0001439222-19-000004 | 10-K | XBRL Viewer | Agios Pharmaceuticals INC

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Document and Entity Information - USD ($)	12 Months Ended
Document and Entity Information - USD ($)	Dec. 31, 2018	Feb. 08, 2019	Jun. 29, 2018
Document And Entity Information [Abstract]
Entity Registrant Name	AGIOS PHARMACEUTICALS INC
Trading Symbol	AGIO
Entity Central Index Key	0001439222
Current Fiscal Year End Date	--12-31
Entity Filer Category	Large Accelerated Filer
Document Type	10-K
Document Period End Date	Dec. 31, 2018
Document Fiscal Year Focus	2018
Document Fiscal Period Focus	FY
Amendment Flag	false
Entity Common Stock, Shares Outstanding		58,395,419
Entity Well-known Seasoned Issuer	Yes
Entity Voluntary Filers	No
Entity Current Reporting Status	Yes
Entity Public Float			$ 4,271,074,700

Consolidated Balance Sheets - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Current assets:
Cash and cash equivalents	$ 70,502	$ 102,724
Marketable securities	514,800	321,212
Accounts receivable, net	5,076	0
Collaboration receivable – related party	2,462	2,448
Collaboration receivable – other	670	0
Royalty receivable – related party	2,234	1,222
Inventory	869	0
Prepaid expenses and other current assets	17,167	17,655
Total current assets	613,780	445,261
Marketable securities	220,119	143,814
Property and equipment, net	24,320	24,431
Other non-current assets	238	891
Total assets	858,457	614,397
Current liabilities:
Accounts payable	17,880	22,767
Accrued expenses	42,147	34,031
Deferred revenue – related party	32,710	37,842
Deferred rent	766	301
Total current liabilities	93,503	94,941
Deferred revenue, net of current portion – related party	59,809	125,798
Deferred rent, net of current portion	17,608	18,155
Total liabilities	170,920	238,894
Commitments and contingent liabilities (Note 8)
Stockholders’ equity:
Preferred stock, $0.001 par value; 25,000,000 shares authorized, no shares issued and outstanding at December 31, 2018 and 2017	0	0
Common stock, $0.001 par value; 125,000,000 shares authorized and 58,218,651 and 48,826,153 shares issued and outstanding at December 31, 2018 and 2017, respectively	58	49
Additional paid-in capital	1,794,283	1,174,904
Accumulated other comprehensive loss	(2,171)	(1,389)
Accumulated deficit	(1,104,633)	(798,061)
Total stockholders’ equity	687,537	375,503
Total liabilities and stockholders’ equity	$ 858,457	$ 614,397

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	$ 0
Preferred stock, shares authorized (in shares)	25,000,000	25,000,000
Preferred stock, shares issued (in shares)	0	0
Preferred stock, shares outstanding (in shares)	0	0
Common stock, par value (in usd per share)	$ 0	$ 0
Common stock, shares authorized (in shares)	125,000,000	125,000,000
Common stock, shares issued (in shares)	58,218,653	48,826,153
Common stock, shares outstanding (in shares)	58,218,653	48,826,153

Consolidated Statements of Operations - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Revenues:
Revenues	$ 94,387	$ 43,011	$ 69,892
Costs and expenses:
Cost of sales	1,397	0	0
Research and development expense	341,324	292,681	220,163
Selling, general and administrative	114,145	71,124	50,714
Total cost and expenses	456,866	363,805	270,877
Loss from operations	(362,479)	(320,794)	(200,985)
Interest income	16,451	6,124	2,514
Net loss	$ (346,028)	$ (314,670)	$ (198,471)
Net loss per share - basic and diluted (in usd per share)	$ (6.03)	$ (6.75)	$ (5.07)
Weighted-average number of common shares used in computing net loss per share - basic and diluted (in shares)	57,418,300	46,587,631	39,126,400
Product revenue, net
Revenues:
Revenues	$ 13,841	$ 0	$ 0
Collaboration revenue – related party
Revenues:
Revenues	60,661	41,074	69,892
Collaboration revenue – other
Revenues:
Revenues	12,670	0	0
Royalty revenue – related party
Revenues:
Revenues	$ 7,215	$ 1,937	$ 0

Consolidated Statements of Operations (Parenthetical) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Income Statement [Abstract]
Reduction of research and development costs	$ 0	$ 7,811	$ 19,714

Consolidated Statements of Comprehensive Loss - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Statement of Comprehensive Income [Abstract]
Net loss	$ (346,028)	$ (314,670)	$ (198,471)
Other comprehensive (loss) income:
Unrealized (loss) gain on available-for-sale securities	(782)	(1,076)	5
Comprehensive loss	$ (346,810)	$ (315,746)	$ (198,466)

Consolidated Statements of Stockholders' Equity - USD ($) $ in Thousands	Total	Common Stock	Additional Paid-In Capital	Accumulated Other Comprehensive Income (Loss)	Accumulated Deficit
Beginning balance (in shares) at Dec. 31, 2015		37,696,502
Beginning balance at Dec. 31, 2015	$ 345,118	$ 38	$ 630,078	$ (318)	$ (284,680)
Unrealized gain (loss) on available-for-sale securities	5			5
Net loss	(198,471)				(198,471)
Stock-based compensation expense	42,086		42,086
Issuance of common stock under stock incentive and employee stock purchase plan (in shares)		647,539
Issuance of common stock under stock incentive and employee stock purchase plan	7,703	$ 0	7,703
Issuance of common stock for follow-on offering (in shares)		3,876,403
Issuance of common stock for follow-on offering	162,150	$ 4	162,146
Ending balance (in shares) at Dec. 31, 2016		42,220,444
Ending balance at Dec. 31, 2016	358,591	$ 42	842,013	(313)	(483,151)
Unrealized gain (loss) on available-for-sale securities	(1,076)			(1,076)
Net loss	(314,670)				(314,670)
Stock-based compensation expense	47,809		47,809
Issuance of common stock under stock incentive and employee stock purchase plan (in shares)		797,629
Issuance of common stock under stock incentive and employee stock purchase plan	14,190	$ 1	14,189
Issuance of common stock for follow-on offering (in shares)		5,808,080
Issuance of common stock for follow-on offering	270,250	$ 6	270,244
Other	409		649		(240)
Ending balance (in shares) at Dec. 31, 2017		48,826,153
Ending balance at Dec. 31, 2017	375,503	$ 49	1,174,904	(1,389)	(798,061)
Unrealized gain (loss) on available-for-sale securities	(782)			(782)
Net loss	(346,028)				(346,028)
Stock-based compensation expense	$ 73,357		73,357
Issuance of common stock under stock incentive and employee stock purchase plan (in shares)	1,125,009	1,239,514
Issuance of common stock under stock incentive and employee stock purchase plan	$ 30,216	$ 1	30,215
Issuance of common stock for follow-on offering (in shares)		8,152,986
Issuance of common stock for follow-on offering	516,206	$ 8	516,198
Other	(391)		(391)
Ending balance (in shares) at Dec. 31, 2018		58,218,653
Ending balance at Dec. 31, 2018	$ 687,537	$ 58	$ 1,794,283	$ (2,171)	$ (1,104,633)

Consolidated Statements of Cash Flows - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Operating Activities
Net loss	$ (346,028)	$ (314,670)	$ (198,471)
Adjustments to reconcile net loss to net cash (used in) provided by operating activities:
Depreciation	7,172	6,432	5,708
Stock-based compensation expense	73,357	47,809	42,086
Net (accretion of discount) amortization of premium on marketable securities	(3,837)	(11)	773
Loss on disposal of property and equipment	20	40	0
Changes in operating assets and liabilities:
Accounts receivable, net	(5,076)	0	0
Collaboration receivable – related party	(14)	2,438	3,339
Collaboration receivable – other	(670)	0	0
Royalty receivable – related party	(1,012)	(1,222)	0
Inventory	(869)	0	0
Prepaid expenses and other current and non-current assets	1,148	(3,600)	(2,420)
Accounts payable	(5,488)	5,329	3,501
Accrued expenses	8,623	1,522	16,854
Deferred revenue – related party	(31,665)	(26,570)	165,846
Deferred rent	(82)	(2,729)	1,346
Net cash (used in) provided by operating activities	(304,421)	(285,232)	38,562
Investing Activities
Purchases of marketable securities	(933,320)	(688,702)	(506,067)
Proceeds from maturities and sales of marketable securities	666,481	635,421	396,632
Purchases of property and equipment	(6,986)	(4,627)	(9,915)
Net cash used in investing activities	(273,825)	(57,908)	(119,350)
Financing Activities
Proceeds from public offering of common stock, net of reimbursements	516,206	270,250	162,150
(Payment) of public offering costs	(391)		(230)
Reiumbursement of public offering costs		638
Net proceeds from stock option exercises and employee stock purchase plan	30,209	14,222	7,858
Net cash provided by financing activities	546,024	285,110	169,778
Net change in cash and cash equivalents	(32,222)	(58,030)	88,990
Cash and cash equivalents at beginning of the period	102,724	160,754	71,764
Cash and cash equivalents at end of the period	70,502	102,724	160,754
Supplemental disclosure of non-cash investing and financing transactions:
Additions to property and equipment in accounts payable and accrued expenses	1,106	1,011	73
Proceeds from stock option exercises in other current assets	7	0	32
Public offering costs in other receivables, net of amounts in accounts payable and accrued expenses	$ 0	$ 0	$ 230

Nature of Business	12 Months Ended
Nature of Business	Dec. 31, 2018
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Nature of Business	Nature of Business References to Agios Throughout this Annual Report on Form 10-K, “we,” “us,” and “our,” and similar expressions, except where the context requires otherwise, refer to Agios Pharmaceuticals, Inc. and its consolidated subsidiaries, and “our board of directors” refers to the board of directors of Agios Pharmaceuticals, Inc. Overview We are a biopharmaceutical company committed to the fundamental transformation of patients’ lives through scientific leadership in the field of cellular metabolism and adjacent areas of biology, with the goal of making transformative, first- or best-in-class medicines for the treatment of cancer and rare genetic diseases, or RGDs. To address both cancer and RGDs, we take a systems biology approach to deeply understand disease states, drive the discovery and validation of novel therapeutic targets, and define patient selection strategies, thereby increasing the probability that our experimental medicines will have the desired therapeutic effect. We are located in Cambridge, Massachusetts. In July 2018, the U.S. Food and Drug Administration, or FDA, granted us approval of our wholly-owned product, TIBSOVO® (ivosidenib) for the treatment of adult patients with relapsed and refractory acute myeloid leukemia, or R/R AML, with a susceptible isocitrate dehydrogenase 1, or IDH1, mutation as detected by an FDA-approved test. In December 2018, we submitted a Marketing Authorization Application, or MAA, to the European Medicines Agency, or EMA, for TIBSOVO® for the treatment of adult patients with R/R AML. Also in December 2018, we submitted a supplemental new drug application to the FDA for TIBSOVO® for the treatment of patients with newly diagnosed AML with an IDH1 mutation who are not eligible for standard treatment. Our other commercial cancer product is IDHIFA® (enasidenib). In August 2017, the FDA granted our collaboration partner Celgene Corporation, or Celgene, approval of IDHIFA® for the treatment of adult patients with R/R AML and an isocitrate dehydrogenase 2, or IDH2, mutation as detected by an FDA-approved test. IDHIFA®, an oral targeted inhibitor of the mutated IDH2 enzyme, is the first and only FDA-approved therapy for patients with R/R AML and an IDH2 mutation. We are eligible to receive royalties at tiered low-double digit to mid-teen percentage rates on any net sales of IDHIFA® and have exercised our rights to provide up to one-third of the field-based commercialization efforts in the United States. Celgene has submitted an MAA to the EMA for IDHIFA® for IDH2 mutant-positive AML. Our pre-commercial clinical cancer product candidates are vorasidenib (AG-881), AG-270, and AG-636. Vorasidenib (AG-881) is a brain-penetrant pan-IDH mutant inhibitor. These mutations are found in a wide range of hematological malignancies and solid tumors. We expect to initiate a registration-enabling phase 3 study of vorasidenib (AG-881) in low-grade glioma with an IDH1 mutation by the end of 2019. AG-270 is an orally available selective potent inhibitor of methionine adenosyltransferase 2a, or MAT2A. We submitted an investigational new drug application, or IND, for AG-270 in November 2017, and in December 2017 the FDA concluded that we may proceed with our planned phase 1 dose-escalation trial of AG-270 in multiple tumor types carrying a methylthioadenosine phosphorylase, or MTAP, deletion, which we initiated in March 2018. AG-636 is an inhibitor of the metabolic enzyme dihydroorotate dehydrogenase, or DHODH. In October 2018, we submitted an IND for AG-636 for the treatment of hematologic malignancies, which was accepted by the FDA in December 2018. We expect to initiate a phase 1 dose-escalation trial of AG-636 in lymphoma in the first half of 2019. The lead product candidate in our RGD portfolio, mitapivat, targets pyruvate kinase-R for the treatment of pyruvate kinase, or PK, deficiency. PK deficiency is a rare genetic disorder that often results in severe hemolytic anemia, jaundice and lifelong conditions associated with chronic anemia and secondary complications due to inherited mutations in the pyruvate kinase enzyme within red blood cells. In April 2018, we initiated ACTIVATE-T, a single arm, global, pivotal trial of mitapivat in approximately 20 regularly transfused patients with PK deficiency. In June 2018, we initiated ACTIVATE, a 1:1 randomized, placebo-controlled, global, pivotal trial of mitapivat in approximately 80 patients with PK deficiency who do not receive regular transfusions. We also initiated a phase 2 proof of concept trial of mitapivat in thalassemia in December 2018. In addition to the aforementioned development programs, we are seeking to advance a number of early-stage discovery programs in the areas of cancer metabolism, RGDs and metabolic immuno-oncology, or MIO, a developing field which aims to modulate the activity of relevant immune cells by targeting critical metabolic nodes, thereby enhancing the immune mediated anti-tumor response. Liquidity In January 2018, we completed a public offering of 7,089,553 shares of common at an offering price of $67.00 per share. We received net proceeds from this offering of $448.9 million, after deducting underwriting discounts and commissions paid by us. In addition, we granted the underwriters the right to purchase up to an additional 1,063,433 shares of common stock, which was exercised in January 2018, resulting in additional net proceeds to us of $67.3 million, after underwriting discounts and commissions. After giving effect to the full exercise of the over-allotment option, the number of shares sold by us in the public offering totaled 8,152,986 shares, and net proceeds to us totaled $516.2 million, after underwriting discounts and commissions. As of December 31, 2018, we had cash, cash equivalents and marketable securities of $805.4 million. Although we have incurred recurring losses and expect to continue to incur losses for the foreseeable future, we expect our cash, cash equivalents and marketable securities to be sufficient to fund current operations for at least the next twelve months from the issuance of the financial statements.

Summary of Significant Accounting Policies

12 Months Ended

Dec. 31, 2018

Accounting Policies [Abstract]

Summary of Significant Accounting Policies

Principles of consolidation

The consolidated financial statements include our accounts and the accounts of our wholly owned subsidiaries, Agios Securities Corporation, Agios International Sarl, and Agios Limited. All intercompany transactions have been eliminated in consolidation. The consolidated financial statements have been prepared in conformity with U.S. generally accepted accounting principles, or U.S. GAAP.

Use of estimates

The preparation of financial statements in conformity with U.S. GAAP requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities, disclosure of contingent assets and liabilities at the date of the financial statements and the reported amounts of revenue and expenses during the reporting period. We base our estimates on historical experience and on various other assumptions that are believed to be reasonable under the circumstances. Actual results could differ from those estimates.

Cash and cash equivalents

We consider highly liquid investments with a maturity of three months or less when purchased to be cash equivalents. Cash equivalents are stated at fair value.

Marketable securities

Marketable securities at December 31, 2018 and 2017 consisted of investments in certificates of deposit, U.S. Treasuries, government securities and corporate debt securities. We determine the appropriate classification of the securities at the time they are acquired and evaluate the appropriateness of such classifications at each balance sheet date. We classify our marketable securities as available-for-sale pursuant to Accounting Standards Codification, or ASC, 320, Investments – Debt and Equity Securities. Marketable securities are recorded at fair value, with unrealized gains and losses included as a component of accumulated other comprehensive loss in stockholders’ equity and a component of total comprehensive loss in the consolidated statements of comprehensive loss, until realized. Realized gains and losses are included in investment income on a specific-identification basis.

At December 31, 2018 and 2017, we held both current and non-current investments. Investments classified as current have maturities of less than one year. Investments classified as non-current are those that: (i) have a maturity of one to two years, and (ii) we do not intend to liquidate within the next twelve months, although these funds are available for use and therefore classified as available-for-sale.

We review marketable securities for other-than-temporary impairment whenever the fair value of a marketable security is less than the amortized cost and evidence indicates that a marketable security’s carrying amount is not recoverable within a reasonable period of time. Other-than-temporary impairments of investments are recognized in the consolidated statements of operations if we experience a credit loss, have the intent to sell the marketable security, or if it is more likely than not that we will be required to sell the marketable security before recovery of the amortized cost basis. Evidence considered in this assessment includes reasons for the impairment, compliance with our investment policy, the severity and the duration of the impairment, and changes in value subsequent to the end of the period.

Fair value measurements

We record cash equivalents and marketable securities at fair value. ASC 820, Fair Value Measurements and Disclosures, establishes a fair value hierarchy for those instruments measured at fair value that distinguishes between assumptions based on market data (observable inputs) and our own assumptions (unobservable inputs). The hierarchy consists of three levels:

Level 1 – Unadjusted quoted prices in active markets for identical assets or liabilities.

Level 2 – Quoted prices for similar assets and liabilities in active markets, quoted prices in markets that are not active, or inputs which are observable, either directly or indirectly, for substantially the full term of the asset or liability.

Level 3 – Unobservable inputs that reflect our own assumptions about the assumptions market participants would use in pricing the asset or liability in which there is little, if any, market activity for the asset or liability at the measurement date.

Our financial assets, which include cash equivalents and marketable securities, have been initially valued at the transaction price, and subsequently revalued at the end of each reporting period, utilizing third-party pricing services or other observable market data. The pricing services utilize industry standard valuation models, including both income and market based approaches, and observable market inputs to determine value. After completing our validation procedures, we did not adjust or override any fair value measurements provided by the pricing services as of December 31, 2018 or 2017.

There have been no changes to the valuation methods during the years ended December 31, 2018 and 2017. We evaluate transfers between levels at the end of each reporting period.

The carrying amounts of collaboration receivable – related party, royalty receivable – related party, tenant improvement and other receivables, prepaid expenses and other current assets, accounts payable, and accrued expenses approximate their fair values due to their short-term maturities.

