0000950170-23-003096 | 10-K | XBRL Viewer | Ultragenyx Pharmaceutical INC

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Document and Entity Information - USD ($) $ in Billions	12 Months Ended
Document and Entity Information - USD ($) $ in Billions	Dec. 31, 2022	Feb. 13, 2023	Jun. 30, 2022
Cover [Abstract]
Document Type	10-K
Amendment Flag	false
Document Period End Date	Dec. 31, 2022
Document Fiscal Year Focus	2022
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		70,216,689
Entity Public Float			$ 3.3
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 2023 Annual Meeting of Stockholders, to be held on or about June 7, 2023, 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	San Mateo, California

CONSOLIDATED BALANCE SHEETS - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Current assets:
Cash and cash equivalents	$ 132,944	$ 307,584
Marketable debt securities	614,818	432,612
Accounts receivable, net	40,445	28,432
Inventory	26,766	16,231
Prepaid expenses and other current assets	68,926	71,745
Total current assets	883,899	856,604
Property, plant, and equipment, net	259,726	141,247
Equity investments	5,531	34,925
Marketable debt securities	148,970	258,933
Right-of-use assets	25,961	34,936
Intangible assets, net	160,105	130,788
Goodwill	44,406	44,406
Other assets	16,846	20,558
Total assets	1,545,444	1,522,397
Current liabilities:
Accounts payable	43,274	17,138
Accrued liabilities	204,678	145,555
Contract liabilities	1,479	7,609
Lease liabilities	11,779	11,066
Total current liabilities	261,210	181,368
Contract liabilities	0	1,467
Lease liabilities	19,814	30,904
Deferred tax liabilities	31,667	33,306
Liabilities for sales of future royalties	875,439	351,786
Other liabilities	4,820	1,005
Total liabilities	1,192,950	599,836
Commitments and contingencies (Notes 9 and 15)
Stockholders’ equity:
Preferred stock, par value of $0.001 per share - 25,000,000 shares authorized; nil outstanding as of December 31, 2022 and December 31, 2021	0	0
Common stock, par value of $0.001 per share - 250,000,000 shares authorized; 70,197,297 and 69,344,998 shares issued and outstanding as of December 31, 2022 and December 31, 2021, respectively	70	69
Additional paid-in capital	3,140,019	2,997,497
Accumulated other comprehensive loss	(6,573)	(1,404)
Accumulated deficit	(2,781,022)	(2,073,601)
Total stockholders’ equity	352,494	922,561
Total liabilities and stockholders’ equity	$ 1,545,444	$ 1,522,397

CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares	Dec. 31, 2022	Dec. 31, 2021
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	70,197,297	69,344,998
Common stock, shares outstanding	70,197,297	69,344,998

CONSOLIDATED STATEMENTS OF OPERATIONS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Revenues:
Total revenues	$ 363,329	$ 351,406	$ 271,030
Operating expenses:
Cost of sales	28,320	16,008	6,129
Research and development	705,789	497,153	412,084
Selling, general and administrative	278,139	219,982	182,933
Total operating expenses	1,012,248	733,143	601,146
Loss from operations	(648,919)	(381,737)	(330,116)
Interest income	11,074	1,928	7,038
Change in fair value of equity investments	(19,299)	(42,063)	170,403
Non-cash interest expense on liabilities for sales of future royalties	(43,015)	(29,422)	(33,291)
Other income (expense)	(1,566)	(1,687)	607
Loss before income taxes	(701,725)	(452,981)	(185,359)
Provision for income taxes	(5,696)	(1,044)	(1,207)
Net loss	$ (707,421)	$ (454,025)	$ (186,566)
Earnings Per Share, Basic	$ (10.12)	$ (6.70)	$ (3.07)
Earnings Per Share, Diluted	$ (10.12)	$ (6.70)	$ (3.07)
Weighted Average Number of Shares Outstanding, Basic	69,914,225	67,795,540	60,845,550
Weighted Average Number of Shares Outstanding, Diluted	69,914,225	67,795,540	60,845,550
Collaboration and License
Revenues:
Total revenues	$ 222,710	$ 256,438	$ 219,315
Product Sales
Revenues:
Total revenues	118,927	77,017	38,720
Non-cash Collaboration Royalty Revenue
Revenues:
Total revenues	$ 21,692	$ 17,951	$ 12,995

CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Statement of Comprehensive Income [Abstract]
Net loss	$ (707,421)	$ (454,025)	$ (186,566)
Other comprehensive income (loss):
Foreign currency translation adjustments	(724)	(550)	735
Unrealized gain (loss) on available-for-sale securities	(4,445)	(1,543)	101
Other comprehensive income (loss):	(5,169)	(2,093)	836
Total comprehensive loss	$ (712,590)	$ (456,118)	$ (185,730)

- Definition

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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, 2019	$ 653,764	$ 58	$ 2,086,863	$ (147)	$ (1,433,010)
Beginning 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 (loss)	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
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 (loss)	(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
Stock-based compensation	$ 131,710		131,710
Issuance of common stock under equity plan awards, net of tax	10,813	$ 1	10,812
Issuance of common stock under equity plan awards, net of tax, shares		852,299
Other comprehensive income (loss)	(5,169)			(5,169)
Net loss	(707,421)				(707,421)
Ending balance at Dec. 31, 2022	$ 352,494	$ 70	$ 3,140,019	$ (6,573)	$ (2,781,022)
Ending balance, shares at Dec. 31, 2022	70,197,297	70,197,297

CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Operating activities:
Net loss	$ (707,421)	$ (454,025)	$ (186,566)
Adjustments to reconcile net loss to net cash used in operating activities:
Stock-based compensation	130,377	104,952	85,735
Acquired in-process research and development	75,033	0	0
Amortization of premium (discount) on marketable debt securities, net	2,699	6,606	848
Depreciation and amortization	18,220	13,239	12,261
Change in fair value of equity investments	19,299	42,063	(170,403)
Non-cash collaboration royalty revenue	(21,692)	(17,951)	(12,995)
Non-cash interest expense on liabilities for sales of future royalties	43,015	29,422	33,291
Other	(230)	235	946
Changes in operating assets and liabilities:
Accounts receivable	(12,068)	(5,432)	9,840
Inventory	(9,701)	(3,117)	(1,346)
Prepaid expenses and other assets	3,798	(29,508)	2,748
Accounts payable, accrued, and other liabilities	87,442	32,313	26,853
Contract liabilities, net	(7,597)	(57,492)	66,568
Deferred tax liabilities	(1,639)	0	0
Net cash used in operating activities	(380,465)	(338,695)	(132,220)
Investing activities:
Purchase of property, plant, and equipment	(116,123)	(73,093)	(43,905)
Acquisition, net of cash acquired	(75,025)	0	0
Purchase of marketable debt securities	(614,735)	(1,012,187)	(813,237)
Purchase of equity investments	0	0	(37,062)
Proceeds from sale of marketable debt securities	84,275	92,896	50,990
Proceeds from sale of equity investments	10,094	79,843	79,842
Proceeds from maturities of marketable debt securities	450,706	718,111	589,806
Payment for intangible asset	(30,000)	0	0
Other	(844)	(942)	(5,555)
Net cash used in investing activities	(291,652)	(195,372)	(179,121)
Financing activities:
Proceeds from the sale of future royalties, net	490,950	0	0
Proceeds from the issuance of common stock in connection with underwritten public offerings, net	0	0	435,556
Proceeds from the issuance of common stock in connection with the license agreement, net	0	0	55,268
Proceeds from the issuance of common stock in connection with at-the-market offering, net	0	78,943	20,391
Proceeds from the issuance of common stock from exercise of warrants and equity plan awards, net	10,813	40,101	89,293
Other	(555)	(492)	(236)
Net cash provided by financing activities	501,208	118,552	600,272
Effect of exchange rate changes on cash	(1,075)	(1,194)	1,119
Net (decrease) increase in cash, cash equivalents, and restricted cash	(171,984)	(416,709)	290,050
Cash, cash equivalents, and restricted cash at beginning of year	309,585	726,294	436,244
Cash, cash equivalents, and restricted cash at end of year	137,601	309,585	726,294
Supplemental disclosures of non-cash investing and financing information:
Acquired lease liabilities arising from obtaining right-of-use assets	1,168	3,142	18,775
Stock-based compensation capitalized into ending inventory	2,340	1,453	1,304
Costs of property and equipment included in accounts payable, accrued, and other liabilities	17,963	18,993	8,515
Non-cash interest expense on liabilities for sales of future royalties capitalized during the year into ending property, plant and equipment	$ 11,380	$ 4,650	$ 0

Organization and Basis of Presentation

12 Months Ended

Dec. 31, 2021

Organization, Consolidation and Presentation of Financial Statements [Abstract]

Organization and Basis of Presentation

Ultragenyx Pharmaceutical Inc., or 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 and has four commercially approved products.

Crysvita® (burosumab) is approved in the United States, or U.S., the European Union, or EU, and certain other regions for the treatment of X-linked hypophosphatemia, or XLH, in adult and pediatric patients one year of age and older. Crysvita is also approved in the U.S. and certain other regions for the treatment of fibroblast growth factor 23, or FGF23,-related hypophosphatemia in tumor-induced osteomalacia, or TIO, associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adults and pediatric patients 2 years of age and older.

Mepsevii® (vestronidase alfa) is approved in the U.S., the EU and certain other regions, as the first medicine for the treatment of children and adults with mucopolysaccharidosis VII, or MPS VII, also known as Sly syndrome.

Dojolvi® (triheptanoin) is approved in the U.S. and certain other regions for the treatment of pediatric and adult patients severely affected by long-chain fatty acid oxidation disorders, or LC-FAOD.

Evkeeza® (evinacumab) is approved in the U.S. and the European Economic Area, or EEA, for the treatment of homozygous familial hypercholesterolemia, or HoFH. In January 2022, the Company licensed exclusive rights from Regeneron Pharmaceuticals, or Regeneron, to commercialize Evkeeza® (evinacumab) outside of the U.S.

In addition to the approved products, the Company has the following ongoing clinical development programs:

•

UX111 (formerly ABO-102) is an AAV9 gene therapy product candidate for the treatment of patients with Sanfilippo syndrome type A, or MPS IIIA, a rare lysosomal storage disease. In May 2022, the Company announced an exclusive license agreement with Abeona Therapeutics Inc., or Abeona, for UX111 whereby the Company assumed responsibility for the UX111 program, as further described in Note 8;

•

DTX401 is an adeno-associated virus 8, or AAV8, gene therapy product candidate for the treatment of patients with glycogen storage disease type Ia, or GSDIa;

•

DTX301 is an AAV8 gene therapy product candidate in development for the treatment of patients with ornithine transcarbamylase, or OTC deficiency, the most common urea cycle disorder;

•

UX143 (setrusumab), which is subject to the Company’s collaboration agreement with Mereo BioPharma 3, or 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, or OI;

•

GTX-102 is an antisense oligonucleotide, or ASO, which the Company is developing through GeneTx Biotherapeutics LLC, or 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. In July 2022, the Company executed its option to acquire GeneTx as further described in Note 7;

•

UX701 is an adeno-associated virus 9, or AAV9, 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, or mRNA, product candidate designed for the treatment of patients with Glycogen Storage Disease Type III, or GSDIII, a disease caused by a glycogen debranching enzyme, or 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. Management recognizes that the Company will likely need to raise additional capital to fully implement its business plans. Through December 31, 2022, the Company has relied primarily on its sale of equity securities, its revenues from commercial products, its sale of future royalties, and strategic collaboration arrangements, to finance its operations.

The Company expects it will need to 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 Accounting Policies

12 Months Ended

Dec. 31, 2022

Accounting Policies [Abstract]

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, or 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, revenue recognition, and the liabilities for sales 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,
	2022		2021		2020
Cash and cash equivalents	$	132,944	$	307,584	$	713,526
Restricted cash included in prepaid expenses and other current assets		862		—		10,847
Restricted cash included in other assets		3,795		2,001		1,921
Total cash, cash equivalents, and restricted cash shown in the statements of cash flows	$	137,601	$	309,585	$	726,294

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

The Company records investments in equity securities, other than equity method investments, at fair market value, if the fair value is readily determinable. Equity securities with no readily determinable fair values are recorded using the measurement alternative of cost adjusted for observable price changes in orderly transactions for identical or similar investments of the same issuer less impairment, if any. Investments in equity securities are recorded in Equity investments on the Company's Consolidated

Balance Sheets. Unrealized gains and losses are reported in Change in fair value of equity investments on the Company’s Consolidated Statements of Operations. The Company regularly reviews its non-marketable equity securities for indicators of impairment.

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.

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. For trade receivables and other instruments, the Company uses a 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’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. There was no allowance for losses on available-for-sale debt securities which were attributable to credit risk for the years ended December 31, 2022 and 2021.

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 and software		3-5 years
Land		Not applicable
Leasehold improvements		Shorter of lease term or estimated useful life

Intangible Assets

Finite-lived intangibles consist of contractual payments made for certain milestones achieved with collaboration partners. The contractual payments are recorded as intangible assets and are amortized over their estimated useful lives. The Company reviews its definite-lived intangible assets when events or circumstances may indicate that the carrying value of these assets is not recoverable and exceeds their fair value. The Company measures fair value based on the estimated future undiscounted cash flows associated with these assets in addition to other assumptions and projections that the Company deems to be reasonable and supportable.

Indefinite-lived intangibles consist of acquired in-process research and development, or IPR&D. 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 Company tests its 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 an intangible 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 to date.

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, or 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.

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 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.

The Company sold the right to receive certain royalty payments from net sales of Crysvita in certain territories to RPI Finance Trust, or RPI, an affiliate of Royalty Pharma, and to OCM LS23 Holdings LP, an investment vehicle for Ontario Municipal Employees Retirement System, or OMERS, as further described in “Note 10. Liabilities for Sales of Future Royalties”. The Company records the royalty revenue from the net sales of Crysvita in the applicable territories on a prospective basis as non-cash royalty revenue in the Consolidated Statements of Operations over the term of the applicable 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, or 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 9. 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, performance stock options, or PSOs, restricted stock units, or RSUs, and performance stock units, or 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). PSOs and 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 PSOs and 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 the acquisition of Dimension Therapeutics, Inc., or Dimension, 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

12 Months Ended

Dec. 31, 2022

Fair Value Disclosures [Abstract]

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 Therapeutics Holdings Inc., or Arcturus, and Solid Biosciences, Inc., or Solid, by using the quoted market prices, which are Level 1 fair value measurements.

The following tables set forth the fair value of the Company’s financial assets remeasured on a recurring basis based on the three-tier fair value hierarchy (in thousands):


	December 31, 2022
	Level 1		Level 2		Level 3		Total
Financial Assets:
Money market funds	$	102,847	$	—	$	—	$	102,847
Certificates of deposits and time deposits		—		25,972		—		25,972
Corporate bonds		—		427,598		—		427,598
Commercial paper		—		135,393		—		135,393
Asset-backed securities		—		11,980		—		11,980
U.S. Government Treasury and agency securities		27,645		129,345		—		156,990
Debt securities in government-sponsored entities		—		15,855		—		15,855
Investment in Solid common stock		2,807		—		—		2,807
Other		—		4,575		—		4,575
Total	$	133,299	$	750,718	$	—	$	884,017


	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

- Definition

The entire disclosure for the fair value of financial instruments (as defined), including financial assets and financial liabilities (collectively, as defined), and the measurements of those instruments as well as disclosures related to the fair value of non-financial assets and liabilities. Such disclosures about the financial instruments, assets, and liabilities would include: (1) the fair value of the required items together with their carrying amounts (as appropriate); (2) for items for which it is not practicable to estimate fair value, disclosure would include: (a) information pertinent to estimating fair value (including, carrying amount, effective interest rate, and maturity, and (b) the reasons why it is not practicable to estimate fair value; (3) significant concentrations of credit risk including: (a) information about the activity, region, or economic characteristics identifying a concentration, (b) the maximum amount of loss the entity is exposed to based on the gross fair value of the related item, (c) policy for requiring collateral or other security and information as to accessing such collateral or security, and (d) the nature and brief description of such collateral or security; (4) quantitative information about market risks and how such risks are managed; (5) for items measured on both a recurring and nonrecurring basis information regarding the inputs used to develop the fair value measurement; and (6) for items presented in the financial statement for which fair value measurement is elected: (a) information necessary to understand the reasons for the election, (b) discussion of the effect of fair value changes on earnings, (c) a description of [similar groups] items for which the election is made and the relation thereof to the balance sheet, the aggregate carrying value of items included in the balance sheet that are not eligible for the election; (7) all other required (as defined) and desired information.

