Spark Therapeutics (ONCE) 10-K 28 Feb 19 2018 FY Annual report Financial data

Document and Entity Information

Document and Entity Information - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2018	Feb. 15, 2019	Jun. 30, 2018
Document And Entity Information [Abstract]
Entity Registrant Name	Spark Therapeutics, Inc.
Entity Central Index Key	1,609,351
Current Fiscal Year End Date	--12-31
Entity Filer Category	Large Accelerated Filer
Entity Emerging Growth Company	false
Entity Small Business	false
Entity Shell Company	false
Document Type	10-K
Trading Symbol	ONCE
Document Period End Date	Dec. 31, 2018
Document Fiscal Year Focus	2,018
Document Fiscal Period Focus	FY
Amendment Flag	false
Entity Common Stock, Shares Outstanding		37,961,302
Entity Well-known Seasoned Issuer	Yes
Entity Voluntary Filers	No
Entity Current Reporting Status	Yes
Entity Public Float			$ 2,583.3

Consolidated balance sheets

Consolidated balance sheets - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Current assets:
Cash and cash equivalents	$ 95,247	$ 96,748
Marketable securities	358,359	423,419
Trade and other receivables	47,385	7,906
Inventory	25,637	0
Prepaid expenses and other current assets	40,512	5,093
Total current assets	567,140	533,166
Restricted cash	53,000	0
Marketable securities	94,678	20,035
Property and equipment, net	95,998	61,713
Goodwill	1,198	1,254
Other assets	2,338	628
Total assets	814,352	616,796
Current liabilities:
Accounts payable	19,492	14,183
Accrued expenses	34,790	24,697
Current portion of long-term debt	4,822	312
Current portion of deferred rent	1,365	969
Current portion of deferred revenue	0	11,969
Current other liabilities	1,885	1,557
Total current liabilities	62,354	53,687
Long-term debt	46,090	912
Long-term deferred rent	10,885	8,318
Long-term deferred revenue	160,000	0
Other liabilities	38,510	40,255
Total liabilities	317,839	103,172
Stockholders’ equity:
Preferred stock, $0.001 par value. Authorized, 5,000,000 shares; no shares issued or outstanding	0	0
Common stock, $0.001 par value. Authorized, 150,000,000 shares; 37,131,626 shares issued and 37,111,404 shares outstanding as of December 31, 2017; 37,764,213 shares issued and 37,686,301 shares outstanding as of December 31, 2018	38	37
Additional paid-in capital	1,091,873	1,026,590
Accumulated other comprehensive loss	(1,050)	(5,914)
Treasury stock, at cost, 20,222 common shares as of December 31, 2017 and 77,912 common shares as of December 31, 2018	(4,661)	(1,226)
Accumulated deficit	(589,687)	(505,863)
Total stockholders’ equity	496,513	513,624
Total liabilities and stockholders’ equity	$ 814,352	$ 616,796

Consolidated balance sheets (Pa

Consolidated balance sheets (Parenthetical) - $ / shares	Dec. 31, 2018	Dec. 31, 2017
Statement of Financial Position [Abstract]
Preferred stock, par value (in usd per share)	$ 0.001	$ 0.001
Preferred stock, shares authorized	5,000,000	5,000,000
Preferred stock, shares issued	0	0
Preferred stock, shares outstanding	0	0
Common stock, par value (in usd per share)	$ 0.001	$ 0.001
Common stock, shares authorized	150,000,000	150,000,000
Common stock, shares issued	37,764,213	37,131,626
Common stock, shares outstanding	37,686,301	37,111,404
Treasury stock, shares	77,912	20,222

Consolidated statements of oper

Consolidated statements of operations and other comprehensive income (loss) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Total revenues	$ 64,725	$ 12,066	$ 20,183
Operating expenses:
Research and development	125,254	135,160	86,380
Acquired in-process research and development	300	8,604	11,132
Impairment of acquired in-process research and development	0	15,696	0
Selling, general and administrative	124,895	111,124	48,070
Total operating expenses	258,364	270,584	145,582
Loss from operations	(193,639)	(258,518)	(125,399)
Unrealized loss on equity investments	(5,078)	0	0
Interest income, net	9,994	4,073	1,746
Other income	110,000	0	0
Loss before income taxes	(78,723)	(254,445)	(123,653)
Income tax benefit (expense)	(99)	963	0
Net loss	$ (78,822)	$ (253,482)	$ (123,653)
Basic and diluted net loss per common share (in usd per share)	$ (2.11)	$ (7.63)	$ (4.29)
Weighted average basic and diluted common shares outstanding (in shares)	37,366,782	33,242,072	28,804,133
Other comprehensive income (loss):
Unrealized (loss) gain on available-for-sale securities	$ 586	$ (5,163)	$ (801)
Unrealized loss on interest rate swap	(641)	0	0
Foreign exchange translation adjustment	(83)	43	7
Total comprehensive loss	(78,960)	(258,602)	(124,447)
Product [Member]
Total revenues	26,973	0	0
Operating expenses:
Cost of goods sold	1,008	0	0
Contract Revenue [Member]
Total revenues	37,752	12,066	20,183
Operating expenses:
Cost of goods sold	$ 6,907	$ 0	$ 0

Consolidated statements of stoc

Consolidated statements of stockholders' equity - USD ($) $ in Thousands	Total	Common stock [Member]	Additional paid-in capital [Member]	Accumulated other comprehensive loss [Member]	Common stock in treasury [Member]	Accumulated deficit [Member]
Beginning balance (in shares) at Dec. 31, 2015		27,082,493			9,206
Beginning balance at Dec. 31, 2015	$ 290,538	$ 27	$ 419,792	$ 0	$ (553)	$ (128,728)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Issuance of common stock, net of issuance costs (in shares)		3,025,000
Issuance of common stock, net of issuance costs	127,566	$ 3	127,563
Issuance of restricted stock (in shares)		40,000
Issuance of restricted stock	0
Restricted stock canceled (in shares)		(2,213)
Restricted stock canceled	0
Purchase of common stock under ESPP (in shares)		8,012
Purchase of common stock under ESPP	340		340
Issuance of stock for acquisition (in shares)		265,000
Issuance of stock for acquisition	9,151		9,151
Exercise of stock options (in shares)		455,138
Exercise of stock options	2,592	$ 1	2,591
Unrealized (loss) gain on investments	(801)			(801)
Unrealized gain on foreign currency translation	7			7
Stock-based compensation expense	24,537		24,537
Net loss	(123,653)					(123,653)
Ending balance (in shares) at Dec. 31, 2016		30,873,430			9,206
Ending balance at Dec. 31, 2016	330,277	$ 31	583,974	(794)	$ (553)	(252,381)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Issuance of common stock, net of issuance costs (in shares)		5,296,053
Issuance of common stock, net of issuance costs	379,870	$ 5	379,865
Issuance of restricted stock (in shares)		1,193
Issuance of restricted stock	0
Restricted stock canceled (in shares)		(4,107)
Restricted stock canceled	0
Purchase of common stock in treasury (in shares)					(11,016)
Purchase of common stock in treasury	(673)				$ (673)
Purchase of common stock under ESPP (in shares)		11,804
Purchase of common stock under ESPP	$ 646		646
Exercise of stock options (in shares)	953,253	953,253
Exercise of stock options	$ 20,733	$ 1	20,732
Unrealized (loss) gain on investments	(5,163)			(5,163)
Unrealized gain on foreign currency translation	43			43
Stock-based compensation expense	41,373		41,373
Net loss	(253,482)					(253,482)
Ending balance (in shares) at Dec. 31, 2017		37,131,626			20,222
Ending balance at Dec. 31, 2017	513,624	$ 37	1,026,590	(5,914)	$ (1,226)	(505,863)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Issuance of restricted stock (in shares)		172,868
Issuance of restricted stock	0
Restricted stock canceled (in shares)		(25,000)
Restricted stock canceled	0
Purchase of common stock in treasury (in shares)					(57,690)
Purchase of common stock in treasury	(3,435)				$ (3,435)
Purchase of common stock under ESPP (in shares)		30,814
Purchase of common stock under ESPP	$ 1,567		1,567
Exercise of stock options (in shares)	453,905	453,905
Exercise of stock options	$ 15,131	$ 1	15,130
Unrealized (loss) gain on investments	586			586
Unrealized loss on interest rate swap	(641)			(641)
Unrealized gain on foreign currency translation	(83)			(83)
Stock-based compensation expense	48,586		48,586
Net loss	(78,822)					(78,822)
Ending balance (in shares) at Dec. 31, 2018		37,764,213			77,912
Ending balance at Dec. 31, 2018	$ 496,513	$ 38	$ 1,091,873	$ (1,050)	$ (4,661)	$ (589,687)

Consolidated statements of cash

Consolidated statements of cash flows - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Cash flows from operating activities:
Net loss	$ (78,822)	$ (253,482)	$ (123,653)
Adjustments to reconcile net loss to net cash used in operating activities:
Non-cash rent income	(2,490)	(531)	(530)
Depreciation and amortization expense	6,918	4,860	3,600
Loss on disposal of property and equipment	103	32	101
Acquired in-process research and development	300	8,604	11,132
Stock-based compensation expense	48,586	41,373	24,537
Impairment of acquired in-process research and development	0	15,696	0
Non-cash income tax benefit	0	(1,013)	0
Gain from sale of priority review voucher	(110,000)	0	0
Unrealized loss on equity investments	5,078	0	0
Non-cash interest income	(1,112)	(127)	0
Changes in operating assets and liabilities:
Inventory	(25,637)	0	0
Prepaid expenses and other assets	(35,333)	(3,157)	(264)
Trade and other receivables	(39,501)	8,857	(235)
Accounts payable and accrued expenses	8,703	12,981	10,018
Deferred rent	3,972	1,610	0
Deferred revenue	148,031	2,934	(5,182)
Other liabilities	641	6,827	0
Net cash used in operating activities	(70,563)	(154,536)	(80,442)
Cash flows from investing activities:
Proceeds from sale of priority review voucher	110,000	0	0
Payment for license agreement	(2,000)	0	0
Purchase of acquired in-process research and development	(300)	(8,217)	(11,132)
Payment for acquisition, net of cash acquired	0	0	(5,911)
Purchase of marketable securities	(530,989)	(441,486)	(279,945)
Proceeds from maturities of marketable securities	516,273	251,625	20,000
Purchase of property and equipment	(33,821)	(9,654)	(8,532)
Net cash (used in) provided by investing activities	59,163	(207,732)	(285,520)
Cash flows from financing activities:
Proceeds from exercise of options	15,131	20,733	2,592
Purchase of treasury stock	(3,435)	(673)	0
Proceeds from public offerings of common stock, net	0	379,870	126,909
Proceeds from issuance of common stock under ESPP	1,567	646	340
Proceeds from long-term debt	50,000	0	1,550
Payments on long-term debt	(312)	(302)	(25)
Net cash provided by financing activities	62,951	400,274	131,366
Effect of exchange rate changes on cash and cash equivalents and restricted cash	(52)	(181)	(12)
Net (decrease) increase in cash and cash equivalents and restricted cash	51,499	37,825	(234,608)
Cash and cash equivalents and restricted cash, beginning of year	96,748	58,923	293,531
Cash and cash equivalents and restricted cash, end of year	148,247	96,748	58,923
Supplemental disclosure of cash flow information:
Property and equipment purchases included in accounts payable and accrued expenses	9,518	2,789	682
One Drexel Plaza lease cost included in other liabilities	$ 503	$ 34,986	$ 0

Background

Background	12 Months Ended
	Dec. 31, 2018
Accounting Policies [Abstract]
Background	Background Spark Therapeutics, Inc. was formed on March 13, 2013 in the state of Delaware as AAVenue Therapeutics, LLC and amended its Certificate of Formation in October 2013 to change its name to Spark Therapeutics LLC. In May 2014, the Company converted from a limited liability company (LLC) to a C corporation, Spark Therapeutics, Inc. (the Company). The Company is a gene therapy company, seeking to transform the lives of patients suffering from debilitating genetic diseases by developing potentially one-time, life-altering treatments. The Company operates in one segment and has its principal offices in Philadelphia, Pennsylvania. In December 2017, the U.S. Food and Drug Administration, or FDA, approved LUXTURNA TM (voretigene neparvovec-rzyl) for the treatment of patients with viable retinal cells and confirmed biallelic RPE65

Development-stage risks

Development-stage risks	12 Months Ended
	Dec. 31, 2018
Development-stage Risk [Abstract]
Development-stage risks	Development-stage risks The Company has incurred net losses and negative cash flows from operations since inception and expects to incur net losses for the foreseeable future. The Company had an accumulated deficit of $589.7 million as of December 31, 2018 . The Company anticipates incurring additional losses until such time, if ever, that it can generate significant sales of LUXTURNA and its other product candidates in development. Additional financing may be needed by the Company to fund its operations and to commercially develop its other product candidates.

