Ultragenyx Pharmaceutical (RARE) 10-K 15 Feb 22 2021 FY Annual report Financial data

Document and Entity Information

Document and Entity Information - USD ($) $ in Billions	12 Months Ended
	Dec. 31, 2021	Feb. 10, 2022	Jun. 30, 2021
Cover [Abstract]
Document Type	10-K
Amendment Flag	false
Document Period End Date	Dec. 31, 2021
Document Fiscal Year Focus	2021
Document Fiscal Period Focus	FY
Trading Symbol	RARE
Entity Registrant Name	Ultragenyx Pharmaceutical Inc.
Entity Central Index Key	0001515673
Current Fiscal Year End Date	--12-31
Entity Well-known Seasoned Issuer	Yes
Entity Current Reporting Status	Yes
Entity Voluntary Filers	No
Entity Interactive Data Current	Yes
Entity Filer Category	Large Accelerated Filer
Entity Small Business	false
Entity Emerging Growth Company	false
ICFR Auditor Attestation Flag	true
Entity Shell Company	false
Entity Common Stock, Shares Outstanding		69,384,774
Entity Public Float			$ 6.5
Security Exchange Name	NASDAQ
Title of 12(b) Security	Common Stock, $0.001 par value
Entity File Number	001-36276
Entity Incorporation, State or Country Code	DE
Entity Tax Identification Number	27-2546083
Entity Address, Address Line One	60 Leveroni Court
Entity Address, City or Town	Novato
Entity Address, State or Province	CA
Entity Address, Postal Zip Code	94949
City Area Code	415
Local Phone Number	483-8800
Document Annual Report	true
Document Transition Report	false
Documents Incorporated by Reference	DOCUMENTS INCORPORATED BY REFERENCE Portions of the registrant’s definitive proxy statement relating to its 2022 Annual Meeting of Stockholders, to be held on or about June 24, 2022, are incorporated by reference into Part III of this Annual Report on Form 10-K where indicated. Such proxy statement will be filed with the U.S. Securities and Exchange Commission within 120 days after the end of the fiscal year to which this report relates.
Auditor Firm ID	42
Auditor Name	Ernst & Young LLP
Auditor Location	Redwood City, California

CONSOLIDATED BALANCE SHEETS

CONSOLIDATED BALANCE SHEETS - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Current assets:
Cash and cash equivalents	$ 307,584	$ 713,526
Marketable debt securities	432,612	488,007
Accounts receivable, net	28,432	23,093
Inventory	16,231	13,048
Prepaid expenses and other current assets	71,745	57,630
Total current assets	856,604	1,295,304
Property, plant, and equipment, net	141,247	73,515
Equity investments	34,925	155,375
Marketable debt securities	258,933	10,506
Right-of-use assets	34,936	40,524
Intangible assets, net	130,788	131,113
Goodwill	44,406	44,406
Other assets	20,558	8,812
Total assets	1,522,397	1,759,555
Current liabilities:
Accounts payable	17,138	12,923
Accrued liabilities	145,555	108,491
Contract liabilities	7,609	59,219
Lease liabilities	11,066	8,976
Total current liabilities	181,368	189,609
Contract liabilities	1,467	7,349
Lease liabilities	30,904	39,251
Deferred tax liabilities	33,306	33,306
Liability related to the sale of future royalties	351,786	335,665
Other liabilities	1,005
Total liabilities	599,836	605,180
Commitments and contingencies (Notes 8 and 14)
Stockholders’ equity:
Preferred stock, par value of $0.001 per share - 25,000,000 shares authorized; nil outstanding as of December 31, 2021 and December 31, 2020
Common stock, par value of $0.001 per share - 250,000,000 shares authorized; 69,344,998 and 66,818,520 shares issued and outstanding as of December 31, 2021 and December 31, 2020, respectively	69	67
Additional paid-in capital	2,997,497	2,773,195
Accumulated other comprehensive income (loss)	(1,404)	689
Accumulated deficit	(2,073,601)	(1,619,576)
Total stockholders’ equity	922,561	1,154,375
Total liabilities and stockholders’ equity	$ 1,522,397	$ 1,759,555

CONSOLIDATED BALANCE SHEETS (Pa

CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares	Dec. 31, 2021	Dec. 31, 2020
Statement of Financial Position [Abstract]
Preferred stock, par value	$ 0.001	$ 0.001
Preferred stock, shares authorized	25,000,000	25,000,000
Preferred stock, shares outstanding	0	0
Common stock, par value	$ 0.001	$ 0.001
Common stock, shares authorized	250,000,000	250,000,000
Common stock, shares issued	69,344,998	66,818,520
Common stock, shares outstanding	69,344,998	66,818,520

CONSOLIDATED STATEMENTS OF OPER

CONSOLIDATED STATEMENTS OF OPERATIONS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Revenues:
Total revenues	$ 351,406	$ 271,030	$ 103,714
Operating expenses:
Cost of sales	16,008	6,129	9,008
Research and development	497,153	412,084	357,355
Selling, general and administrative	219,982	182,933	161,524
Total operating expenses	733,143	601,146	527,887
Loss from operations	(381,737)	(330,116)	(424,173)
Interest income	1,928	7,038	13,238
Change in fair value of equity investments	(42,063)	170,403	13,413
Non-cash interest expense on liability related to the sale of future royalties	(29,422)	(33,291)	(1,135)
Other income (expense)	(1,687)	607	(787)
Loss before income taxes	(452,981)	(185,359)	(399,444)
Provision for income taxes	(1,044)	(1,207)	(3,283)
Net loss	$ (454,025)	$ (186,566)	$ (402,727)
Net loss per share, basic and diluted	$ (6.70)	$ (3.07)	$ (7.12)
Weighted-average shares used in computing net loss per share, basic and diluted	67,795,540	60,845,550	56,576,885
Collaboration and License
Revenues:
Total revenues	$ 256,438	$ 219,315	$ 83,493
Product Sales
Revenues:
Total revenues	77,017	38,720	$ 20,221
Non-cash Collaboration Royalty Revenue
Revenues:
Total revenues	$ 17,951	$ 12,995

CONSOLIDATED STATEMENTS OF COMP

CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Statement of Comprehensive Income [Abstract]
Net loss	$ (454,025)	$ (186,566)	$ (402,727)
Other comprehensive income (loss):
Foreign currency translation adjustments	(550)	735	23
Unrealized gain (loss) on available-for-sale securities	(1,543)	101	463
Other comprehensive income (loss):	(2,093)	836	486
Total comprehensive loss	$ (456,118)	$ (185,730)	$ (402,241)

CONSOLIDATED STATEMENTS OF STOC

CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY - USD ($) $ in Thousands	Total	Common Stock	Additional Paid-in Capital	Accumulated Other Comprehensive Income (Loss)	Accumulated Deficit
Beginning balance at Dec. 31, 2018	$ 608,908	$ 51	$ 1,639,773	$ (633)	$ (1,030,283)
Beginning balance, shares at Dec. 31, 2018		50,860,588
Issuance of common stock in connection with underwritten public offering, net of issuance costs	330,415	$ 6	330,409
Issuance of common stock in connection with underwritten public offering, net of issuance costs, shares		5,833,333
Issuance of common stock in connection with at-the-market offering, net of issuance costs	24,828		24,828
Issuance of common stock in connection with at-the-market offering, net of issuance costs, shares		468,685
Stock-based compensation	82,025		82,025
Issuance of common stock under equity plan awards, net of tax	9,829	$ 1	9,828
Issuance of common stock under equity plan awards, net of tax, shares		675,614
Other comprehensive income	486			486
Net loss	(402,727)				(402,727)
Ending balance at Dec. 31, 2019	653,764	$ 58	2,086,863	(147)	(1,433,010)
Ending balance, shares at Dec. 31, 2019		57,838,220
Issuance of common stock in connection with underwritten public offering, net of issuance costs	435,556	$ 5	435,551
Issuance of common stock in connection with underwritten public offering, net of issuance costs, shares		5,111,110
Issuance of common stock in connection with license agreement, net of issuance costs	55,268	$ 1	55,267
Issuance of common stock in connection with license agreement, net of issuance costs, shares		1,243,913
Issuance of common stock in connection with at-the-market offering, net of issuance costs	20,391		20,391
Issuance of common stock in connection with at-the-market offering, net of issuance costs, shares		283,333
Stock-based compensation	85,833		85,833
Issuance of common stock upon exercise of warrants and under equity plan awards, net of tax	89,293	$ 3	89,290
Issuance of common stock upon exercise of warrants and under equity plan awards, net of tax, shares		2,341,944
Other comprehensive income	836			836
Net loss	(186,566)				(186,566)
Ending balance at Dec. 31, 2020	$ 1,154,375	$ 67	2,773,195	689	(1,619,576)
Ending balance, shares at Dec. 31, 2020	66,818,520	66,818,520
Issuance of common stock in connection with at-the-market offering, net of issuance costs	$ 78,943	$ 1	78,942
Issuance of common stock in connection with at-the-market offering, net of issuance costs, shares	1,050,372	1,050,372
Stock-based compensation	$ 105,260		105,260
Issuance of common stock under equity plan awards, net of tax	40,101	$ 1	40,100
Issuance of common stock under equity plan awards, net of tax, shares		1,476,106
Other comprehensive income	(2,093)			(2,093)
Net loss	(454,025)				(454,025)
Ending balance at Dec. 31, 2021	$ 922,561	$ 69	$ 2,997,497	$ (1,404)	$ (2,073,601)
Ending balance, shares at Dec. 31, 2021	69,344,998	69,344,998

CONSOLIDATED STATEMENTS OF CASH

CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Operating activities:
Net loss	$ (454,025)	$ (186,566)	$ (402,727)
Adjustments to reconcile net loss to net cash used in operating activities:
Stock-based compensation	104,952	85,735	81,995
Amortization of premium (discount) on marketable debt securities, net	6,606	848	(6,214)
Depreciation and amortization	13,239	12,261	8,539
Change in fair value of equity investments	42,063	(170,403)	(13,413)
Non-cash collaboration royalty revenue	(17,951)	(12,995)
Non-cash interest expense on liability related to the sale of future royalties	29,422	33,291	1,135
Other	235	946	2,621
Changes in operating assets and liabilities:
Accounts receivable	(5,432)	9,840	(20,104)
Inventory	(3,117)	(1,346)	(4,451)
Prepaid expenses and other assets	(29,508)	2,748	(8,216)
Accounts payable, accrued, and other liabilities	32,313	26,853	13,312
Contract liabilities, net	(57,492)	66,568
Deferred tax liabilities			2,140
Net cash used in operating activities	(338,695)	(132,220)	(345,383)
Investing activities:
Purchase of property, plant, and equipment	(73,093)	(43,905)	(24,832)
Purchase of marketable debt securities	(1,012,187)	(813,237)	(692,824)
Purchase of equity investments		(37,062)	(14,339)
Proceeds from sale of marketable debt securities	92,896	50,990	42,718
Proceeds from sale of equity investments	79,843	79,842
Proceeds from maturities of marketable debt securities	718,111	589,806	676,238
Other	(942)	(5,555)
Net cash used in investing activities	(195,372)	(179,121)	(13,039)
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
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	78,943	20,391	24,828
Proceeds from the issuance of common stock from exercise of warrants and equity plan awards, net	40,101	89,293	9,829
Other	(492)	(236)
Net cash provided by financing activities	118,552	600,272	679,306
Effect of exchange rate changes on cash	(1,194)	1,119	(165)
Net (decrease) increase in cash, cash equivalents, and restricted cash	(416,709)	290,050	320,719
Cash, cash equivalents, and restricted cash at beginning of year	726,294	436,244	115,525
Cash, cash equivalents, and restricted cash at end of year	309,585	726,294	436,244
Supplemental disclosures of non-cash investing and financing information:
Acquired lease liabilities arising from obtaining right-of-use assets	3,142	18,775	21,861
Stock-based compensation capitalized into ending inventory	1,453	1,304	1,206
Costs of property and equipment included in accounts payable, accrued, and other liabilities	18,993	$ 8,515	$ 10,367
Non-cash interest expense on liability related to the sale of future royalties capitalized into ending property, plant and equipment	$ 4,650

Organization and Basis of Prese

Organization and Basis of Presentation	12 Months Ended
	Dec. 31, 2021
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Organization and Basis of Presentation	1. Organizat ion and Basis of Presentation Ultragenyx Pharmaceutical Inc. (the Company) is a biopharmaceutical company incorporated in Delaware. 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 operates as one reportable segment. The Company has four commercially approved products. Crysvita® (burosumab) is approved in the United States (U.S.) 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, Colombia, and Mexico, Crysvita is approved for treatment of XLH in adult and pediatric patients one year of age and older. Crysvita is also approved in the U.S. by the FDA 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, is approved in the U.S., Canada, and Brazil for the treatment of pediatric and adult patients severely affected by long-chain fatty acid oxidation disorders (LC-FAOD). On January 7, 2022, the Company announced a collaboration with Regeneron Pharmaceuticals (Regeneron) to commercialize Evkeeza® (evinacumab) outside of the U.S. Evkeeza is approved in the U.S. and the European Economic Area (EEA) for the treatment of homozygous familial hypercholesterolemia (HoFH). 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); • 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 is subject to the Company's collaboration agreement with Mereo BioPharma 3 (Mereo), 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 (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; and • UX053 is a messenger RNA (mRNA) product candidate designed for the treatment of patients with Glycogen Storage Disease Type III (GSDIII), a disease caused by a glycogen debranching enzyme (AGL) deficiency that results in glycogen accumulation in the liver and muscle. 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, 2021, the Company has relied primarily on its sale of equity securities, its revenue from commercial products, 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.

