View Filing Data

Document And Entity Information - USD ($)	12 Months Ended
Document And Entity Information - USD ($)	Dec. 31, 2018	Feb. 26, 2019	Jun. 29, 2018
Document And Entity Information [Abstract]
Document Type	10-K
Amendment Flag	false
Document Period End Date	Dec. 31, 2018
Document Fiscal Year Focus	2018
Document Fiscal Period Focus	FY
Entity Registrant Name	CHIMERIX INC
Entity Central Index Key	0001117480
Entity Voluntary Filers	No
Entity Well-known Seasoned Issuer	No
Entity Current Reporting Status	Yes
Current Fiscal Year End Date	--12-31
Entity Filer Category	Accelerated Filer
Entity Small Business	true
Entity Emerging Growth	false
Entity Shell Company	false
Entity Public Float			$ 124,953,651
Entity Common Stock, Shares Outstanding		50,903,196

Consolidated Balance Sheets - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Current assets:
Cash and cash equivalents	$ 81,106	$ 18,548
Short-term investments, available-for-sale	105,424
Short-term investments, available-for-sale		132,972
Accounts receivable	330	1,682
Prepaid expenses and other current assets	2,598	3,331
Total current assets	189,458	156,533
Long-term investments	0	76,731
Property and equipment, net of accumulated depreciation	1,210	1,894
Other long-term assets	46	72
Total assets	190,714	235,230
Current liabilities:
Accounts payable	4,691	3,812
Accrued liabilities	8,275	9,384
Total current liabilities	12,966	13,196
Lease-related obligations	144	224
Total liabilities	13,110	13,420
Stockholders’ equity:
Preferred stock, $0.001 par value, 10,000,000 shares authorized at December 31, 2018 and 2017; no shares issued and outstanding as of December 31, 2018 and 2017	0	0
Common stock, $0.001 par value; 200,000,000 shares authorized at December 31, 2018 and 2017; 50,735,279 and 47,505,532 shares issued and outstanding at December 31, 2018 and 2017, respectively	51	47
Additional paid-in capital	733,907	709,514
Accumulated other comprehensive loss, net	(92)	(963)
Accumulated deficit	(556,262)	(486,788)
Total stockholders’ equity	177,604	221,810
Total liabilities and stockholders’ equity	$ 190,714	$ 235,230

Consolidated Statements of Operations and Comprehensive Loss - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Revenues:
Contract revenue	$ 7,216	$ 4,494	$ 5,702
Operating expenses:
Research and development	55,239	49,448	58,647
General and administrative	23,582	27,148	25,007
Total operating expenses	78,821	76,596	83,654
Loss from operations	(71,605)	(72,102)	(77,952)
Other (expense) income:
Unrealized loss on equity investment	348
Unrealized loss on equity investment		1,160	0
Interest income and other, net	2,479	2,278	1,562
Net loss	(69,474)	(70,984)	(76,390)
Other comprehensive loss:
Unrealized gain (loss) on investments, net	871	(523)	324
Comprehensive loss	$ (68,603)	$ (71,507)	$ (76,066)
Per share information:
Net loss, basic and diluted (in USD per share)	$ (1.43)	$ (1.51)	$ (1.65)
Weighted-average shares outstanding, basic and diluted (in shares)	48,593,435	46,963,430	46,267,064

Consolidated Statements of Stockholders' Equity (Deficit) - USD ($) $ in Thousands	Total	Common Stock	Additional Paid-in Capital	Accumulated Other Comprehensive Gain (Loss)	Accumulated Deficit
Beginning Balance at Dec. 31, 2015	$ 335,459	$ 46	$ 675,591	$ (764)	$ (339,414)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Share-based compensation	16,223		16,223
Exercise of stock options	168		168
Employee stock purchase plan purchases	440		440
Comprehensive loss:
Unrealized gain (loss) on investments, net	324			324
Net loss	(76,390)				(76,390)
Comprehensive loss	(76,066)
Ending Balance at Dec. 31, 2016	276,224	46	692,422	(440)	(415,804)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Share-based compensation	16,110	1	16,109
Exercise of stock options	121		121
Employee stock purchase plan purchases	712		712
Issuance of common stock, net of issuance costs	150		150
Comprehensive loss:
Unrealized gain (loss) on investments, net	(523)			(523)
Net loss	(70,984)				(70,984)
Comprehensive loss	(71,507)
Ending Balance at Dec. 31, 2017	221,810	47	709,514	(963)	(486,788)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Share-based compensation	13,074	1	13,073
Exercise of stock options	115		115
Employee stock purchase plan purchases	608		608
Issuance of common stock, net of issuance costs	10,600	3	10,597
Comprehensive loss:
Unrealized gain (loss) on investments, net	871			871
Net loss	(69,474)				(69,474)
Comprehensive loss	(68,603)
Ending Balance at Dec. 31, 2018	$ 177,604	$ 51	$ 733,907	$ (92)	$ (556,262)

Consolidated Statements of Cash Flows - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Cash flows from operating activities:
Net loss	$ (69,474)	$ (70,984)	$ (76,390)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation of property and equipment	860	1,091	1,063
Amortization of discount/premium on investments	(852)	(5)	1,223
Share-based compensation	13,074	16,110	16,223
Loss on sale of investments	378	0	0
Unrealized loss on equity investment	348
Unrealized loss on equity investment		1,160	0
Amortization of lease-related obligations	(59)	(319)	132
Changes in operating assets and liabilities:
Accounts receivable	1,352	(83)	861
Prepaid expenses and other assets	643	(168)	3,215
Accounts payable and accrued liabilities	5	3,073	(10,142)
Net cash used in operating activities	(53,725)	(50,125)	(63,815)
Cash flows from investing activities:
Purchases of property and equipment	(181)	(151)	(841)
Purchases of short-term investments	(125,611)	0	(23,992)
Purchases of long-term investments	(6,031)	(162,613)	(79,381)
Proceeds from sales of short-term investments	111,178	13,500	0
Proceeds from maturities of short-term investments	125,740	165,695	198,279
Net cash provided by investing activities	105,095	16,431	94,065
Cash flows from financing activities:
Proceeds from exercise of stock options	115	121	168
Proceeds from employee stock purchase plan	608	712	440
Proceeds from issuance of common stock, net of commissions	10,867	0	0
Payments of deferred offering costs	(402)	(54)	0
Net cash provided by financing activities	11,188	779	608
Net increase (decrease) in cash and cash equivalents	62,558	(32,915)	30,858
Beginning of period	18,548	51,463	20,605
End of period	81,106	18,548	51,463
Supplemental disclosure of cash flow information
Non-cash addition to deferred offering costs	$ 22	$ 276	$ 0

The Business and Summary of Significant Accounting Policies

12 Months Ended

Dec. 31, 2018

Accounting Policies [Abstract]

The Business and Summary of Significant Accounting Policies

Description of Business

Chimerix, Inc. (the Company) is a biopharmaceutical company committed to discovering, developing and commercializing medicines that improve outcomes for immunocompromised patients. The Company was founded in 2000 based on the promise of its proprietary lipid conjugate technology to unlock the potential of some of the most broad-spectrum antivirals by enhancing their antiviral activity and safety profiles in convenient dosing regimens. The Company's lead compound, brincidofovir, is in development as an oral and intravenous (IV) formulation for the prevention and treatment of DNA viruses, including smallpox, adenoviruses, and the human herpesviruses. In addition, the Company has an active discovery program focusing on viral targets for which limited or no therapies are currently available.

Basis of Presentation

The consolidated financial statements include the accounts of the Company, and its wholly owned subsidiaries. The accompanying consolidated financial statements have been prepared in accordance with accounting principles generally accepted in the United States of America (GAAP). The preparation of the Company’s consolidated financial statements requires estimates and assumptions that affect the reported amounts of assets, liabilities, revenues and expenses, and the disclosure of contingent assets and liabilities in the consolidated financial statements and accompanying notes. Although these estimates are based on knowledge of current events and actions the Company may undertake in the future, actual results may ultimately differ from these estimates and assumptions.

Reclassifications

Certain prior period amounts in the accompanying consolidated financial statements have been reclassified to conform to the current year presentation. These reclassifications had no effect on previously reported net income or stockholders' equity (deficit).

Cash and Cash Equivalents

The Company considers any highly liquid instrument with an original maturity of three months or less at acquisition to be a cash equivalent. Cash equivalents consist of money market funds, U.S. Treasury securities, commercial paper, and corporate bonds.

Investments

Investments consist primarily of commercial paper, corporate bonds, U.S. Treasury securities and stock of a U.S. corporation. The Company invests in high-credit quality investments in accordance with its investment policy which minimizes the probability of loss.

Available-for-sale debt securities are carried at fair value as determined by quoted market prices, with the unrealized gains and losses, net of tax, reported as a separate component of stockholders equity. Realized gains and losses are determined using the specific identification method and transactions are recorded on a settlement date basis in interest income and other, net. For the year ended December 31, 2018, $0.4 million of realized losses were reclassified from accumulated other comprehensive loss, net in the Consolidated Balance Sheets to interest income and other, net in the Consolidated Statements of Operations and Comprehensive Loss. Investments with original maturities beyond three months at the date of purchase and which mature on, or less than twelve months from, the balance sheet date are classified as short-term. Investments with a maturity beyond twelve months from the balance sheet date are classified as long-term.

The Company periodically reviews available-for-sale debt securities for other-than-temporary declines in fair value below the cost basis and whenever events or changes in circumstances indicate that the carrying amount of an asset may not be recoverable. The Company evaluates, among other things, the duration and extent to which the fair value of a security is less than its cost; the financial condition of the issuer and any changes thereto; and the Company’s intent to sell, or whether it will more likely than not be required to sell, the security before recovery of its amortized cost basis. The Company does not intend to sell, and is not likely to be required to sell, the available-for-sale debt securities in an unrealized loss position before recovery of the amortized cost bases of the debt securities, which may be maturity. Any such declines in value judged to be other-than-temporary on available-for-sale debt securities are reported in other-than-temporary impairment of investment.

For the year ended December 31, 2017, the Company determined the decline in value for its investment in ContraVir Pharmaceuticals (ContraVir) common stock to be other-than temporary. As such, during the fourth quarter of 2017, the Company reclassified a loss of $1.2 million from accumulated other comprehensive loss, net in the Consolidated Balance Sheets to unrealized loss on equity investment the Consolidated Statements of Operations and Comprehensive Loss. For the year ended December 31, 2018, the Company recorded $0.3 million, of unrealized loss related to the Company's investment in ContraVir common stock to unrealized loss on equity investment in the Consolidated Statements of Operations and Comprehensive Loss. The Company recognizes interest income on an accrual basis in interest income and other, net in the Consolidated Statements of Operations and Comprehensive Loss.

Concentration of Credit Risk

Financial instruments that potentially subject the Company to concentrations of credit risk consist of cash, cash equivalents, short-term investments, long-term investments and accounts receivable. The Company is exposed to credit risk, subject to federal deposit insurance, in the event of default by the financial institutions holding its cash and cash equivalents to the extent of amounts recorded on the balance sheets. Accounts receivable represent amounts due from an agency of the federal government.

Accounts Receivable

Accounts receivable at December 31, 2018 and December 31, 2017 consisted of amounts billed under the Company’s contract with the Biomedical Advanced Research and Development Authority (BARDA). Receivables under the BARDA contract are recorded as qualifying research activities are conducted and invoices from the Company’s vendors are received. The Company carries its accounts receivable at cost less an allowance for doubtful accounts. On a periodic basis, the Company evaluates its accounts receivable and establishes an allowance based on its history of collections and write-offs and the current status of all receivables. The Company does not accrue interest on trade receivables. If accounts become uncollectible, they will be written off through a charge to the allowance for doubtful accounts. The Company has not recorded a charge to allowance for doubtful accounts as management believes all receivables are fully collectible.

