Regulus Therapeutics (RGLS) 10-K 8 Mar 18 2017 FY Annual report Financial data

Document and Entity Information

Document and Entity Information - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2017	Feb. 23, 2018	Jun. 30, 2017
Document And Entity Information [Abstract]
Document Type	10-K
Amendment Flag	false
Document Period End Date	Dec. 31, 2017
Document Fiscal Year Focus	2,017
Document Fiscal Period Focus	FY
Trading Symbol	RGLS
Entity Registrant Name	REGULUS THERAPEUTICS INC.
Entity Central Index Key	1,505,512
Current Fiscal Year End Date	--12-31
Entity Filer Category	Accelerated Filer
Entity Voluntary Filers	No
Entity Well-known Seasoned Issuer	No
Entity Current Reporting Status	Yes
Entity Public Float			$ 51.5
Entity Common Stock, Shares Outstanding		103,959,103

Balance Sheets

Balance Sheets - USD ($) $ in Thousands	Dec. 31, 2017	Dec. 31, 2016
Current assets:
Cash and cash equivalents	$ 13,519	$ 14,941
Short-term investments	46,555	61,170
Contract and other receivables	373	1,657
Prepaid materials, net	4,783	5,552
Prepaid expenses and other current assets	1,506	4,154
Total current assets	66,736	87,474
Property and equipment, net	9,708	11,830
Intangibles, net	775	1,015
Other assets	590	342
Total assets	77,809	100,661
Current liabilities:
Accounts payable	5,743	5,840
Accrued liabilities	4,941	5,577
Accrued compensation	1,985	2,318
Current portion of term loan, less debt issuance costs	19,859	0
Current portion of deferred revenue	72	72
Total current liabilities	32,600	13,807
Term loan, less current portion and debt issuance costs	0	19,802
Deferred revenue, less current portion	1,921	1,993
Deferred rent, less current portion	8,072	8,840
Other long-term liabilities	0	144
Total liabilities	42,593	44,586
Commitments and Contingencies (Note 8)
Stockholders’ equity:
Common stock, $0.001 par value; 200,000,000 shares authorized, 103,955,147 and 52,924,805 shares issued and outstanding at December 31, 2017 and 2016, respectively	104	53
Additional paid-in capital	381,104	329,496
Accumulated other comprehensive loss	(134)	(123)
Accumulated deficit	(345,858)	(273,351)
Total stockholders’ equity	35,216	56,075
Total liabilities and stockholders’ equity	$ 77,809	$ 100,661

Balance Sheets (Parenthetical)

Balance Sheets (Parenthetical) - $ / shares	Dec. 31, 2017	Dec. 31, 2016
Statement of Financial Position [Abstract]
Common stock, par value (in dollars per share)	$ 0.001	$ 0.001
Common stock, shares authorized	200,000,000	200,000,000
Common stock, shares issued	103,955,147	52,924,805
Common stock, shares outstanding	103,955,147	52,924,805

Statements of Operations and Co

Statements of Operations and Comprehensive Loss - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Revenues:
Total revenues	$ 72	$ 1,194	$ 20,759
Operating expenses:
Research and development	53,192	64,305	56,387
General and administrative	17,011	18,391	19,130
Total operating expenses	70,203	82,696	75,517
Loss from operations	(70,131)	(81,502)	(54,758)
Other income (expense):
Interest and other income	752	844	855
Interest and other expense	(2,723)	(1,182)	(52)
Loss from valuation of convertible note payable	0	0	(1,811)
Loss before income taxes	(72,102)	(81,840)	(55,766)
Income tax benefit	197	4	18
Net loss	(71,905)	(81,836)	(55,748)
Other comprehensive loss:
Unrealized (loss) gain on short-term investments, net	(11)	10	64
Comprehensive loss	$ (71,916)	$ (81,826)	$ (55,684)
Net loss per share - basic and diluted (in dollars per share)	$ (0.96)	$ (1.55)	$ (1.08)
Weighted average shares used to compute basic and diluted net loss per share (in shares)	75,230,762	52,813,474	51,411,353
Strategic Alliances and Collaborations
Revenues:
Total revenues	$ 72	$ 1,194	$ 20,759

Statements of Stockholders' Equ

Statements of Stockholders' Equity - USD ($) $ in Thousands	Total	Common stock	Additional paid-in capital	Accumulated other comprehensive income (loss)	Accumulated deficit
Beginning balance (in shares) at Dec. 31, 2014		48,944,530
Beginning balance at Dec. 31, 2014	$ 132,014	$ 49	$ 267,929	$ (197)	$ (135,767)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Issuance of common stock upon exercise of options (in shares)		2,298,618
Issuance of common stock upon exercise of options	6,680	$ 2	6,678
Stock-based compensation expense	15,368		15,368
Issuance of common stock under Employee Stock Purchase Plan (in shares)		69,380
Issuance of common stock under Employee Stock Purchase Plan	492		492
Conversion of convertible note payable into common stock (in shares)		1,356,738
Conversion of convertible note payable into common stock	25,208	$ 2	25,206
Unrealized gain (loss) on short-term investments	64			64
Net loss	(55,748)				(55,748)
Ending balance (in shares) at Dec. 31, 2015		52,669,266
Ending balance at Dec. 31, 2015	124,078	$ 53	315,673	(133)	(191,515)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Issuance of common stock upon exercise of options (in shares)		89,855
Issuance of common stock upon exercise of options	310		310
Stock-based compensation expense	12,872		12,872
Issuance of common stock under Employee Stock Purchase Plan (in shares)		165,684
Issuance of common stock under Employee Stock Purchase Plan	641		641
Unrealized gain (loss) on short-term investments	10			10
Net loss	(81,836)				(81,836)
Ending balance (in shares) at Dec. 31, 2016		52,924,805
Ending balance at Dec. 31, 2016	$ 56,075	$ 53	329,496	(123)	(273,351)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Issuance of common stock upon exercise of options (in shares)	11,000	11,000
Issuance of common stock upon exercise of options	$ 4	$ 0	4
Stock-based compensation expense	7,642		7,642
Issuance of common stock under Employee Stock Purchase Plan (in shares)		419,342
Issuance of common stock under Employee Stock Purchase Plan	419		419
Unrealized gain (loss) on short-term investments	(11)			(11)
Issuance of common stock, net of offering costs (in shares)		50,600,000
Issuance of common stock, net of offering costs	42,992	$ 51	42,941
Cumulative effect of accounting change	0		602		(602)
Net loss	(71,905)				(71,905)
Ending balance (in shares) at Dec. 31, 2017		103,955,147
Ending balance at Dec. 31, 2017	$ 35,216	$ 104	$ 381,104	$ (134)	$ (345,858)

Statements of Stockholders' Eq6

Statements of Stockholders' Equity (Parentheticals) $ in Thousands	12 Months Ended
	Dec. 31, 2017USD ($)
Statement of Stockholders' Equity [Abstract]
Issuance of common stock, offering costs	$ 292

Statements of Cash Flows

Statements of Cash Flows - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Operating activities
Net loss	$ (71,905)	$ (81,836)	$ (55,748)
Adjustments to reconcile net loss to net cash used in operating activities
Depreciation and amortization expense	2,524	2,276	1,591
Loss from valuation of convertible note payable	0	0	1,811
Stock-based compensation	7,642	12,872	15,368
Amortization of premium on investments, net	349	666	1,472
Other	600	1,043	98
Change in operating assets and liabilities:
Contracts and other receivables	1,284	8,364	(9,746)
Prepaid materials	394	(616)	(3,460)
Prepaid expenses and other assets	2,369	(778)	(683)
Accounts payable	(65)	3,123	529
Accrued liabilities	(492)	(871)	2,094
Accrued compensation	(333)	(74)	284
Deferred revenue	(72)	(1,194)	(3,090)
Deferred rent and other liabilities	(1,068)	143	(379)
Net cash used in operating activities	(58,773)	(56,882)	(49,859)
Investing activities
Purchases of short-term investments	(55,686)	(65,110)	(78,401)
Sales and maturities of short-term investments	69,941	101,387	101,306
Purchases of property and equipment	(303)	(913)	(1,363)
Acquisition of intangibles	(16)	(53)	(67)
Net cash provided by investing activities	13,936	35,311	21,475
Financing activities
Proceeds from issuance of common stock, net	43,411	641	492
Proceeds from borrowing under term loan, net	0	19,768	0
Proceeds from exercise of common stock options	4	310	6,680
Principal payments on other long-term obligations	0	(167)	(155)
Net cash provided by financing activities	43,415	20,552	7,017
Net decrease in cash and cash equivalents	(1,422)	(1,019)	(21,367)
Cash and cash equivalents at beginning of period	14,941	15,960	37,327
Cash and cash equivalents at end of period	13,519	14,941	15,960
Supplemental disclosure of cash flow information
Net changes in restricted cash	0	(1,256)	1,256
Interest paid	(1,944)	(981)	(27)
Income taxes paid	(1)	(1)	(1)
Supplemental disclosure of non-cash investing and financing activities
Allowance for tenant improvements	0	6,653	1,656
Amounts accrued for property and equipment	11	292	223
Amounts accrued for patent expenditures	$ 0	$ 0	$ 28