Summary of significant accounti

Summary of significant accounting policies	12 Months Ended
	Dec. 31, 2018
Accounting Policies [Abstract]
Summary of significant accounting policies	Summary of significant accounting policies (a) Use of estimates The preparation of consolidated financial statements in conformity with U.S. generally accepted accounting principles (GAAP) requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and disclosure of contingent assets and liabilities at the date of the consolidated financial statements and the reported amounts of revenues and expenses during the reporting period. Actual results could differ from such estimates. (b) Principles of consolidation The accompanying consolidated financial statements include the accounts of the Company and its wholly-owned subsidiaries: Spark Therapeutics Ireland Limited, Spark Therapeutics UK Limited, Spark Therapeutics Argentina Limited, Spark Therapeutics Switzerland Limited, Spark Therapeutics Germany Limited and Spark Therapeutics France Limited. All intercompany balances and transactions have been eliminated in consolidation. (c) Fair value of financial instruments Management believes that the carrying amounts of the Company’s financial instruments, including cash equivalents, trade and other receivables, accounts payable and accrued expenses, approximate fair value due to the short-term nature of those instruments. Management believes the carrying value of debt approximates fair value as the interest rates are reflective of the rate the Company could obtain on debt with similar terms and conditions. (d) Cash and cash equivalents The Company considers all highly liquid investments that have maturities of three months or less when acquired to be cash equivalents. Cash equivalents as of December 31, 2017 and 2018 consisted of money market funds. (e) Marketable securities The Company classifies its marketable security investments as available-for-sale securities and the securities are stated at fair value. At December 31, 2018 , the balance in the Company’s accumulated other comprehensive loss included activity related to the Company’s available-for-sale marketable securities. There were no material realized gains or losses recognized on the maturity of available-for-sale securities during the year ended December 31, 2018 and, as a result, the Company did not reclassify any amount out of accumulated other comprehensive loss for the same period. In addition, as part of the license and stock purchase agreements entered into with Selecta Biosciences, Inc. (Selecta) (Note 16), the Company purchased common shares of Selecta. The investment is classified as available-for-sale and is stated at fair value, and beginning in 2018 changes in fair value are recognized in the consolidated statements of operations and comprehensive income (loss). (f) Trade and other receivables Trade accounts receivable are recorded at gross value, and reserves for other sales-related allowances, such as discounts, rebates, services and insurance co-pay assistance, are included in accrued expenses on the Company's consolidated balance sheets. (g) Inventory Inventory is stated at the lower of cost or net realizable value and consists of those costs incurred following FDA approval of LUXTURNA. Cost is determined using the first-expired, first-out (FEFO) method. The Company reserves for potentially excess, dated or obsolete inventories based on an analysis of inventory on hand compared to forecasts of future sales. Based on management's assessment, no such inventory reserve is necessary as of December 31, 2018 . (h) Property and equipment Property and equipment consists of computer and laboratory equipment, software, office equipment, furniture and leasehold improvements and is recorded at cost. Maintenance and repairs that do not improve or extend the lives of the respective assets are expensed to operations as incurred. Upon disposal, retirement or sale, the related cost and accumulated depreciation are removed from the accounts and any resulting gain or loss is included in the results of operations. Property and equipment are depreciated on a straight-line basis over their estimated useful lives. The Company uses a life of three years for computer equipment and software, five years for laboratory and office equipment and seven years for furniture. Leasehold improvements are amortized over the shorter of the lease term or the estimated useful life of the asset . The Company reviews long-lived assets, such as property and equipment, for impairment when events or changes in circumstances indicate the carrying value of the assets may not be recoverable. Recoverability is measured by comparison of the book values of the assets to estimated undiscounted future cash flows that the assets are expected to generate. If the carrying amount of an asset exceeds its estimated future cash flows, then an impairment charge is recognized for the amount by which the carrying value of the asset exceeds the fair value of the asset. No impairment charges have been recorded since inception. (i) Net product sales LUXTURNA is distributed in the United States through two distribution models: (1) the traditional buy-and-bill model where the treatment center purchases and pays for the product and then submits a claim to the payer; and (2) the Company's innovative contracting and distribution model, branded Spark PATH (Pioneering Access to Healthcare), which includes options for direct-to-payer contracting and outcomes-based rebates. The Company’s net product sales represent total gross product sales in the United States less allowances for estimated prompt-payment discounts, service fees, rebates and insurance co-payment assistance. Allowances are established based on contractual terms and management’s reasonable estimates, as well as the expectation that 100% of the prompt-payment discounts will be earned. Product shipping and handling costs and distributor reporting fees are included in cost of product sales. The Company evaluated the variable consideration under Accounting Standards Codification (ASC) Topic 606, Revenue from Contracts with Customers (ASC 606), as it relates to the outcomes-based method and determined that based on historical clinical data, no rebate reserves were required for the year ended December 31, 2018 . All sales are recognized when control is transferred, which follows the Company’s verification of a scheduled LUXTURNA treatment. The Company’s product return policy is to provide non-monetary credit or product replacement. As the product is sold in direct relation to a scheduled treatment, Company management estimates that there is minimal risk of product return, including the risk of product expiration. (j) Contract revenue Under certain of the Company’s licensing, supply and collaboration agreements, it is entitled to receive payment upon the achievement of contingent milestone events or the performance of obligations. The Company recognizes revenue based on guidance in ASC 606. Prior to 2018, the Company generated revenue solely through license and collaborative arrangements. In the first quarter of 2018, the Company adopted ASC 606. The adoption of this standard resulted in no cumulative adjustment to the Company’s consolidated financial statements. ASC 606 applies to all contracts with customers, except for contracts that are within the scope of other standards, such as leases, insurance, collaboration arrangements and financial instruments. To determine revenue recognition for arrangements that an entity determines are within the scope of ASC 606, the entity performs the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) the entity satisfies a performance obligation. At contract inception, once the contract is determined to be within the scope of ASC 606, the Company assesses the goods or services promised within each contract and determines those that are performance obligations and assesses whether each promised good or service is distinct. The Company then recognizes as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) the performance obligation is satisfied. Amounts received prior to satisfying the revenue recognition criteria are recorded as deferred revenue on the Company’s consolidated balance sheet. Amounts expected to be recognized as revenue in the next 12 months following the balance sheet date are classified as current liabilities. (k) Research and development and in-process research and development Research and development costs are expensed as incurred. Research and development expenses consist of internal and external expenses. Internal expenses include employee compensation and overhead. External expenses include development, clinical trials, statistical analysis and report writing and regulatory compliance costs incurred with clinical research organizations and other third-party vendors. At the end of the reporting period, the Company compares payments made to third-party service providers to the estimated progress toward completion of the research or development objectives. Such estimates are subject to change as additional information becomes available. Depending on the timing of payments to the service providers and the progress that the Company estimates has been made as a result of the service provided, the Company may record net prepaid or accrued expense relating to these costs. When the Company is reimbursed by a collaboration partner for work performed, the costs incurred are recorded as research and development expenses and the related reimbursement is recorded as a reduction to research and development expenses. Upfront and milestone payments made to third parties that perform research and development services on the Company’s behalf are expensed as services are rendered. Costs incurred in obtaining technology licenses outside of business combinations are charged to research and development expense as acquired in-process research and development if the technology licensed has not reached technological feasibility and has no alternative future use. (l) Income taxes The Company recognizes deferred tax assets and liabilities for temporary differences between the financial reporting basis and the tax basis of its assets and liabilities and the expected benefits of net operating loss and tax credit carryforwards. The impact of changes in tax rates and laws on deferred taxes, if any, is applied during the years in which temporary differences are expected to be settled and net operating losses and tax credits used and is reflected in the consolidated financial statements in the period of enactment. The measurement of deferred tax assets is reduced, if necessary, if, based on weight of the evidence, it is more likely than not that some, or all, of the deferred tax assets will not be realized. As of December 31, 2017 and 2018 , the Company has concluded that a full valuation allowance is necessary for its deferred tax assets. (m) Stock-based compensation and fair value of stock The Company accounts for its stock-based compensation awards in accordance with ASC Topic 718, Compensation-Stock Compensation (ASC 718). ASC 718 requires all stock-based payments to employees, including grants of employee stock options and restricted stock units and modifications to existing stock options, to be recognized in the consolidated statement of operations and comprehensive income(loss) based on their fair values. The Company uses the Black-Scholes option pricing model to determine the fair value of options granted. The Company’s stock-based awards are subject to either service or performance-based vesting conditions. Compensation expense related to awards to employees and directors with service-based vesting conditions is recognized on a straight-line basis based on the grant date fair value over the associated service period of the award, which is generally the vesting term. Compensation expense related to awards to non-employees with service-based vesting conditions is recognized based on the then-current fair value at each financial reporting date prior to the measurement date over the associated service period of the award, which is generally the vesting term. Compensation expense related to awards to employees with performance-based vesting conditions is recognized based on the grant date fair value over the requisite service period to the extent achievement of the performance condition is probable. The Company estimates the fair value of its option awards to employees and directors using the Black-Scholes option pricing model, which requires the input of subjective assumptions, including (i) the expected stock price volatility, (ii) the calculation of the expected term of the award, (iii) the risk-free interest rate and (iv) expected dividends. Due to the lack of substantial Company-specific historical and implied volatility data of its common stock, the Company has based its estimate of expected volatility on the historical volatility of a group of similar companies that are publicly traded. When selecting these public companies on which it has based its expected stock price volatility, the Company selected companies with comparable characteristics to it, including enterprise value, risk profiles, position within the industry and with historical share price information sufficient to meet the expected term of the stock-based awards. The Company computes historical volatility data using the daily closing prices for the selected companies’ shares during the equivalent period of the calculated expected term of the stock-based awards. The Company will continue to apply this process until a sufficient amount of historical information regarding the volatility of its own stock price becomes available. The Company has estimated the expected term of its employee stock options using the “simplified” method, whereby, the expected term equals the arithmetic average of the vesting term and the original contractual term of the option due to its lack of sufficient historical data. The risk-free interest rates for periods within the expected term of the option are based on the U.S. Treasury securities with a maturity date commensurate with the expected term of the associated award. The Company has never paid, and does not expect to pay, dividends in the foreseeable future. The Company accounts for forfeitures when they occur. Consistent with the guidance in ASC Topic 505-50, Equity-Based Payments to Non-Employees , the fair value of each non-employee stock option and restricted stock award is estimated at the date of grant using the Black-Scholes option pricing model with assumptions generally consistent with those used for employee stock options, with the exception of expected term, which is over the contractual life. (n) Net loss per common share Basic and diluted net loss per common share is determined by dividing net loss by the weighted average number of common shares outstanding during the period. For all periods presented, unvested restricted shares and common stock options have been excluded from the calculation because their effect would be anti-dilutive. Therefore, the weighted average shares outstanding used to calculate both basic and diluted loss per share are the same. The following potentially dilutive securities have been excluded from the computations of diluted weighted average shares outstanding for the years ended December 31, 2016 , 2017 and 2018 as they would be anti-dilutive: December 31, 2016 2017 2018 Unvested restricted common shares 251,809 798,501 942,776 Options issued and outstanding 4,181,993 3,522,874 3,487,376 Amounts in the table above reflect the common stock equivalents of the noted instruments. (o) Deferred rent Rent expense, including rent holidays and scheduled rent increases, is recorded on a straight-line basis over the term of the lease commencing on the date the Company takes possession of the leased property. Tenant improvement allowances from the lessor are included in the accompanying consolidated balance sheet as deferred rent and are amortized as a reduction of rent expense over the term of the lease from the possession date. Deferred rent as of December 31, 2017 and 2018 represents the net excess of rent expense over the actual cash paid for rent and the tenant improvement allowances received. (p) Other comprehensive loss The Company follows the provisions of ASC Topic 220, Comprehensive Income , which establishes standards for the reporting and display of comprehensive income and its components. Comprehensive income (loss) is defined to include all changes in equity during a period except those resulting from investments by owners and distributions to owners. Comprehensive income (loss) includes gains and losses related to changes in the fair value of available-for-sale securities, changes in the fair value of an interest rate swap and foreign currency translation. The accumulated balances related to each component of other comprehensive income (loss) are summarized as follows (in thousands): Net unrealized (loss) gain on available-for-sale securities Unrealized loss on interest rate swap Foreign currency translation adjustments Accumulated other comprehensive loss Balance as of December 31, 2017 $ (5,964 ) $ — $ 50 $ (5,914 ) Reclassification of unrealized loss on equity investment to accumulated deficit 5,002 — — 5,002 Current period other comprehensive income (loss) 586 (641 ) (83 ) (138 ) Balance as of December 31, 2018 $ (376 ) $ (641 ) $ (33 ) $ (1,050 ) (q) Recent accounting pronouncements In February 2016, the Financial Accounting Standards Board (FASB) issued Accounting Standards Update (ASU) 2016-02, Leases . ASU 2016-02 requires lessees to apply a two-method approach, classifying leases as either finance or operating leases based on the principle of whether or not the lease is effectively a financed purchase. This classification will determine whether lease expense is recognized based on an effective interest method or on a straight line basis over the term of the lease, respectively. Lessees are also required to record a right-of-use (ROU) asset and a lease liability for all leases with a term greater than 12 months. Leases with a term of 12 months or less will be accounted for similar to existing guidance for operating leases. ASU 2016-02 is effective for interim and annual periods beginning after December 15, 2018. The Company has elected to adopt this standard using the effective date method using a modified retrospective transition approach. The Company expects the adoption of the standard to have a material impact on its consolidated balance sheet, which will result in the removal of the built to suit asset and liability recorded as of December 31, 2018, and the recognition of ROU assets and lease liabilities of approximately $40.0 million to $50.0 million at January 1, 2019. In May 2014, the FASB issued a new standard, ASC 606, regarding the accounting for, and disclosures of, revenue recognition, with an effective date for annual and interim periods beginning after December 15, 2017. ASC 606 provides a single comprehensive model for accounting for revenue from contracts with customers. The model requires that revenue recognized reflect the actual consideration to which the entity expects to be entitled in exchange for the goods or services defined in the contract, including in situations with multiple performance obligations. The Company adopted ASC 606 using the modified retrospective method and the adoption had no cumulative adjustment to its consolidated financial statements as it relates to the Pfizer Inc. (Pfizer) collaboration agreement discussed in Note 16. For the year ended December 31, 2018, there was no impact from the adoption of ASC 606 that resulted in a different revenue recognition amount than under the prior revenue recognition guidance in effect during 2017. In January 2016, the FASB issued ASU 2016-01, Financial Instruments-Overall: Recognition and Measurement of Financial Assets and Financial Liabilities . ASU 2016-01 changes accounting for equity investments, financial liabilities under the fair value option, and presentation and disclosure requirements for financial instruments. ASU 2016-01 does not apply to equity investments in consolidated subsidiaries or those accounted for under the equity method of accounting. In addition, the FASB clarified guidance related to the valuation allowance assessment when recognizing deferred tax assets resulting from unrealized losses on available-for-sale debt securities. Equity investments with readily determinable fair values will be measured at fair value with changes in fair value recognized in net income. Companies have the option to either measure equity investments without readily determinable fair values at fair value or at cost, adjusted for changes in observable prices, minus impairment. Changes in measurement under either alternative will be recognized in net income. Companies that elect the fair value option for financial liabilities must recognize changes in fair value related to instrument-specific credit risk in other comprehensive income. Companies must assess valuation allowances for deferred tax assets related to available-for-sale debt securities in combination with their other deferred tax assets. The Company adopted this guidance effective January 1, 2018, resulting in a reclassification of $5.0 million from accumulated other comprehensive loss to accumulated deficit related to the unrecognized loss on the Company's investment in Selecta. In August 2017, the FASB issued ASU 2017-12, Derivatives and Hedging: Targeted Improvements to Accounting for Hedging Activities

Marketable securities

Marketable securities	12 Months Ended
	Dec. 31, 2018
Investments, Debt and Equity Securities [Abstract]
Marketable securities	Marketable securities The following table summarizes the available-for-sale securities held as of December 31, 2017 and 2018 (in thousands): Description Amortized cost Unrealized gains Unrealized losses Fair value December 31, 2017 U.S. government agency $ 222,180 $ — $ (641 ) $ 221,539 Corporate securities $ 227,238 $ — $ (5,323 ) $ 221,915 December 31, 2018 U.S. government agency $ 223,553 $ 54 $ (123 ) $ 223,484 Corporate securities $ 239,940 $ 34 $ (10,421 ) $ 229,553 No available-for-sale securities held as of December 31, 2018 , had remaining maturities greater than two years

Fair value of financial instrum

Fair value of financial instruments	12 Months Ended
	Dec. 31, 2018
Fair Value Disclosures [Abstract]
Fair value of financial instruments	Fair value of financial instruments The Company follows FASB accounting guidance on fair value measurements for financial assets and liabilities measured on a recurring basis. The guidance requires fair value measurements to maximize the use of “observable inputs.” The three-level hierarchy of inputs to measure fair value are as follows: • Level 1: Unadjusted quoted prices in active markets that are accessible at the measurement date for identical, unrestricted assets or liabilities • Level 2: Significant other observable inputs other than Level 1 prices such as quoted prices in markets that are not active, or inputs that are observable, either directly or indirectly, for substantially the full term of the asset or liability • Level 3: Prices or valuation techniques that require inputs that are both significant to the fair value measurement and unobservable (i.e., supported by little or no market activity) The Company has classified assets and liabilities measured at fair value on a recurring basis as follows (in thousands): Fair value measurements at reporting date using Quoted prices in active markets for identical assets (Level 1) Significant other observable inputs (Level 2) Significant unobservable inputs (Level 3) As of December 31, 2017: Assets: Money market funds (included in cash and cash equivalents) $ 90,348 — — Corporate securities (included in cash and cash equivalents) $ 5,548 — — Marketable securities - U.S. government agencies $ 221,539 — — Marketable securities - corporate securities $ 220,020 $ 1,895 — As of December 31, 2018: Assets: Money market funds (included in cash and cash equivalents) $ 94,216 — — Certificates of deposit - restricted cash $ 53,000 — — Marketable securities - U.S. government agencies $ 223,484 — — Marketable securities - corporate securities $ 229,553 — —

Inventory

Inventory	12 Months Ended
	Dec. 31, 2018
Inventory Disclosure [Abstract]
Inventory	Inventory Inventory consists of the following (in thousands): December 31, Raw materials $ 3,843 Work in process 19,843 Finished goods 1,951 $ 25,637

Business acquisition of Genable

Business acquisition of Genable and impairment of acquired in-process research and development	12 Months Ended
	Dec. 31, 2018
Goodwill and Intangible Assets Disclosure [Abstract]
Business acquisition of Genable and impairment of acquired in-process research and development	Business acquisition of Genable and impairment of acquired in-process research and development On March 7, 2016, the Company acquired Genable Technologies, Ltd. (Genable), an Ireland-based private gene therapy company with which the Company had collaborated since 2014 in the development of Genable's therapeutic program targeting a genetic inherited retinal disease (IRD). With the acquisition, the Company acquired RhoNova™, a potential gene therapy targeting rhodopsin-linked autosomal dominant retinitis pigmentosa (RHO-adRP), an IRD that routinely leads to visual impairment and in the most severe cases to blindness. The consideration paid by the Company to Genable shareholders consisted of $6.1 million in cash and 265,000 shares of the Company's common stock with a fair value of $9.2 million , for total consideration of $15.3 million . In connection with the acquistion, a receivable due from Genable also was settled on the date of acquisition for $0.5 million . The Company incurred acquisition-related costs of approximately $0.3 million , which are included in selling, general and administrative expenses in the consolidated statement of operations for the year ended December 31, 2016. The Company accounted for the acquisition as a business combination under the acquisition method of accounting. The Company allocated the purchase price for the purchase of Genable based upon the estimated fair value of net assets acquired and liabilities assumed at the date of acquisition. Recognition and measurement of assets acquired and liabilities assumed The following table summarizes the fair values of the tangible and intangible assets acquired and liabilities assumed at the acquisition date (in thousands): Cash acquired $ 196 Other current assets 103 Acquired in-process research and development 15,490 Goodwill 1,160 Total assets assumed 16,949 Other non-current liabilities 255 Deferred tax liability 1,000 Total liabilities assumed 1,255 Total allocation of purchase price $ 15,694 Acquired in-process research and development and related impairment The Company’s allocation of purchase price to acquired in-process research and development (IPR&D) was $15.5 million . The estimated fair value of the IPR&D was determined using the “income approach,” which is a valuation technique that provides an estimate of the fair value of an asset based on market participant expectations of the cash flows an asset would generate over its remaining useful life. Some of the more significant assumptions inherent in the development of those asset valuations include the estimated net cash flows for each year for the asset or product (including net revenues, cost of sales, research and development costs, selling and marketing costs and working capital/asset contributory asset charges), the appropriate discount rate to select in order to measure the risk inherent in each future cash flow stream, the assessment of the asset’s life cycle, the potential regulatory and commercial success risks, competitive trends impacting the asset cash flow stream as well as other factors. During the year ended December 31, 2017, the Company determined that it would no longer pursue product candidates utilizing the technology acquired from Genable in March 2016 and, accordingly, recorded an impairment charge of $15.7 million within its consolidated statement of operations. Additionally, the Company recognized an income tax benefit of $1.0 million related to the reversal of the deferred tax liability associated with the IPR&D during the year ended December 31, 2017. Goodwill impairment Goodwill represents the excess of purchase price over the fair value of net assets acquired by the Company. Goodwill is not amortized, but assessed for impairment on an annual basis or more frequently if impairment indicators exist. The Company operates as one reporting unit. The Company has the option to perform a qualitative assessment of goodwill prior to completing the two-step method described below to determine whether or not it is more likely than not that the fair value of its reporting units is less than its carrying amount, including goodwill and other intangible assets. If the Company concludes that this is the case, it must perform the two-step process. The first step compares a reporting unit’s fair value to its carrying amount to identify potential goodwill impairment. If the carrying amount of a reporting unit exceeds the reporting unit’s fair value, the second step of the impairment test must be completed to measure the amount of the reporting unit’s goodwill impairment loss, if any. Step two requires an assignment of the reporting unit’s fair value to the reporting unit’s assets and liabilities to determine the implied fair value of the reporting unit’s goodwill. The implied fair value of the reporting unit’s goodwill is then compared with the carrying amount of the reporting unit’s goodwill to determine the goodwill impairment loss to be recognized, if any. The Company performs its annual goodwill impairment test as of October 1st. The Company performed a qualitative assessment and determined that there was no impairment to goodwill for the years ended December 31, 2016, 2017 and 2018