Accounts receivable, net

Our trade accounts receivable arise from product sales and represent amounts due from specialty distributors and specialty pharmacy providers in the U.S. We monitor the financial performance and creditworthiness of our customers so that we can properly assess and respond to changes in their credit profile. We reserve against these receivables for estimated losses that may arise from a customer’s inability to pay. Amounts determined to be uncollectible are charged or written-off against the reserve.

Concentrations of credit risk

Financial instruments which potentially subject us to credit risk consist primarily of cash, cash equivalents, and marketable securities. We hold these investments in highly rated financial institutions, and, by policy, limit the amounts of credit exposure to any one financial institution. These amounts at times may exceed federally insured limits. We have not experienced any credit losses in such accounts and do not believe we are exposed to any significant credit risk on these funds. We have no off-balance sheet concentrations of credit risk, such as foreign currency exchange contracts, option contracts, or other hedging arrangements.

We are also subject to credit risk on our receivables, including trade receivables from our customers and collaboration and royalty receivables from Celgene and CStone Pharmaceuticals, or CStone. Concentrations of credit risk with respect to receivables, which are typically unsecured, are somewhat mitigated due to the number of customers using our products. Our trade receivables arise from product sales in the U.S. and have standard payment terms that generally require payment within 30 to 60 days. We have evaluated the creditworthiness of our customers, including Celgene, and determined them to be creditworthy. To date we have not experienced any losses with respect to our receivables.

Inventory

Inventory is stated at the lower of cost or estimated net realizable value on a first-in, first-out basis. Prior to the regulatory approval of our product candidates, we incur expenses for the manufacture of drug product that could potentially be available to support the commercial launch of those products. Until the date at which regulatory approval has been received or is otherwise considered probable, we record all such costs as research and development expenses. Upon approval of our wholly owned product, TIBSOVO®, by the FDA on July 20, 2018 for the treatment of adult patients with R/R AML with susceptible IDH1 mutation as detected by an FDA-approved test, we began to capitalize inventories of TIBSOVO®.

We perform an assessment of the recoverability of capitalized inventory during each reporting period and write down any excess and obsolete inventory to its estimated net realizable value in the period in which the impairment is first identified. Such impairment charges, should they occur, are recorded as a component of cost of sales in the condensed consolidated statements of operations. The determination of whether inventory costs will be realizable requires the use of estimates by management. If

actual market conditions are less favorable than projected by management, additional write-downs of inventory may be required.

Property and equipment

Property and equipment consist of laboratory equipment, computer equipment and software, leasehold improvements, furniture and fixtures, and office equipment. Property and equipment is stated at cost, and depreciated using the straight-line method over the estimated useful lives of the respective assets:


Laboratory equipment						5 years
Computer equipment and software						3 years
Leasehold improvements						Shorter of asset’s useful life or remaining term of lease
Furniture and fixtures						5 years
Office equipment						5 years

Costs of major additions and betterment are capitalized; maintenance and repairs, which do not improve or extend the life of the respective assets, are charged to expense as incurred. Upon retirement or sale, the cost of the disposed asset and the related accumulated depreciation are removed from the accounts and the resulting gain or loss is recognized.

Impairment of long-lived assets

We periodically evaluate our long-lived assets for potential impairment in accordance with ASC 360, Property, Plant and Equipment. Potential impairment is assessed when there is evidence that events or changes in circumstances indicate that the carrying amount of an asset may not be recovered. Recoverability of these assets is assessed based on the undiscounted expected future cash flows from the assets, considering a number of factors, including past operating results, budgets and economic projections, market trends and product development cycles. If impairments are identified, assets are written down to their estimated fair value. We did not recognize any impairment charges through December 31, 2018.

Revenue from Contracts with Customers

In May 2014, the Financial Accounting Standards Board, or FASB, issued Accounting Standards Update, or ASU, 2014-09, Revenue from Contracts with Customers (Topic 606), which supersedes all existing revenue recognition requirements, including most industry specific guidance. This standard requires a company to recognize revenues when it transfers goods or services to customers in an amount that reflects the consideration that the company expects to receive for those goods or services.

The FASB subsequently issued the following amendments to ASU 2014-09 that have the same effective date and transition date: ASU 2016-08, Revenue from Contracts with Customers (Topic 606): Principal versus Agent Considerations; ASU 2016-10, Revenue from Contracts with Customers (Topic 606): Identifying Performance Obligations and Licensing; ASU 2016-12, Revenue from Contracts with Customers (Topic 606): Narrow-Scope Improvements and Practical Expedients; and ASU 2016-20, Technical Corrections and Improvements to Topic 606, Revenue from Contracts with Customers. We adopted these amendments with ASU 2014-09, collectively referred to as ASC 606.

We adopted ASC 606 effective January 1, 2018, using the modified retrospective method. Under ASC 606, revenue is recognized when the customer obtains control of promised goods or services, in an amount that reflects the consideration that we expect to receive in exchange for those goods or services. To determine revenue recognition for arrangements that we determined to be within the scope of ASC 606, we perform the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) we satisfy a performance obligation. We only apply the five-step model to contracts when it is probable that we will collect the consideration we are entitled to in exchange for the goods or services it transfers to the customer. At contract inception, once the contract is determined to be within the scope of ASC 606, we assess the goods or services promised within each contract and determines those that are performance obligations, and assess whether each promised good or service is distinct. We will then recognize as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) the performance obligation is satisfied. For a complete discussion of accounting for net product revenue and license, collaboration and other revenues, see Note 9, Product Revenue, and Note 10, Collaboration and License Agreements.

Revenues for the years ended December 31, 2017 and 2016 were recognized under ASC 605, Revenue Recognition. In accordance with ASC 605, revenue is recognized for each unit of accounting when all of the following criteria are met:

•persuasive evidence of an arrangement exists;

•delivery has occurred or services have been rendered;

•the seller’s price to the buyer is fixed or determinable; and

•collectability is reasonably assured.

Amounts received prior to satisfying the revenue recognition criteria are recorded as deferred revenue. Amounts expected to be recognized as revenue within the 12 months following the balance sheet date are classified current and amounts not expected to be recognized as revenue within the 12 months following the balance sheet date are classified as non-current.

Adoption of ASC 606

We adopted ASC 606 using the modified retrospective method. Under this method, we recognized the cumulative effect of the change in the opening balance of accumulated deficit in the current period condensed consolidated balance sheet.

The impact of the cumulative effect of the accounting changes upon the adoption of the standard is as follows (in thousands):


	December 31, 2017		Cumulative Effect		January 1, 2018
Deferred revenue – related party, current and net of current portions	$	163,640	$	(39,456)	$	124,184
Accumulated deficit	(798,061)		39,456		(758,605)

The following tables summarize the effects of adopting ASC 606 on our consolidated financial statements (in thousands, except per share data):

Consolidated Balance Sheets


	December 31, 2018
	Under Topic 606		Under Topic 605		Effect of Change
Accounts receivable, net	$	5,076	$	5,076	$	—
Collaboration receivable – related party	2,462		2,462		—
Collaboration receivable – other	670		230		440
Total current assets	613,780		613,340		440
Total assets	858,457		858,017		440

Deferred revenue – related party	32,710		29,133		3,577
Total current liabilities	93,503		89,926		3,577
Deferred revenue, net of current portion – related party	59,809		101,180		(41,371)
Total liabilities	170,920		208,714		(37,794)
Accumulated deficit	(1,104,633)		(1,142,867)		38,234
Total stockholders’ equity	687,537		649,303		38,234
Total liabilities and stockholders’ equity	858,457		858,017		440

Consolidated Statements of Operations


	Year ended December 31, 2018
	Under Topic 606		Under Topic 605		Effect of Change
Product revenue, net	$	13,841	$	13,841	$	—
Collaboration revenue – related party	60,661		58,994		1,667
Collaboration revenue – other	12,670		12,230		440
Total revenue	94,387		92,280		2,107
Research and development expense	341,324		337,995		3,329
Total cost and expenses	456,866		453,537		3,329
Loss from operations	(362,479)		(361,257)		(1,222)
Net loss	(346,028)		(344,806)		(1,222)
Net loss per share – basic and diluted	(6.03)		(6.01)		(0.02)

Consolidated Statements of Comprehensive Loss


	Year ended December 31, 2018
	Under Topic 606		Under Topic 605		Effect of Change
Net loss	$	(346,028)	$	(344,806)	$	(1,222)
Comprehensive loss	(346,810)		(345,588)		(1,222)

Consolidated Statements of Cash Flows


	Year ended December 31, 2018
	Under Topic 606		Under Topic 605		Effect of Change
Net loss	$	(346,028)	$	(344,806)	$	(1,222)
Adjustments to reconcile net loss to net cash used in operating activities:
Accounts receivable, net	(5,076)		(5,076)		—
Collaboration receivable – related party	(14)		(14)		—
Collaboration receivable – other	(670)		(230)		(440)
Deferred revenue – related party	(31,665)		(33,327)		1,662

Cost of Sales

Cost of sales consists primarily of manufacturing costs of TIBSOVO®. Based on our policy to expense costs associated with the manufacturing of our products prior to regulatory approval, certain of the manufacturing costs associated with product shipments of TIBSOVO® recorded during the year ended December 31, 2018 were expensed prior to July 20, 2018 and, therefore, are not included in costs of sales during the current period.

Research and development costs

Research and development costs are expensed as incurred. These costs include salaries and personnel-related costs, consulting fees, fees paid for contract research services, fees paid to clinical research organizations and other third parties associated with clinical trials, the costs of laboratory equipment and facilities, and other external costs.

Nonrefundable advance payments for goods or services to be received in the future for use in research and development activities are deferred and capitalized. The capitalized amounts are expensed as the related goods are delivered or the services are performed.

Stock-based compensation

We account for stock-based compensation awards in accordance with ASC 718, Compensation –Stock Compensation, or ASC 718. For stock-based awards granted to employees and to members of the board of directors for their services and for participation in employee stock purchase plan, we estimate the grant date fair value of each option award using the Black-Scholes option-pricing model. The use of the Black-Scholes option-pricing model requires us to make assumptions with respect

to the expected term of the option, the expected volatility of the common stock consistent with the expected life of the option, risk-free interest rates and expected dividend yields of the common stock. For awards subject to service-based vesting conditions, we recognize stock-based compensation expense equal to the grant date fair value of stock options on a straight-line basis over the requisite service period. For awards subject to both performance and service-based vesting conditions, we recognize stock-based compensation expense over the remaining service period if the performance condition is considered probable of achievement using management’s best estimates.

In 2017, we adopted ASU 2016-09, Compensation—Stock Compensation (Topic 718): Improvements to Employee Share-Based Payment Accounting, which simplifies several aspects of the accounting for employee share-based payment transactions, including income tax consequences, classification of awards as either equity or liabilities, and classification in the statement of cash flows. Upon adoption of this standard, we recorded a cumulative-effect adjustment of approximately $32.7 million through retained earnings and deferred tax assets.

Income taxes

Income taxes are recorded in accordance with ASC 740, Accounting for Income Taxes, or ASC 740, which provides for deferred taxes using an asset and liability approach. We recognize deferred tax assets and liabilities for the expected future tax consequences of events that have been included in our financial statements or tax returns. We determine our deferred tax assets and liabilities based on differences between the financial reporting and tax bases of assets and liabilities, which are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse. Valuation allowances are provided, if based upon the weight of available evidence, it is more likely than not that some or all of the deferred tax assets will not be realized.

We also account for uncertain tax positions in accordance with the provisions of ASC 740. When uncertain tax positions exist, we recognize the tax benefit of tax positions to the extent that the benefit will more likely than not be realized. The determination as to whether the tax benefit will more likely than not be realized is based upon the technical merits of the tax position as well as consideration of the available facts and circumstances.

Comprehensive income (loss)

Comprehensive income (loss) is defined as the change in equity of a business enterprise during a period from transactions, and other events and circumstances from non-owner sources, and currently consists of net loss and unrealized gains and losses on available-for-sale securities. Accumulated other comprehensive loss consists entirely of unrealized gains and losses from available-for-sale securities as of December 31, 2018 and 2017.

Net loss per share

Basic net loss per share is calculated by dividing net loss by the weighted-average shares outstanding during the period, without consideration for common stock equivalents. Diluted net loss per share is calculated by adjusting weighted-average shares outstanding for the dilutive effect of common stock equivalents outstanding for the period, determined using the treasury-stock method. For purposes of the dilutive net loss per share calculation, stock options, restricted stock units, performance-based stock units for which the performance vesting conditions have been met, and employee stock purchase plan shares are considered to be common stock equivalents but are excluded from the calculation of diluted net loss per share as their effect would be anti-dilutive.

Segment and geographic information

Operating segments are identified as components of an enterprise about which separate discrete financial information is available for evaluation by the chief operating decision maker, or decision-making group, in making decisions on how to allocate resources and assess performance. Our chief operating decision maker is the chief executive officer. Our chief operating decision maker and we view our operations and manage our business as one operating segment.

Recent accounting pronouncements

Leases

In February 2016, the FASB issued ASU 2016-02, Leases (Topic 842), which was codified as ASC 842, Leases, and amended through subsequent ASUs. We adopted ASC 842 effective January 1, 2019 using the modified retrospective transition approach and elected the package of practical expedients, both provided for under ASU 2018-11, Leases (Topic 842): Targeted Improvements. The package of practical expedients allows us not to reassess whether contracts are or contain leases, lease classification, and whether initial direct costs qualify for capitalization. Additionally, as an accounting policy, for our building leases, we chose not to separate the non-lease components from the lease components and, instead, accounted for each non-lease component and lease component as a single component.

We have substantially completed our assessment over the impact of the standard and determined that only material leases that we hold are our building leases. Upon adoption of the standard, we preliminarily expect to record a right of use asset and lease liability of approximately $50.0 million on our consolidated balance sheets. The finalization of our assessment may result in significant changes to our estimates that may materially impact our preliminary estimate of the cumulative effect.

The tax impact of the adoption will also be recorded through accumulated deficit with an offset to the valuation allowance. The only impact of the adoption is on disclosures presented in Note 13, Income Taxes.

Other Recent Accounting Pronouncements

Other accounting standards that have been issued by the FASB or other standards-setting bodies that do not require adoption until a future date are not expected to have a material impact on our financial statements upon adoption.

Subsequent events

We considered events or transactions occurring after the balance sheet date, but prior to the issuance of the consolidated financial statements, for potential recognition or disclosure in our consolidated financial statements. All significant subsequent events have been properly disclosed in the consolidated financial statements.

Fair Value Measurements

12 Months Ended

Dec. 31, 2018

Fair Value Disclosures [Abstract]

Fair Value Measurements

The following table summarizes our cash equivalents and marketable securities measured at fair value on a recurring basis as of December 31, 2018 (in thousands):


	Level 1		Level 2		Level 3		Total
Cash equivalents	$	42,673	$	1,999	$	—	$	44,672
Marketable securities:
Certificates of deposit	—		956		—		956
U.S. Treasuries	—		242,961		—		242,961
Government securities	—		145,213		—		145,213
Corporate debt securities	—		345,789		—		345,789
	$	42,673	$	736,918	$	—	$	779,591

The fair value of Level 2 instruments were determined through third-party pricing services. For a description of our validation procedures related to prices provided by third-party pricing services, refer to Note 2, Summary of Significant Accounting Policies, to these consolidated financial statements. There have been no changes to the valuation methods during the year ended December 31, 2018.

There were no transfers between Level 1 and Level 2 and we had no financial assets or liabilities that were classified as Level 3 at any point during the year ended December 31, 2018.

- Definition

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

+ References + Details

Marketable Securities

12 Months Ended

Dec. 31, 2018

Investments, Debt and Equity Securities [Abstract]

Marketable Securities

Marketable securities at December 31, 2018 consisted of the following (in thousands):


	Amortized Cost		Unrealized Gains		Unrealized Losses		Fair Value
Current:
Certificates of deposit	$	960	$	—	$	(4)	$	956
U.S. Treasuries	231,101		7		(228)		230,880
Government securities	75,335		—		(121)		75,214
Corporate debt securities	208,233		—		(483)		207,750
Non-current:
U.S. Treasuries	12,202		4		(125)		12,081
Government securities	70,177		10		(188)		69,999
Corporate debt securities	139,082		12		(1,055)		138,039
Total marketable securities	$	737,090	$	33	$	(2,204)	$	734,919

Marketable securities at December 31, 2017 consisted of the following (in thousands):


	Amortized Cost		Unrealized Gains		Unrealized Losses		Fair Value
Current:
Certificates of deposit	$	8,081	$	—	$	(11)	$	8,070
U.S. Treasuries	113,852		—		(119)		113,733
Government securities	44,421		—		(57)		44,364
Corporate debt securities	155,222		—		(177)		155,045
Non-current:
Certificates of deposit	960		—		(8)		952
U.S. Treasuries	36,165		—		(311)		35,854
Government securities	23,992		—		(182)		23,810
Corporate debt securities	83,722		—		(524)		83,198
Total marketable securities	$	466,415	$	—	$	(1,389)	$	465,026

There were no material realized gains or losses on marketable securities for the years ended December 31, 2018 and 2017.

At December 31, 2018 and 2017, we held 242 and 240 debt securities that were in an unrealized loss position for less than one year, respectively. The aggregate fair value of debt securities in an unrealized loss position at December 31, 2018 and 2017 was $639.3 million and $439.4 million, respectively. There were no individual securities that were in a significant unrealized loss position as of December 31, 2018 and 2017. Given our intent and ability to hold such securities until recovery, and the lack of material change in the credit risk of these investments, we do not consider these marketable securities to be other-than-temporarily impaired as of December 31, 2018 and 2017.

Property and Equipment, net

12 Months Ended

Dec. 31, 2018

Property, Plant and Equipment [Abstract]

Property and Equipment, net

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


	December 31,
	2018		2017
Laboratory equipment	$	20,165	$	17,524
Computer equipment and software	5,449		4,293
Leasehold improvements	22,084		20,322
Furniture and fixtures	1,065		752
Office equipment	407		319
Construction in progress	1,302		618
Total property and equipment	50,472		43,828
Less: accumulated depreciation	(26,152)		(19,397)
Total property and equipment, net	$	24,320	$	24,431

Depreciation expense for the years ended December 31, 2018, 2017 and 2016 was $7.2 million, $6.4 million and $5.7 million, respectively.

Inventory

12 Months Ended

Dec. 31, 2018

Inventory Disclosure [Abstract]

Inventory

Inventory consisted of the following (in thousands):


	December 31,
	2018		2017
Raw materials	$	—	$	—
Work-in-process	788		—
Finished goods	81		—
Total Inventory	$	869	$	—

Inventory is related to our approved product, TIBSOVO®. There were no write downs for excess and obsolete inventory during the year ended December 31, 2018.