The Business, Basis of Presenta

The Business, Basis of Presentation and Summary of Significant Accounting Policies	12 Months Ended
	Dec. 31, 2017
Accounting Policies [Abstract]
The Business, Basis of Presentation and Summary of Significant Accounting Policies	The Business, Basis of Presentation and Summary of Significant Accounting Policies We are a biopharmaceutical company focused on discovering and developing first-in-class drugs that target microRNAs to treat a broad range of diseases. We were formed in 2007 when Alnylam and Ionis contributed significant intellectual property, know-how and financial and human capital to pursue the development of drugs targeting micro RNAs pursuant to a license and collaboration agreement. Regulus Therapeutics Inc. was converted to a Delaware corporation on January 2, 2009. As used in this report, unless the context suggests otherwise, “the Company,” “our,” “us” and “we” means Regulus Therapeutics Inc. Liquidity The accompanying financial statements have been prepared on a basis which assumes we are a going concern, and does not include any adjustments to reflect the possible future effects on the recoverability and classification of assets or the amounts and classifications of liabilities that may result from any uncertainty related to our ability to continue as a going concern. Through the date of the issuance of these financial statements, we have principally been financed through proceeds received from the sale of our common stock and other equity securities, debt financings, up-front payments and milestones received from collaboration agreements, totaling $406.0 million . As of December 31, 2017, we had approximately $60.1 million of cash, cash equivalents and short-term investments. Based on our operating plans, we believe our cash, cash equivalents and short-term investments may not be sufficient to fund our operations to one year following the issuance of these financial statements. As a result, there is substantial doubt about the Company's ability to continue as a going concern. The principal payments due under the Term Loan have been classified as a current liability as of December 31, 2017 due to the considerations discussed above and the assessment that the material adverse change clause under the Term Loan is not within the Company's control. The Company has not been notified of an event of default by the Lender as of the date of the filing of this Form 10-K. We intend to seek additional capital through equity and/or debt financings, collaborative or other funding arrangements with partners or through other sources of financing. Should we seek additional financing from outside sources, we may not be able to raise such financing on terms acceptable to us or at all. If we are unable to raise additional capital when required or on acceptable terms, we may be required to scale back or discontinue the advancement of product candidates, reduce headcount, file for bankruptcy, reorganize, merge with another entity, or cease operations. If the Company becomes unable to continue as a going concern, we may have to liquidate its assets, and might realize significantly less than the values at which they are carried on our financial statements, and stockholders may lose all or part of their investment in our common stock. Use of Estimates Our financial statements are prepared in accordance with U.S. generally accepted accounting principles ("GAAP"), which requires us to make estimates and assumptions that affect the reported amounts of assets, liabilities, revenues and expenses and the disclosure of contingent assets and liabilities in our financial statements and accompanying notes. An estimated loss contingency is accrued in our financial statements if it is probable that a liability has been incurred and the amount of the loss can be reasonably estimated. Although these estimates are based on our knowledge of current events and actions we may undertake in the future, actual results may ultimately differ from these estimates and assumptions. Revenue Recognition Our revenues generally consist of upfront payments for licenses or options to obtain licenses in the future, milestone payments and payments for other research services under strategic alliance and collaboration agreements. We recognize revenues when all four of the following criteria are met: (1) persuasive evidence of an arrangement exists; (2) delivery of the products and/or services has occurred; (3) the selling price is fixed or determinable; and (4) collectability is reasonably assured. Multiple element arrangements, such as our strategic alliance agreement with Sanofi are analyzed to determine whether the deliverables within the agreement can be separated or whether they must be accounted for as a single unit of accounting. Deliverables under the agreement will be accounted for as separate units of accounting provided that (i) a delivered item has value to the customer on a stand-alone basis; and (ii) if the agreement includes a general right of return relative to the delivered item, delivery or performance of the undelivered item is considered probable and substantially in the control of the vendor. The allocation of consideration amongst the deliverables under the agreement is derived using a “best estimate of selling price” if vendor specific objective evidence and third-party evidence of fair value is not available. If the delivered element does not have stand-alone value, the arrangement is then accounted for as a single unit of accounting, and we recognize the consideration received under the arrangement as revenue on a straight-line basis, which approximates effort over our estimated period of performance, which for us is typically the expected term of the research and development plan. Milestones We apply the milestone method of accounting to recognize revenue from milestone payments when earned, as evidenced by written acknowledgment from the collaborator or other persuasive evidence that the milestone has been achieved and the payment is non-refundable, provided that the milestone event is substantive. A milestone event is defined as an event (i) that can only be achieved based in whole or in part on either our performance or on the occurrence of a specific outcome resulting from our performance; (ii) for which there is substantive uncertainty at the inception of the arrangement that the event will be achieved; and (iii) that would result in additional payments being due to us. Events for which the occurrence is either contingent solely upon the passage of time or the result of a counterparty’s performance are not considered to be milestone events. A milestone event is substantive if all of the following conditions are met: (i) the consideration is commensurate with either our performance to achieve the milestone, or the enhancement of the value to the delivered item(s) as a result of a specific outcome resulting from our performance to achieve the milestone; (ii) the consideration relates solely to past performance; and (iii) the consideration is reasonable relative to all the deliverables and payment terms (including other potential milestone consideration) within the arrangement. We assess whether a milestone is substantive at the inception of each arrangement. If a milestone is deemed non-substantive, we will account for that milestone payment using a method consistent with the related units of accounting for the arrangement over the estimated performance period. Deferred Revenue Amounts received prior to satisfying the above revenue recognition criteria are recorded as deferred revenue in the accompanying balance sheets. Amounts not expected to be recognized within the next 12 months are classified as non-current deferred revenue. Stock-Based Compensation We account for stock-based compensation expense related to stock options granted to employees and members of our board of directors by estimating the fair value of each stock option on the date of grant using the Black-Scholes option pricing model. We recognize stock-based compensation expense using the accelerated multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award was in substance multiple awards, resulting in accelerated expense recognition over the vesting period. For performance-based awards granted to employees (i) the fair value of the award is determined on the grant date, (ii) we assess the probability of the individual milestones under the award being achieved and (iii) the fair value of the shares subject to the milestone is expensed over the implicit service period commencing once management believes the performance criteria is probable of being met. We account for restricted stock units by determining the fair value of each restricted stock unit based on the closing market price of our common stock on the date of grant. We recognize stock-based compensation expense using the accelerated multiple-option approach over the requisite service periods of the awards. Prepaid Materials We capitalize the purchase of certain raw materials and related supplies for use in the manufacturing of drug product in our clinical development programs, as we have determined that these materials have alternative future use. We can use these raw materials and related supplies in multiple clinical drug products, and therefore have future use independent of the development status of any particular drug program until it is utilized in the manufacturing process. We expense the cost of materials when used. We periodically review these capitalized materials for continued alternative future use and write down the asset to its net realizable value in the period in which it is identified. As of December 31, 2017 and 2016 , our net prepaid materials balance was $4.8 million and $5.6 million , respectively. Research and Development Research and development costs are expensed as incurred and consist of costs associated with research activities supporting our drug discovery efforts, compensation and related benefits, non-cash stock-based compensation, license fees, laboratory supplies and associated overhead and facility costs. Income Taxes Income taxes are accounted for under the asset and liability method. This approach requires the recognition of deferred tax assets and liabilities for the expected future tax consequences of the differences between the tax basis of assets or liabilities and their carrying amounts in the financial statements using the enacted tax rates and laws that are anticipated to be in effect when the differences are expected to reverse. We provide a valuation allowance against net deferred tax assets if it is more likely than not that these items will either expire before we are able to realize their benefit or if future deductibility is uncertain. In accordance with the accounting standards for uncertain tax positions, we evaluate the recognition threshold and measurement attribute criteria for the financial statement recognition and measurement of tax positions taken or expected to be taken in a tax return. For those benefits to be recognized, a tax position must be more likely than not to be sustained upon examination by taxing authorities. Fair Value Option Applicable accounting policies permit entities to choose, at specified election dates, to measure specified items at fair value if the decision about the election is: (1) applied instrument by instrument, (2) irrevocable, and (3) applied to an entire instrument. The balance of our convertible note payable, which was valued under the fair value option, was converted into shares of common stock in January 2015 (see Note 9). Clinical Trial and Preclinical Study Accruals We make estimates of our accrued expenses for clinical trial and preclinical study activities as of each balance sheet date in our financial statements based on the facts and circumstances known to us at that time. These accruals are based upon estimates of costs incurred and fees that may be associated with services provided by clinical trial investigational sites, CROs and for other clinical trial-related activities. Payments under certain contracts with such parties depend on factors such as successful enrollment of patients, site initiation and the completion of clinical trial milestones. In accruing for these services, we estimate the time period over which services will be performed and the level of effort to be expended in each period. If possible, we obtain information regarding unbilled services directly from these service providers. However, we may be required to estimate these services based on other information available to us. If we underestimate or overestimate the activities or fees associated with a study or service at a given point in time, adjustments to research and development expenses may be necessary in future periods. Historically, our estimated accrued liabilities have approximated actual expense incurred. Subsequent changes in estimates may result in a material change in our accruals. Cash and Cash Equivalents We classify time deposits and other investments that are highly liquid and have maturities of 90 days or less at the date of purchase as cash equivalents. The carrying amounts approximate fair value due to the short maturities of these instruments. Short-Term Investments We carry short-term investments classified as available-for-sale at fair value as determined by prices for identical or similar securities at the balance sheet date. Our short-term investments consist of both Level 1 and Level 2 financial instruments in the fair value hierarchy. We record unrealized gains and losses as a component of other comprehensive loss within the statements of operations and comprehensive loss and as a separate component of stockholders’ equity. We determine the realized gains or losses of available-for-sale securities using the specific identification method and include net realized gains and losses in interest income. At each balance sheet date, we assess available-for-sale securities in an unrealized loss position to determine whether the unrealized loss is other-than-temporary. We consider factors including: the significance of the decline in value compared to the cost basis, underlying factors contributing to a decline in the prices of securities in a single asset class, the length of time the market value of the security has been less than its cost basis, the security’s relative performance versus its peers, sector or asset class, expected market volatility and the market and economy in general. When we determine that a decline in the fair value below its cost basis is other-than-temporary, we recognize an impairment loss in the year in which the other-than-temporary decline occurred. We determined that there were no other-than-temporary declines in the value of short-term investments as of December 31, 2017 or 2016 . Concentrations of Credit Risk Financial instruments that potentially subject us to significant concentrations of credit risk consist primarily of cash equivalents and short-term investments. We maintain deposits in federally insured financial institutions in excess of federally insured limits. We have not experienced any material losses in such accounts and believe we are not exposed to significant risk. We maintain our cash equivalents and short-term investments with two highly accredited financial institutions. We invest our excess cash primarily in commercial paper, certificates of deposit and debt instruments of financial institutions and corporations, United States Treasury securities and United States government-sponsored enterprise securities. Additionally, we adhere to established guidelines regarding approved investments and maturities of investments, which are designed to preserve their principal value and maintain liquidity. Property and Equipment We carry our property and equipment at cost, which consists of lab equipment, computer equipment and software, furniture and fixtures and leasehold improvements. Property and equipment is depreciated using the straight-line method over the estimated useful lives (generally three to five years). Leasehold improvements are amortized over the lesser of their useful life or the remaining lease term, including any renewal periods that are deemed to be reasonably assured. Repair and maintenance costs that do not improve service potential or extend economic life are expensed as incurred. Intangibles We capitalize costs which consist principally of outside legal costs and filing fees related to obtaining patents. We review our capitalized patent costs periodically to determine that they include costs for patent applications that have future value and an alternative future use. We evaluate costs related to patents that we are not actively pursuing and write off these costs. We amortize patent costs over their patent lives, beginning with the date the patents are issued. The weighted average remaining life of the issued patents was approximately 9 years at December 31, 2017 . We obtain licenses from third parties and capitalize the costs related to exclusive licenses that have alternative future use within multiple potential programs. We amortize capitalized licenses over their estimated useful life or term of the agreement, which for current licenses is 10 years. Impairment of Long-Lived Assets We regularly review the carrying amount of our property, equipment and intangible assets to determine whether indicators of impairment may exist which warrant adjustments to carrying values or estimated useful lives. If indications of impairment exist, projected future undiscounted cash flows associated with the asset are compared to the carrying amount to determine whether the asset’s value is recoverable. If the carrying value of the asset exceeds such projected undiscounted cash flows, the asset will be written down to its estimated fair value. No impairment charges were recorded during the years ended December 31, 2017 , 2016 or 2015 . Segment Reporting Operating segments are identified as components of an enterprise about which separate discrete financial information is available for evaluation by the chief operating decision-maker in making decisions regarding resource allocation and assessing performance. To date, we have viewed our operations and managed our business as one segment operating primarily within the United States. Comprehensive Loss Comprehensive loss is defined as the change in equity during a period from transactions and other events and/or circumstances from non-owner sources. Our only component of other comprehensive loss is unrealized gains (losses) on available-for-sale securities. Comprehensive gains (losses) have been reflected in the statements of operations and comprehensive loss and as a separate component in the statements of stockholders’ equity for all periods presented. Corporate Restructuring In May 2017, we implemented a corporate restructuring to streamline our operations, reduce our operating expenses, extend our cash runway and focus our resources on our most promising programs. In connection with the restructuring, we reduced our total workforce by approximately 30% percent. We completed the workforce reduction in June 2017. We recorded charges of approximately $3.2 million for employee severance and other related termination benefits in the second quarter of 2017, including $1.3 million in net charges related to adjustments to non-cash stock-based compensation. All payments associated with the corporate restructuring were paid in full as of June 30, 2017. Recent Accounting Pronouncements In May 2014, the FASB issued ASU, No. 2014-09, Revenue from Contracts with Customers (Topic 606) , which outlines a single comprehensive model for entities to use in accounting for revenue arising from contracts with customers and supersedes most current revenue recognition guidance, including industry-specific guidance. ASU 2014-09 outlines a five-step process for revenue recognition that focuses on transfer of control, as opposed to transfer of risk and rewards, and also requires enhanced disclosures regarding the nature, amount, timing and uncertainty of revenues and cash flows from contracts with customers. Major provisions include determining which goods and services are distinct and require separate accounting (performance obligations), how variable consideration (which may include change orders and claims) is recognized, whether revenue should be recognized at a point in time or over time and ensuring the time value of money is considered in the transaction price. The FASB subsequently issued amendments to ASU No. 2014-09 that have the same effective date and transition date. These new standards became effective for us on January 1, 2018 and will be adopted using the modified retrospective method through a cumulative-effect adjustment directly to accumulated deficit as of that date. The Company has performed a review of these new standards as compared to our current accounting policies for customer contracts. As of December 31, 2017, we have not identified any accounting changes that would materially impact the amount of historically reported revenues with respect to our grant revenue. The Company is currently evaluating the impact of the new standard on historical revenue recorded for our ongoing collaboration agreement with Sanofi. This ongoing evaluation is dependent upon the resolution of certain questions relating to the application of the new revenue recognition guidance for collaboration agreements which will ultimately determine the impact, if any, the adoption of this standard may have on our financial statements. Our ongoing evaluation will be complete in the first quarter 2018. The company expects the accounting for contingent milestone payments to be the most significant change in accounting for its license and collaboration agreements. Topic 605 provides guidance specific to the accounting for milestone payments, including the ability to defer the recognition of any milestones until received and, if certain criteria are met, the ability to recognize milestone payments as revenue when received. However, Topic 606 does not contain guidance specific to milestone payments, thereby requiring potential milestone payments to be considered in accordance with the overall model of Topic 606. As a result, revenues from contingent milestone payments may be recognized earlier under Topic 606 than under Topic 605, based on an assessment of the probability of achievement of the milestone and the likelihood of a significant reversal of such milestone revenue at each reporting date. This assessment may result in recognizing milestone revenue before the milestone event has been achieved. In addition, Topic 606 changes guidance regarding the accounting for variable consideration received from licensees, which may impact the estimation of, and determination of the timing of, the related revenue recognition. In January 2016, the FASB issued ASU No. 2016-01, Recognition and Measurement of Financial Assets and Financial Liabilities , which eliminates the requirement for public companies to disclose the method(s) and significant assumptions used to estimate the fair value for financial instruments measured at amortized cost on the balance sheet. Additionally, the standard requires public companies to use the exit price notion when measuring the fair value of financial instruments for disclosure purposes. Furthermore, the standard requires presentation of financial assets and liabilities by measurement category and form of financial asset on the balance sheet or accompanying notes to the financial statements. The standard is effective for annual reporting periods beginning after December 15, 2017, including interim periods within those annual reporting periods. Early application is permitted. The adoption of this guidance will have no impact on our financial statements. In February 2016, the FASB issued ASU No. 2016-02, Leases, which increases transparency and comparability among organizations by requiring recognition of lease assets and lease liabilities on the balance sheet and disclosure of key information about leasing arrangements. The standard is effective for annual reporting periods beginning after December 15, 2018, including interim periods within those annual reporting periods. Early application is permitted. We are currently evaluating the impact of adoption on our financial statements. In March 2016, the FASB issued ASU No. 2016-09, Compensation – Stock Compensation: Improvements to Employee Share-Based Payment Accounting, which is intended to simplify various aspects of accounting for share-based payment transactions. The new guidance requires immediate recognition of all excess tax benefits and deficiencies in the income statement, requires classification of excess tax benefits as an operating activity as opposed to a financing activity in the statements of cash flows and allows a company to make an accounting policy election to either estimate the number of awards or account for forfeitures when they occur. The standard is effective for annual reporting periods beginning after December 15, 2016, and interim periods within those annual reporting periods. We applied this standard in the first quarter of 2017 using the modified retrospective method of adoption. In conjunction with this adoption, we made an accounting policy election to account for forfeitures as they occur. Upon adoption, we reversed a deferred tax asset related to the balance of unrecognized excess tax benefits of $7.7 million , with an offsetting adjustment to the valuation allowance. Under the modified retrospective method of adoption, we recorded an adjustment of $0.6 million to accumulated deficit with a corresponding offset to additional paid-in capital. In August 2016, the FASB issued ASU No. 2016-15, Statement of Cash Flows: Classification of Certain Cash Receipts and Cash Payments , which addresses the presentation and classification of certain cash receipts and cash payments in the statement of cash flows under Accounting Standards Codification 230. The standard is effective for annual reporting periods beginning after December 15, 2017, and interim periods within those annual reporting periods. The adoption of this guidance will have no impact on our financial statements. In November 2016, the FASB issued ASU No. 2016-18, Statement of Cash Flows: Restricted Cash , which requires restricted cash and restricted cash equivalents to be included with cash and cash equivalents when reconciling the beginning-of-period and end-of-period total amounts shown on the statement of cash flows. The standard is effective for annual reporting periods beginning after December 15, 2017, and interim periods within those annual reporting periods. Early application is permitted. Upon its adoption in 2018, we will include $1.3 million of restricted cash in our disclosed balance of cash and cash equivalents at the beginning of the period for 2016. We do not expect any additional impact on our financial statements. In May 2017, the FASB issued ASU No. 2017-09, Compensation - Stock Compensation (Topic 718): Scope of Modification Accounting , which provides clarity and guidance around which changes to the terms or conditions of a share-based payment award require an entity to apply modification accounting in Topic 718. The standard is effective for annual reporting periods beginning after December 15, 2017, and interim periods within those annual reporting periods. The adoption of this guidance will have no impact on our financial statements unless we have modification accounting in accordance with Topic 718.

Net Loss Per Share

Net Loss Per Share	12 Months Ended
	Dec. 31, 2017
Earnings Per Share [Abstract]
Net Loss Per Share	Net Loss Per Share Basic net loss per share is calculated by dividing net loss by the weighted average number of common shares outstanding for the period, without consideration for common stock equivalents. Diluted net loss per share is calculated by dividing net loss by the weighted-average number of common share equivalents outstanding for the period determined using the treasury-stock method. Dilutive common stock equivalents are comprised of options outstanding under our stock option plans. For all periods presented, there is no difference in the number of shares used to calculate basic and diluted net loss per share. Potentially dilutive securities not included in the calculation of diluted net loss per share because to do so would be anti-dilutive consisted of 2,968,879 shares attributable to common stock options and restricted stock units for the year ended December 31, 2017 and 5,553,210 and 1,674,119 shares attributable to common stock options for the years ended December 31, 2016 and 2015 , respectively.