+ References + Details

Balance Sheet Components

12 Months Ended

Dec. 31, 2022

Investments, Debt and Equity Securities [Abstract]

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, 2022
			Gross Unrealized
	Amortized Cost		Gains		Losses			Estimated Fair Value
Money market funds	$	102,847	$	—	$	—		$	102,847
Certificates of deposit and time deposits		25,972		—		—			25,972
Corporate bonds		432,211		87		(4,700	)		427,598
Commercial paper		135,393		—		—			135,393
Asset-backed securities		12,002		—		(22	)		11,980
U.S. Government Treasury and agency securities		157,933		320		(1,263	)		156,990
Debt securities in government-sponsored entities		16,005		—		(150	)		15,855
Total	$	882,363	$	407	$	(6,135	)	$	876,635


	December 31, 2021
			Gross Unrealized
	Amortized Cost		Gains		Losses			Estimated Fair Value
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

At December 31, 2022, 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. The unrealized losses on the Company’s investments in marketable debt securities were caused by increases in market yields on these investments. The contractual terms of these investments do not permit the issuers to settle the securities at a price less than the par value. Accordingly, it is expected that the securities will not be settled at a price less than the amortized cost basis of these investments. The Company does not intend to sell the investments and it is not more likely than not that the Company will be required to sell the investments before recovery of their amortized cost basis.

Inventory

Inventory consists of the following (in thousands):


	December 31,
	2022		2021
Work-in-process	$	17,486	$	10,504
Finished goods		9,280		5,727
Total	$	26,766	$	16,231

Property, Plant, and Equipment, net

Property, plant, and equipment, net consists of the following (in thousands):


	December 31,
	2022			2021
Leasehold improvements	$	43,941		$	44,081
Research and development equipment		50,291			38,661
Furniture and office equipment		5,540			5,413
Computer equipment and software		13,876			10,238
Land		16,619			15,487
Construction-in-progress		189,448			76,849
Other		3,392			556
Property, plant, and equipment, gross		323,107			191,285
Less: accumulated depreciation		(63,381	)		(50,038	)
Property, plant, and equipment, net	$	259,726		$	141,247

Depreciation expense for the years ended December 31, 2022, 2021, and 2020 was $15.0 million, $12.9 million and $12.1 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,
	2022		2021
Research, clinical study, and manufacturing expenses	$	73,558	$	40,880
Payroll and related expenses		78,938		62,591
Other		52,182		42,084
Total	$	204,678	$	145,555

Intangible Assets, Net

12 Months Ended

Dec. 31, 2022

Intangible Assets, Net (Excluding Goodwill) [Abstract]

Intangible Assets, Net

Intangible Assets, net

Indefinite-lived Intangibles

The Company has IPR&D assets of $129.0 million as of December 31, 2022 and 2021. 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.

Finite-lived Intangibles

Subsequent to the FDA approval of Dojolvi for the treatment of LC-FAOD in 2020, the Company recorded $4.8 million for the attainment of various development and commercial milestones as finite-lived intangible assets which are amortized over a weighted-average useful life of 5.7 years.

In January 2022, the Company announced a collaboration with Regeneron to commercialize Evkeeza for HoFH outside of the U.S. Upon closing of the transaction in January 2022, the Company paid Regeneron a $30.0 million upfront payment. As the upfront payment was related to the Company’s usage of intellectual property related to Evkeeza for HoFH, the upfront payment was recorded as an intangible asset, which is amortized over its useful life of 10.5 years.

The Company's intangible assets were as follows:


	December 31, 2022
	Gross Carrying Amount		Weighted-Average Life (Years)		Accumulated Amortization			Net Carrying Amount
Indefinite-lived intangibles	$	129,000		—	$	—		$	129,000
Finite-lived intangibles		34,775		9.9	$	(3,670	)	$	31,105
Total intangible assets	$	163,775		—	$	(3,670	)	$	160,105


	December 31, 2021
	Gross Carrying Amount		Weighted-Average Life (Years)		Accumulated Amortization			Net Carrying Amount
Indefinite-lived intangibles	$	129,000		—	$	—		$	129,000
Finite-lived intangibles		2,275		7.0	$	(487	)	$	1,788
Total intangible assets	$	131,275		—	$	(487	)	$	130,788

The Company recorded costs of sales of $3.2 million, $0.3 million and $0.2 million for the years ended December 31, 2022, 2021, and 2020, respectively, related to the amortization of the intangible assets.

The expected amortization of the intangible assets, as of December 31, 2022, for each of the next five years and thereafter is as follows:


2023	$	3,738
2024		3,738
2025		3,738
2026		3,738
2027		3,297
Thereafter		12,856
Total	$	31,105

Revenue

12 Months Ended

Dec. 31, 2022

Revenue from Contract with Customer [Abstract]

Revenue

The following table disaggregates total revenues from external customers by collaboration and license revenue and product sales (in thousands):


	Year Ended December 31,
	2022		2021		2020
Collaboration and license revenue:
Crysvita collaboration revenue in profit-share territory	$	215,024	$	171,198	$	128,597
Crysvita royalty revenue in European territory		—		244		1,498
Daiichi Sankyo		7,686		84,996		89,220
Total collaboration and license revenue		222,710		256,438		219,315
Product sales:
Crysvita		42,678		21,422		10,350
Mepsevii		20,637		16,035		15,342
Dojolvi		55,612		39,560		13,028
Total product sales		118,927		77,017		38,720
Crysvita non-cash collaboration royalty revenue		21,692		17,951		12,995
Total revenues	$	363,329	$	351,406	$	271,030

The following table disaggregates total revenues based on geographic location (in thousands):


	Year Ended December 31,
	2022		2021		2020
North America	$	281,088	$	301,110	$	237,666
Europe		36,369		26,660		21,318
Latin America		44,711		23,636		12,046
Japan		1,161		—		—
Total revenues	$	363,329	$	351,406	$	271,030

The following table presents the activity and ending balances for sales-related accruals and allowances (in thousands):


	Year Ended December 31,
	2022			2021			2020
Balance of product sales reserve at beginning of year	$	7,181		$	3,913		$	1,818
Provisions		13,525			9,586			5,763
Payments		(9,613	)		(6,120	)		(2,785	)
Adjustments		394			(198	)		(883	)
Balance of product sales reserve at end of year	$	11,487		$	7,181		$	3,913

The following table presents changes in the contract assets (liabilities) for the years ended December 31, 2022 and 2021 (in thousands):


	Year Ended December 31,
	2022			2021
Balance of contract liabilities at beginning of period	$	9,076		$	66,568
Additions		89			27,504
Deductions		(7,686	)		(84,996	)
Balance of contract liabilities at end of period, net	$	1,479		$	9,076

See Note 8 for additional details on contract liabilities activities.

The Company’s largest accounts receivable balance was from a collaboration partner and was 68% and 71% of the total accounts receivable balance as of December 31, 2022 and 2021, respectively.

- Definition

The entire disclosure of revenue from contract with customer to transfer good or service and to transfer nonfinancial asset. Includes, but is not limited to, disaggregation of revenue, credit loss recognized from contract with customer, judgment and change in judgment related to contract with customer, and asset recognized from cost incurred to obtain or fulfill contract with customer. Excludes insurance and lease contracts.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-URI https://asc.fasb.org/topic&trid=49130388

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 10
-URI https://asc.fasb.org/extlink&oid=126920106&loc=SL49130551-203045

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 13
-Subparagraph (b)(2)
-URI https://asc.fasb.org/extlink&oid=126920106&loc=SL49130556-203045

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 12
-Subparagraph (b)
-URI https://asc.fasb.org/extlink&oid=126920106&loc=SL49130554-203045

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 9
-URI https://asc.fasb.org/extlink&oid=126920106&loc=SL49130550-203045

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 12
-Subparagraph (e)
-URI https://asc.fasb.org/extlink&oid=126920106&loc=SL49130554-203045

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 12
-Subparagraph (a)
-URI https://asc.fasb.org/extlink&oid=126920106&loc=SL49130554-203045

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 12
-Subparagraph (d)
-URI https://asc.fasb.org/extlink&oid=126920106&loc=SL49130554-203045

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 15
-URI https://asc.fasb.org/extlink&oid=126920106&loc=SL49130558-203045

Reference 10: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 12
-Subparagraph (c)
-URI https://asc.fasb.org/extlink&oid=126920106&loc=SL49130554-203045

+ Details

GeneTx Acquisition

12 Months Ended

Dec. 31, 2022

Business Combinations [Abstract]

Acquisition

GeneTx Acquisition

In August 2019, the Company entered into a Program Agreement and a Unitholder Option Agreement with GeneTx Biotherapeutics LLC, or 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 during the quarter ended March 31, 2020, which was recorded as an in-process research and development expense. In April 2022, the parties entered into an amendment to the Unitholder Option Agreement, or the Amendment, which provided the Company with an additional, earlier option to acquire GeneTx for an option exercise price of $75.0 million based on the earlier of receipt of interim data in the Phase 1/2 study or a specified date, such option, the Interim Option.

During the exclusive option period, GeneTx was responsible for conducting the program based on the development plan agreed upon between the parties and, subject to the terms in the Program Agreement, had the decision-making authority on all matters in connection with the research, development, manufacturing and regulatory activities with respect to the Program.

In July 2022, the Company exercised the Interim Option to acquire GeneTx and entered into a Unit Purchase Agreement, or the Purchase Agreement, pursuant to which the Company purchased all the outstanding units of GeneTx. In accordance with the terms of the Purchase Agreement, the Company paid the option exercise price of $75.0 million and an additional $15.6 million to acquire the outstanding cash of GeneTx, and adjustments for working capital and transaction expenses of $0.6 million, for a total purchase consideration of $91.2 million. Additionally, the Company may make payments of up to $190.0 million upon the achievement of certain milestones, including up to $30.0 million in milestone payments upon achievement of the earlier of initiation of a Phase 3 clinical study or product approvals in Canada and the U.K., up to $85.0 million in additional regulatory approval milestones for the achievement of U.S. and EU product approvals, and up to $75.0 million in commercial milestone payments based on annual worldwide net product sales. In addition, the Company will also pay tiered mid- to high single-digit percentage royalties based on licensed product annual net sales. If the Company receives and resells an FDA priority review voucher, or PRV, in connection with a new drug application approval, GeneTx is entitled to receive a portion of proceeds from the sale or a cash payment from the Company if the Company choses to retain the PRV.

The transaction was accounted as an asset acquisition, as substantially all of the fair value of the gross assets acquired was concentrated in a single identifiable in-process research and development intangible asset. Prior to the achievement of certain development and regulatory milestones, the acquired in-process research and development intangible asset has not yet reached technological feasibility and has no alternative future use. Accordingly, the Company recorded the acquisition price of $75.0 million, net of cash and working capital acquired, as in-process research and development expense during the year ended December 31, 2022.

License and Research Agreements

12 Months Ended

Dec. 31, 2022

Research Grant Agreement [Abstract]

License and Research Agreements

Kyowa Kirin Co., Ltd.

In August 2013, the Company entered into a collaboration and license agreement with Kyowa Kirin Co., Ltd., or KKC (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 the 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 a 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. In April 2023, commercialization responsibilities for Crysvita in the profit-share territory will transition to KKC and KKC will be responsible for the commercialization of Crysvita in the territory at and after April 2023. Thereafter, the Company will be entitled to receive a tiered double-digit revenue share from the mid-20% range up to a maximum rate of 30%.

In September 2022, the Company entered into an amendment to the collaboration agreement which clarified the scope of increased participation by KKC in support of the Company’s commercial activities prior to April 2023 and granted the Company the right to continue to support KKC in commercial field activities in the U.S. through April 2024, subject to the limitations and conditions set forth in the amendment. As a result, KKC will continue to support the Company’s commercial field and marketing efforts through a cost share arrangement through April 2024, subject to the limits and conditions set forth in the amendment. After April 2024, the Company’s rights to promote Crysvita in the U.S. will be limited to medical geneticists and the Company will solely bear its expenses related to the promotion of Crysvita in the profit-share territory.

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.

In July 2022, the Company sold to OMERS its right to receive 30% of the future royalty payments due to the Company based on net sales of Crysvita in the U.S. and Canada, subject to a cap, beginning in April 2023, as further described in Note 10.

Royalty Revenue Related to Sales in the European Territory

KKC has the commercial responsibility for Crysvita in the European territory. In December 2019, the Company sold its right to receive royalty payments based on sales in the European territory to Royalty Pharma, effective January 1, 2020, as further described in “Note 10. Liabilities for Sales 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,
	2022		2021		2020
Company's share of revenue in profit-share territory	$	215,024	$	171,198	$	128,597
Royalty revenue in European territory		—		244		1,498
Non-cash royalty revenue in European territory		21,692		17,951		12,995
Total	$	236,716	$	189,393	$	143,090

Product Revenue Related to Sales in Other Territories

The Company is responsible for commercializing Crysvita in Latin America and Turkey. The Company is considered the principal in these territories as the Company controls the product before it is transferred to the customer. Accordingly, the Company records revenue on a gross basis related to the sale of Crysvita once the product is delivered and the risk and title of the product is transferred to the distributor. The Company recorded product sales of $42.7 million, $21.4 million, and $10.4 million for the years ended December 31, 2022, 2021, and 2020, 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 its territories and is based on 35% of the net sales through December 31, 2022 and 30% thereafter. The Company also pays to KKC a low single-digit royalty on net sales in Latin America.

Cost Sharing Payments

Under the collaboration agreement, KKC and the Company share certain development and commercialization costs. As a result, the Company was reimbursed for these costs and operating expenses were reduced as follows (in thousands):


	Year Ended December 31,
	2022		2021		2020
Research and development	$	15,974	$	21,657	$	21,476
Selling, general and administrative		37,217		32,629		25,186
Total	$	53,191	$	54,286	$	46,662

Collaboration Receivable and Payable

The Company had accounts receivable from KKC in the amount of $27.5 million and $20.2 million from profit-share revenue and royalties and other receivables recorded in prepaid expenses and other current assets of $6.4 million and $16.0 million and accrued liabilities of $3.1 million and $2.3 million from commercial and development activity reimbursements, as of December 31, 2022 and 2021, respectively.

Saint Louis University

In November 2010, the Company entered into a license agreement with Saint Louis University, or 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

In September 2012, the Company entered into a license agreement with Baylor Research Institute, or 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 years ended December 31, 2022, 2021, and 2020, the Company recorded $2.5 million, nil and $2.0 million, respectively, for the attainment of various development and commercial milestones as finite-lived intangible assets. The Company is obligated to make additional future payments of up to $7.5 million contingent upon attainment of various development and commercial 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 REGENXBIO, Inc., or 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 previously had a collaboration and license agreement with Bayer Healthcare LLC, or Bayer, to research, develop and commercialize AAV gene therapy products for the treatment of hemophilia A, or DTX 201. Under this agreement, Bayer had been granted an exclusive license to develop and commercialize one or more novel gene therapies for hemophilia A.