Accrued Expenses

12 Months Ended

Dec. 31, 2018

Payables and Accruals [Abstract]

Accrued Expenses

Accrued expenses and other current liabilities consisted of the following (in thousands):


	December 31,
	2018		2017
Accrued compensation	$	20,843	$	15,693
Accrued research and development costs	14,777		14,849
Accrued professional fees	5,441		3,140
Accrued other	1,086		349
Total accrued expenses	$	42,147	$	34,031

Commitments and Contingent Liabilities

12 Months Ended

Dec. 31, 2018

Commitments and Contingencies Disclosure [Abstract]

Commitments and Contingent Liabilities

Leases

We rent laboratory and office space under non-cancelable operating leases. These lease agreements contain various clauses for renewal at our option and escalation clauses. Rental expense under these leases, net of tenant improvement reimbursements, amounted to $11.4 million, $6.0 million and $6.0 million for the years ended December 31, 2018, 2017 and 2016, respectively.

We provided our landlord a standby letter of credit of $2.9 million as security for our leases. We are not required to maintain any cash collateral for the standby letter of credit.

As of December 31, 2018, minimum rental commitments under non-cancelable leases, for each of the next five years and total thereafter were as follows (in thousands):


2019	$	12,759
2020	13,135
2021	13,473
2022	15,552
2023	17,145
Thereafter	19,223
	$	91,287

In addition to rent, the leases may require us to pay additional amounts for taxes, insurance, maintenance and other operating expenses.

Manufacturing Commitments

We are party to various agreements with contract manufacturing organizations that we are not contractually able to terminate for convenience and avoid any and all future obligations to the vendors. Under such agreements, we are obligated to make certain minimum payments, with the exact amounts in the event of termination to be based on the timing of the termination and the exact terms of the agreement.

Legal Contingencies

From time to time, we may be involved in disputes and legal proceedings in the ordinary course of business. These proceedings may include allegations of infringement of intellectual property, employment or other matters. We do not have any ongoing legal proceedings that, based on our estimates, could have a material effect on our consolidated financial statements.

Product Revenue

12 Months Ended

Dec. 31, 2018

Revenue from Contract with Customer [Abstract]

Product Revenue

Product RevenueOur wholly owned product, TIBSOVO®, received approval from the FDA on July 20, 2018 for the treatment of adult patients with R/R AML with a susceptible IDH1 mutation. Upon FDA approval of TIBSOVO® in the U.S., we began generating product revenue from sales of TIBSOVO®. We sell TIBSOVO® to a limited number of specialty distributors and specialty pharmacy providers in the U.S., or collectively, the Customers. The Customers subsequently resell TIBSOVO® to pharmacies

or dispense directly to patients. In addition to distribution agreements with Customers, we enter into arrangements with healthcare providers and payors that provide for government-mandated and/or privately-negotiated rebates, chargebacks and discounts with respect to the purchase of TIBSOVO®.

The performance obligation related to the sale of TIBSOVO® is satisfied and revenue is recognized when the Customer obtains control of the product, which occurs at a point in time, typically upon delivery to the Customer.

Reserves for Variable Consideration

Revenues from product sales are recorded at the net sales price, or transaction price, which includes estimates of variable consideration for which reserves are established and result from contractual adjustments, government rebates, returns and other allowances that are offered within the contracts with our Customers, healthcare providers, payors and other indirect customers relating to the sale of our products.

Contractual Adjustments

We generally provide Customers with discounts, including prompt pay discounts, and allowances that are explicitly stated in the contracts and are recorded as a reduction of revenue in the period the related product revenue is recognized.

Chargebacks and discounts represent the estimated obligations resulting from contractual commitments to sell products to qualified healthcare providers at prices lower than the list prices charged to Customers who directly purchase the product from us. Customers charge us for the difference between what they pay for the product and the ultimate selling price to the qualified healthcare providers. These reserves are estimated using the expected value method, based upon a range of possible outcomes that are probability-weighted for the estimated channel mix and are established in the same period that the related revenue is recognized, resulting in a reduction of product revenue.

Government Rebates

Government rebates consist of Medicare, TriCare, and Medicaid rebates, which we estimate using the expected value method, based upon a range of possible outcomes that are probability-weighted for the estimated payor mix. These reserves are recorded in the same period the related revenue is recognized, resulting in a reduction of product revenue. For Medicare, we also estimate the number of patients in the prescription drug coverage gap for whom we will owe an additional liability under the Medicare Part D program.

Returns

We estimate the amount of product sales that may be returned by Customers and record this estimate as a reduction of revenue in the period the related product revenue is recognized. We currently estimate product return liabilities using the expected value method, based on available industry data, including our visibility into the inventory remaining in the distribution channel.

To date, our source of product revenue has been U.S. sales of TIBSOVO®. Total net product revenue was $13.8 million for the year ended December 31, 2018. The following table summarizes balances and activity in each of the product revenue allowance and reserve categories for the year ended December 31, 2018 (in thousands):


	Contractual Adjustments	Government Rebates	Returns	Total
Balance at December 31, 2017	—	—	—	—
Current provisions relating to sales in the current year	1,777	422	334	2,533
Adjustments relating to prior years	—	—	—	—
Payments/returns relating to sales in the current year	(1,185)	(97)	—	(1,282)
Payments/returns relating to sales in the prior years	—	—	—	—
Balance at December 31, 2018	592	325	334	1,251

Total revenue-related reserves above, included in our condensed consolidated balance sheets, are summarized as follows (in thousands):


	December 31, 2018
Reduction of accounts receivable	$	326
Component of accrued expenses	925
Total revenue-related reserves	$	1,251

The following table presents changes in our contract assets and liabilities during the year ended December 31, 2018 (in thousands):


	December 31, 2017		Additions		Deductions		December 31, 2018
Contract assets
Accounts receivable, net (1)	$	—	$	16,374	$	(11,298)	$	5,076

(1) Additions to accounts receivable, net relate to amounts billed to Customers for product sales and deductions primarily relate to collection of receivables during the reporting period.

Collaboration and License Agreements

12 Months Ended

Dec. 31, 2018

Revenue Recognition and Deferred Revenue [Abstract]

Collaboration and License Agreements

Celgene Corporation

To date, our revenue has primarily been generated from our collaboration agreements with Celgene, or collectively, the Collaboration Agreements. Celgene is a related party through ownership of our common stock. In April 2010, we entered into a discovery and development collaboration and license agreement focused on cancer metabolism, or the 2010 Agreement. The 2010 Agreement was amended in October 2011 and July 2014. In April 2015, we entered into a joint worldwide development and profit share collaboration and license agreement with Celgene, and our wholly owned subsidiary, Agios International Sarl, entered into a collaboration and license agreement with Celgene International II Sarl, or collectively, the AG-881 Agreements, to establish a worldwide collaboration focused on the development and commercialization of vorasidenib (AG-881) products. The AG-881 Agreements were terminated effective September 4, 2018. In May 2016, we entered into a master research and collaboration agreement with Celgene, or the 2016 Agreement.

2016 Agreement

In May 2016, we entered into the 2016 Agreement focused on MIO, a developing field which aims to modulate the activity of relevant immune cells by targeting critical metabolic nodes, thereby enhancing the immune mediated anti-tumor response. In addition to new programs identified under the 2016 Agreement, both parties also agreed that all future development and commercialization of two remaining cancer metabolism programs discovered under the 2010 Agreement, including AG-270, will now be governed by the 2016 Agreement.

During the research term of the 2016 Agreement, we plan to conduct research programs focused on discovering compounds that are active against metabolic targets in the immuno-oncology, or IO, field. The initial four-year research term will expire on May 17, 2020, and may be extended for up to two, or in specified cases, up to four additional one-year terms.

For each program under the 2016 Agreement, we may nominate compounds that meet specified criteria as development candidates and, in limited circumstances, Celgene may also nominate compounds as development candidates for each such program. Celgene may designate the applicable program for further development following any such nomination, after which we may conduct, at our expense, additional preclinical and clinical development for such program through the completion of an initial phase 1 dose escalation study.

At the end of the research term, Celgene may designate for continued development up to three research programs for which development candidates have yet to be nominated, which are referred to as continuation programs. We may conduct further research and preclinical and clinical development activities on any continuation program, at our expense, through the completion of an initial phase 1 dose escalation study.

We granted Celgene the right to obtain exclusive options for development and commercialization rights for each program that Celgene has designated for further development, and for each continuation program. Celgene may exercise each such option beginning on the designation of a development candidate for such program (or on the designation of such program as a continuation program) and ending on the earlier of: (i) the end of a specified period after we have furnished Celgene with specified information about the initial phase 1 dose escalation study for such program, or (ii) January 1, 2030. Research programs that have applications in the inflammation or autoimmune, or I&I, field that may result from the 2016 Agreement will also be subject to the exclusive options described above.

We will retain rights to any program that Celgene does not designate for further development or as to which it does not exercise its option.

Under the terms of the 2016 Agreement, following Celgene’s exercise of its option with respect to a program, the parties will enter into either a co-development and co-commercialization agreement if such program is in the IO field, or a license agreement if such program is in the I&I field. Under each co-development and co-commercialization agreement, the two parties will co-develop and co-commercialize licensed products worldwide. Either we or Celgene will lead development and

commercialization of licensed products for the United States, and Celgene will lead development and commercialization of licensed products outside of the United States. Depending on the country, the parties will each have the right to provide a portion of field-based marketing activities. Under each license agreement, Celgene will have the sole right to develop and commercialize licensed products worldwide.

Co-development and co-commercialization agreements

Under each co-development and co-commercialization agreement entered into under the 2016 Agreement, the parties will split all post-option exercise worldwide development costs, subject to specified exceptions, as well as any profits from any net sales of, or commercialization losses related to, licensed products in the IO field. Celgene has the option to designate one program in the IO field as the 65/35 program, for which Celgene will be the lead party for the United States and will have a 65% profit or loss share. For programs in the IO field other than the 65/35 program, we and Celgene will alternate, on a program-by-program basis, being the lead party for the United States, with us having the right to be the lead party for the first such program, and each party will have a 50% profit or loss share. The lead party for the United States will book commercial sales of licensed products, if any, in the United States, and Celgene will book commercial sales of licensed products, if any, outside of the United States.

License agreements

Under each license agreement under the 2016 Agreement, Celgene will be responsible for all post-option exercise worldwide development and associated costs, subject to specified exceptions, as well as worldwide commercialization and associated costs, for licensed products in the I&I field.

Financial terms

Under the terms of the 2016 Agreement, we received an initial upfront payment in the amount of $200.0 million. The 2016 Agreement provides specified rights to extend the research term for up to two, or in specified cases, up to four, additional years by paying a $40.0 million per-year extension fee. Celgene will pay an $8.0 million designation fee for each program that Celgene designates for further development and for each continuation program. During the year ended December 31, 2017, we received $8.0 million from Celgene upon the designation of AG-270 as a development candidate. For each program as to which Celgene exercises its option to develop and commercialize, subject to antitrust clearance, Celgene will pay an option exercise fee of at least $30.0 million for any designated development program and at least $35.0 million for any continuation programs. In certain cases, Celgene may exercise its option to develop and commercialize two early-stage I&I programs, prior to Celgene designating the program for further development, by paying an option exercise fee of $10.0 million.

We are eligible to receive the following milestone-based payments associated with the 2016 Agreement:

Program

Milestone

Amount

65/35 program in IO field

Specified clinical development event

$25.0 million

65/35 program in IO field

Specified regulatory milestone events

Up to $183.8 million

50/50 program in IO field

Specified clinical development event

$20.0 million

50/50 program in IO field

Specified regulatory milestone events

Up to $148.8 million

I&I field

Specified clinical development event

$25.0 million

I&I field

Specified regulatory milestone events

Up to $236.3 million

I&I field

Specified commercial milestone events

Up to $125.0 million

Additionally, for each licensed program in the I&I field, we are eligible to receive royalties at tiered, low double-digit percentage rates on Celgene’s net sales, if any, of the applicable licensed products.

Opt-out right

Under the 2016 Agreement, we may elect to opt out of the cost and profit share under any co-development and co-commercialization agreement, subject to specified exceptions. Upon opting out, Celgene will have the sole right to develop, manufacture and commercialize the applicable licensed products throughout the world, at its cost, and we will undertake transitional activities reasonably necessary to transfer the development, manufacture and commercialization of such licensed products to Celgene, at our expense. Further, in lieu of the profit or loss sharing described above, we would be eligible to receive royalties at tiered, low double-digit percentage rates on Celgene’s net sales, if any, of the applicable licensed products. However, we would continue to be eligible to receive the developmental and regulatory milestone-based payments described above.

Term

The term of the 2016 Agreement commenced on May 17, 2016 and, if not terminated earlier, will expire upon the later of the last-to-expire of the research term and all option exercise periods, or, if an option is exercised by Celgene for one or more programs in the collaboration, upon the termination or expiration of the last-to-exist co-development and co-commercialization agreement or license agreement, as applicable, for any such program.

Termination

Subject to specified exceptions, Celgene may terminate the 2016 Agreement in its entirety for any reason by providing us with prior written notice if there are no active co-development and co-commercialization agreements or license agreements in place or on a program-by-program basis if there are no active co-development and co-commercialization agreements or license agreements in place for the terminated program(s). Either party may terminate the 2016 Agreement for the insolvency of the other party. On a program-by-program basis, prior to the exercise of an option, either party may terminate the 2016 Agreement either in its entirety or with respect to one or more programs on prior written notice to the other party in the case of an uncured material breach by the other party that frustrates the fundamental purpose of the 2016 Agreement. Following the exercise of an option for a program, either party may terminate the 2016 Agreement with respect to such program if such party terminates the co-development and co-commercialization agreement or license agreement for such program for an uncured material breach by the other party that frustrates the fundamental purpose of such agreement. Either party may terminate a co-development and co-commercialization agreement or a license agreement upon the bankruptcy or insolvency of the other party. Either party also has the right to terminate the co-development and co-commercialization agreement or license agreement if the other party or any of its affiliates challenges the validity, scope or enforceability of or otherwise opposes, any patent included within the intellectual property rights licensed to the other party under such agreement.

Exclusivity

While any of Celgene’s options remain available under the 2016 Agreement, subject to specified exceptions, we may not directly or indirectly develop, manufacture or commercialize, outside of the 2016 Agreement, any therapeutic modality in the IO or I&I field with specified activity against a metabolic target.

During the term of each co-development and co-commercialization agreement and license agreement, subject to specified exceptions, neither we nor Celgene may directly or indirectly develop, manufacture or commercialize outside of such agreement any therapeutic modality in any field with specified activity against the metabolic target that is the focus of the program licensed under such agreement.

Ivosidenib Letter Agreement

In May 2016, we entered into a letter agreement with Celgene regarding ivosidenib, or the Ivosidenib Letter Agreement. Under the Ivosidenib Letter Agreement, the parties agreed to terminate the 2010 Agreement, effective as of August 15, 2016, as to the program directed to the IDH1 target, for which ivosidenib is the lead development candidate. Under the 2010 Agreement, Celgene had held development and commercialization rights to the IDH1 program outside of the United States, and we held such rights inside the United States. As a result of the Ivosidenib Letter Agreement, we obtained global rights to ivosidenib and the IDH1 program. Neither party will have any further financial obligation, including royalties or milestone payments, to the other concerning ivosidenib or the IDH1 program. Under the terms of the Ivosidenib Letter Agreement, the parties also agreed to conduct specified transitional activities in connection with the termination. In addition, pursuant to the Ivosidenib Letter Agreement, the parties are released from their exclusivity obligations under the 2010 Agreement with respect to the IDH1 program. The Ivosidenib Letter Agreement does not affect the AG-881 Agreements, which were directed to both the IDH1 target and the IDH2 target, and were subsequently terminated in September 2018 as discussed below.

Termination of AG-881 Agreements

We and Celgene terminated the AG-881 Agreements, effective as of September 4, 2018. From and after September 4, 2018, we obtained sole global rights to vorasidenib (AG-881). Neither we nor Celgene will have any further financial obligation under the AG-881 Agreements, including milestones, royalties or other payments, except that (a) Celgene shall be eligible to receive royalties from us at a low single-digit percentage rate on worldwide net sales of products containing vorasidenib (AG-881) and (b) we and Celgene shall split certain agreed-upon worldwide development costs for vorasidenib (AG-881) until December 31, 2018. In addition, for a specified period and subject to specified exceptions, Celgene and its affiliates shall be prohibited from developing, manufacturing or commercializing any product that inhibits IDH1 at specified levels of binding for any indication and we shall be prohibited from developing, manufacturing or commercializing vorasidenib (AG-881) in hematologic indications.

2010 Agreement

In April 2010, we entered into the 2010 Agreement, which was amended in October 2011 and July 2014. The goal of the collaboration was to discover, develop and commercialize disease-altering therapies in oncology based on our cancer metabolism research platform. We initially led discovery, preclinical and early clinical development for all cancer metabolism programs under the collaboration. The discovery phase of the 2010 Agreement expired in April 2016.

Upon agreement to terminate the 2010 Agreement, effective as of August 15, 2016, as to the program directed to the IDH1 target, for which ivosidenib is the lead development candidate, the sole program remaining under the 2010 Agreement is IDHIFA®, a co-commercialized licensed program for which Celgene leads and funds global development and commercialization activities. We have exercised our right to participate in a portion of commercialization activities in the United States for IDHIFA® in accordance with the applicable commercialization plan. On August 1, 2017, the FDA granted Celgene approval of IDHIFA® for the treatment of adult patients with R/R AML with an IDH2 mutation as detected by an FDA-approved test.

Under the remaining terms of the 2010 Agreement, we are eligible to receive up to $80.0 million in potential milestone payments for the IDHIFA® program. The potential milestone payments are comprised of: (i) up to $55.0 million in milestone payments upon achievement of specified ex-U.S. regulatory milestone events, of which $35.0 million relates to the first regulatory approval in any of China, Japan or a major European country, and (ii) a $25.0 million milestone payment upon achievement of a specified commercial milestone event.

Under the 2010 Agreement, we receive royalties at tiered, low-double digit to mid-teen percentage rates on net sales of IDHIFA®.

Unless terminated earlier by either party, the term of the 2010 Agreement will continue until the expiration of all royalty terms with respect to IDHIFA®. Celgene may terminate this agreement for convenience in its entirety upon ninety days written notice to us. If either party is in material breach and fails to cure such breach within the specified cure period, the other party may terminate the 2010 Agreement in its entirety. Either party may terminate the agreement in the event of specified insolvency events involving the other party.

Accounting analysis and revenue recognition – collaboration revenue

On January 1, 2018 we adopted ASC 606 under the modified retrospective method. Prior to January 1, 2018 we accounted for the Collaboration Agreements under ASC 605-25, Multiple Element Arrangements.