Summary of Significant Accounti

Summary of Significant Accounting Policies	12 Months Ended
	Dec. 31, 2021
Accounting Policies [Abstract]
Summary of Significant Accounting Policies	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. 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 Statements of Cash Flows (in thousands): December 31, 2021 2020 2019 Cash and cash equivalents $ 307,584 $ 713,526 $ 433,584 Restricted cash included in prepaid expenses and — 10,847 161 Restricted cash included in other assets 2,001 1,921 2,499 Total cash, cash equivalents, and restricted cash $ 309,585 $ 726,294 $ 436,244 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 Arcturus common stock and received an option to purchase an additional 600,000 shares of Arcturus common stock, which was exercised in May 2020. During the years ended December 31, 2021 and 2020 , the Company sold 1,700,000 shares and 800,000 shares, respectively, of Arcturus common stock . 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 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 Consolidated 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 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 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 years ended December 31, 2021 and 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. Interest costs incurred during the construction of major capital projects are capitalized until the underlying asset is ready to be placed in service, at which point the interest costs are amortized as depreciation expense over the life of the underlying asset. 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. When development of the project 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. 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 Statements 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 Company sold the right to receive certain royalty payments from net sales of Crysvita to RPI Finance Trust (RPI), an affiliate of Royalty Pharma, as further described in “Note 9. 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. 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 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 a material effect on earnings in the period of the adjustment. Leases Lease agreements are evaluated to determine whether an arrangement is or contains a lease in accordance with ASC 842, Leases . 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. The Company has elected to not separate lease and non-lease components. See “Note 8. Leases” for further disclosure. 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.

Fair Value Measurements

Fair Value Measurements	12 Months Ended
	Dec. 31, 2021
Fair Value Disclosures [Abstract]
Fair Value Measurements	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, U.S. Government Treasury and agency securities, and debt securities in government-sponsored entities 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. 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, 2021 Level 1 Level 2 Level 3 Total Financial Assets: Money market funds $ 266,765 $ — $ — $ 266,765 Certificates of deposits and time deposits — 16,000 — 16,000 Corporate bonds — 349,691 — 349,691 Commercial paper — 187,624 — 187,624 Asset-backed securities — 41,245 — 41,245 U.S. Government Treasury and agency securities — 87,435 — 87,435 Debt securities in government-sponsored entities — 19,549 — 19,549 Investments in Arcturus and Solid common stock 32,200 — — 32,200 Other — 942 — 942 Total $ 298,965 $ 702,486 $ — $ 1,001,451 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 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 using a Black-Scholes option pricing model. As of December 31, 2021 and 2020 , the balance of the convertible promissory note was $ 2.4 million and $ 2.1 million, respectively, including $ 0.5 million and $ 0.2 million, respectively, in interest receivable, and was recorded in other assets, and the allocated fair value of the warrant was $ 0.6 million and $ 0.6 million, respectively, and was recorded in equity investments. In December 2020, the Company invested $ 1.4 million in a private pharmaceutical company in the form of a convertible promissory note (Note). In October 2021, pursuant to a qualified financing event, the outstanding balance of the Note was fully converted into 606,506 shares of preferred stock. The equity investment is recorded at cost less impairment, if any, adjusted for observable price changes in orderly transactions for identical or similar investments. As of December 31, 2021, the carrying value of the investment was $ 2.1 million.

Balance Sheet Components

Balance Sheet Components	12 Months Ended
	Dec. 31, 2021
Investments, Debt and Equity Securities [Abstract]
Balance Sheet Components	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, 2021 Gross Unrealized Amortized Gains Losses Estimated Money market funds $ 266,765 $ — $ — $ 266,765 Certificates of deposit and time deposits 16,000 — — 16,000 Corporate bonds 350,667 3 ( 979 ) 349,691 Commercial paper 187,624 — — 187,624 Asset-backed securities 41,282 1 ( 38 ) 41,245 U.S. Government Treasury and agency securities 87,642 1 ( 208 ) 87,435 Debt securities in government-sponsored entities 19,612 — ( 63 ) 19,549 Total $ 969,592 $ 5 $ ( 1,288 ) $ 968,309 December 31, 2020 Gross Unrealized Amortized Cost Gains Losses Estimated 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 At December 31, 2021 , the remaining contractual maturities of available-for-sale securities were less than three 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, 2021 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, 2021 2020 Work-in-process $ 10,504 $ 7,184 Finished goods 5,727 5,864 Total $ 16,231 $ 13,048 Property, Plant, and Equipment, net Property, plant, and equipment, net consists of the following (in thousands): December 31, 2021 2020 Leasehold improvements $ 44,081 $ 39,356 Research and development equipment 38,661 28,394 Furniture and office equipment 5,413 5,051 Computer equipment and software 10,238 8,181 Land 15,487 11,722 Construction-in-progress 76,849 17,649 Other 556 554 Property, plant, and equipment, gross 191,285 110,907 Less accumulated depreciation ( 50,038 ) ( 37,392 ) Property, plant, and equipment, net $ 141,247 $ 73,515 Depreciation expense for the years ended December 31, 2021, 2020, and 2019 was $ 12.9 million, $ 12.1 million and $ 8.3 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. Accrued Liabilities Accrued liabilities consists of the following (in thousands): December 31, 2021 2020 Research, clinical study, and manufacturing expenses $ 40,880 $ 25,875 Payroll and related expenses 62,591 58,176 Other 42,084 24,440 Total $ 145,555 $ 108,491

Intangible Assets, Net

Intangible Assets, Net	12 Months Ended
	Dec. 31, 2021
Intangible Assets, Net (Excluding Goodwill) [Abstract]
Intangible Assets, Net	5. Intangible Assets, net The Company has IPR&D assets of $ 129.0 million and $ 129.0 million as of December 31, 2021 and 2020, respectively. 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. 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 $ 0.3 million, $ 0.2 million, and $ 0.2 million for the years ended December 31, 2021, 2020, and 2019, 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.

Revenue

Revenue	12 Months Ended
	Dec. 31, 2021
Revenue from Contract with Customer [Abstract]
Revenue	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, 2021 2020 2019 Collaboration and license revenue: Crysvita collaboration revenue in profit-share territory $ 171,198 $ 128,597 $ 74,869 Crysvita royalty revenue in European territory 244 1,498 8,120 Daiichi Sankyo 84,996 89,220 — Bayer — — 504 Total collaboration and license revenue 256,438 219,315 83,493 Product sales: Crysvita 21,422 10,350 4,286 Mepsevii 16,035 15,342 12,634 Dojolvi 39,560 13,028 3,301 Total product sales 77,017 38,720 20,221 Crysvita non-cash collaboration royalty revenue 17,951 12,995 — Total revenues $ 351,406 $ 271,030 $ 103,714 The following table disaggregates total revenues based on geographic location (in thousands): Year Ended December 31, 2021 2020 2019 North America $ 301,110 $ 237,666 $ 86,442 Europe 26,660 21,318 12,085 All other 23,636 12,046 5,187 Total revenues $ 351,406 $ 271,030 $ 103,714 The following table presents the activity and ending balances for sales-related accruals and allowances (in thousands): Year Ended December 31, 2021 2020 2019 Balance of product sales reserve at beginning of year $ 3,913 $ 1,818 $ 1,240 Provisions 9,586 5,763 3,846 Payments ( 6,120 ) ( 2,785 ) ( 2,739 ) Adjustments ( 198 ) ( 883 ) ( 529 ) Balance of product sales reserve at end of year $ 7,181 $ 3,913 $ 1,818 The following table presents changes in the contract assets (liabilities) for the years ended December 31, 2021 and 2020 (in thousands): December 31, 2021 2020 Balance of contract liabilities at beginning of period $ ( 66,568 ) $ — Additions ( 27,504 ) ( 155,788 ) Deductions 84,996 89,220 Balance of contract liabilities at end of period, net $ ( 9,076 ) $ ( 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 71 % of the total accounts receivable balance as of December 31, 2021 and 2020 , respectively.

License and Research Agreements

License and Research Agreements	12 Months Ended
	Dec. 31, 2021
Research Grant Agreement [Abstract]
License and Research Agreements	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 U.S. 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 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. In April 2023, which is the transition date for the profit-share 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. The collaboration and license agreements are within the scope of ASC 808, which provides guidance on the presentation and disclosure of collaborative arrangements. 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 9. 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 years ended December 31, 2021 and 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 $ 0.2 million and $ 1.5 million, respectively, as royalty revenue in the European territory. The Company’s share of collaboration and royalty revenue related to Crysvita was as follows (in thousands): Year Ended December 31, 2021 2020 2019 Company's share of revenue in profit-share territory $ 171,198 $ 128,597 $ 74,869 Royalty revenue in European territory 244 1,498 8,120 Non-cash royalty revenue in European territory 17,951 12,995 — Total $ 189,393 $ 143,090 $ 82,989 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. The Company recorded product sales of $ 21.4 million, $ 10.4 million, and $ 4.3 million for the years ended December 31, 2021, 2020, and 2019, 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 Latin America 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, 2021 2020 2019 Research and development $ 21,657 $ 21,476 $ 27,309 Selling, general and administrative 32,629 25,186 21,828 Total $ 54,286 $ 46,662 $ 49,137 Collaboration receivable and payable The Company had accounts receivable from KKC in the amount of $ 20.2 million and $ 16.4 million from profit-share revenue and royalties and other receivables recorded in prepaid and other current assets of $ 16.0 million and $ 9.6 million and accrued liabilities of $ 2.3 million and $ 2.4 million from commercial and development activity reimbursements, as of December 31, 2021 and 2020, respectively. 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, as amended, BRI exclusively licensed to the Company its territories for certain intellectual property related to Dojolvi (triheptanoin) for the treatment of LC-FAOD. For the year ended December 31, 2020, the Company paid $ 2.0 million 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 was 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. The Company has no further obligations under the contract. The Company may record future milestone payments as revenue if it becomes probable that a significant reversal in the amount of revenue recognized will not occur and when the uncertainty associated with the variable consideration is subsequently resolved. University of Pennsylvania The Company has a research, collaboration, and license agreement with University of Pennsylvania School of Medicine (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. 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, as well as low to mid-single-digit royalties on net sales of each licensed product. Arcturus Research Collaboration and License Agreement In October 2015, the Company entered into a Research Collaboration and License Agreement with Arcturus Therapeutics Holdings Inc. (Arcturus) to collaborate on the research and development of therapies for select rare diseases. Arcturus was responsible for conducting certain research services, funded by the Company, and the Company was responsible for development and commercialization costs. On a product-by-product basis, the Company is obligated to make development and regulatory milestone payments of up to $ 24.5 million, and commercial milestone payments of up to $ 45.0 million, if certain milestones are achieved. For the year ended December 31, 2021, the Company achieved a $ 1.0 million development milestone related to UX053, which was paid with a corresponding credit received from Arcturus for prior research and collaboration activities. The Company is also obligated to pay Arcturus royalties on any net sales of products incorporating the licensed intellectual property that may range from a mid single-digit to low double-digit percentage. Pursuant to the agreement, the Company incurred nil , $ 0.4 million, and $ 0.8 million for the years ended December 31, 2021, 2020, and 2019, 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 (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 under the License Agreement, Arcturus common stock, and an option to purchase an additional 600,000 shares of Arcturus’ common stock at $ 16.00 per share. In May 2020, the Company exercised its option to purchase 600,000 shares of Arcturus common stock for a total purchase price of $ 9.6 million. During the years ended December 31, 2021 and 2020 , the Company sold 1,700,000 shares and 800,000 shares of Arcturus common stock, at a weighted-average price of $ 47.44 and $ 100.81 , respectively. As of December 31, 2021 and 2020 , the Company held 500,000 shares and 2,200,000 shares, respectively, of Arcturus common stock. Due to the decrease in ownership and in accordance with the terms of the Equity Purchase Agreement, the Company no longer had the right to have its director nominee included in the annual slate of Arcturus director nominees and as a result, the Company’s director designee resigned from the Arcturus board of directors effective August 25, 2021. The Company will continue to apply the fair value option to account for the equity investment. 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 Arcturus common stock Total 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 Change in fair value 2,912 — 2,912 Sale of shares ( 79,843 ) — ( 79,843 ) December 31, 2021 $ 18,505 $ — $ 18,505 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 a $ 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 P roducer 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. The Company may also provide strategic consultation to Daiichi Sankyo on the development of both AAV-based gene therapy products and other products for rare diseases. Under the terms of the License Agreement, Daiichi Sankyo made an upfront payment of $ 125.0 million and an additional $ 25.0 million payment upon achievement of the milestones related to technology transfer of the PCL and HEK293 platforms in the fourth quarter of 2021. Daiichi Sankyo is also obligated to pay a single-digit royalties on net sales of products manufactured in the technology platforms. Daiichi Sankyo will reimburse the Company for all costs associated with the transfer of the manufacturing technology. In March 2020, the Company also entered into a Stock Purchase Agreement (SPA) 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. 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 SPA. 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 SPA are being accounted for as one arrangement because they were entered into at or near the same time and were 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 PCL and HEK293 transient transfection manufacturing technology platforms together with the initial technical assistance and technology transfer services, which were substantially 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. As of December 31, 2021, the Company has determined that the total transaction price of the License Agreement was $ 183.3 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 $ 5.6 million estimated reimbursement amount for delivering the license and technology services. Total revenue recognized under the license agreement through December 31, 2021 is $ 174.2 million. 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 is being recognized over an initial period which is substantially complete and was based on 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. 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 years ended December 31, 2021 and 2020 , the Company recognized $ 85.0 million and $ 89.2 million, respectively, in revenue related to this arrangement. The Company had recorded contract liabilities of $ 9.1 million and $ 66.6 million and an accounts receivable related to the above agreements of $ 0.1 million and $ 1.2 million, respectively, as of December 31, 2021 and 2020. Solid Biosciences, Inc. In October 2020, the Company entered into a strategic Collaboration and License Agreement with Solid Biosciences Inc. (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 is collaborating to develop products that combine Solid’s differentiated microdystrophin construct, the Company’s PCL manufacturing platform, and the Company’s AAV8 variants. Solid is providing 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. 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 $ 26,843 Change in fair value 32,477 December 31, 2020 59,320 Change in fair value ( 45,625 ) December 31, 2021 $ 13,695

