License Agreement In November 2010, the Company entered into a license agreement with Saint Louis University (SLU). Under the terms of this license agreement, SLU granted the Company an exclusive worldwide license to make, have made, use, import, offer for sale, and sell therapeutics related to SLU’s beta-glucuronidase product for use in the treatment of human diseases. The Company made a milestone payment of $ 0.1 million upon approval of Mepsevii for treatment of MPS 7. The Company is required to pay to SLU a low single-digit royalty on net sales of the licensed products in any country or region, upon reaching a certain level of cumulative worldwide sales of the product. Baylor Research Institute License Agreement In September 2012, the Company entered into a license agreement with Baylor Research Institute (BRI). Under the terms of this license agreement, BRI exclusively licensed to the Company its territories for certain intellectual property related to Dojolvi (triheptanoin) for the treatment of LC-FAOD. For the years ended December 31, 2020 and 2019, the Company paid $ 2.0 million and $ 0.8 million, respectively, for the attainment of various development milestones related to the development of LC-FAOD. The Company may be obligated to make additional future payments of up to $ 2.5 million contingent upon attainment of various development milestones relating to the development of LC-FAOD and $ 7.5 million contingent upon attainment of various sales milestones. Additionally, the Company is paying BRI a mid-single-digit royalty on net sales of the licensed product in the licensed territories. REGENXBIO, Inc. The Company has a license agreement with REGENX, for an exclusive, sublicensable, worldwide commercial license under certain intellectual property for preclinical and clinical research and development, and commercialization of drug therapies using REGENX 's licensed patents for the treatment of hemophilia A, OTC deficiency, and GSD1a. The Company will pay an annual fee and certain milestone fees per disease indication, low to mid-single-digit royalty percentages on net sales of licensed products, and milestone and sublicense fees owed by REGENX to its licensors, contingent upon the attainment of certain development activities as outlined in the agreement. The Company also has an option and license agreement with REGENX under which the Company has an exclusive, sublicensable, worldwide license to make, have made, use, import, sell, and offer for sale licensed products to treat Wilson disease and CDKL5 deficiency. For each disease indication, the Company is obligated to pay an annual maintenance fee of $ 0.1 million and up to $ 9.0 million upon achievement of various milestones, as well as mid to high single-digit royalties on net sales of licensed products and mid-single-digit to low double-digit percentage sublicenses fees, if any. In March 2020, the Company entered into a license agreement with REGENX, for an exclusive, sublicensable, worldwide license to REGENX’s NAV AAV8 and AAV9 vectors for the development and commercialization of gene therapy treatments for a rare metabolic disorder. In return for these rights, the Company made an upfront payment of $ 7.0 million, which was recorded as an in-process research and development expense during the year ended December 31, 2020. The Company will pay certain annual fees of $ 0.1 million, milestone payments of up to $ 14.0 million, and royalties on any net sales of products incorporating the licensed intellectual property that range from a high single-digit to low double-digit royalty . Bayer HealthCare LLC The Company has an agreement with Bayer Healthcare LLC (Bayer) to research, develop and commercialize AAV gene therapy products for the treatment of hemophilia A (DTX 201). Under this agreement, Bayer has been granted an exclusive license to develop and commercialize one or more novel gene therapies for hemophilia A. The agreement requires that Bayer use commercially reasonable efforts to conduct and fund a proof-of-concept (POC) clinical trial and any subsequent clinical trials and commercialization of gene therapy products for treatment of hemophilia A. Bayer will have worldwide rights to commercialize the potential future product. Bayer is responsible for funding certain research and development services performed by the Company in the performance of its obligations under the annual research plan and budget. Under the terms of the agreement with Bayer, the Company is eligible to receive development and commercialization milestone payments of up to $ 232.0 million, as well as, royalty payments ranging in the high single-digit to low double-digit percentages, not exceeding the mid-teens, of net sales of licensed products. The Company achieved the first milestone in December 2017, the second milestone in April 2018, and has received $ 15.0 million for such milestones to date. As of the acquisition date of Dimension on November 7, 2017 , the Company valued the contract under ASC 805 and recorded an intangible asset of $ 13.5 million. The intangible asset was amortized to research and development expense over the research term and was completed in 2019 . The Company recorded research and development expense of $ 0.2 million and $ 12.3 million for the years ended December 31, 2019 and 2018, respectively, for the amortization of the intangible asset. F-22 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) The Company evaluated the agreement under ASC 606 and recorded a contract liability as of November 7, 2017 of $ 2.5 million. It was determined that the performance obligations under the agreement include (i) research and development services to be provided over the research term, (ii) a development and commercialization license, and (iii) the Company’s participation in certain committees. It was determined that these performance obligations are not distinct in the context of the contract and therefore are a single performance obligation. The Company calculated the transaction price by including the unconstrained milestones along with the estimated payments for research and development services and recorded $ 0.5 million and $ 23.5 million as collaboration and license revenue for the years ended December 31, 2019 and 2018, respectively, by measuring the progress toward complete satisfaction of the performance obligation using an input measure. University of Pennsylvania The Company has an agreement with University of Pennsylvania School of Medicine (Penn) to sponsor certain research related to liver and hemophilia gene therapy. In consideration for funding such research, Penn granted the Company an option to obtain a worldwide, non-exclusive or exclusive, royalty-bearing license, with the right to sublicense, under certain patent rights conceived, created or reduced to practice in the conduct of the research. The Company is required to reimburse Penn for filing, prosecuting and maintaining such patent rights unless and until the Company declines to exercise its option. Penn provides the Company with task-based, scientific reports of progress and results of the research, and granted the Company a royalty-free, nontransferable, non-exclusive right to copy and distribute any research reports furnished to the Company for any reasonable purpose, provided the results are not made publicly