Investments

Investments	12 Months Ended
	Dec. 31, 2017
Investments, Debt and Equity Securities [Abstract]
Investments	Investments We invest our excess cash primarily in commercial paper and debt instruments of financial institutions, corporations, U.S. government-sponsored agencies and the U.S. treasury. As of December 31, 2017 , our short-term investments had a weighted average maturity of less than one year. We generally hold our investments to maturity and do not sell our investments before we have recovered our amortized cost basis. The following tables summarize our short-term investments (in thousands): Maturity (in years) Amortized cost Unrealized Estimated fair value Gains Losses As of December 31, 2017 Corporate debt securities 1 or less $ 32,922 $ — $ (55 ) $ 32,867 Certificates of deposit 1 or less 8,216 — — 8,216 U.S. treasury securities 1 or less 3,996 — (18 ) 3,978 Debt securities of U.S. government-sponsored agencies 1 or less 1,498 — (4 ) 1,494 Total $ 46,632 $ — $ (77 ) $ 46,555 Maturity (in years) Amortized cost Unrealized Estimated fair value Gains Losses As of December 31, 2016 Corporate debt securities 2 or less $ 49,185 $ 12 $ (77 ) $ 49,120 Certificates of deposit 1 or less 9,291 — — 9,291 U.S. treasury securities 1 or less $ 1,001 $ — $ (1 ) $ 1,000 U.S. government-sponsored enterprise securities 1 or less $ 512 $ — $ — $ 512 Commercial paper 1 or less $ 1,247 $ — $ — $ 1,247 Total $ 61,236 $ 12 $ (78 ) $ 61,170

Fair Value Measurements

Fair Value Measurements	12 Months Ended
	Dec. 31, 2017
Fair Value Disclosures [Abstract]
Fair Value Measurements	Fair Value Measurements We have certain financial assets recorded at fair value which have been classified as Level 1, 2, or 3 within the fair value hierarchy as described in the accounting standards for fair value measurements. Accounting standards define fair value as the exchange price that would be received for an asset or paid to transfer a liability (an exit price) in the principal or most advantageous market for the asset or liability in an orderly transaction between market participants as of the measurement date. Market participants are buyers and sellers in the principal market that are (i) independent, (ii) knowledgeable, (iii) able to transact, and (iv) willing to transact. The accounting standards provide an established hierarchy for inputs used in measuring fair value that maximizes the use of observable inputs and minimizes the use of unobservable inputs by requiring that the most observable inputs be used when available. Observable inputs are inputs that market participants would use in valuing the asset or liability and are developed based on market data obtained from independent sources. Unobservable inputs are inputs that reflect our assumptions about the factors that market participants would use in valuing the asset or liability. The accounting standards prioritize the inputs used in measuring the fair value into the following hierarchy: • Level 1 includes financial instruments for which quoted market prices for identical instruments are available in active markets. • Level 2 includes financial instruments for which there are inputs other than quoted prices included within Level 1 that are observable for the instrument such as quoted prices for similar instruments in active markets, quoted prices for identical or similar instruments in markets with insufficient volume or infrequent transactions (less active markets) or model-driven valuations in which significant inputs are observable or can be derived principally from, or corroborated by, observable market data. • Level 3 includes financial instruments for which fair value is derived from valuation techniques in which one or more significant inputs are unobservable, including management’s own assumptions. The following table presents our fair value hierarchy for assets measured at fair value on a recurring basis as of December 31, 2017 and December 31, 2016 (in thousands): Fair value as of December 31, 2017 Total Level 1 Level 2 Level 3 Assets: Cash equivalents $ 10,847 $ 10,847 $ — $ — Corporate debt securities 32,867 — 32,867 — Certificates of deposit 8,216 — 8,216 — U.S. treasury securities 3,978 — 3,978 — Debt securities of U.S. government-sponsored agencies 1,494 — 1,494 — $ 57,402 $ 10,847 $ 46,555 $ — Fair value as of December 31, 2016 Total Level 1 Level 2 Level 3 Assets: Cash equivalents $ 13,578 $ 13,578 $ — $ — Corporate debt securities 49,120 — 49,120 — Certificates of deposit 9,291 — 9,291 — U.S. treasury securities 1,000 — 1,000 — Debt securities of U.S. government-sponsored agencies 512 — 512 — Commercial paper 1,247 — 1,247 — $ 74,748 $ 13,578 $ 61,170 $ — We obtain pricing information from quoted market prices or quotes from brokers/dealers. We generally determine the fair value of our investment securities using standard observable inputs, including reported trades, broker/dealer quotes, bids and/or offers. Refer to Note 3 for information regarding our investments.

Strategic Alliances and Collabo

Strategic Alliances and Collaborations	12 Months Ended
	Dec. 31, 2017
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Strategic Alliances and Collaborations	Strategic Alliances and Collaborations The following table summarizes our total revenues from our strategic alliances and collaborations during the periods presented (in thousands): Year ended December 31, 2017 2016 2015 Sanofi $ 72 $ 72 $ 71 AstraZeneca — 1,122 18,871 Biogen — — 1,817 Total $ 72 $ 1,194 $ 20,759 Sanofi In July 2012, we amended and restated our collaboration and license agreement with Sanofi to expand the potential therapeutic applications of the micro RNA alliance targets to be developed under such agreement. We determined that the elements within the strategic alliance agreement with Sanofi should be treated as a single unit of accounting because the delivered elements did not have stand-alone value to Sanofi. The following elements were delivered as part of the strategic alliance with Sanofi: (1) a license for up to four micro RNA targets; and (2) a research license under our technology alliance. In June 2013, the original research term expired, upon which we and Sanofi entered into an option agreement pursuant to which Sanofi was granted an exclusive right to negotiate the co-development and commercialization of certain of our unencumbered micro RNA programs and we were granted the exclusive right to negotiate with Sanofi for co-development and commercialization of certain miR-21 anti-miRs in oncology and Alport syndrome. In July 2013, we received an upfront payment of $2.5 million , of which $1.25 million is creditable against future amounts payable by Sanofi to us under any future co-development and commercialization agreement we enter pursuant to the option agreement. Revenue associated with the creditable portion of this option payment remained deferred as of December 31, 2017 . The non-creditable portion of this payment, $1.25 million , was recognized as revenue over the option period from the effective date of the option agreement in June 2013 through the expiration of the option period in January 2014. In February 2014, we and Sanofi entered into a second amended and restated collaboration and license agreement (the “2014 Sanofi Amendment”) to renew our strategic alliance to discover, develop and commercialize micro RNA therapeutics to focus on specific orphan disease and oncology targets. Under the terms of our renewed alliance, Sanofi has opt-in rights to our clinical fibrosis program targeting miR-21 for the treatment of Alport syndrome, our preclinical program targeting miR-21 for oncology indications, and our preclinical program targeting miR-221/222 for HCC. We are responsible for developing each of these programs to proof-of-concept, at which time Sanofi has an exclusive option on each program. If Sanofi chooses to exercise its option on any of these programs, Sanofi will reimburse us for a significant portion of our preclinical and clinical development costs and will also pay us an option exercise fee for any such program, provided that $1.25 million of the $2.5 million upfront option fee paid to us by Sanofi in connection with the June 2013 option agreement will be creditable against such option exercise fee. We are eligible to receive royalties on micro RNA therapeutic products commercialized by Sanofi and will have the right to co-promote these products. In connection with the 2014 Sanofi Amendment, we entered into a Common Stock Purchase Agreement (the “Purchase Agreement”), pursuant to which we sold 1,303,780 shares of our common stock to Aventisub LLC (“Aventis”), an entity affiliated with Sanofi, in a private placement at a price per share of $7.67 for an aggregate purchase price of $10.0 million . Under the terms of the Purchase Agreement, Aventis was not permitted to sell, transfer, make any short sale of, or grant any option for the sale of any common stock for the 12 -month period following its effective date. The Purchase Agreement and the 2014 Sanofi Amendment were negotiated concurrently and were therefore evaluated as a single agreement. Based upon restricted stock studies of similar duration and a Black-Scholes valuation to measure the discount for lack of marketability, approximately $0.4 million of the proceeds from the Purchase Agreement was attributed to the 2014 Sanofi Amendment, and represents consideration for the value of the program targeting miR-221/222 for HCC. As this element does not have stand-alone value, we are recognizing the $0.4 million allocated consideration into revenue ratably over the estimated period of performance of the miR-221/222 program. As of December 31, 2017 , deferred revenue associated with the Purchase Agreement and the 2014 Sanofi Amendment was $0.1 million , which we are expecting to recognize over the remaining estimated period of performance of approximately two years. We are eligible to receive milestone payments of up to $101.8 million for proof-of-concept option exercise fees (net of $1.25 million creditable, as noted above), $15.0 million for clinical milestones and up to $300.0 million for regulatory and commercial milestones. In addition, we are entitled to receive royalties based on a percentage of net sales of any products from the miR-21 and miR-221/222 programs which, in the case of sales in the United States, will be in the middle of the 10 to 20% range, and, in the case of sales outside of the United States, will range from the low end to the middle of the 10 to 20% range, depending upon the volume of sales. If we exercise our option to co-promote a product, we will continue to be eligible to receive royalties on net sales of each product in the United States at the same rate, unless we elect to share a portion of Sanofi’s profits from sales of such product in the United States in lieu of royalties. We have evaluated the contingent event-based payments under the 2014 Sanofi Amendment and determined that the milestone payments meet the definition of substantive milestones. Accordingly, revenue for these achievements will be recognized in their entirety in the period when the milestone is achieved and collectability is reasonably assured. Other contingent event-based payments under the 2014 Sanofi Amendment for which payment is contingent upon the results of Sanofi’s performance will not be accounted for using the milestone method. Such payments will be recognized as revenue over the remaining estimated period of performance, if any, and when collectability is reasonably assured. AstraZeneca In August 2012, we entered into a collaboration and license agreement with AstraZeneca. Under the terms of the agreement, we agreed to collaborate with AstraZeneca to identify, research and develop compounds targeting three micro RNA alliance targets primarily in the fields of cardiovascular diseases, metabolic diseases and oncology. Pursuant to the agreement, we granted AstraZeneca an exclusive, worldwide license to develop, manufacture and commercialize lead compounds designated by AstraZeneca in the course of the collaboration activities against the alliance targets for all human therapeutic uses. Under the terms of the agreement we were required to use commercially reasonable efforts to perform all research, development and manufacturing activities described in the research plan, at our cost, until the acceptance of an investigational new drug application ("IND") or the end of the research term, which expired in August 2016. Under the terms of the agreement, we received an upfront payment of $3.0 million in October 2012, which was recognized as revenue over the period of performance of four years , which expired in August 2016. In connection with the collaboration and license agreement and concurrently with our initial public offering, we sold AstraZeneca 6,250,000 shares of our common stock in a private placement at a price per share of $4.00 . Under the terms of the Common Stock Purchase Agreement ("CSPA"), AstraZeneca could not sell, transfer, make any short sale of, or grant any option for the sale of any common stock for a 365 -day period following the effective date of our initial public offering. The CSPA and collaboration and license agreement were negotiated concurrently and were therefore evaluated as a single agreement. Based upon restricted stock studies of similar duration and a Black-Scholes valuation to measure a discount for lack of marketability, $4.3 million was attributed to the collaboration and license agreement. We recognized the $4.3 million into revenue ratably over the period of performance of the research and development plan under the collaboration, which expired in August 2016. In March 2015, we earned a $2.5 million preclinical milestone and in December 2015, we earned a $10.0 million clinical milestone. We determined the milestones to be substantive and recognized revenue upon achievement of each milestone. In June 2017, AstraZeneca delivered written notice of their election to terminate the collaboration and license agreement. Effective upon the termination of the agreement, AstraZeneca’s rights with respect to RG-125(AZD4076) will revert back to us. In accordance with the Agreement, the termination will become effective in June 2018, 12 months following the date of delivery of the notice by AstraZeneca. Biogen In August 2014, we entered into a collaboration and license agreement with Biogen to collaborate on micro RNA biomarkers for multiple sclerosis. Pursuant to the terms of the collaboration and license agreement, we received an upfront payment of $2.0 million , which was recognized on a straight-line basis over the estimated period of performance, ending September 2015. The research term was subsequently extended through November 2015. In January 2015, May 2015, and September 2015, we earned research milestone payments under the collaboration and license agreement of $0.1 million , $0.3 million and $0.3 million , respectively, which were recognized in the period the milestones were achieved and collectability was reasonably assured.

Property and Equipment, net

Property and Equipment, net	12 Months Ended
	Dec. 31, 2017
Property, Plant and Equipment [Abstract]
Property and Equipment, net	Property and Equipment, net The following table summarizes our major classes of property and equipment (in thousands): December 31, 2017 2016 Laboratory equipment $ 8,430 $ 7,932 Computer equipment and software 281 265 Furniture and fixtures 706 706 Leasehold improvements 8,550 10,469 Construction in progress — 261 17,967 19,633 Less accumulated depreciation and amortization (8,259 ) (7,803 ) Property and equipment, net $ 9,708 $ 11,830 Depreciation and amortization of property and equipment of $2.4 million , $2.2 million and $1.5 million was recorded for the years ended December 31, 2017 , 2016 and 2015 , respectively.

Intangible Assets, net

Intangible Assets, net	12 Months Ended
	Dec. 31, 2017
Goodwill and Intangible Assets Disclosure [Abstract]
Intangible Assets, net	Intangible Assets, net The following table summarizes our major classes of intangible assets (in thousands): December 31, 2017 2016 Patents $ 871 $ 1,102 Licenses 379 379 1,250 1,481 Accumulated amortization (475 ) (466 ) Intangibles, net $ 775 $ 1,015 Intangible asset amortization of $0.1 million was recorded for each of the years ended December 31, 2017 , 2016 and 2015 , respectively. Amortization of these intangible assets over the next five years is expected to be approximately $0.1 million per year.

Commitments and Contingencies

Commitments and Contingencies	12 Months Ended
	Dec. 31, 2017
Commitments and Contingencies Disclosure [Abstract]
Commitments and Contingencies	Commitments and Contingencies Operating Lease In July 2015, we entered into an operating lease agreement (the "Lease") for an office and laboratory facility in San Diego, California, for a term of 96 months from the lease commencement date, and moved our headquarters into this facility in May 2016. In conjunction with the Lease, we received $1.4 million in August 2015 for assistance with costs associated with the relocation of our corporate headquarters. These funds were received for a specific and limited purpose, and therefore were classified as restricted cash and tenant incentive obligation on our balance sheet. The restricted cash balance was zero as of December 31, 2017 and 2016. In addition, the Lease provided a tenant improvement allowance of up to $8.5 million , which was to be used for non-structural leasehold improvements. The improvements were complete in the second half of 2016, with approximately $8.2 million of the allowance having been used. The $0.3 million unused tenant improvement allowance was applied as a credit against future rent payments. The $1.4 million tenant incentive and $8.2 million tenant improvement allowance were classified as deferred rent on our balance sheet and are being amortized against rent expense on a straight-line basis over the term of the lease. Rent expense for the years ended December 31, 2017 , 2016 and 2015 was $1.4 million , $1.2 million and $0.6 million , respectively. We account for the difference between the minimum lease payments and the straight-line amount as deferred rent. Deferred rent under the Lease, which is included in other liabilities, was $9.3 million and $10.1 million as of December 31, 2017 and 2016 , respectively. We also pay property taxes, maintenance and insurance, which are expensed as incurred. The Lease includes an option to extend the lease term for an additional 5 year period subsequent to the lease expiration date. The future minimum payment summary below includes amounts payable over the remaining period of the Lease. As of December 31, 2017 , aggregate future annual minimum lease payments for the Lease are as follows (in thousands): 2018 $ 2,576 2019 2,654 2020 2,733 2021 2,815 2022 2,901 Thereafter 3,991 $ 17,670 License Agreements We have license agreements with third parties that require us to make annual license maintenance payments and future payments upon the success of licensed products that include milestones and/or royalties. Minimum future payments over the next five years are not material.

Convertible Note Payable

Convertible Note Payable	12 Months Ended
	Dec. 31, 2017
Debt Disclosure [Abstract]
Convertible Note Payable	Convertible Note Payable In October 2012, in conjunction with our initial public offering, we issued a convertible note to GSK LLC (the "GSK Note") in the principal amount of $5.4 million , with a maturity date of October 9, 2015 . On January 29, 2015, the principal amount outstanding under the GSK Note of $5.4 million was converted into 1,356,738 shares of our common stock at a conversion price of $4.00 per share. We recorded a loss from the change in valuation of the convertible note payable of $1.8 million upon its conversion.