Leases

Leases	12 Months Ended
	Dec. 31, 2021
Lessee Disclosure [Abstract]
Leases	8. Leases 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 components of lease expense were as follows (in thousands): Year Ended December 31, 2021 2020 Operating lease expense $ 11,209 $ 10,164 Variable lease expense 4,142 3,298 Financing: Amortization 310 158 Interest expense 58 40 Total $ 15,719 $ 13,660 Cash paid for amounts included in the measurement of operating lease liabilities for the year ended December 31, 2021 was $ 11.8 million and was included in net cash used in operating activities in the Consolidated Statements of Cash Flows. Future minimum lease payments under non-cancellable leases as of December 31, 2021 were as follows (in thousands): Year Ending December 31, Operating Financing Total 2022 $ 12,873 $ 606 $ 13,479 2023 13,072 349 13,421 2024 11,092 75 11,167 2025 6,247 — 6,247 2026 2,681 — 2,681 Thereafter 776 — 776 Total future lease payments 46,741 1,030 47,771 Less: Amount representing interest ( 5,749 ) ( 52 ) ( 5,801 ) Present value of future lease payments 40,992 978 41,970 Less: Lease liabilities, current ( 10,498 ) ( 568 ) ( 11,066 ) Lease liabilities , non-curre nt $ 30,494 $ 410 $ 30,904 Lease liabilities are based on the net present value of the remaining lease payments over the remaining lease term. As of December 31, 2021 , the weighted-average remaining operating and financing lease terms were 3.84 years and 3.88 years, respectively, and the weighted-average discount rates used to determine the lease liability for operating and financing leases were 6.64 % and 5.44 %, respectively.

Liability Related to the Sale o

Liability Related to the Sale of Future Royalties	12 Months Ended
	Dec. 31, 2021
Deferred Revenue Disclosure [Abstract]
Liability Related to the Sale of Future Royalties	9. Liability Related to the Sale of Future Royalties In December 2019, the Company entered into a Royalty Purchase Agreement with RPI. Pursuant to the agreement, 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. The Company's effective annual interest rate was approximately 9.6 % as of December 31, 2021. 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 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 December 31, 2019 $ 315,369 Non-cash collaboration royalty revenue ( 12,995 ) Non-cash interest expense 33,291 December 31, 2020 335,665 Non-cash collaboration royalty revenue ( 17,951 ) Non-cash interest expense 34,072 December 31, 2021 $ 351,786

Equity

Equity	12 Months Ended
	Dec. 31, 2021
Equity [Abstract]
Equity	10. Equity At-the-Market Offerings In July 2017, the Company entered into an at-the-market (ATM) sales agreement with Cowen and Company, LLC (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 and 2019, the Company sold 283,333 and 468,685 shares of common stock, respectively, resulting in net proceeds of approximately $ 20.4 million and $ 24.8 million, respectively, after commissions and other offering costs. T he Company has completed the sale of all available amounts under this ATM facility. In May 2021, the Company entered into an Open Market Sale Agreement with Jefferies LLC (Jefferies) pursuant to which the Company may offer and sell shares of the Company’s common stock having an aggregate offering proceeds up to $ 350.0 million, from time to time, in ATM offerings through Jefferies. For the year ended December 31, 2021 , the Company sold 1,050,372 shares under the arrangement resulting in net proceeds of approximately $ 78.9 million. Underwritten Public Offering 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, 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.

Stock-Based Awards

Stock-Based Awards	12 Months Ended
	Dec. 31, 2021
Share-based Payment Arrangement [Abstract]
Stock-Based Awards	11. 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 . In February 2021, the Company adopted the Employment Inducement Plan (the Inducement Plan), with a maximum of 500,000 shares available for grant under the Inducement Plan. Under the terms of the 2014 Plan and Inducement 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 and Inducement 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 of December 31, 2021 , an aggregate of 12,462,795 shares of common stock have been authorized for issuance under the 2011 Plan, the 2014 Plan, and the Inducement Plan. Stock Option Activity The following table summarizes activity under the Company’s stock option 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, 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 Options granted 1,217,820 128.63 Options exercised ( 687,835 ) 53.14 Options cancelled ( 336,383 ) 81.78 Outstanding — December 31, 2021 6,198,205 $ 75.96 6.81 $ 112,242 Vested and exercisable — December 31, 2021 3,669,577 $ 64.93 5.66 $ 80,283 Vested and expected to vest — December 31, 2021 5,951,372 $ 75.09 6.73 $ 109,665 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, 2021, 2020, and 2019 was $ 38.3 million, $ 56.9 million, and $ 6.5 million, respectively. Cash received from the exercise of options was $ 36.6 million, $ 88.1 million, and $ 7.7 million as of December 31, 2021, 2020, and 2019, respectively. The weighted-average estimated fair value of stock options granted was $ 70.84 , $ 35.22 , and $ 37.15 per share of the Company’s common stock during the years ended December 31, 2021, 2020, and 2019, respectively. The total estimated grant date fair value of options vested during the years ended December 31, 2021, 2020, and 2019 was $ 48.1 million, $ 45.4 million, and $ 45.3 million, respectively. Restricted Stock Units The following table summarizes activity under the Company’s Restricted Stock Units (RSU) plans and related information: RSUs Outstanding Number Weighted- Average Grant Date Fair Value 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 RSUs granted 738,905 122.71 RSUs vested ( 559,595 ) 63.41 RSUs cancelled ( 187,852 ) 80.55 Unvested — December 31, 2021 1,672,625 $ 87.48 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, 2021, 2020, and 2019 was $ 35.5 million, $ 27.2 million, and $ 20.8 million, respectively. The aggregate intrinsic value of the shares of the RSUs vested during the years ended December 31, 2021, 2020, and 2019 was $ 69.9 million, $ 29.5 million, and $ 18.4 million, respectively. Performance Stock Units The following table summarizes activity under the Company’s Performance Stock Units (PSUs) from the 2014 Plan and related information: PSUs Outstanding Number Weighted- Average Grant Date Fair Value 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 PSUs granted 62,000 158.11 PSUs vested ( 168,274 ) 54.40 PSUs cancelled ( 12,400 ) 54.28 Unvested — December 31, 2021 93,892 $ 123.46 The fair value of the PSUs is determined on the grant date based on the fair value of the Company’s common stock, except for certain PSUs with a market vesting condition, for which fair value is estimated using a Monte Carlo simulation model. 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, including both performance conditions and market conditions. As of December 31, 2021, the specified criteria were deemed probable of achievement or already achieved. Stock-based compensation for 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, 2021, 2020, and 2019 was $ 9.2 million, $ 10.3 million, and $ 3.2 million, respectively, with an aggregate intrinsic value of the shares of $ 18.9 million, $ 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, 2021 , the Company issued 69,738 shares of common stock under the ESPP. As of December 31, 2021 , an aggregate of 3,925,798 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, 2021 2020 2019 Cost of sales $ 871 $ 827 $ 1,084 Research and development 59,097 47,949 44,205 Selling, general and administrative 45,011 36,959 36,706 Total stock-based compensation expense $ 104,979 $ 85,735 $ 81,995 Stock-based compensation of $ 1.7 million, $ 1.2 million, and $ 1.4 million was capitalized into inventory for the years ended December 31, 2021, 2020, and 2019, respectively. Capitalized stock-based compensation is recognized as cost of sales when the related product is sold. As of December 31, 2021 , the total unrecognized compensation expense related to unvested equity awards, net of estimated forfeitures, was $ 200.0 million, which the Company expects to recognize over an estimated weighted-average period of 2.33 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, 2021 2020 2019 Expected term (years) 6.06 6.20 6.22 Expected volatility 60 % 61 % 61 % Risk-free interest rate 1.0 % 0.8 % 2.4 % Expected dividend rate 0.0 % 0.0 % 0.0 %

Defined Contribution Plan

Defined Contribution Plan	12 Months Ended
	Dec. 31, 2021
Defined Contribution Pension And Other Post Retirement Plans Disclosure [Abstract]
Defined Contribution Plan	12. Defined Contribution Plan The Company sponsors a retirement plan in which substantially all of its full-time employees in the U.S. 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 $ 5.5 million, $ 4.3 million, and $ 3.6 million as contribution expenses for the years ended December 31, 2021, 2020, and 2019 , respectively.

Income Taxes

Income Taxes	12 Months Ended
	Dec. 31, 2021
Income Tax Disclosure [Abstract]
Income Taxes	13. Income Taxes The components of the Company’s loss before income taxes were as follows (in thousands): Year Ended December 31, 2021 2020 2019 Domestic $ 455,314 $ 189,449 $ 399,709 Foreign ( 2,333 ) ( 4,090 ) ( 265 ) Total loss before income taxes $ 452,981 $ 185,359 $ 399,444 The components of the Company’s income tax provision were as follows (in thousands): Year Ended December 31, 2021 2020 2019 Current provision for income taxes: Federal $ — $ — $ — State ( 14 ) 15 51 International 1,058 1,192 1,092 Total current tax provision 1,044 1,207 1,143 Deferred tax provision: Federal — — — State — — 2,140 International — — — Total deferred tax provision — — 2,140 Total provision for income taxes $ 1,044 $ 1,207 $ 3,283 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, 2021 2020 2019 Federal statutory income tax rate 21.0 % 21.0 % 21.0 % State income taxes, net of federal benefit — — ( 0.5 ) Federal tax credits 7.2 13.7 5.2 Other 0.5 ( 0.5 ) ( 0.2 ) Premium on equity issuance — 2.2 — Nondeductible permanent items ( 0.8 ) ( 0.9 ) ( 0.4 ) Stock-based compensation 1.3 0.9 ( 1.0 ) Uncertain tax positions ( 1.4 ) ( 2.7 ) ( 1.0 ) Change in valuation allowance ( 27.9 ) ( 33.9 ) ( 23.6 ) Foreign rate differential ( 0.1 ) ( 0.5 ) ( 0.3 ) Provision for income taxes ( 0.2 ) % ( 0.7 ) % ( 0.8 ) % 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, 2021 2020 Deferred tax assets: Loss carryforwards $ 306,119 $ 222,902 Tax credits 218,131 184,961 Stock options 33,564 39,154 Accruals and reserves 25,735 24,922 Fixed assets and intangibles 18,263 7,242 Liability related to sale of future royalties 90,826 86,664 Basis difference in equity investments 3,912 — Other 13,060 28,642 Gross deferred tax assets 709,610 594,487 Valuation allowance ( 700,669 ) ( 561,139 ) Total deferred tax assets 8,941 33,348 Deferred tax liabilities: In-process research and development ( 33,306 ) ( 33,306 ) Basis difference in equity investments — ( 23,019 ) Right-of-use lease assets ( 8,941 ) ( 10,329 ) Gross deferred tax liabilities ( 42,247 ) ( 66,654 ) Net deferred tax liabilities $ ( 33,306 ) $ ( 33,306 ) As of December 31, 2021 and 2020 , the Company had approximately $ 1,085.4 million and $ 750.2 million, respectively, of federal net operating loss carryforwards available to reduce future taxable income that will begin to expire in 2031 . As of December 31, 2021 and 2020 , the Company had approximately $ 777.0 million and $ 616.8 million, respectively, of state net operating loss carryforwards available to reduce future taxable income that will begin to expire in 2031 . As of December 31, 2021 and 2020 , the Company had federal research tax credit carryforwards of $ 22.9 million and $ 17.7 million, respectively, available to reduce future tax liabilities that will begin to expire in 2030 . As of December 31, 2021 and 2020 , the Company had state research credit carryforwards of $ 44.6 million and $ 34.5 million, respectively, available to reduce future tax liabilities that will be carried forward indefinitely. As of December 31, 2021 and 2020 , the Company had federal Orphan Drug Credits of $ 208.1 million and $ 179.8 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, 2021. The valuation allowance increased by $ 139.5 million and $ 74.3 million during the years ended December 31, 2021 and 2020, 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, 2021 2020 2019 Balance at beginning of year $ 46,662 $ 39,954 $ 33,727 Additions based on tax positions related to current 8,542 6,950 5,575 Additions for tax positions of prior years 356 382 652 Reductions for tax positions of prior years ( 200 ) ( 624 ) — Balance at end of year $ 55,360 $ 46,662 $ 39,954 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, 2021 and 2020 , 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, 2021 , the Company had not made a provision for any incremental foreign withholding taxes on approximately $ 4.1 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, forty state tax jurisdictions, and ten foreign countries. The federal and state income tax returns from inception to December 31, 2021 remain subject to examination.