Sale of priority review voucher

Sale of priority review voucher Sale of priority review voucher	12 Months Ended
	Dec. 31, 2018
Goodwill and Intangible Assets Disclosure [Abstract]
Sale of priority review voucher	Sale of priority review voucher In May 2018, the Company sold the rare pediatric disease priority review voucher (PRV) it received from FDA in connection with the United States approval of LUXTURNA to Jazz Pharmaceuticals Ireland Limited for consideration of $110.0 million

Property and equipment, net

Property and equipment, net	12 Months Ended
	Dec. 31, 2018
Property, Plant and Equipment [Abstract]
Property and equipment, net	Property and equipment, net Property and equipment consist of the following (in thousands): December 31, 2017 2018 Laboratory equipment $ 6,381 $ 8,272 Computer and software 1,325 2,773 Furniture and fixtures 1,770 2,564 Office equipment 726 1,394 Leasehold improvements 23,653 54,541 One Drexel Plaza (built-to-suit) 34,993 34,789 Construction in progress 3,187 7,869 Property and equipment, gross 72,035 112,202 Less accumulated depreciation and amortization (10,322 ) (16,204 ) Property and equipment, net $ 61,713 $ 95,998 Depreciation and amortization expense was $3.6 million , $4.9 million and $6.9 million for the years ended December 31, 2016 , 2017 and 2018

Accrued expenses

Accrued expenses	12 Months Ended
	Dec. 31, 2018
Payables and Accruals [Abstract]
Accrued expenses	Accrued expenses Accrued expenses consist of the following (in thousands): December 31, 2017 2018 Compensation and benefits $ 15,012 $ 15,575 Consulting and professional fees 4,846 13,904 Research and development 2,809 2,706 Other 2,030 2,605 $ 24,697 $ 34,790

Debt

Debt	12 Months Ended
	Dec. 31, 2018
Debt Disclosure [Abstract]
Debt	Debt The Company's debt consists of the following (in thousands): December 31, 2017 2018 Term loan outstanding $ — $ 50,000 MELF loan outstanding 1,224 912 Less: current portion of long-term debt (312 ) (4,822 ) Total long-term debt due after one year $ 912 $ 46,090 In July 2018, the Company entered into a credit agreement with Wells Fargo Bank, National Association (Wells Fargo) as lender (the Credit Agreement), pursuant to which Wells Fargo extended a $50.0 million term loan to the Company, which bears interest at one-month LIBOR plus 0.65% , which rate is converted to a fixed rate per annum of 3.463% under the swap agreement discussed below. The term loan was fully drawn on the date of the Credit Agreement and matures on July 3, 2023 (Maturity Date). Through June 2019, the Company will only be obligated to make monthly interest payments with respect to the term loan. Thereafter, the term loan will amortize in equal monthly installments through the maturity date. For the year ended December 31, 2018 , the Company recorded interest expense of $0.7 million related to the Credit Agreement. In order to manage the interest risk associated with the term loan, the Company entered into an interest rate swap with Wells Fargo on an initial notional amount of $50.0 million . Under this interest rate swap agreement, which expires on July 3, 2023, the Company receives a floating rate based on 1-month LIBOR plus 0.65% and pays a fixed rate of 3.463% . The Company designated this interest rate swap as a cash flow hedge of the forecasted interest payments related to the debt issuance. To maintain this rate, the Company entered into a cash collateral agreement with Wells Fargo that requires the Company to maintain a restricted cash balance equal to at least the principal balance of the term loan. At December 31, 2018 , the fair value of the derivative liability was $0.6 million , of which $0.1 million was recognized within other current liabilities and $0.5 million was recognized within other long-term liabilities. The effective portion of the swap is reported as a component of accumulated other comprehensive loss. There was no hedge ineffectiveness as of December 31, 2018 . Changes in the fair value are reclassified from accumulated other comprehensive loss into operations in the same period that the hedged item affects earnings. During the year ended December 31, 2018 , the Company reclassified $0.2 million from accumulated other comprehensive loss into interest expense related to the effective portion of the swap. Over the next 12 months, $0.6 million of the effective portion of the interest rate swap is expected to be reclassified from accumulated other comprehensive loss into interest expense. If, at any time, the interest rate swap is determined to be ineffective, in whole or in part, due to changes in the interest rate swap or underlying debt agreements, the fair value of the portion of the interest rate swap determined to be ineffective will be recognized as a gain or loss in the statement of operations and comprehensive income (loss) for the applicable period. In August 2016, the Company executed an agreement with the Commonwealth of Pennsylvania to fund machinery and equipment and other assets purchased (MELF Loan) in the amount of $1.6 million . Borrowings under the MELF Loan are secured by equipment, as defined in the loan agreement. Under the terms of the MELF Loan, the Company has a five -year period of monthly payments of $29 thousand of principal and interest at an annual interest rate of 3.25% . For the years ended December 31, 2016, 2017 and 2018 , the Company recorded interest expense of $15 thousand , $48 thousand and $34 thousand

Stockholders' equity

Stockholders' equity	12 Months Ended
	Dec. 31, 2018
Equity [Abstract]
Stockholders' equity	Stockholders’ equity The Company’s certificate of incorporation and bylaws contain the rights, preferences and privileges of the Company’s stockholders and their respective shares. The Company has authorized 150,000,000 shares of common stock and 5,000,000 shares of preferred stock. In 2013 and 2014, the Company issued restricted stock to various employees, directors and consultants of the Company. The vesting terms of the restricted stock issued varied, but primarily, shares vested 25% on the first anniversary of the vesting commencement date and then quarterly over three years , with accelerated vesting in the event of a change in control, as defined. Any unvested shares are forfeited in the event that the individual ceases to provide services to the Company. Additionally, in 2014, 200,000 restricted shares of common stock were issued to The Trustees of the University of Pennsylvania (Penn) in connection with a license agreement, of which 175,000 shares have vested. The remaining shares were canceled during the year ended December 31, 2018. For the year ended December 31, 2016 , the Company recorded compensation expense of $0.1 million and $1.3 million in selling, general and administrative expense and research and development expense, respectively, related to the restricted shares. For the year ended December 31, 2017 , the Company recorded compensation expense of $34 thousand and $4.4 million in selling, general and administrative expense and research and development expense, respectively, related to the restricted shares. For the year ended December 31, 2018 , the Company recorded an immaterial amount of compensation expense in selling, general and administrative expense and $2.2 million of expense in research and development expense related to the restricted shares. The following table summarizes restricted stock activity for the instruments discussed above: Number of shares Weighted- average grant date fair value Nonvested shares at December 31, 2016 174,876 $ 5.78 Shares canceled (3,107 ) $ 1.15 Shares vested (70,935 ) $ 3.60 Nonvested shares at December 31, 2017 100,834 $ 7.45 Shares canceled (25,000 ) $ 7.50 Shares vested (75,834 ) $ 7.44 Nonvested shares at December 31, 2018 — On June 20, 2016, the Company completed a follow-on public offering, having sold 3,025,000 shares of common stock at an offering price of $45.00 per share, for aggregate gross proceeds of $136.1 million . The Company received net proceeds from the public offering of $127.6 million , after deducting underwriting discounts and commissions and other offering costs. On August 9, 2017, the Company completed a follow-on public offering, having sold 5,296,053 shares of common stock at an offering price of $76.00 per share, for aggregate gross proceeds of $402.5 million . The Company received net proceeds from the public offering of $379.9 million

Stock incentive plans

Stock incentive plans	12 Months Ended
	Dec. 31, 2018
Disclosure of Compensation Related Costs, Share-based Payments [Abstract]
Stock incentive plans	Stock incentive plans The Company's 2015 Stock Incentive Plan (the 2015 Plan) provides for the grant of incentive stock options, nonstatutory stock options, stock appreciation rights, restricted stock awards, restricted stock units and other stock-based awards to employees, officers, directors, consultants and advisors. In January 2018, the number of shares of common stock authorized for issuance under the 2015 Plan automatically increased, pursuant to the terms of the 2015 Plan, by 1,485,322 shares. As of December 31, 2018, 1,422,190 shares were available for future grants under the 2015 Plan. In January 2018, the number of shares of common stock authorized for issuance under the 2015 Employee Stock Purchase Plan (ESPP) automatically increased, pursuant to the terms of the 2015 ESPP, by 371,330 shares. The 2015 ESPP provides participating employees with the opportunity to purchase an aggregate of 1,120,188 shares of common stock as of December 31, 2018 . Stock-based compensation expense Stock-based compensation expense by award type was as follows (in thousands): Year ended December 31, 2016 2017 2018 Stock options $ 22,377 $ 28,001 $ 29,674 Restricted stock 632 8,452 16,141 Employee stock purchase plan 178 438 610 $ 23,187 $ 36,891 $ 46,425 Of the $46.4 million of stock-based compensation expense incurred during the year ended December 31, 2018, $18.0 million is classified as research and development expense and $28.4 million is classified as selling, general and administrative expense in the consolidated statement of operations and comprehensive income (loss). Of the $36.9 million of stock-based compensation expense incurred during the year ended December 31, 2017, $15.1 million is classified as research and development expense and $21.8 million is classified as selling, general and administrative expense in the consolidated statement of operations and comprehensive income (loss). Of the $23.2 million of stock-based compensation expense incurred during the year ended December 31, 2016, $9.6 million is classified as research and development expense and $13.6 million is classified as selling, general and administrative expense in the consolidated statement of operations and comprehensive income (loss). Stock options The following table summarizes stock option activity: Number of shares Weighted- average exercise price Aggregate intrinsic value(a) Outstanding at December 31, 2016 4,181,993 $ 33.25 Granted 701,300 $ 56.78 Exercised (953,253 ) $ 21.75 Forfeited (407,166 ) $ 41.30 Outstanding at December 31, 2017 3,522,874 $ 40.11 Granted 671,500 $ 52.02 Exercised (453,905 ) $ 33.34 Forfeited (253,093 ) $ 52.32 Outstanding at December 31, 2018 3,487,376 $ 42.40 Vested at December 31, 2018 1,934,833 $ 35.17 $ 25,798,486 Vested at December 31, 2018 and expected to vest 3,315,852 $ 41.92 $ 26,194,775 (a) The aggregate intrinsic value is calculated as the difference between the exercise price of the underlying options and the fair value of the common stock that were in the money at December 31, 2018 . The weighted average remaining contractual term of options outstanding as of December 31, 2018 is 7.2 years. The weighted-average remaining contractual term of options exercisable as of December 31, 2018 is 6.4 years. At December 31, 2018 , there was $42.2 million of unrecognized compensation expense related to stock options, which is expected to be recognized over a weighted-average period of 2.2 years. The intrinsic value of options exercised during the years ended December 31, 2017 and 2018 was $45.9 million and $16.6 million , respectively. The weighted-average grant date fair value of the options granted in 2016 , 2017 and 2018 was $28.56 , $39.27 and $35.14 per share, respectively, using the Black-Scholes option-pricing model with the following weighted-average assumptions: Years Ended December 31, 2016 2017 2018 Expected volatility 75.2 % 78.1 % 75.7 % Risk-free interest rate 1.71 % 2.06 % 2.50 % Expected term (in years) 5.95 6.10 6.21 Expected dividend yield 0.0 % 0.0 % 0.0 % Restricted stock The following table summarizes restricted common stock activity: Number Weighted- Nonvested shares at December 31, 2016 76,933 $ 49.90 Shares granted 713,400 $ 63.34 Shares canceled (55,457 ) $ 48.93 Shares vested (37,209 ) $ 55.77 Nonvested shares at December 31, 2017 697,667 $ 63.40 Shares granted 553,300 $ 54.29 Shares canceled (123,656 ) $ 60.75 Shares vested (184,535 ) $ 61.87 Nonvested shares at December 31, 2018 942,776 $ 58.71 At December 31, 2018 , there was $43.1 million of unrecognized compensation expense related to the restricted common stock, which is expected to be recognized over a weighted average period of 2.8 years. ESPP stock activity: For the year ended December 31, 2017 , 11,804 shares were issued under the 2015 ESPP. For the year ended December 31, 2018 , 30,814 shares were issued under the 2015 ESPP. At December 31, 2018 , there was $0.3 million

Commitments and contingencies

Commitments and contingencies	12 Months Ended
	Dec. 31, 2018
Commitments and Contingencies Disclosure [Abstract]
Commitments and contingencies	Commitments and contingencies (a) Leases In March 2014, the Company entered into an operating lease for laboratory and office space at its corporate headquarters in Philadelphia, Pennsylvania, through October 2025. Under this lease, the Company received $8.0 million of tenant improvement allowances during 2014. In November 2015, the Company entered into a sublease agreement for approximately 14,000 square feet of additional office space at its corporate headquarters. The sublease terminated on November 30, 2018. In February 2016, the Company leased 6,500 square feet of additional office space in Philadelphia under a lease that expires in June 2021. In November 2016, the Company entered into a lease agreement for approximately 49,000 square feet of office space in Philadelphia that will terminate on March 31, 2027. Under this lease, the Company received $1.6 million of tenant improvement allowances during 2017. In January 2017, the Company amended its lease for office space in Philadelphia to lease an additional 24,800 square feet that commenced on January 1, 2018, and will terminate on December 31, 2028. In November 2017, the Company amended this lease to accelerate the termination date of approximately 50,000 square feet of office space, with such termination to occur, at the latest, in December 2022. The Company recorded an expense of $6.9 million associated with the change in termination date in 2017. As of December 31, 2018 , $3.5 million is recorded as long-term other liabilities and $1.8 million is recorded as current other liabilities on the accompanying consolidated balance sheet related to the termination expense. The following table reconciles the termination cost discussed above (in thousands): Balance as of December 31, 2017 Recognized during the year Balance as of December 31, 2018 Contract termination liability $6,827 $1,557 $5,270 In November 2017, the Company entered into a lease for the new research facility at One Drexel Plaza in Philadelphia, Pennsylvania for approximately 108,000 square feet through June 2033. Under this lease, the Company received $3.9 million of tenant improvement allowances during 2018. Based on the terms of the lease agreement for One Drexel Plaza, the Company had construction period risks during the construction period and the Company was deemed the owner of the building (for accounting purposes only) during the construction period. Accordingly, the Company recorded an asset of $35.0 million as of December 31, 2017, representing the Company’s leased portion of the building, and recorded a corresponding liability. Upon completion of leasehold improvement construction, the Company may not meet the sale-leaseback criteria for de-recognition of the building asset and liability. Therefore, the lease may be accounted for as a financing obligation. The asset will be depreciated over the expected duration of the lease of 15.5 years, and rental payments will be treated as principal and interest payments on the lease financing obligation liability. The underlying accounting for this transaction has no impact on cash flows associated with the underlying lease or construction in process. At December 31, 2017 and 2018 , the lease financing obligation balance was $35.0 million and $34.5 million , respectively, and was recorded as a long-term liability within other liabilities on the consolidated balance sheets. The remaining future minimum payments under the lease financing obligation as of December 31, 2018 are included in the table below. In May 2018, the Company entered into a lease agreement for approximately 14,000 square feet of office space in Philadelphia that will terminate in April 2020. Under this lease, the Company received $0.1 million of tenant improvement allowances during 2018. Rent expense under these leases was $1.9 million , $10.5 million and $3.9 million for the years ended December 31, 2016 , 2017 and 2018 , respectively. Future minimum lease payments under these leases are as follows (in thousands): Year Ending December 31, 2019 $ 8,102 2020 11,044 2021 10,073 2022 10,156 2023 9,228 2024 and thereafter 78,079 $ 126,682 (b) Manufacturing agreement In August 2018, the Company entered into a Dedicated Manufacturing and Commercial Supply Agreement (the Brammer Agreement) with Brammer Bio MA, LLC (Brammer), pursuant to which Brammer has agreed to manufacture and supply certain products for the Company for clinical trial and commercial purposes. The term of the agreement continues until March 2026 and shall automatically renew for successive three ( 3 ) year terms unless the Company notifies Brammer of its intention not to renew no less than two ( 2 ) years prior to the expiration of the original term. During the term of the agreement, the Company will have access to a dedicated, specified portion of the manufacturing capacity in Brammer’s manufacturing facility located in Cambridge, Massachusetts, as well as non-dedicated capacity at Brammer’s facilities for manufacturing and other supply-related activities. Under the Brammer Agreement, the Company made an upfront payment of $4.0 million to Brammer upon execution of the agreement, which is included as a prepaid asset on the consolidated balance sheet and will be credited towards future capacity access amounts owed under the Brammer Agreement. The Company is obligated to pay yearly capacity access fees and is required to purchase a minimum dollar amount of manufactured batches per year. (c) License agreements See Note 15 for a discussion of the Children's Hospital of Philadelphia (CHOP) license agreement. In October 2013, the Company entered into a patent license agreement with Penn, as amended, for certain intellectual property licenses to be provided by Penn to the Company in the fields of research, development, manufacture and commercialization. The license agreement requires the Company to reimburse Penn for the patent costs related to the underlying licensed rights. The Company is obligated to make payments to Penn upon the occurrence of first commercial sale for certain licensed products in both the United States and Europe. The Company must pay a low-single-digit royalty based on net sales of licensed products by territory, which royalties will be reduced if the Company is required to license patents or intellectual property from third parties. In December 2014, the Company entered into a license agreement with Penn for certain intellectual property licenses. The Company issued to Penn 200,000 shares of restricted common stock (Note 12), which were subject to performance-based vesting conditions, in connection with the agreement and is obligated to make milestone payments upon the achievement of certain regulatory milestones up to $5.5 million in the aggregate. Additionally, the Company is obligated to pay Penn single-digit-royalties based on its net sales of licensed products by territory.