Term Loan

Term Loan	12 Months Ended
	Dec. 31, 2017
Debt Disclosure [Abstract]
Term Loan	Term Loan On June 17, 2016, we entered into a loan and security agreement ("Loan Agreement") with Oxford Finance, LLC, ("Oxford"), pursuant to which Oxford agreed to lend us up to $30.0 million , issuable in two separate term loans of $20.0 million (the "Term A Loan") and $10.0 million (the "Term B Loan"). On June 22, 2016, we received $20.0 million in proceeds from the Term A Loan, net of debt issuance costs. The ability to borrow on the Term B Loan expired on March 31, 2017, and no amounts were borrowed under the Term B Loan. We refer to all amounts outstanding under the Loan Agreement as the Term Loan. The outstanding Term Loan will mature on June 1, 2020 (the “Maturity Date”) and we will have interest-only payments through June 1, 2018, followed by 24 equal monthly payments of principal and unpaid accrued interest. The Term Loan will bear interest at a floating per annum rate equal to (i) 8.51% plus (ii) the greater of (a) the 30 day U.S. Dollar LIBOR rate reported in The Wall Street Journal on the last business day of the month that immediately precedes the month in which the interest will accrue and (b) 0.44% . We have the option to prepay all, but not less than all, of the borrowed amount, provided that we will be obligated to pay a prepayment fee equal to (i) 2% of the outstanding principal balance of the Term Loan if prepayment is made prior to the second anniversary of the funding date of the Term Loan, or (ii) 1% of the Term Loan prepaid thereafter and prior to the Maturity Date. We will be required to make a final payment of 5.5% of the principal balance, payable on the earlier of (i) the Maturity Date, (ii) acceleration of the Term Loan, or (iii) the prepayment of the Term Loan. We may use the proceeds from the Term Loan solely for working capital and to fund our general business requirements. Our obligations under the Loan Agreement are secured by a first priority security interest in substantially all of our current and future assets, other than our intellectual property. We have also agreed not to encumber our intellectual property assets, except as permitted by the Loan Agreement. The Loan Agreement includes customary events of default, including instances of a material adverse change in our operations, that may require prepayment of the outstanding Term Loan. The principal payments due under the Term Loan have been classified as a current liability as of December 31, 2017 due to the considerations discussed in Note 1 and the assessment that the material adverse change clause under the Term Loan is not within the Company's control. The Company has not been notified of an event of default by the Lender as of the date of the filing of this Form 10-K. As of December 31, 2017 , we had $20.0 million outstanding under the Term Loan. The Term Loan was recorded at its initial carrying value of $20.0 million , less debt issuance costs of approximately $0.2 million . In connection with the Term Loan, the debt issuance costs have been recorded as a debt discount in our balance sheets, which are being accreted to interest expense over the life of the Term Loan using an effective interest rate of 8.98% . The exit fee is being accrued over the life of the Term Loan through interest expense. As of December 31, 2017 , we were in compliance with all covenants under the Loan Agreement. Future principal payments for the Term Loan due under the Loan Agreement are as follows (in thousands): 2018 $ 5,000 2019 10,000 2020 5,000 $ 20,000

Common Stock and Stockholders'

Common Stock and Stockholders' Equity	12 Months Ended
	Dec. 31, 2017
Equity [Abstract]
Common Stock and Stockholders’ Equity	Common Stock and Stockholders’ Equity Common Stock As of December 31, 2017 , there were 103,955,147 shares of common stock outstanding. Each share of common stock is entitled to one vote. The holders of the common stock are also entitled to receive dividends whenever funds are legally available and when declared by our Board of Directors. Public Offering In July 2017, we completed an underwritten public offering of 50,600,000 shares of common stock at an offering price of $0.91 per share. We received net proceeds from the offering of $43.0 million after deducting underwriting discounts, commissions and other offering expenses payable by us. Shares Reserved for Future Issuance The following shares of common stock were reserved for future issuance as of December 31, 2017 : Common stock options outstanding 10,648,523 Restricted stock units outstanding 415,728 Common stock available for future grant under the 2012 Plan 649,590 Common stock available for future grant under the Inducement Plan 41,948 Common stock available for future purchase under the 2012 Employee Stock Purchase Plan 1,675,110 Total common shares reserved for future issuance 13,430,899 The following table summarizes our stock option activity under all equity incentive plans for the year ended December 31, 2017 (shares and aggregate intrinsic value in thousands): Number of options Weighted average exercise price Weighted average remaining contractual term Aggregate intrinsic value Options outstanding at December 31, 2016 8,931 $ 6.70 Granted 5,126 $ 1.35 Exercised (11 ) $ 0.38 Canceled/forfeited/expired (3,397 ) $ 5.75 Options outstanding at December 31, 2017 10,649 $ 4.44 6.46 $ 227 Exercisable at December 31, 2017 5,099 $ 6.34 3.59 $ 119 The weighted average grant date fair value per share of employee stock options granted during the years ended December 31, 2017 , 2016 and 2015 was $1.00 , $3.47 and $7.47 , respectively. The total intrinsic value of stock options exercised was less than $0.1 million , $0.2 million and $21.4 million during the years ended December 31, 2017 , 2016 and 2015 , respectively. Cash received from the exercise of stock options was less than $0.1 million for the year ended December 31, 2017 and approximately $0.3 million and $6.7 million for the years ended December 31, 2016 and 2015 , respectively. We granted 415,728 restricted stock units during the year ended December 31, 2017 with a weighted average grant date fair value per share of $0.89 . There was no other restricted stock unit activity during the year ended December 31, 2017 and there was no restricted stock unit activity during the years ended December 31, 2016 and 2015 . The total compensation cost related to non-vested awards not yet recognized was $0.3 million as of December 31, 2017 . The weighted-average period over which this expense is expected to be recognized is approximately 0.6 years . Stock-Based Compensation The following table summarizes the weighted average assumptions used to estimate the fair value of stock options and performance stock awards granted to employees under our 2012 Equity Incentive Plan and 2015 Inducement Plan and the shares purchasable under our Employee Stock Purchase Plan during the periods presented: Year ended December 31, 2017 2016 2015 Stock options Risk-free interest rate 2.0 % 1.5 % 1.8 % Volatility 89.4 % 82.7 % 78.9 % Dividend yield — — — Expected term (years) 6.1 6.0 6.1 Performance stock options Risk-free interest rate 2.1 % 1.4 % 1.8 % Volatility 89.2 % 82.4 % 76.7 % Dividend yield — — — Expected term (years) 5.7 5.9 6.0 Employee stock purchase plan shares Risk-free interest rate 0.9 % 0.5 % 0.1 % Volatility 105.6 % 93.7 % 76.1 % Dividend yield — — — Expected term (years) 0.5 0.5 0.5 Risk-free interest rate - The risk-free interest rate assumption was based on observed interest rates appropriate for the expected term of the stock option grants. Expected dividend yield - The expected dividend yield assumption was based on the fact that we have never paid cash dividends and have no present intention to pay cash dividends. Expected volatility - The expected volatility assumption was based on the historical volatility of the trading price of our common stock. Expected term - The expected term represents the period of time that options are expected to be outstanding. Because we do not have sufficient historical exercise behavior data, we determine the expected life using the simplified method, which was an average of the contractual term of the option and its ordinary vesting period. Forfeitures - We made an accounting policy election to account for forfeitures as they occur upon adoption of ASU No. 2016-09 in the first quarter of 2017. We applied ASU No. 2016-09 using the modified retrospective method of adoption and recorded an adjustment of $0.6 million to accumulated deficit with a corresponding offset to additional paid-in capital. Prior to adoption, we reduced stock-based compensation expense for estimated forfeitures. The following table summarizes the allocation of our stock-based compensation expense for all stock awards during the periods presented, including the adjustments to stock-based compensation expense associated with our May 2017 corporate restructuring (in thousands): Year ended December 31, 2017 2016 2015 Research and development $ 2,862 $ 5,458 $ 8,075 Research and development-restructuring related adjustments (1,399 ) — — General and administrative 3,500 7,414 7,293 General and administrative-restructuring related adjustments 2,679 — — Total $ 7,642 $ 12,872 $ 15,368 In connection with our May 2017 corporate restructuring we recorded a reversal of stock-based compensation in research and development expenses of $1.4 million as a result of the cancellation of unvested stock options. Additionally, we recorded additional stock-based compensation in general and administrative expenses of $2.7 million as a result of termination provisions within certain employment agreements. The total compensation cost related to non-vested awards not yet recognized was $5.1 million as of December 31, 2017 . The weighted-average period over which this expense is expected to be recognized is approximately 2.5 years. Employee Stock Purchase Plan In October 2012, we adopted the 2012 Employee Stock Purchase Plan (“2012 Purchase Plan”), which enables participants to contribute up to 15% of such participant’s eligible compensation during a defined six-month period to purchase our common stock. The purchase price of common stock under the 2012 Purchase Plan will be the lesser of: (i) 85% of the fair market value of our common stock at the inception of the enrollment period or (ii) 85% of the fair market value of our common stock at the applicable purchase date. As of December 31, 2017 , 740,526 shares of our common stock had been issued under the 2012 Purchase Plan, with 419,342 shares of common stock issued for the year ended December 31, 2017 . Under the 2012 Purchase Plan, 1,675,110 shares of our common stock were reserved for future issuance and have been authorized for purchase as of December 31, 2017 . Inducement Plan On July 17, 2015, our Board of Directors adopted the Inducement Plan, which became effective immediately. Stockholder approval of the Inducement Plan was not required pursuant to Rule 5635 (c)(4) of the NASDAQ Listing Rules. The Inducement Plan initially reserved 1,000,000 shares of common stock and provides for the grant of NSOs that was used exclusively for grants to individuals that were not previously employees or directors of the Company, as an inducement material to the individual’s entry into employment with the Company. Under the Inducement Plan, options were granted with varying vesting terms, but typically vest over four years , with 25% of the total grant vesting on the first anniversary of the effective date of the option grant and the remaining grant vesting monthly thereafter over the following 36 months. All options granted under the Inducement Plan expire ten years from the date of grant. As of December 31, 2017, 41,948 shares were reserved under the Inducement Plan.

Defined Contribution Plan

Defined Contribution Plan	12 Months Ended
	Dec. 31, 2017
Retirement Benefits [Abstract]
Defined Contribution Plan	Defined Contribution Plan In 2009, we established an employee 401(k) salary deferral plan (“401(k) Plan”) covering all eligible employees. Active employees who are at least 18 years old and are not otherwise disqualified under the terms of the 401(k) Plan are eligible to participate. Employees may contribute up to 50% of their compensation per year (subject to a maximum limit prescribed by federal tax law). Under the 401(k) Plan, we may elect to match a discretionary percentage of employee contributions. We elected to match 25% of employees’ contributions up to 6% of the employees’ eligible salary for the periods presented. We made matching contributions of $0.1 million , $0.2 million and $0.1 million for the years ended December 31, 2017 , 2016 , and 2015 , respectively.

Income Taxes

Income Taxes	12 Months Ended
	Dec. 31, 2017
Income Tax Disclosure [Abstract]
Income Taxes	Income Taxes The following table summarizes the components of our income tax (benefit) expense (in thousands): Year ended December 31, 2017 2016 2015 Current: Federal $ (143 ) $ — $ — State 1 1 1 (142 ) 1 1 Deferred: Federal (55 ) (5 ) (17 ) State — — (2 ) (55 ) (5 ) (19 ) Income tax (benefit) $ (197 ) $ (4 ) $ (18 ) The following is a reconciliation of the expected statutory federal income tax provision to our actual income tax provision (in thousands): Year ended December 31, 2017 2016 2015 Expected income tax benefit at federal statutory tax rate $ (24,515 ) $ (27,826 ) $ (18,960 ) State income taxes, net of federal benefit 1 (1,152 ) (1,580 ) Tax credits (5,151 ) (5,447 ) (5,039 ) Change in fair value of convertible note payable — — 616 Change in valuation allowance (8,705 ) 31,990 23,216 Prior year true-up 1 (1,320 ) 110 Stock compensation 1,135 2,458 1,161 Reserve for uncertain tax positions 311 1,314 254 Tax Cuts and Jobs Act rate change 36,249 — — Other 477 (21 ) 204 Income tax (benefit) $ (197 ) $ (4 ) $ (18 ) The following table summarizes the significant components of our deferred tax assets and liabilities (in thousands): December 31, 2017 2016 Deferred tax assets: Net operating loss carryovers $ 66,549 $ 70,739 Research and development and other tax credits 29,702 22,613 Deferred revenue 419 735 Stock compensation expense 4,238 5,664 Other 2,196 4,679 Total deferred tax assets 103,104 104,430 Total deferred tax liabilities (408 ) (799 ) Net deferred tax asset 102,696 103,631 Valuation allowance (102,641 ) (103,631 ) Net deferred tax asset $ 55 $ — For all periods presented, we have determined that it is more likely than not that our deferred tax asset will not be realized. Accordingly, we have recorded a valuation allowance to offset the net deferred tax asset of $102.6 million . As of December 31, 2017, we had federal and California tax net operating loss carryforwards of $265.8 million and $146.3 million , respectively, which begin to expire in 2030 and 2031. Upon adoption of ASU 2016-09 during 2017, the balance of the unrecognized excess tax benefits of $7.7 million has been reversed with the impact recorded to accumulated deficit, offset by a corresponding change in the valuation allowance. As of December 31, 2017, we also had federal and California research and development tax credit carryforwards of $27.5 million and $8.1 million , respectively. The federal research and development tax credit carryforwards will begin to expire in 2029. The California research and development tax credit carryforwards are available indefinitely. As of December 31, 2017, we also had $0.1 million of Federal Alternative Minimum Tax Credit carryforwards that are available indefinitely. The future utilization of our research and development credit carryforwards and net operating loss carryforwards to offset future taxable income may be subject to an annual limitation as a result of ownership changes that have occurred previously or may occur in the future. The Tax Reform Act of 1986 (the Act) limits a company’s ability to utilize certain tax credit carryforwards and net operating loss carryforwards in the event of a cumulative change in ownerships in excess of 50% as defined in the Act. The following table summarizes the changes in the amount of our unrecognized tax benefits (in thousands): Year Ended December 31, 2017 2016 2015 Beginning balance of unrecognized tax benefits $ 5,632 $ 2,298 $ 1,853 (Decrease) increase for prior year tax positions (2,466 ) 1,991 (250 ) Increase for current year tax positions 1,255 1,343 695 Total $ 4,421 $ 5,632 $ 2,298 Included in unrecognized tax benefits of $4.4 million at December 31, 2017 was $3.7 million of tax benefits that, if recognized, would reduce our annual effective tax rate, subject to valuation allowance. We are subject to taxation in the United States and California. Our tax years for 2009 and forward are subject to examination by the U.S. tax authorities and our tax years for 2009 and forward are subject to examination by the California tax authorities due to carryforward of unutilized net operating losses and research and development credits. It is our practice to recognize interest and/or penalties related to income tax matters in income tax expense. For the years ended December 31, 2017 , 2016 and 2015 , we have not recognized any interest or penalties related to income taxes. On December 22, 2017, the President of the United States signed into law the Tax Cuts and Jobs Act (the "Act"). The Act amends the Internal Revenue Code to reduce tax rates and modify policies, credits, and deductions for individuals and businesses. For businesses, the Act reduces the corporate tax rate from a maximum of 35% to a flat 21% rate. The rate reduction is effective on January 1, 2018. At December 31, 2017, we had not yet completed our accounting assessment for the tax effects of the enactment of the Act; however, as described below, we have made a reasonable estimate of the effects on our existing deferred tax balances. As a result of the lower enacted corporate tax rate, we have provisionally reduced the deferred tax asset balance as of December 31, 2017 by $36.2 million . Due to our full valuation allowance position, we have also reduced the valuation allowance by the same amount. Due to uncertainties which currently exist in the interpretation of the provisions of the Act regarding Internal Revenue Code Section 162(m), we have not completed our evaluation of the potential impacts of IRC Section 162(m) as amended by the Act on its financial statements. On December 22, 2017, Staff Accounting Bulletin No. 118 ("SAB 118") was issued to address the application of US GAAP in situations when a registrant does not have the necessary information available, prepared, or analyzed (including computations) in reasonable detail to complete the accounting for certain income tax effects of the Act. In accordance with SAB 118, the we have provisionally determined that there is no deferred tax benefit or expense with respect to the remeasurement of certain deferred tax assets and liabilities due to the full valuation allowance against net deferred tax assets. Additional analysis of the law and the impact to the company will be performed and any impact will be recorded in the respective quarter in 2018.