Commitments and Contingencies

Commitments and Contingencies	12 Months Ended
	Dec. 31, 2021
Commitments and Contingencies Disclosure [Abstract]
Commitments and Contingencies	14. 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, 2021, the aggregate payments under contractually binding manufacturing and service agreements are as follows (in thousands): Year Ended December 31, 2022 2023 Manufacturing and Services 19,225 774 The terms of certain of the Company’s licenses, royalties, development and collaboration agreements, as well as other research and development activities, require the Company to pay potential future milestone payments based on product development success. The amount and timing of such obligations are unknown or uncertain. These potential obligations are further described in “Note 7. License and Research Agreements”. 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.

Net Loss per Share

Net Loss per Share	12 Months Ended
	Dec. 31, 2021
Earnings Per Share [Abstract]
Net Loss per Share	15. 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, 2021, 2020, and 2019 (in thousands, except share and per share data): Year Ended December 31, 2021 2020 2019 Numerator: Net loss $ ( 454,025 ) $ ( 186,566 ) $ ( 402,727 ) Denominator: Weighted-average shares used to compute net loss per 67,795,540 60,845,550 56,576,885 Net loss per share, basic and diluted $ ( 6.70 ) $ ( 3.07 ) $ ( 7.12 ) 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, 2021 2020 2019 Options to purchase common stock, RSUs, and PSUs 8,214,063 8,532,236 7,978,666 Employee stock purchase plan 3,511 2,626 3,953 Common stock warrants — 29,449 149,700 8,217,574 8,564,311 8,132,319

Accumulated Other Comprehensive

Accumulated Other Comprehensive Income (Loss)	12 Months Ended
	Dec. 31, 2021
Other Comprehensive Income (Loss), Net of Tax [Abstract]
Accumulated Other Comprehensive Income (Loss)	16. Accumulated Other Comprehensive Income (Loss) Total accumulated other comprehensive income (loss) consisted of the following (in thousands): Year Ended December 31, 2021 2020 Cumulative foreign currency translation adjustment $ ( 121 ) $ 429 Unrealized gain (loss) on securities available-for-sale ( 1,283 ) 260 Total accumulated other comprehensive income (loss) $ ( 1,404 ) $ 689

Subsequent Event

Subsequent Event	12 Months Ended
	Dec. 31, 2021
Subsequent Events [Abstract]
Subsequent Event	17. Subsequent Events On January 7, 2022, the Company announced a collaboration with Regeneron to commercialize Evkeeza for HoFH outside of the U.S. Under the terms of the agreement, Regeneron received a $ 30.0 million upfront payment and is eligible to receive up to $ 63.0 million in future milestone payments, contingent upon the achievement of certain regulatory and sales milestones. Pursuant to the terms of the agreement, the Company received the rights to develop, commercialize and distribute the product in countries outside of the U.S. and will make payments to Regeneron based on net sales of the product. The Company will share in certain costs for global trials led by Regeneron and also have the right to opt into other potential indications.

Summary of Significant Accoun_2

Summary of Significant Accounting Policies (Policies)	12 Months Ended
	Dec. 31, 2021
Accounting Policies [Abstract]
Basis of Consolidation	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	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.
Cash, Cash Equivalents, and Restricted Cash	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 Statements of Cash Flows (in thousands): December 31, 2021 2020 2019 Cash and cash equivalents $ 307,584 $ 713,526 $ 433,584 Restricted cash included in prepaid expenses and — 10,847 161 Restricted cash included in other assets 2,001 1,921 2,499 Total cash, cash equivalents, and restricted cash $ 309,585 $ 726,294 $ 436,244
Marketable Debt Securities	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	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 Arcturus common stock and received an option to purchase an additional 600,000 shares of Arcturus common stock, which was exercised in May 2020. During the years ended December 31, 2021 and 2020 , the Company sold 1,700,000 shares and 800,000 shares, respectively, of Arcturus common stock . 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 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	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 Consolidated 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 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 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 years ended December 31, 2021 and 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	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 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. Interest costs incurred during the construction of major capital projects are capitalized until the underlying asset is ready to be placed in service, at which point the interest costs are amortized as depreciation expense over the life of the underlying asset. 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	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. When development of the project 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. 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 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	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	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	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 Statements 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 Company sold the right to receive certain royalty payments from net sales of Crysvita to RPI Finance Trust (RPI), an affiliate of Royalty Pharma, as further described in “Note 9. 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. 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 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 a material effect on earnings in the period of the adjustment.
Leases	Leases Lease agreements are evaluated to determine whether an arrangement is or contains a lease in accordance with ASC 842, Leases . 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. The Company has elected to not separate lease and non-lease components. See “Note 8. Leases” for further disclosure.
Comprehensive Loss	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 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 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	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	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	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.

Summary of Significant Accoun_3

Summary of Significant Accounting Policies (Tables)	12 Months Ended
	Dec. 31, 2021
Accounting Policies [Abstract]
Summary of Reconciliation of Cash, Cash Equivalents and Restricted Cash	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 Statements of Cash Flows (in thousands): December 31, 2021 2020 2019 Cash and cash equivalents $ 307,584 $ 713,526 $ 433,584 Restricted cash included in prepaid expenses and — 10,847 161 Restricted cash included in other assets 2,001 1,921 2,499 Total cash, cash equivalents, and restricted cash $ 309,585 $ 726,294 $ 436,244
Summary of Useful Lives of Property, Plant and Equipment	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

Fair Value Measurements (Tables

Fair Value Measurements (Tables)	12 Months Ended
	Dec. 31, 2021
Fair Value Disclosures [Abstract]
Summary of Financial Assets and Liabilities Measured on Recurring Basis	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, 2021 Level 1 Level 2 Level 3 Total Financial Assets: Money market funds $ 266,765 $ — $ — $ 266,765 Certificates of deposits and time deposits — 16,000 — 16,000 Corporate bonds — 349,691 — 349,691 Commercial paper — 187,624 — 187,624 Asset-backed securities — 41,245 — 41,245 U.S. Government Treasury and agency securities — 87,435 — 87,435 Debt securities in government-sponsored entities — 19,549 — 19,549 Investments in Arcturus and Solid common stock 32,200 — — 32,200 Other — 942 — 942 Total $ 298,965 $ 702,486 $ — $ 1,001,451 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

Balance Sheet Components (Table

Balance Sheet Components (Tables)	12 Months Ended
	Dec. 31, 2021
Investments, Debt and Equity Securities [Abstract]
Summary of Cash Equivalents and Marketable Debt Securities Classified as Available For Sale 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, 2021 Gross Unrealized Amortized Gains Losses Estimated Money market funds $ 266,765 $ — $ — $ 266,765 Certificates of deposit and time deposits 16,000 — — 16,000 Corporate bonds 350,667 3 ( 979 ) 349,691 Commercial paper 187,624 — — 187,624 Asset-backed securities 41,282 1 ( 38 ) 41,245 U.S. Government Treasury and agency securities 87,642 1 ( 208 ) 87,435 Debt securities in government-sponsored entities 19,612 — ( 63 ) 19,549 Total $ 969,592 $ 5 $ ( 1,288 ) $ 968,309 December 31, 2020 Gross Unrealized Amortized Cost Gains Losses Estimated 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
Summary of Inventory	Inventory consists of the following (in thousands): December 31, 2021 2020 Work-in-process $ 10,504 $ 7,184 Finished goods 5,727 5,864 Total $ 16,231 $ 13,048
Summary of Property, Plant and Equipment, Net	Property, plant, and equipment, net consists of the following (in thousands): December 31, 2021 2020 Leasehold improvements $ 44,081 $ 39,356 Research and development equipment 38,661 28,394 Furniture and office equipment 5,413 5,051 Computer equipment and software 10,238 8,181 Land 15,487 11,722 Construction-in-progress 76,849 17,649 Other 556 554 Property, plant, and equipment, gross 191,285 110,907 Less accumulated depreciation ( 50,038 ) ( 37,392 ) Property, plant, and equipment, net $ 141,247 $ 73,515
Accrued Liabilities	Accrued liabilities consists of the following (in thousands): December 31, 2021 2020 Research, clinical study, and manufacturing expenses $ 40,880 $ 25,875 Payroll and related expenses 62,591 58,176 Other 42,084 24,440 Total $ 145,555 $ 108,491

Revenue (Tables)

Revenue (Tables)	12 Months Ended
	Dec. 31, 2021
Revenue from Contract with Customer [Abstract]
Summary of Disaggregation of Total Revenues	The following table disaggregates total revenues from external customers by collaboration and license revenue and product sales (in thousands): Year Ended December 31, 2021 2020 2019 Collaboration and license revenue: Crysvita collaboration revenue in profit-share territory $ 171,198 $ 128,597 $ 74,869 Crysvita royalty revenue in European territory 244 1,498 8,120 Daiichi Sankyo 84,996 89,220 — Bayer — — 504 Total collaboration and license revenue 256,438 219,315 83,493 Product sales: Crysvita 21,422 10,350 4,286 Mepsevii 16,035 15,342 12,634 Dojolvi 39,560 13,028 3,301 Total product sales 77,017 38,720 20,221 Crysvita non-cash collaboration royalty revenue 17,951 12,995 — Total revenues $ 351,406 $ 271,030 $ 103,714 The following table disaggregates total revenues based on geographic location (in thousands): Year Ended December 31, 2021 2020 2019 North America $ 301,110 $ 237,666 $ 86,442 Europe 26,660 21,318 12,085 All other 23,636 12,046 5,187 Total revenues $ 351,406 $ 271,030 $ 103,714
Schedule of Sales-Related Accruals and Allowances	The following table presents the activity and ending balances for sales-related accruals and allowances (in thousands): Year Ended December 31, 2021 2020 2019 Balance of product sales reserve at beginning of year $ 3,913 $ 1,818 $ 1,240 Provisions 9,586 5,763 3,846 Payments ( 6,120 ) ( 2,785 ) ( 2,739 ) Adjustments ( 198 ) ( 883 ) ( 529 ) Balance of product sales reserve at end of year $ 7,181 $ 3,913 $ 1,818
Summary of Changes in Contract Assets (Liabilities)	The following table presents changes in the contract assets (liabilities) for the years ended December 31, 2021 and 2020 (in thousands): December 31, 2021 2020 Balance of contract liabilities at beginning of period $ ( 66,568 ) $ — Additions ( 27,504 ) ( 155,788 ) Deductions 84,996 89,220 Balance of contract liabilities at end of period, net $ ( 9,076 ) $ ( 66,568 )

License and Research Agreemen_2

License and Research Agreements (Tables)	12 Months Ended
	Dec. 31, 2021
Share of Collaboration and Royalty Revenue Related to Crysvita	The Company’s share of collaboration and royalty revenue related to Crysvita was as follows (in thousands): Year Ended December 31, 2021 2020 2019 Company's share of revenue in profit-share territory $ 171,198 $ 128,597 $ 74,869 Royalty revenue in European territory 244 1,498 8,120 Non-cash royalty revenue in European territory 17,951 12,995 — Total $ 189,393 $ 143,090 $ 82,989
Schedule of 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, 2021 2020 2019 Research and development $ 21,657 $ 21,476 $ 27,309 Selling, general and administrative 32,629 25,186 21,828 Total $ 54,286 $ 46,662 $ 49,137
Solid Biosciences, Inc.
Schedule of Changes in Fair Value of Investment in Securities	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 $ 26,843 Change in fair value 32,477 December 31, 2020 59,320 Change in fair value ( 45,625 ) December 31, 2021 $ 13,695
Arcturus
Schedule of Changes in Fair Value of Equity Investment	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 Arcturus common stock Total 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 Change in fair value 2,912 — 2,912 Sale of shares ( 79,843 ) — ( 79,843 ) December 31, 2021 $ 18,505 $ — $ 18,505

Leases (Tables)