Fair Value of Financial Instruments

The carrying amounts of certain financial instruments, including accounts receivable, accounts payable and accrued expenses approximate their fair values due to the short-term nature of such instruments.

For assets and liabilities recorded at fair value, it is the Company’s policy to maximize the use of observable inputs and minimize the use of unobservable inputs when developing fair value measurements, in accordance with the fair value hierarchy. Fair value measurements for assets and liabilities where there exists limited or no observable market data are based primarily upon estimates and are often calculated based on the economic and competitive environment, the characteristics of the asset or liability and other factors. Therefore, fair value measurements cannot be determined with precision and may not be realized in an actual sale or immediate settlement of the asset or liability. Additionally, there may be inherent weaknesses in any calculation technique and changes in the underlying assumptions used, including discount rates and estimates of future cash flows, could significantly affect the calculated current or future fair values. The Company utilizes fair value measurements to record fair value adjustments to certain assets and liabilities and to determine fair value disclosures.

The Company groups assets and liabilities at fair value in three levels, based on the markets in which the assets and liabilities are traded and the reliability of the assumptions used to determine fair value. The determination of where an asset or liability falls in the hierarchy requires significant judgment. These levels are:


•	Level 1 — Valuations based on unadjusted quoted prices in active markets for identical assets or liabilities that the Company has the ability to access.


•	Level 2 — Valuations based on quoted prices for similar assets or liabilities in active markets, quoted prices for identical or similar assets or liabilities in markets that are not active, and models for which all significant inputs are observable, either directly or indirectly.


•	Level 3 — Valuations based on inputs that are unobservable and significant to the overall fair value measurement.

At December 31, 2018, the Company had cash equivalents, including money market funds and U.S. Treasury securities, and short-term investments, including U.S. Treasury securities. At December 31, 2017, the Company had cash equivalents, including money market funds, and short-term and long-term investments, including U.S. Treasury securities, whose value is based on using quoted market prices. Accordingly, these securities are classified as Level 1.

At December 31, 2018 and 2017, the Company had short-term investments, including stock of a U.S. corporation. The Company's investment in ContraVir Pharmaceuticals (ContraVir) common stock was categorized as a Level 1 asset and had a value based on ContraVir's common stock value at December 31, 2018 and 2017. For the twelve months ended December 31, 2018 and 2017, the Company recorded $0.3 million and $1.2 million, respectively, of unrealized loss related to the Company's investment in ContraVir common stock to unrealized loss on equity investment in the Consolidated Statements of Operations and Comprehensive Loss. For the twelve months ended December 31, 2016, the Company recorded $0.2 million of unrealized loss related to the Company's investment in ContraVir common stock to unrealized gain (loss) on investments, net in the Consolidated Statements of Operations and Comprehensive Loss.

At December 31, 2018, the Company had cash equivalents, including commercial paper and corporate bonds, and short-term investments including, commercial paper and corporate bonds. At December 31, 2017, the Company had cash equivalents including commercial paper. As quoted prices are not available for these securities, they are valued using independent pricing models or other model-based valuation techniques such as the present value of future cash flows, adjusted for the security’s credit rating, prepayment assumptions and other factors such as credit loss assumptions. Accordingly, these securities are classified as Level 2.

There was no material re-measurement to fair value of financial assets and liabilities that are not measured at fair value on a recurring basis. For additional information regarding the Company's investments, please refer to Note 2, "Investments."

Below is a table that presents information about certain assets measured at fair value on a recurring basis (in thousands):



			Fair Value Measurements
			December 31, 2018
	Total		Quoted Prices in Active Markets for Identical Assets (Level 1)		Significant Other Observable Inputs (Level 2)		Significant Unobservable Inputs (Level 3)
Cash equivalents
Money market funds	$	30,726	$	30,726	$	—	$	—
U.S. Treasury securities	11,482		11,482		—		—
Commercial paper	29,677		—		29,677		—
Corporate bonds	4,008		—		4,008		—
Total cash equivalents	75,893		42,208		33,685		—
Short-term investments
U.S. Treasury securities	12,589		12,589		—		—
Common stock of U.S. corporation	38		38		—		—
Commercial paper	60,114		—		60,114		—
Corporate bonds	32,683		—		32,683		—
Total short-term investments	105,424		12,627		92,797		—
Total assets	$	181,317	$	54,835	$	126,482	$	—



			Fair Value Measurements
			December 31, 2017
	Total		Quoted Prices in Active Markets for Identical Assets (Level 1)		Significant Other Observable Inputs (Level 2)		Significant Unobservable Inputs (Level 3)
Cash equivalents
Money market funds	$	10,816	$	10,816	$	—	$	—
Commercial paper	3,995		—		3,995		—
Total cash equivalents	14,811		10,816		3,995		—
Short-term investments
U.S. Treasury securities	132,586		132,586		—		—
Common stock of U.S. corporation	386		386		—		—
Total short-term investments	132,972		132,972		—		—
Long-term investments
U.S. Treasury securities	76,731		76,731		—		—
Total long-term investments	76,731		76,731		—		—
Total assets	$	224,514	$	220,519	$	3,995	$	—

Prepaid Expenses and Other Current Assets

Prepaid expenses and other current assets consisted of the following (in thousands):



	December 31,
	2018		2017
Prepaid research and development expenses	$	1,071	$	1,138
Interest receivable	259		601
Prepaid insurance	382		481
Other prepaid expenses and current assets	886		1,111
Total prepaid expenses and other current assets	$	2,598	$	3,331

Property and Equipment

Property and equipment are stated at cost, less accumulated depreciation. Depreciation is determined on a straight-line basis over the estimated useful lives of the assets, which generally range from three to five years. Leasehold improvements are amortized over the shorter of the useful life of the asset or the term of the related lease. Maintenance and repairs are charged against expense as incurred.

Impairment of Property and Equipment

The Company evaluates property and equipment for impairment whenever events or changes in circumstances indicate that the carrying value of an asset may not be recoverable. If the estimated future cash flows (undiscounted and without interest charges) from the use of an asset are less than the carrying value, a write-down would be recorded to reduce the related asset to its estimated fair value. To date, no such write-downs have occurred.

Deferred Lease Obligations

The Company recognizes rent expense on a straight-line basis over the non-cancelable term of its operating lease and records the difference between cash rent payments and the recognition of rent expense as a deferred rent liability. The Company also records landlord-funded lease incentives, such as reimbursable leasehold improvements, as a deferred rent liability, which is amortized as a reduction of rent expense over the non-cancelable term of its operating lease.

Accrued Liabilities

Accrued liabilities consisted of the following (in thousands):



	December 31,
	2018		2017
Accrued compensation	$	2,469	$	3,678
Accrued research and development expenses	4,525		3,384
Accrued indemnification claim	—		1,000
Other accrued liabilities	1,281		1,322
Total accrued liabilities	$	8,275	$	9,384

Revenue Recognition

Policy

The Company’s revenues generally consist of (i) contract revenue - revenue generated under federal contracts, and (ii) collaboration and licensing revenue - revenue related to non-refundable upfront fees, royalties and milestone payments earned under license agreements. Revenue is recognized in accordance with the criteria outlined in Accounting Standards Codification (ASC) 606 issued by the Financial Accounting Standards Board (FASB). Following this accounting pronouncement, a five-step approach is applied for recognizing revenue, including (1) identify the contract with a customer; (2) identify the performance obligations in the contract; (3) determine the transaction price; (4) allocate the transaction price to the performance obligations in the contract; and (5) recognize revenue when, or as, the entity satisfies a performance obligation.

Biomedical Advanced Research and Development Authority (BARDA)

In February 2011, the Company entered into a contract with BARDA for the advanced development of brincidofovir as a medical countermeasure in the event of a smallpox release. Under the contract, the Company may receive up to $75.8 million in expense reimbursement and $5.3 million in fees over the performance of 1 base segment and 4 option segments. Exercise of each option segment is solely at the discretion of BARDA. Currently, option segments 1 through 3 have been exercised. The Company assessed the services in accordance with the authoritative guidance and concluded that there is a potential of 5 separate contracts (1 base segment and four option segments) within this agreement, each of which has a single performance obligation. The transaction price for each segment, based on the transaction price as defined in each segment contract, is allocated to the single performance obligation for each contract. The transaction price is recognized over time by measuring the progress toward complete satisfaction of the performance obligation. The progress toward complete satisfaction is estimated based on the costs incurred to date relative to the total estimated costs per the terms of each contract. The Company typically invoices BARDA monthly as costs are incurred. The base segment and first option segment were completed prior to adoption of ASC 606. The Company is currently performing under the second and third option segments of the contract during which the Company may receive up to a total of $23.9 million and $14.1 million in expense reimbursement and fees, respectively. The second option segment is scheduled to end on August 1, 2019 and the third option segments is scheduled to end on March 30, 2019.

ContraVir Pharmaceuticals

The Company entered into a license agreement with ContraVir on December 17, 2014 for the development and commercialization of CMX157 for certain antiviral indications. The Company is eligible to receive up to approximately $20 million in clinical, regulatory and initial commercial milestones as well as royalties and additional milestones based on commercial sales. The Company assessed the agreement in accordance with the authoritative guidance and concluded that the ContraVir contract includes multiple performance obligations, which had all been satisfied in 2015 prior to the adoption of ASC 606. The ContraVir contract has one fixed and several variable transaction amounts. The fixed fee portion of the contract was for the license to CMX157 rights. The Company recognized revenue for the fixed fee portion of the contract in 2015 when the performance obligations were satisfied. All variable transaction amounts, which relate to clinical, regulatory and commercial milestones as well as royalties and milestones based on commercial sales, are fully constrained. The Company will begin recognizing revenue on the variable transaction amounts when those transaction amounts are no longer fully constrained.

Research and Development Prepaids and Accruals

As part of the process of preparing financial statements, the Company is required to estimate its expenses resulting from its obligation under contracts with vendors and consultants and clinical site agreements in connection with its research and development efforts. The financial terms of these contracts are subject to negotiations which vary contract to contract and may result in payment flows that do not match the periods over which materials or services are provided to the Company under such contracts.

The Company’s objective is to reflect the appropriate research and development expenses in its financial statements by matching those expenses with the period in which services and efforts are expended. The Company accounts for these expenses according to the progress of its research and development efforts. The Company determines prepaid and accrual estimates through discussion with applicable personnel and outside service providers as to the progress or state of communication of clinical trials, or other services completed. The Company adjusts its rate of research and development expense recognition if actual results differ from its estimates. The Company makes estimates of its prepaid and accrued expenses as of each balance sheet date in its financial statements based on facts and circumstances known at that time. Although the Company does not expect its estimates to be materially different from amounts actually incurred, its understanding of status and timing of services performed relative to the actual status and timing of services performed may vary and may result in the Company reporting amounts that are too high or too low for any particular period. Through December 31, 2018, there had been no material adjustments to the Company’s prior period estimates of prepaid and accruals for research and development expenses. The Company’s research and development prepaids and accruals are dependent upon the timely and accurate reporting of contract research organizations and other third-party vendors.

Research and Development Expenses

Major components of research and development costs include cash compensation, stock based compensation, pre-clinical studies, clinical trial and related clinical manufacturing, drug development, materials and supplies, legal, regulatory compliance, and fees paid to consultants and other entities that conduct certain research and development activities on the Company’s behalf. Research and development costs, including upfront fees and milestones paid to contract research organizations, are expensed as goods are received or services rendered. Costs incurred in connection with clinical trial activities for which the underlying nature of the activities themselves do not directly relate to active research and development, such as costs incurred for market research and focus groups linked to clinical strategy as well as costs to build the Company’s brand, are not included in research and development costs but are reflected as general and administrative costs.