In October 2022, the Collaboration and License Agreement for DTX201 with Bayer was terminated and all licensed rights to DTX201 have reverted back to the Company. The Company also obtained rights to all necessary data and information to further develop DTX201 or another hemophilia A program through a royalty-free, worldwide, sublicensable, perpetual license.

University of Pennsylvania

The Company has a research, collaboration, and license agreement with University of Pennsylvania School of Medicine, or 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 is also 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 Therapeutics Holdings Inc.

In October 2015, the Company entered into a Research Collaboration and License Agreement with Arcturus Therapeutics Holdings Inc., or 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, nil, and $0.4 million for the years ended December 31, 2022, 2021, and 2020, 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, or 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, 2022 and 2021, the Company sold 500,000 shares and 1,700,000 shares of Arcturus common stock, at a weighted-average price of $20.39 and $47.44, respectively. As of December 31, 2022 and 2021, the Company held nil and 500,000 shares, respectively, of Arcturus common stock.

The Company’s investment in Arcturus was accounted at fair value, as the fair value was readily determinable. All remaining shares of Arcturus held by the Company were sold during the year ended December 31, 2022.

The changes in the fair value of the Company’s equity investment in Arcturus were as follows (in thousands):


	Arcturus Common Stock
December 31, 2020	$	95,436
Change in fair value		2,912
Sale of shares		(79,843	)
December 31, 2021		18,505
Change in fair value		(8,411	)
Sale of shares		(10,094	)
December 31, 2022	$	—

Daiichi Sankyo

In March 2020, the Company executed a License and Technology Access Agreement, or the License Agreement, with Daiichi Sankyo Co., Ltd., or 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 Pinnacle PCLTM producer cell line platform, or Pinnacle PCL Platform, 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 completion of the technology transfer of the Pinnacle PCL Platform and HEK293 platform. Daiichi Sankyo reimbursed the Company for all costs associated with the transfer of the manufacturing technology and will pay single-digit royalties on net sales of products manufactured in either system.

The Company also entered into a Stock Purchase Agreement, or 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 during the first quarter of 2020. The fair market value of the common stock issued to Daiichi Sankyo was $55.3 million based on the stock price of $44.43 per share on the date of issuance, resulting in a $19.7 million premium on the 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, or 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 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 Pinnacle PCL Platform and HEK293 transient transfection manufacturing technology platform together with the initial technical assistance and technology transfer services, which was completed in the first quarter of 2022, and (ii) the transfer of any know-how and improvements after the completion of the initial technology transfer through the end of the three year technology transfer period ending March 2023.

As of December 31, 2022, 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 SPA, 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, 2022 was $181.9 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 was recognized over an initial period which was completed during the first quarter of 2022.Progress toward complete satisfaction of the individual performance obligation used an input measure. Revenue for know-how and improvements after the completion of technology transfer is 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.

The Company recognized $7.7 million, $85.0 million, and $89.2 million respectively, for the years ended December 31, 2022, 2021, and 2020 in revenue related to this arrangement. As of December 31, 2022 and 2021, the Company had recorded contract liabilities of $1.5 million and $9.1 million and an accounts receivable related to the above agreements of nil and $0.1 million, respectively.

Mereo

In December 2020, the Company entered into a License and Collaboration Agreement with Mereo BioPharma 3, or Mereo, to collaborate on the development of setrusumab. Under the terms of the agreement, the Company will lead future global development of setrusumab in both pediatric and adult patients with OI. The Company was granted an exclusive license to develop and commercialize setrusumab in the U.S., Turkey, and the rest of the world, excluding the EEA, U.K., and Switzerland, or the Mereo territory, where Mereo retains commercial rights. Each party will be responsible for post-marketing commitments and commercial supply in their respective territories.

Upon the closing of the transaction in January 2021, the Company made a payment of $50.0 million to Mereo and will be required to make payments of up to $254.0 million upon the achievement of certain clinical, regulatory, and commercial milestones. The Company will pay for all global development costs as well as tiered double-digit percentage royalties to Mereo on net sales in the U.S., Turkey, and the rest of the world (excluding the Mereo Territory), and Mereo will pay the Company a fixed double-digit percentage royalty on net sales in the Mereo Territory.

Although Mereo 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 Mereo. Prior to the achievement of certain development milestones, all consideration paid to Mereo represents rights to potential future benefits associated with Mereo’s in-process research and development activities, which have not reached technological feasibility and have no alternative future use. Accordingly, for the three months ended March 31, 2021, the Company recorded the upfront payment of $50.0 million as in-process research and development expense.

Regeneron

In January 2022, the Company announced a collaboration with Regeneron Pharmaceuticals, or Regeneron, to commercialize Evkeeza for HoFH outside of the U.S. Evkeeza is approved in the U.S., where it is marketed by Regeneron, and in the EU and U.K. as a first-in-class therapy for use together with diet and other low-density lipoprotein-cholesterol-lowering therapies to treat adults and adolescents aged 12 years and older with HoFH. Pursuant to the terms of the agreement, the Company received the rights to develop, commercialize and distribute the product for HoFH in countries outside of the U.S. The Company is obligated to pay up to $63.0 million in future milestone payments, contingent upon the achievement of certain regulatory and sales milestones. The Company may share in certain costs for global trials led by Regeneron and also received the right to opt into other potential indications, including a right to negotiate a separate agreement with Regeneron to collaborate on the Regeneron’s investigational antibody for the treatment of fibrodysplasia ossificans progressiva, or FOP, which expired in July 2022.

The collaboration agreement is within the scope of ASC 808 which provides guidance on the presentation and disclosure of collaborative arrangements. As the Company would be the principal in future sale transactions with the customer, the Company will recognize product sales and cost of sales in the period the related sales occur and the related revenue recognition criteria are met.

Under the collaboration agreement, Regeneron will supply the product and will charge the Company a transfer price from the low 20% range up to 40% on net sales, which will be recognized as cost of sales in the Company’s Statement of Operations.

Upon the closing of the transaction in January 2022, the Company paid Regeneron a $30.0 million upfront payment. As the upfront payment was related to the Company’s usage of intellectual property related to Evkeeza for HoFH, the upfront payment was recorded as an intangible asset, which is amortized over its useful life of 10.5 years.

The Company recorded costs of sales of $2.9 million, for the year ended December 31, 2022, related to the amortization of the intangible asset. Further, the Company reimbursed Regeneron for certain costs of $7.3 million that was recorded as research and development expense for the year ended December 31, 2022. No sales of Evkeeza were recorded for the year ended December 31, 2022.

Abeona

In May 2022, the Company announced an exclusive License Agreement for the AAV gene therapy for UX111 with Abeona for the treatment of MPS IIIA. Under the terms of the agreement, the Company assumed responsibility for the UX111 program and in return, Abeona is eligible to receive tiered royalties of up to 10% on net sales and commercial milestone payments of up to $30.0 million following regulatory approval of the product. Additionally, the Company entered into an Assignment and Assumption Agreement with Abeona to transfer and assign to the Company the exclusive license agreement between Nationwide Children’s Hospital, or NCH, and Abeona for certain rights related to UX111. Under this agreement, NCH is eligible to receive from the Company up to $1.0 million in development and regulatory milestones as well as royalties in the low single-digits of net sales.

The Company is obligated to pay Abeona certain prior development costs and other transition costs related to UX111. Prior to product regulatory approval, all consideration paid to Abeona represents rights to potential future benefits associated with Abeona’s in-process research and development activities, which have not reached technological feasibility and have no alternative future use. Accordingly, the value of the acquired intellectual property rights and clinical inventory as well as prior development costs and transition costs of $3.1 million were recorded as research and development expense for the year ended December 31, 2022.

Solid Biosciences, Inc.

In October 2020, the Company entered into a strategic Collaboration and License Agreement with Solid Biosciences Inc., or Solid, and received an exclusive license for any pharmaceutical product that expresses Solid’s proprietary microdystrophin construct from AAV8 and variants thereof in clade E for use in the treatment of Duchenne muscular dystrophy and other diseases resulting from lack of functional dystrophin, including Becker muscular dystrophy. The Company is collaborating to develop products that combine Solid’s differentiated microdystrophin construct, the Company’s Pinnacle PCL 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 is 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. In October 2022, Solid announced a 1 for 15 reverse stock split. After the split, the Company holds 521,719 shares in Solid. 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
December 31, 2020	$	59,320
Change in fair value		(45,625	)
December 31, 2021		13,695
Change in fair value		(10,888	)
December 31, 2022	$	2,807

Leases

12 Months Ended

Dec. 31, 2022

Lessee Disclosure [Abstract]

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,
	2022		2021		2020
Operating lease expense	$	11,775	$	11,209	$	10,164
Variable lease expense		4,785		4,142		3,298
Financing:
Amortization		343		310		158
Interest expense		37		58		40
Total	$	16,940	$	15,719	$	13,660

Cash paid for amounts included in the measurement of operating lease liabilities for the years ended December 31, 2022, 2021, and 2020 was $13.1 million, $11.8 million, and $10.3 million, respectively, and was included in net cash used in operating activities in the Consolidated Statements of Cash Flows.

The following table summarizes maturities of lease liabilities and the reconciliation of lease liabilities as of December 31, 2022:


Year Ending December 31,	Operating			Financing			Total
2023	$	13,244		$	187		$	13,431
2024		11,372			—			11,372
2025		6,530			—			6,530
2026		2,964			—			2,964
2027		446			—			446
Thereafter		376			—			376
Total future lease payments		34,932			187			35,119
Less: Amount representing interest		(3,522	)		(4	)		(3,526	)
Present value of future lease payments		31,410			183			31,593
Less: Lease liabilities, current		(11,596	)		(183	)		(11,779	)
Lease liabilities, non-current	$	19,814		$	—		$	19,814

The table above excludes $23.4 million of legally binding minimum lease payments for a lease that was executed during the year ended December 31, 2022, but whose term had not commenced. The Company is also obligated to pay $9.9 million of fit-out costs related to this lease.

Lease liabilities are based on the net present value of the remaining lease payments over the remaining lease term. For the years ended December 31, 2022 and 2021, the weighted-average remaining operating lease terms were 3.01 years and 3.84 years, respectively, the weighted-average remaining financing lease terms were 2.81 years and 3.88 years, respectively, the weighted-average discount rates used to determine the lease liability for operating leases were 6.72% and 6.64%, respectively, and the weighted-average discount rates used to determine the lease liability for finance leases were 5.13% and 5.44% respectively.

Liabilities for Sales of Future Royalties

12 Months Ended

Dec. 31, 2022

Deferred Revenue Disclosure [Abstract]

Liabilities for Sales of Future Royalties

10.

Liabilities for Sales 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 EU, the U.K., and Switzerland under the terms of the Company’s Collaboration and License Agreement with KKC dated August 29, 2013, as amended, or the KKC Collaboration Agreement. 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, or when aggregate royalty payments received by RPI are equal to $800.0 million.

In July 2022, the Company entered into a Royalty Purchase Agreement with OMERS. Pursuant to the agreement, OMERS paid $500.0 million to the Company in consideration for the right to receive 30% of the future royalty payments due to the Company from KKC based on net sales of Crysvita in the U.S. and Canada under the terms of the KKC Collaboration Agreement. The calculation of royalty payments to OMERS will be based on net sales of Crysvita beginning in April 2023 and will expire upon the earlier of the date on which aggregate payments received by OMERS equals $725.0 million or the date the final royalty payment is made to the Company under the KKC Collaboration Agreement.

Proceeds from these transactions were recorded as liabilities for sales of future royalties on the Consolidated Balance Sheets. Upon inception of the respective arrangements, the Company recorded $320.0 million and $500.0 million, net of transaction costs of $5.8 million and $9.1 million for RPI and OMERS, respectively, using the effective interest method over the estimated life of the applicable arrangement. In order to determine the amortization of the liabilities, the Company is required to estimate the total amount of future royalty payments to be received by the Company and paid to RPI and OMERS, subject to the capped amount, over the life of the arrangements. The excess of future estimated royalty payments (subject to the capped amount), over the $314.2 million and $491.0 million, respectively, of net proceeds, is recorded as non-cash interest expense over the life of the arrangements. Consequently, the Company estimates an imputed interest on the unamortized portion of the liabilities and records interest expense relating to the transactions. The Company records the royalty revenue arising from the net sales of Crysvita in the applicable territories as non-cash royalty revenue in the Consolidated Statements of Operations over the term of the arrangements.

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 liabilities and the effective interest rate. The Company’s effective annual interest rate was approximately 9.3% and 8.4%, for RPI and OMERS, respectively, as of December 31, 2022.

There are a number of factors that could materially affect the amount and timing of royalty payments from KKC in the applicable 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, macroeconomic and inflationary pressures, the introduction of competing products, pricing for reimbursement in various 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, or USD, while significant portions of the underlying sales of Crysvita are made in currencies other than USD, and other events or circumstances that could result in reduced royalty payments from 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 the relevant territories 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 arrangements.

The following table shows the activity within the liability account (in thousands):



	Liabilities for Sales of Future Royalties
	RPI			OMERS		Total
December 31, 2020	$	335,665		$	—	$	335,665
Non-cash collaboration royalty revenue		(17,951	)		—		(17,951	)
Non-cash interest expense		34,072			—		34,072
December 31, 2021		351,786			—		351,786
Net proceeds from sale of future royalties		—			490,950		490,950
Non-cash collaboration royalty revenue		(21,692	)		—		(21,692	)
Non-cash interest expense		35,095			19,300		54,395
December 31, 2022	$	365,189		$	510,250	$	875,439

11.

Equity

Equity

12 Months Ended

Dec. 31, 2022

Equity [Abstract]

Equity

At-the-Market Offerings

In May 2021, the Company entered into an Open Market Sale Agreement with Jefferies LLC, or 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. As of December 31, 2022, the Company has sold 1,050,372 shares under the arrangement resulting in net proceeds of approximately $78.9 million. No shares were sold under the arrangement for the year ended December 31, 2022.

Underwritten Public Offering

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.

- Definition

The entire disclosure for shareholders' equity comprised of portions attributable to the parent entity and noncontrolling interest, including other comprehensive income. Includes, but is not limited to, balances of common stock, preferred stock, additional paid-in capital, other capital and retained earnings, accumulated balance for each classification of other comprehensive income and amount of comprehensive income.

+ References

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+ Details

Stock-Based Awards

12 Months Ended

Dec. 31, 2022

Share-Based Payment Arrangement [Abstract]

Stock-Based Awards

12.

Stock-Based Awards

Equity Plan Awards

In 2011, the Company adopted the 2011 Equity Incentive Plan, or 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, or 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, or 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, 2022, an aggregate of 14,211,103 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, 2021		6,198,205		$	75.96	6.81	$	112,242
Options granted		2,293,950			64.88
Options exercised		(130,865	)		47.70
Options cancelled		(587,923	)		84.06
Outstanding — December 31, 2022		7,773,367		$	72.56	6.60	$	8,476
Vested and exercisable — December 31, 2022		4,577,580		$	70.89	5.14	$	7,658
Vested and expected to vest — December 31, 2022		7,471,015		$	72.50	6.51	$	8,371

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, 2022, 2021, and 2020 was $2.6 million, $38.3 million, and $56.9 million, respectively. Cash received from the exercise of options was $6.2 million, $36.6 million, and $88.1 million for the years ended December 31, 2022, 2021, and 2020, respectively.

The weighted-average estimated fair value of stock options granted was $34.77, $70.84, and $35.22 per share of the Company’s common stock during the years ended December 31, 2022, 2021, and 2020, respectively. The total estimated grant date fair value of options vested during the years ended December 31, 2022, 2021, and 2020 was $58.7 million, $48.1 million, and $45.4 million, respectively.