Leases (Tables)	12 Months Ended
	Dec. 31, 2021
Lessee Disclosure [Abstract]
Summary of Components of Lease Expense	The components of lease expense were as follows (in thousands): Year Ended December 31, 2021 2020 Operating lease expense $ 11,209 $ 10,164 Variable lease expense 4,142 3,298 Financing: Amortization 310 158 Interest expense 58 40 Total $ 15,719 $ 13,660
Schedule of Future Minimum Lease Payments under Non-cancellable Leases	Future minimum lease payments under non-cancellable leases as of December 31, 2021 were as follows (in thousands): Year Ending December 31, Operating Financing Total 2022 $ 12,873 $ 606 $ 13,479 2023 13,072 349 13,421 2024 11,092 75 11,167 2025 6,247 — 6,247 2026 2,681 — 2,681 Thereafter 776 — 776 Total future lease payments 46,741 1,030 47,771 Less: Amount representing interest ( 5,749 ) ( 52 ) ( 5,801 ) Present value of future lease payments 40,992 978 41,970 Less: Lease liabilities, current ( 10,498 ) ( 568 ) ( 11,066 ) Lease liabilities , non-curre nt $ 30,494 $ 410 $ 30,904

Liability Related to the Sale_2

Liability Related to the Sale of Future Royalties (Tables)	12 Months Ended
	Dec. 31, 2021
Deferred Revenue Disclosure [Abstract]
Schedule of Activity Within Liability Related to Sale of Future Royalties	The following table shows the activity within the liability account (in thousands): Liability related to the sale December 31, 2019 $ 315,369 Non-cash collaboration royalty revenue ( 12,995 ) Non-cash interest expense 33,291 December 31, 2020 335,665 Non-cash collaboration royalty revenue ( 17,951 ) Non-cash interest expense 34,072 December 31, 2021 $ 351,786

Stock-Based Awards (Tables)

Stock-Based Awards (Tables)	12 Months Ended
	Dec. 31, 2021
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Summary of Activity Under Stock Option Plans Including 2011 Plan and 2014 Plan	Stock Option Activity The following table summarizes activity under the Company’s stock option 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, 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 Options granted 1,217,820 128.63 Options exercised ( 687,835 ) 53.14 Options cancelled ( 336,383 ) 81.78 Outstanding — December 31, 2021 6,198,205 $ 75.96 6.81 $ 112,242 Vested and exercisable — December 31, 2021 3,669,577 $ 64.93 5.66 $ 80,283 Vested and expected to vest — December 31, 2021 5,951,372 $ 75.09 6.73 $ 109,665
Summary of Stock-Based Compensation Expense	Total stock-based compensation recognized was as follows (in thousands): Year Ended December 31, 2021 2020 2019 Cost of sales $ 871 $ 827 $ 1,084 Research and development 59,097 47,949 44,205 Selling, general and administrative 45,011 36,959 36,706 Total stock-based compensation expense $ 104,979 $ 85,735 $ 81,995
Fair Value of Stock Option Awards Granted Estimated Using Black-Scholes Option-Pricing Model	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, 2021 2020 2019 Expected term (years) 6.06 6.20 6.22 Expected volatility 60 % 61 % 61 % Risk-free interest rate 1.0 % 0.8 % 2.4 % Expected dividend rate 0.0 % 0.0 % 0.0 %
Restricted Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Summary of Activity Under Stock Units from 2014 Plan	The following table summarizes activity under the Company’s Restricted Stock Units (RSU) plans and related information: RSUs Outstanding Number Weighted- Average Grant Date Fair Value 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 RSUs granted 738,905 122.71 RSUs vested ( 559,595 ) 63.41 RSUs cancelled ( 187,852 ) 80.55 Unvested — December 31, 2021 1,672,625 $ 87.48
Performance Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Summary of Activity Under Stock Units from 2014 Plan	The following table summarizes activity under the Company’s Performance Stock Units (PSUs) from the 2014 Plan and related information: PSUs Outstanding Number Weighted- Average Grant Date Fair Value 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 PSUs granted 62,000 158.11 PSUs vested ( 168,274 ) 54.40 PSUs cancelled ( 12,400 ) 54.28 Unvested — December 31, 2021 93,892 $ 123.46

Income Taxes (Tables)

Income Taxes (Tables)	12 Months Ended
	Dec. 31, 2021
Income Tax Disclosure [Abstract]
Components of Company's Loss Before Income Taxes	The components of the Company’s loss before income taxes were as follows (in thousands): Year Ended December 31, 2021 2020 2019 Domestic $ 455,314 $ 189,449 $ 399,709 Foreign ( 2,333 ) ( 4,090 ) ( 265 ) Total loss before income taxes $ 452,981 $ 185,359 $ 399,444
Components of Company's Income Tax Provision	The components of the Company’s income tax provision were as follows (in thousands): Year Ended December 31, 2021 2020 2019 Current provision for income taxes: Federal $ — $ — $ — State ( 14 ) 15 51 International 1,058 1,192 1,092 Total current tax provision 1,044 1,207 1,143 Deferred tax provision: Federal — — — State — — 2,140 International — — — Total deferred tax provision — — 2,140 Total provision for income taxes $ 1,044 $ 1,207 $ 3,283
Effective Tax Rate of Provision for Income Taxes from Federal Statutory Rate	The effective tax rate of our provision for income taxes differs from the federal statutory rate as follows: Year Ended December 31, 2021 2020 2019 Federal statutory income tax rate 21.0 % 21.0 % 21.0 % State income taxes, net of federal benefit — — ( 0.5 ) Federal tax credits 7.2 13.7 5.2 Other 0.5 ( 0.5 ) ( 0.2 ) Premium on equity issuance — 2.2 — Nondeductible permanent items ( 0.8 ) ( 0.9 ) ( 0.4 ) Stock-based compensation 1.3 0.9 ( 1.0 ) Uncertain tax positions ( 1.4 ) ( 2.7 ) ( 1.0 ) Change in valuation allowance ( 27.9 ) ( 33.9 ) ( 23.6 ) Foreign rate differential ( 0.1 ) ( 0.5 ) ( 0.3 ) Provision for income taxes ( 0.2 ) % ( 0.7 ) % ( 0.8 ) %
Schedule of Tax Effect of Temporary Differences to Significant Portions of Deferred Tax Assets	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, 2021 2020 Deferred tax assets: Loss carryforwards $ 306,119 $ 222,902 Tax credits 218,131 184,961 Stock options 33,564 39,154 Accruals and reserves 25,735 24,922 Fixed assets and intangibles 18,263 7,242 Liability related to sale of future royalties 90,826 86,664 Basis difference in equity investments 3,912 — Other 13,060 28,642 Gross deferred tax assets 709,610 594,487 Valuation allowance ( 700,669 ) ( 561,139 ) Total deferred tax assets 8,941 33,348 Deferred tax liabilities: In-process research and development ( 33,306 ) ( 33,306 ) Basis difference in equity investments — ( 23,019 ) Right-of-use lease assets ( 8,941 ) ( 10,329 ) Gross deferred tax liabilities ( 42,247 ) ( 66,654 ) Net deferred tax liabilities $ ( 33,306 ) $ ( 33,306 )
Unrecognized Tax Benefits	A reconciliation of the Company’s unrecognized tax benefits follows (in thousands): December 31, 2021 2020 2019 Balance at beginning of year $ 46,662 $ 39,954 $ 33,727 Additions based on tax positions related to current 8,542 6,950 5,575 Additions for tax positions of prior years 356 382 652 Reductions for tax positions of prior years ( 200 ) ( 624 ) — Balance at end of year $ 55,360 $ 46,662 $ 39,954

Commitments and Contingencies (

Commitments and Contingencies (Tables)	12 Months Ended
	Dec. 31, 2021
Commitments and Contingencies Disclosure [Abstract]
Summary of Aggregate Payments under Contractually Binding Manufacturing and Service Agreements	As of December 31, 2021, the aggregate payments under contractually binding manufacturing and service agreements are as follows (in thousands): Year Ended December 31, 2022 2023 Manufacturing and Services 19,225 774

Net Loss per Share (Tables)

Net Loss per Share (Tables)	12 Months Ended
	Dec. 31, 2021
Earnings Per Share [Abstract]
Computation of Basic and Diluted 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, 2021, 2020, and 2019 (in thousands, except share and per share data): Year Ended December 31, 2021 2020 2019 Numerator: Net loss $ ( 454,025 ) $ ( 186,566 ) $ ( 402,727 ) Denominator: Weighted-average shares used to compute net loss per 67,795,540 60,845,550 56,576,885 Net loss per share, basic and diluted $ ( 6.70 ) $ ( 3.07 ) $ ( 7.12 )
Outstanding Shares of Common Stock Equivalents Excluded from Computation of Diluted Net Loss per Share	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, 2021 2020 2019 Options to purchase common stock, RSUs, and PSUs 8,214,063 8,532,236 7,978,666 Employee stock purchase plan 3,511 2,626 3,953 Common stock warrants — 29,449 149,700 8,217,574 8,564,311 8,132,319

Accumulated Other Comprehensi_2

Accumulated Other Comprehensive Income (Loss) (Tables)	12 Months Ended
	Dec. 31, 2021
Other Comprehensive Income (Loss), Net of Tax [Abstract]
Schedule of Total Accumulated Other Comprehensive Income (Loss)	Total accumulated other comprehensive income (loss) consisted of the following (in thousands): Year Ended December 31, 2021 2020 Cumulative foreign currency translation adjustment $ ( 121 ) $ 429 Unrealized gain (loss) on securities available-for-sale ( 1,283 ) 260 Total accumulated other comprehensive income (loss) $ ( 1,404 ) $ 689

Organization and Basis of Pre_2

Organization and Basis of Presentation - Additional Information (Details)	12 Months Ended
	Dec. 31, 2021Segment
Organization And Nature Of Business [Line Items]
Number of reportable segments	1

Summary of Significant Accoun_4

Summary of Significant Accounting Policies - Summary of Reconciliation of Cash, Cash Equivalents and Restricted Cash (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Accounting Policies [Abstract]
Cash and cash equivalents	$ 307,584	$ 713,526	$ 433,584
Restricted cash included in prepaid expenses and other current assets		$ 10,847	$ 161
Restricted Cash and Cash Equivalents, Current, Asset, Statement of Financial Position [Extensible List]	Prepaid and Other Current Assets	Prepaid and Other Current Assets	Prepaid and Other Current Assets
Restricted cash included in other assets	$ 2,001	$ 1,921	$ 2,499
Restricted Cash and Cash Equivalents, Noncurrent, Asset, Statement of Financial Position [Extensible List]	us-gaap:OtherNoncurrentAssetsMember	us-gaap:OtherNoncurrentAssetsMember	us-gaap:OtherNoncurrentAssetsMember
Total cash, cash equivalents, and restricted cash shown in the statements of cash flows	$ 309,585	$ 726,294	$ 436,244	$ 115,525

Summary of Significant Accoun_5

Summary of Significant Accounting Policies - Additional Information (Details) - USD ($)	1 Months Ended			12 Months Ended
	Oct. 31, 2020	May 31, 2020	Jun. 30, 2019	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Summary Of Significant Accounting Policies [Line Items]
Common stock, shares issued				69,344,998	66,818,520
Number of option exercised				687,835	1,505,486	235,678
Allowance for doubtful accounts				$ 0	$ 0
Unrecognized tax benefits related to interest or penalties				$ 0
Arcturus
Summary Of Significant Accounting Policies [Line Items]
Common stock, shares issued			2,400,000
Option to purchase additional common stock, shares			600,000
Number of option exercised		600,000
Common stock shares sold				1,700,000	800,000
Collaboration Agreement
Summary Of Significant Accounting Policies [Line Items]
Number of common stock purchased	7,825,797

Summary of Significant Accoun_6

Summary of Significant Accounting Policies - Summary of Useful Lives of Property, Plant and Equipment (Details)	12 Months Ended
	Dec. 31, 2021
Research and Development Equipment
Property Plant And Equipment [Line Items]
Property plant and equipment useful life	5 years
Furniture and Office Equipment
Property Plant And Equipment [Line Items]
Property plant and equipment useful life	5 years
Computer Equipment
Property Plant And Equipment [Line Items]
Property plant and equipment useful life	3 years
Software | Minimum
Property Plant And Equipment [Line Items]
Property plant and equipment useful life	3 years
Software | Maximum
Property Plant And Equipment [Line Items]
Property plant and equipment useful life	5 years
Land
Property Plant And Equipment [Line Items]
Property plant and equipment useful life	Not applicable
Leasehold Improvements
Property Plant And Equipment [Line Items]
Property plant and equipment useful life	Shorter of lease term or estimated useful life

Fair Value Measurements - Summa

Fair Value Measurements - Summary of Financial Assets and Liabilities Measured on Recurring Basis (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	$ 1,001,451	$ 1,327,662
Level 1
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	298,965	921,115
Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	702,486	406,547
Money Market Funds
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	266,765	598,392
Money Market Funds | Level 1
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	266,765	598,392
Asset-backed Securities
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	41,245	11,225
Asset-backed Securities | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	41,245	11,225
Certificate of Deposits and Time Deposits
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	16,000
Certificate of Deposits and Time Deposits | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	16,000
Time Deposits
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value		10,000
Time Deposits | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value		10,000
Corporate Bonds
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	349,691	193,802
Corporate Bonds | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	349,691	193,802
Commercial Paper
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	187,624	173,859
Commercial Paper | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	187,624	173,859
U.S. Government Treasury and Agency Securities
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	87,435	185,628
U.S. Government Treasury and Agency Securities | Level 1
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value		167,967
U.S. Government Treasury and Agency Securities | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	87,435	17,661
Debt Securities in Government Sponsored Entities
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	19,549
Debt Securities in Government Sponsored Entities | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	19,549
Investments in Arcturus and Solid Common Stock
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	32,200	154,756
Investments in Arcturus and Solid Common Stock | Level 1
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	32,200	$ 154,756
Other
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	942
Other | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	$ 942