available until certain conditions are met, and the right to use, disclose and otherwise exploit the research results for any reasonable purpose, subject to similar restrictions on our public disclosure of the research results. Otherwise, the sponsored research agreement contains customary confidentiality provisions. The Company also has a research, collaboration, and license agreement with Penn, which provides the terms for the Company and Penn to collaborate with respect to the pre-clinical development of gene therapy products for the treatment of certain indications. Under the agreement, Penn granted the Company an exclusive, worldwide license to certain patent rights arising out of the research program, subject to certain retained rights, and a non-exclusive, worldwide license to certain Penn intellectual property, in each case to research, develop, make, have made, use, sell, offer for sale, commercialize and import licensed products in each indication for the term of the agreement. The Company will fund the cost of the research program in accordance with a mutually agreed-upon research budget and will be responsible for clinical development, manufacturing and commercialization of each indication. The Company may be obligated to make milestone payments of up to $ 5.0 million for each indication, if certain development milestones are achieved over time, as well as low to mid-single-digit royalties on net sales of each licensed product. The Company may also be obligated to make milestone payments of up to $ 25.0 million per approved product if certain commercial milestones are achieved. Arcturus Research Collaboration and License Agreement In October 2015, the Company entered into a Research Collaboration and License Agreement with Arcturus. The Company and Arcturus are collaborating on the research and development of therapies for select rare diseases. As consideration for entering into the arrangement, the Company paid Arcturus an upfront fee of $ 10.0 million. Arcturus was responsible for conducting certain research services, funded by the Company, and the Company was responsible for development and commercialization costs. Pursuant to the agreement, the Company incurred $ 0.4 million, $ 0.8 million, and $ 1.9 million for the years ended December 31, 2020, 2019, and 2018, respectively, in research and development expense for the funding of certain research services received from Arcturus. In June 2019, the Company entered into an Equity Purchase Agreement and an amendment to the Research Collaboration and License Agreement to expand the field of use and increase the number of disease targets to include mRNA, DNA and siRNA therapeutics for up to 12 rare diseases. Pursuant to the agreements, the Company paid $ 6.0 million in cash upfront to Arcturus and purchased 2,400,000 shares of Arcturus’ common stock at a stated value of $ 10.00 per share, resulting in a total of $ 30.0 million of consideration paid at the close of the transaction. As a result, the Company received expanded license rights; the Arcturus common stock; an option to purchase an additional 600,000 shares of Arcturus’ common stock at $ 16.00 per share. The Company also received the right to nominate one member to the Arcturus Board of Directors as well as one Board observer. In May 2020, the Company exercised the option to purchase 600,000 shares for a total purchase price of $ 9.6 million. Under the amended license agreement, certain early-stage milestone payments are reduced and the total potential milestone payments are increased due to the expanded number of targets. Arcturus is also entitled to reimbursement of related research expenses and royalties on commercial sales. The Company recorded the common stock investment at $ 13.9 million on the transaction date, which was based on the quoted market price on the closing date. The Company elected to apply the fair value option to account for the equity investment in Arcturus. The Company also accounted for the option to purchase additional shares of Arcturus common stock at fair value, which was recorded at $ 0.5 million on the transaction date based on the Black-Scholes option pricing method. The remaining $ 15.6 million of the total $ 30.0 million paid as consideration was attributed to the additional license rights obtained and was recorded as in-process research and development expense. In December 2020, the Company sold 800,000 shares of Arcturus’ common stock at a weighted-average price of $ 100.81 per share and net proceeds of $ 79.8 million. F-23 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) The changes in the fair value of the Company’s equity investment in Arcturus were as follows (in thousands): Arcturus common stock Option to purchase additional shares of Arcturus common stock Total Acquisition of equity investment in Arcturus in June 2019 $ 13,872 $ 467 $ 14,339 Change in fair value 12,216 1,197 13,413 December 31, 2019 26,088 1,664 27,752 Change in fair value 113,978 23,948 137,926 Transfer of value upon option exercise 35,212 ( 25,612 ) 9,600 Sale of shares ( 79,842 ) — ( 79,842 ) December 31, 2020 $ 95,436 $ — $ 95,436 GeneTx In August 2019, the Company entered into a Program Agreement and a Unitholder Option Agreement with GeneTx to collaborate on the development of GeneTx’s GTX-102, an ASO for the treatment of Angelman syndrome. Pursuant to the terms of the Unitholder Option Agreement, the Company made an upfront payment of $ 20.0 million for an exclusive option to acquire GeneTx, which was exercisable any time prior to 30 days following FDA acceptance of the IND for GTX-102. Pursuant to the agreement, upon acceptance of the IND, which occurred in January 2020, the Company elected to extend the option period by paying an option extension payment of $ 25.0 million (option extension premium) during the year ended December 31, 2020. The Company has a right to acquire GeneTx for a payment of $ 125.0 million, at any time, until the earlier of 30 months from the first dosing of a patient in a planned Phase 1/2 study (subject to extensions) or 90 days after results are available from that study. This exclusive option to acquire GeneTx can be extended under certain circumstances, by up to four additional three-month periods, by paying an additional extension fee for each three-month period. During the exclusive option period, GeneTx is responsible for conducting the program based on the development plan agreed between the parties and, subject to the terms in the Program Agreement, has the decision-making authority on all matters in connection with the research, development, manufacturing and regulatory activities with respect to the Program. The Company will provide support, at its discretion, including strategic guidance and clinical expertise. The Company and GeneTx will collaborate on the management of the Phase 1/2 study in patients with Angelman syndrome. If the Company acquires GeneTx, the Company will then be responsible for all development and commercialization activities from the date of acquisition. The Company would also be required to make payments upon achievement of certain development and commercial milestones, as well as royalties, depending upon the success of the program. Although GeneTx is a variable interest entity, the Company is not the primary beneficiary as it currently does not