Related Party Transactions

Related Party Transactions	12 Months Ended
	Dec. 31, 2017
Related Party Transactions [Abstract]
Related Party Transactions	Related Party Transactions In September 2014, we entered into an agreement with Sanofi-Aventis Deutschland GmbH (“Sanofi Deutschland”), a contract manufacturing subsidiary of Sanofi, for the manufacture of certain drug substance requirements and other services to support our preclinical and clinical activities associated with the RG-012 program. Pursuant to this agreement, we engaged Sanofi Deutschland to manufacture RG-012 drug product and perform stability studies on our behalf. Expenses incurred under the agreement for services performed or out-of-pocket expenses were less than $0.1 million , $0.9 million and $0.4 million for the years ended December 31, 2017 , 2016 and 2015 , respectively. In February 2015, we entered into a letter agreement with Alnylam pursuant to which we and Alnylam agreed to the financial terms for certain technology acquired by Alnylam within the licensed patent rights under our Amended and Restated License and Collaboration Agreement (the “Additional Patent Rights”) with Alnylam and Ionis. In addition to any royalties payable by us to Alnylam pursuant to the terms of the Amended and Restated License and Collaboration Agreement, we agreed to pay Alnylam an additional low single-digit royalty on net sales of certain products utilizing the Additional Patent Rights, with the exact royalty percentage payable being dependent on the total amount of net sales during the calendar year. We also agreed to pay Alnylam milestone payments on certain products utilizing the additional patent rights of up to $33.0 million per product upon the achievement of certain regulatory milestone events. There was no activity under this agreement for the years ended December 31, 2017 , 2016 and 2015.

Selected Quarterly Financial Da

Selected Quarterly Financial Data (Unaudited)	12 Months Ended
	Dec. 31, 2017
Quarterly Financial Information Disclosure [Abstract]
Selected Quarterly Financial Data (Unaudited)	Selected Quarterly Financial Data (Unaudited) The following financial information reflects all normal recurring adjustments, which are, in the opinion of management, necessary for a fair statement of the results of the interim periods. Summarized quarterly data for 2017 and 2016 are as follows (in thousands, except per share data): For the quarters ending March 31 June 30 September 30 December 31 2017 Total revenues $ 18 $ 18 $ 18 $ 18 Total operating expenses 19,711 21,335 15,433 13,724 Net loss (20,021 ) (21,608 ) (15,828 ) (14,448 ) Net loss per share, basic and diluted (1) $ (0.38 ) $ (0.41 ) $ (0.18 ) $ (0.14 ) 2016 Total revenues $ 489 $ 483 $ 204 $ 18 Total operating expenses 21,867 21,671 19,396 19,762 Net loss (21,207 ) (21,090 ) (19,519 ) (20,020 ) Net loss per share, basic and diluted (1) $ (0.40 ) $ (0.40 ) $ (0.37 ) $ (0.38 ) (1) Net loss per share is computed independently for each of the quarters presented. Therefore, the sum of the quarterly per-share calculations will not necessarily equal the annual per share calculation.

The Business, Basis of Presen23

The Business, Basis of Presentation and Summary of Significant Accounting Policies (Policies)	12 Months Ended
	Dec. 31, 2017
Accounting Policies [Abstract]
Use of Estimates	Use of Estimates Our financial statements are prepared in accordance with U.S. generally accepted accounting principles ("GAAP"), which requires us to make estimates and assumptions that affect the reported amounts of assets, liabilities, revenues and expenses and the disclosure of contingent assets and liabilities in our financial statements and accompanying notes. An estimated loss contingency is accrued in our financial statements if it is probable that a liability has been incurred and the amount of the loss can be reasonably estimated. Although these estimates are based on our knowledge of current events and actions we may undertake in the future, actual results may ultimately differ from these estimates and assumptions.
Revenue Recognition	Revenue Recognition Our revenues generally consist of upfront payments for licenses or options to obtain licenses in the future, milestone payments and payments for other research services under strategic alliance and collaboration agreements. We recognize revenues when all four of the following criteria are met: (1) persuasive evidence of an arrangement exists; (2) delivery of the products and/or services has occurred; (3) the selling price is fixed or determinable; and (4) collectability is reasonably assured. Multiple element arrangements, such as our strategic alliance agreement with Sanofi are analyzed to determine whether the deliverables within the agreement can be separated or whether they must be accounted for as a single unit of accounting. Deliverables under the agreement will be accounted for as separate units of accounting provided that (i) a delivered item has value to the customer on a stand-alone basis; and (ii) if the agreement includes a general right of return relative to the delivered item, delivery or performance of the undelivered item is considered probable and substantially in the control of the vendor. The allocation of consideration amongst the deliverables under the agreement is derived using a “best estimate of selling price” if vendor specific objective evidence and third-party evidence of fair value is not available. If the delivered element does not have stand-alone value, the arrangement is then accounted for as a single unit of accounting, and we recognize the consideration received under the arrangement as revenue on a straight-line basis, which approximates effort over our estimated period of performance, which for us is typically the expected term of the research and development plan. Milestones We apply the milestone method of accounting to recognize revenue from milestone payments when earned, as evidenced by written acknowledgment from the collaborator or other persuasive evidence that the milestone has been achieved and the payment is non-refundable, provided that the milestone event is substantive. A milestone event is defined as an event (i) that can only be achieved based in whole or in part on either our performance or on the occurrence of a specific outcome resulting from our performance; (ii) for which there is substantive uncertainty at the inception of the arrangement that the event will be achieved; and (iii) that would result in additional payments being due to us. Events for which the occurrence is either contingent solely upon the passage of time or the result of a counterparty’s performance are not considered to be milestone events. A milestone event is substantive if all of the following conditions are met: (i) the consideration is commensurate with either our performance to achieve the milestone, or the enhancement of the value to the delivered item(s) as a result of a specific outcome resulting from our performance to achieve the milestone; (ii) the consideration relates solely to past performance; and (iii) the consideration is reasonable relative to all the deliverables and payment terms (including other potential milestone consideration) within the arrangement. We assess whether a milestone is substantive at the inception of each arrangement. If a milestone is deemed non-substantive, we will account for that milestone payment using a method consistent with the related units of accounting for the arrangement over the estimated performance period. Deferred Revenue Amounts received prior to satisfying the above revenue recognition criteria are recorded as deferred revenue in the accompanying balance sheets. Amounts not expected to be recognized within the next 12 months are classified as non-current deferred revenue.
Stock-Based Compensation	Stock-Based Compensation We account for stock-based compensation expense related to stock options granted to employees and members of our board of directors by estimating the fair value of each stock option on the date of grant using the Black-Scholes option pricing model. We recognize stock-based compensation expense using the accelerated multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award was in substance multiple awards, resulting in accelerated expense recognition over the vesting period. For performance-based awards granted to employees (i) the fair value of the award is determined on the grant date, (ii) we assess the probability of the individual milestones under the award being achieved and (iii) the fair value of the shares subject to the milestone is expensed over the implicit service period commencing once management believes the performance criteria is probable of being met.
Prepaid Materials	Prepaid Materials We capitalize the purchase of certain raw materials and related supplies for use in the manufacturing of drug product in our clinical development programs, as we have determined that these materials have alternative future use. We can use these raw materials and related supplies in multiple clinical drug products, and therefore have future use independent of the development status of any particular drug program until it is utilized in the manufacturing process. We expense the cost of materials when used. We periodically review these capitalized materials for continued alternative future use and write down the asset to its net realizable value in the period in which it is identified.
Research and Development	Research and Development Research and development costs are expensed as incurred and consist of costs associated with research activities supporting our drug discovery efforts, compensation and related benefits, non-cash stock-based compensation, license fees, laboratory supplies and associated overhead and facility costs.
Income Tax, Policy	Income Taxes Income taxes are accounted for under the asset and liability method. This approach requires the recognition of deferred tax assets and liabilities for the expected future tax consequences of the differences between the tax basis of assets or liabilities and their carrying amounts in the financial statements using the enacted tax rates and laws that are anticipated to be in effect when the differences are expected to reverse. We provide a valuation allowance against net deferred tax assets if it is more likely than not that these items will either expire before we are able to realize their benefit or if future deductibility is uncertain. In accordance with the accounting standards for uncertain tax positions, we evaluate the recognition threshold and measurement attribute criteria for the financial statement recognition and measurement of tax positions taken or expected to be taken in a tax return. For those benefits to be recognized, a tax position must be more likely than not to be sustained upon examination by taxing authorities.
Fair Value Option	Fair Value Option Applicable accounting policies permit entities to choose, at specified election dates, to measure specified items at fair value if the decision about the election is: (1) applied instrument by instrument, (2) irrevocable, and (3) applied to an entire instrument. Fair Value Measurements We have certain financial assets recorded at fair value which have been classified as Level 1, 2, or 3 within the fair value hierarchy as described in the accounting standards for fair value measurements. Accounting standards define fair value as the exchange price that would be received for an asset or paid to transfer a liability (an exit price) in the principal or most advantageous market for the asset or liability in an orderly transaction between market participants as of the measurement date. Market participants are buyers and sellers in the principal market that are (i) independent, (ii) knowledgeable, (iii) able to transact, and (iv) willing to transact. The accounting standards provide an established hierarchy for inputs used in measuring fair value that maximizes the use of observable inputs and minimizes the use of unobservable inputs by requiring that the most observable inputs be used when available. Observable inputs are inputs that market participants would use in valuing the asset or liability and are developed based on market data obtained from independent sources. Unobservable inputs are inputs that reflect our assumptions about the factors that market participants would use in valuing the asset or liability. The accounting standards prioritize the inputs used in measuring the fair value into the following hierarchy: • Level 1 includes financial instruments for which quoted market prices for identical instruments are available in active markets. • Level 2 includes financial instruments for which there are inputs other than quoted prices included within Level 1 that are observable for the instrument such as quoted prices for similar instruments in active markets, quoted prices for identical or similar instruments in markets with insufficient volume or infrequent transactions (less active markets) or model-driven valuations in which significant inputs are observable or can be derived principally from, or corroborated by, observable market data. • Level 3 includes financial instruments for which fair value is derived from valuation techniques in which one or more significant inputs are unobservable, including management’s own assumptions.
Clinical Trial and Preclinical Study Accruals	Clinical Trial and Preclinical Study Accruals We make estimates of our accrued expenses for clinical trial and preclinical study activities as of each balance sheet date in our financial statements based on the facts and circumstances known to us at that time. These accruals are based upon estimates of costs incurred and fees that may be associated with services provided by clinical trial investigational sites, CROs and for other clinical trial-related activities. Payments under certain contracts with such parties depend on factors such as successful enrollment of patients, site initiation and the completion of clinical trial milestones. In accruing for these services, we estimate the time period over which services will be performed and the level of effort to be expended in each period. If possible, we obtain information regarding unbilled services directly from these service providers. However, we may be required to estimate these services based on other information available to us. If we underestimate or overestimate the activities or fees associated with a study or service at a given point in time, adjustments to research and development expenses may be necessary in future periods. Historically, our estimated accrued liabilities have approximated actual expense incurred. Subsequent changes in estimates may result in a material change in our accruals.
Cash and Cash Equivalents	Cash and Cash Equivalents We classify time deposits and other investments that are highly liquid and have maturities of 90 days or less at the date of purchase as cash equivalents. The carrying amounts approximate fair value due to the short maturities of these instruments.
Short-Term Investments	Short-Term Investments We carry short-term investments classified as available-for-sale at fair value as determined by prices for identical or similar securities at the balance sheet date. Our short-term investments consist of both Level 1 and Level 2 financial instruments in the fair value hierarchy. We record unrealized gains and losses as a component of other comprehensive loss within the statements of operations and comprehensive loss and as a separate component of stockholders’ equity. We determine the realized gains or losses of available-for-sale securities using the specific identification method and include net realized gains and losses in interest income. At each balance sheet date, we assess available-for-sale securities in an unrealized loss position to determine whether the unrealized loss is other-than-temporary. We consider factors including: the significance of the decline in value compared to the cost basis, underlying factors contributing to a decline in the prices of securities in a single asset class, the length of time the market value of the security has been less than its cost basis, the security’s relative performance versus its peers, sector or asset class, expected market volatility and the market and economy in general. When we determine that a decline in the fair value below its cost basis is other-than-temporary, we recognize an impairment loss in the year in which the other-than-temporary decline occurred. We determined that there were no other-than-temporary declines in the value of short-term investments as of December 31, 2017 or 2016 .
Concentration of Credit Risk	Concentrations of Credit Risk Financial instruments that potentially subject us to significant concentrations of credit risk consist primarily of cash equivalents and short-term investments. We maintain deposits in federally insured financial institutions in excess of federally insured limits. We have not experienced any material losses in such accounts and believe we are not exposed to significant risk. We maintain our cash equivalents and short-term investments with two highly accredited financial institutions. We invest our excess cash primarily in commercial paper, certificates of deposit and debt instruments of financial institutions and corporations, United States Treasury securities and United States government-sponsored enterprise securities. Additionally, we adhere to established guidelines regarding approved investments and maturities of investments, which are designed to preserve their principal value and maintain liquidity.
Property and Equipment	Property and Equipment We carry our property and equipment at cost, which consists of lab equipment, computer equipment and software, furniture and fixtures and leasehold improvements. Property and equipment is depreciated using the straight-line method over the estimated useful lives (generally three to five years). Leasehold improvements are amortized over the lesser of their useful life or the remaining lease term, including any renewal periods that are deemed to be reasonably assured. Repair and maintenance costs that do not improve service potential or extend economic life are expensed as incurred.
Intangibles	Intangibles We capitalize costs which consist principally of outside legal costs and filing fees related to obtaining patents. We review our capitalized patent costs periodically to determine that they include costs for patent applications that have future value and an alternative future use. We evaluate costs related to patents that we are not actively pursuing and write off these costs. We amortize patent costs over their patent lives, beginning with the date the patents are issued. The weighted average remaining life of the issued patents was approximately 9 years at December 31, 2017 . We obtain licenses from third parties and capitalize the costs related to exclusive licenses that have alternative future use within multiple potential programs. We amortize capitalized licenses over their estimated useful life or term of the agreement, which for current licenses is 10 years.
Impairment of Long-Lived Assets	Impairment of Long-Lived Assets We regularly review the carrying amount of our property, equipment and intangible assets to determine whether indicators of impairment may exist which warrant adjustments to carrying values or estimated useful lives. If indications of impairment exist, projected future undiscounted cash flows associated with the asset are compared to the carrying amount to determine whether the asset’s value is recoverable. If the carrying value of the asset exceeds such projected undiscounted cash flows, the asset will be written down to its estimated fair value.
Segment Reporting	Segment Reporting Operating segments are identified as components of an enterprise about which separate discrete financial information is available for evaluation by the chief operating decision-maker in making decisions regarding resource allocation and assessing performance. To date, we have viewed our operations and managed our business as one segment operating primarily within the United States.
Comprehensive Loss	Comprehensive Loss Comprehensive loss is defined as the change in equity during a period from transactions and other events and/or circumstances from non-owner sources. Our only component of other comprehensive loss is unrealized gains (losses) on available-for-sale securities. Comprehensive gains (losses) have been reflected in the statements of operations and comprehensive loss and as a separate component in the statements of stockholders’ equity for all periods presented.
Recent Accounting Pronouncements	Recent Accounting Pronouncements In May 2014, the FASB issued ASU, No. 2014-09, Revenue from Contracts with Customers (Topic 606) , which outlines a single comprehensive model for entities to use in accounting for revenue arising from contracts with customers and supersedes most current revenue recognition guidance, including industry-specific guidance. ASU 2014-09 outlines a five-step process for revenue recognition that focuses on transfer of control, as opposed to transfer of risk and rewards, and also requires enhanced disclosures regarding the nature, amount, timing and uncertainty of revenues and cash flows from contracts with customers. Major provisions include determining which goods and services are distinct and require separate accounting (performance obligations), how variable consideration (which may include change orders and claims) is recognized, whether revenue should be recognized at a point in time or over time and ensuring the time value of money is considered in the transaction price. The FASB subsequently issued amendments to ASU No. 2014-09 that have the same effective date and transition date. These new standards became effective for us on January 1, 2018 and will be adopted using the modified retrospective method through a cumulative-effect adjustment directly to accumulated deficit as of that date. The Company has performed a review of these new standards as compared to our current accounting policies for customer contracts. As of December 31, 2017, we have not identified any accounting changes that would materially impact the amount of historically reported revenues with respect to our grant revenue. The Company is currently evaluating the impact of the new standard on historical revenue recorded for our ongoing collaboration agreement with Sanofi. This ongoing evaluation is dependent upon the resolution of certain questions relating to the application of the new revenue recognition guidance for collaboration agreements which will ultimately determine the impact, if any, the adoption of this standard may have on our financial statements. Our ongoing evaluation will be complete in the first quarter 2018. The company expects the accounting for contingent milestone payments to be the most significant change in accounting for its license and collaboration agreements. Topic 605 provides guidance specific to the accounting for milestone payments, including the ability to defer the recognition of any milestones until received and, if certain criteria are met, the ability to recognize milestone payments as revenue when received. However, Topic 606 does not contain guidance specific to milestone payments, thereby requiring potential milestone payments to be considered in accordance with the overall model of Topic 606. As a result, revenues from contingent milestone payments may be recognized earlier under Topic 606 than under Topic 605, based on an assessment of the probability of achievement of the milestone and the likelihood of a significant reversal of such milestone revenue at each reporting date. This assessment may result in recognizing milestone revenue before the milestone event has been achieved. In addition, Topic 606 changes guidance regarding the accounting for variable consideration received from licensees, which may impact the estimation of, and determination of the timing of, the related revenue recognition. In January 2016, the FASB issued ASU No. 2016-01, Recognition and Measurement of Financial Assets and Financial Liabilities , which eliminates the requirement for public companies to disclose the method(s) and significant assumptions used to estimate the fair value for financial instruments measured at amortized cost on the balance sheet. Additionally, the standard requires public companies to use the exit price notion when measuring the fair value of financial instruments for disclosure purposes. Furthermore, the standard requires presentation of financial assets and liabilities by measurement category and form of financial asset on the balance sheet or accompanying notes to the financial statements. The standard is effective for annual reporting periods beginning after December 15, 2017, including interim periods within those annual reporting periods. Early application is permitted. The adoption of this guidance will have no impact on our financial statements. In February 2016, the FASB issued ASU No. 2016-02, Leases, which increases transparency and comparability among organizations by requiring recognition of lease assets and lease liabilities on the balance sheet and disclosure of key information about leasing arrangements. The standard is effective for annual reporting periods beginning after December 15, 2018, including interim periods within those annual reporting periods. Early application is permitted. We are currently evaluating the impact of adoption on our financial statements. In March 2016, the FASB issued ASU No. 2016-09, Compensation – Stock Compensation: Improvements to Employee Share-Based Payment Accounting, which is intended to simplify various aspects of accounting for share-based payment transactions. The new guidance requires immediate recognition of all excess tax benefits and deficiencies in the income statement, requires classification of excess tax benefits as an operating activity as opposed to a financing activity in the statements of cash flows and allows a company to make an accounting policy election to either estimate the number of awards or account for forfeitures when they occur. The standard is effective for annual reporting periods beginning after December 15, 2016, and interim periods within those annual reporting periods. We applied this standard in the first quarter of 2017 using the modified retrospective method of adoption. In conjunction with this adoption, we made an accounting policy election to account for forfeitures as they occur. Upon adoption, we reversed a deferred tax asset related to the balance of unrecognized excess tax benefits of $7.7 million , with an offsetting adjustment to the valuation allowance. Under the modified retrospective method of adoption, we recorded an adjustment of $0.6 million to accumulated deficit with a corresponding offset to additional paid-in capital. In August 2016, the FASB issued ASU No. 2016-15, Statement of Cash Flows: Classification of Certain Cash Receipts and Cash Payments , which addresses the presentation and classification of certain cash receipts and cash payments in the statement of cash flows under Accounting Standards Codification 230. The standard is effective for annual reporting periods beginning after December 15, 2017, and interim periods within those annual reporting periods. The adoption of this guidance will have no impact on our financial statements. In November 2016, the FASB issued ASU No. 2016-18, Statement of Cash Flows: Restricted Cash , which requires restricted cash and restricted cash equivalents to be included with cash and cash equivalents when reconciling the beginning-of-period and end-of-period total amounts shown on the statement of cash flows. The standard is effective for annual reporting periods beginning after December 15, 2017, and interim periods within those annual reporting periods. Early application is permitted. Upon its adoption in 2018, we will include $1.3 million of restricted cash in our disclosed balance of cash and cash equivalents at the beginning of the period for 2016. We do not expect any additional impact on our financial statements. In May 2017, the FASB issued ASU No. 2017-09, Compensation - Stock Compensation (Topic 718): Scope of Modification Accounting , which provides clarity and guidance around which changes to the terms or conditions of a share-based payment award require an entity to apply modification accounting in Topic 718. The standard is effective for annual reporting periods beginning after December 15, 2017, and interim periods within those annual reporting periods. The adoption of this guidance will have no impact on our financial statements unless we have modification accounting in accordance with Topic 718.