Performance Stock Options

The following table summarizes activity under the Company’s Performance Stock Option, or PSO, plans and related information:


	PSOs Outstanding
	Number of Options			Weighted- Average Exercise Price		Weighted-Average Remaining Contractual Term (Years)		Aggregate Intrinsic Value
Outstanding — December 31, 2021		—		$	—		—	$	—
PSOs granted		1,827,449			67.37
PSOs cancelled		(202,850	)		67.37
Outstanding — December 31, 2022		1,624,599		$	67.37		4.14	$	—
Vested and exercisable — December 31, 2022		-		$	—		—	$	—
Vested and expected to vest — December 31, 2022		1,081,597		$	67.37		4.14	$	—

During the year ended December 31, 2022, PSOs were granted to certain nonexecutive employees. PSOs are subject to vest only if specified operational milestones are achieved and the employees’ continued service with the Company. The Company uses the Black-Scholes method to calculate the fair value at the grant date and is recognizing stock-based compensation expense for the PSOs that are expected to vest. Stock-based compensation for PSOs is recognized over the service period, beginning in the period the Company determines it is probable that a milestone will be achieved. Forfeitures of PSOs are recognized as they occur. The Company reassesses the probability of the performance condition at each reporting period and adjusts the compensation cost based on the probability assessment. As of December 31, 2022, certain operational milestones were deemed probable of achievement. The aggregate intrinsic values of PSOs outstanding, vested and exercisable, and vested and expected to vest were calculated as the difference between the exercise price of the PSOs and the fair value of the Company’s common stock. No PSOs vested or were exercised during the year ended December 31, 2022. The weighted-average estimated fair value of PSOs granted was $28.76 during the year ended December 31, 2022.

Restricted Stock Units

The following table summarizes activity under the Company’s Restricted Stock Units, or RSU, plans and related information:


	RSUs Outstanding
	Number of Shares			Weighted- Average Grant Date Fair Value
Unvested — December 31, 2021		1,672,625		$	87.48
RSUs granted		1,347,125			63.22
RSUs vested		(591,837	)		79.59
RSUs cancelled		(298,760	)		81.84
Unvested — December 31, 2022		2,129,153		$	75.11

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, 2022, 2021, and 2020 was $47.1 million, $35.5 million, and $27.2 million, respectively. The aggregate intrinsic value of the shares of the RSUs vested during the years ended December 31, 2022, 2021, and 2020 was $37.8 million, $69.9 million, and $29.5 million, respectively.

Performance Stock Units

The following table summarizes activity under the Company’s Performance Stock Units, or PSUs, from the 2014 Plan and related information:


	PSUs Outstanding
	Number of Shares			Weighted- Average Grant Date Fair Value
Unvested — December 31, 2021		93,892		$	123.46
PSUs granted		166,730			75.90
PSUs vested		(28,990	)		56.08
PSUs cancelled		(22,402	)		93.61
Unvested — December 31, 2022		209,230		$	98.09

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, 2022, 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, 2022, 2021, and 2020 was $1.6 million, $9.2 million, and $10.3 million, respectively, with an aggregate intrinsic value of the shares of $2.0 million, $18.9 million and $14.4 million, respectively.

Employee Stock Purchase Plan

In January 2014, the Company adopted the 2014 Employee Stock Purchase Plan, or 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, 2022, the Company issued 112,974 shares of common stock under the ESPP. As of December 31, 2022, an aggregate of 4,585,921 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,
	2022		2021		2020
Cost of sales	$	902	$	871	$	827
Research and development		74,464		59,097		47,949
Selling, general and administrative		55,002		45,011		36,959
Total stock-based compensation expense	$	130,368	$	104,979	$	85,735

Stock-based compensation of $2.2 million, $1.7 million, and $1.2 million was capitalized into inventory for the years ended December 31, 2022, 2021, and 2020, respectively. Capitalized stock-based compensation is recognized as cost of sales when the related product is sold. As of December 31, 2022, the total unrecognized compensation expense related to unvested equity awards, net of estimated forfeitures, was $229.4 million, which the Company expects to recognize over an estimated weighted-average period of 2.28 years. In determining the estimated fair value of the stock options, PSOs 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.

Strike price for options awards and PSOs is equal to the closing market value of our common stock on the date of grant.

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,
	2022	2021	2020
Expected term (years)	6.07	6.06	6.20
Expected volatility	56%	60%	61%
Risk-free interest rate	2.0%	1.0%	0.8%
Expected dividend rate	0.0%	0.0%	0.0%

The fair value of PSOs 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,
		2022
Expected term (years)		3.60
Expected volatility		57%
Risk-free interest rate		1.5%
Expected dividend rate		0.0%

Defined Contribution Plan	12 Months Ended
Defined Contribution Plan	Dec. 31, 2022
UnableToMigrateMatchesIfrsDefinedContributionPensionAndOtherPostRetirementPlansDisclosure[Abstract]
Defined Contribution Plan	13. 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 $9.0 million, $5.5 million, and $4.3 million as expense related to the plan for the years ended December 31, 2022, 2021, and 2020, respectively.

Income Taxes

12 Months Ended

Dec. 31, 2022

Income Tax Disclosure [Abstract]

Income Taxes

14.

Income Taxes

The components of the Company’s loss before income taxes were as follows (in thousands):


	Year Ended December 31,
	2022			2021			2020
Domestic	$	703,411		$	455,314		$	189,449
Foreign		(1,686	)		(2,333	)		(4,090	)
Total loss before income taxes	$	701,725		$	452,981		$	185,359

The components of the Company’s income tax provision were as follows (in thousands):


	Year Ended December 31,
	2022			2021			2020
Current provision for income taxes:
Federal	$	—		$	—		$	—
State		6,062			(14	)		15
International		1,274			1,058			1,192
Total current tax provision		7,336			1,044			1,207
Deferred tax provision:
Federal		—			—			—
State		(1,640	)		—			—
International		—			—			—
Total deferred tax provision		(1,640	)		—			—
Total provision for income taxes	$	5,696		$	1,044		$	1,207

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.

Beginning in 2022, the Tax Cuts and Jobs Act of 2017 eliminated the right to deduct research and development expenditures for tax purposes in the period the expenses were incurred and instead requires all U.S. and foreign research and development expenditures to be amortized over five and fifteen tax years, respectively. Due to this required capitalization of research and development expenditures and the significant taxable income generated as a result of our sale of royalties in July 2022, the Company has recorded current state income tax expense of $6.1 million for the year ended December 31, 2022. The current income tax provision is primarily for state taxes the Company anticipates paying as a result of statutory limitations on the Company's ability to offset expected taxable income with net operating loss carry forwards in certain states.

The effective tax rate of our provision for income taxes differs from the federal statutory rate as follows:


	Year Ended December 31,
	2022				2021				2020
Federal statutory income tax rate		21.0		%		21.0		%		21.0		%
State income taxes, net of federal benefit		(0.4	)			—				—
Federal tax credits		5.9				7.2				13.7
Other		(0.1	)			0.5				(0.5	)
Premium on equity issuance		—				—				2.2
Nondeductible permanent items		(0.6	)			(0.8	)			(0.9	)
Stock-based compensation		(1.2	)			1.3				0.9
Uncertain tax positions		(1.2	)			(1.4	)			(2.7	)
Change in valuation allowance		(24.0	)			(27.9	)			(33.9	)
Foreign rate differential		(0.2	)			(0.1	)			(0.5	)
Provision for income taxes		(0.8	)	%		(0.2	)	%		(0.7	)	%

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,
	2022			2021
Deferred tax assets:
Loss carryforwards	$	231,835		$	306,119
Tax credits		260,546			218,131
Stock options		39,784			33,564
Accruals and reserves		27,029			25,735
Fixed assets and intangibles		39,233			18,263
Liabilities for sales of future royalties		214,900			90,826
Basis difference in equity investments		8,971			3,912
Capitalized research and development costs		75,335			—
Other		3,028			13,060
Gross deferred tax assets		900,661			709,610
Valuation allowance		(894,518	)		(700,669	)
Total deferred tax assets		6,143			8,941
Deferred tax liabilities:
In-process research and development		(31,667	)		(33,306	)
Right-of-use lease assets		(6,143	)		(8,941	)
Gross deferred tax liabilities		(37,810	)		(42,247	)
Net deferred tax liabilities	$	(31,667	)	$	(33,306	)

As of December 31, 2022 and 2021, the Company had approximately $756.6 million and $1,085.4 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, 2022 and 2021, the Company had approximately $710.0 million and $777.0 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, 2022 and 2021, the Company had federal research tax credit carryforwards of approximately $32.6 million and $22.9 million, respectively, available to reduce future tax liabilities that will begin to expire in 2030. As of December 31, 2022 and 2021, the Company had state research credit carryforwards of $59.9 million and $44.6 million, respectively, available to reduce future tax liabilities that will be carried forward indefinitely.

As of December 31, 2022 and 2021, the Company had federal Orphan Drug Credits of $239.3 million and $208.1 million, respectively, 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.

The valuation allowance increased by $193.8 million and $139.5 million during the years ended December 31, 2022 and 2021, 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,
	2022			2021			2020
Balance at beginning of year	$	55,360		$	46,662		$	39,954
Additions based on tax positions related to current year		11,316			8,542			6,950
Additions for tax positions of prior years		377			356			382
Reductions for tax positions of prior years		(259	)		(200	)		(624	)
Balance at end of year	$	66,794		$	55,360		$	46,662

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, 2022, 2021, and 2020, the Company did not 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, 2022, the Company had not made a provision for any incremental foreign withholding taxes on approximately $10.9 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, 2022 remain subject to examination.

- Definition

The entire disclosure for income taxes. Disclosures may include net deferred tax liability or asset recognized in an enterprise's statement of financial position, net change during the year in the total valuation allowance, approximate tax effect of each type of temporary difference and carryforward that gives rise to a significant portion of deferred tax liabilities and deferred tax assets, utilization of a tax carryback, and tax uncertainties information.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
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-Paragraph 21
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Reference 2: http://www.xbrl.org/2003/role/disclosureRef
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Reference 3: http://www.xbrl.org/2003/role/disclosureRef
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Reference 4: http://www.xbrl.org/2003/role/disclosureRef
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-SubTopic 10
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-URI https://asc.fasb.org/extlink&oid=121826272&loc=d3e32705-109319

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
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-Name Accounting Standards Codification
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Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-URI https://asc.fasb.org/topic&trid=2144680

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-SubTopic 30
-Section 50
-Paragraph 2
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-URI https://asc.fasb.org/extlink&oid=6424122&loc=d3e41874-109331

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 235
-SubTopic 10
-Section S99
-Paragraph 1
-Subparagraph (SX 210.4-08(h)(2))
-URI https://asc.fasb.org/extlink&oid=120395691&loc=d3e23780-122690

+ Details

Commitments and Contingencies

12 Months Ended

Dec. 31, 2022

Commitments and Contingencies Disclosure [Abstract]

Commitments and Contingencies

15.

Commitments and Contingencies

The Company has various manufacturing, construction, 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.

Manufacturing and service contract obligations primarily relate to the manufacture of inventory for our approved products, the majority of which are due in the next 12 months.

As of December 31, 2022, the aggregate payments under contractually-binding manufacturing and service agreements are as follows (in thousands):


	Year Ended December 31,
	2023		2024		2025		Total
Manufacturing and Services	$	22,892	$	4,467	$	1,597	$	28,956

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 8. License and Research Agreements.”

See “Note 9. 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.

Related Party Transaction	12 Months Ended
Related Party Transaction	Dec. 31, 2022
Related Party Transactions [Abstract]
Related Party Transaction	16. Related Party Transaction In July 2022, the Company entered into an agreement with a non-profit foundation in which two of the Company’s board members, including the Company’s Chief Executive Officer, are also board members of the foundation, whereby a $1.0 million contribution will be paid out to the foundation over a four-year period, beginning in the third quarter of 2022, to support rare disease education and awareness. As a result, the Company recorded $0.3 million as research and development expense for this agreement for the year ended December 31, 2022.

Net Loss per Share

12 Months Ended

Dec. 31, 2022

Earnings Per Share [Abstract]

Net Loss per Share

17.

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, 2022, 2021, and 2020 (in thousands, except share and per share data):


	Year Ended December 31,
	2022			2021			2020
Numerator:
Net loss	$	(707,421	)	$	(454,025	)	$	(186,566	)
Denominator:
Weighted-average shares used to compute net loss per share, basic and diluted		69,914,225			67,795,540			60,845,550
Net loss per share, basic and diluted	$	(10.12	)	$	(6.70	)	$	(3.07	)

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,
	2022		2021		2020
Options to purchase common stock, RSUs, and PSUs		11,290,935		8,214,063		8,532,236
Employee stock purchase plan		7,581		3,511		2,626
Common stock warrants		—		—		29,449
		11,298,516		8,217,574		8,564,311

Accumulated Other Comprehensive Loss

12 Months Ended

Dec. 31, 2022

Other Comprehensive Income (Loss), Net of Tax [Abstract]

Accumulated Other Comprehensive Loss

18.

Accumulated Other Comprehensive Loss

Total accumulated other comprehensive loss consisted of the following (in thousands):


	Year Ended December 31,
	2022			2021
Cumulative foreign currency translation adjustment	$	(845	)	$	(121	)
Unrealized loss on securities available-for-sale		(5,728	)		(1,283	)
Total accumulated other comprehensive loss	$	(6,573	)	$	(1,404	)

Summary of Significant Accounting Policies (Policies)

12 Months Ended

Dec. 31, 2022

Accounting Policies [Abstract]

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

Cash, Cash Equivalents, and Restricted Cash

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.