have the power to direct the activities that would most significantly impact the economic performance of GeneTx. Prior to product regulatory approval, all consideration paid to GeneTx represents rights to potential future benefits associated with GeneTx’s in-process research and development activities, which have not reached technological feasibility and have no alternative future use. Accordingly, for the years ended December 31, 2020 and 2019, the Company recorded the option extension payment of $ 25.0 million and $ 20.0 million upfront payment as an in-process research and development expense, respectively. Daiichi Sankyo In March 2020, the Company entered into a License and Technology Access Agreement (the License Agreement) with Daiichi Sankyo Co., Ltd. (Daiichi Sankyo). Pursuant to the License Agreement, the Company granted Daiichi Sankyo a non-exclusive license to intellectual property, including know-how and patent applications, with respect to its HeLa producer cell line (PCL) and HEK293 transient transfection manufacturing technology platforms for AAV-based gene therapy products. The Company retains the exclusive right to use the manufacturing technology for its current target indications and additional indications identified now and in the future. The Company will provide certain technical assistance and technology transfer services during the technology transfer period of three years to enable Daiichi Sankyo to use the technologies for its internal gene therapy programs. Daiichi Sankyo has an option to extend the technology transfer period including know-how improvements by two additional one-year periods by paying a fixed amount for each additional year. Daiichi Sankyo will be responsible for the manufacturing, development, and commercialization of products manufactured with the licensed technology; however, the Company has the option to co-develop and co-commercialize rare disease products at the IND stage. Ultragenyx may also provide strategic consultation to Daiichi Sankyo on the development of both AAV-based gene therapy products and other products for rare diseases. F-24 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) Under the terms of the License Agreement, Daiichi Sankyo made an upfront payment of $ 125.0 million and will pay an additional $ 25.0 million upon completion of the technology transfer of the HeLa PCL and HEK293 platforms, as well as single-digit royalties on net sales of products manufactured in either system. Daiichi Sankyo will reimburse the Company for all costs associated with the transfer of the manufacturing technology. The Company also entered into a Stock Purchase Agreement with Daiichi Sankyo, pursuant to which Daiichi Sankyo purchased 1,243,913 shares of the Company’s common stock in exchange for $ 75.0 million in cash during the first quarter of 2020. The fair market value of the common stock issued to Daiichi Sankyo was $ 55.3 million based on the stock price of $ 44.43 per share on the date of issuance, resulting in a $ 19.7 million premium on the Stock Purchase Agreement . Daiichi Sankyo is also subject to a three-year standstill and restrictions on sale of the shares (subject to customary exceptions or release). In June 2020, the Company executed a subsequent license agreement (the Sublicense Agreement) with Daiichi Sankyo for transfer of certain technology in consideration for an upfront payment of $ 8.0 million and annual maintenance fees, milestone payments, and royalties on any net sales of products incorporating the licensed intellectual property. The License Agreement, the Sublicense Agreement, and the Stock Purchase Agreement are being accounted for as one arrangement because they were entered into at or near the same time and negotiated in contemplation of one another. The Company evaluated the License Agreement and the Sublicense Agreement under ASC 606 and determined that the performance obligations under the agreements are (i) intellectual property with respect to its HeLa PCL and HEK293 transient transfection manufacturing technology platforms together with the initial technical assistance and technology transfer services, which are expected to be completed in the fourth quarter of 2021, and (ii) the transfer of any know-how and improvements after the completion of the initial technology transfer through the end of the three year technology transfer period ending March 2023. The Company determined that the total transaction price of the License Agreement was $ 183.7 million which was comprised of the $ 19.7 million premium from the Stock Purchase Agreement , the $ 125.0 million upfront payment, the $ 25.0 million in unconstrained milestone payments, $ 8.0 million from the Sublicense Agreement, and the $ 6.0 million estimated reimbursement amount for delivering the license and technology services. The Company allocated the total transaction price to the two performance obligations on a relative stand-alone selling price basis. Revenue allocated to the intellectual property and the technology transfer services will be recognized over an initial period which is estimated to end in the fourth quarter of 2021, measuring the progress toward complete satisfaction of the individual performance obligation using an input measure. Revenue for know-how and improvements after the completion of technology transfer will be recognized on a straight-line basis over the remaining technology transfer period, which ends in March 2023, as it is expected that Daiichi Sankyo will receive and consume the benefits consistently throughout the period. The estimated period to complete the technology transfer services and the related milestones payments, if any, are subject to revised estimates which could be impacted by limitations or delays from the COVID-19 pandemic, successful scale-up of the manufacturing, and other changes that may impact timing. Royalties from commercial sales will be accounted for as revenue upon achievement of such sales, assuming all other revenue recognition criteria are met. For the year ended December 31, 2020, the Company recognized $ 89.2 million in revenue related to this arrangement. Accordingly, the Company had recorded $ 66.6 million as contract liabilities, net, as of December 31 , 2020. The Company recorded an accounts receivable related to the License Agreement of $ 1.2 million as of December 31, 2020. Solid Biosciences, Inc. In October 2020, the Company entered into a strategic Collaboration and License Agreement with Solid Biosciences Inc., or Solid, and received an exclusive license for any pharmaceutical product that expresses Solid’s proprietary microdystrophin construct from AAV8 and variants thereof in clade E for use in the treatment of Duchenne muscular dystrophy and other diseases resulting from lack of functional dystrophin, including Becker muscular dystrophy. The Company will collaborate to develop products that combine Solid’s differentiated microdystrophin construct, the Company’s HeLa PCL manufacturing platform, and the Company’s AAV8 variants. Solid will also provide development support and was granted an exclusive option to co-invest in products the Company develops for profit share participation in certain territories. On a product-by-product basis, the Company may be obligated to make development milestone payments of up to $ 25.0 million, regulatory