Related-party transactions

Related-party transactions	12 Months Ended
	Dec. 31, 2018
Related Party Transactions [Abstract]
Related-party transactions	Related-party transactions As of December 31, 2018 , CHOP was considered a significant equity holder. In October 2013, the Company entered into technology and license agreements with CHOP for certain commercialization licenses to be provided to the Company in order to develop services, methods and marketable products for commercialization. The license agreement requires the Company to reimburse CHOP for the patent costs related to the underlying licensed rights incurred after the effective date. For the years ended December 31, 2016 , 2017 and 2018 , the Company recorded $0.9 million , $0.8 million and $1.2 million , respectively, of selling, general and administrative expense related to the reimbursement of such patent costs in the accompanying consolidated statements of operations and comprehensive income (loss). In 2013, the Company entered into a number of services agreements with CHOP. The Master Research Services Agreement provides for certain research, development and manufacturing services to be provided to the Company by CHOP. A separate Services Agreement provides for clinical, technical and administrative services to be provided by CHOP to the Company. For the years ended December 31, 2016 , 2017 and 2018 , the Company recorded $7.4 million , $6.1 million and $5.7 million , respectively, as research and development expense. As of December 31, 2017 , $0.3 million and $1.4 million were recorded in accrued expenses and accounts payable, respectively, as amounts due to CHOP. As of December 31, 2018 , $0.7 million and $0.5 million

Collaboration and license agree

Collaboration and license agreements	12 Months Ended
	Dec. 31, 2018
Collaboration and License Agreements [Abstract]
Collaboration and license agreements	Collaboration and license agreements (a) Pfizer In December 2014, the Company entered into a global collaboration agreement with Pfizer for the development and commercialization of SPK-FIX product candidates for the treatment of hemophilia B. Under the agreement, the Company granted Pfizer an exclusive worldwide license to any factor IX gene therapy that it develops, manufactures or commercializes prior to December 31, 2024. The Company is primarily responsible for conducting all research and development activities through completion of Phase 1/2 clinical trials of hemophilia B product candidates. Pfizer and the Company will share development costs incurred under an agreed product development plan for each product candidate with the Company’s share of development costs under the agreement limited to $10.6 million . Following the completion of Phase 1/2 clinical trials, Pfizer will be primarily responsible for development, manufacture, regulatory approval and commercialization, including all costs associated therewith. In connection with this agreement, the Company received a $20.0 million upfront payment for the license in December 2014. As there was no stand-alone value for the license, the Company recognized revenue through the estimated completion date of Phase 1/2 clinical trials. In November 2017, the Company amended its global collaboration agreement with Pfizer. Under the terms of this amendment, the Company received $15.0 million in payments upfront, and an additional $10.0 million upon completion of certain transition activities. The $25.0 million of consideration was recognized as revenue over the estimated performance period associated with the global collaboration agreement. The Company is eligible to receive up to an additional $230.0 million in aggregate milestone payments, $110.0 million of which relate to potential development, regulatory and commercial milestones for the first product candidate to achieve each milestone and $120.0 million of which relate to potential regulatory milestones for additional product candidates. In addition, the Company is entitled to receive royalties calculated as a low-teen percentage of net sales of licensed products. The royalties may be subject to certain reductions, including for a specified portion of royalty payments that Pfizer may become required to pay under any third-party license agreements, subject to a minimum royalty. Under the agreement, the Company remains solely responsible for the payment of license payments payable by the Company under specified license agreements. The agreement will expire on a country-by-country basis upon the latest of: (i) the expiration of the last-to-expire valid claim, as defined in the agreement, in licensed patent rights covering a licensed product; (ii) the expiration of the last-to-expire regulatory exclusivity granted with respect to a licensed product; or (iii) 15 years after the first commercial sale of the last licensed product to be launched, in each case, in the applicable country. Pfizer may terminate the agreement on a licensed product-by-licensed product and country-by-country basis, or in its entirety, for any or no reason subject to notice requirements. In February 2018, the Company entered into a supply agreement with Pfizer for production in 2018, of one batch of drug substance expected to be used for Phase 3 development. The Company received $7.0 million upfront and received $7.0 million upon delivery in July 2018. The $14.0 million of consideration was recognized as contract revenue as the batch of the drug substance was completed. During the years ended December 31, 2016, 2017 and 2018, the Company recognized $20.2 million , $12.1 million and $36.0 million of contract revenue, respectively, related to the Company's agreements with Pfizer. During the years ended December 31, 2016, 2017 and 2018, the Company recorded $2.4 million , $2.9 million and $3.0 million , respectively, as a reduction to research and development expenses for the reimbursement of costs from Pfizer. In July 2018, Pfizer announced the initiation of a Phase 3 program following the Company's transfer of responsibility for the hemophilia B gene therapy program to Pfizer. (b) Novartis In January 2018, the Company entered into a licensing and commercialization agreement (Novartis License Agreement) with Novartis Pharma AG (Novartis) to develop and commercialize voretigene neparvovec (also known as LUXTURNA) outside the United States. Under the terms of the Novartis License Agreement, the Company has granted Novartis an exclusive right and license, with the right to grant certain sublicenses, under the Company’s intellectual property reasonably necessary or useful for the development or commercialization of LUXTURNA for the treatment, prevention, cure or control of RPE65-mediated IRD in humans outside the United States. Under the terms of the Novartis License Agreement, the Company received a non-refundable, one-time payment of $105.0 million in the first quarter of 2018, and is eligible to receive up to an additional $65.0 million in milestone payments. The Company also is entitled to receive royalty payments at a percentage of net sales on a royalty-region by royalty-region basis, subject to reduction and extension in certain circumstances. In conjunction with the Novartis License Agreement, the Company and Novartis also entered into a Supply Agreement, under which the Company has agreed to supply all of the commercial supply of voretigene neparvovec required by Novartis, subject to certain conditions. The Supply Agreement continues until the expiration or early termination of the Novartis License Agreement. In addition, either party may terminate the Supply Agreement upon the other party’s uncured material breach of the Supply Agreement, insolvency or bankruptcy. The Company evaluated whether or not the performance obligations granted under the License and Supply Agreements were distinct and concluded that they were not distinct as Novartis could not benefit from the Novartis License Agreement without the services under the Supply Agreement. As such, the performance obligations granted under the Novartis License Agreement and Supply Agreement are combined to constitute a single performance obligation and the Company accounts for them as a single contract. During the fourth quarter of 2018, and in conjunction with the European Commission granting marketing authorization for LUXTURNA, the Company earned an additional $25.0 million milestone payment and recorded an additional $30.0 million of variable consideration that was no longer constrained which, along with the $105.0 million upfront payment, is included as deferred revenue on the accompanying consolidated balance sheet as of December 31, 2018. The Company allocated $160.0 million in license fees and milestone payments that were not constrained to the single performance obligation in the combined contracts. The Company expects to recognize the $160.0 million and variable amounts under the Supply Agreement over time using an outputs method based on vials supplied to Novartis. The Company expects to begin manufacturing product for Novartis in 2019 and expects to continue to do so throughout the life of the contract. At December 31, 2018, the remaining $10.0 million in milestone payments under the Novartis License Agreement remains constrained, due to additional regulatory approvals, and will not begin to be recognized until such amount becomes unconstrained. In determining the transaction price, the Company analyzed the variable consideration and whether or not such variable consideration was constrained. The Company will reassess this variable consideration at each reporting period and adjust the transaction price, if necessary. The total vials that the Company expects to manufacture for Novartis over the life of the Supply Agreement will be a significant judgment that will be relied upon when using the point in time method to recognize revenue once the Company begins to manufacture product for Novartis. (c) Selecta In December 2016, the Company entered into a License and Option Agreement (Selecta License Agreement) with Selecta that provides the Company with exclusive worldwide rights to Selecta’s proprietary Synthetic Vaccine Particles (SVP™) platform technology for co-administration with gene therapy targets. Under the terms of the Selecta License Agreement, Selecta has granted the Company certain exclusive, worldwide, royalty-bearing licenses to Selecta’s intellectual property and know-how relating to its SVP technology to research, develop and commercialize gene therapies for factor VIII, an essential blood clotting protein relevant to the treatment of hemophilia A, which is the initial target under the license. In addition, for a specified period of time, the Company may exercise options to research, develop and commercialize gene therapies utilizing the SVP technology for up to four additional targets, subject to the Company’s payment of the applicable option exercise fee, in a range of $1.4 million to $2.0 million depending on the incidence of the applicable indication, to Selecta in each case. Pursuant to a letter agreement (Letter Agreement), entered into between the Company and Selecta on June 6, 2017, Selecta agreed to reimburse the Company for all costs and expenses related to research and development for any licensed products for a specified amount of time, up to an agreed upon cap. Additionally, the Company has agreed to reimburse Selecta in respect of full-time equivalents and out-of-pocket costs incurred in performing certain tasks or assistance specifically requested by the Company. Selecta retains the responsibility to manufacture the Company’s preclinical, clinical and commercial requirements for the SVP technology, subject to the terms of the Selecta License Agreement. In connection with the execution of the Selecta License Agreement, the Company paid Selecta an upfront payment of $10.0 million in December 2016. Additional payments in the aggregate of $5.0 million were paid in June 2017 and October 2017 pursuant to the terms of the Selecta License Agreement and the Letter Agreement. On a target-by-target basis, the Company will be responsible to pay up to an aggregate of $430.0 million in milestone payments for each target, with up to $65.0 million being based on the Company’s achievement of specified development and regulatory milestones and up to $365.0 million for commercial milestones, as well as tiered royalties on global net sales at percentages ranging from mid-single to low-double digits. For a period of three years, the Company has the right to fund up to 50% of any development or regulatory milestone payable to Selecta by issuing to Selecta shares of the Company’s common stock having a fair market value equal to the percentage of such development or regulatory milestone, as applicable. The Selecta License Agreement will continue on a country-by-country and product-by-product basis until the expiration of the Company's royalty payment obligations with respect to such product in such country unless earlier terminated by the parties. The Selecta License Agreement may be terminated by the Company for convenience upon 90 days ’ notice and the Company will not be required to make any payments. Either party may terminate the Selecta License Agreement on a target-by-target basis for material breach with respect to such target. In connection with the Selecta License Agreement, the Company entered into a Stock Purchase Agreement (SPA) with Selecta pursuant to which the Company purchased 197,238 unregistered shares of Selecta's common stock for $5.0 million in December 2016. An additional 324,362 unregistered shares of Selecta's common stock were purchased for $5.0 million in June 2017, and 205,254 unregistered shares of Selecta's common stock were purchased for $5.0 million in October 2017. These shares are classified as available-for-sale securities as of December 31, 2018 . In December 2016, the Company accounted for the payments under the Selecta License Agreement and SPA as a basket transaction and allocated the $15.0 million in cash payments to the shares of Selecta’s common stock and the Selecta License Agreement in the amounts of $3.5 million and $11.5 million , respectively. The Company calculated the $3.5 million allocated for the Selecta shares acquired based on the closing market price on the date of purchase. The Company allocated the remaining $11.5 million to the Selecta License Agreement, which was expensed as acquired in-process research and development as the Company determined there was no alternative future use. In June 2017, the Company accounted for the payments under the Selecta License Agreement, Letter Agreement and SPA as a basket transaction and allocated the $7.5 million in cash payments to the shares of Selecta’s common stock and the Selecta License Agreement in the amounts of $4.4 million and $3.1 million , respectively. The Company calculated the $4.4 million allocated to the Selecta shares acquired based on the closing market price on the date of purchase. The Company allocated the remaining $3.1 million to the Selecta License Agreement, which was expensed as acquired in-process research and development as the Company determined there was no alternative future use. In October 2017, the Company accounted for the payments under the Selecta License Agreement, Letter Agreement and SPA as a basket transaction and allocated the $7.5 million in cash payments to the shares of Selecta’s common stock and the Selecta License Agreement in the amounts of $4.1 million and $3.4 million , respectively. The Company calculated the $4.1 million allocated to the Selecta shares acquired based on the closing market price on the date of purchase. The Company allocated the remaining $3.4 million

Income taxes Income taxes

Income taxes Income taxes	12 Months Ended
	Dec. 31, 2018
Income Tax Disclosure [Abstract]
Income taxes	Income taxes On December 22, 2017, the U.S. government enacted comprehensive tax legislation commonly referred to as the Tax Cuts and Jobs Act (the Tax Act). The Tax Act makes broad and complex changes to the U.S. tax code, including, but not limited to, reducing the U.S. federal corporate tax rate from 35 percent to 21 percent; eliminating the corporate alternative minimum tax (AMT) and changing how existing AMT credits can be realized; creating a new limitation on deductible interest expense; changing rules related to uses and limitations of net operating loss carryforwards created in tax years beginning after December 31, 2017; limitations on the deductibility of certain executive compensation; and changes to the calculation of the orphan drug credit. In December 2017, the SEC issued Staff Accounting Bulletin No. 118 (SAB 118), which addresses situations where the accounting is incomplete for the income tax effects of the Tax Act. SAB 118 directs taxpayers to consider the impact of the Tax Act as “provisional” when the Company does not have the necessary information available, prepared or analyzed (including computations) to finalize the accounting for the change in tax law. Companies were provided a measurement period of up to one year to obtain, prepare, and analyze information necessary to finalize the accounting for provisional amounts or amounts that could not be estimated as of December 31, 2017. With regards to the Tax Act impact on the tax provision as it relates to the Company for the year ended December 31, 2018, the Company has recognized the final impact of tax reform related to the revaluation of deferred tax assets and liabilities from 34% to 21% of $0.5 million of tax expense, which is offset by a reduction in the valuation allowance. As a result of changes made by the Tax Act, starting with executive compensation paid in 2018, Section 162(m) of the Internal Revenue Code will limit the Company from deducting compensation, including performance-based compensation, in excess of $1.0 million paid to certain executives. The only exception to this rule is for compensation that is paid pursuant to a binding contract in effect on November 2, 2017 that would have otherwise been deductible under the prior Section 162(m) rules. The Company reviewed the binding contract requirement on the various compensation plans and determined that there was no impact of the law change to its deferred tax asset for stock compensation. With regards to the one-time transition tax, the Company did not record any tax liability as the accumulated earnings and profits of foreign subsidiaries were in a deficit position. The Company reviewed the new international tax provisions included in the Tax Act and determined that no adjustments were necessary under ASC Topic 740, Income Taxes . Income (loss) before income taxes attributable to domestic and international operations, consists of the following (in thousands): Year Ended December 31, 2016 2017 2018 Domestic $ (122,810 ) $ (239,301 ) $ (78,956 ) Foreign (843 ) (15,144 ) 233 Loss before income taxes $ (123,653 ) $ (254,445 ) $ (78,723 ) Income tax expense (benefit) consists of the following (in thousands): Year Ended December 31, 2016 2017 2018 Current tax: Domestic $ — $ — $ — Foreign — 110 99 Deferred tax: Domestic — — — Foreign — (1,073 ) — Total income tax benefit (expense) $ — $ (963 ) $ 99 A reconciliation of income tax benefit computed at the statutory federal income tax rate to income taxes as reflected in the consolidated financial statements is as follows: Year Ended December 31, 2016 2017 2018 Federal income tax benefit at statutory rate 34.0 % 34.0 % 21.0 % State and local tax, net of federal benefit 10.4 10.3 7.5 Permanent differences 3.1 (0.3 ) 3.6 Tax credits 9.1 9.2 17.7 Tax Cuts and Jobs Act impact — (17.6 ) (0.6 ) Foreign rate differential (0.1 ) (1.3 ) — Change in valuation allowance (56.5 ) (33.9 ) (42.9 ) Change in tax reserve — — (5.5 ) Other — — (0.9 ) Effective income tax rate — % 0.4 % (0.1 )% Deferred taxes are recognized for temporary differences between the basis of assets and liabilities for financial statement and income tax purposes and for net operating loss and tax credit carryforwards. The significant components of the Company’s deferred tax assets are comprised of the following (in thousands): December 31, 2017 2018 Deferred tax assets (liabilities): Net operating loss carryforwards $ 114,152 $ 127,012 Tax credit carryforwards 51,586 60,174 Stock-based compensation 14,644 20,475 Deferred rent 4,697 1,149 Deferred revenue 956 — Accruals and other 8,998 17,151 Fixed assets — 1,875 Total deferred tax assets 195,033 227,836 Less valuation allowance (193,796 ) (227,836 ) Net deferred tax assets $ 1,237 $ — Fixed assets (1,237 ) — Total deferred tax liabilities $ (1,237 ) $ — Net deferred tax asset $ — $ — As of December 31, 2018 , the Company had U.S. federal net operating loss carryforwards of $318.3 million , which may be available to offset future income tax liabilities and will expire beginning in 2034. In addition, the Company had federal net operating loss carryforwards of $58.3 million that arose after the 2017 tax year, which are available to reduce future federal taxable income, if any, over an indefinite period. The utilization of those net operating loss carryforwards is limited to 80% of taxable income in any given year. As of December 31, 2018 , the Company also had U.S. state net operating loss carryforwards of $376.4 million , which may be available to offset future income tax liabilities and will expire beginning in 2034 , and foreign net operating losses of $8.6 million which can be carried forward indefinitely. The Company has recorded a full valuation allowance against its net deferred tax assets as of December 31, 2017 and 2018 because the Company has determined that is it more likely than not that these assets will not be fully realized due to historic net operating losses incurred. The Company experienced a net change in valuation allowance of $86.2 million and $34.0 million in the years ended December 31, 2017 and 2018 , respectively. As of December 31, 2018 , the Company had federal research and development and orphan drug tax credit carryforwards of $7.5 million and $52.7 million , respectively, available to reduce future tax liabilities, which expire beginning in 2034 . Under the provisions of the Internal Revenue Code, the net operating loss and tax credit carryforwards are subject to review and possible adjustment by the Internal Revenue Service and state tax authorities. Net operating loss and tax credit carryforwards may become subject to an annual limitation in the event of certain cumulative changes in the ownership interest of significant shareholders over a three-year period in excess of 50%, as defined under Sections 382 and 383 of the Internal Revenue Code, respectively, as well as similar state provisions. This could limit the amount of tax attributes that can be utilized annually to offset future taxable income or tax liabilities. The amount of the annual limitation is determined based on the value of the Company immediately prior to the ownership change. Subsequent ownership changes may further affect the limitation in future years. The Company has completed financings since its inception which may have resulted in a change in control as defined by Sections 382 and 383 of the Internal Revenue Code, or could result in a change in control in the future. The Company files tax returns as prescribed by the tax laws of the jurisdictions in which it operates. In the normal course of business, the Company is subject to examination by federal, state, and foreign jurisdictions, where applicable. The Company’s tax years are still open under status from 2014 to present. All open years may be examined to the extent that tax credit or net operating loss carryforwards are used in future periods. The Company recognizes in its consolidated financial statements the impact of a tax position, if it is more likely than not that such a position will be sustained on audit, based solely on the technical merits of the position. A reconciliation of the beginning and ending amounts of gross unrecognized tax benefits is as follows (in thousands): December 31, 2018 Gross unrecognized tax benefits at January 1 $ — Increases related to prior year tax positions 3,858 Increases related to current year tax positions 483 Gross unrecognized tax benefits at December 31 $ 4,341 The Company recognizes interest and penalties related to uncertain tax positions in income tax expense. As of December 31, 2018