	December 31,
	2022		2021		2020
Cash and cash equivalents	$	132,944	$	307,584	$	713,526
Restricted cash included in prepaid expenses and other current assets		862		—		10,847
Restricted cash included in other assets		3,795		2,001		1,921
Total cash, cash equivalents, and restricted cash shown in the statements of cash flows	$	137,601	$	309,585	$	726,294

Marketable Debt Securities

Equity Investments

Concentration of Credit Risk, Credit Losses, and Other Risks and Uncertainties

Inventory

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 and software		3-5 years
Land		Not applicable
Leasehold improvements		Shorter of lease term or estimated useful life

Intangible Assets

Goodwill

Impairment of Long-Lived Assets

Accruals of Research and Development Costs

Revenue Recognition

Collaboration and License Revenue

Product Sales

Leases

Comprehensive Loss

Research and Development

Stock-Based Compensation

Income Taxes

Foreign Currency

Net Loss per Share

Summary of Significant Accounting Policies (Tables)

12 Months Ended

Dec. 31, 2022

Accounting Policies [Abstract]

Summary of Reconciliation of Cash, Cash Equivalents and Restricted Cash


	December 31,
	2022		2021		2020
Cash and cash equivalents	$	132,944	$	307,584	$	713,526
Restricted cash included in prepaid expenses and other current assets		862		—		10,847
Restricted cash included in other assets		3,795		2,001		1,921
Total cash, cash equivalents, and restricted cash shown in the statements of cash flows	$	137,601	$	309,585	$	726,294

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 and software		3-5 years
Land		Not applicable
Leasehold improvements		Shorter of lease term or estimated useful life

Fair Value Measurements (Tables)

12 Months Ended

Dec. 31, 2022

Fair Value Disclosures [Abstract]

Summary of Financial Assets Measured on Recurring Basis

The following tables set forth the fair value of the Company’s financial assets remeasured on a recurring basis based on the three-tier fair value hierarchy (in thousands):


	December 31, 2022
	Level 1		Level 2		Level 3		Total
Financial Assets:
Money market funds	$	102,847	$	—	$	—	$	102,847
Certificates of deposits and time deposits		—		25,972		—		25,972
Corporate bonds		—		427,598		—		427,598
Commercial paper		—		135,393		—		135,393
Asset-backed securities		—		11,980		—		11,980
U.S. Government Treasury and agency securities		27,645		129,345		—		156,990
Debt securities in government-sponsored entities		—		15,855		—		15,855
Investment in Solid common stock		2,807		—		—		2,807
Other		—		4,575		—		4,575
Total	$	133,299	$	750,718	$	—	$	884,017


	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

Balance Sheet Components (Tables)

12 Months Ended

Dec. 31, 2022

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, 2022
			Gross Unrealized
	Amortized Cost		Gains		Losses			Estimated Fair Value
Money market funds	$	102,847	$	—	$	—		$	102,847
Certificates of deposit and time deposits		25,972		—		—			25,972
Corporate bonds		432,211		87		(4,700	)		427,598
Commercial paper		135,393		—		—			135,393
Asset-backed securities		12,002		—		(22	)		11,980
U.S. Government Treasury and agency securities		157,933		320		(1,263	)		156,990
Debt securities in government-sponsored entities		16,005		—		(150	)		15,855
Total	$	882,363	$	407	$	(6,135	)	$	876,635


	December 31, 2021
			Gross Unrealized
	Amortized Cost		Gains		Losses			Estimated Fair Value
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

Summary of Inventory

Inventory consists of the following (in thousands):


	December 31,
	2022		2021
Work-in-process	$	17,486	$	10,504
Finished goods		9,280		5,727
Total	$	26,766	$	16,231

Summary of Property, Plant and Equipment, Net

Property, plant, and equipment, net consists of the following (in thousands):


	December 31,
	2022			2021
Leasehold improvements	$	43,941		$	44,081
Research and development equipment		50,291			38,661
Furniture and office equipment		5,540			5,413
Computer equipment and software		13,876			10,238
Land		16,619			15,487
Construction-in-progress		189,448			76,849
Other		3,392			556
Property, plant, and equipment, gross		323,107			191,285
Less: accumulated depreciation		(63,381	)		(50,038	)
Property, plant, and equipment, net	$	259,726		$	141,247

Accrued Liabilities

Accrued liabilities consists of the following (in thousands):


	December 31,
	2022		2021
Research, clinical study, and manufacturing expenses	$	73,558	$	40,880
Payroll and related expenses		78,938		62,591
Other		52,182		42,084
Total	$	204,678	$	145,555

Intangible Assets, net (Table)

12 Months Ended

Dec. 31, 2022

Intangible Assets, Net (Excluding Goodwill) [Abstract]

Schedule of Intangible Assets

The Company's intangible assets were as follows:


	December 31, 2022
	Gross Carrying Amount		Weighted-Average Life (Years)		Accumulated Amortization			Net Carrying Amount
Indefinite-lived intangibles	$	129,000		—	$	—		$	129,000
Finite-lived intangibles		34,775		9.9	$	(3,670	)	$	31,105
Total intangible assets	$	163,775		—	$	(3,670	)	$	160,105


	December 31, 2021
	Gross Carrying Amount		Weighted-Average Life (Years)		Accumulated Amortization			Net Carrying Amount
Indefinite-lived intangibles	$	129,000		—	$	—		$	129,000
Finite-lived intangibles		2,275		7.0	$	(487	)	$	1,788
Total intangible assets	$	131,275		—	$	(487	)	$	130,788

Schedule of Expected Amortization of the Intangible Assets

The expected amortization of the intangible assets, as of December 31, 2022, for each of the next five years and thereafter is as follows:


2023	$	3,738
2024		3,738
2025		3,738
2026		3,738
2027		3,297
Thereafter		12,856
Total	$	31,105

Revenue (Tables)

12 Months Ended

Dec. 31, 2022

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,
	2022		2021		2020
Collaboration and license revenue:
Crysvita collaboration revenue in profit-share territory	$	215,024	$	171,198	$	128,597
Crysvita royalty revenue in European territory		—		244		1,498
Daiichi Sankyo		7,686		84,996		89,220
Total collaboration and license revenue		222,710		256,438		219,315
Product sales:
Crysvita		42,678		21,422		10,350
Mepsevii		20,637		16,035		15,342
Dojolvi		55,612		39,560		13,028
Total product sales		118,927		77,017		38,720
Crysvita non-cash collaboration royalty revenue		21,692		17,951		12,995
Total revenues	$	363,329	$	351,406	$	271,030

The following table disaggregates total revenues based on geographic location (in thousands):


	Year Ended December 31,
	2022		2021		2020
North America	$	281,088	$	301,110	$	237,666
Europe		36,369		26,660		21,318
Latin America		44,711		23,636		12,046
Japan		1,161		—		—
Total revenues	$	363,329	$	351,406	$	271,030

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,
	2022			2021			2020
Balance of product sales reserve at beginning of year	$	7,181		$	3,913		$	1,818
Provisions		13,525			9,586			5,763
Payments		(9,613	)		(6,120	)		(2,785	)
Adjustments		394			(198	)		(883	)
Balance of product sales reserve at end of year	$	11,487		$	7,181		$	3,913

Summary of Changes in Contract Assets (Liabilities)

The following table presents changes in the contract assets (liabilities) for the years ended December 31, 2022 and 2021 (in thousands):


	Year Ended December 31,
	2022			2021
Balance of contract liabilities at beginning of period	$	9,076		$	66,568
Additions		89			27,504
Deductions		(7,686	)		(84,996	)
Balance of contract liabilities at end of period, net	$	1,479		$	9,076

License and Research Agreements (Tables)

12 Months Ended

Dec. 31, 2022

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,
	2022		2021		2020
Company's share of revenue in profit-share territory	$	215,024	$	171,198	$	128,597
Royalty revenue in European territory		—		244		1,498
Non-cash royalty revenue in European territory		21,692		17,951		12,995
Total	$	236,716	$	189,393	$	143,090

Schedule of Cost Sharing Payments


	Year Ended December 31,
	2022		2021		2020
Research and development	$	15,974	$	21,657	$	21,476
Selling, general and administrative		37,217		32,629		25,186
Total	$	53,191	$	54,286	$	46,662

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
December 31, 2020	$	59,320
Change in fair value		(45,625	)
December 31, 2021		13,695
Change in fair value		(10,888	)
December 31, 2022	$	2,807

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
December 31, 2020	$	95,436
Change in fair value		2,912
Sale of shares		(79,843	)
December 31, 2021		18,505
Change in fair value		(8,411	)
Sale of shares		(10,094	)
December 31, 2022	$	—

Leases (Tables)

12 Months Ended

Dec. 31, 2022

Lessee Disclosure [Abstract]

Summary of Components of Lease Expense

The components of lease expense were as follows (in thousands):


	Year Ended December 31,
	2022		2021		2020
Operating lease expense	$	11,775	$	11,209	$	10,164
Variable lease expense		4,785		4,142		3,298
Financing:
Amortization		343		310		158
Interest expense		37		58		40
Total	$	16,940	$	15,719	$	13,660

Schedule of Maturities of Lease Liabilities and the Reconciliation of Lease Liabilities

The following table summarizes maturities of lease liabilities and the reconciliation of lease liabilities as of December 31, 2022:


Year Ending December 31,	Operating			Financing			Total
2023	$	13,244		$	187		$	13,431
2024		11,372			—			11,372
2025		6,530			—			6,530
2026		2,964			—			2,964
2027		446			—			446
Thereafter		376			—			376
Total future lease payments		34,932			187			35,119
Less: Amount representing interest		(3,522	)		(4	)		(3,526	)
Present value of future lease payments		31,410			183			31,593
Less: Lease liabilities, current		(11,596	)		(183	)		(11,779	)
Lease liabilities, non-current	$	19,814		$	—		$	19,814

Liabilities for Sales of Future Royalties (Tables)

12 Months Ended

Dec. 31, 2022

Deferred Revenue Disclosure [Abstract]

Schedule of activity within liability for sale of future royalties

The following table shows the activity within the liability account (in thousands):



	Liabilities for Sales of Future Royalties
	RPI			OMERS		Total
December 31, 2020	$	335,665		$	—	$	335,665
Non-cash collaboration royalty revenue		(17,951	)		—		(17,951	)
Non-cash interest expense		34,072			—		34,072
December 31, 2021		351,786			—		351,786
Net proceeds from sale of future royalties		—			490,950		490,950
Non-cash collaboration royalty revenue		(21,692	)		—		(21,692	)
Non-cash interest expense		35,095			19,300		54,395
December 31, 2022	$	365,189		$	510,250	$	875,439

11.

Equity

Stock-Based Awards (Tables)

12 Months Ended

Dec. 31, 2022

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, 2021		6,198,205		$	75.96	6.81	$	112,242
Options granted		2,293,950			64.88
Options exercised		(130,865	)		47.70
Options cancelled		(587,923	)		84.06
Outstanding — December 31, 2022		7,773,367		$	72.56	6.60	$	8,476
Vested and exercisable — December 31, 2022		4,577,580		$	70.89	5.14	$	7,658
Vested and expected to vest — December 31, 2022		7,471,015		$	72.50	6.51	$	8,371

Summary of Stock-Based Compensation Expense

Total stock-based compensation recognized was as follows (in thousands):


	Year Ended December 31,
	2022		2021		2020
Cost of sales	$	902	$	871	$	827
Research and development		74,464		59,097		47,949
Selling, general and administrative		55,002		45,011		36,959
Total stock-based compensation expense	$	130,368	$	104,979	$	85,735

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,
	2022	2021	2020
Expected term (years)	6.07	6.06	6.20
Expected volatility	56%	60%	61%
Risk-free interest rate	2.0%	1.0%	0.8%
Expected dividend rate	0.0%	0.0%	0.0%

The fair value of PSOs 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,
		2022
Expected term (years)		3.60
Expected volatility		57%
Risk-free interest rate		1.5%
Expected dividend rate		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, or RSU, plans and related information:


	RSUs Outstanding
	Number of Shares			Weighted- Average Grant Date Fair Value
Unvested — December 31, 2021		1,672,625		$	87.48
RSUs granted		1,347,125			63.22
RSUs vested		(591,837	)		79.59
RSUs cancelled		(298,760	)		81.84
Unvested — December 31, 2022		2,129,153		$	75.11

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, or PSUs, from the 2014 Plan and related information:


	PSUs Outstanding
	Number of Shares			Weighted- Average Grant Date Fair Value
Unvested — December 31, 2021		93,892		$	123.46
PSUs granted		166,730			75.90
PSUs vested		(28,990	)		56.08
PSUs cancelled		(22,402	)		93.61
Unvested — December 31, 2022		209,230		$	98.09

Performance Stock Options [Member]

Share Based Compensation Arrangement By Share Based Payment Award [Line Items]

Summary of Activity Under Stock Option Plans Including 2011 Plan and 2014 Plan

The following table summarizes activity under the Company’s Performance Stock Option, or PSO, plans and related information:


	PSOs Outstanding
	Number of Options			Weighted- Average Exercise Price		Weighted-Average Remaining Contractual Term (Years)		Aggregate Intrinsic Value
Outstanding — December 31, 2021		—		$	—		—	$	—
PSOs granted		1,827,449			67.37
PSOs cancelled		(202,850	)		67.37
Outstanding — December 31, 2022		1,624,599		$	67.37		4.14	$	—
Vested and exercisable — December 31, 2022		-		$	—		—	$	—
Vested and expected to vest — December 31, 2022		1,081,597		$	67.37		4.14	$	—

Income Taxes (Tables)

12 Months Ended

Dec. 31, 2022

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,
	2022			2021			2020
Domestic	$	703,411		$	455,314		$	189,449
Foreign		(1,686	)		(2,333	)		(4,090	)
Total loss before income taxes	$	701,725		$	452,981		$	185,359

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,
	2022			2021			2020
Current provision for income taxes:
Federal	$	—		$	—		$	—
State		6,062			(14	)		15
International		1,274			1,058			1,192
Total current tax provision		7,336			1,044			1,207
Deferred tax provision:
Federal		—			—			—
State		(1,640	)		—			—
International		—			—			—
Total deferred tax provision		(1,640	)		—			—
Total provision for income taxes	$	5,696		$	1,044		$	1,207

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,
	2022				2021				2020
Federal statutory income tax rate		21.0		%		21.0		%		21.0		%
State income taxes, net of federal benefit		(0.4	)			—				—
Federal tax credits		5.9				7.2				13.7
Other		(0.1	)			0.5				(0.5	)
Premium on equity issuance		—				—				2.2
Nondeductible permanent items		(0.6	)			(0.8	)			(0.9	)
Stock-based compensation		(1.2	)			1.3				0.9
Uncertain tax positions		(1.2	)			(1.4	)			(2.7	)
Change in valuation allowance		(24.0	)			(27.9	)			(33.9	)
Foreign rate differential		(0.2	)			(0.1	)			(0.5	)
Provision for income taxes		(0.8	)	%		(0.2	)	%		(0.7	)	%

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,
	2022			2021
Deferred tax assets:
Loss carryforwards	$	231,835		$	306,119
Tax credits		260,546			218,131
Stock options		39,784			33,564
Accruals and reserves		27,029			25,735
Fixed assets and intangibles		39,233			18,263
Liabilities for sales of future royalties		214,900			90,826
Basis difference in equity investments		8,971			3,912
Capitalized research and development costs		75,335			—
Other		3,028			13,060
Gross deferred tax assets		900,661			709,610
Valuation allowance		(894,518	)		(700,669	)
Total deferred tax assets		6,143			8,941
Deferred tax liabilities:
In-process research and development		(31,667	)		(33,306	)
Right-of-use lease assets		(6,143	)		(8,941	)
Gross deferred tax liabilities		(37,810	)		(42,247	)
Net deferred tax liabilities	$	(31,667	)	$	(33,306	)

Unrecognized Tax Benefits

A reconciliation of the Company’s unrecognized tax benefits follows (in thousands):


	December 31,
	2022			2021			2020
Balance at beginning of year	$	55,360		$	46,662		$	39,954
Additions based on tax positions related to current year		11,316			8,542			6,950
Additions for tax positions of prior years		377			356			382
Reductions for tax positions of prior years		(259	)		(200	)		(624	)
Balance at end of year	$	66,794		$	55,360		$	46,662

Commitments and Contingencies (Tables)

12 Months Ended

Dec. 31, 2022

Commitments and Contingencies Disclosure [Abstract]

Summary of Aggregate Payments under Contractually Binding Manufacturing and Service Agreements

As of December 31, 2022, the aggregate payments under contractually-binding manufacturing and service agreements are as follows (in thousands):


	Year Ended December 31,
	2023		2024		2025		Total
Manufacturing and Services	$	22,892	$	4,467	$	1,597	$	28,956

Net Loss per Share (Tables)

12 Months Ended

Dec. 31, 2022

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, 2022, 2021, and 2020 (in thousands, except share and per share data):


	Year Ended December 31,
	2022			2021			2020
Numerator:
Net loss	$	(707,421	)	$	(454,025	)	$	(186,566	)
Denominator:
Weighted-average shares used to compute net loss per share, basic and diluted		69,914,225			67,795,540			60,845,550
Net loss per share, basic and diluted	$	(10.12	)	$	(6.70	)	$	(3.07	)

Outstanding Shares of Common Stock Equivalents Excluded from Computation of Diluted Net Loss per Share


	Year Ended December 31,
	2022		2021		2020
Options to purchase common stock, RSUs, and PSUs		11,290,935		8,214,063		8,532,236
Employee stock purchase plan		7,581		3,511		2,626
Common stock warrants		—		—		29,449
		11,298,516		8,217,574		8,564,311