milestone payments of up to $ 65.0 million, and commercial milestone payments of up to $ 165.0 million, if such milestones are achieved, as well as royalties on any net sales of products incorporating the licensed intellectual property that range from a low to mid-double-digit percentage. The royalty rate changes to mid to high double-digit percentage if Solid decides to co-invest in the product. F-25 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) The Company also entered into a Stock Purchase Agreement and the Investor Agreement with Solid, pursuant to which, the Company purchased 7,825,797 shares of Solid’s common stock for an aggregate purchase price of $ 40.0 million. Subject to the terms of the Investor Agreement, the Company is restricted from selling, transferring or otherwise disposing of the shares without the prior approval of Solid until the earlier of (i) 18 months following the closing of the transaction, (ii) the termination of the Collaboration and License Agreement and (iii) certain other specified events. The Company also agreed to customary standstill restrictions in accordance with the terms of the Investor Agreement until the earlier of (a) 24 months after the closing of the transaction and (b) certain specified events. The Company’s investment in Solid is being accounted at fair value, as the fair value is readily determinable. The Company recorded the common stock investment at $ 26.8 million on the transaction date, which was based on the quoted market price on the closing date. Although Solid is a variable interest entity, the Company is not the primary beneficiary as it does not have the power to direct the activities that would most significantly impact the economic performance of Solid. Prior to the achievement of certain development milestones, all consideration paid to Solid represents rights to potential future benefits associated with Solid’s in-process research and development activities, which have not reached technological feasibility and have no alternative future use. Accordingly, the remaining $ 13.2 million of the total $ 40.0 million paid as consideration was attributed to the license rights obtained and was recorded as in-process research and development expense during the year ended December 31, 2020. The changes in the fair value of the Company’s investment in Solid’s common stock were as follows (in thousands): Solid common stock Acquisition of investment in Solid common stock in October 2020 $ 26,843 Change in fair value 32,477 December 31, 2020 $ 59,320 8. Leases As described in “Note 2. Summary of Significant Accounting Policies”, the Company adopted Topic 842 as of January 1, 2019. Prior period amounts have not been adjusted and continue to be reported in accordance with historic accounting under Topic 840 . The Company leases office space and research, testing and manufacturing laboratory space in various facilities in Novato and Brisbane, California, in Cambridge and Woburn, Massachusetts, and in certain foreign countries, under operating agreements expiring at various dates through 2028 . Certain lease agreements include options for the Company to extend the lease for multiple renewal periods and also provide for annual minimum increases in rent, usually based on a consumer price index or annual minimum increases. None of these optional periods have been considered in the determination of the right-of-use lease asset or the lease liability for the leases as the Company did not consider it reasonably certain that it would exercise any such options. The Company recognizes lease expense on a straight-line basis over the non-cancelable term of its operating leases. The variable lease expense primarily consists of common area maintenance and other operating costs. The Company recognizes rent expense on a straight-line basis over the noncancelable term of its operating leases. Prior to adoption of Topic 842 , under Topic 840 , rent expense was $ 6.4 million during the year ended December 31, 2018. The components of lease expense were as follows (in thousands): Year Ended December 31, 2020 2019 Operating lease expense $ 10,164 $ 9,163 Variable lease expense 3,298 2,779 Financing: Amortization 158 — Interest expense 40 — Total $ 13,660 $ 11,942 Cash paid for amounts included in the measurement of operating lease liabilities for the year ended December 31, 2020 was $ 10.3 million and was included in net cash used in operating activities in the Consolidated Statements of Cash Flows. F-26 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) Future minimum lease payments under non-cancellable leases as of December 31, 2020 were as follows (in thousands): Year Ending December 31, Operating Financing Total 2021 $ 11,418 $ 513 $ 11,931 2022 11,904 495 12,399 2023 12,148 237 12,385 2024 10,319 — 10,319 2025 6,247 — 6,247 Thereafter 3,456 — 3,456 Total future lease payments 55,492 1,245 56,737 Less: Amount representing interest ( 8,426 ) ( 84 ) ( 8,510 ) Present value of future lease payments 47,066 1,161 48,227 Less: Lease liabilities, current ( 8,516 ) ( 460 ) ( 8,976 ) Lease liabilities, non-current $ 38,550 $ 701 $ 39,251 Lease liabilities are based on the net present value of the remaining lease payments over the remaining lease term. As of December 31, 2020, the weighted-average remaining operating and financing lease terms were 4.82 years and 4.51 years, respectively, and the weighted-average discount rates used to determine the lease liability for operating and financing leases were 6.70 % and 5.58 %, respectively. 9. Gain from Sale of Priority Review Vouchers In January 2018, the Company completed the sale of a Rare Pediatric Disease Priority Review Voucher (PRV) it received in connection with the approval of Mepsevii for $ 130.0 million. In June 2018, the Company also completed the sale of the PRV it received in connection with the approval of Crysvita for $ 80.6 million, net, which was shared equally with KKC. As the PRVs did not have a carrying value, the gain recognized was equal to the net proceeds received. The Company recorded $ 170.3 million for its portion of the net proceeds for the year ended December 31, 2018, as a gain from the sale of the priority review vouchers. 10. Liability Related to the Sale of Future Royalties In December 2019, the Company entered into a Royalty Purchase Agreement with RPI and RPI paid $ 320.0 million to the Company in consideration for the right to receive royalty payments effective January 1, 2020, arising from the net sales of Crysvita in the European Union, the United Kingdom, and Switzerland under the terms of the Company’s Collaboration and License Agreement with KKC dated August 29, 2013, as amended. The agreement with RPI will automatically terminate, and the payment of royalties to RPI will cease, in the event aggregate royalty payments received by RPI are equal to or greater than $ 608.0 million prior to December 31, 2030, or in the event aggregate royalty payments received by RPI are less than $ 608.0 million prior to December 31, 2030, when aggregate royalty payments received by RPI are equal to $ 800.0 million. Proceeds from the transaction were recorded as a liability (liability related to sale of future royalties on the Consolidated Balance Sheets). The Company amortizes $ 320.0 million, net of transaction cost of $ 5.8 million using the