Unrealized Loss on Equity Investment

As of December 31, 2018, unrealized loss on equity investment consists of the decrease in fair value of our investment in ContraVir common stock. As of December 31, 2017, unrealized loss on equity investment consists of the write-down in fair value of our investment in ContraVir common stock which was judged to be other-than-temporarily impaired.

Interest Income and Other, Net

Interest income and other, net primarily includes interest earned on short-term and long-term investments and realized gains on the sale of short-term investments.

Income Taxes

Deferred tax assets and liabilities are determined based on differences between the financial and tax reporting bases of assets and liabilities and are measured using enacted tax rates and laws that are expected to be in effect when the differences are expected to reverse. Valuation allowances are established when the Company determines that it is more likely than not that some portion of a deferred tax asset will not be realized. The Company has incurred operating losses from April 7, 2000 (inception) through December 31, 2018, and therefore has not recorded any current provision for income taxes.

Additionally, the Company recognizes the tax benefit from an uncertain tax position only if it is more likely than not that the tax position will be sustained on examination by the taxing authorities based on the technical merits of the position. The tax benefit recognized in the financial statements for a particular tax position is based on the largest benefit that is more likely than not to be realized upon settlement. Accordingly, the Company establishes reserves for uncertain tax positions.

The FASB Staff Q&A, Topic 740, No. 5, Accounting for Global Intangible Low-Taxed Income (GILTI), states that an entity can make an accounting policy election to either recognized deferred taxes for temporary basis differences expected to reverse as GILTI in future years or to provide for the tax expense related to GILTI in the year the tax is incurred as a period expense only. The Company has elected to account for GILTI as a period expense in the year the tax is incurred.

Share-Based Compensation

The Company measures and recognizes compensation expense for all share-based payment awards made to employees and directors, including employee stock options, restricted stock units and the employee stock purchase plan purchase rights, based on estimated fair values. The fair value of employee stock options and employee stock purchase plan purchase rights is estimated on the grant date using the Black-Scholes valuation model. The grant-date fair value for restricted stock units is based upon the market price of the Company's common stock on the date of the grant. The value of the portion of the award that is ultimately expected to vest is recorded as expense over the requisite service periods. For performance-based awards compensation cost is recognized when it is probable that the performance criteria will be met.

The Company estimates forfeitures at the time of grant, and revises those estimates in subsequent periods if actual forfeitures differ from its estimates. The Company uses historical data to estimate forfeitures and records share-based compensation expense only for those awards that are expected to vest. To the extent that actual forfeitures differ from the Company’s estimates, the difference is recorded as a cumulative adjustment in the period the estimates were revised. For the years ended December 31, 2018, 2017 and 2016, the Company applied a forfeiture rate based on the Company’s historical forfeitures.

401(k) Plan

The Company maintains a defined contribution employee retirement plan (“401(k) plan”). For the years ended December 31, 2018, 2017 and 2016, the Company recognized expenses for matching contributions of $0.4 million, $0.3 million and $0.4 million, respectively.

Basic and Dilutive Net Loss Per Share of Common Stock

Basic net loss per share of common stock is computed by dividing net loss by the weighted-average number of shares of common stock outstanding during the period, excluding the dilutive effects of warrants to purchase common stock, non-vested restricted stock, stock options, and employee stock purchase plan purchase rights. Diluted net loss per share of common stock is computed by dividing net loss by the sum of the weighted-average number of shares of common stock outstanding during the period plus the potential dilutive effects of warrants to purchase common stock, non-vested restricted stock, stock options, and employee stock purchase plan purchase rights outstanding during the period calculated in accordance with the treasury stock method, but are excluded if their effect is anti-dilutive. Because the impact of these items is anti-dilutive during the periods of net loss, there was no difference between basic and diluted loss per share of common stock at December 31, 2018, 2017 and 2016.

Segments

The Company operates in only one segment. The chief operating decision-makers, who are the members of the Office of the Chief Executive Officer, and management use cash flows as the primary measure to manage the business and do not segment the business for internal reporting or decision making.

Impact of Recently Issued Accounting Standards

In February 2016, the FASB issued Accounting Standards Update (ASU) No. 2016-02, “Leases (Topic 842)”, and amended through subsequent ASUs, which increases transparency and comparability among companies accounting for lease transactions. The most significant change of this update will require the recognition of lease assets and liabilities on the balance sheet for lessees for operating lease arrangements with lease terms greater than 12 months. This ASU is effective for financial statements issued for annual periods and interim periods within those annual periods, beginning after December 15, 2018. The Company adopted this standard effective January 1, 2019 using the alternative adoption method allowed by ASU 2018-11. The Company elected to use the package of three practical expedients which allows the Company not to reassess whether contracts are or contain leases, lease classification, and whether initial direct costs qualify for capitalization. The Company has substantially completed its assessment over the impact of the standard and determined that the only material leases that the Company holds are real estate operating lease commitments. Upon adoption of the standard, the Company preliminarily expects to record a right of use asset and lease liability of approximately $1.6 million on its consolidated balance sheets. The finalization of the Company's assessment may result in significant changes to its estimates that may materially impact its preliminary estimate of the cumulative effect.

Impact of Recently Adopted Accounting Standards

In May 2014, the FASB issued ASU No. 2014-09, “Revenue from Contracts with Customers (Topic 606).” The ASU establishes a principles-based approach for accounting for revenue arising from contracts with customers and supersedes existing revenue recognition guidance. The ASU provides that an entity should apply a five-step approach for recognizing revenue, including (1) identify the contract with a customer; (2) identify the performance obligations in the contract; (3) determine the transaction price; (4) allocate the transaction price to the performance obligations in the contract; and (5) recognize revenue when, or as, the entity satisfies a performance obligation. Also, the entity must provide various disclosures concerning the nature, amount and timing of revenue and cash flows arising from contracts with customers. The FASB has issued several updates to the standard which (1) deferred the original effective date to annual periods and interim periods within those annual periods beginning after December 15, 2017, while allowing for early adoption as of January 1, 2017 (ASU 2015-14); (2) clarify the application of the principal versus agent guidance (ASU 2016-08); and (3) clarify the guidance on inconsequential and perfunctory promises and licensing (ASU 2016-10). The Company adopted ASU No. 2014-09 as of January 1, 2018 using the full retrospective approach and determined that there was no impact on its consolidated financial statements. In preparation for adoption of the standard, the Company implemented internal controls to enable the preparation of financial information, including the assessment of the impact of the standard.

In January 2016, the FASB issued ASU No. 2016-01, “Financial Instruments-Overall (Subtopic 825-10)-Recognition and Measurement of Financial Assets and Financial Liabilities.” The new standard enhances reporting for financial instruments. The ASU is effective for financial statements issued for annual periods and interim periods within those annual periods beginning after December 15, 2017. The Company adopted ASU No. 2016-01 on January 1, 2018 on a prospective basis. As a result of this standard, changes in fair value of available-for-sale equity securities that were previously recognized in other comprehensive income are now recognized in earnings. As of January 1, 2018, the Company had no unrealized gains or losses in other comprehensive income that had to be reclassified to retained earnings.

Stockholders' Equity (Deficit)

12 Months Ended

Dec. 31, 2018

Stockholders' Equity Note [Abstract]

Stockholders' Equity (Deficit)

Stockholders’ Equity (Deficit)

Common Stock

The Company’s common stock consists of 200 million authorized shares at December 31, 2018 and 2017, and 50.7 million and 47.5 million shares issued and outstanding at December 31, 2018 and December 31, 2017, respectively.

Shares Reserved for Future Issuance

The Company has reserved shares of common stock for future issuances as follows:



	December 31,
	2018	2017
For exercise of common stock warrants	—	227,794
For exercise of outstanding common stock options	6,429,638	4,996,661
For delivery upon vesting of outstanding restricted stock units	656,169	956,299
For future equity awards under the 2013 Equity Incentive Plan	1,587,670	1,082,608
For future purchases under the 2013 Employee Stock Purchase Plan	2,120,290	1,861,472
Total shares of common stock reserved for future issuances	10,793,767	9,124,834

Stock Options

In connection with the Company’s IPO, the Company adopted the 2013 Equity Incentive Plan (the 2013 Plan). The 2013 Plan provides for the grant of incentive stock options (ISOs), nonstatutory stock options (NSOs), stock appreciation rights, restricted stock awards, restricted stock unit (RSU) awards, performance-based stock awards, and other forms of equity compensation (collectively, stock awards), all of which may be granted to employees, including officers, non-employee directors and consultants of the Company and its affiliates. Additionally, the 2013 Plan provides for the grant of performance cash awards. ISOs may be granted only to employees. All other awards may be granted to employees, including officers, and to non-employee directors and consultants. The number of shares of common stock reserved for issuance under the 2013 Plan will automatically increase on January 1 of each year, continuing through and including January 1, 2023, by 4.0% of the total number of shares of capital stock outstanding on December 31 of the preceding calendar year, or a lesser number of shares determined by the Company’s board of directors.

The Company estimates the fair value of its share-based awards to employees, directors and consultants using the Black-Scholes option-pricing model. The Black-Scholes model requires the input of highly complex and subjective assumptions, including (a) the expected stock price volatility, (b) the calculation of expected term of the award, (c) the risk-free interest rate and (d) expected dividends. Due to the Company’s limited operating history and historical and implied volatility data, the Company has based its estimates of expected volatility on a blend of Company specific historical data and a group of similar public traded companies. When selecting these public companies on which it has based its expected stock price volatility, the Company selected companies with comparable characteristics to it, including enterprise value, risk profiles, positions within the industry, and with historical share price information sufficient to meet the expected life of its stock options. For employee stock options, the Company uses historical exercise data to estimate the expected life. The risk-free interest rates for the periods within the expected life of the option are based on the U.S. Treasury instrument with a life that is similar to the expected life of the option grant. The Company has never paid, and does not expect to pay, dividends in the foreseeable future.

The following table illustrates the assumptions for the Black-Scholes model used in determining the fair value of the stock options granted:



	Years Ended December 31,
	2018			2017			2016
Expected volatility	85.83		%	85.51		%	85.16		%
Expected term (in years)	5.9			5.9			6.0
Weighted-average risk-free interest rate	2.52		%	2.02		%	1.70		%
Expected dividend yield	—		%	—		%	—		%
Weighted-average fair value per option	$	3.43		$	3.71		$	5.62

A summary of activity related to the Company’s stock options is as follows:



	Number of Options Outstanding		Weighted-Average Exercise Price		Weighted-Average Remaining Contractual Life (in Years)	Total Intrinsic Value
Balance, December 31, 2016	4,342,466		$	17.81	8.09
Granted	928,816		5.17		—
Exercised	(38,885	)	3.98		—
Forfeited	(235,736	)	19.10		—
Balance, December 31, 2017	4,996,661		$	15.51	7.59
Granted	2,050,995		4.73		—
Exercised	(29,262	)	3.93		—
Forfeited	(588,756	)	12.31		—
Balance, December 31, 2018	6,429,638		$	12.41	7.37	$	39,873
Exercisable at December 31, 2018	4,119,234		$	15.94	6.75	$	39,873
Vested or expected to vest at December 31, 2018	6,366,085		$	12.47	7.36	$	39,873

As of December 31, 2018, there was approximately $8.7 million of total unrecognized compensation cost related to non-vested stock options granted under the 2013 Plan. That compensation cost is expected to be recognized over a weighted-average period of approximately 2.00 years years.