Investments (Tables)

Investments (Tables)	12 Months Ended
	Dec. 31, 2017
Investments, Debt and Equity Securities [Abstract]
Summary of Short-Term Investments	The following tables summarize our short-term investments (in thousands): Maturity (in years) Amortized cost Unrealized Estimated fair value Gains Losses As of December 31, 2017 Corporate debt securities 1 or less $ 32,922 $ — $ (55 ) $ 32,867 Certificates of deposit 1 or less 8,216 — — 8,216 U.S. treasury securities 1 or less 3,996 — (18 ) 3,978 Debt securities of U.S. government-sponsored agencies 1 or less 1,498 — (4 ) 1,494 Total $ 46,632 $ — $ (77 ) $ 46,555 Maturity (in years) Amortized cost Unrealized Estimated fair value Gains Losses As of December 31, 2016 Corporate debt securities 2 or less $ 49,185 $ 12 $ (77 ) $ 49,120 Certificates of deposit 1 or less 9,291 — — 9,291 U.S. treasury securities 1 or less $ 1,001 $ — $ (1 ) $ 1,000 U.S. government-sponsored enterprise securities 1 or less $ 512 $ — $ — $ 512 Commercial paper 1 or less $ 1,247 $ — $ — $ 1,247 Total $ 61,236 $ 12 $ (78 ) $ 61,170

Fair Value Measurements (Tables

Fair Value Measurements (Tables)	12 Months Ended
	Dec. 31, 2017
Fair Value Disclosures [Abstract]
Fair Value Hierarchy for Assets and Liabilities Measured at Fair Value on Recurring Basis	The following table presents our fair value hierarchy for assets measured at fair value on a recurring basis as of December 31, 2017 and December 31, 2016 (in thousands): Fair value as of December 31, 2017 Total Level 1 Level 2 Level 3 Assets: Cash equivalents $ 10,847 $ 10,847 $ — $ — Corporate debt securities 32,867 — 32,867 — Certificates of deposit 8,216 — 8,216 — U.S. treasury securities 3,978 — 3,978 — Debt securities of U.S. government-sponsored agencies 1,494 — 1,494 — $ 57,402 $ 10,847 $ 46,555 $ — Fair value as of December 31, 2016 Total Level 1 Level 2 Level 3 Assets: Cash equivalents $ 13,578 $ 13,578 $ — $ — Corporate debt securities 49,120 — 49,120 — Certificates of deposit 9,291 — 9,291 — U.S. treasury securities 1,000 — 1,000 — Debt securities of U.S. government-sponsored agencies 512 — 512 — Commercial paper 1,247 — 1,247 — $ 74,748 $ 13,578 $ 61,170 $ —

Strategic Alliances and Colla26

Strategic Alliances and Collaborations (Tables)	12 Months Ended
	Dec. 31, 2017
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Revenue from Strategic Alliances	The following table summarizes our total revenues from our strategic alliances and collaborations during the periods presented (in thousands): Year ended December 31, 2017 2016 2015 Sanofi $ 72 $ 72 $ 71 AstraZeneca — 1,122 18,871 Biogen — — 1,817 Total $ 72 $ 1,194 $ 20,759

Property and Equipment, net (Ta

Property and Equipment, net (Tables)	12 Months Ended
	Dec. 31, 2017
Property, Plant and Equipment [Abstract]
Property, Plant and Equipment	The following table summarizes our major classes of property and equipment (in thousands): December 31, 2017 2016 Laboratory equipment $ 8,430 $ 7,932 Computer equipment and software 281 265 Furniture and fixtures 706 706 Leasehold improvements 8,550 10,469 Construction in progress — 261 17,967 19,633 Less accumulated depreciation and amortization (8,259 ) (7,803 ) Property and equipment, net $ 9,708 $ 11,830

Intangible Assets, net (Tables)

Intangible Assets, net (Tables)	12 Months Ended
	Dec. 31, 2017
Goodwill and Intangible Assets Disclosure [Abstract]
Schedule of Finite-Lived Intangible Assets	The following table summarizes our major classes of intangible assets (in thousands): December 31, 2017 2016 Patents $ 871 $ 1,102 Licenses 379 379 1,250 1,481 Accumulated amortization (475 ) (466 ) Intangibles, net $ 775 $ 1,015

Commitments and Contingencies (

Commitments and Contingencies (Tables)	12 Months Ended
	Dec. 31, 2017
Commitments and Contingencies Disclosure [Abstract]
Schedule of Future Minimum Rental Payments for Operating Leases	As of December 31, 2017 , aggregate future annual minimum lease payments for the Lease are as follows (in thousands): 2018 $ 2,576 2019 2,654 2020 2,733 2021 2,815 2022 2,901 Thereafter 3,991 $ 17,670

Term Loan (Tables)

Term Loan (Tables)	12 Months Ended
	Dec. 31, 2017
Debt Disclosure [Abstract]
Schedule of Future Principal Payments	Future principal payments for the Term Loan due under the Loan Agreement are as follows (in thousands): 2018 $ 5,000 2019 10,000 2020 5,000 $ 20,000

Common Stock and Stockholders31

Common Stock and Stockholders' Equity (Tables)	12 Months Ended
	Dec. 31, 2017
Equity [Abstract]
Common Stock Reserved for Future Issuance	The following shares of common stock were reserved for future issuance as of December 31, 2017 : Common stock options outstanding 10,648,523 Restricted stock units outstanding 415,728 Common stock available for future grant under the 2012 Plan 649,590 Common stock available for future grant under the Inducement Plan 41,948 Common stock available for future purchase under the 2012 Employee Stock Purchase Plan 1,675,110 Total common shares reserved for future issuance 13,430,899
Stock Option Activity	The following table summarizes our stock option activity under all equity incentive plans for the year ended December 31, 2017 (shares and aggregate intrinsic value in thousands): Number of options Weighted average exercise price Weighted average remaining contractual term Aggregate intrinsic value Options outstanding at December 31, 2016 8,931 $ 6.70 Granted 5,126 $ 1.35 Exercised (11 ) $ 0.38 Canceled/forfeited/expired (3,397 ) $ 5.75 Options outstanding at December 31, 2017 10,649 $ 4.44 6.46 $ 227 Exercisable at December 31, 2017 5,099 $ 6.34 3.59 $ 119
Assumptions Used to Estimate Fair Value of Stock Options and Performance Stock and Employee Stock Purchase Plan	The following table summarizes the weighted average assumptions used to estimate the fair value of stock options and performance stock awards granted to employees under our 2012 Equity Incentive Plan and 2015 Inducement Plan and the shares purchasable under our Employee Stock Purchase Plan during the periods presented: Year ended December 31, 2017 2016 2015 Stock options Risk-free interest rate 2.0 % 1.5 % 1.8 % Volatility 89.4 % 82.7 % 78.9 % Dividend yield — — — Expected term (years) 6.1 6.0 6.1 Performance stock options Risk-free interest rate 2.1 % 1.4 % 1.8 % Volatility 89.2 % 82.4 % 76.7 % Dividend yield — — — Expected term (years) 5.7 5.9 6.0 Employee stock purchase plan shares Risk-free interest rate 0.9 % 0.5 % 0.1 % Volatility 105.6 % 93.7 % 76.1 % Dividend yield — — — Expected term (years) 0.5 0.5 0.5
Stock-Based Compensation	The following table summarizes the allocation of our stock-based compensation expense for all stock awards during the periods presented, including the adjustments to stock-based compensation expense associated with our May 2017 corporate restructuring (in thousands): Year ended December 31, 2017 2016 2015 Research and development $ 2,862 $ 5,458 $ 8,075 Research and development-restructuring related adjustments (1,399 ) — — General and administrative 3,500 7,414 7,293 General and administrative-restructuring related adjustments 2,679 — — Total $ 7,642 $ 12,872 $ 15,368

Income Taxes (Tables)