effective interest method over the estimated life of the arrangement. In order to determine the amortization of the liability, the Company is required to estimate the total amount of future royalty payments to be received by the Company and paid to RPI, subject to the capped amount, over the life of the arrangement. The excess of future estimated royalty payments (subject to the capped amount), over the $ 314.2 million of net proceeds, is recorded as non-cash interest expense over the life of the arrangement. Consequently, the Company estimates an imputed interest on the unamortized portion of the liability and records interest expense relating to the transaction. The Company records the royalty revenue arising from the net sales of Crysvita in the applicable European territories as non-cash royalty revenue in the Consolidated Statements of Operations over the term of the arrangement. The Company periodically assesses the expected royalty payments using a combination of historical results, internal projections and forecasts from external sources. To the extent such payments are greater or less than the Company’s initial estimates or the timing of such payments is materially different than its original estimates, the Company will prospectively adjust the amortization of the liability and the effective interest rate. For the three months ended December 31, 2020, the effective annual interest rate was approximately 9.8 %. There are a number of factors that could materially affect the amount and timing of royalty payments from KKC in the applicable European territories, most of which are not within the Company’s control. Such factors include, but are not limited to, the success of KKC’s sales and promotion of Crysvita, changing standards of care, delays or disruptions related to the COVID-19 pandemic, the introduction of competing products, pricing for reimbursement in various European territories, manufacturing or other delays, intellectual property matters, adverse events that result in governmental health authority imposed restrictions on the use of Crysvita, significant changes in foreign exchange rates as the royalty payments are made in U.S. dollars (USD) while significant portions of the underlying European sales of Crysvita are made in currencies other than USD, and other events or circumstances that could result in reduced royalty payments from European sales of Crysvita, all of which would result in a reduction of non-cash royalty F-27 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) revenue and the non-cash interest expense over the life of the arrangement. Conversely, if sales of Crysvita in Europe are more than expected, the non-cash royalty revenue and the non-cash interest expense recorded by the Company would be greater over the term of the arrangement. The following table shows the activity within the liability account (in thousands): Liability related to the sale of future royalties Proceeds from sale of future royalties in December 2019 $ 314,234 Non-cash interest expense 1,135 December 31, 2019 315,369 Non-cash collaboration royalty revenue ( 12,995 ) Non-cash interest expense 33,291 December 31, 2020 $ 335,665 11. Equity At-the-Market Offerings In July 2017, the Company entered into an additional ATM sales agreement with Cowen whereby the Company could sell up to $ 150.0 million in aggregate proceeds of common stock from time to time, through Cowen as its sales agent. During the years ended December 31, 2020, 2019, and 2018, the Company sold 283,333 , 468,685 , and 640,257 shares of common stock, respectively, resulting in net proceeds of approximately $ 20.4 million, $ 24.8 million, and $ 38.1 million, respectively, after commissions and other offering costs. As of June 30 , 2020 , the Company completed the sale of all available amounts under the ATM facility. Underwritten Public Offering In January 2018, the Company completed an underwritten public offering in which 5,043,860 shares of common stock were sold, which includes 657,895 shares purchased by the underwriters pursuant to an option granted to them in connection with the offering, at a public offering price of $ 57.00 per share. The total proceeds that the Company received from the offering were approximately $ 271.0 million, net of underwriting discounts and commissions. In February 2019, the Company completed an underwritten public offering in which 5,833,333 shares of common stock were sold, which included 760,869 shares purchased by the underwriters pursuant to an option granted to them in connection with the offering, at a public offering price of $ 60.00 per share. The total proceeds that the Company received from the offering were approximately $ 330.4 million, net of underwriting discounts and commissions. In October 2020, the Company completed an underwritten public offering in which 5,111,110 shares of common stock were sold, which included 666,666 shares purchased by the underwriters pursuant to an option granted to them in connection with the offering, at a public offering price of $ 90.00 per share. The total proceeds that the Company received from the offering were approximately $ 435.6 million, net of underwriting discounts and commissions. Common Stock Warrants As of December 31, 2019 and 2018, there was an aggregate of 149,700 of common stock warrants outstanding with exercise price of $ 3.01 and expiration dates in 2020 and 2021 . In March 2020, all of the outstanding common stock warrants were exercised . F-28 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) 12. Stock-Based Awards Equity Plan Awards In 2011, the Company adopted the 2011 Equity Incentive Plan (the 2011 Plan). The 2011 Plan provides for the granting of stock-based awards to employees, directors, and consultants under terms and provisions established by the board of directors. In 2014, the Company adopted the 2014 Incentive Plan (the 2014 Plan). The 2014 Plan had 2,250,000 shares of common stock available for future issuance at the time of its inception, which included 655,038 shares available under the 2011 Plan, which were transferred to the 2014 Plan upon adoption. No further grants subsequent to the IPO were made under the 2011 Plan. The 2014 Plan provides for automatic annual increases in shares available for grant, beginning on January 1, 2015 through January 1, 2024 . Under the terms of the 2014 Plan, awards may be granted at an exercise price not less than fair market value. For employees holding more than 10 % of the voting rights of all classes of stock, the exercise prices for awards must be at least 110 % of fair market of the common stock on the grant date, as determined by the board of directors. The term of an award granted under the 2014 Plan may not exceed ten years . Typically, the vesting schedule for option grants to the employees provides that 1/4 of the grant vests upon the first anniversary of the date of grant, with the remainder of the shares vesting monthly thereafter at a rate of 1/48 of the total shares subject to the option. Typically, the vesting schedule for RSU grants provides that 1/4 of the grant vests upon the annual anniversary of the date of grant over the period of four years . As part of the acquisition of Dimension, the Company assumed an equivalent 639,897 options to purchase shares of common stock of the Company from the equity