Fair Value Measurements - Addit

Fair Value Measurements - Additional Information (Details) - USD ($)	1 Months Ended		12 Months Ended
	Oct. 31, 2021	Jul. 31, 2020	Dec. 31, 2021	Dec. 31, 2020
Preferred Stock
Schedule Of Available For Sale Securities [Line Items]
Net carrying value of investments			$ 2,100,000
Convertible Promissory Note
Schedule Of Available For Sale Securities [Line Items]
Investment amount		$ 2,500,000
Debt instrument maturity period		2 years
Debt instrument, face amount			2,400,000	$ 2,100,000
Interest receivable			500,000	200,000
Allocated fair value of warrant			$ 600,000	600,000
Convertible Promissory Note | Mahzi Therapeutics, Inc.
Schedule Of Available For Sale Securities [Line Items]
Investment amount				$ 1,400,000
Convertible Promissory Note | Mahzi Therapeutics, Inc. | Preferred Stock
Schedule Of Available For Sale Securities [Line Items]
Debt conversion, converted instrument, shares issued	606,506
Maximum | Convertible Promissory Note | Dia Carta Ltd
Schedule Of Available For Sale Securities [Line Items]
Warrants issued to purchase preferred stock		$ 1,000,000

Balance Sheet Components - Summ

Balance Sheet Components - Summary of Cash Equivalents and Marketable Debt Securities Classified as Available For Sale Securities (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	$ 969,592	$ 1,172,646
Gross Unrealized Gains	5	277
Gross Unrealized Losses	(1,288)	(17)
Estimated Fair Value	968,309	1,172,906
Money Market Funds
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	266,765	598,392
Estimated Fair Value	266,765	598,392
Asset-backed Securities
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	41,282	11,224
Gross Unrealized Gains	1	1
Gross Unrealized Losses	(38)
Estimated Fair Value	41,245	11,225
Certificate of Deposits and Time Deposits
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	16,000
Estimated Fair Value	16,000
Time Deposits
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost		10,000
Estimated Fair Value		10,000
Corporate Bonds
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	350,667	193,610
Gross Unrealized Gains	3	209
Gross Unrealized Losses	(979)	(17)
Estimated Fair Value	349,691	193,802
Commercial Paper
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	187,624	173,859
Estimated Fair Value	187,624	173,859
U.S. Government Treasury and Agency Securities
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	87,642	185,561
Gross Unrealized Gains	1	67
Gross Unrealized Losses	(208)
Estimated Fair Value	87,435	$ 185,628
Debt Securities in Government Sponsored Entities
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	19,612
Gross Unrealized Losses	(63)
Estimated Fair Value	$ 19,549

Balance Sheet Components - Addi

Balance Sheet Components - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Schedule Of Available For Sale Securities [Line Items]
Depreciation expense	$ 12.9	$ 12.1	$ 8.3
Maximum
Schedule Of Available For Sale Securities [Line Items]
Available-for-sale securities remaining contractual maturities	3 years

Balance Sheet Components - Su_2

Balance Sheet Components - Summary of Inventory (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Investments, Debt and Equity Securities [Abstract]
Work-in-process	$ 10,504	$ 7,184
Finished goods	5,727	5,864
Total	$ 16,231	$ 13,048

Balance Sheet Components - Su_3

Balance Sheet Components - Summary of Property, Plant and Equipment, Net (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Property Plant And Equipment [Line Items]
Property, plant, and equipment, gross	$ 191,285	$ 110,907
Less accumulated depreciation	(50,038)	(37,392)
Property, plant, and equipment, net	141,247	73,515
Leasehold Improvements
Property Plant And Equipment [Line Items]
Property, plant, and equipment, gross	44,081	39,356
Research and Development Equipment
Property Plant And Equipment [Line Items]
Property, plant, and equipment, gross	38,661	28,394
Furniture and Office Equipment
Property Plant And Equipment [Line Items]
Property, plant, and equipment, gross	5,413	5,051
Computer Equipment and Software
Property Plant And Equipment [Line Items]
Property, plant, and equipment, gross	10,238	8,181
Land
Property Plant And Equipment [Line Items]
Property, plant, and equipment, gross	15,487	11,722
Construction-in-progress
Property Plant And Equipment [Line Items]
Property, plant, and equipment, gross	76,849	17,649
Other
Property Plant And Equipment [Line Items]
Property, plant, and equipment, gross	$ 556	$ 554

Balance Sheet Components - Accr

Balance Sheet Components - Accrued Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Payables and Accruals [Abstract]
Research, clinical study, and manufacturing expenses	$ 40,880	$ 25,875
Payroll and related expenses	62,591	58,176
Other	42,084	24,440
Total	$ 145,555	$ 108,491

Intangible Assets, Net - Additi

Intangible Assets, Net - Additional Information (Details) - USD ($)	1 Months Ended	12 Months Ended
	Jun. 30, 2020	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Finite Lived Intangible Assets [Line Items]
Research and development expense related to amortization of assets		$ 497,153,000	$ 412,084,000	$ 357,355,000
Intangible asset impairment charges		0
IPR&D Assets
Finite Lived Intangible Assets [Line Items]
Business combination recognized intangible assets		$ 129,000,000	129,000,000
Dimension
Finite Lived Intangible Assets [Line Items]
Contractual payments received	$ 2,300,000
Intangible assets, remaining amortization period		7 years
Research and development expense related to amortization of assets		$ 300,000	$ 200,000	$ 200,000

Revenue - Summary of Disaggrega

Revenue - Summary of Disaggregation of Total Revenues from Customers (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Total revenues
Total revenues	$ 351,406	$ 271,030	$ 103,714
Collaboration and License
Total revenues
Total revenues	256,438	219,315	83,493
Collaboration and License | Crysvita
Total revenues
Total revenues	171,198	128,597	74,869
Collaboration and License | Royalty Revenue in European Territory | Crysvita
Total revenues
Total revenues	244	1,498	8,120
Collaboration and License | Daiichi Sankyo
Total revenues
Total revenues	84,996	89,220
Collaboration and License | Bayer HealthCare LLC
Total revenues
Total revenues			504
Product Sales
Total revenues
Total revenues	77,017	38,720	20,221
Product Sales | Crysvita
Total revenues
Total revenues	21,422	10,350	4,286
Product Sales | Mepsevii
Total revenues
Total revenues	16,035	15,342	12,634
Product Sales | Dojolvi
Total revenues
Total revenues	39,560	13,028	$ 3,301
Non-cash Collaboration Royalty Revenue
Total revenues
Total revenues	17,951	12,995
Non-cash Collaboration Royalty Revenue | Crysvita
Total revenues
Total revenues	$ 17,951	$ 12,995

Revenue - Summary of Disaggre_2

Revenue - Summary of Disaggregation of Total Revenues (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Disaggregation Of Revenue [Line Items]
Total revenues	$ 351,406	$ 271,030	$ 103,714
North America
Disaggregation Of Revenue [Line Items]
Total revenues	301,110	237,666	86,442
Europe
Disaggregation Of Revenue [Line Items]
Total revenues	26,660	21,318	12,085
All other
Disaggregation Of Revenue [Line Items]
Total revenues	$ 23,636	$ 12,046	$ 5,187

Revenue - Schedule of Sales-Rel

Revenue - Schedule of Sales-Related Accruals and Allowances (Details) - Product Sales - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Disaggregation Of Revenue [Line Items]
Balance of product sales reserve at beginning of year	$ 3,913	$ 1,818	$ 1,240
Provisions	9,586	5,763	3,846
Payments	(6,120)	(2,785)	(2,739)
Adjustments	(198)	(883)	(529)
Balance of product sales reserve at end of year	$ 7,181	$ 3,913	$ 1,818

Revenue - Summary of Changes in

Revenue - Summary of Changes in Contract Assets (Liabilities) (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Disaggregation of Revenue [Abstract]
Balance of contract liabilities at beginning of period	$ (66,568)
Additions	(27,504)	$ (155,788)
Deductions	84,996	89,220
Balance of contract liabilities at end of period, net	$ (9,076)	$ (66,568)

Revenue - Additional Informatio

Revenue - Additional Information (Details)	Dec. 31, 2021	Dec. 31, 2020
Disaggregation of Revenue [Abstract]
Percentage of gross accounts receivable balance	71.00%	71.00%

License and Research Agreemen_3

License and Research Agreements - Additional Information (Details)	Jan. 01, 2023	Oct. 31, 2020USD ($)shares	May 31, 2020USD ($)shares	Mar. 31, 2020USD ($)$ / sharesshares	Aug. 31, 2019USD ($)	Jun. 30, 2019USD ($)DiseaseTarget$ / sharesshares	Oct. 31, 2015USD ($)	Dec. 31, 2021USD ($)$ / sharesshares	Dec. 31, 2021USD ($)qtr$ / sharesshares	Dec. 31, 2020USD ($)$ / sharesshares	Dec. 31, 2019USD ($)	Dec. 31, 2022
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Collaboration and license revenue									$ 351,406,000	$ 271,030,000	$ 103,714,000
Research and development									$ 497,153,000	$ 412,084,000	357,355,000
Common stock purchased | shares								69,344,998	69,344,998	66,818,520
Common stock. per share | $ / shares								$ 0.001	$ 0.001	$ 0.001
Common stock investment value								$ 69,000	$ 69,000	$ 67,000
Common stock, par value | $ / shares								$ 0.001	$ 0.001	$ 0.001
Proceeds from issuance of common stock in connection with license agreement										$ 55,268,000
Issuance of common stock in connection with license agreement, net of issuance costs										55,268,000
Daiichi Sankyo
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Deferred revenue								$ 9,100,000	$ 9,100,000	66,600,000
Revenue recognized									85,000,000	89,200,000
Receivable related to Daiichi Sankyo license agreement								100,000	100,000	1,200,000
Solid Biosciences, Inc.
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Business acquisition, consideration transferred										40,000,000
Common stock investment value		$ 26,800,000
Remaining consideration paid										13,200,000
Product Sales
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Collaboration and license revenue									77,017,000	38,720,000	20,221,000
Kyowa Kirin Collaboration | License Agreement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Collaboration and license revenue									200,000	1,500,000
Kyowa Kirin Collaboration | License Agreement | Prepaid and Other Current Assets
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
License agreement other receivables								16,000,000	16,000,000	9,600,000
Kyowa Kirin Collaboration | License Agreement | Product Sales
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Collaboration and license revenue									21,400,000	10,400,000	4,300,000
Kyowa Kirin Collaboration | License Agreement | Profit Share Revenue
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
License agreement accounts receivable								20,200,000	20,200,000	16,400,000
Kyowa Kirin Collaboration | License Agreement | Commercial and Development Activity Reimbursements
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
License agreement accrued liabilities								2,300,000	$ 2,300,000	2,400,000
Kyowa Kirin Collaboration | License Agreement | Scenario Forecast
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Profit loss sharing percentage on net sales	30.00%											35.00%
Kyowa Kirin Collaboration | License Agreement | Profit Share Territory
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Remaining profit or loss share percentage on commercializing products									50.00%
Tiered double-digit revenue share percentage entitled to receive									20.00%
Kyowa Kirin Collaboration | License Agreement | Royalty Revenue in European Territory
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Percentage of royalty on net sales receives									10.00%
Saint Louis University License Agreement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Milestone payments paid									$ 100,000
Baylor Research Institute License Agreement | Development Milestones
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Contingent milestone payment										2,000,000
Baylor Research Institute License Agreement | Development Milestones | Maximum
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future milestone payments								2,500,000	2,500,000
Baylor Research Institute License Agreement | Sales Milestones
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future milestone payments								7,500,000	$ 7,500,000
Option and License Agreement | REGENXBIO, Inc.
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Option and license agreement description									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.
Annual maintenance fee for each option exercised									$ 100,000
Option and License Agreement | Maximum | REGENXBIO, Inc.
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future milestone payments								9,000,000	9,000,000
License Agreement | REGENXBIO, Inc.
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Upfront payment for in-process research and development expense				$ 7,000,000
Annual fees payable									100,000
License Agreement | Maximum | REGENXBIO, Inc.
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future milestone payments								14,000,000	14,000,000
Research, Develop and Commercialize AAV Gene Therapy Products | Bayer HealthCare LLC
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Milestone payments received									15,000,000
Research, Develop and Commercialize AAV Gene Therapy Products | Maximum | Bayer HealthCare LLC
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future milestone payments								232,000,000	232,000,000
Research Collaboration and License Agreement Development Milestones | Maximum | University of Pennsylvania School of Medicine (Penn)
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future milestone payments								5,000,000	5,000,000
Research Collaboration and License Agreement Commercial Milestones | Maximum | University of Pennsylvania School of Medicine (Penn)
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future milestone payments								$ 25,000,000	25,000,000
Arcturus Research Collaboration and License Agreement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Milestone payments received									1,000,000
Research and development										$ 400,000	800,000
Upfornt cash payment paid						$ 6,000,000
Common stock purchased | shares						2,400,000
Common stock. per share | $ / shares						$ 10		$ 47.44	$ 47.44	$ 100.81
Business acquisition, consideration transferred						$ 30,000,000
Additional option to purchase common stock | shares						600,000
Additional option to purchase common stock value per share | $ / shares						$ 16
Number of shares purchased on exercise of common stock option | shares			600,000
Purchase price of shares purchased on exercise of common stock option			$ 9,600,000
Common stock shares sold | shares									1,700,000	800,000
Common stock, par value | $ / shares						$ 10		$ 47.44	$ 47.44	$ 100.81
Number of common stock held | shares								500,000	500,000	2,200,000
Arcturus Research Collaboration and License Agreement | Maximum
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Number of disease targets | DiseaseTarget						12
Regulatory milestone payments							$ 24,500,000
Commercial milestone payments							$ 45,000,000
Program Agreement and Unitholder Option Agreement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Upfront payment for in-process research and development expense										$ 25,000,000	$ 20,000,000
Program Agreement and Unitholder Option Agreement | GeneTx Biotherapeutics LLC
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Business acquisition, consideration transferred					$ 125,000,000
Upfront payment for exclusive option to acquisition					20,000,000
Business acquisition option exercise period, description									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.
Option extension Premium					$ 25,000,000
Exercise of option extension, right to acquire condition									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.
Program Agreement and Unitholder Option Agreement | Maximum | GeneTx Biotherapeutics LLC
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Extension period available for right to acquisition | qtr									4
License and Technology Access Agreement | Daiichi Sankyo
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Revenue recognized									$ 174,200,000
Deferred revenue								$ 25,000,000	25,000,000
Upfront payment received								125,000,000	125,000,000
Premium from stock purchase agreement									19,700,000
Transaction price of license agreement									183,300,000
Estimated reimbursement of delivering license and technology services									5,600,000
License and Technology Access Agreement | HeLA PCL Platform | Daiichi Sankyo
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Deferred revenue								$ 25,000,000	25,000,000
License and Technology Access Agreement | Sublicense Agreement | Daiichi Sankyo
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Revenue from sublicense agreement									8,000,000
Stock Purchase Agreement | Daiichi Sankyo
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Issuance of common stock in connection with license agreement, net of issuance costs, shares | shares				1,243,913
Proceeds from issuance of common stock in connection with license agreement				$ 75,000,000
Issuance of common stock in connection with license agreement, net of issuance costs				$ 55,300,000
Stock price | $ / shares				$ 44.43
Premium from stock purchase agreement				$ 19,700,000
Sublicense Agreement | Daiichi Sankyo
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Upfront payment received									$ 8,000,000
Collaboration and License Agreement | Maximum | Solid Biosciences, Inc.
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Development milestone payments		25,000,000
Regulatory milestone payments		65,000,000
Commercial milestone payments		$ 165,000,000
Collaboration Agreement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Number of common stock purchased | shares		7,825,797
Collaboration Agreement | Solid Biosciences, Inc.
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Number of common stock purchased | shares		7,825,797
Aggregate purchase price		$ 40,000,000