Accounting under ASC 606

In adopting ASC 606, we applied the practical expedient that permits aggregating the effect of all contract modifications that occurred prior to January 1, 2018. No other practical expedients were used. Similar to the accounting under ASC 605-25, the 2016 Agreement was determined to be a modification of the 2010 Agreement and the AG-881 Agreements. In determining the appropriate amount of revenue to be recognized under ASC 606, we performed the following steps: (i) identified the promised goods or services in the contract; (ii) determined whether the promised goods or services are performance obligations including whether they are distinct in the context of the contract; (iii) measured the transaction price, including the constraint on variable consideration; (iv) allocated the transaction price to the performance obligations; and (v) recognized revenue when (or as) we satisfied each performance obligation.

As part of the accounting for these arrangements, we must develop assumptions that require judgment to determine the stand-alone selling price, or SSP, for each performance obligation identified in the contract. We use key assumptions to determine the SSP, which include forecast of revenues, development timelines, reimbursement rates for personnel costs, discount rates and probabilities of technical and regulatory success.

The satisfied and unsatisfied performance obligations at the time of the ASC 606 adoption, each of which are considered by us to be distinct within the context of the contract, their SSP, the method of recognizing the allocated consideration, and the period through which they are expected to be recognized are as follows:

Performance
Obligations

SSP

No. of Performance
Obligations

Recognition
Method

Fully satisfied at time of adoption

Licenses (1)

86.7

million

Fully satisfied; recognized upon adoption of ASC 606

Research and development services (2)

350.7

million

Fully satisfied; recognized upon adoption of ASC 606

Partially satisfied at time of adoption

Research and development services (2)

266.6

million

Proportionally as services are delivered over the performance period, expected to be through September 2022 (3)

(1) The SSP was developed by probability weighting multiple cash flow scenarios using the income approach. Our management estimates within the models include the expected, probability-weighted net profits from estimated future sales, an estimate of the direct cost incurred to generate future cash flows, a discount rate and other business forecast factors. There are significant judgments and estimates inherent in the determination of the SSP of these units of accounting. These judgments and estimates include assumptions regarding future operating performance, the timelines of the clinical trials and regulatory approvals, and other factors. If different reasonable assumptions are utilized, the SSP and revenue recognized would vary.

(2) The SSP was developed using our management’s best estimate of the cost of obtaining these services at arm’s length from a third-party provider and using internal full time equivalent costs to support the development services.

(3) We determined that recognizing revenue on a proportional basis using the ratio of effort incurred to date compared to the total estimated effort required to complete the performance obligation best depicts the satisfaction of our obligations under the Collaboration Agreements.

During the year ended December 31, 2018, we recognized the following as collaboration revenue (in thousands):


Performance Obligation	Under Topic 606		Under Topic 605		Effect of Change
Collaboration revenue - related party
Licenses	$	15,000	$	15,000	$	—
Research and development services	40,575		38,733		1,842
Committee participation	—		175		(175)
Reduction of research and development expenses
Development services	—		3,329		(3,329)

During the years ended December 31, 2018, 2017 and 2016, we recognized as collaboration revenue the following non-contingent consideration allocated to each performance obligation (in thousands):


	Years ended December 31,
	2018		2017		2016
Licenses	$	15,000	$	—	$	1,356
On-going research and development services	40,575		37,953		41,993
Committee participation	—		167		181
Additional development services	—		—		—

Consideration for development and commercialization services performed by us, that were not considered performance obligations as of the modification dates, are recognized as collaboration revenue or a reduction of research and development expenses in the period in which they are earned. There was no impact from the adoption of ASC 606 on these obligations.

For the years ended December 31, 2018, 2017 and 2016, we recognized the following collaboration revenue and reduction of research and development expenses related to such services (in thousands):


	Years ended December 31,
	2018		2017		2016
Collaboration revenue - related party
Development activities	$	1,342	$	—	$	1,192
Commercialization activities	3,744		2,954		170
Reduction of research and development expenses
Research and development activities	—		14		6,596

For the years ended December 31, 2018, 2017 and 2016, we recognized the following totals of collaboration revenue and reduction of research and development expenses (in thousands):


	Years ended December 31,
	2018		2017		2016
Collaboration revenue - related party	$	60,661	$	41,074	$	44,892
Reduction of research and development expenses	—		7,811		19,714

The following table presents changes in our contract assets and liabilities during the year ended December 31, 2018 (in thousands):


	December 31, 2017		Additions		Deductions		December 31, 2018
Contract assets
Collaboration receivable – related party (1)	$	2,448	$	28,695	$	(28,681)	$	2,462
Royalty receivable – related party (1)	1,222		7,087		(6,075)		2,234
Contract liabilities
Deferred revenue – related party, current and net of current portions (2)	163,640		9,237		(80,358)		92,519

(1) Additions to receivables relate to amounts billed to Celgene for reimbursable costs incurred by us during the reporting period. Deductions to receivables relate to collection of receivables during the reporting period.

(2) Additions to deferred revenue relate to consideration from Celgene during the reporting period. Deductions relate to deferred revenue recognized as revenue during the reporting period and the cumulative catch-up adjustment recognized upon adoption of ASC 606 on January 1, 2018.

During the year ended December 31, 2018, we recognized the following as revenue due to changes in the contract liability balances (in thousands):


Amounts included in the contract liability at the beginning of the period	$	37,590
Performance obligations satisfied in previous periods	469

As of December 31, 2018, the aggregate amount of the transaction price allocated to performance obligations that are partially unsatisfied was $100.3 million.

Accounting analysis and revenue recognition – royalty revenue

For arrangements that include sales-based royalties and sales-based milestones and in which the license is deemed to be the predominant item to which the royalties relate, we recognize royalty revenue upon the later of (i) when the related sales occur, or (ii) when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied).

As the underlying performance obligation, or delivery of the enasidenib license, had been satisfied as of June 2014, royalty revenue is recognized as the related sales occur.

During the years ended December 31, 2018, 2017 and 2016, we recognized the following as royalty revenue (in thousands):


	Years ended December 31,
	2018		2017		2016
Royalty revenue – related party	$	7,215	$	1,937	$	—

Accounting analysis and revenue recognition – milestone revenue

At each reporting period we evaluate whether milestones are considered probable of being reached and, to the extent that a significant reversal would not occur in future periods, estimate the amount to be included in the transaction price using the most likely amount method. Milestone payments that are not within our control, such as regulatory approvals, are not considered probable of being achieved and are excluded from the transaction price until those approvals are received.

During the year ended December 31, 2018, Celgene submitted an MAA to the EMA for IDHIFA® for IDH2 mutant-positive R/R AML. As a result of the filing, we determined that a $15.0 million milestone payment for the filing of a first new drug application equivalent in an ex-U.S. country was considered probable of being reached and that a significant reversal of revenue would not occur in future periods. As the underlying performance obligation, or delivery of the license to IDHIFA®, had been satisfied as of June 2014, the milestone payment was recognized in full as collaboration revenue.

During the year ended December 31, 2016, upon the initiation of IDHENTIFY phase 3 study of enasidenib, we earned and received a milestone payment of $25.0 million, which was recognized as collaboration revenue.

The next potential milestone expected to be achieved under our collaboration agreements with Celgene is the first regulatory approval in any of China, Japan or a major European country. Achievement of this event will result in a milestone payment of $35.0 million under the 2010 Agreement.

CStone Pharmaceuticals

In June 2018, we entered into an exclusive license agreement with CStone, or the CStone Agreement, to grant CStone specified intellectual property licenses to enable CStone to develop and commercialize certain products containing ivosidenib in mainland China, Hong Kong, Macau, and Taiwan. We retain development and commercialization rights for the rest of the world. Pursuant to the CStone Agreement, CStone will initially be responsible for the development and commercialization of ivosidenib in AML, cholangiocarcinoma, and, at our discretion, brain cancer indications.

Under the terms of the CStone Agreement, we received an initial upfront payment in the amount of $12.0 million and are entitled to receive up to an additional $412.0 million in milestone payments upon the achievement of certain development, regulatory and sales milestone events. Approximately half of the milestone payments are related to the development and commercialization of ivosidenib in AML, cholangiocarcinoma and the other half of the milestone payments are related to brain cancer indications, including glioma. We will also be entitled to receive tiered royalties, ranging from 15% to 19% percent, on annual net sales, if any, of ivosidenib.

CStone is responsible for all costs it incurs in developing, obtaining regulatory approval of, and commercializing ivosidenib in China, Hong Kong, Macau, and Taiwan, as well as certain costs incurred by us.

During the term of the CStone Agreement, each party and its affiliates are prohibited from developing or commercializing any other compound or product that inhibits IDH1 mutations at specified levels of binding, in the case of CStone, anywhere in the world, and in our case, in China, Hong Kong, Macau, and Taiwan.

Termination

Unless earlier terminated, the CStone Agreement will expire upon the expiration of the last royalty term for the last licensed product within the scope of the CStone Agreement. At any time after CStone has obtained regulatory approval in mainland China in R/R AML and the last patient has been enrolled in a specified clinical trial (or, if earlier, at any time that CStone acquires or is acquired by an entity with a competing or restricted product), CStone may terminate the CStone Agreement in its entirety by providing us with prior written notice. Either party may, subject to specified cure periods, terminate the CStone Agreement in the event of the other party’s uncured material breach. Either party may terminate the CStone Agreement under specified circumstances relating to the other party’s insolvency. We have the right to terminate the CStone Agreement immediately if CStone or its affiliates or sublicensees or subcontractors challenges the validity, patentability, or enforceability of certain patent rights that relate to ivosidenib and are owned by or licensed to us or our affiliates.

Accounting analysis and revenue recognition - collaboration revenue

The CStone Agreement was determined to be within the scope of ASC 606. Accordingly, in determining the appropriate amount of revenue to be recognized, we performed the following steps: (i) identified the promised goods or services in the contract; (ii) determined whether the promised goods or services are performance obligations including whether they are distinct in the context of the contract; (iii) measured the transaction price, including the constraint on variable consideration; (iv) allocated the transaction price to the performance obligations; and (v) recognized revenue when (or as) we satisfied each performance obligation.

As part of the accounting for the CStone Agreement, we developed assumptions that require judgment to determine the SSP for each performance obligation identified in the contract. We use key assumptions to determine the SSP, which include forecast of revenues, development timelines, reimbursement rates, discount rates and probabilities of technical and regulatory success.

The satisfied and unsatisfied performance obligations, each of which are considered by us to be distinct within the context of the contract, their SSP, the method of recognizing the allocated consideration, and the period through which they are expected to be recognized are as follows:

Performance
Obligations

SSP

No. of Performance Obligation(s)

Recognition
Method

Licenses (1)

16.4

million

Fully satisfied; recognized upon delivery of license

Other services (2)

1.7

million

As services are delivered, expected to be through September 2019

(1) The SSP was developed by probability weighting multiple cash flow scenarios using the income approach. Our management estimates within the models include the expected, probability-weighted net profits from estimated future sales, an estimate of the direct costs incurred to generate future cash flows, a discount rate and other business forecast factors. There are significant judgments and estimates inherent in the determination of the SSP of these units of accounting. These judgments and estimates include assumptions regarding future operating performance, the timelines of the clinical trials and regulatory approvals, and other factors. If different reasonable assumptions are utilized, the SSP and revenue recognized would vary.

(2) The SSP was developed using our management’s best estimate of the cost of obtaining these services at arm’s length from a third-party provider.

During the year ended December 31, 2018, we recognized as collaboration revenue the following non-contingent consideration allocated to each performance obligation (in thousands):


	Under Topic 606		Under Topic 605		Effect of Change
Collaboration revenue – other
License	$	12,440	$	12,000	$	440

During the year ended December 31, 2018, we recognized $0.2 million as collaboration revenue - other for certain other services provided by us, that were not considered performance obligations as of the inception date of the CStone Agreement.

The following table presents changes in our contract assets during the year ended December 31, 2018 (in thousands):


	December 31, 2017		Additions		Deductions		December 31 2018
Contract assets
Collaboration receivable – other (1)	$	—	$	12,670	$	(12,000)	$	670

(1) Additions to contract assets relate to receivables from CStone and deductions to contract assets relate to collection of receivables during the reporting period.

As of December 31, 2018, the aggregate amount of the transaction price allocated to performance obligations that are partially unsatisfied was $1.3 million.

Aurigene Discovery Technologies Limited

In April 2017, we entered into a global license agreement with Aurigene Discovery Technologies Limited, or Aurigene, to research, develop and commercialize small molecule inhibitors for DHODH, or the Aurigene Agreement.

Under the terms of the Aurigene Agreement, Aurigene will provide us exclusive rights to its portfolio of novel small molecules for DHODH. Financial terms of the Aurigene Agreement include a $3.0 million upfront payment and potential future milestone payments of up to $17.0 million if we achieve certain development and regulatory milestones. The next potential milestone

expected to be achieved under the Aurigene Agreement is the initiation of the first phase 1 clinical trial for DHODH. Achievement of this event will result in milestone payments owed to Aurigene of $2.0 million.

Aurigene is also eligible to receive low single-digit royalties on net product sales, if any. We will conduct preclinical studies and, if successful, fund further global research and development, as well as regulatory and commercial activities.

The term of the Aurigene Agreement will continue until the earlier of: (a) termination for convenience at our sole discretion upon 90 days prior written notice, (b) termination by either party for material breach, or (c) the expiration of the last-to-expire of all payment obligations hereunder with respect to all licensed products under the Aurigene Agreement.

Accounting analysis

The $3.0 million upfront payment was incurred in the year ended December 31, 2017 and recorded as research and development expense. Costs incurred and milestone payments due to Aurigene prior to regulatory approval are recognized as expenses in the period incurred. Payments due to Aurigene upon or subsequent to regulatory approval will be capitalized and amortized over the shorter of the remaining license or product patent life.

Common Stock	12 Months Ended
Common Stock	Dec. 31, 2018
Equity [Abstract]
Common Stock	Common StockWe are authorized to issue 125,000,000 shares of our common stock. Holders of common stock are entitled to one vote per share. Additionally, holders of common stock are entitled to receive dividends, if and when declared by our board of directors, and to share ratably in our assets legally available for distribution to our shareholders in the event of liquidation.

Share-Based Payments

12 Months Ended

Dec. 31, 2018

Disclosure of Compensation Related Costs, Share-based Payments [Abstract]

Share-Based Payments

Stock incentive plans

In June 2013, our Board of Directors adopted and, in July 2013 our stockholders approved, the 2013 Stock Incentive Plan, or the 2013 Plan. The 2013 Plan became effective upon the closing of our initial public offering and provides for the grant of incentive stock options, non-qualified stock options, stock appreciation rights, restricted stock awards, restricted stock units, or RSUs, performance-based stock units, or PSUs, and other stock-based awards to employees, non-employees and non-employee directors. Following the adoption of the 2013 Plan, we granted no further stock options or other awards under the 2007 Stock Incentive Plan, or the 2007 Plan. Any options or awards outstanding under the 2007 Plan at the time of adoption of the 2013 Plan remain outstanding and effective. As of December 31, 2018, the total number of shares reserved under the 2007 Plan and the 2013 Plan are 7,973,725, and we had 1,856,481 shares available for future issuance under the 2013 Plan.

The 2013 Plan provides for an annual increase, to be added on the first day of each fiscal year, beginning with the fiscal year ending December 31, 2014 and continuing until the expiration of the 2013 Plan, equal to the lesser of (i) 2,000,000 shares of common stock, (ii) 4% of the outstanding shares of common stock on such date or (iii) an amount determined by our Board of Directors. On January 1, 2019, the annual increase for the 2013 Plan resulted in an additional 2,000,000 shares authorized for issuance.

Stock options

The following table summarizes the stock option activity of all stock incentive plans for the year ended December 31, 2018:


	Number of Stock Options	Weighted- Average Exercise Price		Weighted- Average Remaining Contractual Term (in years)	Aggregate Intrinsic Value (in thousands)
Outstanding at December 31, 2017	5,577,562	$	49.58	7.27	$	94,336
Granted	1,346,745	78.10
Exercised	(1,125,009)	24.01
Forfeited/Expired	(383,229)	76.26
Outstanding at December 31, 2018	5,416,069	$	60.10	7.30	$	27,941
Exercisable at December 31, 2018	2,933,538	$	55.43	6.22	$	26,559
Vested and expected to vest at December 31, 2018	5,416,069	$	60.10	7.30	$	27,941

The weighted-average grant date fair value of options granted was $53.22, $35.24 and $28.41 during the years ended December 31, 2018, 2017 and 2016, respectively. The total intrinsic value of options exercised was $65.1 million, $31.5 million and $26.4 million during the years ended December 31, 2018, 2017 and 2016, respectively.

At December 31, 2018, the total unrecognized compensation expense related to unvested stock option awards was $95.1 million, which we expect to recognize over a weighted-average period of approximately 2.58 years.

Restricted stock units

Upon vesting, each RSU entitles the holder to receive a specified number of shares of our common stock. The following table presents RSU activity for the year ended December 31, 2018:


	Number of Stock Units	Weighted-Average Grant Date Fair Value
Unvested shares at December 31, 2017	125,584	$	47.46
Granted	496,106	78.36
Vested	(59,250)	42.11
Forfeited	(30,296)	72.14
Unvested shares at December 31, 2018	532,144	$	75.45

As of December 31, 2018, there was approximately $27.2 million of total unrecognized compensation expense related to RSUs, which we expect to be recognized over a weighted-average period of 1.92 years.

Performance-based stock units

At the achievement of the performance-based and service-based vesting criteria, each PSU entitles the holder to receive a specified number of shares of our common stock. The following table presents PSU activity for the year ended December 31, 2018:


	Number of Stock Units	Weighted-Average Grant Date Fair Value
Unvested shares at December 31, 2017	176,186	$	52.98
Granted	4,000	79.05
Vested	(2,000)	79.05
Forfeited	(9,155)	64.44
Unvested shares at December 31, 2018	169,031	$	52.67

2013 Employee Stock Purchase Plan

In June 2013, our Board of Directors adopted, and in July 2013 our stockholders approved, the 2013 Employee Stock Purchase Plan, or the 2013 ESPP. We issued 53,255 shares and 59,651 shares during the years ended December 31, 2018 and 2017, respectively, under the 2013 ESPP. The 2013 ESPP provides participating employees with the opportunity to purchase up to an aggregate of 327,272 shares of our common stock. As of December 31, 2018, we had 160,536 shares available for future issuance under the 2013 ESPP.