plans of Dimension. No further grants subsequent to the acquisition are available under these equity plans. As of December 31, 2020, an aggregate of 10,878,499 shares of common stock have been authorized for issuance under the 2011 Plan, the 2014 Plan, and the assumed equity awards from the Dimension plans. Stock Option Activity The following table summarizes activity under the Company’s stock option plans, including the 2011 Plan, the 2014 Plan, the assumed equity awards from the Dimension plans and related information: Options Outstanding Number of Options Weighted- Average Exercise Price Weighted-Average Remaining Contractual Term (Years) Aggregate Intrinsic Value (In thousands) Outstanding — December 31, 2017 5,399,410 $ 62.75 7.40 $ 37,687 Options granted 1,479,451 55.54 Options exercised ( 713,263 ) 36.21 Options cancelled ( 812,474 ) 74.80 Outstanding — December 31, 2018 5,353,124 $ 62.46 7.22 $ 23,243 Options granted 1,762,075 63.03 Options exercised ( 235,678 ) 32.87 Options cancelled ( 766,457 ) 72.48 Outstanding — December 31, 2019 6,113,064 $ 62.51 7.00 $ 18,989 Options granted 1,849,106 62.51 Options exercised ( 1,505,486 ) 58.51 Options cancelled ( 452,081 ) 69.38 Outstanding — December 31, 2020 6,004,603 $ 62.99 7.21 $ 453,253 Vested and exercisable — December 31, 2020 2,989,891 $ 64.35 5.68 $ 221,488 Vested and expected to vest — December 31, 2020 5,699,638 $ 62.99 7.12 $ 430,243 The aggregate intrinsic values of options outstanding, vested and exercisable, and vested and expected to vest were calculated as the difference between the exercise price of the options and the fair value of the Company’s common stock. The total intrinsic value of options exercised during the years ended December 31, 2020, 2019, and 2018 was $ 56.9 million, $ 6.5 million and $ 22.9 million, respectively. Cash received from the exercise of options was $ 88.1 million, $ 7.7 million, and $ 25.8 million as of December 31, 2020, 2019, and 2018, respectively. F-29 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) The weighted-average estimated fair value of stock options granted was $ 35.22 , $ 37.15 and $ 33.32 per share of the Company’s common stock during the years ended December 31, 2020, 2019, and 2018, respectively. The total estimated grant date fair value of options vested during the years ended December 31, 2020, 2019, and 2018 was $ 45.4 million, $ 45.3 million, and $ 51.7 million, respectively. Restricted Stock Units The following table summarizes activity under the Company’s Restricted Stock Units (RSUs) from the 2014 Plan and related information: RSUs Outstanding Number of Shares Weighted- Average Grant Date Fair Value Unvested — December 31, 2017 821,560 $ 70.71 RSUs granted 555,905 56.01 RSUs vested ( 235,913 ) 71.01 RSUs cancelled ( 187,475 ) 65.37 Unvested — December 31, 2018 954,077 $ 63.12 RSUs granted 863,065 62.78 RSUs vested ( 313,682 ) 66.25 RSUs cancelled ( 205,310 ) 64.28 Unvested — December 31, 2019 1,298,150 $ 61.96 RSUs granted 967,310 64.36 RSUs vested ( 434,153 ) 62.65 RSUs cancelled ( 150,140 ) 61.42 Unvested — December 31, 2020 1,681,167 $ 63.21 The fair value of the RSUs is determined on the grant date based on the fair value of the Company’s common stock. The fair value of the RSUs is recognized as expense ratably over the vesting period of one to four years . The total grant date fair value of the RSUs vested during the years ended December 31, 2020, 2019, and 2018 was $ 27.2 million, $ 20.8 million, and $ 16.8 million, respectively. The aggregate intrinsic value of the shares of the RSUs vested during the years ended December 31, 2020, 2019, and 2018 was $ 29.5 million, $ 18.4 million, and $ 14.9 million, respectively. Performance Stock Units In December 2017, the Company began granting performance stock units (PSUs) to certain employees. The following table summarizes activity under the Company’s PSUs from the 2014 Plan and related information: PSUs Outstanding Number of Shares Weighted- Average Grant Date Fair Value Unvested — December 31, 2017 508,850 $ 48.03 PSUs granted 71,725 59.67 PSUs cancelled ( 97,375 ) 48.58 Unvested — December 31, 2018 483,200 $ 49.65 PSUs granted 61,500 67.31 PSUs vested ( 65,643 ) 48.03 PSUs cancelled ( 79,517 ) 50.01 Unvested — December 31, 2019 399,540 $ 52.56 PSUs granted 47,600 56.08 PSUs vested ( 200,867 ) 51.21 PSUs cancelled ( 33,707 ) 52.48 Unvested — December 31, 2020 212,566 $ 54.64 F-30 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) The fair value of the PSUs is determined on the grant date based on the fair value of the Company’s common stock. PSUs are subject to vest only if certain specified criteria are achieved and the employees’ continued service with the Company after achievement of the specified criteria. For certain PSUs, the number of PSUs that may vest are also subject to the achievement of certain specified criteria. As of December 31, 2020, the specified criteria were deemed probable of achievement or already achieved. Stock-based compensation for these PSUs is recognized over the service period beginning in the period the Company determines it is probable that the performance criteria will be achieved. The total grant date fair value of the PSUs vested during the years ended December 31, 2020 and 2019 was $ 10.3 million and $ 3.2 million, respectively, with an aggregate intrinsic value of the shares of $ 14.4 million and $ 4.2 million, respectively. Employee Stock Purchase Plan In January 2014, the Company adopted the 2014 Employee Stock Purchase Plan (ESPP) and reserved a total of 600,000 shares of common stock for issuance under the ESPP. The ESPP provides for automatic annual increases in shares available for grant, beginning on January 1, 2015 through January 1, 2024 . Eligible employees may purchase common stock at 85 % of the lesser of the fair market value of common stock on the offering date or the purchase date with a six-month look-back feature. ESPP purchases are settled with common stock from the ESPP’s previously authorized and available pool of shares. During the year ended December 31, 2020, the Company issued 112,857 shares of common stock under the ESPP. As of December 31, 2020, an aggregate of 3,248,367 shares of common stock have been authorized for future issuance on the ESPP. Stock-Based Compensation Expense Total stock-based compensation recognized was as follows (in thousands): Year Ended December 31, 2020 2019 2018 Cost of sales $ 827 $ 1,084 $ 146 Research and development 47,949 44,205 45,572 Selling, general and administrative 36,959 36,706 34,389 Total stock-based compensation expense $ 85,735 $ 81,995 $ 80,107 Stock-based compensation of $ 1.2 million, $ 1.4 million, and $ 1.1 million was capitalized into inventory for the years ended December 31, 2020, 2019, and 2018, respectively. Capitalized stock-based compensation is recognized as cost of sales when the related product is sold. As of December 31, 2020, the total unrecognized compensation expense related to unvested equity awards, net of estimated forfeitures, was $ 155.6 million, which the Company expects to recognize over an estimated weighted-average period of 2.48 years. In determining the estimated fair value of the stock options and ESPP, the Company uses the Black-Scholes option-pricing model and assumptions discussed below. Each of these inputs is subjective and