Accumulated Other Comprehensive Income (Loss) (Tables)

12 Months Ended

Dec. 31, 2022

Other Comprehensive Income (Loss), Net of Tax [Abstract]

Schedule of Total Accumulated Other Comprehensive Income (Loss)

Total accumulated other comprehensive loss consisted of the following (in thousands):


	Year Ended December 31,
	2022			2021
Cumulative foreign currency translation adjustment	$	(845	)	$	(121	)
Unrealized loss on securities available-for-sale		(5,728	)		(1,283	)
Total accumulated other comprehensive loss	$	(6,573	)	$	(1,404	)

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

Summary of Significant Accounting Policies - Summary of Reconciliation of Cash, Cash Equivalents and Restricted Cash (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Accounting Policies [Abstract]
Cash and cash equivalents	$ 132,944	$ 307,584	$ 713,526
Restricted cash included in prepaid expenses and other current assets	$ 862	$ 0	$ 10,847
Restricted Cash and Cash Equivalents, Current, Asset, Statement of Financial Position [Extensible List]	Prepaid expenses and other current assets	Prepaid expenses and other current assets	Prepaid expenses and other current assets
Restricted cash included in other assets	$ 3,795	$ 2,001	$ 1,921
Restricted Cash and Cash Equivalents, Noncurrent, Asset, Statement of Financial Position [Extensible List]	Other assets	Other assets	Other assets
Total cash, cash equivalents, and restricted cash shown in the statements of cash flows	$ 137,601	$ 309,585	$ 726,294	$ 436,244

Summary of Significant Accounting Policies - Additional Information (Details) - USD ($)	1 Months Ended	12 Months Ended
	Jun. 30, 2019	Dec. 31, 2022	Dec. 31, 2021
Summary Of Significant Accounting Policies [Line Items]
Common stock, shares issued		70,197,297	69,344,998
Number of option exercised		130,865
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
Common stock shares sold		500,000	1,700,000

Summary of Significant Accounting Policies - Summary of Useful Lives of Property, Plant and Equipment (Details)	12 Months Ended
	Dec. 31, 2022
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 and Software \| Minimum
Property Plant And Equipment [Line Items]
Property plant and equipment useful life	3 years
Computer Equipment and 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 - Summary of Financial Assets Measured on Recurring Basis (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	$ 884,017	$ 1,001,451
Level 1
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	133,299	298,965
Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	750,718	702,486
Money Market Funds
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	102,847	266,765
Money Market Funds \| Level 1
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	102,847	266,765
Asset-backed Securities
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	11,980	41,245
Asset-backed Securities \| Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	11,980	41,245
Certificate of Deposits and Time Deposits
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	25,972	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	25,972	16,000
Corporate Bonds
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	427,598	349,691
Corporate Bonds \| Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	427,598	349,691
Commercial Paper
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	135,393	187,624
Commercial Paper \| Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	135,393	187,624
U.S. Government Treasury and Agency Securities
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	156,990	87,435
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	27,645
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	129,345	87,435
Debt Securities in Government Sponsored Entities
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	15,855	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	15,855	19,549
Investments in Solid Common Stock
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	2,807
Investments in Solid Common Stock \| Level 1
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	2,807
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
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
Other
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	4,575	942
Other \| Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Total fair value	$ 4,575	$ 942

Balance Sheet Components - Summary of Cash Equivalents and Marketable Debt Securities Classified as Available For Sale Securities (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	$ 882,363	$ 969,592
Gross Unrealized Gains	407	5
Gross Unrealized Losses	(6,135)	(1,288)
Estimated Fair Value	876,635	968,309
Money Market Funds
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	102,847	266,765
Estimated Fair Value	102,847	266,765
Asset-backed Securities
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	12,002	41,282
Gross Unrealized Gains	0	1
Gross Unrealized Losses	(22)	(38)
Estimated Fair Value	11,980	41,245
Certificate of Deposits and Time Deposits
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	25,972	16,000
Estimated Fair Value	25,972	16,000
Corporate Bonds
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	432,211	350,667
Gross Unrealized Gains	87	3
Gross Unrealized Losses	(4,700)	(979)
Estimated Fair Value	427,598	349,691
Commercial Paper
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	135,393	187,624
Estimated Fair Value	135,393	187,624
U.S. Government Treasury and Agency Securities
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	157,933	87,642
Gross Unrealized Gains	320	1
Gross Unrealized Losses	(1,263)	(208)
Estimated Fair Value	156,990	87,435
Debt Securities in Government Sponsored Entities
Schedule Of Available For Sale Securities [Line Items]
Amortized Cost	16,005	19,612
Gross Unrealized Losses	(150)	(63)
Estimated Fair Value	$ 15,855	$ 19,549

Balance Sheet Components - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Schedule Of Available For Sale Securities [Line Items]
Depreciation expense	$ 15.0	$ 12.9	$ 12.1
Maximum
Schedule Of Available For Sale Securities [Line Items]
Available-for-sale securities remaining contractual maturities	3 years

Balance Sheet Components - Summary of Inventory (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Investments, Debt and Equity Securities [Abstract]
Work-in-process	$ 17,486	$ 10,504
Finished goods	9,280	5,727
Total	$ 26,766	$ 16,231

Balance Sheet Components - Summary of Property, Plant and Equipment, Net (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Property Plant And Equipment [Line Items]
Property, plant and equipment, gross	$ 323,107	$ 191,285
Less accumulated depreciation	(63,381)	(50,038)
Property, plant and equipment, net	259,726	141,247
Leasehold Improvements
Property Plant And Equipment [Line Items]
Property, plant and equipment, gross	43,941	44,081
Research and Development Equipment
Property Plant And Equipment [Line Items]
Property, plant and equipment, gross	50,291	38,661
Furniture and Office Equipment
Property Plant And Equipment [Line Items]
Property, plant and equipment, gross	5,540	5,413
Computer Equipment and Software
Property Plant And Equipment [Line Items]
Property, plant and equipment, gross	13,876	10,238
Land
Property Plant And Equipment [Line Items]
Property, plant and equipment, gross	16,619	15,487
Construction-in-progress
Property Plant And Equipment [Line Items]
Property, plant and equipment, gross	189,448	76,849
Other
Property Plant And Equipment [Line Items]
Property, plant and equipment, gross	$ 3,392	$ 556

Balance Sheet Components - Accrued Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Payables and Accruals [Abstract]
Research, clinical study, and manufacturing expenses	$ 73,558	$ 40,880
Payroll and related expenses	78,938	62,591
Other	52,182	42,084
Total	$ 204,678	$ 145,555

Intangible Assets, Net - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Finite Lived Intangible Assets [Line Items]
upfront payment	$ 30.0
Acquired Finite Lived Intangible Assets Weighted Average Useful Life	10 years 6 months
IPR&D Assets
Finite Lived Intangible Assets [Line Items]
Business combination recognized intangible assets	$ 129.0	$ 129.0
Cost of sales
Finite Lived Intangible Assets [Line Items]
Costs of sales related to amortization of intangible asset	3.2	$ 0.3	$ 0.2
Dimension
Finite Lived Intangible Assets [Line Items]
Contractual payments received	$ 4.8
Intangible assets, remaining amortization period	5 years 8 months 12 days

Intangible Assets, Net - Summary of Company's Intangible Assets (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Schedule of Finite and Indefinite Lived Intangible Assets [Line Items]
Intangible assets - Gross carrying amount	$ 163,775	$ 131,275
Intangible assets - Accumulated Amortization	(3,670)	(487)
Intangible assets - Net Carrying Amount	160,105	130,788
Indefinite-lived Intangible Assets
Schedule of Finite and Indefinite Lived Intangible Assets [Line Items]
Intangible assets - Gross carrying amount	129,000	129,000
Intangible assets - Net Carrying Amount	129,000	129,000
Finite lived intangible assets
Schedule of Finite and Indefinite Lived Intangible Assets [Line Items]
Intangible assets - Gross carrying amount	$ 34,775	$ 2,275
Intangible assets - Weighted Average Life	9 years 10 months 24 days	7 years
Intangible assets - Accumulated Amortization	$ (3,670)	$ (487)
Intangible assets - Net Carrying Amount	$ 31,105	$ 1,788

Intangible Assets, Net - Schedule of Expected Amortization of the Intangible Assets (Details) $ in Thousands	Dec. 31, 2022 USD ($)
Intangible Assets, Net (Excluding Goodwill) [Abstract]
2023	$ 3,738
2024	3,738
2025	3,738
2026	3,738
2027	3,297
Thereafter	12,856
Total	$ 31,105

Revenue - Summary of Disaggregation of Total Revenues from Customers (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Total revenues
Total revenues	$ 363,329	$ 351,406	$ 271,030
Collaboration and License
Total revenues
Total revenues	222,710	256,438	219,315
Collaboration and License \| Crysvita
Total revenues
Total revenues	215,024	171,198	128,597
Collaboration and License \| Royalty Revenue in European Territory \| Crysvita
Total revenues
Total revenues	0	244	1,498
Collaboration and License \| Daiichi Sankyo
Total revenues
Total revenues	7,686	84,996	89,220
Product Sales
Total revenues
Total revenues	118,927	77,017	38,720
Product Sales \| Crysvita
Total revenues
Total revenues	42,678	21,422	10,350
Product Sales \| Mepsevii
Total revenues
Total revenues	20,637	16,035	15,342
Product Sales \| Dojolvi
Total revenues
Total revenues	55,612	39,560	13,028
Non-cash Collaboration Royalty Revenue
Total revenues
Total revenues	21,692	17,951	12,995
Non-cash Collaboration Royalty Revenue \| Crysvita
Total revenues
Total revenues	$ 21,692	$ 17,951	$ 12,995

Revenue - Summary of Disaggregation of Total Revenues (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Disaggregation Of Revenue [Line Items]
Total revenues	$ 363,329	$ 351,406	$ 271,030
North America
Disaggregation Of Revenue [Line Items]
Total revenues	281,088	301,110	237,666
Europe
Disaggregation Of Revenue [Line Items]
Total revenues	36,369	26,660	21,318
Latin America
Disaggregation Of Revenue [Line Items]
Total revenues	44,711	23,636	12,046
Japan
Disaggregation Of Revenue [Line Items]
Total revenues	$ 1,161	$ 0	$ 0

- Definition

Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 30
-Subparagraph (a)
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e8906-108599

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 40
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e9031-108599

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 41
-Subparagraph (a)
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e9038-108599

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 32
-Subparagraph (b)
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e8933-108599

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 32
-Subparagraph (a)
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e8933-108599

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 4
-Subparagraph (a)
-URI https://asc.fasb.org/extlink&oid=126920106&loc=SL49130543-203045

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 22
-Subparagraph (b)
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e8736-108599

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 22
-Subparagraph (a)
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e8736-108599

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 42
-URI https://asc.fasb.org/extlink&oid=126901519&loc=d3e9054-108599

Reference 10: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 5
-URI https://asc.fasb.org/extlink&oid=126920106&loc=SL49130545-203045

Reference 11: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 924
-SubTopic 10
-Section S99
-Paragraph 1
-Subparagraph (SAB Topic 11.L)
-URI https://asc.fasb.org/extlink&oid=6472922&loc=d3e499488-122856

+ Details

Revenue - Schedule of Sales-Related Accruals and Allowances (Details) - Product Sales - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Disaggregation Of Revenue [Line Items]
Balance of product sales reserve at beginning of year	$ 7,181	$ 3,913	$ 1,818
Provisions	13,525	9,586	5,763
Payments	(9,613)	(6,120)	(2,785)
Adjustments	394	(198)	(883)
Balance of product sales reserve at end of year	$ 11,487	$ 7,181	$ 3,913

Revenue - Summary of Changes in Contract Assets (Liabilities) (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Disaggregation of Revenue [Abstract]
Balance of contract liabilities at beginning of period	$ 9,076	$ 66,568
Additions	89	27,504
Deductions	(7,686)	(84,996)
Balance of contract liabilities at end of period, net	$ 1,479	$ 9,076

Revenue - Additional Information (Details)	Dec. 31, 2022	Dec. 31, 2021
Disaggregation of Revenue [Abstract]
Percentage of gross accounts receivable balance	68.00%	71.00%

GeneTx Acquisition - Additional Information (Details) - USD ($) $ in Thousands	1 Months Ended			12 Months Ended
	Jul. 31, 2022	Apr. 30, 2022	Aug. 31, 2019	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Business Acquisition [Line Items]
Acquired in-process research and development				$ 75,033	$ 0	$ 0
GeneTx [Member]
Business Acquisition [Line Items]
Business acquisition, consideration transferred	$ 75,000
Regulatory Approval Milestones	85,000
Outstanding Cash and Cash Equivalents Acquired	15,600
Amount on adjustments for working capital and transaction expenses	600
Payments to Acquire Businesses, Gross	91,200
GeneTx [Member] \| Maximum
Business Acquisition [Line Items]
Future contingent milestone payments	190,000
Additional Milestone Payments	30,000
Commercial Milestone Payment	$ 75,000
In Process Research and Development [Member] \| GeneTx [Member]
Business Acquisition [Line Items]
Acquired in-process research and development				$ 75,000
Gene Tx Biotherapeutics L L C [Member] \| Program Agreement And Unitholder Option Agreement [Member]
Business Acquisition [Line Items]
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.
Upfront payment for exclusive option to acquisition			$ 20,000
Option extension payment			$ 25,000
Acquisition cost		$ 75,000