Other information regarding the Company’s stock options is as follows (in thousands, except per share data):



	Years Ended December 31,
	2018		2017		2016
Weighted-average grant-date fair value per share of options granted	$	3.43	$	3.71	$	5.62
Total intrinsic value of options exercised	$	31	$	48	$	119
Total fair value of shares vested	$	11,021	$	11,786	$	13,330

The following table summarizes, at December 31, 2018, by price range: (1) for stock option awards outstanding under the 2013 Plan, the number of stock option awards outstanding, their weighted-average remaining life and their weighted-average exercise price; and (2) for stock option awards exercisable under the 2013 Plan, the number of stock option awards exercisable and their weighted-average exercise price:



	Outstanding				Exercisable
Exercise Price Range ($)	Number	Weighted-Average Remaining Contractual Life (in years)	Weighted-Average Exercise Price		Number	Weighted-Average Exercise Price
1.57 to 7.57	3,139,495	8.37	$	4.70	1,323,880	$	4.54
7.58 to 8.06	1,696,746	7.02	8.06		1,239,595	8.06
8.07 to 18.75	261,805	5.07	18.59		261,805	18.59
18.76 to 39.17	559,663	5.55	25.32		556,525	25.25
39.18 to 53.74	771,929	6.22	41.90		737,429	41.71
1.57 to 53.74	6,429,638	7.37	$	12.41	4,119,234	$	15.94

Employee Stock Purchase Plan

In February 2013, the Company’s board of directors adopted the 2013 Employee Stock Purchase Plan (ESPP), which was subsequently ratified by stockholders and became effective in April 2013. The purpose of the ESPP is to retain the services of new employees and secure the services of new and existing employees while providing incentives for such individuals to exert maximum efforts toward the Company’s success and that of its affiliates. The ESPP initially authorized the issuance of 704,225 shares of common stock pursuant to purchase rights granted to the Company’s employees or to employees of any of its designated affiliates. The number of shares of common stock reserved for issuance will automatically increase on January 1 of each calendar year, from January 1, 2014 through January 1, 2023 by the least of (a) 1% of the total number of shares of common stock outstanding on December 31 of the preceding calendar year, (b) 422,535 shares, or (c) a number determined by the Company’s board of directors that is less than (a) and (b). The ESPP is intended to qualify as an “employee stock purchase plan” within the meaning of Section 423 of the Internal Revenue Code of 1986. The common stock reserved for future issuance under the ESPP was automatically increased by an additional 422,535 shares on January 1, 2017 and 2018, bringing the total number of shares of common stock that may be purchased under the ESPP to 2,226,261 and 2,648,796, respectively.

The Company has reserved a total of 2,648,796 shares of common stock to be purchased under the ESPP, of which 2,120,290 and 1,861,472 shares remained available for purchase at December 31, 2018 and 2017, respectively. Eligible employees may authorize an amount up to 15% of their salary to purchase common stock at the lower of a 15% discount to the beginning price of their offering period or a 15% discount to the ending price of each six-month purchase interval. The ESPP also provides for an automatic reset feature to start participants on a new twenty-four month participation period in the event that the common stock market value on a purchase date is less than the common stock value on the first day of the twenty-four month offering period. The Company issued 163,717 and 173,822 shares of common stock pursuant to the ESPP for the year ended December 31, 2018 and 2017, respectively. Compensation expense for purchase rights under the ESPP related to the purchase discount and the “look-back” option were determined using a Black-Scholes option pricing model.

The following table illustrates the assumptions for the Black-Scholes model used in determining the fair value of the ESPP purchase rights:



	Years Ended December 31,
	2018			2017			2016
Expected volatility	44.01		%	77.18		%	111.57		%
Expected term (in years)	1.23			0.97			1.37
Weighted-average risk-free interest rate	2.56		%	0.99		%	0.75		%
Expected dividend yield	—		%	—		%	—		%
Weighted-average option value per share	$	1.36		$	2.65		$	3.20

As of December 31, 2018, the Company had a liability of $0.2 million representing employees' contributions to the ESPP.

Restricted Stock Units

For the years ended December 31, 2018 and 2017, the Company issued RSUs to certain employees which vest based on service criteria. When vested, the RSU represents the right to be issued the number of shares of the Company's common stock that is equal to the number of RSUs granted. The grant date fair value for RSUs is based upon the market price of the Company's common stock on the date of the grant. The fair value is then amortized to compensation expense over the requisite service period or vesting term. For the years ended December 31, 2018 and 2017, the Company issued 233,050 and 744,450 shares of common stock pursuant to the vesting of RSUs, respectively.

In January 2017, the Company also granted performance-based RSUs which, when vested, represent the right to be issued the number of shares of the Company's common stock that is equal to the number of RSUs granted. The grant date fair value for performance-based RSUs is based upon the market price of the Company's common stock on the date of the grant. For the portion of the performance-based RSUs of which the achievement of the performance condition is considered probable, the Company recognizes stock-based compensation expense on the related estimated fair value of such RSUs ratably for each vesting tranche from the service inception date to the end of the requisite service period. For the performance conditions that are not considered probable of achievement at the grant date or upon quarterly re-evaluation, prior to the event actually occurring, the Company begins recognizing the related stock-based compensation expense ratably when the event occurs or when the Company can determine that achievement of the performance condition is probable. In those cases, the Company recognizes the change in estimate at the time it determines the performance condition is probable of achievement (by recognizing stock-based compensation expense as cumulative catch-up adjustment as if the Company had estimated at the grant date that the performance condition would have been achieved) and recognize the remaining compensation cost through the end of the requisite service period. The Company issued no shares of common stock pursuant to the vesting of performance-based RSUs for the year ended December 31, 2018 and 2017.

A summary of activity related to the Company’s RSUs is as follows:



	Number of Restricted Stock Units Outstanding		Weighted-Average Grant-Date Fair Value
Balance, December 31, 2017	956,299		$	5.08
Granted	153,375		4.42
Share issuance	(233,050	)	5.05
Forfeited	(220,455	)	5.12
Balance, December 31, 2018	656,169		$	4.92

The total unrecognized compensation cost related to the non-vested RSUs as of December 31, 2018 was $3.9 million and will be recognized over a weighted average period of approximately 2.14 years years.

Warrants

In February 2011, the Company issued warrants to purchase an aggregate of 5,501,215 shares of Series F redeemable convertible preferred stock at an exercise price of $2.045 per share. Upon the completion of the Company’s IPO in April 2013, these warrants were converted into warrants to purchase 1,549,628 shares of common stock at an exercise price of $7.26 per share. At December 31, 2017, warrants for the purchase of 227,794 shares of common stock were issued, outstanding and exercisable. The warrants were exercisable at any time and expired on February 7, 2018.

Stock-based Compensation

For awards with only service conditions and graded-vesting features, the Company recognizes compensation expense on a straight-line basis over the requisite service period. Total stock-based compensation expense was as follows (in thousands):



	Years Ended December 31,
	2018		2017		2016
Income Statement Classification:
Research and development expense	$	5,343	$	7,047	$	7,137
General and administrative expense	7,731		9,063		9,086
Total stock-based compensation expense	$	13,074	$	16,110	$	16,223

Cash received from exercises under all share-based payment arrangements for 2018, 2017 and 2016 was $0.7 million, $0.8 million and $0.6 million, respectively. There was no actual tax benefit realized for the tax deductions from exercises of the share-based payment arrangements during 2018, 2017 or 2016.

At-The-Market Equity Offering

On November 8, 2017, the Company entered into an at-the-market (ATM) sales agreement with Cowen and Company, LLC to sell up to $75 million of the Company’s common stock under a shelf registration statement filed in November 2017. During the year ended December 31, 2018, the Company sold 2.8 million shares of common stock at a weighted average price per share of $4.00 for $10.9 million of proceeds net of commissions.

Income Taxes

12 Months Ended

Dec. 31, 2018

Income Tax Disclosure [Abstract]

Income Taxes

No income tax expense or benefit has been recorded for the years ended December 31, 2018, 2017 or 2016. This is due to the establishment of a valuation allowance against the deferred tax assets generated during those periods. At December 31, 2018, the Company has concluded that it is more likely than not that the Company may not realize the benefit of its deferred tax assets due to its history of losses. Accordingly, the net deferred tax assets have been fully reserved.

A reconciliation of the difference between the benefit for income taxes and income taxes at the statutory U.S. federal income tax rate is as follows for the years ended December 31, 2018, 2017, and 2016 (in thousands, except percentages):



	2018					2017					2016
	Amount			% of Pretax Earnings		Amount			% of Pretax Earnings		Amount			% of Pretax Earnings
Income tax benefit at statutory rate	$	(14,590	)	21.0	%	$	(24,134	)	34.0	%	$	(25,973	)	34.0	%
State income taxes	(792		)	1.1	%	(1,090		)	1.5	%	(1,544		)	2.0	%
Research and development credits	(1,798		)	2.6	%	(2,039		)	2.9	%	(2,691		)	3.5	%
Foreign rate differential	2			—	%	60			(0.1	)%	(2		)	—	%
Permanent items	1,164			(1.7	)%	1,646			(2.3	)%	2,537			(3.3	)%
Provision to return adjustments	621			(0.9	)%	1,212			(1.7	)%	259			(0.3	)%
Effect of change in federal tax rate	—			—	%	57,950			(81.6	)%	—			—	%
Effect of change in state tax rate	151			(0.2	)%	193			(0.3	)%	1,585			(2.1	)%
Removal of excess tax benefit	—			—	%	(12,930		)	18.2	%	—			—	%
Increase in unrecognized tax benefits	450			(0.7	)%	403			(0.6	)%	444			(0.6	)%
Change in valuation allowance	14,792			(21.2	)%	(21,271		)	30.0	%	25,385			(33.2	)%
Net benefit	$	—		—	%	$	—		—	%	$	—		—	%

The components of deferred tax assets and liabilities at December 31, 2018 and 2017 were as follows (in thousands):



	December 31,
	2018			2017
Deferred tax assets:
Domestic net operating loss carryforwards	$	104,708		$	92,020
Foreign net operating loss carryforwards	71			61
Research and development expenses	1,002			763
Capitalized Section 174 expenses	25			28
Research and development credits	13,789			12,437
Accrued bonuses	500			777
Share-based compensation	7,144			6,156
Other	778			983
Total gross deferred tax assets	128,017			113,225
Valuation allowance	(128,017		)	(113,225		)
Total deferred tax assets	—			—
Deferred tax liabilities:
Other	—			—
Total deferred tax liabilities	—			—
Total deferred tax assets and liabilities, net	$	—		$	—

At December 31, 2018, the Company had net operating loss carryforwards for federal, state, and foreign tax purposes of approximately $465.3 million, $353.8 million and $0.4 million, respectively. At December 31, 2017, the Company had net operating loss carryforwards for federal, state, and foreign tax purposes of approximately $408.1 million, $319.9 million and $0.4 million, respectively. Federal losses of $408.1 million begin to expire in 2020 and $57.2 million of the federal losses carryforward indefinitely. The state losses begin to expire in 2019. The foreign losses do not expire. In addition, the Company has tax credit carryforwards for federal tax purposes of approximately $18.4 million as of December 31, 2018, which begin to expire in 2022. The future utilization of net operating loss and tax credit carryforwards may be limited due to changes in ownership. Management has recorded a valuation allowance for all of the deferred tax assets due to the uncertainty of future taxable income.

The Company incorporated a subsidiary in the United Kingdom in 2014. However, the subsidiary has had minimal activity since inception. The subsidiary has primarily recorded net losses since inception and recorded a net loss as of December 31, 2018 and as such, has no undistributed earnings.

The Company incorporated a subsidiary in Ireland during 2018. However, the subsidiary had minimal activity during the year and as such, has no undistributed earnings.

In general, if the Company experiences a greater than 50% aggregate change in ownership of certain significant stockholders over a three-year period (a Section 382 ownership change), utilization of its pre-change net operating loss carryforwards is subject to an annual limitation under Section 382 of the Internal Revenue Code of 1986, as amended (and similar state laws). The annual limitation generally is determined by multiplying the value of the Company’s stock at the time of such ownership change (subject to certain adjustments) by the applicable long-term tax-exempt rate. Such limitations may result in expiration of a portion of the net operating loss carryforwards before utilization and may be substantial. The ability of the Company to use its net operating loss carryforwards may be limited or lost if the Company experiences a Section 382 ownership change in connection with offerings or as a result of future changes in its stock ownership. Losses from a specific period may be subject to multiple limitations, and would generally be limited by the lowest of those limitations.