Selected quarterly financial da

Selected quarterly financial data (unaudited)	12 Months Ended
	Dec. 31, 2018
Quarterly Financial Information Disclosure [Abstract]
Selected quarterly financial data (unaudited)	Selected quarterly financial data (unaudited) The following table contains quarterly financial information for 2017 and 2018 (in thousands). The Company believes that the following information reflects all normal recurring adjustments necessary for a fair presentation of the information for the periods presented. The operating results for any quarter are not necessarily indicative of results for any future period. 2017 First quarter Second quarter Third quarter Fourth quarter Revenues $ 1,274 $ 1,483 $ 1,900 $ 7,409 Research and development 32,348 32,989 39,342 30,481 Acquired in-process research and development 387 3,070 1,750 3,397 Impairment of acquired in-process research and development — 15,696 — — Selling, general and administrative 21,414 26,729 26,640 36,341 Total operating expenses 54,149 78,484 67,732 70,219 Loss from operations (52,875 ) (77,001 ) (65,832 ) (62,810 ) Net loss $ (52,289 ) $ (74,360 ) $ (65,012 ) $ (61,821 ) Basic and diluted net loss per common share $ (1.70 ) $ (2.40 ) $ (1.90 ) $ (1.68 ) 2018 First Second quarter Third quarter Fourth quarter Revenues $ 15,676 $ 25,185 $ 10,707 $ 13,157 Cost of goods sold 990 4,511 318 2,096 Research and development 30,109 25,524 32,829 36,792 Acquired in-process research and development — — — 300 Selling, general and administrative 33,489 29,749 29,305 32,352 Total operating expenses 64,588 59,784 62,452 71,540 Loss from operations (48,912 ) (34,599 ) (51,745 ) (58,383 ) Net (loss) income $ (46,373 ) $ 80,165 $ (47,357 ) $ (65,257 ) Basic net (loss) income per common share $ (1.25 ) $ 2.15 $ (1.26 ) $ (1.73 ) Diluted net (loss) income per common share $ (1.25 ) $ 2.07 $ (1.26 ) $ (1.73 )

Subsequent events

Subsequent events	12 Months Ended
	Dec. 31, 2018
Subsequent Events [Abstract]
Subsequent events	Subsequent events On February 22, 2019, the Company entered into an Agreement and Plan of Merger (Merger Agreement) with Roche Holdings, Inc., a Delaware corporation (Roche) and 022019 Merger Subsidiary, Inc., a Delaware corporation and wholly owned subsidiary of Roche (Merger Sub). Under the terms of the Merger Agreement, Merger Sub will commence a cash tender offer (Tender Offer) to acquire all of the issued and outstanding shares of common stock of the Company at a price per share equal to $114.50 , net to the seller of such shares in cash, without interest, subject to any withholding of taxes required by applicable law. Following the completion of the Tender Offer, Merger Sub will merge with and into the Company, with the Company surviving as a wholly owned subsidiary of Roche (Merger). The Merger will be governed by Section 251(h) of the General Corporation Law of the State of Delaware, with no stockholder vote required to consummate the Merger. In the Merger, each outstanding share of the Company’s common stock (other than shares of common stock held by the Company as treasury stock, or owned by Roche or Merger Sub or held by stockholders who are entitled to demand, and who properly demand, appraisal rights under Delaware law) will be converted into the right to receive $114.50 per share in cash, without interest, subject to any withholding of taxes required by applicable law. The transaction is expected to close in the second quarter of 2019. The consummation of the Tender Offer and the Merger will be conditioned on (1) at least a majority of the shares of the Company's outstanding common stock having been validly tendered into and not withdrawn from the Tender Offer, (2) receipt of certain regulatory approvals, including expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, (3) the accuracy of certain representations and warranties that the Company made and compliance by the Company with certain covenants contained in the Merger Agreement, subject to qualifications, (4) there not having been a “Company Material Adverse Effect” (as defined in the Merger Agreement) with respect to the Company since the date of the Merger Agreement, and (5) other customary conditions. The Tender Offer and the Merger are not subject to a financing contingency. The Merger Agreement may be terminated by the Company under certain circumstances, including in connection with an Acquisition Proposal (as defined in the Merger Agreement) that the Company’s Board of Directors determines constitutes a Superior Proposal (as defined in the Merger Agreement). Upon the termination of the Merger Agreement, under specified circumstances, the Company will be required to pay to Roche a termination fee of $144.0 million

Summary of significant accoun_2

Summary of significant accounting policies (Policies)	12 Months Ended
	Dec. 31, 2018
Accounting Policies [Abstract]
Use of estimates	Use of estimatesThe preparation of consolidated financial statements in conformity with U.S. generally accepted accounting principles (GAAP) requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and disclosure of contingent assets and liabilities at the date of the consolidated financial statements and the reported amounts of revenues and expenses during the reporting period. Actual results could differ from such estimates.
Principles of consolidation	Principles of consolidationThe accompanying consolidated financial statements include the accounts of the Company and its wholly-owned subsidiaries: Spark Therapeutics Ireland Limited, Spark Therapeutics UK Limited, Spark Therapeutics Argentina Limited, Spark Therapeutics Switzerland Limited, Spark Therapeutics Germany Limited and Spark Therapeutics France Limited. All intercompany balances and transactions have been eliminated in consolidation.
Fair value of financial instruments	Fair value of financial instrumentsManagement believes that the carrying amounts of the Company’s financial instruments, including cash equivalents, trade and other receivables, accounts payable and accrued expenses, approximate fair value due to the short-term nature of those instruments. Management believes the carrying value of debt approximates fair value as the interest rates are reflective of the rate the Company could obtain on debt with similar terms and conditions.
Cash and cash equivalents	Cash and cash equivalents The Company considers all highly liquid investments that have maturities of three months or less when acquired to be cash equivalents. Cash equivalents as of December 31, 2017 and 2018 consisted of money market funds.
Marketable securities	Marketable securities The Company classifies its marketable security investments as available-for-sale securities and the securities are stated at fair value. At December 31, 2018 , the balance in the Company’s accumulated other comprehensive loss included activity related to the Company’s available-for-sale marketable securities. There were no material realized gains or losses recognized on the maturity of available-for-sale securities during the year ended December 31, 2018
Trade and other receivables	Trade and other receivablesTrade accounts receivable are recorded at gross value, and reserves for other sales-related allowances, such as discounts, rebates, services and insurance co-pay assistance, are included in accrued expenses on the Company's consolidated balance sheets.
Inventory	Inventory Inventory is stated at the lower of cost or net realizable value and consists of those costs incurred following FDA approval of LUXTURNA. Cost is determined using the first-expired, first-out (FEFO) method. The Company reserves for potentially excess, dated or obsolete inventories based on an analysis of inventory on hand compared to forecasts of future sales. Based on management's assessment, no such inventory reserve is necessary as of December 31, 2018
Property and equipment	Property and equipment Property and equipment consists of computer and laboratory equipment, software, office equipment, furniture and leasehold improvements and is recorded at cost. Maintenance and repairs that do not improve or extend the lives of the respective assets are expensed to operations as incurred. Upon disposal, retirement or sale, the related cost and accumulated depreciation are removed from the accounts and any resulting gain or loss is included in the results of operations. Property and equipment are depreciated on a straight-line basis over their estimated useful lives. The Company uses a life of three years for computer equipment and software, five years for laboratory and office equipment and seven years for furniture. Leasehold improvements are amortized over the shorter of the lease term or the estimated useful life of the asset . The Company reviews long-lived assets, such as property and equipment, for impairment when events or changes in circumstances indicate the carrying value of the assets may not be recoverable. Recoverability is measured by comparison of the book values of the assets to estimated undiscounted future cash flows that the assets are expected to generate. If the carrying amount of an asset exceeds its estimated future cash flows, then an impairment charge is recognized for the amount by which the carrying value of the asset exceeds the fair value of the asset. No
Net product sales and Contract revenue	Net product sales LUXTURNA is distributed in the United States through two distribution models: (1) the traditional buy-and-bill model where the treatment center purchases and pays for the product and then submits a claim to the payer; and (2) the Company's innovative contracting and distribution model, branded Spark PATH (Pioneering Access to Healthcare), which includes options for direct-to-payer contracting and outcomes-based rebates. The Company’s net product sales represent total gross product sales in the United States less allowances for estimated prompt-payment discounts, service fees, rebates and insurance co-payment assistance. Allowances are established based on contractual terms and management’s reasonable estimates, as well as the expectation that 100% of the prompt-payment discounts will be earned. Product shipping and handling costs and distributor reporting fees are included in cost of product sales. The Company evaluated the variable consideration under Accounting Standards Codification (ASC) Topic 606, Revenue from Contracts with Customers (ASC 606), as it relates to the outcomes-based method and determined that based on historical clinical data, no rebate reserves were required for the year ended December 31, 2018 . All sales are recognized when control is transferred, which follows the Company’s verification of a scheduled LUXTURNA treatment. The Company’s product return policy is to provide non-monetary credit or product replacement. As the product is sold in direct relation to a scheduled treatment, Company management estimates that there is minimal risk of product return, including the risk of product expiration. (j) Contract revenue Under certain of the Company’s licensing, supply and collaboration agreements, it is entitled to receive payment upon the achievement of contingent milestone events or the performance of obligations. The Company recognizes revenue based on guidance in ASC 606. Prior to 2018, the Company generated revenue solely through license and collaborative arrangements. In the first quarter of 2018, the Company adopted ASC 606. The adoption of this standard resulted in no cumulative adjustment to the Company’s consolidated financial statements. ASC 606 applies to all contracts with customers, except for contracts that are within the scope of other standards, such as leases, insurance, collaboration arrangements and financial instruments. To determine revenue recognition for arrangements that an entity determines are within the scope of ASC 606, the entity performs the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) the entity satisfies a performance obligation. At contract inception, once the contract is determined to be within the scope of ASC 606, the Company assesses the goods or services promised within each contract and determines those that are performance obligations and assesses whether each promised good or service is distinct. The Company then recognizes as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) the performance obligation is satisfied.
Research and development and in-process research and development	Research and development and in-process research and development Research and development costs are expensed as incurred. Research and development expenses consist of internal and external expenses. Internal expenses include employee compensation and overhead. External expenses include development, clinical trials, statistical analysis and report writing and regulatory compliance costs incurred with clinical research organizations and other third-party vendors. At the end of the reporting period, the Company compares payments made to third-party service providers to the estimated progress toward completion of the research or development objectives. Such estimates are subject to change as additional information becomes available. Depending on the timing of payments to the service providers and the progress that the Company estimates has been made as a result of the service provided, the Company may record net prepaid or accrued expense relating to these costs. When the Company is reimbursed by a collaboration partner for work performed, the costs incurred are recorded as research and development expenses and the related reimbursement is recorded as a reduction to research and development expenses.
Income tax	Income taxes The Company recognizes deferred tax assets and liabilities for temporary differences between the financial reporting basis and the tax basis of its assets and liabilities and the expected benefits of net operating loss and tax credit carryforwards. The impact of changes in tax rates and laws on deferred taxes, if any, is applied during the years in which temporary differences are expected to be settled and net operating losses and tax credits used and is reflected in the consolidated financial statements in the period of enactment. The measurement of deferred tax assets is reduced, if necessary, if, based on weight of the evidence, it is more likely than not that some, or all, of the deferred tax assets will not be realized. As of December 31, 2017 and 2018
Share-based compensation and fair value of stock	Stock-based compensation and fair value of stock The Company accounts for its stock-based compensation awards in accordance with ASC Topic 718, Compensation-Stock Compensation (ASC 718). ASC 718 requires all stock-based payments to employees, including grants of employee stock options and restricted stock units and modifications to existing stock options, to be recognized in the consolidated statement of operations and comprehensive income(loss) based on their fair values. The Company uses the Black-Scholes option pricing model to determine the fair value of options granted. The Company’s stock-based awards are subject to either service or performance-based vesting conditions. Compensation expense related to awards to employees and directors with service-based vesting conditions is recognized on a straight-line basis based on the grant date fair value over the associated service period of the award, which is generally the vesting term. Compensation expense related to awards to non-employees with service-based vesting conditions is recognized based on the then-current fair value at each financial reporting date prior to the measurement date over the associated service period of the award, which is generally the vesting term. Compensation expense related to awards to employees with performance-based vesting conditions is recognized based on the grant date fair value over the requisite service period to the extent achievement of the performance condition is probable. The Company estimates the fair value of its option awards to employees and directors using the Black-Scholes option pricing model, which requires the input of subjective assumptions, including (i) the expected stock price volatility, (ii) the calculation of the expected term of the award, (iii) the risk-free interest rate and (iv) expected dividends. Due to the lack of substantial Company-specific historical and implied volatility data of its common stock, the Company has based its estimate of expected volatility on the historical volatility of a group of similar companies that are publicly traded. When selecting these public companies on which it has based its expected stock price volatility, the Company selected companies with comparable characteristics to it, including enterprise value, risk profiles, position within the industry and with historical share price information sufficient to meet the expected term of the stock-based awards. The Company computes historical volatility data using the daily closing prices for the selected companies’ shares during the equivalent period of the calculated expected term of the stock-based awards. The Company will continue to apply this process until a sufficient amount of historical information regarding the volatility of its own stock price becomes available. The Company has estimated the expected term of its employee stock options using the “simplified” method, whereby, the expected term equals the arithmetic average of the vesting term and the original contractual term of the option due to its lack of sufficient historical data. The risk-free interest rates for periods within the expected term of the option are based on the U.S. Treasury securities with a maturity date commensurate with the expected term of the associated award. The Company has never paid, and does not expect to pay, dividends in the foreseeable future. The Company accounts for forfeitures when they occur. Consistent with the guidance in ASC Topic 505-50, Equity-Based Payments to Non-Employees
Net loss per common share	Net loss per common shareBasic and diluted net loss per common share is determined by dividing net loss by the weighted average number of common shares outstanding during the period. For all periods presented, unvested restricted shares and common stock options have been excluded from the calculation because their effect would be anti-dilutive. Therefore, the weighted average shares outstanding used to calculate both basic and diluted loss per share are the same.
Deferred rent	Deferred rent Rent expense, including rent holidays and scheduled rent increases, is recorded on a straight-line basis over the term of the lease commencing on the date the Company takes possession of the leased property. Tenant improvement allowances from the lessor are included in the accompanying consolidated balance sheet as deferred rent and are amortized as a reduction of rent expense over the term of the lease from the possession date. Deferred rent as of December 31, 2017 and 2018
Other comprehensive loss	Other comprehensive loss The Company follows the provisions of ASC Topic 220, Comprehensive Income
Recent accounting pronouncements	Recent accounting pronouncements In February 2016, the Financial Accounting Standards Board (FASB) issued Accounting Standards Update (ASU) 2016-02, Leases . ASU 2016-02 requires lessees to apply a two-method approach, classifying leases as either finance or operating leases based on the principle of whether or not the lease is effectively a financed purchase. This classification will determine whether lease expense is recognized based on an effective interest method or on a straight line basis over the term of the lease, respectively. Lessees are also required to record a right-of-use (ROU) asset and a lease liability for all leases with a term greater than 12 months. Leases with a term of 12 months or less will be accounted for similar to existing guidance for operating leases. ASU 2016-02 is effective for interim and annual periods beginning after December 15, 2018. The Company has elected to adopt this standard using the effective date method using a modified retrospective transition approach. The Company expects the adoption of the standard to have a material impact on its consolidated balance sheet, which will result in the removal of the built to suit asset and liability recorded as of December 31, 2018, and the recognition of ROU assets and lease liabilities of approximately $40.0 million to $50.0 million at January 1, 2019. In May 2014, the FASB issued a new standard, ASC 606, regarding the accounting for, and disclosures of, revenue recognition, with an effective date for annual and interim periods beginning after December 15, 2017. ASC 606 provides a single comprehensive model for accounting for revenue from contracts with customers. The model requires that revenue recognized reflect the actual consideration to which the entity expects to be entitled in exchange for the goods or services defined in the contract, including in situations with multiple performance obligations. The Company adopted ASC 606 using the modified retrospective method and the adoption had no cumulative adjustment to its consolidated financial statements as it relates to the Pfizer Inc. (Pfizer) collaboration agreement discussed in Note 16. For the year ended December 31, 2018, there was no impact from the adoption of ASC 606 that resulted in a different revenue recognition amount than under the prior revenue recognition guidance in effect during 2017. In January 2016, the FASB issued ASU 2016-01, Financial Instruments-Overall: Recognition and Measurement of Financial Assets and Financial Liabilities . ASU 2016-01 changes accounting for equity investments, financial liabilities under the fair value option, and presentation and disclosure requirements for financial instruments. ASU 2016-01 does not apply to equity investments in consolidated subsidiaries or those accounted for under the equity method of accounting. In addition, the FASB clarified guidance related to the valuation allowance assessment when recognizing deferred tax assets resulting from unrealized losses on available-for-sale debt securities. Equity investments with readily determinable fair values will be measured at fair value with changes in fair value recognized in net income. Companies have the option to either measure equity investments without readily determinable fair values at fair value or at cost, adjusted for changes in observable prices, minus impairment. Changes in measurement under either alternative will be recognized in net income. Companies that elect the fair value option for financial liabilities must recognize changes in fair value related to instrument-specific credit risk in other comprehensive income. Companies must assess valuation allowances for deferred tax assets related to available-for-sale debt securities in combination with their other deferred tax assets. The Company adopted this guidance effective January 1, 2018, resulting in a reclassification of $5.0 million from accumulated other comprehensive loss to accumulated deficit related to the unrecognized loss on the Company's investment in Selecta. In August 2017, the FASB issued ASU 2017-12, Derivatives and Hedging: Targeted Improvements to Accounting for Hedging Activities