License and Research Agreements - Additional Information (Details)			1 Months Ended											3 Months Ended		12 Months Ended			31 Months Ended	113 Months Ended
	Jan. 01, 2023	Jan. 07, 2022	Apr. 30, 2023	Oct. 31, 2022 shares	Jan. 31, 2022 USD ($)	May 31, 2021 USD ($)	Jan. 31, 2021 USD ($)	Oct. 31, 2020 USD ($) shares	May 31, 2020 USD ($) shares	Mar. 31, 2020 USD ($) $ / shares	Aug. 31, 2019 USD ($)	Jun. 30, 2019 USD ($) DiseaseTarget $ / shares shares	Oct. 31, 2015 USD ($)	Mar. 31, 2021 USD ($)	Mar. 31, 2020 USD ($) $ / shares shares	Dec. 31, 2022 USD ($) $ / shares shares	Dec. 31, 2021 USD ($) $ / shares shares	Dec. 31, 2020 USD ($)	Dec. 31, 2022 USD ($) $ / shares shares	Dec. 31, 2022 USD ($) $ / shares shares
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Collaboration and license revenue																$ 363,329,000	$ 351,406,000	$ 271,030,000
Research and development																$ 705,789,000	$ 497,153,000	412,084,000
Common stock purchased \| shares																70,197,297	69,344,998		70,197,297	70,197,297
Common stock, par value \| $ / shares																$ 0.001	$ 0.001		$ 0.001	$ 0.001
Proceeds from issuance of common stock in connection with license agreement																$ 0	$ 0	55,268,000
Issuance of common stock in connection with license agreement, net of issuance costs																		55,268,000
Common stock. per share \| $ / shares																$ 0.001	$ 0.001		$ 0.001	$ 0.001
Common stock investment value																$ 70,000	$ 69,000		$ 70,000	$ 70,000
Daiichi Sankyo
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Revenue recognized																7,700,000	85,000,000.0	89,200,000
Deferred revenue																1,500,000	9,100,000		1,500,000	1,500,000
Receivable related to Daiichi Sankyo license agreement																$ 0	100,000		0	0
Solid Biosciences, Inc.
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Remaining consideration paid																		13,200,000
Business acquisition, consideration transferred																		40,000,000.0
Common stock investment value								$ 26,800,000
Description of the stock split				In October 2022, Solid announced a 1 for 15 reverse stock split. After the split, the Company holds 521,719 shares in Solid.
stock split conversion ratio				0.0667
Number of common shares held after split \| shares				521,719
Regeneron Pharmaceuticals Inc
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Upfront payments of collaboration					$ 30,000,000.0
Intangible assets, remaining amortization period																10 years 6 months
Costs of sales related to amortization of intangible asset																$ 2,900,000
Development costs																7,300,000
Sales																0	0
Eligible future milestone payments					$ 63,000,000.0
Abeona
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Development and transition costs																$ 3,100,000
Minimum [Member] \| Regeneron Pharmaceuticals Inc
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Profit loss sharing percentage on net sales					20.00%
Maximum [Member] \| Regeneron Pharmaceuticals Inc
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Profit loss sharing percentage on net sales																40.00%
Maximum [Member] \| Abeona
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Eligible future milestone payments																$ 1,000.0			1,000.0	$ 1,000.0
Product Sales
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Collaboration and license revenue																118,927,000	77,017,000	38,720,000
Sublicense Agreement \| Daiichi Sankyo
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Upfront payment received																$ 8,000,000.0
License Agreement \| Profit Share Territory \| Scenario Forecast \| Minimum [Member]
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Tiered double-digit revenue share percentage entitled to receive			20.00%
License and Collaboration Agreement \| Mereo
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Upfront payment for in-process research and development expense														$ 50,000,000.0
Payments made under agreement							$ 50,000,000.0
License and Collaboration Agreement \| Abeona
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Percentage of royalty on net sales receives																10.00%
Commercial milestone payments						$ 30,000,000.0
License and Collaboration Agreement \| Maximum [Member] \| Mereo
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future contingent milestone payments							$ 254,000,000.0
Kyowa Kirin Collaboration \| License Agreement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Profit loss sharing percentage on net sales	30.00%																			35.00%
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																$ 6,400,000	16,000,000.0		6,400,000	$ 6,400,000
Kyowa Kirin Collaboration \| License Agreement \| Product Sales
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Collaboration and license revenue																42,700,000	21,400,000	10,400,000
Kyowa Kirin Collaboration \| License Agreement \| Profit Share Revenue
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
License agreement accounts receivable																27,500,000	20,200,000		27,500,000	27,500,000
Kyowa Kirin Collaboration \| License Agreement \| Commercial and Development Activity Reimbursements
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
License agreement accrued liabilities																$ 3,100,000	2,300,000		3,100,000	3,100,000
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%
Percentage of right to receive royalty payments on net sales		30.00%
Kyowa Kirin Collaboration \| License Agreement \| Profit Share Territory \| Scenario Forecast \| Maximum [Member]
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Tiered double-digit revenue share percentage entitled to receive			30.00%
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
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Milestone payments paid																$ 100,000
Baylor Research Institute \| Development Milestones
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future contingent milestone payments																7,500,000			7,500,000	7,500,000
Baylor Research Institute \| Development Milestones \| Research and Development Expense
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Contingent milestone payment																2,500,000	0	2,000,000.0
Option and License Agreement \| REGENXBIO, Inc.
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future contingent milestone payments																$ 9,000,000.0			9,000,000.0	9,000,000.0
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
License Agreement \| REGENXBIO, Inc.
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future contingent milestone payments																14,000,000.0			14,000,000.0	14,000,000.0
Upfront payment for in-process research and development expense										$ 7,000,000.0
Annual fees payable																100,000
Research Collaboration and License Agreement Development Milestones \| University of Pennsylvania School of Medicine (Penn)
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future contingent milestone payments																5,000,000.0			5,000,000.0	5,000,000.0
Research Collaboration and License Agreement Commercial Milestones \| University of Pennsylvania School of Medicine (Penn)
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future contingent milestone payments																25,000,000.0			$ 25,000,000.0	$ 25,000,000.0
Arcturus Therapeutics Holdings Inc
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Milestone payments received																	1,000,000.0
Research and development																$ 0	$ 0	$ 400,000
Upfornt cash payment paid												$ 6,000,000.0
Common stock purchased \| shares												2,400,000
Common stock shares sold \| shares																500,000	1,700,000
Common stock, par value \| $ / shares												$ 10.00				$ 20.39	$ 47.44		$ 20.39	$ 20.39
Common stock. per share \| $ / shares												$ 10.00				$ 20.39	$ 47.44		$ 20.39	$ 20.39
Business acquisition, consideration transferred												$ 30,000,000.0
Additional option to purchase common stock \| shares												600,000
Additional option to purchase common stock value per share \| $ / shares												$ 16.00
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
Number of common stock held \| shares																500,000	500,000		500,000	500,000
Arcturus Therapeutics Holdings Inc \| Maximum [Member]
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Number of disease targets \| DiseaseTarget												12
Regulatory milestone payments													$ 24,500,000
Commercial milestone payments													$ 45,000,000.0
Program Agreement And Unitholder Option Agreement [Member] \| GeneTx Biotherapeutics LLC
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Upfront payment for exclusive option to acquisition											$ 20,000,000.0
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.
License and Technology Access Agreement \| Daiichi Sankyo
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Deferred revenue																$ 25,000,000.0			$ 25,000,000.0	$ 25,000,000.0
Upfront payment received																125,000,000.0
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 \| PCL and HEK293 Platforms \| Daiichi Sankyo
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Deferred revenue																25,000,000.0			25,000,000.0	$ 25,000,000.0
License and Technology Access Agreement \| Licenses Agreement \| Daiichi Sankyo
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Revenue recognized																			$ 181,900,000
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															$ 75,000,000.0
Issuance of common stock in connection with license agreement, net of issuance costs										$ 55,300,000
Stock price \| $ / shares										$ 44.43					$ 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																$ 8,000,000.0
Collaboration and License Agreement \| Maximum [Member] \| Solid Biosciences, Inc.
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Development milestone payments								25,000,000.0
Regulatory milestone payments								65,000,000.0
Commercial milestone payments								$ 165,000,000.0
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								$ 40,000,000.0

License and Research Agreements - Share of Collaboration and Royalty Revenue Related to Crysvita (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	$ 363,329	$ 351,406	$ 271,030
Collaboration and Royalty \| Kyowa Kirin Collaboration
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	236,716	189,393	143,090
Collaboration and Royalty \| Kyowa Kirin Collaboration \| Profit Share Territory
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	215,024	171,198	128,597
Collaboration and Royalty \| Kyowa Kirin Collaboration \| Royalty Revenue in European Territory
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	0	244	1,498
Non-cash Collaboration Royalty Revenue
Disaggregation Of Revenue [Line Items]
Collaboration and license revenue	21,692	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	$ 21,692	$ 17,951	$ 12,995

- Definition

+ References

+ Details

License and Research Agreements - Schedule of Cost Sharing Payments (Details) - Kyowa Kirin Collaboration - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Cost Sharing Payments [Line Items]
Research and development	$ 15,974	$ 21,657	$ 21,476
Selling, general and administrative	37,217	32,629	25,186
Total	$ 53,191	$ 54,286	$ 46,662

License and Research Agreements - Schedule of Changes in Fair Value of Equity Investment (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Common stock, Beginning balance	$ 1,001,451
Common stock, Ending balance	884,017	$ 1,001,451
Arcturus \| Common Stock
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Common stock, Beginning balance	18,505	95,436
Common stock, Change in fair value	(8,411)	2,912
Common stock, Sale of shares	(10,094)	(79,843)
Common stock, Ending balance	$ 0	$ 18,505

License and Research Agreements - Schedule of Changes in Fair Value of Investment in Securities (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Common stock, Beginning balance	$ 1,001,451
Common stock, Ending balance	884,017	$ 1,001,451
Common Stock \| Solid And Arcturus
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Common stock, Beginning balance	13,695	59,320
Common stock, Change in fair value	(10,888)	(45,625)
Common stock, Ending balance	$ 2,807	$ 13,695

Leases - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Lessee Disclosure [Abstract]
Operating lease extension details	multiple renewal periods
Operating lease, existence of option to extend	true
Operating lease expiry term	2028
Legally binding minimum lease payments	$ 23.4
Fit out costs	9.9
Cash paid for measurement of operating lease liabilities	$ 13.1	$ 11.8	$ 10.3
Operating lease weighted average remaining lease term	3 years 3 days	3 years 10 months 2 days
Financing lease weighted average remaining lease term	2 years 9 months 21 days	3 years 10 months 17 days
Operating lease weighted average discount rate	6.72%	6.64%
Financing lease weighted average discount rate	5.13%	5.44%

Leases - Summary of Components of Lease Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Lease, Cost [Abstract]
Operating lease expense	$ 11,775	$ 11,209	$ 10,164
Variable lease expense	4,785	4,142	3,298
Financing:
Amortization	343	310	158
Interest expense	37	58	40
Total	$ 16,940	$ 15,719	$ 13,660

Leases - Schedule of Maturities of Lease Liabilities and the Reconciliation of Lease Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Operating
2023	$ 13,244
2024	11,372
2025	6,530
2026	2,964
2027	446
Thereafter	376
Total future lease payments	34,932
Less: Amount representing interest	(3,522)
Present value of future lease payments	31,410
Less: Lease liabilities, current	$ (11,596)
Operating Lease, Liability, Statement of Financial Position [Extensible List]	Less: Lease liabilities, current
Lease liabilities, non-current	$ 19,814
Operating Lease, Liability, Statement of Financial Position [Extensible List]	Non-current lease liability
Financing
2023	$ 187
2024	0
2025	0
Total future lease payments	187
Less: Amount representing interest	(4)
Present value of future lease payments	183
Less: Lease liabilities, current	(183)
Lease liabilities, non-current	0
Future Minimum Lease Payments - Operating and Financing Leases
2023	13,431
2024	11,372
2025	6,530
2026	2,964
2027	446
Thereafter	376
Total future lease payments	35,119
Less: Amount representing interest	(3,526)
Present value of future lease payments	31,593
Less: Lease liabilities, current	$ (11,779)	$ (11,066)
Finance Lease, Liability, Current, Statement of Financial Position [Extensible Enumeration]	Less: Lease liabilities, current
Non-current lease liability	$ 19,814	$ 30,904
Finance Lease, Liability, Noncurrent, Statement of Financial Position [Extensible Enumeration]	Non-current lease liability

Liabilities for Sales of Future Royalties - Additional Information (Details) - USD ($) $ in Thousands	1 Months Ended		12 Months Ended
	Jul. 31, 2022	Dec. 31, 2019	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Liability For Sale Of Future Royalties [Line Items]
Net proceeds from sale of future royalties in 2022			$ 490,950	$ 0	$ 0
RPI Finance Trust (RPI)
Liability For Sale Of Future Royalties [Line Items]
Net proceeds from sale of future royalties in 2022			0
OMERS
Liability For Sale Of Future Royalties [Line Items]
Net proceeds from sale of future royalties in 2022			$ 490,950
Royalty Purchase Agreement
Liability For Sale Of Future Royalties [Line Items]
Profit loss sharing percentage on net sales	30.00%
Royalty Purchase Agreement \| RPI Finance Trust (RPI)
Liability For Sale Of Future Royalties [Line Items]
Proceeds from sale of future royalties		$ 320,000
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, or when aggregate royalty payments received by RPI are equal to $800.0 million.
Net proceeds from sale of future royalties in 2022		314,200
Effective annual interest rate			9.30%
Royalties transaction costs net		5,800
Royalty Purchase Agreement \| OMERS
Liability For Sale Of Future Royalties [Line Items]
Proceeds from sale of future royalties			$ 500,000
Royalty payment termination description	In July 2022, the Company entered into a Royalty Purchase Agreement with OMERS. Pursuant to the agreement, OMERS paid $500.0 million to the Company in consideration for the right to receive 30% of the future royalty payments due to the Company from KKC based on net sales of Crysvita in the U.S. and Canada under the terms of the KKC Collaboration Agreement. The calculation of royalty payments to OMERS will be based on net sales of Crysvita beginning in April 2023 and will expire upon the earlier of the date on which aggregate payments received by OMERS equals $725.0 million or the date the final royalty payment is made to the Company under the KKC Collaboration Agreement.
Royalty agreement termination threshold amount	$ 725,000
Payment from sale of future royalties	$ 500,000
Net proceeds from sale of future royalties in 2022			$ 491,000
Effective annual interest rate			8.40%
Royalties transaction costs net			$ 9,100
Royalty Purchase Agreement \| Minimum \| RPI Finance Trust (RPI)
Liability For Sale Of Future Royalties [Line Items]
Royalty agreement termination threshold amount		$ 608,000	608,000
Royalty Purchase Agreement \| Maximum \| RPI Finance Trust (RPI)
Liability For Sale Of Future Royalties [Line Items]
Royalty agreement termination threshold amount			$ 800,000

Liabilities for Sales of Future Royalties - Schedule of Activity Within Liability For Sale of Future Royalties (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Liability For Sale Of Future Royalties [Line Items]
Liability for sale of future royalties at beginning of year	$ 351,786	$ 335,665
Net proceeds from sale of future royalties in 2022	490,950	0	$ 0
Non-cash collaboration royalty revenue	(21,692)	(17,951)	(12,995)
Non-cash interest expense	54,395	34,072
Liability for sale of future royalties at end of year	875,439	351,786	335,665
RPI Finance Trust (RPI)
Liability For Sale Of Future Royalties [Line Items]
Liability for sale of future royalties at beginning of year	351,786	335,665
Net proceeds from sale of future royalties in 2022	0
Non-cash collaboration royalty revenue	(21,692)	(17,951)
Non-cash interest expense	35,095	34,072
Liability for sale of future royalties at end of year	365,189	351,786	335,665
OMERS
Liability For Sale Of Future Royalties [Line Items]
Liability for sale of future royalties at beginning of year	0	0
Net proceeds from sale of future royalties in 2022	490,950
Non-cash collaboration royalty revenue	0	0
Non-cash interest expense	19,300	0
Liability for sale of future royalties at end of year	$ 510,250	$ 0	$ 0

Equity - Additional Information (Details) - USD ($) $ / shares in Units, $ in Thousands	1 Months Ended		12 Months Ended
	May 31, 2021	Oct. 31, 2020	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Stockholders Equity [Line Items]
Net proceeds from sale of common stock			$ 0	$ 0	$ 435,556
Stock sold in at-the-market offering				1,050,372
Net proceeds from at-the-market offering			$ 0	$ 78,943	$ 20,391
Underwritten Public Offering
Stockholders Equity [Line Items]
Common stock shares sold		5,111,110
Net proceeds from sale of common stock		$ 435,600
Shares purchased by underwriters		666,666
Public offering price		$ 90.00
Open Market Sale
Stockholders Equity [Line Items]
Common stock shares sold			0
Option to sell common stock aggregate offering price	$ 350,000