Stock-based compensation expense

During the years ended December 31, 2018, 2017 and 2016, we recorded stock-based compensation expense for employee and non-employee stock options and performance-based stock options, RSUs, PSUs and ESPP shares. Stock-based compensation expense by award type included within the consolidated statements of operations is as follows (in thousands):


	Years Ended December 31,
	2018		2017		2016
Stock options and performance-based stock options	$	51,460	$	43,997	$	39,351
Restricted stock units	12,032		2,858		1,964
Performance-based stock units	8,717		—		—
Employee Stock Purchase Plan	1,148		954		771
Total stock-based compensation expense	$	73,357	$	47,809	$	42,086

Expenses related to equity-based awards were allocated as follows in the consolidated statements of operations (in thousands):


	Years Ended December 31,
	2018		2017		2016
Research and development expense	$	41,982	$	30,807	$	25,386
Selling, general and administrative expense	31,375		17,002		16,700
	$	73,357	$	47,809	$	42,086

No related tax benefits were recognized for the years ended December 31, 2018, 2017 and 2016.

The fair value of each stock option granted to employees is estimated on the date of grant using the Black-Scholes option-pricing model. For non-employees, the fair value of each stock option is estimated on each vesting and reporting date using the Black-Scholes option-pricing model. The following table summarizes the weighted average assumptions used in calculating the grant date fair value of the awards:


	Years Ending December 31,
	2018		2017		2016
Risk-free interest rate	2.71	%	2.05	%	1.42	%
Expected dividend yield	—		—		—
Expected term (in years)	6.06		6.05		6.05
Expected volatility	76.62	%	77.73	%	72.84	%

Expected term

We use the “simplified method” as prescribed by the Securities and Exchange Commission Staff Accounting Bulletin No. 107, Share Based Payments, to estimate the expected term of stock option grants. Under this approach, the weighted-average expected life is presumed to be the average of the contractual term of ten years and the weighted-average vesting term of the stock options, taking into consideration multiple vesting tranches. We utilize this method due to lack of historical data and the plain-vanilla nature of our share-based awards.

Volatility

We use a weighted-average of expected volatility based on the volatilities of a representative group of publicly traded biopharmaceutical companies, including ourselves. The expected volatility has been determined using a weighted-average of the historical volatilities of the representative group of companies for a period equal to the expected term of the option grant.

Risk-free rate

The risk-free rate is based on the yield curve of U.S. Treasury securities with periods commensurate with the expected term of the options being valued.

Dividends

We have never paid, and do not anticipate paying, any cash dividends in the foreseeable future, and, therefore, use an expected dividend yield of zero in the option-pricing model.

Forfeitures

We account for forfeitures as they occur and, therefore, do not estimate forfeitures.

Income Taxes

12 Months Ended

Dec. 31, 2018

Income Tax Disclosure [Abstract]

Income Taxes

The domestic and foreign components of loss before income taxes are as follows (in thousands):


	Years Ended December 31,
	2018		2017		2016
Domestic	$	(311,159)	$	(290,423)	$	(179,896)
Foreign	(34,869)		(24,247)		(18,575)
Total	$	(346,028)	$	(314,670)	$	(198,471)

We did not have any provision for income taxes for the years ended December 31, 2018, 2017 and 2016.

A reconciliation of the expected income tax benefit (expense) computed using the federal statutory income tax rate to our effective income tax rate is as follows for the years ended December 31, 2018, 2017 and 2016:


	Years Ended December 31,
	2018		2017		2016
Income tax benefit computed at federal statutory tax rate	21.0	%	35.0	%	35.0	%
State taxes, net of federal benefit	0.8	%	4.0	%	2.9	%
Change in valuation allowance	(28.4)	%	(19.4)	%	(43.4)	%
General business credits and other credits	5.7	%	10.4	%	9.5	%
Permanent differences and other adjustments	(0.7)	%	—	%	(0.3)	%
Incentive stock options	2.2	%	0.3	%	(1.8)	%
Foreign rate differential	(0.6)	%	(1.6)	%	(1.9)	%
Impact of federal rate change	—	%	(28.7)	%	—	%
Total	—	%	—	%	—	%

Deferred income taxes reflect the net tax effects of temporary differences between the carrying amount of assets and liabilities for financial reporting purposes and the amounts used for income tax purposes. Significant components of our deferred tax assets and liabilities for the years ended December 31, 2018 and 2017 are as follows (in thousands):


	December 31,
	2018		2017
Deferred tax assets:
Net operating loss carryforwards	$	211,563	$	131,165
Deferred revenue	21,956		41,243
Tax credit carryforwards	120,605		100,791
Purchased intangible assets	3,204		3,906
Stock-based compensation	27,636		20,539
Deferred rent	4,458		5,042
Non-deductible accruals and reserves, including inventory	4,900		3,778
Total deferred tax assets	394,322		306,464
Depreciation and amortization	(3,569)		(4,549)
Less: valuation allowance	(390,753)		(301,915)
Net deferred taxes	$	—	$	—

In December 2017, the Tax Cuts and Jobs Act, or TCJA, was signed into law. Among other things, the TCJA permanently lowers the corporate federal income tax rate to 21% from the existing maximum rate of 35%, effective for tax years including or commencing January 1, 2018. As a result of the reduction of the corporate federal income tax rate to 21%, U.S. GAAP requires companies to revalue their deferred tax assets and deferred tax liabilities as of the date of enactment, with the resulting tax effects accounted for in the reporting period of enactment. This revaluation resulted in a provision of $90.0 million to income tax expense in continuing operations and a corresponding reduction in the valuation allowance. As a result, there was no impact on our consolidated statements of operations from the reduction in tax rate. The other provisions of the TCJA did not have a material impact on the consolidated financial statements.

As of December 31, 2018, we had net operating loss carryforwards, or NOLs, available to reduce federal, state and foreign income taxes of approximately $774.8 million, $586.4 million and $80.8 million, respectively. If not utilized, these NOLs begin to expire in 2033 (for pre-2018 NOLs), 2032 and 2022, respectively. Approximately $311.5 million of federal NOLs can be carried forward indefinitely. At December 31, 2018, we also had available research and development tax credits for federal and state income tax purposes of approximately $24.4 million and $11.9 million, respectively. If not utilized, the credits begin to expire in 2027 and 2020 for federal and state income tax purposes, respectively. We engaged in clinical testing activities and incurred expenses that qualify for the federal orphan drug tax credit. At December 31, 2018, we had available orphan drug tax credits for federal purposes only of approximately $86.8 million. If not utilized, the orphan drug credits begin to expire in 2035.

As provided by Section 382 of the Internal Revenue Code of 1986, or Section 382, and similar state provisions, utilization of NOLs and tax credit carryforwards may be subject to substantial annual limitations due to ownership change limitations that

have previously occurred or that could occur in the future. Ownership changes may limit the amount of NOLs and tax credit carryforwards that can be utilized annually to offset future taxable income and tax, respectively. In general, an ownership change, as defined by Section 382, results from transactions that increase the ownership of five percent stockholders in the stock of a corporation by more than 50 percent in the aggregate over a three year period. We completed a review of our changes in ownership through December 31, 2018 and determined that transactions have resulted in no ownership changes during the year ended December 31, 2018, as defined by Section 382. The impact of the historical ownership changes has been reflected in our deferred tax assets in the table above. There could be additional ownership changes after December 31, 2018 that could further limit the amount of NOLs and tax credit carryforwards that we can utilize.

As required by ASC 740, we have evaluated the positive and negative evidence bearing upon the realizability of our deferred tax assets. Based on the weight of available evidence, both positive and negative, we recorded a valuation allowance of $390.8 million and $301.9 million as of December 31, 2018 and December 31, 2017, respectively, because we have determined that it is more likely than not that these assets will not be fully realized. The valuation allowance increased by $88.8 million and $93.9 million for the years ended December 31, 2018 and, 2017, respectively.

We apply the accounting guidance in ASC 740 related to accounting for uncertainty in income taxes. Our reserves related to taxes are based on a determination of whether, and how much of, a tax benefit taken by us in our tax filings or positions is more likely than not to be realized following resolution of any potential contingencies present related to the tax benefit.

The following table presents our unrecognized tax benefits activity for the years ended December 31, 2018 and 2017 (in thousands):


	December 31,
	2018		2017
Unrecognized tax benefits at Unrecogized tax benefits at the beginning of the year	$	11,263	$	—
Gross increases - current period tax positions	3,025		11,263
Unrecognized tax benefits at Unrecognized tax benefits at the end of the year	$	14,288	$	11,263

The uncertain tax position does not impact our effective income tax rate due to the full valuation allowance.

We are subject to taxation in the United States and Switzerland. The statute of limitations for assessment by the IRS and state tax authorities is open for tax years ending December 31, 2018, 2017, 2016, and 2015, although carryforward attributes that were generated for tax years prior to 2015 may still be adjusted upon examination by the IRS or state tax authorities if they either have been, or will be, used in a future period. The statute of limitations for assessment in Switzerland remains open for tax year ending December 31, 2018, 2017, 2016, and 2015. There are currently no federal, state or foreign audits in progress.

Defined Contribution Benefit Plan	12 Months Ended
Defined Contribution Benefit Plan	Dec. 31, 2018
Retirement Benefits [Abstract]
Defined Contribution Benefit Plan	Defined Contribution Benefit PlanWe sponsor a 401(k) retirement plan, in which substantially all of our full-time employees are eligible to participate. Participants may contribute a percentage of their annual compensation to this plan, subject to statutory limitations. We will make matching contributions equal to 100% of the employee’s contributions, subject to a maximum of 4% of eligible compensation.

Net Loss per Share

12 Months Ended

Dec. 31, 2018

Earnings Per Share [Abstract]

Net Loss per Share

Since we had a net loss for all periods presented, the effect of all potentially dilutive securities is anti-dilutive. Accordingly, basic and diluted net loss per share was the same for the years ended December 31, 2018, 2017 and 2016.

The following common stock equivalents were excluded from the calculation of diluted net loss per share applicable to common stockholders for the periods indicated because including them would have had an anti-dilutive effect:


	Years ended December 31,
	2018	2017	2016
Stock options	5,416,069	5,577,562	5,218,880
Restricted stock units	532,144	125,584	77,050
Performance-based stock units	169,031	—	—
Employee Stock Purchase Plan shares	32,304	22,062	24,018
	6,149,548	5,725,208	5,319,948

Selected Quarterly Financial Data (Unaudited)

12 Months Ended

Dec. 31, 2018

Quarterly Financial Information Disclosure [Abstract]

Selected Quarterly Financial Data (Unaudited)

The following table contains quarterly financial information for 2018 and 2017 (in thousands, except per share data):


2018	First Quarter		Second Quarter		Third Quarter		Fourth Quarter
Total revenue	$	8,762	$	40,414	$	15,198	$	30,013
Loss from operations	(94,012)		(72,949)		(99,162)		(96,356)
Net loss	(90,825)		(68,745)		(94,664)		(91,794)
Net loss per share – basic and diluted	(1.63)		(1.19)		(1.63)		(1.58)

2017	First Quarter		Second Quarter		Third Quarter		Fourth Quarter
Total revenue	$	10,508	$	11,346	$	11,358	$	9,799
Loss from operations	(67,047)		(84,600)		(79,017)		(90,130)
Net loss	(66,166)		(83,082)		(77,137)		(88,285)
Net loss per share – basic and diluted	(1.56)		(1.78)		(1.59)		(1.81)

Summary of Significant Accounting Policies (Policies)

12 Months Ended

Dec. 31, 2018

Accounting Policies [Abstract]

Principles of consolidation

Use of estimates

Cash and cash equivalents

We consider highly liquid investments with a maturity of three months or less when purchased to be cash equivalents. Cash equivalents are stated at fair value.

Marketable securities

Fair value measurements

Level 1 – Unadjusted quoted prices in active markets for identical assets or liabilities.

There have been no changes to the valuation methods during the years ended December 31, 2018 and 2017. We evaluate transfers between levels at the end of each reporting period.

Accounts receivable, net

Concentrations of credit risk

Inventory

actual market conditions are less favorable than projected by management, additional write-downs of inventory may be required.

Property and equipment


Laboratory equipment						5 years
Computer equipment and software						3 years
Leasehold improvements						Shorter of asset’s useful life or remaining term of lease
Furniture and fixtures						5 years
Office equipment						5 years

Impairment of long-lived assets

Revenue from Contracts with Customers

•persuasive evidence of an arrangement exists;

•delivery has occurred or services have been rendered;

•the seller’s price to the buyer is fixed or determinable; and

•collectability is reasonably assured.

Adoption of ASC 606

Cost of Sales

Cost of SalesCost of sales consists primarily of manufacturing costs of TIBSOVO®. Based on our policy to expense costs associated with the manufacturing of our products prior to regulatory approval, certain of the manufacturing costs associated with product shipments of TIBSOVO® recorded during the year ended December 31, 2018 were expensed prior to July 20, 2018 and, therefore, are not included in costs of sales during the current period.

Research and development costs

Stock-based compensation

Income taxes

Comprehensive income (loss)

Net loss per share

Segment and geographic information

Recent accounting pronouncements

Leases

Other Recent Accounting Pronouncements

Subsequent events

Summary of Significant Accounting Policies (Tables)

12 Months Ended

Dec. 31, 2018

Accounting Policies [Abstract]

Estimated Useful Lives of Property and Equipment

Property and equipment is stated at cost, and depreciated using the straight-line method over the estimated useful lives of the respective assets:


Laboratory equipment						5 years
Computer equipment and software						3 years
Leasehold improvements						Shorter of asset’s useful life or remaining term of lease
Furniture and fixtures						5 years
Office equipment						5 years

Schedule of Impact of New Accounting Pronouncements

The impact of the cumulative effect of the accounting changes upon the adoption of the standard is as follows (in thousands):


	December 31, 2017		Cumulative Effect		January 1, 2018
Deferred revenue – related party, current and net of current portions	$	163,640	$	(39,456)	$	124,184
Accumulated deficit	(798,061)		39,456		(758,605)

The following tables summarize the effects of adopting ASC 606 on our consolidated financial statements (in thousands, except per share data):

Consolidated Balance Sheets


	December 31, 2018
	Under Topic 606		Under Topic 605		Effect of Change
Accounts receivable, net	$	5,076	$	5,076	$	—
Collaboration receivable – related party	2,462		2,462		—
Collaboration receivable – other	670		230		440
Total current assets	613,780		613,340		440
Total assets	858,457		858,017		440

Deferred revenue – related party	32,710		29,133		3,577
Total current liabilities	93,503		89,926		3,577
Deferred revenue, net of current portion – related party	59,809		101,180		(41,371)
Total liabilities	170,920		208,714		(37,794)
Accumulated deficit	(1,104,633)		(1,142,867)		38,234
Total stockholders’ equity	687,537		649,303		38,234
Total liabilities and stockholders’ equity	858,457		858,017		440

Consolidated Statements of Operations


	Year ended December 31, 2018
	Under Topic 606		Under Topic 605		Effect of Change
Product revenue, net	$	13,841	$	13,841	$	—
Collaboration revenue – related party	60,661		58,994		1,667
Collaboration revenue – other	12,670		12,230		440
Total revenue	94,387		92,280		2,107
Research and development expense	341,324		337,995		3,329
Total cost and expenses	456,866		453,537		3,329
Loss from operations	(362,479)		(361,257)		(1,222)
Net loss	(346,028)		(344,806)		(1,222)
Net loss per share – basic and diluted	(6.03)		(6.01)		(0.02)

Consolidated Statements of Comprehensive Loss


	Year ended December 31, 2018
	Under Topic 606		Under Topic 605		Effect of Change
Net loss	$	(346,028)	$	(344,806)	$	(1,222)
Comprehensive loss	(346,810)		(345,588)		(1,222)

Consolidated Statements of Cash Flows


	Year ended December 31, 2018
	Under Topic 606		Under Topic 605		Effect of Change
Net loss	$	(346,028)	$	(344,806)	$	(1,222)
Adjustments to reconcile net loss to net cash used in operating activities:
Accounts receivable, net	(5,076)		(5,076)		—
Collaboration receivable – related party	(14)		(14)		—
Collaboration receivable – other	(670)		(230)		(440)
Deferred revenue – related party	(31,665)		(33,327)		1,662

Fair Value Measurements (Tables)

12 Months Ended

Dec. 31, 2018

Fair Value Disclosures [Abstract]

Cash Equivalents and Marketable Securities Measured at Fair Value on a Recurring Basis

The following table summarizes our cash equivalents and marketable securities measured at fair value on a recurring basis as of December 31, 2018 (in thousands):


	Level 1		Level 2		Level 3		Total
Cash equivalents	$	42,673	$	1,999	$	—	$	44,672
Marketable securities:
Certificates of deposit	—		956		—		956
U.S. Treasuries	—		242,961		—		242,961
Government securities	—		145,213		—		145,213
Corporate debt securities	—		345,789		—		345,789
	$	42,673	$	736,918	$	—	$	779,591

Marketable Securities (Tables)

12 Months Ended

Dec. 31, 2018

Investments, Debt and Equity Securities [Abstract]

Summary of Marketable Securities

Marketable securities at December 31, 2018 consisted of the following (in thousands):


	Amortized Cost		Unrealized Gains		Unrealized Losses		Fair Value
Current:
Certificates of deposit	$	960	$	—	$	(4)	$	956
U.S. Treasuries	231,101		7		(228)		230,880
Government securities	75,335		—		(121)		75,214
Corporate debt securities	208,233		—		(483)		207,750
Non-current:
U.S. Treasuries	12,202		4		(125)		12,081
Government securities	70,177		10		(188)		69,999
Corporate debt securities	139,082		12		(1,055)		138,039
Total marketable securities	$	737,090	$	33	$	(2,204)	$	734,919

Marketable securities at December 31, 2017 consisted of the following (in thousands):


	Amortized Cost		Unrealized Gains		Unrealized Losses		Fair Value
Current:
Certificates of deposit	$	8,081	$	—	$	(11)	$	8,070
U.S. Treasuries	113,852		—		(119)		113,733
Government securities	44,421		—		(57)		44,364
Corporate debt securities	155,222		—		(177)		155,045
Non-current:
Certificates of deposit	960		—		(8)		952
U.S. Treasuries	36,165		—		(311)		35,854
Government securities	23,992		—		(182)		23,810
Corporate debt securities	83,722		—		(524)		83,198
Total marketable securities	$	466,415	$	—	$	(1,389)	$	465,026

Property and Equipment, net (Tables)

12 Months Ended

Dec. 31, 2018

Property, Plant and Equipment [Abstract]

Summary of Property and Equipment

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


	December 31,
	2018		2017
Laboratory equipment	$	20,165	$	17,524
Computer equipment and software	5,449		4,293
Leasehold improvements	22,084		20,322
Furniture and fixtures	1,065		752
Office equipment	407		319
Construction in progress	1,302		618
Total property and equipment	50,472		43,828
Less: accumulated depreciation	(26,152)		(19,397)
Total property and equipment, net	$	24,320	$	24,431

Inventory (Tables)

12 Months Ended

Dec. 31, 2018

Inventory Disclosure [Abstract]

Schedule of Inventory

Inventory consisted of the following (in thousands):


	December 31,
	2018		2017
Raw materials	$	—	$	—
Work-in-process	788		—
Finished goods	81		—
Total Inventory	$	869	$	—

Accrued Expenses (Tables)

12 Months Ended

Dec. 31, 2018

Payables and Accruals [Abstract]

Summary of Accrued Expenses

Accrued expenses and other current liabilities consisted of the following (in thousands):


	December 31,
	2018		2017
Accrued compensation	$	20,843	$	15,693
Accrued research and development costs	14,777		14,849
Accrued professional fees	5,441		3,140
Accrued other	1,086		349
Total accrued expenses	$	42,147	$	34,031

Commitments and Contingent Liabilities (Tables)

12 Months Ended

Dec. 31, 2018

Commitments and Contingencies Disclosure [Abstract]

Summary of Future Annual Minimum Lease Payments Due Under Operating Leases

As of December 31, 2018, minimum rental commitments under non-cancelable leases, for each of the next five years and total thereafter were as follows (in thousands):


2019	$	12,759
2020	13,135
2021	13,473
2022	15,552
2023	17,145
Thereafter	19,223
	$	91,287

Product Revenue (Tables)

12 Months Ended

Dec. 31, 2018

Revenue from Contract with Customer [Abstract]

Schedule of Product Revenue Allowance and Reserves

The following table summarizes balances and activity in each of the product revenue allowance and reserve categories for the year ended December 31, 2018 (in thousands):


	Contractual Adjustments	Government Rebates	Returns	Total
Balance at December 31, 2017	—	—	—	—
Current provisions relating to sales in the current year	1,777	422	334	2,533
Adjustments relating to prior years	—	—	—	—
Payments/returns relating to sales in the current year	(1,185)	(97)	—	(1,282)
Payments/returns relating to sales in the prior years	—	—	—	—
Balance at December 31, 2018	592	325	334	1,251

Schedule of Revenue Related Reserves

Total revenue-related reserves above, included in our condensed consolidated balance sheets, are summarized as follows (in thousands):


	December 31, 2018
Reduction of accounts receivable	$	326
Component of accrued expenses	925
Total revenue-related reserves	$	1,251

Schedule of Changes in Contract Assets and Liabilities

The following table presents changes in our contract assets and liabilities during the year ended December 31, 2018 (in thousands):


	December 31, 2017		Additions		Deductions		December 31, 2018
Contract assets
Accounts receivable, net (1)	$	—	$	16,374	$	(11,298)	$	5,076

(1) Additions to accounts receivable, net relate to amounts billed to Customers for product sales and deductions primarily relate to collection of receivables during the reporting period.