Summary of significant accoun_3

Summary of significant accounting policies (Tables)	12 Months Ended
	Dec. 31, 2018
Accounting Policies [Abstract]
Schedule of Potentially Dilutive Securities Excluded from Computation of Diluted Weighted Average Shares Outstanding	The following potentially dilutive securities have been excluded from the computations of diluted weighted average shares outstanding for the years ended December 31, 2016 , 2017 and 2018 as they would be anti-dilutive: December 31, 2016 2017 2018 Unvested restricted common shares 251,809 798,501 942,776 Options issued and outstanding 4,181,993 3,522,874 3,487,376
Schedule of Accumulated Other Comprehensive Income (Loss)	The accumulated balances related to each component of other comprehensive income (loss) are summarized as follows (in thousands): Net unrealized (loss) gain on available-for-sale securities Unrealized loss on interest rate swap Foreign currency translation adjustments Accumulated other comprehensive loss Balance as of December 31, 2017 $ (5,964 ) $ — $ 50 $ (5,914 ) Reclassification of unrealized loss on equity investment to accumulated deficit 5,002 — — 5,002 Current period other comprehensive income (loss) 586 (641 ) (83 ) (138 ) Balance as of December 31, 2018 $ (376 ) $ (641 ) $ (33 ) $ (1,050 )

Marketable securities (Tables)

Marketable securities (Tables)	12 Months Ended
	Dec. 31, 2018
Investments, Debt and Equity Securities [Abstract]
Marketable Securities	The following table summarizes the available-for-sale securities held as of December 31, 2017 and 2018 (in thousands): Description Amortized cost Unrealized gains Unrealized losses Fair value December 31, 2017 U.S. government agency $ 222,180 $ — $ (641 ) $ 221,539 Corporate securities $ 227,238 $ — $ (5,323 ) $ 221,915 December 31, 2018 U.S. government agency $ 223,553 $ 54 $ (123 ) $ 223,484 Corporate securities $ 239,940 $ 34 $ (10,421 ) $ 229,553

Fair value of financial instr_2

Fair value of financial instruments (Tables)	12 Months Ended
	Dec. 31, 2018
Fair Value Disclosures [Abstract]
Summary of Assets and Liabilities Measured at Fair Value on Recurring Basis	The Company has classified assets and liabilities measured at fair value on a recurring basis as follows (in thousands): Fair value measurements at reporting date using Quoted prices in active markets for identical assets (Level 1) Significant other observable inputs (Level 2) Significant unobservable inputs (Level 3) As of December 31, 2017: Assets: Money market funds (included in cash and cash equivalents) $ 90,348 — — Corporate securities (included in cash and cash equivalents) $ 5,548 — — Marketable securities - U.S. government agencies $ 221,539 — — Marketable securities - corporate securities $ 220,020 $ 1,895 — As of December 31, 2018: Assets: Money market funds (included in cash and cash equivalents) $ 94,216 — — Certificates of deposit - restricted cash $ 53,000 — — Marketable securities - U.S. government agencies $ 223,484 — — Marketable securities - corporate securities $ 229,553 — —

Inventory (Tables)

Inventory (Tables)	12 Months Ended
	Dec. 31, 2018
Inventory Disclosure [Abstract]
Schedule of Inventory	Inventory consists of the following (in thousands): December 31, Raw materials $ 3,843 Work in process 19,843 Finished goods 1,951 $ 25,637

Business acquisition of Genab_2

Business acquisition of Genable and impairment of acquired in-process research and development (Tables)	12 Months Ended
	Dec. 31, 2018
Goodwill and Intangible Assets Disclosure [Abstract]
Summarized Fair Value of Tanigle and Intangible Assets Acquired and Liabilities Assumed	The following table summarizes the fair values of the tangible and intangible assets acquired and liabilities assumed at the acquisition date (in thousands): Cash acquired $ 196 Other current assets 103 Acquired in-process research and development 15,490 Goodwill 1,160 Total assets assumed 16,949 Other non-current liabilities 255 Deferred tax liability 1,000 Total liabilities assumed 1,255 Total allocation of purchase price $ 15,694

Property and equipment, net (Ta

Property and equipment, net (Tables)	12 Months Ended
	Dec. 31, 2018
Property, Plant and Equipment [Abstract]
Schedule of property and equipment, net	Property and equipment consist of the following (in thousands): December 31, 2017 2018 Laboratory equipment $ 6,381 $ 8,272 Computer and software 1,325 2,773 Furniture and fixtures 1,770 2,564 Office equipment 726 1,394 Leasehold improvements 23,653 54,541 One Drexel Plaza (built-to-suit) 34,993 34,789 Construction in progress 3,187 7,869 Property and equipment, gross 72,035 112,202 Less accumulated depreciation and amortization (10,322 ) (16,204 ) Property and equipment, net $ 61,713 $ 95,998

Accrued expenses (Tables)

Accrued expenses (Tables)	12 Months Ended
	Dec. 31, 2018
Payables and Accruals [Abstract]
Schedule of Accrued Expenses	Accrued expenses consist of the following (in thousands): December 31, 2017 2018 Compensation and benefits $ 15,012 $ 15,575 Consulting and professional fees 4,846 13,904 Research and development 2,809 2,706 Other 2,030 2,605 $ 24,697 $ 34,790

Debt (Tables)

Debt (Tables)	12 Months Ended
	Dec. 31, 2018
Debt Disclosure [Abstract]
Schedule of debt	The Company's debt consists of the following (in thousands): December 31, 2017 2018 Term loan outstanding $ — $ 50,000 MELF loan outstanding 1,224 912 Less: current portion of long-term debt (312 ) (4,822 ) Total long-term debt due after one year $ 912 $ 46,090

Stockholders' equity (Tables)

Stockholders' equity (Tables)	12 Months Ended
	Dec. 31, 2018
Equity [Abstract]
Summary of Restricted Common Stock Activity	The following table summarizes restricted stock activity for the instruments discussed above: Number of shares Weighted- average grant date fair value Nonvested shares at December 31, 2016 174,876 $ 5.78 Shares canceled (3,107 ) $ 1.15 Shares vested (70,935 ) $ 3.60 Nonvested shares at December 31, 2017 100,834 $ 7.45 Shares canceled (25,000 ) $ 7.50 Shares vested (75,834 ) $ 7.44 Nonvested shares at December 31, 2018 — Number Weighted- Nonvested shares at December 31, 2016 76,933 $ 49.90 Shares granted 713,400 $ 63.34 Shares canceled (55,457 ) $ 48.93 Shares vested (37,209 ) $ 55.77 Nonvested shares at December 31, 2017 697,667 $ 63.40 Shares granted 553,300 $ 54.29 Shares canceled (123,656 ) $ 60.75 Shares vested (184,535 ) $ 61.87 Nonvested shares at December 31, 2018 942,776 $ 58.71

Stock incentive plans (Tables)

Stock incentive plans (Tables)	12 Months Ended
	Dec. 31, 2018
Disclosure of Compensation Related Costs, Share-based Payments [Abstract]
Schedule of Stock-based Compensation Expense	Stock-based compensation expense by award type was as follows (in thousands): Year ended December 31, 2016 2017 2018 Stock options $ 22,377 $ 28,001 $ 29,674 Restricted stock 632 8,452 16,141 Employee stock purchase plan 178 438 610 $ 23,187 $ 36,891 $ 46,425
Summary of Stock Option Activity	The following table summarizes stock option activity: Number of shares Weighted- average exercise price Aggregate intrinsic value(a) Outstanding at December 31, 2016 4,181,993 $ 33.25 Granted 701,300 $ 56.78 Exercised (953,253 ) $ 21.75 Forfeited (407,166 ) $ 41.30 Outstanding at December 31, 2017 3,522,874 $ 40.11 Granted 671,500 $ 52.02 Exercised (453,905 ) $ 33.34 Forfeited (253,093 ) $ 52.32 Outstanding at December 31, 2018 3,487,376 $ 42.40 Vested at December 31, 2018 1,934,833 $ 35.17 $ 25,798,486 Vested at December 31, 2018 and expected to vest 3,315,852 $ 41.92 $ 26,194,775 (a) The aggregate intrinsic value is calculated as the difference between the exercise price of the underlying options and the fair value of the common stock that were in the money at December 31, 2018
Summary of Weighted-Average Assumptions	The weighted-average grant date fair value of the options granted in 2016 , 2017 and 2018 was $28.56 , $39.27 and $35.14 per share, respectively, using the Black-Scholes option-pricing model with the following weighted-average assumptions: Years Ended December 31, 2016 2017 2018 Expected volatility 75.2 % 78.1 % 75.7 % Risk-free interest rate 1.71 % 2.06 % 2.50 % Expected term (in years) 5.95 6.10 6.21 Expected dividend yield 0.0 % 0.0 % 0.0 %
Summary of Restricted Common Stock Activity	The following table summarizes restricted stock activity for the instruments discussed above: Number of shares Weighted- average grant date fair value Nonvested shares at December 31, 2016 174,876 $ 5.78 Shares canceled (3,107 ) $ 1.15 Shares vested (70,935 ) $ 3.60 Nonvested shares at December 31, 2017 100,834 $ 7.45 Shares canceled (25,000 ) $ 7.50 Shares vested (75,834 ) $ 7.44 Nonvested shares at December 31, 2018 — Number Weighted- Nonvested shares at December 31, 2016 76,933 $ 49.90 Shares granted 713,400 $ 63.34 Shares canceled (55,457 ) $ 48.93 Shares vested (37,209 ) $ 55.77 Nonvested shares at December 31, 2017 697,667 $ 63.40 Shares granted 553,300 $ 54.29 Shares canceled (123,656 ) $ 60.75 Shares vested (184,535 ) $ 61.87 Nonvested shares at December 31, 2018 942,776 $ 58.71

Commitments and contingencies (

Commitments and contingencies (Tables)	12 Months Ended
	Dec. 31, 2018
Commitments and Contingencies Disclosure [Abstract]
Reconciliation of Lease Termination Costs	The following table reconciles the termination cost discussed above (in thousands): Balance as of December 31, 2017 Recognized during the year Balance as of December 31, 2018 Contract termination liability $6,827 $1,557 $5,270
Schedule of Future Minimum Rental Payments for Operating Leases	Future minimum lease payments under these leases are as follows (in thousands): Year Ending December 31, 2019 $ 8,102 2020 11,044 2021 10,073 2022 10,156 2023 9,228 2024 and thereafter 78,079 $ 126,682

Income taxes (Tables)

Income taxes (Tables)	12 Months Ended
	Dec. 31, 2018
Income Tax Disclosure [Abstract]
Schedule of Loss Before Income Taxes Attributable to Domestic and International Operations	Income (loss) before income taxes attributable to domestic and international operations, consists of the following (in thousands): Year Ended December 31, 2016 2017 2018 Domestic $ (122,810 ) $ (239,301 ) $ (78,956 ) Foreign (843 ) (15,144 ) 233 Loss before income taxes $ (123,653 ) $ (254,445 ) $ (78,723 )
Schedule of Components of Income Tax Expense (Benefit)	Income tax expense (benefit) consists of the following (in thousands): Year Ended December 31, 2016 2017 2018 Current tax: Domestic $ — $ — $ — Foreign — 110 99 Deferred tax: Domestic — — — Foreign — (1,073 ) — Total income tax benefit (expense) $ — $ (963 ) $ 99
Schedule of Effective Income Tax Rate Reconciliation	A reconciliation of income tax benefit computed at the statutory federal income tax rate to income taxes as reflected in the consolidated financial statements is as follows: Year Ended December 31, 2016 2017 2018 Federal income tax benefit at statutory rate 34.0 % 34.0 % 21.0 % State and local tax, net of federal benefit 10.4 10.3 7.5 Permanent differences 3.1 (0.3 ) 3.6 Tax credits 9.1 9.2 17.7 Tax Cuts and Jobs Act impact — (17.6 ) (0.6 ) Foreign rate differential (0.1 ) (1.3 ) — Change in valuation allowance (56.5 ) (33.9 ) (42.9 ) Change in tax reserve — — (5.5 ) Other — — (0.9 ) Effective income tax rate — % 0.4 % (0.1 )%
Schedule of Deferred Tax Assets	The significant components of the Company’s deferred tax assets are comprised of the following (in thousands): December 31, 2017 2018 Deferred tax assets (liabilities): Net operating loss carryforwards $ 114,152 $ 127,012 Tax credit carryforwards 51,586 60,174 Stock-based compensation 14,644 20,475 Deferred rent 4,697 1,149 Deferred revenue 956 — Accruals and other 8,998 17,151 Fixed assets — 1,875 Total deferred tax assets 195,033 227,836 Less valuation allowance (193,796 ) (227,836 ) Net deferred tax assets $ 1,237 $ — Fixed assets (1,237 ) — Total deferred tax liabilities $ (1,237 ) $ — Net deferred tax asset $ — $ —
Schedule of Unrecognized Tax Benefits	A reconciliation of the beginning and ending amounts of gross unrecognized tax benefits is as follows (in thousands): December 31, 2018 Gross unrecognized tax benefits at January 1 $ — Increases related to prior year tax positions 3,858 Increases related to current year tax positions 483 Gross unrecognized tax benefits at December 31 $ 4,341

Selected quarterly financial _2

Selected quarterly financial data (unaudited) (Tables)	12 Months Ended
	Dec. 31, 2018
Quarterly Financial Information Disclosure [Abstract]
Schedule of quarterly financial information	The following table contains quarterly financial information for 2017 and 2018 (in thousands). The Company believes that the following information reflects all normal recurring adjustments necessary for a fair presentation of the information for the periods presented. The operating results for any quarter are not necessarily indicative of results for any future period. 2017 First quarter Second quarter Third quarter Fourth quarter Revenues $ 1,274 $ 1,483 $ 1,900 $ 7,409 Research and development 32,348 32,989 39,342 30,481 Acquired in-process research and development 387 3,070 1,750 3,397 Impairment of acquired in-process research and development — 15,696 — — Selling, general and administrative 21,414 26,729 26,640 36,341 Total operating expenses 54,149 78,484 67,732 70,219 Loss from operations (52,875 ) (77,001 ) (65,832 ) (62,810 ) Net loss $ (52,289 ) $ (74,360 ) $ (65,012 ) $ (61,821 ) Basic and diluted net loss per common share $ (1.70 ) $ (2.40 ) $ (1.90 ) $ (1.68 ) 2018 First Second quarter Third quarter Fourth quarter Revenues $ 15,676 $ 25,185 $ 10,707 $ 13,157 Cost of goods sold 990 4,511 318 2,096 Research and development 30,109 25,524 32,829 36,792 Acquired in-process research and development — — — 300 Selling, general and administrative 33,489 29,749 29,305 32,352 Total operating expenses 64,588 59,784 62,452 71,540 Loss from operations (48,912 ) (34,599 ) (51,745 ) (58,383 ) Net (loss) income $ (46,373 ) $ 80,165 $ (47,357 ) $ (65,257 ) Basic net (loss) income per common share $ (1.25 ) $ 2.15 $ (1.26 ) $ (1.73 ) Diluted net (loss) income per common share $ (1.25 ) $ 2.07 $ (1.26 ) $ (1.73 )