generally requires significant judgment to determine. Expected Term —The Company’s expected term represents the period that the Company’s stock-based awards are expected to be outstanding and is determined using the simplified method (based on the mid-point between the vesting date and the end of the contractual term). Expected Volatility —The Company’s expected volatility is based on historical volatility over the look-back period corresponding to the expected term. Risk-Free Interest Rate —The risk-free interest rate is based on the U.S. Treasury zero coupon issues in effect at the time of grant for periods corresponding with the expected term of option. Expected Dividend —The Company has never paid dividends on its common stock and has no plans to pay dividends on its common stock. Therefore, the Company used an expected dividend yield of zero. The fair value of stock option awards granted was estimated at the date of grant using a Black-Scholes option-pricing model with the following weighted-average assumptions: Year Ended December 31, 2020 2019 2018 Expected term (years) 6.20 6.22 6.23 Expected volatility 61 % 61 % 62 % Risk-free interest rate 0.8 % 2.4 % 2.7 % Expected dividend rate 0.0 % 0.0 % 0.0 % F-31 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) 13. Defined Contribution Plan The Company sponsors a retirement plan in which substantially all of its full-time employees in the United States and certain other foreign countries are eligible to participate. Eligible participants may contribute a percentage of their annual compensation to this plan, subject to statutory limitations. The Company recorded $ 4.3 million, $ 3.6 million, and $ 2.9 million as contribution expenses for the years ended December 31, 2020, 2019, and 2018, respectively. 14. Income Taxes The components of the Company’s loss before income taxes were as follows (in thousands): Year Ended December 31, 2020 2019 2018 Domestic $ 189,449 $ 399,709 $ 205,440 Foreign ( 4,090 ) ( 265 ) ( 8,343 ) Total loss before income taxes $ 185,359 $ 399,444 $ 197,097 The components of the Company’s income tax provision were as follows (in thousands): Year Ended December 31, 2020 2019 2018 Current provision for income taxes: Federal $ — $ — $ — State 15 51 14 International 1,192 1,092 500 Total current tax provision 1,207 1,143 514 Deferred tax provision: Federal — — — State — 2,140 — International — — — Total deferred tax provision — 2,140 — Total provision for income taxes $ 1,207 $ 3,283 $ 514 The Company has incurred net operating losses since inception. The Company has not reflected any benefit of such net operating loss carryforwards in the accompanying financial statements. The Company has established a full valuation allowance against its deferred tax assets due to the uncertainty surrounding the realization of such assets. The effective tax rate of our provision for income taxes differs from the federal statutory rate as follows: Year Ended December 31, 2020 2019 2018 Federal statutory income tax rate 21.0 % 21.0 % 21.0 % State income taxes, net of federal benefit — ( 0.5 ) — Federal tax credits 13.7 5.2 9.5 Other ( 0.5 ) ( 0.2 ) ( 0.2 ) Premium on equity issuance 2.2 — — Nondeductible permanent items ( 0.9 ) ( 0.4 ) ( 0.8 ) Stock-based compensation 0.9 ( 1.0 ) ( 0.8 ) Uncertain tax positions ( 2.7 ) ( 1.0 ) ( 1.9 ) Change in valuation allowance ( 33.9 ) ( 23.6 ) ( 26.8 ) Foreign rate differential ( 0.5 ) ( 0.3 ) ( 0.3 ) Provision for income taxes ( 0.7 ) % ( 0.8 ) % ( 0.3 ) % F-32 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) The tax effect of temporary differences that give rise to significant portions of the deferred tax assets is presented below (in thousands): Year Ended December 31, 2020 2019 Deferred tax assets: Loss carryforwards $ 222,902 $ 185,892 Tax credits 184,961 158,791 Stock options 39,154 40,676 Accruals and reserves 24,922 19,622 Fixed assets and intangibles 7,242 3,870 Liability related to sale of future royalties 86,664 81,424 Other 28,642 4,183 Gross deferred tax assets 594,487 494,458 Valuation allowance ( 561,139 ) ( 486,796 ) Total deferred tax assets 33,348 7,662 Deferred tax liabilities: In-process research and development ( 33,306 ) ( 33,306 ) Basis difference in equity investments ( 23,019 ) — Right-of-use lease assets ( 10,329 ) ( 7,662 ) Gross deferred tax liabilities ( 66,654 ) ( 40,968 ) Net deferred tax liabilities $ ( 33,306 ) $ ( 33,306 ) As of December 31, 2020 and 2019, the Company had approximately $ 750.2 million and $ 549.9 million of federal net operating loss carryforwards available to reduce future taxable income that will begin to expire in 2032 . As of December 31, 2020 and 2019, the Company had approximately $ 616.8 million and $ 520.2 million of state net operating loss carryforwards available to reduce future taxable income that will begin to expire in 2031 . As of December 31, 2020 and 2019, the Company had federal research tax credit carryforwards of $ 17.7 million and $ 11.7 million available to reduce future tax liabilities that will begin to expire in 2030 . As of December 31, 2020 and 2019, the Company had state research credit carryforwards of $ 34.5 million and $ 25.5 million available to reduce future tax liabilities that will be carried forward indefinitely. As of December 31, 2020 and 2019, the Company had federal Orphan Drug Credits of $ 179.8 million and $ 160.0 million available to reduce future tax liabilities that will begin to expire in 2031 . The Company’s ability to use net operating loss and tax credit carryforwards to reduce future taxable income and liabilities may be subject to annual limitations pursuant to Internal Revenue Code Sections 382 and 383 as a result of ownership changes in the past and future. As a result of ownership changes in 2012 and 2011, $ 3.6 million of federal net operating loss carryforwards, $ 3.6 million of state net operating loss carryforwards, and $ 0.2 million of federal tax credits are permanently limited. Deferred tax assets for net operating losses and tax credits have been reduced and a corresponding adjustment to the valuation allowance has been recorded. Based upon information available through the reporting date, the Company is not aware of any other changes in ownership that would result in material limitations under Section 382 as of December 31, 2020. The valuation allowance increased by $ 74.3 million and $ 125.1 million during the year ended December 31, 2020 and 2019, respectively. The Company recorded unrecognized tax benefits for uncertainties in income taxes. A reconciliation of the Company’s unrecognized tax benefits follows (in thousands): December 31, 2020 2019 2018 Balance at beginning of year $ 39,954 $ 33,727 $ 28,377 Additions based on tax positions related to current year 6,950 5,575 4,750 Additions for tax positions of prior years 382 652 600 Reductions for tax positions of prior years ( 624 ) — — Balance at end of year $ 46,662 $ 39,954 $ 33,727 F-33 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) The entire amount of the unrecognized tax benefits would not impact the Company’s effective tax rate if recognized. The Company has elected to include interest and penalties as a component of tax expense. During the years ended December 31, 2020 and 2019, the Company did no t recognize accrued interest and penalties related to unrecognized tax benefits. The Company does not anticipate that the amount of existing unrecognized tax benefits will significantly increase or decrease during the next year. It is the Company’s intention to reinvest the earnings of its non-U.S. subsidiaries in their operations. As of December 31, 2020, the Company had not made a provision for any incremental foreign withholding taxes on approximately $ 6.3 million of the excess of the amount of net income for financial reporting over the tax basis of investments in foreign subsidiaries that are essentially permanent in duration. If these earnings were repatriated to the U.S., the deferred tax liability associated with these temporary differences would result in a nominal amount of withholding taxes. The Company files income tax returns in the U.S. federal, California, and other state tax jurisdictions. The federal and state income tax returns from inception to December 31, 2020 remain subject to examination. 