The Company has determined that a Section 382 ownership change occurred in 2002, and as such, losses incurred prior to that date are subject to an annual limitation of at least $64,000. Additionally, the Company has determined that a Section 382 ownership change occurred in 2007, and as such, losses incurred prior to that date are subject to an annual limitation of at least $762,000. The Company evaluated Section 382 ownership changes subsequent to 2007 through September 30, 2018 and concluded that a Section 382 ownership change occurred in 2013 as a result of the initial public offering. As such, losses incurred prior to that date are subject to an annual limitation of at least $6.7 million.

As of December 31, 2017, the Company has adopted ASU 2016-09 which is effective for public companies for annual periods beginning after December 15, 2016. The ASU requires all excess tax benefits and tax deficiencies to be recognized as income tax expense or benefit in the income statement in the year in which they occur. As such, the Company has grossed up its net operating loss deferred tax asset to include all excess tax benefits as of December 31, 2017.

The Company has determined that there may be a future limitation on the Company’s ability to utilize its entire federal R&D credit carryover. Therefore, the Company recognized an uncertain tax benefit associated with the federal R&D credit carryover during the years ended December 31, 2018 and 2017, as follows (in thousands):



Balance at December 31, 2016	$	2,400
Increases related to 2017	403
Increases related to prior periods	473
Balance at December 31, 2017	3,276
Increases related to 2018	450
Increases related to prior periods	—
Balance at December 31, 2018	$	3,726

The change in the amount of the unrecognized tax benefits accrued for prior years is due to the change in the federal tax rate and is reflected as a component of such in the statutory rate reconciliation.

The Company has determined that it had no other material uncertain tax benefits for the year ended December 31, 2018. As of January 1, 2019, due to the carry forward of unutilized net operating losses and research and development credits, the Company is subject to U.S. federal and state income tax examinations for the tax years 2000 through 2018. The Company recognizes accrued interest related to unrecognized tax benefits in interest expense and penalties in operating expense. No amounts were accrued for the payment of interest and penalties at December 31, 2018.

On December 22, 2017, the Tax Act was enacted into law, which reduced the federal corporate income tax rate to 21% for tax years beginning after December 31, 2017. As a result of the revised tax rate, the Company adjusted its deferred tax assets as of December 31, 2017 by applying the revised 21% rate, which resulted in a decrease to the deferred tax assets and a corresponding decrease to the valuation allowance of approximately $58 million.

The Tax Act also implements a territorial tax system. Under the territorial tax system, in general, the Company's foreign earnings will no longer be subject to tax in the U.S. As part of the transition to the territorial tax system the Tax Act included a mandatory deemed repatriation of all undistributed foreign earnings that are subject to a U.S. income tax. The Company has determined that the deemed repatriation applicable to the year ended December 31, 2017 does not result in an additional U.S. income tax liability as it has no undistributed foreign earnings.

The Tax Act subjects a US shareholder to tax on global intangible low-taxed income (GILTI) earned by certain foreign subsidiaries. The FASB Staff Q&A, Topic 740, No. 5, Accounting for Global Intangible Low-Taxed Income, states that an entity can make an accounting policy election to either recognized deferred taxes for temporary basis differences expected to reverse as GILTI in future years or to provide for the tax expense related to GILTI in the year the tax is incurred as a period expense only. Because the Company was evaluating the provision of GILTI as of December 31, 2017, no GILTI-related deferred amounts were recorded in 2017. The Company has elected to account for GILTI in the year the tax is incurred. The Company does not have a GILTI inclusion in 2018; therefore, no GILTI tax has been recorded for the year ended December 31, 2018.

The SEC staff issued Staff Accounting Bulletin No. 118, Income Tax Accounting Implications of the Tax Cuts and Jobs Act (SAB 118) which allows the Company to record provisional amounts during a measurement period which is similar to the measurement period used when accounting for business combinations. At December 31, 2017 provisional amounts were recorded related to deferred taxes for stock compensation and the deferred rate change. At December 31, 2018 the measurement period has ended and the Company's accounting related to the Tax Act is complete. The Company did not make any measurement-period adjustments related to the provisional items recorded as of December 31, 2017.

Significant Agreements	12 Months Ended
Significant Agreements	Dec. 31, 2018
Contractors [Abstract]
Significant Agreements	Significant Agreements The Regents of the University of California In May 2002, the Company entered into a license agreement with The Regents of the University of California (UC) under which the Company obtained an exclusive, worldwide license to UC’s patent rights in certain inventions (the UC Patent Rights) related to lipid-conjugated antiviral compounds and their use, including certain patents relating to brincidofovir. The license agreement was amended in September 2002 in order to expand the scope of the license and again in December 2010 in order to modify certain financial terms. The agreement was amended a third time in September 2011 to add additional patents related to certain metabolically stable lipid-conjugate compounds. A fourth amendment was executed in July 2012 to alter the rights and obligations of the parties in light of the Company’s current business plans. In April 2018, a fifth amendment was executed to alter the rights and obligations of the parties in light of the Company's current business plans and to extend the term of the agreement to the later of the longest-lived Patent Rights (as defined in the agreement) or May 2028. Under the license agreement, the Company is permitted to research, develop, manufacture and commercialize products utilizing the UC Patent Rights for all human and veterinary uses, and to sublicense such rights. UC retained the right, on behalf of itself and other non-profit institutions, to use the UC Patent Rights for educational and research purposes and to publish information about the UC Patent Rights. In consideration for the rights granted under the license agreement, the Company has issued UC an aggregate of 64,788 shares of common stock. As additional consideration, the Company is required to pay certain cash milestone payments in connection with the development and commercialization of compounds that are covered by the UC Patent Rights, plus certain annual fees to maintain such patents until the Company commercializes a product utilizing UC Patent Rights. In connection with the development and commercialization of brincidofovir and CMX157, the Company could be required to pay UC up to an aggregate of $3.4 million in milestone payments, assuming the achievement of all applicable milestone events under the license agreement. In addition, upon commercialization of any product utilizing the UC Patent Rights (which would include the commercialization of brincidofovir), the Company will be required to pay low single digit royalties on net sales of such product. The license agreement requires that we diligently develop, manufacture and commercialize compounds that are covered by the UC Patent Rights, and we have agreed to meet certain development and commercialization milestones. UC may, at its option, either terminate the license agreement or change the license granted from an exclusive license to a non-exclusive license if we fail to meet such development and commercialization milestones. We are currently in compliance with these milestone requirements. In the event the Company sublicenses a UC Patent Right (including UC Patent Rights relating to brincidofovir or CMX157) the Company is obligated to pay to UC a fee, which amount will vary depending upon the amount of any payments the Company receives and the clinical development stage of the compound being sublicensed, but which could be up to approximately 50% of the sublicense fee in certain circumstances. With respect to brincidofovir, the fee payable to UC will not exceed 5% of the sublicense fee. In addition, the Company will also be required to pay to UC a low single digit sublicense royalty on net sales of products that use the sublicensed UC Patent Rights, but in no event will the Company be required to pay more than 50% of the royalties it receives in connection with the relevant sublicense. Any such royalty payment will be reduced by other payments the Company is required to make to third parties until a minimum royalty has been reached. Biomedical Advanced Research and Development Authority (BARDA) In February 2011, the Company entered into a contract with BARDA for the advanced development of brincidofovir as a medical countermeasure in the event of a smallpox release. Under the contract, BARDA will reimburse the Company, plus pay a fixed fee, for the research and development of brincidofovir as a broad-spectrum therapeutic antiviral for the treatment of smallpox infections. The contract consists of an initial performance period, referred to as the base performance segment, plus up to four extension periods, referred to as option segments, each of which may be exercised at BARDA’s sole discretion. The Company must complete the agreed upon milestones and deliverables in each discrete work segment before the next option segment is eligible to be exercised. Under the contract as currently in effect, the Company may receive up to $75.8 million in expense reimbursement and $5.3 million in fees. The Company is currently performing under the second and third option segments of the contract during which the Company may receive up to a total of $23.9 million and $14.1 million in expense reimbursement and fees, respectively. The second option segment is scheduled to end on August 1, 2019 and the third option segments is scheduled to end on March 30, 2019. Of the $75.8 million in expense reimbursement and $5.3 million in fees that the Company may receive, approximately $74.3 million in expense reimbursement and fees has been funded. As of December 31, 2018, of the total funding the Company had invoiced an aggregate of $62.6 million with respect to the base performance segment and the first three extension periods. For the years ended December 31, 2018, 2017, and 2016, the Company recognized revenue under this contract of $7.2 million, $4.5 million and $5.7 million, respectively. ContraVir Pharmaceuticals On December 17, 2014, the Company entered into a license agreement with ContraVir Pharmaceuticals (Nasdaq: CTRV) for the development and commercialization of CMX157 for certain antiviral indications. Under the terms of the agreement, ContraVir has sole responsibility with respect to the control of the development and commercialization of CMX157. In exchange for the license to CMX157 rights, the Company received an upfront payment consisting of ContraVir Series B Convertible Preferred Stock which the Company converted into shares of ContraVir common stock in 2016. As of December 31, 2018 and 2017, the fair value of the investment was recorded as a short-term investment of $38 thousand and $0.4 million, respectively. In addition, the Company is eligible to receive up to approximately $20 million in clinical, regulatory and initial commercial milestones in the United States and Europe, as well as royalties and additional milestones based on commercial sales in those territories. Either party may terminate the license agreement upon the occurrence of a material breach by the other party (subject to standard cure periods), or upon certain events involving the bankruptcy or insolvency of the other party. ContraVir may also terminate the license agreement without cause on a country-by-country basis upon sixty days’ prior written notice. University of Michigan In 2006, the Company entered into a license agreement with The Regents of the University of Michigan (UM) under which the Company obtained an exclusive, worldwide license to UM’s patent rights in certain inventions (UM Patent Rights) related to certain compounds originally synthesized at UM. Under the license agreement, the Company is permitted to research, develop, manufacture and commercialize products utilizing the UM Patent Rights, and to sublicense such rights subject to certain sublicensing fees and royalty payments. In consideration for the rights granted to the Company, under the license agreement as amended in December 2016, the Company paid UM $50,000 in fees in 2016 and in January 2017 issued UM an aggregate of 33,058 shares of its common stock. In connection with the Company's commercialization or sublicensing of certain products covered by the license agreement, including CMX521, the Company could be required to pay royalties on net sales of such products ranging from 0.25% to 2%. Beginning in 2024, the Company is also subject to certain minimum annual royalty payments. The UM license agreement requires that the Company uses commercially reasonable efforts to develop and make commercially available licensed products as soon as practicable. Specifically, the Company has agreed to make the first commercial sale of a licensed product by June of 2026. UM may terminate the license agreement if the Company materially breaches the license agreement. The Company is currently in compliance with its milestone requirements.

The Business and Summary of Significant Accounting Policies (Policies)

12 Months Ended

Dec. 31, 2018

Accounting Policies [Abstract]

Basis of Presentation

Reclassifications

Cash and Cash Equivalents

Investments and Unrealized Loss on Equity Investment

Unrealized Loss on Equity Investment

Investments

Concentration of Credit Risk

Accounts Receivable

Fair Value of Financial Instruments


•	Level 1 — Valuations based on unadjusted quoted prices in active markets for identical assets or liabilities that the Company has the ability to access.


•	Level 2 — Valuations based on quoted prices for similar assets or liabilities in active markets, quoted prices for identical or similar assets or liabilities in markets that are not active, and models for which all significant inputs are observable, either directly or indirectly.


•	Level 3 — Valuations based on inputs that are unobservable and significant to the overall fair value measurement.