Collaboration and License Agreements (Tables)

12 Months Ended

Dec. 31, 2018

Revenue Recognition and Deferred Revenue [Abstract]

Schedule of Milestone-Based Payments Associated With 2016 Agreement

We are eligible to receive the following milestone-based payments associated with the 2016 Agreement:

Program

Milestone

Amount

65/35 program in IO field

Specified clinical development event

$25.0 million

65/35 program in IO field

Specified regulatory milestone events

Up to $183.8 million

50/50 program in IO field

Specified clinical development event

$20.0 million

50/50 program in IO field

Specified regulatory milestone events

Up to $148.8 million

I&I field

Specified clinical development event

$25.0 million

I&I field

Specified regulatory milestone events

Up to $236.3 million

I&I field

Specified commercial milestone events

Up to $125.0 million

Schedule of Satisfied and Unsatisfied Performance Obligations

Performance
Obligations

SSP

No. of Performance
Obligations

Recognition
Method

Fully satisfied at time of adoption

Licenses (1)

86.7

million

Fully satisfied; recognized upon adoption of ASC 606

Research and development services (2)

350.7

million

Fully satisfied; recognized upon adoption of ASC 606

Partially satisfied at time of adoption

Research and development services (2)

266.6

million

Proportionally as services are delivered over the performance period, expected to be through September 2022 (3)

Schedule of Impact of New Accounting Pronouncements, Impact on Collaboration Revenue

During the year ended December 31, 2018, we recognized the following as collaboration revenue (in thousands):


Performance Obligation	Under Topic 606		Under Topic 605		Effect of Change
Collaboration revenue - related party
Licenses	$	15,000	$	15,000	$	—
Research and development services	40,575		38,733		1,842
Committee participation	—		175		(175)
Reduction of research and development expenses
Development services	—		3,329		(3,329)

Summary of Multiple-deliverable Arrangements Revenue, Allocated to Each Performance Obligation

During the years ended December 31, 2018, 2017 and 2016, we recognized as collaboration revenue the following non-contingent consideration allocated to each performance obligation (in thousands):


	Years ended December 31,
	2018		2017		2016
Licenses	$	15,000	$	—	$	1,356
On-going research and development services	40,575		37,953		41,993
Committee participation	—		167		181
Additional development services	—		—		—

Summary of Multiple-deliverable Arrangements Revenue

For the years ended December 31, 2018, 2017 and 2016, we recognized the following collaboration revenue and reduction of research and development expenses related to such services (in thousands):


	Years ended December 31,
	2018		2017		2016
Collaboration revenue - related party
Development activities	$	1,342	$	—	$	1,192
Commercialization activities	3,744		2,954		170
Reduction of research and development expenses
Research and development activities	—		14		6,596

For the years ended December 31, 2018, 2017 and 2016, we recognized the following totals of collaboration revenue and reduction of research and development expenses (in thousands):


	Years ended December 31,
	2018		2017		2016
Collaboration revenue - related party	$	60,661	$	41,074	$	44,892
Reduction of research and development expenses	—		7,811		19,714

Schedule of Changes in Contract Assets and Liabilities

The following table presents changes in our contract assets and liabilities during the year ended December 31, 2018 (in thousands):


	December 31, 2017		Additions		Deductions		December 31, 2018
Contract assets
Collaboration receivable – related party (1)	$	2,448	$	28,695	$	(28,681)	$	2,462
Royalty receivable – related party (1)	1,222		7,087		(6,075)		2,234
Contract liabilities
Deferred revenue – related party, current and net of current portions (2)	163,640		9,237		(80,358)		92,519

During the year ended December 31, 2018, we recognized the following as revenue due to changes in the contract liability balances (in thousands):


Amounts included in the contract liability at the beginning of the period	$	37,590
Performance obligations satisfied in previous periods	469

Schedule of Royalty Revenue

During the years ended December 31, 2018, 2017 and 2016, we recognized the following as royalty revenue (in thousands):


	Years ended December 31,
	2018		2017		2016
Royalty revenue – related party	$	7,215	$	1,937	$	—

Summary of Performance Obligations, CStone Agreement

Performance
Obligations

SSP

No. of Performance Obligation(s)

Recognition
Method

Licenses (1)

16.4

million

Fully satisfied; recognized upon delivery of license

Other services (2)

1.7

million

As services are delivered, expected to be through September 2019

(1) The SSP was developed by probability weighting multiple cash flow scenarios using the income approach. Our management estimates within the models include the expected, probability-weighted net profits from estimated future sales, an estimate of the direct costs incurred to generate future cash flows, a discount rate and other business forecast factors. There are significant judgments and estimates inherent in the determination of the SSP of these units of accounting. These judgments and estimates include assumptions regarding future operating performance, the timelines of the clinical trials and regulatory approvals, and other factors. If different reasonable assumptions are utilized, the SSP and revenue recognized would vary.

(2) The SSP was developed using our management’s best estimate of the cost of obtaining these services at arm’s length from a third-party provider.

Summary of Multiple-deliverable Arrangements Revenue, Allocated to Each Performance Obligation, CStone Agreement

During the year ended December 31, 2018, we recognized as collaboration revenue the following non-contingent consideration allocated to each performance obligation (in thousands):


	Under Topic 606		Under Topic 605		Effect of Change
Collaboration revenue – other
License	$	12,440	$	12,000	$	440

Schedule of Changes in Contract Assets and Liabilities, CStone Agreement

The following table presents changes in our contract assets during the year ended December 31, 2018 (in thousands):


	December 31, 2017		Additions		Deductions		December 31 2018
Contract assets
Collaboration receivable – other (1)	$	—	$	12,670	$	(12,000)	$	670

(1) Additions to contract assets relate to receivables from CStone and deductions to contract assets relate to collection of receivables during the reporting period.

Share-Based Payments (Tables)

12 Months Ended

Dec. 31, 2018

Disclosure of Compensation Related Costs, Share-based Payments [Abstract]

Summary of Company's Stock Option Activity of all Stock Incentive Plans

The following table summarizes the stock option activity of all stock incentive plans for the year ended December 31, 2018:


	Number of Stock Options	Weighted- Average Exercise Price		Weighted- Average Remaining Contractual Term (in years)	Aggregate Intrinsic Value (in thousands)
Outstanding at December 31, 2017	5,577,562	$	49.58	7.27	$	94,336
Granted	1,346,745	78.10
Exercised	(1,125,009)	24.01
Forfeited/Expired	(383,229)	76.26
Outstanding at December 31, 2018	5,416,069	$	60.10	7.30	$	27,941
Exercisable at December 31, 2018	2,933,538	$	55.43	6.22	$	26,559
Vested and expected to vest at December 31, 2018	5,416,069	$	60.10	7.30	$	27,941

Unvested Stock Unit Activity

The following table presents RSU activity for the year ended December 31, 2018:


	Number of Stock Units	Weighted-Average Grant Date Fair Value
Unvested shares at December 31, 2017	125,584	$	47.46
Granted	496,106	78.36
Vested	(59,250)	42.11
Forfeited	(30,296)	72.14
Unvested shares at December 31, 2018	532,144	$	75.45

Schedule of Performance-Based Units

The following table presents PSU activity for the year ended December 31, 2018:


	Number of Stock Units	Weighted-Average Grant Date Fair Value
Unvested shares at December 31, 2017	176,186	$	52.98
Granted	4,000	79.05
Vested	(2,000)	79.05
Forfeited	(9,155)	64.44
Unvested shares at December 31, 2018	169,031	$	52.67

Schedule of Stock-Based Compensation Expense by Award Type Included Within the Condensed Consolidated Statements of Operations

Stock-based compensation expense by award type included within the consolidated statements of operations is as follows (in thousands):


	Years Ended December 31,
	2018		2017		2016
Stock options and performance-based stock options	$	51,460	$	43,997	$	39,351
Restricted stock units	12,032		2,858		1,964
Performance-based stock units	8,717		—		—
Employee Stock Purchase Plan	1,148		954		771
Total stock-based compensation expense	$	73,357	$	47,809	$	42,086

Stock-Based Compensation Expense for Employee and Non-Employee Stock Options, Restricted Stock Units, Performance-Based Stock Options, Performance-Based Stock Units and Employee Stock Purchase Plan Shares

Expenses related to equity-based awards were allocated as follows in the consolidated statements of operations (in thousands):


	Years Ended December 31,
	2018		2017		2016
Research and development expense	$	41,982	$	30,807	$	25,386
Selling, general and administrative expense	31,375		17,002		16,700
	$	73,357	$	47,809	$	42,086

Schedule of Grant Date Fair Value Option Award Weighted Average Assumptions Used

The following table summarizes the weighted average assumptions used in calculating the grant date fair value of the awards:


	Years Ending December 31,
	2018		2017		2016
Risk-free interest rate	2.71	%	2.05	%	1.42	%
Expected dividend yield	—		—		—
Expected term (in years)	6.06		6.05		6.05
Expected volatility	76.62	%	77.73	%	72.84	%

Income Taxes (Tables)

12 Months Ended

Dec. 31, 2018

Income Tax Disclosure [Abstract]

Schedule of Domestic and Foreign Components of Loss Before Income Taxes

The domestic and foreign components of loss before income taxes are as follows (in thousands):


	Years Ended December 31,
	2018		2017		2016
Domestic	$	(311,159)	$	(290,423)	$	(179,896)
Foreign	(34,869)		(24,247)		(18,575)
Total	$	(346,028)	$	(314,670)	$	(198,471)

Reconciliation of Expected Income Tax Benefit (Expense) Computed Using Federal Statutory Income Tax Rate


	Years Ended December 31,
	2018		2017		2016
Income tax benefit computed at federal statutory tax rate	21.0	%	35.0	%	35.0	%
State taxes, net of federal benefit	0.8	%	4.0	%	2.9	%
Change in valuation allowance	(28.4)	%	(19.4)	%	(43.4)	%
General business credits and other credits	5.7	%	10.4	%	9.5	%
Permanent differences and other adjustments	(0.7)	%	—	%	(0.3)	%
Incentive stock options	2.2	%	0.3	%	(1.8)	%
Foreign rate differential	(0.6)	%	(1.6)	%	(1.9)	%
Impact of federal rate change	—	%	(28.7)	%	—	%
Total	—	%	—	%	—	%

Company's Deferred Tax Assets and Liabilities

Significant components of our deferred tax assets and liabilities for the years ended December 31, 2018 and 2017 are as follows (in thousands):


	December 31,
	2018		2017
Deferred tax assets:
Net operating loss carryforwards	$	211,563	$	131,165
Deferred revenue	21,956		41,243
Tax credit carryforwards	120,605		100,791
Purchased intangible assets	3,204		3,906
Stock-based compensation	27,636		20,539
Deferred rent	4,458		5,042
Non-deductible accruals and reserves, including inventory	4,900		3,778
Total deferred tax assets	394,322		306,464
Depreciation and amortization	(3,569)		(4,549)
Less: valuation allowance	(390,753)		(301,915)
Net deferred taxes	$	—	$	—

Schedule of Unrecognized Tax Benefits Rollforward

The following table presents our unrecognized tax benefits activity for the years ended December 31, 2018 and 2017 (in thousands):


	December 31,
	2018		2017
Unrecognized tax benefits at Unrecogized tax benefits at the beginning of the year	$	11,263	$	—
Gross increases - current period tax positions	3,025		11,263
Unrecognized tax benefits at Unrecognized tax benefits at the end of the year	$	14,288	$	11,263

Net Loss per Share (Tables)

12 Months Ended

Dec. 31, 2018

Earnings Per Share [Abstract]

Common Stock Excluded from Calculation of Diluted Earnings Per Share


	Years ended December 31,
	2018	2017	2016
Stock options	5,416,069	5,577,562	5,218,880
Restricted stock units	532,144	125,584	77,050
Performance-based stock units	169,031	—	—
Employee Stock Purchase Plan shares	32,304	22,062	24,018
	6,149,548	5,725,208	5,319,948

Selected Quarterly Financial Data (Unaudited) (Tables)

12 Months Ended

Dec. 31, 2018

Quarterly Financial Information Disclosure [Abstract]

Summary of Quarterly Financial Data

The following table contains quarterly financial information for 2018 and 2017 (in thousands, except per share data):


2018	First Quarter		Second Quarter		Third Quarter		Fourth Quarter
Total revenue	$	8,762	$	40,414	$	15,198	$	30,013
Loss from operations	(94,012)		(72,949)		(99,162)		(96,356)
Net loss	(90,825)		(68,745)		(94,664)		(91,794)
Net loss per share – basic and diluted	(1.63)		(1.19)		(1.63)		(1.58)

2017	First Quarter		Second Quarter		Third Quarter		Fourth Quarter
Total revenue	$	10,508	$	11,346	$	11,358	$	9,799
Loss from operations	(67,047)		(84,600)		(79,017)		(90,130)
Net loss	(66,166)		(83,082)		(77,137)		(88,285)
Net loss per share – basic and diluted	(1.56)		(1.78)		(1.59)		(1.81)

Nature of Business - 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
Subsidiary, Sale of Stock [Line Items]
Number of shares issued from public offering (in shares)	8,152,986
Net proceeds from public offering	$ 516,200	$ 516,206	$ 270,250	$ 162,150
Cash, cash equivalents and marketable securities		$ 805,400
Public Offering
Subsidiary, Sale of Stock [Line Items]
Number of shares issued from public offering (in shares)	7,089,553
Offering price (in usd per share)	$ 67.00
Net proceeds from public offering	$ 448,900
Over-Allotment Option
Subsidiary, Sale of Stock [Line Items]
Number of shares issued from public offering (in shares)	1,063,433
Net proceeds from public offering	$ 67,300

Summary of Significant Accounting Policies - Additional Information (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2018 USD ($) segment	Dec. 31, 2017 USD ($)	Jan. 01, 2019 USD ($)	Jan. 01, 2018 USD ($)
Schedule of Significant Accounting Policies [Line Items]
Minimum period to liquidate	12 months
Accumulated deficit	$ (1,104,633)	$ (798,061)		$ (758,605)
Number of operating segments \| segment	1
ASU 2016-09
Schedule of Significant Accounting Policies [Line Items]
Deferred tax assets		32,700
Accumulated deficit		$ 32,700
ASU 2016-02 \| Pro Forma
Schedule of Significant Accounting Policies [Line Items]
Right-of-use asset			$ 50,000
Lease liability			$ 50,000
Minimum
Schedule of Significant Accounting Policies [Line Items]
Investment maturity period, non-current	1 year	1 year
Maximum
Schedule of Significant Accounting Policies [Line Items]
Investment maturity period, current	1 year	1 year
Investment maturity period, non-current	2 years

Summary of Significant Accounting Policies - Estimated Useful Lives of Property and Equipment (Details)	12 Months Ended
	Dec. 31, 2018
Laboratory equipment
Property, Plant and Equipment [Line Items]
Estimated useful lives of property and equipment	5 years
Computer equipment and software
Property, Plant and Equipment [Line Items]
Estimated useful lives of property and equipment	3 years
Furniture and fixtures
Property, Plant and Equipment [Line Items]
Estimated useful lives of property and equipment	5 years
Office equipment
Property, Plant and Equipment [Line Items]
Estimated useful lives of property and equipment	5 years