Income Taxes (Tables)	12 Months Ended
	Dec. 31, 2017
Income Tax Disclosure [Abstract]
Schedule of Components of Income Tax Expense (Benefit)	The following table summarizes the components of our income tax (benefit) expense (in thousands): Year ended December 31, 2017 2016 2015 Current: Federal $ (143 ) $ — $ — State 1 1 1 (142 ) 1 1 Deferred: Federal (55 ) (5 ) (17 ) State — — (2 ) (55 ) (5 ) (19 ) Income tax (benefit) $ (197 ) $ (4 ) $ (18 )
Schedule of Effective Income Tax Rate Reconciliation	The following is a reconciliation of the expected statutory federal income tax provision to our actual income tax provision (in thousands): Year ended December 31, 2017 2016 2015 Expected income tax benefit at federal statutory tax rate $ (24,515 ) $ (27,826 ) $ (18,960 ) State income taxes, net of federal benefit 1 (1,152 ) (1,580 ) Tax credits (5,151 ) (5,447 ) (5,039 ) Change in fair value of convertible note payable — — 616 Change in valuation allowance (8,705 ) 31,990 23,216 Prior year true-up 1 (1,320 ) 110 Stock compensation 1,135 2,458 1,161 Reserve for uncertain tax positions 311 1,314 254 Tax Cuts and Jobs Act rate change 36,249 — — Other 477 (21 ) 204 Income tax (benefit) $ (197 ) $ (4 ) $ (18 )
Schedule of Deferred Tax Assets and Liabilities	The following table summarizes the significant components of our deferred tax assets and liabilities (in thousands): December 31, 2017 2016 Deferred tax assets: Net operating loss carryovers $ 66,549 $ 70,739 Research and development and other tax credits 29,702 22,613 Deferred revenue 419 735 Stock compensation expense 4,238 5,664 Other 2,196 4,679 Total deferred tax assets 103,104 104,430 Total deferred tax liabilities (408 ) (799 ) Net deferred tax asset 102,696 103,631 Valuation allowance (102,641 ) (103,631 ) Net deferred tax asset $ 55 $ —
Summary of Income Tax Contingencies	The following table summarizes the changes in the amount of our unrecognized tax benefits (in thousands): Year Ended December 31, 2017 2016 2015 Beginning balance of unrecognized tax benefits $ 5,632 $ 2,298 $ 1,853 (Decrease) increase for prior year tax positions (2,466 ) 1,991 (250 ) Increase for current year tax positions 1,255 1,343 695 Total $ 4,421 $ 5,632 $ 2,298

Selected Quarterly Financial 33

Selected Quarterly Financial Data (Unaudited) (Tables)	12 Months Ended
	Dec. 31, 2017
Quarterly Financial Information Disclosure [Abstract]
Schedule of Quarterly Financial Information	Summarized quarterly data for 2017 and 2016 are as follows (in thousands, except per share data): For the quarters ending March 31 June 30 September 30 December 31 2017 Total revenues $ 18 $ 18 $ 18 $ 18 Total operating expenses 19,711 21,335 15,433 13,724 Net loss (20,021 ) (21,608 ) (15,828 ) (14,448 ) Net loss per share, basic and diluted (1) $ (0.38 ) $ (0.41 ) $ (0.18 ) $ (0.14 ) 2016 Total revenues $ 489 $ 483 $ 204 $ 18 Total operating expenses 21,867 21,671 19,396 19,762 Net loss (21,207 ) (21,090 ) (19,519 ) (20,020 ) Net loss per share, basic and diluted (1) $ (0.40 ) $ (0.40 ) $ (0.37 ) $ (0.38 ) (1) Net loss per share is computed independently for each of the quarters presented. Therefore, the sum of the quarterly per-share calculations will not necessarily equal the annual per share calculation.

The Business, Basis of Presen34

The Business, Basis of Presentation and Summary of Significant Accounting Policies - Narrative (Details) - USD ($) $ in Millions	Dec. 31, 2017	Dec. 31, 2016
Accounting Policies [Abstract]
Prepaid materials	$ 4.8	$ 5.6

The Business, Basis of Presen35

The Business, Basis of Presentation and Summary of Significant Accounting Policies - Property and Equipment (Details)	12 Months Ended
	Dec. 31, 2017
Minimum
Property, Plant and Equipment [Line Items]
Useful life, in years	3 years
Maximum
Property, Plant and Equipment [Line Items]
Useful life, in years	5 years

The Business, Basis of Presen36

The Business, Basis of Presentation and Summary of Significant Accounting Policies - Intangibles (Details)	12 Months Ended
	Dec. 31, 2017
Licenses
Finite-Lived Intangible Assets [Line Items]
Finite-lived intangible asset, useful life	10 years
Weighted Average | Patents
Finite-Lived Intangible Assets [Line Items]
Finite-lived intangible asset, useful life	9 years

The Business, Basis of Presen37

The Business, Basis of Presentation and Summary of Significant Accounting Policies - Segment Reporting (Details)	12 Months Ended
	Dec. 31, 2017segment
Accounting Policies [Abstract]
Number of operating segments	1

The Business, Basis of Presen38

The Business, Basis of Presentation and Summary of Significant Accounting Policies - Liquidity (Details) $ in Millions	12 Months Ended
	Dec. 31, 2017USD ($)
Accounting Policies [Abstract]
Financing from sale proceeds, debt, and agreement revenues	$ 406
Cash and cash equivalents, and short-term investments	$ 60.1

The Business, Basis of Presen39

The Business, Basis of Presentation and Summary of Significant Accounting Policies - Corporate Restructuring (Details) - USD ($) $ in Millions	1 Months Ended
	Jun. 30, 2017	May 31, 2017
Accounting Policies [Abstract]
Workforce reduction, commitment, rate		30.00%
Severance costs	$ 3.2
Employee benefits and share-based compensation, noncash	$ 1.3

The Business, Basis of Presen40

The Business, Basis of Presentation and Summary of Significant Accounting Policies - Recent Accounting Pronouncements (Details) - USD ($)	3 Months Ended	12 Months Ended
	Mar. 31, 2017	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Excess tax benefit amount		$ (7,700,000)
Stock-based compensation expenses		7,642,000	$ 12,872,000	$ 15,368,000
Restricted cash		0
Accounting Standard Update 2016-18
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Restricted cash		$ 1,300,000
Accounting Standards Update 2016-09
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Stock-based compensation expenses	$ 600,000
Additional paid-in capital | Accounting Standards Update 2016-09
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Cumulative effect of new accounting principle	$ 600,000

Net Loss Per Share - Potentiall

Net Loss Per Share - Potentially Dilutive Securities Not Included in Calculation of Diluted Net Loss per Share (Details) - shares	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Earnings Per Share [Abstract]
Potentially dilutive securities not included in calculation of diluted net loss per share (in shares)	2,968,879	5,553,210	1,674,119

Investments - Summary of Short-

Investments - Summary of Short-Term Investments (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016
Investment [Line Items]
Maturity weighted average period, in years (less than)	1 year
Amortized cost	$ 46,632	$ 61,236
Unrealized Gains	0	12
Unrealized Losses	(77)	(78)
Estimated fair value	$ 46,555	$ 61,170
Corporate debt securities
Investment [Line Items]
Maturity (or less) (in years)	1 year	2 years
Amortized cost	$ 32,922	$ 49,185
Unrealized Gains	0	12
Unrealized Losses	(55)	(77)
Estimated fair value	$ 32,867	$ 49,120
Certificates of deposit
Investment [Line Items]
Maturity (or less) (in years)	1 year	1 year
Amortized cost	$ 8,216	$ 9,291
Unrealized Gains	0	0
Unrealized Losses	0	0
Estimated fair value	$ 8,216	$ 9,291
U.S. treasury securities
Investment [Line Items]
Maturity (or less) (in years)	1 year	1 year
Amortized cost	$ 3,996	$ 1,001
Unrealized Gains	0	0
Unrealized Losses	(18)	(1)
Estimated fair value	$ 3,978	$ 1,000
Debt securities of U.S. government-sponsored agencies
Investment [Line Items]
Maturity (or less) (in years)	1 year	1 year
Amortized cost	$ 1,498	$ 512
Unrealized Gains	0	0
Unrealized Losses	(4)	0
Estimated fair value	$ 1,494	$ 512
Commercial paper
Investment [Line Items]
Maturity (or less) (in years)		1 year
Amortized cost		$ 1,247
Unrealized Gains		0
Unrealized Losses		0
Estimated fair value		$ 1,247

Fair Value Measurements - Fair

Fair Value Measurements - Fair Value Hierarchy for Assets and Liabilities Measured at Fair Value on Recurring Basis (Details) - USD ($) $ in Thousands	Dec. 31, 2017	Dec. 31, 2016
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	$ 57,402	$ 74,748
Cash equivalents
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	10,847	13,578
Corporate debt securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	32,867	49,120
Certificates of deposit
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	8,216	9,291
U.S. treasury securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	3,978	1,000
Debt securities of U.S. government-sponsored agencies
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	1,494	512
Commercial paper
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis		1,247
Fair Value, Inputs, Level 1
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	10,847	13,578
Fair Value, Inputs, Level 1 | Cash equivalents
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	10,847	13,578
Fair Value, Inputs, Level 1 | Corporate debt securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	0	0
Fair Value, Inputs, Level 1 | Certificates of deposit
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	0	0
Fair Value, Inputs, Level 1 | U.S. treasury securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	0	0
Fair Value, Inputs, Level 1 | Debt securities of U.S. government-sponsored agencies
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	0	0
Fair Value, Inputs, Level 1 | Commercial paper
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis		0
Fair Value, Inputs, Level 2
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	46,555	61,170
Fair Value, Inputs, Level 2 | Cash equivalents
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	0	0
Fair Value, Inputs, Level 2 | Corporate debt securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	32,867	49,120
Fair Value, Inputs, Level 2 | Certificates of deposit
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	8,216	9,291
Fair Value, Inputs, Level 2 | U.S. treasury securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	3,978	1,000
Fair Value, Inputs, Level 2 | Debt securities of U.S. government-sponsored agencies
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	1,494	512
Fair Value, Inputs, Level 2 | Commercial paper
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis		1,247
Fair Value, Inputs, Level 3
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	0	0
Fair Value, Inputs, Level 3 | Cash equivalents
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	0	0
Fair Value, Inputs, Level 3 | Corporate debt securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	0	0
Fair Value, Inputs, Level 3 | Certificates of deposit
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	0	0
Fair Value, Inputs, Level 3 | U.S. treasury securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	0	0
Fair Value, Inputs, Level 3 | Debt securities of U.S. government-sponsored agencies
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis	$ 0	0
Fair Value, Inputs, Level 3 | Commercial paper
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets measured at fair value on a recurring basis		$ 0

Strategic Alliances and Colla44

Strategic Alliances and Collaborations - Revenue from Strategic Alliances (Details) - USD ($) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2016	Sep. 30, 2016	Jun. 30, 2016	Mar. 31, 2016	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Revenue from External Customer [Line Items]
Total revenues	$ 18	$ 18	$ 18	$ 18	$ 18	$ 204	$ 483	$ 489	$ 72	$ 1,194	$ 20,759
Strategic Alliances and Collaborations
Revenue from External Customer [Line Items]
Total revenues									72	1,194	20,759
Strategic Alliances and Collaborations | Sanofi
Revenue from External Customer [Line Items]
Total revenues									72	72	71
Strategic Alliances and Collaborations | AstraZeneca
Revenue from External Customer [Line Items]
Total revenues									0	1,122	18,871
Strategic Alliances and Collaborations | Biogen
Revenue from External Customer [Line Items]
Total revenues									$ 0	$ 0	$ 1,817

Strategic Alliances and Colla45

Strategic Alliances and Collaborations (Details) $ / shares in Units, $ in Thousands

1 Months Ended

8 Months Ended

12 Months Ended

Jul. 31, 2017USD ($)

Dec. 31, 2015USD ($)

Sep. 30, 2015USD ($)

May 31, 2015USD ($)

Mar. 31, 2015USD ($)

Jan. 31, 2015USD ($)

Aug. 31, 2014USD ($)

Feb. 28, 2014USD ($)$ / sharesshares

Jul. 31, 2013USD ($)

Oct. 31, 2012USD ($)$ / sharesshares

Aug. 31, 2012agreement

Jul. 31, 2010target

Jan. 31, 2014USD ($)

Dec. 31, 2017USD ($)shares

Dec. 31, 2016USD ($)shares

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Common stock, shares issued | shares

103,955,147

52,924,805

Common stock value

$ 104

$ 53

Sanofi

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Number of collaborative areas granted | target

4

Upfront payment received

$ 400

Sanofi | Private Placement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Common stock, shares issued | shares

1,303,780

Price per share (in dollars per share) | $ / shares

$ 7.67

Common stock value

$ 10,000

Restriction period in which Alliances could not sell, transfer, make any short sale of, or grant any option for the sale of any common stock

12 months

Sanofi | Development Commercialization And License Agreement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Initial upfront option payment

$ 2,500

$ 2,500

Upfront payment non-creditable portion recognized

$ 1,250

Deferred revenue creditable against future milestones

$ 1,250

$ 1,250

$ 1,250

Sanofi | Minimum | United States

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Royalties based on percentage of net sales

10.00%

Sanofi | Minimum | Outside of the US

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Royalties based on percentage of net sales

10.00%

Sanofi | Maximum | United States

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Royalties based on percentage of net sales

20.00%

Sanofi | Maximum | Outside of the US

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Royalties based on percentage of net sales

20.00%

Sanofi | Clinical

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Expected revenue through milestone payments

$ 15,000

Sanofi | Common Stock Purchase Agreement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Deferred revenue

$ 100

Deferred revenue recognition period

2 years

Sanofi | Proof-of-Concept Trial

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Expected revenue through milestone payments

$ 101,800

Sanofi | Regulatory and Commercialization Milestones

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Expected revenue through milestone payments

$ 300,000

AstraZeneca

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Number of collaborative areas granted | agreement

3

Initial upfront option payment

$ 3,000

Common stock, shares issued | shares

6,250,000

Price per share (in dollars per share) | $ / shares

$ 4

Restriction period in which Alliances could not sell, transfer, make any short sale of, or grant any option for the sale of any common stock

365 days

Upfront payment received

$ 4,300

Expected term of research and development plan

4 years

AstraZeneca | Preclinical

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Milestone payments, earned

$ 2,500

AstraZeneca | Clinical

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Milestone payments, earned

$ 10,000

Biogen

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Initial upfront option payment

$ 2,000

Biogen | Research and development

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Milestone payments, earned

$ 300

$ 300

$ 100

Property and Equipment, net (De

Property and Equipment, net (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Property, Plant and Equipment [Line Items]
Property, Plant and Equipment, Gross	$ 17,967	$ 19,633
Less accumulated depreciation and amortization	(8,259)	(7,803)
Property and equipment, net	9,708	11,830
Depreciation and amortization expense	2,524	2,276	$ 1,591
Laboratory equipment
Property, Plant and Equipment [Line Items]
Property, Plant and Equipment, Gross	8,430	7,932
Computer equipment and software
Property, Plant and Equipment [Line Items]
Property, Plant and Equipment, Gross	281	265
Furniture and fixtures
Property, Plant and Equipment [Line Items]
Property, Plant and Equipment, Gross	706	706
Leasehold improvements
Property, Plant and Equipment [Line Items]
Property, Plant and Equipment, Gross	8,550	10,469
Construction in progress
Property, Plant and Equipment [Line Items]
Property, Plant and Equipment, Gross	$ 0	$ 261

Intangible Assets, net (Details

Intangible Assets, net (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Finite-Lived Intangible Assets [Line Items]
Finite-lived intangible assets, gross	$ 1,250	$ 1,481
Accumulated amortization	(475)	(466)
Intangibles, net	775	1,015
Intangible asset amortization	100	100	$ 100
Finite-lived intangible assets, amortization expense, next 12 months	100
Finite-lived intangible assets, amortization expense, year two	100
Finite-lived intangible assets, amortization expense, year three	100
Finite-lived intangible assets, amortization expense, year four	100
Finite-lived intangible assets, amortization expense, year five	100
Patents
Finite-Lived Intangible Assets [Line Items]
Finite-lived intangible assets, gross	871	1,102
Licenses
Finite-Lived Intangible Assets [Line Items]
Finite-lived intangible assets, gross	$ 379	$ 379