15. Commitments and Contingencies The Company has various manufacturing, clinical, research, and other contracts with vendors in the conduct of the normal course of its business. Other than as noted below, contracts are terminable, with varying provisions regarding termination. If a contract with a specific vendor were to be terminated, the Company would only be obligated for the products or services that the Company had received at the time the termination became effective. As of December 31, 2020, the aggregate payments under contractually binding manufacturing and service agreements are as follows (in thousands): Year Ended December 31, 2021 2022 Manufacturing and Services $ 4,330 $ 472 Land and Building Construction 26,078 382 Total $ 30,408 $ 854 See “Note 8. Leases” for lease commitments. Contingencies While there are no material legal proceedings the Company is aware of, the Company may become party to various claims and complaints arising in the ordinary course of business. Management does not believe that any ultimate liability resulting from any of these claims will have a material adverse effect on its results of operations, financial position, or liquidity. However, management cannot give any assurance regarding the ultimate outcome of these claims, and their resolution could be material to operating results for any particular period, depending upon the level of income for the period. Guarantees and Indemnifications The Company indemnifies each of its directors and officers for certain events or occurrences, subject to certain limits, while the director is or was serving at the Company’s request in such capacity, as permitted under Delaware law and in accordance with its certificate of incorporation and bylaws. The term of the indemnification period lasts as long as a director may be subject to any proceeding arising out of acts or omissions of such director in such capacity. The maximum amount of potential future indemnification is unlimited; however, the Company currently holds director liability insurance. This insurance allows the transfer of risk associated with the Company’s exposure and may enable it to recover a portion of any future amounts paid. The Company believes that the fair value of these indemnification obligations is minimal. Accordingly, it has not recognized any liabilities relating to these obligations for any period presented. F-34 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) 16. Net Loss per Share The following table sets forth the computation of the basic and diluted net loss per share during the years ended December 31, 2020, 2019, and 2018 (in thousands, except share and per share data): Year Ended December 31, 2020 2019 2018 Numerator: Net loss $ ( 186,566 ) $ ( 402,727 ) $ ( 197,611 ) Denominator: Weighted-average shares used to compute net loss per share, basic and diluted 60,845,550 56,576,885 49,775,223 Net loss per share, basic and diluted $ ( 3.07 ) $ ( 7.12 ) $ ( 3.97 ) The following weighted-average outstanding common stock equivalents were excluded from the computation of diluted net loss per share for the periods presented because including them would have been antidilutive: Year Ended December 31, 2020 2019 2018 Options to purchase common stock, RSUs, and PSUs 8,532,236 7,978,666 7,301,431 Employee stock purchase plan 2,626 3,953 3,345 Common stock warrants 29,449 149,700 149,700 8,564,311 8,132,319 7,454,476 17. Accumulated Other Comprehensive Income (Loss) Total accumulated other comprehensive income (loss) consisted of the following (in thousands) : Year Ended December 31, 2020 2019 Cumulative foreign currency translation adjustment $ 429 $ ( 306 ) Unrealized gain on securities available-for-sale 260 159 Total accumulated other comprehensive income (loss) $ 689 $ ( 147 ) 18. Quarterly Financial Data (unaudited) The following table presents certain unaudited quarterly financial information. This information has been prepared on the same basis as the audited financial statements and includes all adjustments (consisting only of normal recurring adjustments) necessary to present fairly the unaudited quarterly results of operations set forth herein (in thousands, except per share data): 2020 March 31, June 30, September 30, December 31, Revenue $ 36,309 $ 61,709 $ 81,470 $ 91,542 Operating expenses $ 156,974 $ 124,764 $ 131,785 $ 187,623 Change in fair value of equity investments $ 7,668 $ 95,200 $ ( 11,520 ) $ 79,055 Net income (loss) $ ( 119,025 ) $ 25,315 $ ( 68,845 ) $ ( 24,011 ) Net income (loss) per share, basic $ ( 2.05 ) $ 0.42 $ ( 1.13 ) $ ( 0.37 ) Net income (loss) per share, diluted $ ( 2.05 ) $ 0.41 $ ( 1.13 ) $ ( 0.37 ) 2019 March 31, June 30, September 30, December 31, Revenue $ 18,172 $ 24,149 $ 25,800 $ 35,593 Operating expenses $ 117,386 $ 136,623 $ 143,833 $ 130,045 Change in fair value of equity investments $ — $ 9,828 $ 2,166 $ 1,419 Net loss $ ( 96,756 ) $ ( 99,172 ) $ ( 112,994 ) $ ( 93,805 ) Net loss per share, basic and diluted $ ( 1.82 ) $ ( 1.72 ) $ ( 1.96 ) $ ( 1.62 ) F-35 ULTRAGENYX PHARMACEUTICAL INC. Notes to Consolidated Financial Statements (continued) 19. Subsequent Event In December 2020, the Company entered into a License and Collaboration Agreement with Mereo BioPharma 3 Limited (Mereo) to collaborate on the development of setrusumab. Under the terms of the agreement, the Company will lead future global development of setrusumab in both pediatric and adult patients with Osteogenesis Imperfecta, and was granted an exclusive license to develop and commercialize setrusumab in the U.S., Turkey, and the rest of the world, excluding the European Economic Area, United Kingdom, and Switzerland (the Mereo territory), where Mereo retains commercial rights. Each party will be responsible for post-marketing commitments and commercial supply in their respective territories. Upon the closing of the transaction under the agreement in January 2021, the Company made a payment of $ 50.0 million to Mereo and will be required to make payments of up to $ 254.0 million upon the achievement of certain clinical, regulatory, and commercial milestones. The Company will pay for all global development costs as well as tiered double-digit percentage royalties to Mereo on net sales in the U.S., Turkey, and the rest of the world, and Mereo will pay the Company a fixed double-digit percentage royalty on net sales in the Mereo Territory. F-36