Property and Equipment

Impairment of Property and Equipment

Deferred Lease Obligation

Deferred Lease Obligations

Revenue Recognition

Policy

Research and Development Prepaids and Accruals

Research and Development Expenses

Interest Income and Other, Net

Interest income and other, net primarily includes interest earned on short-term and long-term investments and realized gains on the sale of short-term investments.

Income Taxes

Share-Based Compensation

401(k) Plan

The Company maintains a defined contribution employee retirement plan (“401(k) plan”).

Basic and Dilutive Net Loss Per Share of Common Stock

Segments

Impact of Recently Issued Accounting Standards and Impact of Recently Adopted Accounting Standards

Impact of Recently Issued Accounting Standards

Impact of Recently Adopted Accounting Standards

Stockholders' Equity (Deficit) (Tables)

12 Months Ended

Dec. 31, 2018

Stockholders' Equity Note [Abstract]

Schedule of Shares Reserved for Future Issuance

The Company has reserved shares of common stock for future issuances as follows:



	December 31,
	2018	2017
For exercise of common stock warrants	—	227,794
For exercise of outstanding common stock options	6,429,638	4,996,661
For delivery upon vesting of outstanding restricted stock units	656,169	956,299
For future equity awards under the 2013 Equity Incentive Plan	1,587,670	1,082,608
For future purchases under the 2013 Employee Stock Purchase Plan	2,120,290	1,861,472
Total shares of common stock reserved for future issuances	10,793,767	9,124,834

Schedule of Fair Value Assumptions, Stock Options

The following table illustrates the assumptions for the Black-Scholes model used in determining the fair value of the stock options granted:



	Years Ended December 31,
	2018			2017			2016
Expected volatility	85.83		%	85.51		%	85.16		%
Expected term (in years)	5.9			5.9			6.0
Weighted-average risk-free interest rate	2.52		%	2.02		%	1.70		%
Expected dividend yield	—		%	—		%	—		%
Weighted-average fair value per option	$	3.43		$	3.71		$	5.62

Summary of Activity Related to Stock Options

A summary of activity related to the Company’s stock options is as follows:



	Number of Options Outstanding		Weighted-Average Exercise Price		Weighted-Average Remaining Contractual Life (in Years)	Total Intrinsic Value
Balance, December 31, 2016	4,342,466		$	17.81	8.09
Granted	928,816		5.17		—
Exercised	(38,885	)	3.98		—
Forfeited	(235,736	)	19.10		—
Balance, December 31, 2017	4,996,661		$	15.51	7.59
Granted	2,050,995		4.73		—
Exercised	(29,262	)	3.93		—
Forfeited	(588,756	)	12.31		—
Balance, December 31, 2018	6,429,638		$	12.41	7.37	$	39,873
Exercisable at December 31, 2018	4,119,234		$	15.94	6.75	$	39,873
Vested or expected to vest at December 31, 2018	6,366,085		$	12.47	7.36	$	39,873

Schedule of Other Information Regarding Stock Options

Other information regarding the Company’s stock options is as follows (in thousands, except per share data):



	Years Ended December 31,
	2018		2017		2016
Weighted-average grant-date fair value per share of options granted	$	3.43	$	3.71	$	5.62
Total intrinsic value of options exercised	$	31	$	48	$	119
Total fair value of shares vested	$	11,021	$	11,786	$	13,330

Schedule of Share-based Compensation, Shares Authorized



	Outstanding				Exercisable
Exercise Price Range ($)	Number	Weighted-Average Remaining Contractual Life (in years)	Weighted-Average Exercise Price		Number	Weighted-Average Exercise Price
1.57 to 7.57	3,139,495	8.37	$	4.70	1,323,880	$	4.54
7.58 to 8.06	1,696,746	7.02	8.06		1,239,595	8.06
8.07 to 18.75	261,805	5.07	18.59		261,805	18.59
18.76 to 39.17	559,663	5.55	25.32		556,525	25.25
39.18 to 53.74	771,929	6.22	41.90		737,429	41.71
1.57 to 53.74	6,429,638	7.37	$	12.41	4,119,234	$	15.94

Schedule of Fair Value Assumptions, Employee Stock Purchase Plan

The following table illustrates the assumptions for the Black-Scholes model used in determining the fair value of the ESPP purchase rights:



	Years Ended December 31,
	2018			2017			2016
Expected volatility	44.01		%	77.18		%	111.57		%
Expected term (in years)	1.23			0.97			1.37
Weighted-average risk-free interest rate	2.56		%	0.99		%	0.75		%
Expected dividend yield	—		%	—		%	—		%
Weighted-average option value per share	$	1.36		$	2.65		$	3.20

Summary of Activity Related to Restricted Stock Units

A summary of activity related to the Company’s RSUs is as follows:



	Number of Restricted Stock Units Outstanding		Weighted-Average Grant-Date Fair Value
Balance, December 31, 2017	956,299		$	5.08
Granted	153,375		4.42
Share issuance	(233,050	)	5.05
Forfeited	(220,455	)	5.12
Balance, December 31, 2018	656,169		$	4.92

Schedule of Employee Service Share-based Compensation, Allocation of Recognized Period Costs



	Years Ended December 31,
	2018		2017		2016
Income Statement Classification:
Research and development expense	$	5,343	$	7,047	$	7,137
General and administrative expense	7,731		9,063		9,086
Total stock-based compensation expense	$	13,074	$	16,110	$	16,223

The Business and Summary of Significant Accounting Policies (Narrative) (Details)		12 Months Ended			95 Months Ended	98 Months Ended	102 Months Ended
	Dec. 17, 2014 USD ($)	Dec. 31, 2018 USD ($) segment	Dec. 31, 2017 USD ($)	Dec. 31, 2016 USD ($)	Dec. 31, 2018 USD ($)	Mar. 30, 2019 USD ($)	Aug. 01, 2019 USD ($) base_segment option_segment revenue_contract	Jan. 01, 2019 USD ($)
Investments
Realized losses on available for sale debt securities		$ 400,000
Unrealized loss on equity investment		348,000
Unrealized loss on equity investment			$ 1,160,000	$ 0
Unrealized loss on equity investment				200,000
Property and Equipment
Impairment of long-lived assets		0
Revenue Recognition
Contract revenue		7,216,000	4,494,000	5,702,000
Defined Contribution Plan [Abstract]
Defined contribution plan, cost recognized		$ 400,000	300,000	400,000
Segments
Number of operating segments \| segment		1
Minimum
Property and Equipment
Property and equipment, useful life		3 years
Maximum
Property and Equipment
Property and equipment, useful life		5 years
BARDA
Revenue Recognition
Contract revenue		$ 7,200,000	$ 4,500,000	$ 5,700,000	$ 62,600,000
ContraVir Pharmaceuticals
Revenue Recognition
Future licenses revenue	$ 20,000,000
ContraVir Pharmaceuticals \| Maximum
Revenue Recognition
Future licenses revenue	$ 20,000,000
Scenario, Forecast \| BARDA
Revenue Recognition
Contract revenue							$ 74,300,000
Number of base segments \| base_segment							1
Number of option segments \| option_segment							4
Number of contracts \| revenue_contract							5
Scenario, Forecast \| Second Option Segment
Revenue Recognition
Contract revenue							$ 23,900,000
Scenario, Forecast \| Third Option Segment
Revenue Recognition
Contract revenue						$ 14,100,000
Scenario, Forecast \| Expense Reimbursement \| BARDA \| Maximum
Revenue Recognition
Contract revenue							75,800,000
Scenario, Forecast \| Fees \| BARDA \| Maximum
Revenue Recognition
Contract revenue							$ 5,300,000
Subsequent Event \| Accounting Standards Update 2016-02 \| Scenario, Forecast
Leases
Lease asset								$ 2,000,000
Lease liability								$ 1,600,000

The Business and Summary of Significant Accounting Policies (Assets and Liabilities Measured at Fair Value on a Recurring Basis) (Details) - Fair value, measurements, recurring - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	$ 75,893	$ 14,811
Short-term Investments	105,424	132,972
Long-term investments		76,731
Total assets	181,317	224,514
Quoted Prices in Active Markets for Identical Assets (Level 1)
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	42,208	10,816
Short-term Investments	12,627	132,972
Long-term investments		76,731
Total assets	54,835	220,519
Significant Other Observable Inputs (Level 2)
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	33,685	3,995
Short-term Investments	92,797	0
Long-term investments		0
Total assets	126,482	3,995
Significant Unobservable Inputs (Level 3)
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	0	0
Short-term Investments	0	0
Long-term investments		0
Total assets	0	0
Money market funds
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	30,726	10,816
Money market funds \| Quoted Prices in Active Markets for Identical Assets (Level 1)
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	30,726	10,816
Money market funds \| Significant Other Observable Inputs (Level 2)
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	0	0
Money market funds \| Significant Unobservable Inputs (Level 3)
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	0	0
U.S. Treasury securities
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	11,482
Short-term Investments	12,589	132,586
Long-term investments		76,731
U.S. Treasury securities \| Quoted Prices in Active Markets for Identical Assets (Level 1)
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	11,482
Short-term Investments	12,589	132,586
Long-term investments		76,731
U.S. Treasury securities \| Significant Other Observable Inputs (Level 2)
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	0
Short-term Investments	0	0
Long-term investments		0
U.S. Treasury securities \| Significant Unobservable Inputs (Level 3)
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	0
Short-term Investments	0	0
Long-term investments		0
Common stock of U.S. corporation
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Short-term Investments	38	386
Common stock of U.S. corporation \| Quoted Prices in Active Markets for Identical Assets (Level 1)
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Short-term Investments	38	386
Common stock of U.S. corporation \| Significant Other Observable Inputs (Level 2)
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Short-term Investments	0	0
Common stock of U.S. corporation \| Significant Unobservable Inputs (Level 3)
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Short-term Investments	0	0
Commercial paper
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	29,677	3,995
Short-term Investments	60,114
Commercial paper \| Quoted Prices in Active Markets for Identical Assets (Level 1)
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	0	0
Short-term Investments	0
Commercial paper \| Significant Other Observable Inputs (Level 2)
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	29,677	3,995
Short-term Investments	60,114
Commercial paper \| Significant Unobservable Inputs (Level 3)
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	0	$ 0
Short-term Investments	0
Corporate bonds
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	4,008
Short-term Investments	32,683
Corporate bonds \| Quoted Prices in Active Markets for Identical Assets (Level 1)
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	0
Short-term Investments	0
Corporate bonds \| Significant Other Observable Inputs (Level 2)
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Cash equivalents	4,008
Short-term Investments	32,683
Corporate bonds \| Significant Unobservable Inputs (Level 3)
Schedule of Fair Value of Separate Accounts by Major Category of Investment [Line Items]
Short-term Investments	$ 0