Summary of Significant Accounting Policies and Recent Accounting Pronouncements - Impact of Accounting Changes Upon Adoption of ASC 606 (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	Jan. 01, 2018	Dec. 31, 2015
Cumulative Effect of Accounting Changes [Abstract]
Deferred revenue - related party, current and net of current portions												$ 124,184
Accumulated deficit	$ (1,104,633)				$ (798,061)				$ (1,104,633)	$ (798,061)		(758,605)
Statement of Financial Position [Abstract]
Accounts receivable, net	5,076				0				5,076	0
Collaboration receivable – related party	2,462				2,448				2,462	2,448
Collaboration receivable – other	670				0				670	0
Total current assets	613,780				445,261				613,780	445,261
Total assets	858,457				614,397				858,457	614,397
Deferred revenue – related party	32,710				37,842				32,710	37,842
Total current liabilities	93,503				94,941				93,503	94,941
Deferred revenue, net of current portion – related party	59,809				125,798				59,809	125,798
Total liabilities	170,920				238,894				170,920	238,894
Total stockholders’ equity	687,537				375,503				687,537	375,503	$ 358,591		$ 345,118
Total liabilities and stockholders’ equity	858,457				614,397				858,457	614,397
Income Statement [Abstract]
Revenues									94,387	43,011	69,892
Research and development expense									341,324	292,681	220,163
Total cost and expenses									456,866	363,805	270,877
Loss from operations	$ (96,356)	$ (99,162)	$ (72,949)	$ (94,012)	$ (90,130)	$ (79,017)	$ (84,600)	$ (67,047)	(362,479)	(320,794)	(200,985)
Net loss									$ (346,028)	$ (314,670)	$ (198,471)
Net loss per share - basic and diluted (in usd per share)	$ (1.58)	$ (1.63)	$ (1.19)	$ (1.63)	$ (1.81)	$ (1.59)	$ (1.78)	$ (1.56)	$ (6.03)	$ (6.75)	$ (5.07)
Statement of Comprehensive Income [Abstract]
Comprehensive loss									$ (346,810)	$ (315,746)	$ (198,466)
Adjustments to reconcile net loss to net cash (used in) provided by operating activities:
Accounts receivable, net									(5,076)	0	0
Collaboration receivable – related party									(14)	2,438	3,339
Collaboration receivable – other									(670)	0	0
Deferred revenue – related party									(31,665)	(26,570)	165,846
Product revenue, net
Income Statement [Abstract]
Revenues									13,841	0	0
Collaboration revenue – related party
Income Statement [Abstract]
Revenues									60,661	41,074	69,892
Collaboration revenue – other
Income Statement [Abstract]
Revenues									12,670	0	$ 0
Under Topic 605
Cumulative Effect of Accounting Changes [Abstract]
Deferred revenue - related party, current and net of current portions					$ 163,640					163,640
Accumulated deficit	$ (1,142,867)				$ (798,061)				(1,142,867)	$ (798,061)
Statement of Financial Position [Abstract]
Accounts receivable, net	5,076								5,076
Collaboration receivable – related party	2,462								2,462
Collaboration receivable – other	230								230
Total current assets	613,340								613,340
Total assets	858,017								858,017
Deferred revenue – related party	29,133								29,133
Total current liabilities	89,926								89,926
Deferred revenue, net of current portion – related party	101,180								101,180
Total liabilities	208,714								208,714
Total stockholders’ equity	649,303								649,303
Total liabilities and stockholders’ equity	858,017								858,017
Income Statement [Abstract]
Revenues									92,280
Research and development expense									337,995
Total cost and expenses									453,537
Loss from operations									(361,257)
Net loss									$ (344,806)
Net loss per share - basic and diluted (in usd per share)									$ (6.01)
Statement of Comprehensive Income [Abstract]
Comprehensive loss									$ (345,588)
Adjustments to reconcile net loss to net cash (used in) provided by operating activities:
Accounts receivable, net									(5,076)
Collaboration receivable – related party									(14)
Collaboration receivable – other									(230)
Deferred revenue – related party									(33,327)
Under Topic 605 \| Product revenue, net
Income Statement [Abstract]
Revenues									13,841
Under Topic 605 \| Collaboration revenue – related party
Income Statement [Abstract]
Revenues									58,994
Under Topic 605 \| Collaboration revenue – other
Income Statement [Abstract]
Revenues									12,230
ASU 2014-09 \| Cumulative Effect and Effect of Change
Cumulative Effect of Accounting Changes [Abstract]
Deferred revenue - related party, current and net of current portions												(39,456)
Accumulated deficit	38,234								38,234			$ 39,456
Statement of Financial Position [Abstract]
Accounts receivable, net	0								0
Collaboration receivable – related party	0								0
Collaboration receivable – other	440								440
Total current assets	440								440
Total assets	440								440
Deferred revenue – related party	3,577								3,577
Total current liabilities	3,577								3,577
Deferred revenue, net of current portion – related party	(41,371)								(41,371)
Total liabilities	(37,794)								(37,794)
Total stockholders’ equity	38,234								38,234
Total liabilities and stockholders’ equity	$ 440								440
Income Statement [Abstract]
Revenues									2,107
Research and development expense									3,329
Total cost and expenses									3,329
Loss from operations									(1,222)
Net loss									$ (1,222)
Net loss per share - basic and diluted (in usd per share)									$ (0.02)
Statement of Comprehensive Income [Abstract]
Comprehensive loss									$ (1,222)
Adjustments to reconcile net loss to net cash (used in) provided by operating activities:
Accounts receivable, net									0
Collaboration receivable – related party									0
Collaboration receivable – other									(440)
Deferred revenue – related party									1,662
ASU 2014-09 \| Cumulative Effect and Effect of Change \| Product revenue, net
Income Statement [Abstract]
Revenues									0
ASU 2014-09 \| Cumulative Effect and Effect of Change \| Collaboration revenue – related party
Income Statement [Abstract]
Revenues									1,667
ASU 2014-09 \| Cumulative Effect and Effect of Change \| Collaboration revenue – other
Income Statement [Abstract]
Revenues									$ 440

Fair Value Measurements - Cash Equivalents and Marketable Securities Measured at Fair Value on a Recurring Basis (Details) - Fair Value, Measurements, Recurring $ in Thousands	Dec. 31, 2018 USD ($)
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Cash equivalents	$ 44,672
Total cash equivalents and marketable securities	779,591
Certificates of deposit
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Marketable securities	956
U.S. Treasuries
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Marketable securities	242,961
Government securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Marketable securities	145,213
Corporate debt securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Marketable securities	345,789
Level 1
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Cash equivalents	42,673
Total cash equivalents and marketable securities	42,673
Level 1 \| Certificates of deposit
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Marketable securities	0
Level 1 \| U.S. Treasuries
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Marketable securities	0
Level 1 \| Government securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Marketable securities	0
Level 1 \| Corporate debt securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Marketable securities	0
Level 2
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Cash equivalents	1,999
Total cash equivalents and marketable securities	736,918
Level 2 \| Certificates of deposit
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Marketable securities	956
Level 2 \| U.S. Treasuries
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Marketable securities	242,961
Level 2 \| Government securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Marketable securities	145,213
Level 2 \| Corporate debt securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Marketable securities	345,789
Level 3
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Cash equivalents	0
Total cash equivalents and marketable securities	0
Level 3 \| Certificates of deposit
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Marketable securities	0
Level 3 \| U.S. Treasuries
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Marketable securities	0
Level 3 \| Government securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Marketable securities	0
Level 3 \| Corporate debt securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Marketable securities	$ 0

Fair Value Measurements - Additional Information (Details)	Dec. 31, 2018 USD ($)
Fair Value, Measurements, Recurring \| Level 3
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Fair value of assets (liabilities)	$ 0

Marketable Securities - Summary of Marketable Securities (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Current: \| Certificates of deposit
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	$ 960	$ 8,081
Unrealized Gains	0	0
Unrealized Losses	(4)	(11)
Fair Value	956	8,070
Current: \| U.S. Treasuries
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	231,101	113,852
Unrealized Gains	7	0
Unrealized Losses	(228)	(119)
Fair Value	230,880	113,733
Current: \| Government securities
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	75,335	44,421
Unrealized Gains	0	0
Unrealized Losses	(121)	(57)
Fair Value	75,214	44,364
Current: \| Corporate debt securities
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	208,233	155,222
Unrealized Gains	0	0
Unrealized Losses	(483)	(177)
Fair Value	207,750	155,045
Non-current:
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	737,090	466,415
Unrealized Gains	33	0
Unrealized Losses	(2,204)	(1,389)
Fair Value	734,919	465,026
Non-current: \| Certificates of deposit
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost		960
Unrealized Gains		0
Unrealized Losses		(8)
Fair Value		952
Non-current: \| U.S. Treasuries
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	12,202	36,165
Unrealized Gains	4	0
Unrealized Losses	(125)	(311)
Fair Value	12,081	35,854
Non-current: \| Government securities
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	70,177	23,992
Unrealized Gains	10	0
Unrealized Losses	(188)	(182)
Fair Value	69,999	23,810
Non-current: \| Corporate debt securities
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	139,082	83,722
Unrealized Gains	12	0
Unrealized Losses	(1,055)	(524)
Fair Value	$ 138,039	$ 83,198

Marketable Securities - Additional Information (Details) $ in Millions	12 Months Ended
	Dec. 31, 2018 USD ($) security	Dec. 31, 2017 USD ($) security
Investments, Debt and Equity Securities [Abstract]
Realized gain (loss) on marketable securities	$ 0.0	$ 0.0
Debt securities in an unrealized loss position \| security	242	240
Aggregate fair value of debt securities in an unrealized loss position	$ 639.3	$ 439.4

Property and Equipment, net - Summary of Property and Equipment (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Property, Plant and Equipment [Line Items]
Total property and equipment	$ 50,472	$ 43,828
Less: accumulated depreciation	(26,152)	(19,397)
Total property and equipment, net	24,320	24,431
Laboratory equipment
Property, Plant and Equipment [Line Items]
Total property and equipment	20,165	17,524
Computer equipment and software
Property, Plant and Equipment [Line Items]
Total property and equipment	5,449	4,293
Leasehold improvements
Property, Plant and Equipment [Line Items]
Total property and equipment	22,084	20,322
Furniture and fixtures
Property, Plant and Equipment [Line Items]
Total property and equipment	1,065	752
Office equipment
Property, Plant and Equipment [Line Items]
Total property and equipment	407	319
Construction in progress
Property, Plant and Equipment [Line Items]
Total property and equipment	$ 1,302	$ 618

Property and Equipment, net - Additional Information (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Property, Plant and Equipment [Abstract]
Depreciation expense	$ 7,172	$ 6,432	$ 5,708

Inventory - Schedule of Inventory (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Inventory Disclosure [Abstract]
Raw materials	$ 0	$ 0
Work-in-process	788	0
Finished goods	81	0
Total Inventory	$ 869	$ 0

Inventory - Additional Information (Details)	12 Months Ended
Inventory - Additional Information (Details)	Dec. 31, 2018 USD ($)
Inventory Disclosure [Abstract]
Inventory write-downs	$ 0

Accrued Expenses - Summary of Accrued Expenses and Other Current Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Payables and Accruals [Abstract]
Accrued compensation	$ 20,843	$ 15,693
Accrued research and development costs	14,777	14,849
Accrued professional fees	5,441	3,140
Accrued other	1,086	349
Total accrued expenses	$ 42,147	$ 34,031

Commitments and Contingent Liabilities - Additional Information (Details) $ in Millions	12 Months Ended
	Dec. 31, 2018 USD ($) security	Dec. 31, 2017 USD ($)	Dec. 31, 2016 USD ($)
Commitments and Contingencies Disclosure [Abstract]
Rent expense	$ 11.4	$ 6.0	$ 6.0
Standby letter of credit	$ 2.9
Legal proceedings \| security	0

Commitments and Contingent Liabilities - Future Annual Minimum Lease Payments Due Under Operating Leases (Details) $ in Thousands	Dec. 31, 2018 USD ($)
Commitments and Contingencies Disclosure [Abstract]
2019	$ 12,759
2020	13,135
2021	13,473
2022	15,552
2023	17,145
Thereafter	19,223
Total minimum lease payments	$ 91,287

Product Revenue - Additional Information (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Disaggregation of Revenue [Line Items]
Revenues	$ 94,387	$ 43,011	$ 69,892
Product revenue, net
Disaggregation of Revenue [Line Items]
Revenues	$ 13,841	$ 0	$ 0

Product Revenue - Schedule of Product Revenue Allowance and Reserves (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017
Contractual Adjustments [Roll Forward]
Contractual adjustments, beginning balance	$ 0
Contractual adjustments, current provisions relating to sales in the current year	1,777
Contractual adjustments, adjustments relating to prior years	0
Contractual adjustments, payments/returns relating to sales in the current year	(1,185)
Contractual adjustments, payments/returns relating to sales in the prior year	0
Contractual adjustments, ending balance	592
Government Rebates [Roll Forward]
Government rebates, beginning balance	0
Government rebates, current provisions relating to sales in the current year	422
Government rebates, adjustments relating to prior years	0
Government rebates, payments/returns relating to sales in the current year	(97)
Government rebates, payments/returns relating to sales in the prior years	0
Government rebates, ending balance	325
Product Returns [Roll Forward]
Returns, beginning balance	0
Returns, current provisions relating to sales in the current year	334
Returns, adjustments relating to prior years	0
Returns, payments/returns relating to sales in the current year	0
Returns, payments/returns relating to sales in the prior years	0
Returns, ending balance	334
Allowance for Doubtful Accounts Receivable [Roll Forward]
Total revenue-related reserves	1,251	$ 0
Total allowances and reserves, current provisions relating to sales in the current year	2,533
Total allowances and reserves, adjustments relating to prior years	0
Total allowances and reserves, payments/returns relating to sales in the current year	(1,282)
Total allowances and reserves, payments/returns relating to sales in the prior years	$ 0

Product Revenue - Schedule of Revenue-Related Reserves (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Revenue from Contract with Customer [Abstract]
Reduction of accounts receivable	$ 326
Component of accrued expenses	925
Total revenue-related reserves	$ 1,251	$ 0

Product Revenue - Schedule of Changes in Contract Assets and Liabilities (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2018 USD ($)
Contract Assets and Liabilities [Roll Forward]
Contract assets, beginning balance	$ 0
Additions	16,374
Deductions	(11,298)
Contract assets, ending balance	$ 5,076

Collaboration and License Agreements - Additional Information (Details)		1 Months Ended			12 Months Ended
	May 17, 2016 USD ($)	Jun. 30, 2018 USD ($)	Apr. 30, 2017 USD ($)	May 31, 2016 Program extension program	Dec. 31, 2018 USD ($)	Dec. 31, 2017 USD ($)	Dec. 31, 2016 USD ($)
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Remaining unsatisfied performance obligation					$ 100,300,000
Milestone revenue					15,000,000.0		$ 25,000,000.0
Upfront payment for research and development					341,324,000	$ 292,681,000	$ 220,163,000
2010 Agreement
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Milestone-based receivable payments, eligible to be received					80,000,000.0
Milestone payments upon achievement of specified regulatory milestone events					55,000,000.0
Milestone payment upon achievement of a specified commercial milestone event					25,000,000.0
2010 Agreement \| Non-US
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Milestone payments upon achievement of specified regulatory milestone events					35,000,000.0
AG-881 program licenses
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Milestone payment for filing of first NDA					35,000,000.0
Celgene \| 2016 Agreement
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Number of cancer metabolism programs discovered under previous agreement, now governed by current agreement \| Program				2
Initial research term				4 years
Extension period \| extension				2
Number of allowable special case extensions \| extension				4
Special case extension term				1 year
Number of programs that may be designated for continued development for which development candidates have yet to be nominated \| program				3
Initial payment received	$ 200,000,000.0					8,000,000.0
Celgene \| Co-Development and Co-Commercialization Agreements \| 65/35 Program
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Profit or loss share percentage				65.00%
Celgene \| Co-Development and Co-Commercialization Agreements \| Other Than 65/35 Program
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Profit or loss share percentage				50.00%
CStone Pharmaceuticals \| CStone Agreement
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Remaining unsatisfied performance obligation					1,300,000
Initial payment received		$ 12,000,000.0
Potential future milestone payments					412,000,000.0
CStone Pharmaceuticals \| CStone Agreement \| Minimum
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Royalty percentage		15.00%
CStone Pharmaceuticals \| CStone Agreement \| Maximum
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Royalty percentage		19.00%
Aurigene Discovery Technologies Limited
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Upfront payment for research and development			$ 3,000,000.0			$ 3,000,000.0
Potential future milestone payments			$ 17,000,000.0
Aurigene Discovery Technologies Limited \| DHODH Phase One Clinical Trial
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Potential future milestone payments					$ 2,000,000.0

Collaboration and License Agreements - Financial Terms (Details) - Celgene - 2016 Agreement		1 Months Ended	12 Months Ended
	May 17, 2016 USD ($)	May 31, 2016 USD ($) extension	Dec. 31, 2017 USD ($)
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Initial payment received	$ 200,000,000.0		$ 8,000,000.0
Extension period \| extension		2
Number of allowable special case extensions \| extension		4
Upfront payment agreement extension fee receivable		$ 40,000,000.0
Designation fee	8,000,000.0
Option exercise fee receivable	30,000,000.0
Additional option exercise fee for further development	10,000,000.0
Minimum
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Minimum option exercise fee receivable for continuation program	$ 35,000,000.0

Collaboration and License Agreements - Summary of Milestone-Based Receivable Payments (Details) - Celgene $ in Millions	May 31, 2016 USD ($)
Specified clinical development event \| Co Commercial Agreement
Revenue Recognition, Milestone Method [Line Items]
Milestone-based receivable payments, eligible to be received	$ 25.0
Specified clinical development event \| 65/35 Program \| Co-Development and Co-Commercialization Agreements
Revenue Recognition, Milestone Method [Line Items]
Milestone-based receivable payments, eligible to be received	25.0
Specified clinical development event \| Other Than 65/35 Program \| Co-Development and Co-Commercialization Agreements
Revenue Recognition, Milestone Method [Line Items]
Milestone-based receivable payments, eligible to be received	20.0
Specified regulatory milestone events \| Maximum \| Co Commercial Agreement
Revenue Recognition, Milestone Method [Line Items]
Milestone-based receivable payments, eligible to be received	236.3
Specified regulatory milestone events \| Maximum \| 65/35 Program \| Co-Development and Co-Commercialization Agreements
Revenue Recognition, Milestone Method [Line Items]
Milestone-based receivable payments, eligible to be received	183.8
Specified regulatory milestone events \| Maximum \| Other Than 65/35 Program \| Co-Development and Co-Commercialization Agreements
Revenue Recognition, Milestone Method [Line Items]
Milestone-based receivable payments, eligible to be received	148.8
Specified commercial milestone events \| Maximum \| Co Commercial Agreement
Revenue Recognition, Milestone Method [Line Items]
Milestone-based receivable payments, eligible to be received	$ 125.0

Collaboration and License Agreements - Schedule of Satisfied and Unsatisfied Performance Obligations (Details) $ in Millions	12 Months Ended
	Dec. 31, 2018 USD ($) performance_obligation
Licenses \| Transferred at Point in Time
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Stand-alone selling price \| $	$ 86.7
No. of Performance Obligation(s) \| performance_obligation	4
Licenses \| Transferred at Point in Time \| CStone Agreement
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Stand-alone selling price \| $	$ 16.4
No. of Performance Obligation(s) \| performance_obligation	1
Research and development services \| Transferred at Point in Time
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Stand-alone selling price \| $	$ 350.7
No. of Performance Obligation(s) \| performance_obligation	10
Research and development services \| Transferred over Time
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Stand-alone selling price \| $	$ 266.6
No. of Performance Obligation(s) \| performance_obligation	6
Other services \| Transferred over Time \| CStone Agreement
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Stand-alone selling price \| $	$ 1.7
No. of Performance Obligation(s) \| performance_obligation	1