Stock-Based Awards - Additional Information (Details) - USD ($) $ / shares in Units, $ in Millions	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020	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	$ 2.6	$ 38.3	$ 56.9
Cash received from exercise of options	$ 6.2	$ 36.6	$ 88.1
weighted-average estimated fair value	$ 34.77	$ 70.84	$ 35.22
Total estimated fair value of options vested	$ 58.7	$ 48.1	$ 45.4
Total unrecognized compensation cost	$ 229.4
Weighted-average period to recognize cost	2 years 3 months 10 days
Stock-based compensation capitalized to inventory	$ 2.2	$ 1.7	$ 1.2
Share-Based Compensation Arrangement by Share-Based Payment Award, Options, Grants in Period, Weighted Average Grant Date Fair Value	$ 34.77	$ 70.84	$ 35.22
Restricted Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Total fair value of shares vested	$ 47.1	$ 35.5	$ 27.2
Aggregate intrinsic value	37.8	69.9	29.5
Performance Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Total fair value of shares vested	1.6	9.2	10.3
Aggregate intrinsic value	$ 2.0	$ 18.9	$ 14.4
Performance Stock Options [Member]
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
weighted-average estimated fair value	$ 28.76
Share-Based Compensation Arrangement by Share-Based Payment Award, Options, Grants in Period, Weighted Average Grant Date Fair Value	$ 28.76
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. 01, 2015
Shares available for grant, ending date		Jan. 01, 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	14,211,103
2014 Employee Stock Purchase Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Share of common stock authorized for future issuance	4,585,921
Automatic increases in shares available for grant effective date	Jan. 01, 2015
Shares available for grant, ending date	Jan. 01, 2024
Share of common stock available for future issuance						600,000
Percentage of statutory stock awards	85.00%
Common stock shares issued	112,974
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 Activity Under Stock Option Plans Including 2011 Plan and 2014 Plan (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Share-Based Payment Arrangement [Abstract]
Number of Options, Outstanding, Beginning Balance	6,198,205
Number of Options, Options granted	2,293,950
Number of Options, Options exercised	(130,865)
Number of Options, Options cancelled	(587,923)
Number of Options, Outstanding, Ending Balance	7,773,367	6,198,205
Vested and exercisable December 31, 2022	4,577,580
Vested and expected to vest December 31, 2022	7,471,015
Weighted Average Exercise Price, Outstanding, Beginning Balance	$ 75.96
Weighted Average Exercise Price, Options granted	64.88
Weighted Average Exercise Price, Options exercised	47.70
Weighted Average Exercise Price, Options cancelled	84.06
Weighted Average Exercise Price, Outstanding, Ending Balance	72.56	$ 75.96
Weighted- Average Exercise Price,Weighted Average Exercise Price	70.89
Weighted Average Exercise Price, Vested and expected to vest December 31,2022	$ 72.50
Weighted Average Remaining Contractual Term (Years), Outstanding	6 years 7 months 6 days	6 years 9 months 21 days
Weighted Average Remaining Contractual Term (Years), Vested and exercisable - December 31, 2022	5 years 1 month 20 days
Weighted-Average Remaining Contractual Term,Vested and expected to vest December 31, 2022	6 years 6 months 3 days
Aggregate Intrinsic Value, Outstanding	$ 8,476	$ 112,242
Aggregate Intrinsic Value, Vested and exercisable - December 31, 2022	7,658
Aggregate Intrinsic Value, Vested and expected to vest - December 31, 2022	$ 8,371

Stock-Based Awards- Summary Activity Under the Performance Stock Option (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021
Share-Based Compensation Arrangement by Share-Based Payment Award [Line Items]
Vested and exercisable December 31, 2022	4,577,580
Vested and expected to vest December 31, 2022	7,471,015
Weighted- Average Exercise Price,Weighted Average Exercise Price	$ 70.89
Weighted Average Exercise Price, Vested and expected to vest December 31,2022	$ 72.50
Weighted-Average Remaining Contractual Term,Vested and expected to vest December 31, 2022	6 years 6 months 3 days
Share-Based Compensation Arrangement by Share-Based Payment Award, Options, Vested and Expected to Vest, Exercisable, Aggregate Intrinsic Value	$ 7,658
Share-Based Compensation Arrangement by Share-Based Payment Award, Options, Vested and Expected to Vest, Outstanding, Aggregate Intrinsic Value	$ 8,371
Performance Stock Options [Member]
Share-Based Compensation Arrangement by Share-Based Payment Award [Line Items]
Outstanding, Number of Shares, Unvested, Beginning Balance	0
PSOs granted	1,827,449
PSOs cancelled	(202,850)
Outstanding, Number of Shares, Unvested, Ending Balance	1,624,599
Vested and expected to vest December 31, 2022	1,081,597
Outstanding, Weighted-Average Grant Date Fair Value, Unvested, Beginning Balance	$ 0
Weighted Average Exercise Price,PSOs granted	67.37
Weighted Average Exercise Price ,PSOs cancelled	67.37
Weighted- Average Exercise Price,Outstanding December 31, 2022	67.37
Weighted Average Exercise Price, Vested and expected to vest December 31,2022	$ 67.37
Weighted-Average Remaining Contractual Term,Outstanding at June 30, 2022	4 years 1 month 20 days
Weighted-Average Remaining Contractual Term,Vested and expected to vest December 31, 2022	4 years 1 month 20 days
Share-Based Compensation Arrangement by Share-Based Payment Award, Equity Instruments Other than Options, Aggregate Intrinsic Value, Outstanding	$ 0	$ 0
Share-Based Compensation Arrangement by Share-Based Payment Award, Options, Vested and Expected to Vest, Exercisable, Aggregate Intrinsic Value	0
Share-Based Compensation Arrangement by Share-Based Payment Award, Options, Vested and Expected to Vest, Outstanding, Aggregate Intrinsic Value	$ 0

Stock-Based Awards - Summary of Activity Under Restricted Stock Units (RSUs) from 2014 Plan (Details) - Restricted Stock Units	12 Months Ended
	Dec. 31, 2022 $ / shares shares
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Outstanding, Number of Shares, Unvested, Beginning Balance \| shares	1,672,625
Number of shares, granted \| shares	1,347,125
Number of shares, vested \| shares	(591,837)
Number of shares, cancelled \| shares	(298,760)
Outstanding, Number of Shares, Unvested, Ending Balance \| shares	2,129,153
Outstanding, Weighted-Average Grant Date Fair Value, Unvested, Beginning Balance \| $ / shares	$ 87.48
Weighted-Average Grant Date Fair Value, granted \| $ / shares	63.22
Weighted-Average Grant Date Fair Value, vested \| $ / shares	79.59
Weighted-Average Grant Date Fair Value, cancelled \| $ / shares	81.84
Weighted- Average Exercise Price,Outstanding December 31, 2022 \| $ / shares	$ 75.11

Stock-Based Awards - Summary of Activity Under PSUs from 2014 Plan (Details) - Performance Stock Units	12 Months Ended
	Dec. 31, 2022 $ / shares shares
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Outstanding, Number of Shares, Unvested, Beginning Balance \| shares	93,892
Number of shares, granted \| shares	166,730
Number of shares, vested \| shares	(28,990)
Number of shares, cancelled \| shares	(22,402)
Outstanding, Number of Shares, Unvested, Ending Balance \| shares	209,230
Outstanding, Weighted-Average Grant Date Fair Value, Unvested, Beginning Balance \| $ / shares	$ 123.46
Weighted-Average Grant Date Fair Value, granted \| $ / shares	75.90
Weighted-Average Grant Date Fair Value, vested \| $ / shares	56.08
Weighted-Average Grant Date Fair Value, cancelled \| $ / shares	93.61
Weighted- Average Exercise Price,Outstanding December 31, 2022 \| $ / shares	$ 98.09

Stock-Based Awards - Summary of Stock-Based Compensation Recognized (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Stock-based compensation expense	$ 130,368	$ 104,979	$ 85,735
Cost of sales
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Stock-based compensation expense	902	871	827
Research and development
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Stock-based compensation expense	74,464	59,097	47,949
Selling, general and administrative
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Stock-based compensation expense	$ 55,002	$ 45,011	$ 36,959

Stock-Based Awards - Fair Value of Stock Option Awards Granted Estimated Using Black-Scholes Option-Pricing Model (Details)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Stock Options
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Expected term (years)	6 years 25 days	6 years 21 days	6 years 2 months 12 days
Expected volatility	56.00%	60.00%	61.00%
Risk-free interest rate	2.00%	1.00%	0.80%
Expected dividend rate	0.00%	0.00%	0.00%
Granted [Member]
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Expected term (years)		3 years 7 months 6 days
Expected volatility		57.00%
Risk-free interest rate		1.50%
Expected dividend rate		0.00%

Defined Contribution Plan - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Defined Contribution Pension And Other Post Retirement Plan Disclosure [Abstract]
Contribution expenses	$ 9.0	$ 5.5	$ 4.3

Income Taxes - Components of Company's Loss Before Income Taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Income Tax Disclosure [Abstract]
Domestic	$ 703,411	$ 455,314	$ 189,449
Foreign	(1,686)	(2,333)	(4,090)
Total loss before income taxes	$ 701,725	$ 452,981	$ 185,359

- Definition

Amount of income (loss) from continuing operations, including income (loss) from equity method investments, before deduction of income tax expense (benefit), and income (loss) attributable to noncontrolling interest.

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+ Details

Income Taxes - Components of Company's Income Tax Provision (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Current provision for income taxes:
State	$ 6,062	$ (14)	$ 15
International	1,274	1,058	1,192
Total current tax provision	7,336	1,044	1,207
Deferred tax provision:
State	(1,640)
Total deferred tax provision	(1,640)
Total provision for income taxes	$ 5,696	$ 1,044	$ 1,207

- Definition

Amount of current income tax expense (benefit) and deferred income tax expense (benefit) pertaining to continuing operations.

+ References + Details

Income Taxes - Additional Information (Details) - USD ($)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2012	Dec. 31, 2011
Tax Credit Carryforward [Line Items]
Current state income tax expense	$ 7,336,000	$ 1,044,000	$ 1,207,000
Deferred tax assets net operating loss carryforwards	231,835,000	306,119,000		$ 200,000	$ 200,000
Valuation allowance increased	193,800,000	139,500,000
Unrecognized tax benefits, income tax penalties and interest accrued	0	0	$ 0
Undistributed earnings of foreign subsidiaries	10,900,000
Federal
Tax Credit Carryforward [Line Items]
Deferred tax assets operating loss carryforwards subject to expiration	$ 756,600,000	1,085,400,000
Operating loss carryforwards expiration year	2031
Tax credit carryforwards	$ 32,600,000	22,900,000
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	$ 239,300,000	208,100,000
Operating loss carryforwards expiration year	2031
State
Tax Credit Carryforward [Line Items]
Current state income tax expense	$ 6,100,000
Deferred tax assets operating loss carryforwards subject to expiration	$ 710,000,000.0	777,000,000.0
Operating loss carryforwards expiration year	2031
Tax credit carryforwards	$ 59,900,000	$ 44,600,000
Deferred tax assets net operating loss carryforwards				$ 3,600,000	$ 3,600,000

Income Taxes - Effective Tax Rate of Provision for Income Taxes from Federal Statutory Rate (Details)	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
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	(0.40%)
Federal tax credits	5.90%	7.20%	13.70%
Other	(0.10%)	0.50%	(0.50%)
Premium on equity issuance			2.20%
Nondeductible permanent items	(0.60%)	(0.80%)	(0.90%)
Stock-based compensation	(1.20%)	1.30%	0.90%
Uncertain tax positions	(1.20%)	(1.40%)	(2.70%)
Change in valuation allowance	(24.00%)	(27.90%)	(33.90%)
Foreign rate differential	(0.20%)	(0.10%)	(0.50%)
Provision for income taxes	(0.80%)	(0.20%)	(0.70%)

Income Taxes - Schedule of Tax Effect of Temporary Differences to Significant Portions of Deferred Tax Assets (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2012	Dec. 31, 2011
Deferred tax assets:
Loss carryforwards	$ 231,835	$ 306,119	$ 200	$ 200
Tax credits	260,546	218,131
Stock options	39,784	33,564
Accruals and reserves	27,029	25,735
Fixed assets and intangibles	39,233	18,263
Liabilities for sales of future royalties	214,900	90,826
Basis difference in equity investments	8,971	3,912
Capitalized research and development costs	75,335
Other	3,028	13,060
Gross deferred tax assets	900,661	709,610
Valuation allowance	(894,518)	(700,669)
Total deferred tax assets	6,143	8,941
Deferred tax liabilities:
Gross deferred tax liabilities	(37,810)	(42,247)
Net deferred tax liabilities	(31,667)	(33,306)
Right-of-use Lease Assets
Deferred tax liabilities:
Gross deferred tax liabilities	(6,143)	(8,941)
In-process Research and Development
Deferred tax liabilities:
Gross deferred tax liabilities	$ (31,667)	$ (33,306)

Income Taxes - Unrecognized Tax Benefits (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Income Tax Disclosure [Abstract]
Balance at beginning of year	$ 55,360	$ 46,662	$ 39,954
Additions based on tax positions related to current year	11,316	8,542	6,950
Additions for tax positions of prior years	377	356	382
Reductions for tax positions of prior years	(259)	(200)	(624)
Balance at end of year	$ 66,794	$ 55,360	$ 46,662

Commitments and Contingencies - Additional Information (Details)	12 Months Ended
	Dec. 31, 2022
Manufacturing And Services [Member]
Commitments And Contingencies Disclosure [Line Items]
Contractual Obligation Maturity Period	12 months

Commitments and Contingencies - Summary of Aggregate Payments under Contractually Binding Manufacturing and Service Agreements (Details) - Manufacturing and Services $ in Thousands	Dec. 31, 2022 USD ($)
Commitments And Contingencies Disclosure [Line Items]
2023	$ 22,892
2024	4,467
2025	1,597
Total	$ 28,956

Related Party Transaction - Additional Information (Details) - USD ($) $ in Thousands	1 Months Ended	12 Months Ended
	Jul. 31, 2022	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Related Party Transaction [Line Items]
Contribution amount paid	$ 1,000
Contribution period	4 years
Research and development		$ 705,789	$ 497,153	$ 412,084
Rare Disease Education And Awareness \| Non Profit Foundation
Related Party Transaction [Line Items]
Research and development		$ 300

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, 2022	Dec. 31, 2021	Dec. 31, 2020
Numerator:
Net loss	$ (707,421)	$ (454,025)	$ (186,566)
Denominator:
Weighted-average shares used to computing net loss per share, basic	69,914,225	67,795,540	60,845,550
Weighted-average shares used to computing net loss per share, diluted	69,914,225	67,795,540	60,845,550
Net loss per share, basic	$ (10.12)	$ (6.70)	$ (3.07)
Net loss per share, diluted	$ (10.12)	$ (6.70)	$ (3.07)

- Definition

The amount of net income (loss) for the period per each share of common stock or unit outstanding during the reporting period.

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- Definition

The amount of net income (loss) for the period available to each share of common stock or common unit outstanding during the reporting period and to each share or unit that would have been outstanding assuming the issuance of common shares or units for all dilutive potential common shares or units outstanding during the reporting period.

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+ Details

- Definition

The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.

+ References

+ Details

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, 2022	Dec. 31, 2021	Dec. 31, 2020
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Common stock equivalents excluded from computation of diluted net loss per share	11,298,516	8,217,574	8,564,311
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	11,290,935	8,214,063	8,532,236
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
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	7,581	3,511	2,626

Accumulated Other Comprehensive Loss - Schedule of Total Accumulated Other Comprehensive income (Loss) (Details) - USD ($) $ in Thousands	Dec. 31, 2022	Dec. 31, 2021
Accumulated Other Comprehensive Income (Loss), Net of Tax [Abstract]
Cumulative foreign currency translation adjustment	$ (845)	$ (121)
Unrealized loss on securities available-for-sale	(5,728)	(1,283)
Total accumulated other comprehensive loss	$ (6,573)	$ (1,404)

- Definition

Accumulated change in equity from transactions and other events and circumstances from non-owner sources, net of tax effect, at period end. Excludes Net Income (Loss), and accumulated changes in equity from transactions resulting from investments by owners and distributions to owners. Includes foreign currency translation items, certain pension adjustments, unrealized gains and losses on certain investments in debt and equity securities, other than temporary impairment (OTTI) losses related to factors other than credit losses on available-for-sale and held-to-maturity debt securities that an entity does not intend to sell and it is not more likely than not that the entity will be required to sell before recovery of the amortized cost basis, as well as changes in the fair value of derivatives related to the effective portion of a designated cash flow hedge.

+ References + Details