License and Research Agreemen_4

License and Research Agreements - Share of Collaboration and Royalty Revenue Related to Crysvita (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	$ 351,406	$ 271,030	$ 103,714
Collaboration and Royalty | Kyowa Kirin Collaboration
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	189,393	143,090	82,989
Collaboration and Royalty | Kyowa Kirin Collaboration | Profit Share Territory
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	171,198	128,597	74,869
Collaboration and Royalty | Kyowa Kirin Collaboration | Royalty Revenue in European Territory
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	244	1,498	$ 8,120
Non-cash Collaboration Royalty Revenue
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	17,951	12,995
Non-cash Collaboration Royalty Revenue | Kyowa Kirin Collaboration | Royalty Revenue in European Territory
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	$ 17,951	$ 12,995

License and Research Agreemen_5

License and Research Agreements - Schedule of Cost Sharing Payments (Details) - Kyowa Kirin Collaboration - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Cost Sharing Payments [Line Items]
Research and development	$ 21,657	$ 21,476	$ 27,309
Selling, general and administrative	32,629	25,186	21,828
Total	$ 54,286	$ 46,662	$ 49,137

License and Research Agreemen_6

License and Research Agreements - Schedule of Changes in Fair Value of Equity Investment (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Common stock, Beginning balance	$ 1,327,662
Common stock, Ending balance	1,001,451	$ 1,327,662
Arcturus
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Common stock, Beginning balance	95,436	27,752
Common stock, Change in fair value	2,912	137,926
Common stock, Transfer of value upon option exercise		9,600
Common stock, Sale of shares	(79,843)	(79,842)
Common stock, Ending balance	18,505	95,436
Fair value of option to purchase common stock, Beginning balance		1,664
Fair value of option to purchase common stock, Change in fair value		23,948
Fair value of option to purchase of common stock, Transfer of value upon option exercise		(25,612)
Arcturus | Common Stock
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Common stock, Beginning balance	95,436	26,088
Common stock, Change in fair value	2,912	113,978
Common stock, Transfer of value upon option exercise		35,212
Common stock, Sale of shares	(79,843)	(79,842)
Common stock, Ending balance	$ 18,505	$ 95,436

License and Research Agreemen_7

License and Research Agreements - Schedule of Changes in Fair Value of Investment in Securities (Details) - USD ($) $ in Thousands	3 Months Ended	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2021
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Common stock, Beginning balance		$ 1,327,662
Common stock, Ending balance	$ 1,327,662	1,001,451
Common Stock | Solid Biosciences, Inc.
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Common stock, Beginning balance		59,320
Common stock, Acquisition of investment in securities	26,843
Common stock, Change in fair value	32,477	(45,625)
Common stock, Ending balance	$ 59,320	$ 13,695

Leases - Additional Information

Leases - Additional Information (Details) $ in Millions	12 Months Ended
	Dec. 31, 2021USD ($)
Lessee Disclosure [Abstract]
Operating lease extension details	multiple renewal periods
Operating lease, existence of option to extend	true
Operating lease expiry term	2028
Cash paid for measurement of operating lease liabilities	$ 11.8
Operating lease weighted average remaining lease term	3 years 10 months 2 days
Financing lease weighted average remaining lease term	3 years 10 months 17 days
Operating lease weighted average discount rate	6.64%
Financing lease weighted average discount rate	5.44%

Leases - Summary of Components

Leases - Summary of Components of Lease Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Lease, Cost [Abstract]
Operating lease expense	$ 11,209	$ 10,164
Variable lease expense	4,142	3,298
Financing:
Amortization	310	158
Interest expense	58	40
Total	$ 15,719	$ 13,660

Leases - Summary of Future Mini

Leases - Summary of Future Minimum Lease Payments under Non-cancellable Leases (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Operating
2022	$ 12,873
2023	13,072
2024	11,092
2025	6,247
2026	2,681
Thereafter	776
Total future lease payments	46,741
Less: Amount representing interest	(5,749)
Present value of future lease payments	40,992
Less: Lease liabilities, current	$ (10,498)
Operating Lease, Liability, Statement of Financial Position [Extensible List]	Less: Lease liabilities, current
Lease liabilities, non-current	$ 30,494
Operating Lease, Liability, Statement of Financial Position [Extensible List]	Non-current lease liability
Financing
2022	$ 606
2023	349
2024	75
Total future lease payments	1,030
Less: Amount representing interest	(52)
Present value of future lease payments	978
Less: Lease liabilities, current	(568)
Lease liabilities, non-current	410
Future Minimum Lease Payments - Operating and Financing Leases
2022	13,479
2023	13,421
2024	11,167
2025	6,247
2026	2,681
Thereafter	776
Total future lease payments	47,771
Less: Amount representing interest	(5,801)
Present value of future lease payments	41,970
Less: Lease liabilities, current	$ (11,066)	$ (8,976)
Finance Lease, Liability, Current, Statement of Financial Position [Extensible Enumeration]	Less: Lease liabilities, current
Non-current lease liability	$ 30,904	$ 39,251
Finance Lease, Liability, Noncurrent, Statement of Financial Position [Extensible Enumeration]	Non-current lease liability

Liability Related to the Sale_3

Liability Related to the Sale of Future Royalties - Additional Information (Details) - USD ($)	1 Months Ended	12 Months Ended
	Dec. 31, 2019	Dec. 31, 2021	Dec. 31, 2019
Liability Related To Sale Of Future Royalties [Line Items]
Proceeds from the sale of future royalties, net			$ 314,234,000
Royalty Purchase Agreement | RPI Finance Trust (RPI)
Liability Related To Sale Of Future Royalties [Line Items]
Proceeds from sale of future royalties	$ 320,000,000
Royalty payment termination description		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.
Royalties transaction costs net	5,800,000
Proceeds from the sale of future royalties, net	314,200,000
Effective annual interest rate		9.60%
Royalty Purchase Agreement | Minimum | RPI Finance Trust (RPI)
Liability Related To Sale Of Future Royalties [Line Items]
Royalty agreement termination threshold amount	608,000,000		608,000,000
Royalty Purchase Agreement | Maximum | RPI Finance Trust (RPI)
Liability Related To Sale Of Future Royalties [Line Items]
Royalty agreement termination threshold amount	$ 800,000,000		$ 800,000,000

Liability Related to the Sale_4

Liability Related to the Sale of Future Royalties - Schedule of Activity Within Liability Related to Sale of Future Royalties (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020
Deferred Revenue Disclosure [Abstract]
Liability related to the sale of future royalties at beginning of year	$ 335,665	$ 315,369
Non-cash collaboration royalty revenue	(17,951)	(12,995)
Non-cash interest expense	34,072	33,291
Liability related to the sale of future royalties at end of year	$ 351,786	$ 335,665

Equity - Additional Information

Equity - Additional Information (Details) - USD ($) $ / shares in Units, $ in Thousands	1 Months Ended				12 Months Ended
	May 31, 2021	Oct. 31, 2020	Feb. 28, 2019	Jul. 31, 2017	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Stockholders Equity [Line Items]
Net proceeds from sale of common stock						$ 435,556	$ 330,415
Stock sold in at-the-market offering					1,050,372
Net proceeds from at-the-market offering					$ 78,943	$ 20,391	$ 24,828
Common Stock Warrants Expiring on 2020
Stockholders Equity [Line Items]
Common stock warrants outstanding							149,700	149,700
Common stock warrants, exercise price							$ 3.01	$ 3.01
Common stock warrants, expiration period							2020	2020
Common Stock Warrants Expiring on 2021
Stockholders Equity [Line Items]
Common stock warrants outstanding							149,700	149,700
Common stock warrants, exercise price							$ 3.01	$ 3.01
Common stock warrants, expiration period							2021	2021
Additional ATM Sales Agreement
Stockholders Equity [Line Items]
Option to sell common stock for cash				$ 150,000
Common stock shares sold						283,333	468,685
Net proceeds from sale of common stock						$ 20,400	$ 24,800
Underwritten Public Offering
Stockholders Equity [Line Items]
Common stock shares sold		5,111,110	5,833,333
Net proceeds from sale of common stock		$ 435,600	$ 330,400
Shares purchased by underwriters		666,666	760,869
Public offering price		$ 90	$ 60
Open Market Sale
Stockholders Equity [Line Items]
Option to sell common stock aggregate offering price	$ 350,000

Stock-Based Awards - Additional

Stock-Based Awards - Additional Information (Details) - USD ($) $ / shares in Units, $ in Millions	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019	Feb. 01, 2021	Feb. 05, 2014	Jan. 31, 2014
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Total intrinsic value of options exercised	$ 38.3	$ 56.9	$ 6.5
Cash received from exercise of options	$ 36.6	$ 88.1	$ 7.7
Weighted-average estimated fair value of stock option	$ 70.84	$ 35.22	$ 37.15
Total estimated fair value of options vested	$ 48.1	$ 45.4	$ 45.3
Total unrecognized compensation cost	$ 200
Weighted-average period to recognize cost	2 years 3 months 29 days
Stock-based compensation capitalized to inventory	$ 1.7	1.2	1.4
Restricted Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Total fair value of shares vested	35.5	27.2	20.8
Aggregate intrinsic value	69.9	29.5	18.4
Performance Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Total fair value of shares vested	9.2	10.3	3.2
Aggregate intrinsic value	$ 18.9	$ 14.4	$ 4.2
Maximum | Restricted Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Stock based awards vesting period	4 years
Minimum | Restricted Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Stock based awards vesting period	1 year
2014 Incentive Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Share of common stock authorized for future issuance					2,250,000
Automatic increases in shares available for grant effective date	Jan. 1, 2015
Shares available for grant, ending date	Jan. 1, 2024
2014 Incentive Plan | Employee Stock Option
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Minimum percentage of voting rights of all classes of stock	10.00%
Percentage of statutory stock awards	110.00%
2014 Incentive Plan | Maximum | Employee Stock Option
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Award expiration period	10 years
2011 Equity Incentive Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Share of common stock authorized for future issuance					655,038
2011 Equity Incentive Plan | Restricted Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Option vesting rights, percentage	25.00%
Stock based awards vesting period	4 years
2011 Equity Incentive Plan | First Anniversary | Employee Stock Option
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Option vesting rights, percentage	25.00%
2011 Equity Incentive Plan | Shares Vesting Monthly After First Anniversary | Employee Stock Option
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Option vesting rights, percentage	2.08%
2011 Equity Incentive, 2014 Incentive and Employment Inducement Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Share of common stock authorized for future issuance	12,462,795
2014 Employee Stock Purchase Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Share of common stock authorized for future issuance	3,925,798
Automatic increases in shares available for grant effective date	Jan. 1, 2015
Shares available for grant, ending date	Jan. 1, 2024
Share of common stock available for future issuance						600,000
Percentage of statutory stock awards	85.00%
Common stock shares issued	69,738
Employment Inducement Plan | Maximum
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Share of common stock available for future issuance				500,000