Investments - Summary of Investments with Unrealized Losses, Aggregated by Investment Type and the Length of Time (Details) $ in Thousands	Dec. 31, 2018 USD ($) security	Dec. 31, 2017 USD ($) security
Schedule of Investments [Line Items]
Fair Value, Less than 12 Months		$ 170,390
Fair Value, Less than 12 Months	$ 105,386
Unrealized Loss, Less than 12 Months		(871)
Unrealized Loss, Less than 12 Months	(89)
Fair Value, Greater than 12 Months		38,927
Fair Value, Greater than 12 Months	0
Unrealized Loss, Greater than 12 Months		(92)
Unrealized Loss, Greater than 12 Months	0
Fair Value, Total		209,317
Fair Value, Total	105,386
Unrealized Loss, Total		$ (963)
Unrealized Loss, Total	$ (89)
Number of securities with unrealized losses, Less than 12 Months \| security		39
Number of securities with unrealized losses, Less than 12 Months \| security	36
Number of securities with unrealized losses, Greater than 12 Months \| security		7
Number of securities with unrealized losses, Greater than 12 Months \| security	0
Number of securities with unrealized losses, Total \| security		46
Number of securities with unrealized losses, Total \| security	36
Corporate bonds
Schedule of Investments [Line Items]
Fair Value, Less than 12 Months	$ 32,683
Unrealized Loss, Less than 12 Months	(41)
Fair Value, Greater than 12 Months	0
Unrealized Loss, Greater than 12 Months	0
Fair Value, Total	32,683
Unrealized Loss, Total	(41)
Commercial paper
Schedule of Investments [Line Items]
Fair Value, Less than 12 Months	60,114
Unrealized Loss, Less than 12 Months	(45)
Fair Value, Greater than 12 Months	0
Unrealized Loss, Greater than 12 Months	0
Fair Value, Total	60,114
Unrealized Loss, Total	(45)
U.S. Treasury securities
Schedule of Investments [Line Items]
Fair Value, Less than 12 Months		$ 170,390
Fair Value, Less than 12 Months	12,589
Unrealized Loss, Less than 12 Months		(871)
Unrealized Loss, Less than 12 Months	(3)
Fair Value, Greater than 12 Months		38,927
Fair Value, Greater than 12 Months	0
Unrealized Loss, Greater than 12 Months		(92)
Unrealized Loss, Greater than 12 Months	0
Fair Value, Total		209,317
Fair Value, Total	12,589
Unrealized Loss, Total		$ (963)
Unrealized Loss, Total	$ (3)

Stockholders' Equity (Deficit) (Narrative) (Details) - USD ($)			12 Months Ended
	Jan. 01, 2018	Jan. 01, 2017	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016	Nov. 08, 2017	Apr. 30, 2013	Feb. 28, 2013	Feb. 28, 2011
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Common stock, shares authorized (in shares)			200,000,000	200,000,000
Common stock, shares issued (in shares)			50,735,279	47,505,532
Common stock, shares outstanding (in shares)			50,735,279	47,505,532
Shares reserved for future issuance (in shares)			10,793,767	9,124,834
Liability			$ 8,275,000	$ 9,384,000
Shares issued pursuant to vesting of RSUs (in shares)			233,050	744,450
Number of shares called by warrants (in share)				227,794
Warrants outstanding and exercisable (in shares)				227,794
Proceeds from exercise of all share-based payment arrangements			$ 700,000	$ 800,000	$ 600,000
Tax benefit from share-based payment arrangements			$ 0	$ 0	$ 0
Performance Shares
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares issued pursuant to vesting of RSUs (in shares)			0	0
Restricted stock units (RSUs)
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized compensation costs, period of recognition			2 years 51 days
Shares reserved for future issuance (in shares)			656,169	956,299
Share-based compensation, nonvested awards, compensation cost not recognized			$ 3,900,000.0
The 2013 Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, equity increase percentage			4.00%
Share-based compensation, nonvested awards, compensation not yet recognized, stock options			$ 8,700,000
Unrecognized compensation costs, period of recognition			2 years
Shares reserved for future issuance (in shares)			1,587,670	1,082,608
The 2013 Employee Stock Purchase Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, equity increase percentage			1.00%
Number of shares authorized to be granted (in shares)								704,225
Number of shares authorized, increase amount (in shares)			422,535
Number of additional shares authorized (in shares)	422,535	422,535
Number of shares available for grant (in shares)	2,648,796	2,226,261	2,648,796
Shares reserved for future issuance (in shares)			2,120,290	1,861,472
Percentage of pay that employee can contribute, maximum			15.00%
Discount from market price, entry date			15.00%
Discount from market price, purchase date			15.00%
Employee stock purchase plan, automatic reset participation period			24 months
Shares issued during period, employee stock purchase plans (in shares)			163,717	173,822
ESPP purchase period			6 months
Liability			$ 200,000
Private Placement
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Sale of common stock, amount authorized						$ 75,000,000
Common stock sold (in shares)			2,800,000
Sale of common stock, weighted average price of shares sold (in usd per share)			$ 4.00
Sale of common stock, net offering proceeds			$ 10,900,000
Common Stock \| IPO
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Number of shares called by warrants (in share)							1,549,628
Exercise price of warrants (in usd per share)							$ 7.26
Series F
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Number of shares called by warrants (in share)									5,501,215
Exercise price of warrants (in usd per share)									$ 2.045

Stockholders' Equity (Deficit) (Summary of Activity Related to Stock Options) (Details) - USD ($)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Number of Options Outstanding
Beginning balance (in shares)	4,996,661	4,342,466
Granted (in shares)	2,050,995	928,816
Exercised (in shares)	(29,262)	(38,885)
Forfeited (in shares)	(588,756)	(235,736)
Ending balance (in shares)	6,429,638	4,996,661	4,342,466
Exercisable (in shares)	4,119,234
Vested and expected to vest (in shares)	6,366,085
Weighted-Average Exercise Price
Beginning balance (in usd per share)	$ 15.51	$ 17.81
Granted (in usd per share)	4.73	5.17
Exercised (in usd per share)	3.93	3.98
Forfeited (in usd per share)	12.31	19.10
Ending balance (in usd per share)	12.41	$ 15.51	$ 17.81
Exercisable (in usd per share)	15.94
Vested or expected to vest (in usd per share)	$ 12.47
Additional Disclosure
Weighted-average remaining contractual life (in years)	7 years 135 days	7 years 215 days	8 years 1 month 2 days
Weighted-average remaining contractual life (in years), Exercisable	6 years 274 days
Weighted-average remaining contractual life (in years), Vested or expected to vest	7 years 131 days
Total intrinsic value of options outstanding	$ 39,873
Total intrinsic value of options exercisable	39,873
Total intrinsic value of options vested or expected to vest	$ 39,873

Stockholders' Equity (Deficit) (Schedule of Share-based Compensation, Shares Authorized) (Details)	12 Months Ended
	Dec. 31, 2018 $ / shares shares
1.57 to 7.57
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, number of outstanding options (in shares) \| shares	3,139,495
Share-based compensation, outstanding options, weighted average remaining contractual term	8 years 135 days
Share-based compensation, outstanding options, weighted average exercise price (in usd per share)	$ 4.70
Share-based compensation, number of exercisable options (in shares) \| shares	1,323,880
Share-based compensation, exercisable options, weighted average exercise price (in usd per share)	$ 4.54
7.58 to 8.06
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, number of outstanding options (in shares) \| shares	1,696,746
Share-based compensation, outstanding options, weighted average remaining contractual term	7 years 7 days
Share-based compensation, outstanding options, weighted average exercise price (in usd per share)	$ 8.06
Share-based compensation, number of exercisable options (in shares) \| shares	1,239,595
Share-based compensation, exercisable options, weighted average exercise price (in usd per share)	$ 8.06
8.07 to 18.75
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, number of outstanding options (in shares) \| shares	261,805
Share-based compensation, outstanding options, weighted average remaining contractual term	5 years 26 days
Share-based compensation, outstanding options, weighted average exercise price (in usd per share)	$ 18.59
Share-based compensation, number of exercisable options (in shares) \| shares	261,805
Share-based compensation, exercisable options, weighted average exercise price (in usd per share)	$ 18.59
18.76 to 39.17
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, number of outstanding options (in shares) \| shares	559,663
Share-based compensation, outstanding options, weighted average remaining contractual term	5 years 201 days
Share-based compensation, outstanding options, weighted average exercise price (in usd per share)	$ 25.32
Share-based compensation, number of exercisable options (in shares) \| shares	556,525
Share-based compensation, exercisable options, weighted average exercise price (in usd per share)	$ 25.25
39.18 to 53.74
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, number of outstanding options (in shares) \| shares	771,929
Share-based compensation, outstanding options, weighted average remaining contractual term	6 years 80 days
Share-based compensation, outstanding options, weighted average exercise price (in usd per share)	$ 41.90
Share-based compensation, number of exercisable options (in shares) \| shares	737,429
Share-based compensation, exercisable options, weighted average exercise price (in usd per share)	$ 41.71
1.57 to 53.74
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, number of outstanding options (in shares) \| shares	6,429,638
Share-based compensation, outstanding options, weighted average remaining contractual term	7 years 135 days
Share-based compensation, outstanding options, weighted average exercise price (in usd per share)	$ 12.41
Share-based compensation, number of exercisable options (in shares) \| shares	4,119,234
Share-based compensation, exercisable options, weighted average exercise price (in usd per share)	$ 15.94
Minimum \| 1.57 to 7.57
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, lower range limit (in usd per share)	1.57
Minimum \| 7.58 to 8.06
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, lower range limit (in usd per share)	7.58
Minimum \| 8.07 to 18.75
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, lower range limit (in usd per share)	8.07
Minimum \| 18.76 to 39.17
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, lower range limit (in usd per share)	18.76
Minimum \| 39.18 to 53.74
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, lower range limit (in usd per share)	39.18
Minimum \| 1.57 to 53.74
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, lower range limit (in usd per share)	1.57
Maximum \| 1.57 to 7.57
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, upper range limit (in usd per share)	7.57
Maximum \| 7.58 to 8.06
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, upper range limit (in usd per share)	8.06
Maximum \| 8.07 to 18.75
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, upper range limit (in usd per share)	18.75
Maximum \| 18.76 to 39.17
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, upper range limit (in usd per share)	39.17
Maximum \| 39.18 to 53.74
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, upper range limit (in usd per share)	53.74
Maximum \| 1.57 to 53.74
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based compensation, upper range limit (in usd per share)	$ 53.74

Income Taxes (Reconciliation of the Difference between the Benefit for Income Taxes and Income Taxes at the Statutory U.S. Federal Income Tax Rate) (Alternate) (Details) - USD ($)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Amount
Income tax benefit at statutory rate	$ (14,590,000)	$ (24,134,000)	$ (25,973,000)
State income taxes	(792,000)	(1,090,000)	(1,544,000)
Research and development credits	(1,798,000)	(2,039,000)	(2,691,000)
Foreign rate differential	2,000	60,000	(2,000)
Permanent items	1,164,000	1,646,000	2,537,000
Provision to return adjustments	621,000	1,212,000	259,000
Effect of change in federal tax rate	0	57,950,000	0
Effect of change in state tax rate	151,000	193,000	1,585,000
Removal of excess tax benefit	0	(12,930,000)	0
Increase in unrecognized tax benefits	450,000	403,000	444,000
Change in valuation allowance	14,792,000	(21,271,000)	25,385,000
Net benefit	$ 0	$ 0	$ 0
% of Pretax Earnings
Income tax benefit at statutory rate	21.00%	34.00%	34.00%
State income taxes	1.10%	1.50%	2.00%
Research and development credits	2.60%	2.90%	3.50%
Foreign rate differential	0.00%	(0.10%)	0.00%
Permanent items	(1.70%)	(2.30%)	(3.30%)
Provision to return adjustments	(0.90%)	(1.70%)	(0.30%)
Effect of change in federal tax rate	0.00%	(81.60%)	0.00%
Effect of change in state tax rate	(0.20%)	(0.30%)	(2.10%)
Removal of excess tax benefit	0.00%	18.20%	0.00%
Increase in unrecognized tax benefits	(0.70%)	(0.60%)	(0.60%)
Change in valuation allowance	(21.20%)	30.00%	(33.20%)
Net benefit	0.00%	0.00%	0.00%

Income Taxes (Components of Deferred Tax Assets and Liabilities) (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Deferred tax assets:
Domestic net operating loss carryforwards	$ 104,708	$ 92,020
Foreign net operating loss carryforwards	71	61
Research and development expenses	1,002	763
Capitalized Section 174 expenses	25	28
Research and development credits	13,789	12,437
Accrued bonuses	500	777
Share-based compensation	7,144	6,156
Other	778	983
Total gross deferred tax assets	128,017	113,225
Valuation allowance	(128,017)	(113,225)
Total deferred tax assets	0	0
Deferred tax liabilities:
Other	0	0
Total deferred tax liabilities	0	0
Total deferred tax assets and liabilities, net	$ 0	$ 0