Background - Additional informa

Background - Additional information (Details)	12 Months Ended
	Dec. 31, 2018segment
Accounting Policies [Abstract]
Number of operating segments	1

Development-stage risks - Addit

Development-stage risks - Additional information (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Development-stage Risk [Abstract]
Accumulated deficit	$ 589,687	$ 505,863

Summary of significant accoun_4

Summary of significant accounting policies - Additional information (Details)	12 Months Ended	70 Months Ended
	Dec. 31, 2018distribution_model	Dec. 31, 2018USD ($)distribution_model	Jan. 01, 2019USD ($)	Jan. 01, 2018USD ($)
Property, Plant and Equipment [Line Items]
Impairment charges of long-lived assets		$ 0
Number of distribution models | distribution_model	2	2
Reclassification of unrealized loss on equity investment to accumulated deficit				$ 0
Computers [Member]
Property, Plant and Equipment [Line Items]
Property and equipment useful life	3 years
Software [Member]
Property, Plant and Equipment [Line Items]
Property and equipment useful life	3 years
Laboratory and Office Equipment [Member]
Property, Plant and Equipment [Line Items]
Property and equipment useful life	5 years
Furniture [Member]
Property, Plant and Equipment [Line Items]
Property and equipment useful life	7 years
Subsequent event [Member] | Scenario, Forecast [Member] | Minimum [Member] | ASU 2016-02 [Member]
Property, Plant and Equipment [Line Items]
Right of use assets			$ 40,000,000
Lease liabilities			40,000,000
Subsequent event [Member] | Scenario, Forecast [Member] | Maximum [Member] | ASU 2016-02 [Member]
Property, Plant and Equipment [Line Items]
Right of use assets			50,000,000
Lease liabilities			$ 50,000,000
Accumulated other comprehensive loss [Member]
Property, Plant and Equipment [Line Items]
Reclassification of unrealized loss on equity investment to accumulated deficit				5,002,000
Accumulated other comprehensive loss [Member] | ASU 2016-01 [Member]
Property, Plant and Equipment [Line Items]
Reclassification of unrealized loss on equity investment to accumulated deficit				5,000,000
Accumulated deficit [Member]
Property, Plant and Equipment [Line Items]
Reclassification of unrealized loss on equity investment to accumulated deficit				(5,002,000)
Accumulated deficit [Member] | ASU 2016-01 [Member]
Property, Plant and Equipment [Line Items]
Reclassification of unrealized loss on equity investment to accumulated deficit				$ (5,000,000)

Summary of significant accoun_5

Summary of significant accounting policies - Schedule of antidilutive securities excluded from computation of diluted weighted average shares outstanding (Details) - shares	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Unvested restricted common shares [Member]
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Antidilutive securities excluded from computation of diluted weighted average shares outstanding	942,776	798,501	251,809
Options issued and outstanding [Member]
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Antidilutive securities excluded from computation of diluted weighted average shares outstanding	3,487,376	3,522,874	4,181,993

Summary of significant accoun_6

Summary of significant accounting policies - Accumulated other comprehensive loss (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Jan. 01, 2018
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Beginning balance	$ 513,624
Reclassification of unrealized loss on equity investment to accumulated deficit		$ 0
Ending balance	496,513
Net unrealized (loss) gain on available-for-sale securities
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Beginning balance	(5,964)
Reclassification of unrealized loss on equity investment to accumulated deficit		5,002
Current period other comprehensive income (loss)	586
Ending balance	(376)
Unrealized loss on interest rate swap
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Beginning balance	0
Reclassification of unrealized loss on equity investment to accumulated deficit		0
Current period other comprehensive income (loss)	(641)
Ending balance	(641)
Foreign currency translation adjustments
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Beginning balance	50
Reclassification of unrealized loss on equity investment to accumulated deficit		0
Current period other comprehensive income (loss)	(83)
Ending balance	(33)
Accumulated other comprehensive loss
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Beginning balance	(5,914)
Reclassification of unrealized loss on equity investment to accumulated deficit		$ 5,002
Current period other comprehensive income (loss)	(138)
Ending balance	$ (1,050)

Marketable securities - Schedul

Marketable securities - Schedule of available-for-sale securities (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
U.S. government agencies [Member]
Debt Securities, Available-for-sale [Line Items]
Amortized cost	$ 223,553	$ 222,180
Unrealized gains	54	0
Unrealized losses	(123)	(641)
Fair value	223,484	221,539
Corporate securities [Member]
Debt Securities, Available-for-sale [Line Items]
Amortized cost	239,940	227,238
Unrealized gains	34	0
Unrealized losses	(10,421)	(5,323)
Fair value	$ 229,553	$ 221,915

Fair value of financial instr_3

Fair value of financial instruments - Summary of assets and liabilities measured at fair value on recurring basis (Details) - Fair Value Measurements Recurring [Member] - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Money market funds [Member] | Quoted prices in active markets for identical assets (Level 1) [Member]
Assets:
Money market funds/Corporate securities (included in cash and cash equivalents)	$ 94,216	$ 90,348
Money market funds [Member] | Significant other observable inputs (Level 2) [Member]
Assets:
Money market funds/Corporate securities (included in cash and cash equivalents)	0	0
Money market funds [Member] | Significant unobservable inputs (Level 3) [Member]
Assets:
Money market funds/Corporate securities (included in cash and cash equivalents)	0	0
Certificates of deposit [Member] | Quoted prices in active markets for identical assets (Level 1) [Member]
Assets:
Certificates of deposit - restricted cash	53,000
Certificates of deposit [Member] | Significant other observable inputs (Level 2) [Member]
Assets:
Certificates of deposit - restricted cash	0
Certificates of deposit [Member] | Significant unobservable inputs (Level 3) [Member]
Assets:
Certificates of deposit - restricted cash	0
Corporate securities [Member] | Quoted prices in active markets for identical assets (Level 1) [Member]
Assets:
Money market funds/Corporate securities (included in cash and cash equivalents)		5,548
Marketable securities	229,553	220,020
Corporate securities [Member] | Significant other observable inputs (Level 2) [Member]
Assets:
Money market funds/Corporate securities (included in cash and cash equivalents)		0
Marketable securities	0	1,895
Corporate securities [Member] | Significant unobservable inputs (Level 3) [Member]
Assets:
Money market funds/Corporate securities (included in cash and cash equivalents)		0
Marketable securities	0	0
U.S. government agencies [Member] | Quoted prices in active markets for identical assets (Level 1) [Member]
Assets:
Marketable securities	223,484	221,539
U.S. government agencies [Member] | Significant other observable inputs (Level 2) [Member]
Assets:
Marketable securities	0	0
U.S. government agencies [Member] | Significant unobservable inputs (Level 3) [Member]
Assets:
Marketable securities	$ 0	$ 0

Inventory (Details)

Inventory (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Inventory Disclosure [Abstract]
Raw materials	$ 3,843
Work in process	19,843
Finished goods	1,951
Inventory	$ 25,637	$ 0

Sale of priority review vouch_2

Sale of priority review voucher Sale of priority review voucher (Details) - USD ($) $ in Thousands	1 Months Ended	12 Months Ended
	May 31, 2018	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Goodwill and Intangible Assets Disclosure [Abstract]
Proceeds from sale of priority review voucher	$ 110,000	$ 110,000	$ 0	$ 0

Business acquisition of Genab_3

Business acquisition of Genable and impairment of acquired in-process research and development - Additional information (Details)	Mar. 07, 2016USD ($)shares	Dec. 31, 2018USD ($)reporting_unit	Dec. 31, 2017USD ($)	Dec. 31, 2016USD ($)
Business Acquisition [Line Items]
Impairment of acquired in-process research and development		$ 0	$ 15,696,000	$ 0
Non-cash income tax benefit			1,000,000
Number of reporting units | reporting_unit		1
Impairment of goodwill		$ 0	$ 0	$ 0
Genable [Member]
Business Acquisition [Line Items]
Consideration paid	$ 6,100,000
Fair value of shares issued for consideration	9,200,000
Consideration transferred	15,300,000
Acquisition related costs	$ 300,000
Common stock [Member] | Genable [Member]
Business Acquisition [Line Items]
Shares issued for consideration (in shares) | shares	265,000
Genable [Member] | Genable [Member]
Business Acquisition [Line Items]
Receivables due from acquisition	$ 500,000
In-process research and development [Member] | Genable [Member]
Business Acquisition [Line Items]
Acquired in-process research and development	$ 15,500,000

Business acquisition of Genab_4

Business acquisition of Genable and impairment of acquired in-process research and development - Allocation of purchase price (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017	Mar. 07, 2016
Business Acquisition [Line Items]
Goodwill	$ 1,198	$ 1,254
Genable [Member]
Business Acquisition [Line Items]
Cash acquired			$ 196
Other current assets			103
Acquired in-process research and development			15,490
Goodwill			1,160
Total assets assumed			16,949
Other non-current liabilities			255
Deferred tax liability			1,000
Total liabilities assumed			1,255
Total allocation of purchase price			$ 15,694

Property and equipment, net - S

Property and equipment, net - Schedule of property and equipment, net (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Property, Plant and Equipment [Line Items]
Property and equipment, gross	$ 112,202	$ 72,035
Less accumulated depreciation and amortization	(16,204)	(10,322)
Property and equipment, net	95,998	61,713
Depreciation and amortization expense	6,918	4,860	$ 3,600
Laboratory Equipment [Member]
Property, Plant and Equipment [Line Items]
Property and equipment, gross	8,272	6,381
Computer and Software [Member]
Property, Plant and Equipment [Line Items]
Property and equipment, gross	2,773	1,325
Furniture & Fixtures [Member]
Property, Plant and Equipment [Line Items]
Property and equipment, gross	2,564	1,770
Office Equipment [Member]
Property, Plant and Equipment [Line Items]
Property and equipment, gross	1,394	726
Leasehold Improvements [Member]
Property, Plant and Equipment [Line Items]
Property and equipment, gross	54,541	23,653
Construction in Progress [Member]
Property, Plant and Equipment [Line Items]
Property and equipment, gross	7,869	3,187
One Drexel Plaza Research Facility [Member]
Property, Plant and Equipment [Line Items]
Construction in progress		35,000
One Drexel Plaza Research Facility [Member] | Built-to-suit [Member]
Property, Plant and Equipment [Line Items]
Property and equipment, gross	$ 34,789	$ 34,993

Accrued expenses - Schedule of

Accrued expenses - Schedule of accrued expenses (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Payables and Accruals [Abstract]
Compensation and benefits	$ 15,575	$ 15,012
Consulting and professional fees	13,904	4,846
Research and development	2,706	2,809
Other	2,605	2,030
Accrued expenses	$ 34,790	$ 24,697

Debt - Schedule of Debt (Detail

Debt - Schedule of Debt (Details) - USD ($) $ in Thousands	1 Months Ended
	Aug. 31, 2016	Dec. 31, 2018	Dec. 31, 2017
Debt Instrument [Line Items]
Less: current portion of long-term debt		$ (4,822)	$ (312)
Total long-term debt due after one year		46,090	912
Secured Debt [Member] | Term Loan [Member]
Debt Instrument [Line Items]
Loan amount		50,000	0
Secured Debt [Member] | MELF Loan [Member]
Debt Instrument [Line Items]
Debt term	5 years
Loan amount		$ 912	$ 1,224

Debt - Additional Information (

Debt - Additional Information (Details) - USD ($)	Jul. 03, 2018	Aug. 31, 2016	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Line of Credit Facility [Line Items]
Effective portion of interest rate expected to be reclassified from AOCL into interest expense over next 12 months			$ 600,000
Proceeds from long-term debt			50,000,000	$ 0	$ 1,550,000
Secured Debt [Member] | Term Loan [Member]
Line of Credit Facility [Line Items]
Amount extended under term loan	$ 50,000,000
Debt interest expense			700,000
Secured Debt [Member] | MELF Loan [Member]
Line of Credit Facility [Line Items]
Debt interest expense			34,000	$ 48,000	$ 15,000
Debt term		5 years
Principle and interest payment		$ 29,000
Stated percentage rate		3.25%
Proceeds from long-term debt		$ 1,600,000
London Interbank Offered Rate (LIBOR) [Member] | Secured Debt [Member] | Term Loan [Member]
Line of Credit Facility [Line Items]
Basis spread on variable rate	0.65%
Swap agreement [Member] | Term Loan [Member]
Line of Credit Facility [Line Items]
Fixed rate per annum under swap	3.463%
Designated as Hedging Instrument [Member] | Swap agreement [Member]
Line of Credit Facility [Line Items]
Notional amount	$ 50,000,000
Derivative liability			600,000
Cash Flow Hedging [Member] | Designated as Hedging Instrument [Member] | Swap agreement [Member]
Line of Credit Facility [Line Items]
Amount reclassified from AOCL into interest expense			200,000
Other current liabilities [Member] | Designated as Hedging Instrument [Member] | Swap agreement [Member]
Line of Credit Facility [Line Items]
Derivative liability			100,000
Other long-term liabilities [Member] | Designated as Hedging Instrument [Member] | Swap agreement [Member]
Line of Credit Facility [Line Items]
Derivative liability			$ 500,000

Stockholders' equity - Addition

Stockholders' equity - Additional information (Details) - USD ($) $ / shares in Units, $ in Thousands	Aug. 09, 2017	Jun. 20, 2016	Dec. 31, 2014	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2014	Dec. 31, 2018
Class of Stock [Line Items]
Common stock, shares authorized (in shares)				150,000,000	150,000,000			150,000,000
Preferred stock, shares authorized (in shares)				5,000,000	5,000,000			5,000,000
Compensation expense				$ 46,425	$ 36,891	$ 23,187
General and administrative expense [Member]
Class of Stock [Line Items]
Compensation expense				28,400	21,800	13,600
Research and development expense [Member]
Class of Stock [Line Items]
Compensation expense				$ 18,000	$ 15,100	9,600
Common stock [Member] | Tranche One [Member]
Class of Stock [Line Items]
Percentage of vesting of units on first anniversary				25.00%
Common stock [Member] | Tranche Two [Member]
Class of Stock [Line Items]
Units, vesting period				3 years
License agreement [Member] | University of Pennsylvania [Member]
Class of Stock [Line Items]
Issuance of restricted stock in connection with license agreement (in shares)			200,000				200,000
Shares vested (in shares)								175,000
Restricted shares [Member]
Class of Stock [Line Items]
Shares vested (in shares)				75,834	70,935
Restricted shares [Member] | General and administrative expense [Member]
Class of Stock [Line Items]
Compensation expense					$ 34	100
Restricted shares [Member] | Research and development expense [Member]
Class of Stock [Line Items]
Compensation expense				$ 2,200	$ 4,400	$ 1,300
Public stock offering [Member] | Common stock [Member]
Class of Stock [Line Items]
Number of shares issued (in shares)	5,296,053	3,025,000
Shares issuance price per share (in dollars per share)	$ 76	$ 45
Proceeds from follow-on public offering	$ 402,500	$ 136,100
Net proceeds from sale of stock	$ 379,900	$ 127,600

Stockholders' equity - Summary

Stockholders' equity - Summary of restricted stock activity (Details) - Restricted shares [Member] - $ / shares	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017
Number of shares (in shares):
Nonvested beginning balance (in shares)	100,834	174,876
Shares canceled (in shares)	(25,000)	(3,107)
Shares vested (in shares)	(75,834)	(70,935)
Nonvested ending balance (in shares)	0	100,834
Weighted-average grant date fair value (in dollars per share):
Nonvested shares beginning balance (in usd per share)	$ 7.45	$ 5.78
Shares canceled (in dollars per share)	7.50	1.15
Shares vested (in usd per share)	7.44	3.60
Nonvested shares ending balance (in usd per share)		$ 7.45

Stock incentive plans - Additio

Stock incentive plans - Additional information (Details) - USD ($) $ / shares in Units, $ in Thousands	1 Months Ended	12 Months Ended
	Jan. 31, 2018	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Compensation expense		$ 46,425	$ 36,891	$ 23,187
Weighted average remaining contractual term of options outstanding		7 years 2 months 12 days
Weighted average remaining contractual term of options exercisable		6 years 4 months 24 days
Weighted average grant date fair value of options (in usd per share)		$ 35.14	$ 39.27	$ 28.56
Unrecognized compensation expense related to the performance-based restricted common stock		$ 0
Research and development expense [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Compensation expense		18,000	$ 15,100	$ 9,600
General and administrative expense [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Compensation expense		28,400	21,800	13,600
ESPP [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Compensation expense		610	$ 438	178
Unrecognized compensation expense related to the performance-based restricted common stock		$ 300
Purchase of common stock under ESPP (in shares)		30,814	11,804
Stock options [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Compensation expense		$ 29,674	$ 28,001	22,377
Unrecognized compensation expense related to stock options		$ 42,200
Weighted average period recognition for unrecognized compensation expense		2 years 2 months 12 days
Intrinsic value of options exercised		$ 16,600	45,900
Restricted stock [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Compensation expense		$ 16,141	$ 8,452	$ 632
Weighted average period recognition for unrecognized compensation expense		2 years 9 months 18 days
Unrecognized compensation expense related to the performance-based restricted common stock		$ 43,100
2015 Stock Incentive Plan [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares automatically increased (in shares)	1,485,322
Common stock reserved for issuance (in shares)		1,422,190
2015 Employee Stock Purchase Plan [Member] | ESPP [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares automatically increased (in shares)	371,330
Common stock reserved for issuance (in shares)		1,120,188