Collaboration and License Agreements - Summary of Collaboration Revenue and Reduction of Research and Development Expenses (Details) - USD ($) $ 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
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue – related party									$ 60,661	$ 41,074	$ 44,892
Reduction of research and development costs									0	7,811	19,714
Collaboration revenue	$ 30,013	$ 15,198	$ 40,414	$ 8,762	$ 9,799	$ 11,358	$ 11,346	$ 10,508
Licenses
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue – related party									15,000
Licenses \| Collaborative arrangement, product
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue									15,000	0	1,356
Licenses \| CStone Agreement
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue									12,440
Licenses \| Under Topic 605 \| ASU 2014-09
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue – related party									15,000
Licenses \| Under Topic 605 \| ASU 2014-09 \| CStone Agreement
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue									12,000
Licenses \| Cumulative Effect and Effect of Change \| ASU 2014-09
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue – related party									0
Licenses \| Cumulative Effect and Effect of Change \| ASU 2014-09 \| CStone Agreement
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue									440
Research and development services
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue – related party									40,575
Research and development services \| Collaborative arrangement, product
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue									40,575	37,953	41,993
Research and development services \| Under Topic 605 \| ASU 2014-09
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue – related party									38,733
Research and development services \| Cumulative Effect and Effect of Change \| ASU 2014-09
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue – related party									1,842
Committee participation
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue – related party									0
Committee participation \| Collaborative arrangement, product
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue									0	167	181
Committee participation \| Under Topic 605 \| ASU 2014-09
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue – related party									175
Committee participation \| Cumulative Effect and Effect of Change \| ASU 2014-09
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue – related party									(175)
Development services
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Reduction of research and development costs									0
Development services \| Under Topic 605 \| ASU 2014-09
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Reduction of research and development costs									3,329
Development services \| Cumulative Effect and Effect of Change \| ASU 2014-09
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Reduction of research and development costs									(3,329)
Additional development services \| Collaborative arrangement, product
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue									0	0	0
Development activities \| Collaborative arrangement, product \| Not Included in Modification Due to High Level of Uncertainty
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue – related party									1,342	0	1,192
Commercialization activities \| Collaborative arrangement, product \| Not Included in Modification Due to High Level of Uncertainty
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue – related party									3,744	2,954	170
Research and development activities \| Collaborative arrangement, product \| Not Included in Modification Due to High Level of Uncertainty
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Reduction of research and development costs									0	$ 14	$ 6,596
Other services
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Collaboration revenue									$ 200

Collaboration and License Agreements - Schedule of Changes in Contract Assets and Liabilities (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2018 USD ($)
Change In Contract With Customer, Asset [Roll Forward]
Contract assets, beginning balance	$ 0
Additions	16,374
Deductions	(11,298)
Contract assets, ending balance	5,076
Change in Contract with Customer, Liability [Roll Forward]
Additions	37,590
Collaboration receivable – related party
Change In Contract With Customer, Asset [Roll Forward]
Contract assets, beginning balance	2,448
Additions	28,695
Deductions	(28,681)
Contract assets, ending balance	2,462
Collaboration receivable – related party \| CStone Agreement
Change In Contract With Customer, Asset [Roll Forward]
Contract assets, beginning balance	0
Additions	12,670
Deductions	(12,000)
Contract assets, ending balance	670
Royalty receivable – related party
Change In Contract With Customer, Asset [Roll Forward]
Contract assets, beginning balance	1,222
Additions	7,087
Deductions	(6,075)
Contract assets, ending balance	2,234
Deferred revenue – related party, current and net of current portion
Change in Contract with Customer, Liability [Roll Forward]
Contract liabilities, beginning balance	163,640
Additions	9,237
Deductions	(80,358)
Contract liabilities, ending balance	$ 92,519

Collaboration and License Agreements - Schedule of Revenues as a Result of Changes in Contract Asset and Contract Liabilities (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2018 USD ($)
Revenue Recognition and Deferred Revenue [Abstract]
Amounts included in the contract liability at the beginning of the period	$ 37,590
Performance obligations satisfied in previous periods	$ 469

Collaboration and License Agreements - Royalty Revenue (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Revenues	$ 94,387	$ 43,011	$ 69,892
Royalty revenue – related party
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Revenues	$ 7,215	$ 1,937	$ 0

Common Stock - Additional Information (Details) - shares	Dec. 31, 2018	Dec. 31, 2017
Equity [Abstract]
Common stock, shares authorized (in shares)	125,000,000	125,000,000

Share-Based Payments - Additional Information (Details) - USD ($)		12 Months Ended
	Jan. 01, 2018	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Tax benefits related to stock based compensation		$ 0	$ 0	$ 0
Expected contractual term			10 years
Expected dividend yield		0.00%	0.00%	0.00%
Restricted stock units
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total unrecognized compensation expense related to stock option		$ 27,200,000
Weighted-average period to recognize compensation expense		1 year 11 months 1 day
2007 Plan and 2013 Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share based awards reserved for issuance (in shares)		7,973,725
Shares available for future issuance under 2013 ESPP (in shares)		1,856,481
2013 Stock Incentive Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Annual increase in common stock (in shares)		2,000,000
Percentage of outstanding shares of common stock (in shares)		4.00%
Additional shares authorized for issuance (in shares)	2,000,000
Weighted-average grant date fair value of options (in usd per share)		$ 53.22	$ 35.24	$ 28.41
Intrinsic value of options exercised		$ 65,100,000	$ 31,500,000	$ 26,400,000
Total unrecognized compensation expense related to stock option		$ 95,100,000
Weighted-average period to recognize compensation expense		2 years 6 months 29 days
Employee Stock Purchase Plan 2013
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares available for future issuance under 2013 ESPP (in shares)		160,536
Shares issued under 2013 ESPP (in shares)		53,255	59,651
Opportunity to purchase common stock (in shares)		327,272

Share-Based Payments - Summary of Company's Stock Option Activity of all Stock Incentive Plans (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017
Share-based Compensation Arrangement by Share-based Payment Award, Options, Outstanding [Roll Forward]
Number of stock options, outstanding, beginning balance (in shares)	5,577,562
Number of stock options, granted (in shares)	1,346,745
Number of stock options, exercised (in shares)	(1,125,009)
Number of stock options, forfeited/expired (in shares)	(383,229)
Number of stock options, outstanding, ending balance (in shares)	5,416,069	5,577,562
Share-based Compensation Arrangement by Share-based Payment Award, Options, Outstanding, Weighted Average Exercise Price [Abstract]
Weighted-average exercise price, outstanding, beginning balance (in usd per share)	$ 49.58
Weighted-average exercise price, granted (in usd per share)	78.10
Weighted-average exercise price, exercised (in usd per share)	24.01
Weighted-average exercise price, forfeited/expired (in usd per share)	76.26
Weighted-average exercise price, outstanding, ending balance (in usd per share)	$ 60.10	$ 49.58
Share-based Compensation Arrangement by Share-based Payment Award, Options, Additional Disclosures [Abstract]
Weighted-average remaining contractual term, outstanding (in years)	7 years 3 months 18 days	7 years 3 months 7 days
Aggregate intrinsic value, outstanding	$ 27,941	$ 94,336
Number of stock options, exercisable (in shares)	2,933,538
Weighted-average exercise price, exercisable (in usd per share)	$ 55.43
Weighted-average remaining contractual term, exercisable (in years)	6 years 2 months 19 days
Aggregate intrinsic value, exercisable	$ 26,559
Number of stock options, vested and expected to vest (in shares)	5,416,069
Weighted-average exercise price, vested and expected to vest (in usd per share)	$ 60.10
Weighted-average remaining contractual term, vested and expected to vest (in years)	7 years 3 months 18 days
Aggregate intrinsic value, vested and expected to vest	$ 27,941

Share-Based Payments - Summary of Unvested RSUs and Performance-Based Stock Unit Activity (Details)	12 Months Ended
	Dec. 31, 2018 $ / shares shares
Restricted stock units
Share-based Compensation Arrangement by Share-based Payment Award, Equity Instruments Other than Options, Nonvested, Number of Shares [Roll Forward]
Unvested shares beginning of period (in shares) \| shares	125,584
Granted (in shares) \| shares	496,106
Vested (in shares) \| shares	(59,250)
Forfeited (in shares) \| shares	(30,296)
Unvested shares end of period (in shares) \| shares	532,144
Share-based Compensation Arrangement by Share-based Payment Award, Equity Instruments Other than Options, Nonvested, Weighted Average Grant Date Fair Value [Abstract]
Weighted-average grant date fair value, unvested shares beginning of period (in usd per share) \| $ / shares	$ 47.46
Weighted-average grant date fair value, granted (in usd per share) \| $ / shares	78.36
Weighted-average grant date fair value, vested (in usd per share) \| $ / shares	42.11
Weighted-average grant date fair value, forfeited/expired (in usd per share) \| $ / shares	72.14
Weighted-average grant date fair value, unvested shares end of period (in usd per share) \| $ / shares	$ 75.45
Performance-Based Stock Units (PSUs)
Share-based Compensation Arrangement by Share-based Payment Award, Equity Instruments Other than Options, Nonvested, Number of Shares [Roll Forward]
Unvested shares beginning of period (in shares) \| shares	176,186
Granted (in shares) \| shares	4,000
Vested (in shares) \| shares	(2,000)
Forfeited (in shares) \| shares	(9,155)
Unvested shares end of period (in shares) \| shares	169,031
Share-based Compensation Arrangement by Share-based Payment Award, Equity Instruments Other than Options, Nonvested, Weighted Average Grant Date Fair Value [Abstract]
Weighted-average grant date fair value, unvested shares beginning of period (in usd per share) \| $ / shares	$ 52.98
Weighted-average grant date fair value, granted (in usd per share) \| $ / shares	79.05
Weighted-average grant date fair value, vested (in usd per share) \| $ / shares	79.05
Weighted-average grant date fair value, forfeited/expired (in usd per share) \| $ / shares	64.44
Weighted-average grant date fair value, unvested shares end of period (in usd per share) \| $ / shares	$ 52.67

Share-Based Payments - Schedule of Stock-Based Compensation by Award Type Included Within the Consolidated Statements of Operations (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]
Total stock-based compensation expense	$ 73,357	$ 47,809	$ 42,086
Stock options and performance-based stock options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total stock-based compensation expense	51,460	43,997	39,351
Restricted stock units
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total stock-based compensation expense	12,032	2,858	1,964
Performance-based stock units
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total stock-based compensation expense	8,717	0	0
Employee stock purchase plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Total stock-based compensation expense	$ 1,148	$ 954	$ 771

Share-Based Payments - Stock-Based Compensation Expense for Equity-Based Awards (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]
Allocated share based compensation expense	$ 73,357	$ 47,809	$ 42,086
Research and development expense
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Allocated share based compensation expense	41,982	30,807	25,386
Selling, general and administrative expense
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Allocated share based compensation expense	$ 31,375	$ 17,002	$ 16,700

Share-Based Payments - Schedule of Grant Date Fair Value Option Award Weighted Average Assumptions Used (Details)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Disclosure of Compensation Related Costs, Share-based Payments [Abstract]
Risk-free interest rate	2.71%	2.05%	1.42%
Expected dividend yield	0.00%	0.00%	0.00%
Expected term (in years)	6 years 21 days	6 years 18 days	6 years 18 days
Expected volatility	76.62%	77.73%	72.84%

Income Taxes - Schedule of Domestic and Foreign Components of Loss Before Income Taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Income Tax Disclosure [Abstract]
Domestic	$ (311,159)	$ (290,423)	$ (179,896)
Foreign	(34,869)	(24,247)	(18,575)
Total	$ (346,028)	$ (314,670)	$ (198,471)

Income Taxes - Reconciliation of Expected Income Tax Benefit (Expense) Computed Using Federal Statutory Income Tax Rate (Details)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Income Tax Disclosure [Abstract]
Income tax benefit computed at federal statutory tax rate	21.00%	35.00%	35.00%
State taxes, net of federal benefit	0.80%	4.00%	2.90%
Change in valuation allowance	(28.40%)	(19.40%)	(43.40%)
General business credits and other credits	5.70%	10.40%	9.50%
Permanent differences and other adjustments	(0.70%)	0.00%	(0.30%)
Incentive stock options	2.20%	0.30%	(1.80%)
Foreign rate differential	(0.60%)	(1.60%)	(1.90%)
Impact of federal rate change	0.00%	(28.70%)	0.00%
Total	0.00%	0.00%	0.00%

Income Taxes - Company's Deferred Tax Assets and Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Deferred tax assets:
Net operating loss carryforwards	$ 211,563	$ 131,165
Deferred revenue	21,956	41,243
Tax credit carryforwards	120,605	100,791
Purchased intangible assets	3,204	3,906
Stock-based compensation	27,636	20,539
Deferred rent	4,458	5,042
Non-deductible accruals and reserves, including inventory	4,900	3,778
Total deferred tax assets	394,322	306,464
Depreciation and amortization	(3,569)	(4,549)
Less: valuation allowance	(390,753)	(301,915)
Net deferred taxes	$ 0	$ 0

Income Taxes - Additional Information (Details)	12 Months Ended
Income Taxes - Additional Information (Details)	Dec. 31, 2018 USD ($) Ownership Audit	Dec. 31, 2017 USD ($)	Dec. 31, 2016 USD ($)
Income Taxes Disclosure [Line Items]
Provision for income taxes	$ 0	$ 0	$ 0
Adjustment to income tax expense related to tax reform		90,000,000.0
Percentage of stock owned resulting in an ownership change	50.00%
Aggregate period	3 years
Number of ownership changes \| Ownership	0
Valuation allowance	$ 390,753,000	301,915,000
Increase (decrease) in valuation allowance	$ 88,800,000	$ 93,900,000
Number of federal, state or foreign audits in process \| Audit	0
Federal Orphan Drug Tax Credit
Income Taxes Disclosure [Line Items]
Research and development tax credit	$ 86,800,000
Federal
Income Taxes Disclosure [Line Items]
Net operating loss carryforwards	774,800,000
Net operating loss, indefinite carryforward	311,500,000
Federal \| Research Tax Credit Carryforward
Income Taxes Disclosure [Line Items]
Research and development tax credit	24,400,000
State and Local Jurisdiction
Income Taxes Disclosure [Line Items]
Net operating loss carryforwards	586,400,000
State and Local Jurisdiction \| Research Tax Credit Carryforward
Income Taxes Disclosure [Line Items]
Research and development tax credit	11,900,000
Foreign Income Tax
Income Taxes Disclosure [Line Items]
Net operating loss carryforwards	$ 80,800,000

Income Taxes - Unrecognized Tax Benefits Rollforward (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017
Reconciliation of Unrecognized Tax Benefits, Excluding Amounts Pertaining to Examined Tax Returns [Roll Forward]
Unrecognized tax benefits, beginning balance	$ 11,263	$ 0
Gross increases - current period tax positions	3,025	11,263
Unrecognized tax benefits, ending balance	$ 14,288	$ 11,263

Defined Contribution Benefit Plan - Additional Information (Details)	12 Months Ended
	Dec. 31, 2018
Retirement Benefits [Abstract]
Employer's matching contribution percentage	100.00%
Employer's contribution percentage of eligible compensation	4.00%

Net Loss per Share - Common Stock Excluded from Calculation of Diluted Net Loss Per Share (Detail) - shares	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Antidilutive securities excluded from computation of earnings per share (in shares)	6,149,548	5,725,208	5,319,948
Stock options
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Antidilutive securities excluded from computation of earnings per share (in shares)	5,416,069	5,577,562	5,218,880
Restricted stock units
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Antidilutive securities excluded from computation of earnings per share (in shares)	532,144	125,584	77,050
Performance-Based Stock Units (PSUs)
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Antidilutive securities excluded from computation of earnings per share (in shares)	169,031	0	0
Employee Stock Purchase Plan shares
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Antidilutive securities excluded from computation of earnings per share (in shares)	32,304	22,062	24,018

Selected Quarterly Financial Data (Unaudited) - Summary of Quarterly Financial Data (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]
Total revenue	$ 30,013	$ 15,198	$ 40,414	$ 8,762	$ 9,799	$ 11,358	$ 11,346	$ 10,508
Loss from operations	(96,356)	(99,162)	(72,949)	(94,012)	(90,130)	(79,017)	(84,600)	(67,047)	$ (362,479)	$ (320,794)	$ (200,985)
Net loss	$ (91,794)	$ (94,664)	$ (68,745)	$ (90,825)	$ (88,285)	$ (77,137)	$ (83,082)	$ (66,166)
Net loss per share - basic and diluted (in usd per share)	$ (1.58)	$ (1.63)	$ (1.19)	$ (1.63)	$ (1.81)	$ (1.59)	$ (1.78)	$ (1.56)	$ (6.03)	$ (6.75)	$ (5.07)

Label	Element	Value
Accounting Standards Update 2014-09 [Member]
Cumulative Effect of New Accounting Principle in Period of Adoption	us-gaap_CumulativeEffectOfNewAccountingPrincipleInPeriodOfAdoption	$ 39,456,000
Accounting Standards Update 2014-09 [Member] \| Retained Earnings [Member]
Cumulative Effect of New Accounting Principle in Period of Adoption	us-gaap_CumulativeEffectOfNewAccountingPrincipleInPeriodOfAdoption	$ 39,456,000

Collaboration and License Agreements - Schedule of Satisfied and Unsatisfied Performance Obligations (Details) $ in Millions	12 Months Ended
	Dec. 31, 2018 USD ($) performance_obligation
Licenses \| Transferred at Point in Time
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Stand-alone selling price \| $	$ 86.7
No. of Performance Obligation(s) \| performance_obligation	4
Licenses \| Transferred at Point in Time \| CStone Agreement
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Stand-alone selling price \| $	$ 16.4
No. of Performance Obligation(s) \| performance_obligation	1
Research and development services \| Transferred at Point in Time
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Stand-alone selling price \| $	$ 350.7
No. of Performance Obligation(s) \| performance_obligation	10
Research and development services \| Transferred over Time
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Stand-alone selling price \| $	$ 266.6
No. of Performance Obligation(s) \| performance_obligation	6
Other services \| Transferred over Time \| CStone Agreement
Revenue, Initial Application Period Cumulative Effect Transition [Line Items]
Stand-alone selling price \| $	$ 1.7
No. of Performance Obligation(s) \| performance_obligation	1