Significant Agreements (Details)		1 Months Ended			12 Months Ended			95 Months Ended	98 Months Ended	102 Months Ended
Significant Agreements (Details)	Dec. 17, 2014 USD ($)	Jan. 31, 2017 shares	Dec. 31, 2016 USD ($)	May 31, 2002 USD ($) shares	Dec. 31, 2018 USD ($)	Dec. 31, 2017 USD ($)	Dec. 31, 2016 USD ($)	Dec. 31, 2018 USD ($) period	Mar. 30, 2019 USD ($)	Aug. 01, 2019 USD ($) extension
Long-term Purchase Commitment [Line Items]
Contract revenue					$ 7,216,000	$ 4,494,000	$ 5,702,000
Regents of University of California
Long-term Purchase Commitment [Line Items]
Stock issued during period, issued for services (in shares) \| shares				64,788
BARDA
Long-term Purchase Commitment [Line Items]
Contract revenue					$ 7,200,000	4,500,000	$ 5,700,000	$ 62,600,000
Number of extension periods \| period								3
ContraVir Pharmaceuticals
Long-term Purchase Commitment [Line Items]
Future licenses revenue	$ 20,000,000
License agreement, termination notice period	60 days
The Regents of the University of Michigan
Long-term Purchase Commitment [Line Items]
Stock issued during period, issued for services (in shares) \| shares		33,058
License and Service \| The Regents of the University of Michigan
Long-term Purchase Commitment [Line Items]
Cost of sales			$ 50,000
Scenario, Forecast \| BARDA
Long-term Purchase Commitment [Line Items]
Number of extension periods \| extension										4
Contract revenue										$ 74,300,000
Scenario, Forecast \| Second Option Segment
Long-term Purchase Commitment [Line Items]
Contract revenue										23,900,000
Scenario, Forecast \| Third Option Segment
Long-term Purchase Commitment [Line Items]
Contract revenue									$ 14,100,000
Maximum \| Regents of University of California
Long-term Purchase Commitment [Line Items]
Milestone payments				$ 3,400,000
Sublicense fee percentage				50.00%
Royalties percentage				50.00%
Maximum \| ContraVir Pharmaceuticals
Long-term Purchase Commitment [Line Items]
Future licenses revenue	$ 20,000,000
Maximum \| The Regents of the University of Michigan
Long-term Purchase Commitment [Line Items]
Royalties percentage					2.00%
Maximum \| Brincidofovir \| Regents of University of California
Long-term Purchase Commitment [Line Items]
Sublicense fee amount payable fee percentage				5.00%
Maximum \| Scenario, Forecast \| Expense Reimbursement \| BARDA
Long-term Purchase Commitment [Line Items]
Contract revenue										75,800,000
Maximum \| Scenario, Forecast \| Fees \| BARDA
Long-term Purchase Commitment [Line Items]
Contract revenue										$ 5,300,000
Minimum \| The Regents of the University of Michigan
Long-term Purchase Commitment [Line Items]
Royalties percentage					0.25%
ContraVir Investment \| Common Stock
Long-term Purchase Commitment [Line Items]
Short-term investments					$ 38,000	$ 400,000		$ 38,000

Subsequent Events	12 Months Ended
Subsequent Events	Dec. 31, 2018
Subsequent Events [Abstract]
Subsequent Events	Subsequent Events The Company has evaluated subsequent events through the issuance date of these financial statements to ensure that this filing includes appropriate disclosure of events both recognized in the financial statements as of December 31, 2018, and events which occurred subsequently but were not recognized in the financial statements.

Investments - Summary of Available-for-Sale Securities (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Schedule of Investments [Line Items]
Amortized Cost		$ 210,280
Amortized Cost	$ 105,475
Gross Unrealized Gains		0
Gross Unrealized Gains	0
Gross Unrealized Losses		(963)
Gross Unrealized Losses	(89)
Estimated Fair Value		209,317
Estimated Fair Value	105,386
Corporate bonds
Schedule of Investments [Line Items]
Amortized Cost	32,724
Gross Unrealized Gains	0
Gross Unrealized Losses	(41)
Estimated Fair Value	32,683
Commercial paper
Schedule of Investments [Line Items]
Amortized Cost	60,159
Gross Unrealized Gains	0
Gross Unrealized Losses	(45)
Estimated Fair Value	60,114
U.S. Treasury securities
Schedule of Investments [Line Items]
Amortized Cost		210,280
Amortized Cost	12,592
Gross Unrealized Gains		0
Gross Unrealized Gains	0
Gross Unrealized Losses		(963)
Gross Unrealized Losses	(3)
Estimated Fair Value		$ 209,317
Estimated Fair Value	$ 12,589

Investments - Available for Sale Securities (Details) $ in Thousands	Dec. 31, 2018 USD ($)
Investments [Abstract]
Maturing in one year or less	$ 105,386
Total debt investments	105,386
Common stock of U.S. corporation	38
Total investments	$ 105,424

Property and Equipment (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Property, Plant and Equipment [Line Items]
Property and equipment	$ 5,850	$ 5,738
Less accumulated depreciation	(4,640)	(3,844)
Property and equipment, net of accumulated depreciation	1,210	1,894
Lab equipment
Property, Plant and Equipment [Line Items]
Property and equipment	2,599	2,496
Leasehold improvements
Property, Plant and Equipment [Line Items]
Property and equipment	1,550	1,552
Computer equipment
Property, Plant and Equipment [Line Items]
Property and equipment	1,181	1,170
Office furniture and equipment
Property, Plant and Equipment [Line Items]
Property and equipment	$ 520	$ 520

Commitments and Contingencies (Schedule of Future Minimum Rental Payments for Operating Leases) (Details) $ in Thousands	Dec. 31, 2018 USD ($)
Operating Leases, Future Minimum Payments Due, Fiscal Year Maturity [Abstract]
2019	$ 786
2020	797
2021	235
Total future minimum rental payments	$ 1,818

Consolidated Balance Sheets (Parenthetical) - $ / shares	Dec. 31, 2018	Dec. 31, 2017
Statement of Financial Position [Abstract]
Preferred stock, par value (in USD per share)	$ 0.001	$ 0.001
Preferred stock, shares authorized (in shares)	10,000,000	10,000,000
Preferred stock, shares issued (in shares)	0	0
Preferred stock, shares outstanding (in shares)	0	0
Common stock, par value (in USD per share)	$ 0.001	$ 0.001
Common stock, shares authorized (in shares)	200,000,000	200,000,000
Common stock, shares issued (in shares)	50,735,279	47,505,532
Common stock, shares outstanding (in shares)	50,735,279	47,505,532

The Business and Summary of Significant Accounting Policies (Schedule of Prepaid and Other Current Assets) (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Accounting Policies [Abstract]
Prepaid research and development expenses	$ 1,071	$ 1,138
Interest receivable	259	601
Prepaid insurance	382	481
Other prepaid expenses and current assets	886	1,111
Total prepaid expenses and other current assets	$ 2,598	$ 3,331

The Business and Summary of Significant Accounting Policies (Schedule of Accrued Liabilities) (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Accounting Policies [Abstract]
Accrued compensation	$ 2,469	$ 3,678
Accrued research and development expenses	4,525	3,384
Accrued indemnification claim	0	1,000
Other accrued liabilities	1,281	1,322
Total accrued liabilities	$ 8,275	$ 9,384

Commitments and Contingencies (Narrative) (Details)	12 Months Ended
Commitments and Contingencies (Narrative) (Details)	Dec. 31, 2018 USD ($) ft²	Dec. 31, 2017 USD ($)	Dec. 31, 2016 USD ($)
Commitments and Contingencies Disclosure [Abstract]
Operating leases, rent expense	$ 600,000	$ 500,000	$ 700,000
Area of sublease property (in sqft) \| ft²	3,537
Refundable Agreements \| BARDA
Other Commitments [Line Items]
Provision for refundable amounts	$ 0	$ 0

Commitments and Contingencies (Schedule of Future Minimum Sublease Rental Payments for Operating Leases) (Details) (Details) $ in Thousands	Dec. 31, 2018 USD ($)
Operating Leases, Future Minimum Payments Due, Fiscal Year Maturity [Abstract]
2019	$ 78
2020	81
2021	14
Total future minimum sublease rentals	$ 173

Stockholders' Equity (Deficit) (Summary of Activity Related to Restricted Stock Units) (Details) - Restricted stock units (RSUs)	12 Months Ended
	Dec. 31, 2018 $ / shares shares
Number of Restricted Stock Units Outstanding
Beginning Balance (in shares) \| shares	956,299
Granted (in shares) \| shares	153,375
Shares issuance (in shares) \| shares	(233,050)
Forfeited (in shares) \| shares	(220,455)
Ending Balance (in shares) \| shares	656,169
Weighted-Average Grant-Date Fair Value
Beginning Balance (in usd per share) \| $ / shares	$ 5.08
Granted (in usd per share) \| $ / shares	4.42
Shares issuance (in usd per share) \| $ / shares	5.05
Forfeited (in usd per share) \| $ / shares	5.12
Ending Balance (in usd per share) \| $ / shares	$ 4.92

Income Taxes (Narrative) (Details) - USD ($)	12 Months Ended
Income Taxes (Narrative) (Details) - USD ($)	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2013	Dec. 31, 2007	Dec. 31, 2002
Operating Loss Carryforwards [Line Items]
Undistributed earnings of foreign subsidiary	$ 0	$ 0
Loss limitation ownership change benchmark amount					$ 762,000	$ 64,000
Annual limitation of operating loss carryforwards				$ 6,700,000
Penalties and interest accrued	0
Effect of change in federal tax rate	0	57,950,000	$ 0
Federal
Operating Loss Carryforwards [Line Items]
Operating loss carryforwards	465,300,000
Operating loss carryforwards, subject to expiration	408,100,000
Operating loss carryforwards, not subject to expiration	57,200,000
Tax credit carryforward	18,400,000
State
Operating Loss Carryforwards [Line Items]
Operating loss carryforwards	353,800,000	319,900,000
Foreign
Operating Loss Carryforwards [Line Items]
Operating loss carryforwards	$ 400,000	$ 400,000

Income Taxes (Summary of Uncertain Tax Benefit) (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]
Beginning balance	$ 3,276	$ 2,400
Increase related to current year tax positions	450	403
Increase related to prior periods	0	473
Ending balance	$ 3,726	$ 3,276

Selected Quarterly Financial Data (Unaudited) (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2018	Sep. 30, 2018	Jun. 30, 2018	Mar. 31, 2018	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Selected Quarterly Financial Information [Abstract]
Revenue	$ 4,864	$ 369	$ 1,193	$ 790	$ 1,844	$ 897	$ 675	$ 1,078
Operating loss	(15,419)	(16,710)	(19,169)	(20,307)	(18,687)	(17,910)	(17,245)	(18,260)	$ (71,605)	$ (72,102)	$ (77,952)
Net loss	$ (14,956)	$ (16,079)	$ (18,613)	$ (19,826)	$ (19,238)	$ (17,312)	$ (16,680)	$ (17,754)	$ (69,474)	$ (70,984)	$ (76,390)
Net loss per share, basic and diluted (in USD per share)	$ (0.29)	$ (0.33)	$ (0.39)	$ (0.42)	$ (0.41)	$ (0.37)	$ (0.36)	$ (0.38)	$ (1.43)	$ (1.51)	$ (1.65)
Weighted-average shares outstanding, basic and diluted (in shares)	50,722,655	48,172,354	47,811,552	47,637,907	47,341,271	47,065,756	46,863,753	46,573,394	48,593,435	46,963,430	46,267,064