Stock incentive plans - Compens

Stock incentive plans - Compensation expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Compensation expense	$ 46,425	$ 36,891	$ 23,187
Stock options [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Compensation expense	29,674	28,001	22,377
Restricted stock [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Compensation expense	16,141	8,452	632
ESPP [Member]
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Compensation expense	$ 610	$ 438	$ 178

Stock incentive plans - Summary

Stock incentive plans - Summary of stock option activity (Details) - USD ($)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017
Number of shares
Outstanding beginning balance (in shares)	3,522,874	4,181,993
Granted (in shares)	671,500	701,300
Exercised (in shares)	(453,905)	(953,253)
Forfeited (in shares)	(253,093)	(407,166)
Outstanding ending balance (in shares)	3,487,376	3,522,874
Vested, outstanding (in shares)	1,934,833
Vested and expected to vest, outstanding (in shares)	3,315,852
Weighted-average exercise price
Outstanding beginning balance (in usd per share)	$ 40.11	$ 33.25
Granted (in usd per share)	52.02	56.78
Exercised (in usd per share)	33.34	21.75
Forfeited (in usd per share)	52.32	41.30
Outstanding ending balance (in usd per share)	42.40	$ 40.11
Vested, outstanding, weighted-average exercise price (in usd per share)	35.17
Vested and expected to vest, outstanding, weighted-average exercise price (in usd per share)	$ 41.92
Vested, outstanding, aggregate intrinsic value	$ 25,798,486
Vested and expected to vest, outstanding, aggregate intrinsic value	$ 26,194,775

Stock incentive plans - Summa_2

Stock incentive plans - Summary of weighted-average assumptions (Details) - Stock options [Member]	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Expected volatility	75.70%	78.10%	75.20%
Risk-free interest rate	2.50%	2.06%	1.71%
Expected term	6 years 2 months 15 days	6 years 1 month 6 days	5 years 11 months 12 days
Expected dividend yield	0.00%	0.00%	0.00%

Stock incentive plans - Summa_3

Stock incentive plans - Summary of restricted common stock activity (Details) - Restricted stock [Member] - $ / shares	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017
Number of shares (in shares):
Nonvested beginning balance (in shares)	697,667	76,933
Shares granted (in shares)	553,300	713,400
Shares canceled (in shares)	(123,656)	(55,457)
Shares vested (in shares)	(184,535)	(37,209)
Nonvested ending balance (in shares)	942,776	697,667
Weighted-average grant date fair value (in dollars per share):
Nonvested shares beginning balance (in usd per share)	$ 63.40	$ 49.90
Shares granted (in usd per share)	54.29	63.34
Shares canceled (in dollars per share)	60.75	48.93
Shares vested (in usd per share)	61.87	55.77
Nonvested shares ending balance (in usd per share)	$ 58.71	$ 63.40

Commitments and contingencies -

Commitments and contingencies - Additional information (Details) $ in Thousands

1 Months Ended

12 Months Ended

Aug. 31, 2018USD ($)

Nov. 30, 2017USD ($)ft²

Nov. 30, 2016USD ($)ft²

Dec. 31, 2014USD ($)shares

Dec. 31, 2018USD ($)

Dec. 31, 2017USD ($)

Dec. 31, 2016USD ($)

Dec. 31, 2014USD ($)shares

May 31, 2018ft²

Nov. 20, 2017ft²

Jan. 31, 2017ft²

Feb. 29, 2016ft²

Nov. 30, 2015ft²

Property Subject to or Available for Operating Lease [Line Items]

Long-term other liabilities

$ 38,510

$ 40,255

Current other liabilities

1,885

1,557

Reconciliation Of Termination Cost [Roll Forward]

Contractual obligation

34,500

35,000

Rent expense

3,900

10,500

$ 1,900

Capital Leases, Future Minimum Payments Due, Fiscal Year Maturity [Abstract]

2,019

8,102

2,020

11,044

2,021

10,073

2,022

10,156

2,023

9,228

2024 and thereafter

78,079

Total

126,682

University of Pennsylvania [Member] | License agreement [Member]

Reconciliation Of Termination Cost [Roll Forward]

Issuance of restricted stock in connection with license agreement (in shares) | shares

200,000

200,000

Lease of Laboratory and Office Space [Member]

Property Subject to or Available for Operating Lease [Line Items]

Allowance for leasehold improvements

$ 8,000

Lease of office space [Member]

Property Subject to or Available for Operating Lease [Line Items]

Loss on contract termination

$ 6,900

Long-term other liabilities

3,500

Current other liabilities

1,800

Reconciliation Of Termination Cost [Roll Forward]

Balance as of December 31, 2017

6,827

Recognized during the year

1,557

Balance as of December 31, 2018

5,270

6,827

Lease of office space [Member] | Corporate HQ [Member]

Property Subject to or Available for Operating Lease [Line Items]

Area of real estate property (in sq ft) | ft²

49,000

24,800

6,500

Terminated lease property (in sq ft) | ft²

50,000

Lease of office space [Member] | Philadelphia property [Member]

Property Subject to or Available for Operating Lease [Line Items]

Allowance for leasehold improvements

100

Area of real estate property (in sq ft) | ft²

14,000

Sublease of office space [Member] | Corporate HQ [Member]

Property Subject to or Available for Operating Lease [Line Items]

Allowance for leasehold improvements

$ 1,600

Area of real estate property (in sq ft) | ft²

14,000

One Drexel Plaza Research Facility [Member]

Property Subject to or Available for Operating Lease [Line Items]

Allowance for leasehold improvements

$ 3,900

Area of real estate property (in sq ft) | ft²

108,000

Reconciliation Of Termination Cost [Roll Forward]

Construction in progress

$ 35,000

Leased asset under construction, useful life

15 years 6 months

Maximum [Member] | Milestone payments [Member] | University of Pennsylvania [Member] | License agreement [Member]

Reconciliation Of Termination Cost [Roll Forward]

Agreement obligation, milestone payments

$ 5,500

$ 5,500

Brammer Bio Agreement [Member]

Reconciliation Of Termination Cost [Roll Forward]

Product and supply manufacturing renewal term

3 years

Product manufacturing and supply, period prior to renewal term expiration to cancel renewal

2 years

Upfront payment included in prepaid asset

$ 4,000

Related-party transactions - Ad

Related-party transactions - Additional information (Details) - CHOP [Member] - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Related Party Transaction [Line Items]
Accrued expenses due to related party	$ 0.7	$ 0.3
Accounts payable due to related party	0.5	1.4
Master Research Services Agreement [Member]
Related Party Transaction [Line Items]
Research and development expense related to agreements	5.7	6.1	$ 7.4
Technology and License Agreement [Member]
Related Party Transaction [Line Items]
Reimbursement of patent costs	$ 1.2	$ 0.8	$ 0.9

Collaboration and license agr_2

Collaboration and license agreements Collaboration and license agreements - Pfizer (Details) - USD ($)

1 Months Ended

3 Months Ended

11 Months Ended

12 Months Ended

Jul. 31, 2018

Feb. 28, 2018

Nov. 30, 2017

Dec. 31, 2014

Dec. 31, 2018

Sep. 30, 2018

Jun. 30, 2018

Mar. 31, 2018

Dec. 31, 2017

Sep. 30, 2017

Jun. 30, 2017

Mar. 31, 2017

Dec. 31, 2018

Dec. 31, 2018

Dec. 31, 2017

Dec. 31, 2016

Dec. 31, 2014

Research and Development Arrangement, Contract to Perform for Others [Line Items]

Additional revenue potential to be earned

$ 230,000,000

Total revenues

$ 13,157,000

$ 10,707,000

$ 25,185,000

$ 15,676,000

$ 7,409,000

$ 1,900,000

$ 1,483,000

$ 1,274,000

64,725,000

$ 12,066,000

$ 20,183,000

Pfizer collaboration and license agreement [Member]

Research and Development Arrangement, Contract to Perform for Others [Line Items]

Research and development expense related to agreements

$ 10,600,000

Upfront payment received for license

$ 7,000,000

$ 7,000,000

$ 15,000,000

$ 20,000,000

$ 14,000,000

Revenue recognition from aggregate milestone payments

10,000,000

$ 110,000,000

Deferred revenue

$ 25,000,000

Collaboration agreement expiration, period

15 years

Collaborative Arrangement, License Revenue

12,100,000

20,200,000

Additional product candidates [Member]

Research and Development Arrangement, Contract to Perform for Others [Line Items]

Additional revenue potential to be earned

$ 120,000,000

Contract Revenue [Member]

Research and Development Arrangement, Contract to Perform for Others [Line Items]

Total revenues

37,752,000

12,066,000

20,183,000

Contract Revenue [Member] | Pfizer collaboration and license agreement [Member]

Research and Development Arrangement, Contract to Perform for Others [Line Items]

Total revenues

36,000,000

Research and development expense [Member] | Pfizer collaboration and license agreement [Member]

Research and Development Arrangement, Contract to Perform for Others [Line Items]

Total revenues

$ 3,000,000

Collaborative Arrangement, Reimbursement Revenue

$ 2,900,000

$ 2,400,000

Collaboration and license agr_3

Collaboration and license agreements Collaboration and license agreements - Novartis (Details) - USD ($) $ in Millions	3 Months Ended		12 Months Ended
	Dec. 31, 2018	Mar. 31, 2018	Dec. 31, 2018
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Additional revenue potential to be earned			$ 230
Novartis Licensing And Commercialization Agreement [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Upfront payment received for license		$ 105
Additional revenue potential to be earned	$ 25	$ 65
Deferred revenue	105		105
Additional variable consideration not constrained	$ 30
License fees and milestone payments not constrained			160
Remaining milestone payments constrained			$ 10

Collaboration and license agr_4

Collaboration and license agreements Collaboration and license agreements - Selecta (Details) $ in Thousands	1 Months Ended			5 Months Ended	12 Months Ended
	Oct. 31, 2017USD ($)shares	Jun. 30, 2017USD ($)shares	Dec. 31, 2016USD ($)targetshares	Oct. 31, 2017USD ($)shares	Dec. 31, 2018USD ($)	Dec. 31, 2017USD ($)	Dec. 31, 2016USD ($)shares
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Purchase of acquired in-process research and development					$ 300	$ 8,217	$ 11,132
Selecta license agreement [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Prepaid expense, current			$ 10,000	$ 5,000
Shares purchased (in shares) | shares	205,254	324,362	197,238	205,254			197,238
Investment shares purchased, amount	$ 5,000	$ 5,000	$ 5,000
Payments to acquire project	7,500	7,500	15,000
Purchase of acquired in-process research and development	3,400	3,100	11,500
Development and regulatory milestone [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Milestone payments			$ 65,000
Collaboration agreement expiration, period			90 days
Commercial milestone [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Milestone payments			$ 365,000
Minimum [Member] | Selecta license agreement [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Number of additional licensing targets | target			4
Option exercise fees			$ 1,400
Maximum [Member] | Selecta license agreement [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Option exercise fees			2,000
Milestone payments			$ 430,000
Milestone payment, rights to fund percentage			50.00%
Common stock [Member] | Selecta license agreement [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Payments to acquire project	4,100	4,400	$ 3,500
Licensing agreements [Member] | Selecta license agreement [Member]
Research and Development Arrangement, Contract to Perform for Others [Line Items]
Payments to acquire project	$ 3,400	$ 3,100	$ 11,500

Income taxes - Narrative (Detai

Income taxes - Narrative (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017
Operating Loss Carryforwards [Line Items]
Tax Act, provisional impact of tax reform from revaluation of deferred taxes	$ 0.5
Valuation allowance changes	34	$ 86.2
Domestic Tax Authority [Member]
Operating Loss Carryforwards [Line Items]
Operating loss carryforwards	318.3
State and Local Jurisdiction [Member]
Operating Loss Carryforwards [Line Items]
Operating loss carryforwards	376.4
Foreign Tax Authority [Member]
Operating Loss Carryforwards [Line Items]
Operating loss carryforwards	8.6
Research Tax Credit Carryforward [Member] | Domestic Tax Authority [Member]
Operating Loss Carryforwards [Line Items]
Tax credit carryforward, amount	7.5
Orphan Drug Tax Credit Carryforward [Member] | Domestic Tax Authority [Member]
Operating Loss Carryforwards [Line Items]
Tax credit carryforward, amount	52.7
Tax Year 2017 [Member] | Domestic Tax Authority [Member]
Operating Loss Carryforwards [Line Items]
Operating loss carryforwards	$ 58.3

Income taxes - Loss from domest

Income taxes - Loss from domestic and foreign operations (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Income Tax Disclosure [Abstract]
Domestic	$ (78,956)	$ (239,301)	$ (122,810)
Foreign	233	(15,144)	(843)
Loss before income taxes	$ (78,723)	$ (254,445)	$ (123,653)

Income taxes - Components of in

Income taxes - Components of income tax expense (benefit) (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Current tax:
Domestic	$ 0	$ 0	$ 0
Foreign	99	110	0
Deferred tax:
Domestic	0	0	0
Foreign	0	(1,073)	0
Total income tax benefit (expense)	$ 99	$ (963)	$ 0

Income taxes - Effective rate r

Income taxes - Effective rate reconciliation (Details)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Income Tax Disclosure [Abstract]
Federal income tax benefit at statutory rate	21.00%	34.00%	34.00%
State and local tax, net of federal benefit	7.50%	10.30%	10.40%
Permanent differences	3.60%	(0.30%)	3.10%
Tax credits	17.70%	9.20%	9.10%
Tax Cuts and Jobs Act impact	(0.60%)	(17.60%)	0.00%
Foreign rate differential	0.00%	(1.30%)	(0.10%)
Change in valuation allowance	(42.90%)	(33.90%)	(56.50%)
Change in tax reserve	(5.50%)	0.00%	0.00%
Other	(0.90%)	0.00%	0.00%
Effective income tax rate	(0.10%)	0.40%	0.00%

Income taxes - Deferred tax ass

Income taxes - Deferred tax assets (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Income Tax Disclosure [Abstract]
Net operating loss carryforwards	$ 127,012	$ 114,152
Tax credit carryforwards	60,174	51,586
Stock-based compensation	20,475	14,644
Deferred rent	1,149	4,697
Deferred revenue	0	956
Accruals and other	17,151	8,998
Fixed assets	1,875	0
Total deferred tax assets	227,836	195,033
Less valuation allowance	(227,836)	(193,796)
Net deferred tax assets	0	1,237
Fixed assets	0	(1,237)
Total deferred tax liabilities	0	(1,237)
Net deferred tax asset	$ 0	$ 0

Income taxes - Unrecognized tax

Income taxes - Unrecognized tax benefits (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2018USD ($)
Reconciliation of Unrecognized Tax Benefits, Excluding Amounts Pertaining to Examined Tax Returns [Roll Forward]
Gross unrecognized tax benefits at January 1	$ 0
Increases related to prior year tax positions	3,858
Increases related to current year tax positions	483
Gross unrecognized tax benefits at December 31	$ 4,341

Selected quarterly financial _3

Selected quarterly financial data (unaudited) (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2018	Sep. 30, 2018	Jun. 30, 2018	Mar. 31, 2018	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Quarterly Financial Information Disclosure [Abstract]
Revenues	$ 13,157	$ 10,707	$ 25,185	$ 15,676	$ 7,409	$ 1,900	$ 1,483	$ 1,274	$ 64,725	$ 12,066	$ 20,183
Cost of goods sold	2,096	318	4,511	990
Research and development	36,792	32,829	25,524	30,109	30,481	39,342	32,989	32,348	125,254	135,160	86,380
Acquired in-process research and development	300	0	0	0	3,397	1,750	3,070	387	300	8,604	11,132
Impairment of acquired in-process research and development					0	0	15,696	0	0	15,696	0
Selling, general and administrative	32,352	29,305	29,749	33,489	36,341	26,640	26,729	21,414	124,895	111,124	48,070
Total operating expenses	71,540	62,452	59,784	64,588	70,219	67,732	78,484	54,149	258,364	270,584	145,582
Loss from operations	(58,383)	(51,745)	(34,599)	(48,912)	(62,810)	(65,832)	(77,001)	(52,875)	(193,639)	(258,518)	(125,399)
Net loss	$ (65,257)	$ (47,357)	$ 80,165	$ (46,373)	$ (61,821)	$ (65,012)	$ (74,360)	$ (52,289)	$ (78,822)	$ (253,482)	$ (123,653)
Basic and diluted net loss per common share (in usd per share)					$ (1.68)	$ (1.90)	$ (2.40)	$ (1.70)	$ (2.11)	$ (7.63)	$ (4.29)
Basic net (loss) income per common share (in usd per share)	$ (1.73)	$ (1.26)	$ 2.15	$ (1.25)
Diluted net (loss) income per common share (in usd per share)	$ (1.73)	$ (1.26)	$ 2.07	$ (1.25)

Subsequent events - Additional

Subsequent events - Additional information (Details) - Roche Holdings, Inc. (Merger Sub) [Member] - Subsequent event [Member] $ / shares in Units, $ in Millions	Feb. 22, 2019USD ($)$ / shares
Subsequent Event [Line Items]
Merger agreement, share price | $ / shares	$ 114.50
Merger agreement, termination fee under specified circumstances | $	$ 144