Stock-Based Awards - Summary of

Stock-Based Awards - Summary of Activity Under Stock Option Plans Including 2011 Plan and 2014 Plan (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Share-based Payment Arrangement [Abstract]
Number of Options, Outstanding, Beginning Balance	6,004,603	6,113,064	5,353,124
Number of Options, Options granted	1,217,820	1,849,106	1,762,075
Number of Options, Options exercised	(687,835)	(1,505,486)	(235,678)
Number of Options, Options cancelled	(336,383)	(452,081)	(766,457)
Number of Options, Outstanding, Ending Balance	6,198,205	6,004,603	6,113,064	5,353,124
Number of Options, Vested and exercisable - December 31, 2021	3,669,577
Number of Options, Vested and expected to vest - December 31, 2021	5,951,372
Weighted Average Exercise Price, Outstanding, Beginning Balance	$ 62.99	$ 62.51	$ 62.46
Weighted Average Exercise Price, Options granted	128.63	62.51	63.03
Weighted Average Exercise Price, Options exercised	53.14	58.51	32.87
Weighted Average Exercise Price, Options cancelled	81.78	69.38	72.48
Weighted Average Exercise Price, Outstanding, Ending Balance	75.96	$ 62.99	$ 62.51	$ 62.46
Weighted Average Exercise Price, Vested and exercisable - December 31, 2021	64.93
Weighted Average Exercise Price, Vested and expected to vest - December 31, 2021	$ 75.09
Weighted Average Remaining Contractual Term (Years), Outstanding	6 years 9 months 21 days	7 years 2 months 15 days	7 years	7 years 2 months 19 days
Weighted Average Remaining Contractual Term (Years), Vested and exercisable - December 31, 2021	5 years 7 months 28 days
Weighted Average Remaining Contractual Term (Years), Vested and expected to vest - December 31, 2021	6 years 8 months 23 days
Aggregate Intrinsic Value, Outstanding	$ 112,242	$ 453,253	$ 18,989	$ 23,243
Aggregate Intrinsic Value, Vested and exercisable - December 31, 2021	80,283
Aggregate Intrinsic Value, Vested and expected to vest - December 31, 2021	$ 109,665

Stock-Based Awards - Summary _2

Stock-Based Awards - Summary of Activity Under Restricted Stock Units (RSUs) from 2014 Plan (Details) - Restricted Stock Units - $ / shares	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Outstanding, Number of Shares, Unvested, Beginning Balance	1,681,167	1,298,150	954,077
Number of Shares, granted	738,905	967,310	863,065
Number of Shares, vested	(559,595)	(434,153)	(313,682)
Number of Shares, cancelled	(187,852)	(150,140)	(205,310)
Outstanding, Number of Shares, Unvested, Ending Balance	1,672,625	1,681,167	1,298,150
Outstanding, Weighted-Average Grant Date Fair Value, Unvested, Beginning Balance	$ 63.21	$ 61.96	$ 63.12
Weighted-Average Grant Date Fair Value, granted	122.71	64.36	62.78
Weighted-Average Grant Date Fair Value, vested	63.41	62.65	66.25
Weighted-Average Grant Date Fair Value, cancelled	80.55	61.42	64.28
Outstanding, Weighted-Average Grant Date Fair Value, Unvested, Ending Balance	$ 87.48	$ 63.21	$ 61.96

Stock-Based Awards - Summary _3

Stock-Based Awards - Summary of Activity Under PSUs from 2014 Plan (Details) - Performance Stock Units - $ / shares	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Outstanding, Number of Shares, Unvested, Beginning Balance	212,566	399,540	483,200
Number of Shares, granted	62,000	47,600	61,500
Number of Shares, vested	(168,274)	(200,867)	(65,643)
Number of Shares, cancelled	(12,400)	(33,707)	(79,517)
Outstanding, Number of Shares, Unvested, Ending Balance	93,892	212,566	399,540
Outstanding, Weighted-Average Grant Date Fair Value, Unvested, Beginning Balance	$ 54.64	$ 52.56	$ 49.65
Weighted-Average Grant Date Fair Value, granted	158.11	56.08	67.31
Weighted-Average Grant Date Fair Value, vested	54.40	51.21	48.03
Weighted-Average Grant Date Fair Value, cancelled	54.28	52.48	50.01
Outstanding, Weighted-Average Grant Date Fair Value, Unvested, Ending Balance	$ 123.46	$ 54.64	$ 52.56

Stock-Based Awards - Summary _4

Stock-Based Awards - Summary of Stock-Based Compensation Recognized (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Stock-based compensation expense	$ 104,979	$ 85,735	$ 81,995
Cost of sales
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Stock-based compensation expense	871	827	1,084
Research and development
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Stock-based compensation expense	59,097	47,949	44,205
Selling, general and administrative
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Stock-based compensation expense	$ 45,011	$ 36,959	$ 36,706

Stock-Based Awards - Fair Value

Stock-Based Awards - Fair Value of Stock Option Awards Granted Estimated Using Black-Scholes Option-Pricing Model (Details) - Stock Options	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Expected term (years)	6 years 21 days	6 years 2 months 12 days	6 years 2 months 19 days
Expected volatility	60.00%	61.00%	61.00%
Risk-free interest rate	1.00%	0.80%	2.40%
Expected dividend rate	0.00%	0.00%	0.00%

Defined Contribution Plan - Add

Defined Contribution Plan - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Defined Contribution Pension And Other Post Retirement Plans Disclosure [Abstract]
Contribution expenses	$ 5.5	$ 4.3	$ 3.6

Income Taxes - Components of Co

Income Taxes - Components of Company's Loss Before Income Taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Income Tax Disclosure [Abstract]
Domestic	$ 455,314	$ 189,449	$ 399,709
Foreign	(2,333)	(4,090)	(265)
Total loss before income taxes	$ 452,981	$ 185,359	$ 399,444

Income Taxes - Components of _2

Income Taxes - Components of Company's Income Tax Provision (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Current provision for income taxes:
State	$ (14)	$ 15	$ 51
International	1,058	1,192	1,092
Total current tax provision	1,044	1,207	1,143
Deferred tax provision:
State			2,140
Total deferred tax provision			2,140
Total provision for income taxes	$ 1,044	$ 1,207	$ 3,283

Income Taxes - Effective Tax Ra

Income Taxes - Effective Tax Rate of Provision for Income Taxes from Federal Statutory Rate (Details)	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Effective Income Tax Rate Reconciliation, Percent [Abstract]
Federal statutory income tax rate	21.00%	21.00%	21.00%
State income taxes, net of federal benefit			(0.50%)
Federal tax credits	7.20%	13.70%	5.20%
Other	0.50%	(0.50%)	(0.20%)
Premium on equity issuance		2.20%
Nondeductible permanent items	(0.80%)	(0.90%)	(0.40%)
Stock-based compensation	1.30%	0.90%	(1.00%)
Uncertain tax positions	(1.40%)	(2.70%)	(1.00%)
Change in valuation allowance	(27.90%)	(33.90%)	(23.60%)
Foreign rate differential	(0.10%)	(0.50%)	(0.30%)
Provision for income taxes	(0.20%)	(0.70%)	(0.80%)

Income Taxes - Schedule of Tax

Income Taxes - Schedule of Tax Effect of Temporary Differences to Significant Portions of Deferred Tax Assets (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2012	Dec. 31, 2011
Deferred tax assets:
Loss carryforwards	$ 306,119	$ 222,902	$ 200	$ 200
Tax credits	218,131	184,961
Stock options	33,564	39,154
Accruals and reserves	25,735	24,922
Fixed assets and intangibles	18,263	7,242
Liability related to sale of future royalties	90,826	86,664
Basis difference in equity investments	3,912
Other	13,060	28,642
Gross deferred tax assets	709,610	594,487
Valuation allowance	(700,669)	(561,139)
Total deferred tax assets	8,941	33,348
Deferred tax liabilities:
Gross deferred tax liabilities	(42,247)	(66,654)
Net deferred tax liabilities	(33,306)	(33,306)
Right-of-use Lease Assets
Deferred tax liabilities:
Gross deferred tax liabilities	(8,941)	(10,329)
Basis Difference in Equity Investments
Deferred tax liabilities:
Gross deferred tax liabilities		(23,019)
In-process Research and Development
Deferred tax liabilities:
Gross deferred tax liabilities	$ (33,306)	$ (33,306)

Income Taxes - Additional Infor

Income Taxes - Additional Information (Details) - USD ($)	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2012	Dec. 31, 2011
Tax Credit Carryforward [Line Items]
Deferred tax assets net operating loss carryforwards	$ 306,119,000	$ 222,902,000	$ 200,000	$ 200,000
Valuation allowance increased	139,500,000	74,300,000
Unrecognized tax benefits, income tax penalties and interest accrued	0	0
Undistributed earnings of foreign subsidiaries	4,100,000
Federal
Tax Credit Carryforward [Line Items]
Deferred tax assets operating loss carryforwards subject to expiration	$ 1,085,400,000	750,200,000
Operating loss carryforwards expiration year	2031
Tax credit carryforwards	$ 22,900,000	17,700,000
Tax credit carryforwards expiration year	2030
Deferred tax assets net operating loss carryforwards			3,600,000	3,600,000
Federal | Orphan Drug Credits [Member]
Tax Credit Carryforward [Line Items]
Deferred tax assets operating loss carryforwards subject to expiration	$ 208,100,000	179,800,000
Operating loss carryforwards expiration year	2031
State
Tax Credit Carryforward [Line Items]
Deferred tax assets operating loss carryforwards subject to expiration	$ 777,000,000	616,800,000
Operating loss carryforwards expiration year	2031
Tax credit carryforwards	$ 44,600,000	$ 34,500,000
Deferred tax assets net operating loss carryforwards			$ 3,600,000	$ 3,600,000

Income Taxes - Unrecognized Tax

Income Taxes - Unrecognized Tax Benefits (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Income Tax Disclosure [Abstract]
Balance at beginning of year	$ 46,662	$ 39,954	$ 33,727
Additions based on tax positions related to current year	8,542	6,950	5,575
Additions for tax positions of prior years	356	382	652
Reductions for tax positions of prior years	(200)	(624)
Balance at end of year	$ 55,360	$ 46,662	$ 39,954

Commitments and Contingencies -

Commitments and Contingencies - Summary of Aggregate Payments under Contractually Binding Manufacturing and Service Agreements (Details) - Manufacturing and Services $ in Thousands	Dec. 31, 2021USD ($)
Commitments And Contingencies Disclosure [Line Items]
2022	$ 19,225
2023	$ 774

Net Loss per Share - Computatio

Net Loss per Share - Computation of Basic and Diluted Net Loss per Share (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Numerator:
Net loss	$ (454,025)	$ (186,566)	$ (402,727)
Denominator:
Weighted-average shares used in computing net loss per share, basic and diluted	67,795,540	60,845,550	56,576,885
Net loss per share, basic and diluted	$ (6.70)	$ (3.07)	$ (7.12)

Net Loss per Share - Outstandin

Net Loss per Share - Outstanding Shares of Common Stock Equivalents Excluded from Computation of Diluted Net Loss per Share (Details) - shares	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Common stock equivalents excluded from computation of diluted net loss per share	8,217,574	8,564,311	8,132,319
Options to Purchase Common Stock, RSUs, and PSUs
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Common stock equivalents excluded from computation of diluted net loss per share	8,214,063	8,532,236	7,978,666
Common Stock Warrants
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Common stock equivalents excluded from computation of diluted net loss per share		29,449	149,700
Employee Stock Purchase Plan
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Common stock equivalents excluded from computation of diluted net loss per share	3,511	2,626	3,953

Accumulated Other Comprehensi_3

Accumulated Other Comprehensive Income (Loss) - Schedule of Total Accumulated Other Comprehensive income (Loss) (Details) - USD ($) $ in Thousands	Dec. 31, 2021	Dec. 31, 2020
Accumulated Other Comprehensive Income (Loss), Net of Tax [Abstract]
Cumulative foreign currency translation adjustment	$ (121)	$ 429
Unrealized gain (loss) on securities available-for-sale	(1,283)	260
Total accumulated other comprehensive income (loss)	$ (1,404)	$ 689

Subsequent Event - Additional I

Subsequent Event - Additional Information (Details) - Subsequent Event - Regeneron $ in Millions	Jan. 07, 2022USD ($)
Subsequent Event [Line Items]
Upfront payments of collaboration	$ 30
Eligible future milestone payments	$ 63