Commitments and Contingencies48

Commitments and Contingencies (Details) - USD ($)	1 Months Ended	12 Months Ended
	Jul. 31, 2015	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015	Aug. 31, 2015
Other Commitments [Line Items]
Term of lease	96 months
Tenant incentive					$ 1,400,000
Restricted cash		$ 0
Tenant improvement allowance used	$ 8,500,000	8,200,000
Unused tenant improvement		300,000
Rent expense		1,400,000	$ 1,200,000	$ 600,000
Deferred rent, less current portion		$ 8,072,000	8,840,000
Renewal term		5 years
Prior Lease
Other Commitments [Line Items]
Other liabilities, current			200,000
Other Noncurrent Liabilities
Other Commitments [Line Items]
Deferred rent, less current portion		$ 9,300,000	10,100,000
Other Noncurrent Liabilities | Prior Lease
Other Commitments [Line Items]
Deferred rent, less current portion			$ 0

Commitments and Contingencies -

Commitments and Contingencies - Summary of Future Annual Minimum Lease Payments for Operating Leases (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Commitments and Contingencies Disclosure [Abstract]
Rent expense	$ 1,400	$ 1,200	$ 600
Operating Leases, Future Minimum Payments Due, Fiscal Year Maturity [Abstract]
Operating Leases, Future Minimum Payments Due in 2017	2,576
Operating Leases, Future Minimum Payments, Due in 2018	2,654
Operating Leases, Future Minimum Payments, Due in 2019	2,733
Operating Leases, Future Minimum Payments, Due in 2020	2,815
Operating Leases, Future Minimum Payments, Due in 2021	2,901
Operating Leases, Future Minimum Payments, Due Thereafter	3,991
Operating Leases, Future Minimum Payments Due	$ 17,670

Convertible Note Payable - Addi

Convertible Note Payable - Additional Information (Details) - USD ($) $ / shares in Units, $ in Thousands	Jan. 29, 2015	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015	Oct. 31, 2012
Debt Instrument [Line Items]
Number of shares resulting from conversion of note payable	1,356,738
Conversion price per share (dollars per share)	$ 4
Loss from valuation of convertible note payable		$ 0	$ 0	$ (1,811)
Convertible Debt | GSK
Debt Instrument [Line Items]
Notes payable					$ 5,400

Term Loan (Details)

Term Loan (Details)	Jun. 22, 2016USD ($)	Jun. 17, 2016USD ($)loan	Dec. 31, 2017USD ($)	Dec. 31, 2016USD ($)	Dec. 31, 2015USD ($)	Mar. 31, 2017USD ($)
Debt Instrument [Line Items]
Proceeds from borrowing under term loan			$ 0	$ 19,768,000	$ 0
Term loan, less current portion and debt issuance costs			$ 0	$ 19,802,000
Debt Financing Agreement
Debt Instrument [Line Items]
Maximum borrowing capacity		$ 30,000,000
Number of term loans | loan		2
Period for principal and interest payments		24 months
Stated interest rate, percentage		8.51%
Prepayment fee, option one			2.00%
Prepayment fee, option two			1.00%
Debt extinguishment fee			5.50%
Term loan, less current portion and debt issuance costs			$ 20,000,000
Amounts borrowed			20,000,000
Deferred finance costs			$ 200,000
Debt instrument effective rate			8.98%
Debt Financing Agreement | London Interbank Offered Rate (LIBOR)
Debt Instrument [Line Items]
Basis spread on variable rate, percentage		0.44%
Debt Financing Agreement Tranche A
Debt Instrument [Line Items]
Maximum borrowing capacity		$ 20,000,000
Proceeds from borrowing under term loan	$ 20,000,000
Term loan, less current portion and debt issuance costs			$ 20,000,000
Debt Financing Agreement Tranche B
Debt Instrument [Line Items]
Maximum borrowing capacity		$ 10,000,000
Long-term Line of Credit						$ 0

Term Loan - Future Principal Pa

Term Loan - Future Principal Payments (Details) - USD ($) $ in Thousands	Dec. 31, 2017	Dec. 31, 2016
Debt Instrument [Line Items]
Long-term Debt	$ 0	$ 19,802
Debt Financing Agreement Tranche A
Debt Instrument [Line Items]
Future Repayments of Principal, 2018	5,000
Future Repayments of Principal, 2019	10,000
Future Repayments of Principal, 2020	5,000
Long-term Debt	$ 20,000

Common Stock and Stockholders53

Common Stock and Stockholders' Equity (Details 1) $ / shares in Units, $ in Millions	1 Months Ended
	Jul. 31, 2017USD ($)$ / sharesshares	Dec. 31, 2017voteshares	Dec. 31, 2016shares	Dec. 31, 2015shares	Dec. 31, 2014shares
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Common stock voting rights per share (vote) | vote		1
Common stock options outstanding (in shares)		10,648,523	8,931,000
Total common shares reserved for future issuance (in shares)		13,430,899
Public Offering
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Number of shares issued	50,600,000
Sale of stock (usd per share) | $ / shares	$ 0.91
Consideration received | $	$ 43
Common stock available for future grant under the 2012 Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Restricted stock units outstanding		649,590
Inducement Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Restricted stock units outstanding		41,948
Common stock available for future purchase under the 2012 Employee Stock Purchase Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Restricted stock units outstanding		1,675,110
Common stock
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares outstanding (in shares)		103,955,147	52,924,805	52,669,266	48,944,530
Restricted Stock Units (RSUs)
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Share-based Compensation Arrangement by Share-based Payment Award, Non-Option Equity Instruments, Outstanding, Number		415,728

Common Stock and Stockholders54

Common Stock and Stockholders' Equity - Stock Option Activity (Details) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2017USD ($)$ / sharesshares
Number of options
Beginning number of options (in shares), outstanding | shares	8,931,000
Number of options, Granted (in shares) | shares	5,126,000
Number of options, Exercised (in shares) | shares	(11,000)
Number of options, Canceled/forfeited/expired (in shares) | shares	(3,397,000)
End number of options (in shares), outstanding | shares	10,648,523
Number of options, Exercisable (in shares) | shares	5,099,000
Weighted average exercise price
Beginning, Weighted average exercise price, Options outstanding (in dollars per share) | $ / shares	$ 6.70
Weighted average exercise price, Granted (in dollars per share) | $ / shares	1.35
Weighted average exercise price, Exercised (in dollars per share) | $ / shares	0.38
Weighted average exercise price, Canceled/forfeited/expired (in dollars per share) | $ / shares	5.75
Ending, Weighted average exercise price, Options outstanding (in dollars per share) | $ / shares	4.44
Weighted average exercise price, Exercisable (in dollars per share) | $ / shares	$ 6.34
Weighted average remaining contractual term
Weighted average remaining contractual term, Options outstanding	6 years 5 months 16 days
Weighted average remaining contractual term, Exercisable	3 years 7 months 2 days
Aggregate intrinsic value
Aggregate intrinsic value, Options outstanding | $	$ 227
Aggregate intrinsic value, Exercisable | $	$ 119

Common Stock and Stockholders55

Common Stock and Stockholders' Equity (Narrative 2) (Details) - USD ($) $ / shares in Units, $ in Thousands	Jul. 17, 2015	Oct. 31, 2012	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015	Dec. 31, 2017
Class of Stock [Line Items]
Weighted average grant date fair value of employee stock options (in dollars per share)			$ 1	$ 3.47	$ 7.47
Total intrinsic value of stock options exercised			$ 100	$ 200	$ 21,400
Proceeds from stock options exercised (less than in 2017)			4	$ 310	$ 6,680
Compensation cost related to non-vested awards not yet recognized			$ 5,100			$ 5,100
Weighted-average recognition period of compensation cost related to non-vested awards not yet recognized			2 years 6 months
Restricted Stock Units (RSUs)
Class of Stock [Line Items]
Share granted (in shares)			415,728
Weighted average grant date fair value (usd per shares)			$ 0.89
Compensation cost related to non-vested awards not yet recognized			$ 300			$ 300
Weighted-average recognition period of compensation cost related to non-vested awards not yet recognized			7 months 6 days
Employee Stock Purchase Plan 2012
Class of Stock [Line Items]
Percentage of participants eligible compensation		15.00%
Shares issued (in shares)			419,342			740,526
Common stock shares reserved for future issuance and authorized for purchase			1,675,110			1,675,110
Option One - at inception of enrollment period
Class of Stock [Line Items]
Percentage of fair market value of common stock		85.00%
Option Two - at applicable purchase date
Class of Stock [Line Items]
Percentage of fair market value of common stock		85.00%
Inducement Plan
Class of Stock [Line Items]
Common stock shares reserved for future issuance and authorized for purchase	1,000,000		41,948			41,948
Vesting period	4 years
Awards vesting, first anniversary	25.00%
Remaining vesting period after initial 25%, on a monthly basis (months)	36 months
Maximum | Inducement Plan
Class of Stock [Line Items]
Award expiration period	10 years

Common Stock and Stockholders56

Common Stock and Stockholders' Equity - Assumptions Used to Estimate Fair Value of Stock Options and Performance Stock and Employee Stock Purchase Plan (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015	Mar. 31, 2017
Stock options
Weighted average assumptions
Risk-free interest rate	2.00%	1.50%	1.80%
Volatility	89.40%	82.70%	78.90%
Dividend yield	0.00%	0.00%	0.00%
Expected term (years)	6 years 1 month 6 days	6 years	6 years 1 month 6 days
Performance stock options
Weighted average assumptions
Risk-free interest rate	2.10%	1.40%	1.80%
Volatility	89.20%	82.40%	76.70%
Dividend yield	0.00%	0.00%	0.00%
Expected term (years)	5 years 8 months 12 days	5 years 10 months 24 days	6 years
Common stock available for future purchase under the 2012 Employee Stock Purchase Plan
Weighted average assumptions
Risk-free interest rate	0.90%	0.50%	0.10%
Volatility	105.60%	93.70%	76.10%
Dividend yield	0.00%	0.00%	0.00%
Expected term (years)	6 months	6 months	6 months
Accounting Standards Update 2016-09 | Additional paid-in capital
Weighted average assumptions
Cumulative effect of new accounting principle				$ 0.6

Common Stock and Stockholders57

Common Stock and Stockholders' Equity - Schedule of Compensation Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Employee Service Share-based Compensation, Allocation of Recognized Period Costs [Line Items]
Stock-based compensation expenses	$ 7,642	$ 12,872	$ 15,368
Research and development
Employee Service Share-based Compensation, Allocation of Recognized Period Costs [Line Items]
Stock-based compensation expenses	2,862	5,458	8,075
Research and development-restructuring related adjustments
Employee Service Share-based Compensation, Allocation of Recognized Period Costs [Line Items]
Stock-based compensation expenses	(1,399)	0	0
General and administrative
Employee Service Share-based Compensation, Allocation of Recognized Period Costs [Line Items]
Stock-based compensation expenses	3,500	7,414	7,293
General and administrative-restructuring related adjustments
Employee Service Share-based Compensation, Allocation of Recognized Period Costs [Line Items]
Stock-based compensation expenses	$ 2,679	$ 0	$ 0

Defined Contribution Plan (Deta

Defined Contribution Plan (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Retirement Benefits [Abstract]
Defined contribution minimum age requirement of eligible employees	18 years
Maximum 401 (K) plan contribution rates as percentage of employees compensation	50.00%
Rate of contribution to 401(K) plan as a percentage of employees contribution	25.00%
Percentage of employee's earnings the company may contribute to the 401(k) plan	6.00%
Employer contribution to 401(k) plan	$ 0.1	$ 0.2	$ 0.1

Income Taxes - Components of In

Income Taxes - Components of Income Tax (Benefit) Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Current:
Federal	$ (143)	$ 0	$ 0
State	1	1	1
Current Income Tax Expense (Benefit), total	(142)	1	1
Deferred:
Federal	(55)	(5)	(17)
State	0	0	(2)
Deferred Income Tax Expense (Benefit), total	(55)	(5)	(19)
Income tax (benefit)	$ (197)	$ (4)	$ (18)

Income Taxes - Reconciliation o

Income Taxes - Reconciliation of Expected Statutory Federal Income Tax Provision to Actual Income Tax Provision (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Effective Income Tax Rate Reconciliation, Amount [Abstract]
Expected income tax benefit at federal statutory tax rate	$ (24,515)	$ (27,826)	$ (18,960)
State income taxes, net of federal benefit	1	(1,152)	(1,580)
Tax credits	(5,151)	(5,447)	(5,039)
Change in fair value of convertible note payable	0	0	616
Change in valuation allowance	(8,705)	31,990	23,216
Prior year true-up	1	(1,320)	110
Stock compensation	1,135	2,458	1,161
Reserve for uncertain tax positions	311	1,314	254
Tax Cuts and Jobs Act rate change	36,249	0	0
Other	477	(21)	204
Income tax (benefit)	$ (197)	$ (4)	$ (18)

Income Taxes - Components of De

Income Taxes - Components of Deferred Tax Assets and Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2017	Dec. 31, 2016
Deferred tax assets:
Net operating loss carryovers	$ 66,549	$ 70,739
Research and development and other tax credits	29,702	22,613
Deferred revenue	419	735
Stock compensation expense	4,238	5,664
Other	2,196	4,679
Total deferred tax assets	103,104	104,430
Total deferred tax liabilities	(408)	(799)
Net deferred tax asset	102,696	103,631
Valuation allowance	(102,641)	(103,631)
Net deferred tax asset	$ 55	$ 0

Income Taxes - Narrative (Detai

Income Taxes - Narrative (Details) - USD ($)	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015	Dec. 31, 2014
Operating Loss Carryforwards [Line Items]
Net deferred tax assets	$ 102,696,000	$ 103,631,000
Net operating loss carryovers	66,549,000	70,739,000
Excess tax benefit amount	(7,700,000)
Federal Alternative Minimum Tax Credit carryforwards	$ 100,000
Net operating loss carryforward limitation on use percentage ownership change minimum	50.00%
Unrecognized tax benefits	$ 4,421,000	5,632,000	$ 2,298,000	$ 1,853,000
Unrecognized tax benefits that would impact effective tax rate	3,700,000
Tax penalties and interest	0	$ 0	$ 0
Deferred tax asset, income tax (benefit) expense	(36,200,000)
Internal Revenue Service (IRS)
Operating Loss Carryforwards [Line Items]
Net operating loss carryovers	265,800,000
Internal Revenue Service (IRS) | Research Tax Credit Carryforward
Operating Loss Carryforwards [Line Items]
Research and development tax credits carryforward	27,500,000
California
Operating Loss Carryforwards [Line Items]
Net operating loss carryovers	146,300,000
California | Research Tax Credit Carryforward
Operating Loss Carryforwards [Line Items]
Research and development tax credits carryforward	$ 8,100,000

Income Taxes - Changes in Amoun

Income Taxes - Changes in Amount of Unrecognized Tax Benefits (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Reconciliation of Unrecognized Tax Benefits, Excluding Amounts Pertaining to Examined Tax Returns [Roll Forward]
Beginning balance of unrecognized tax benefits	$ 5,632	$ 2,298	$ 1,853
(Decrease) increase for prior year tax positions	(2,466)	1,991	(250)
Increase for current year tax positions	1,255	1,343	695
Total	$ 4,421	$ 5,632	$ 2,298

Related Party Transactions (Det

Related Party Transactions (Details) - USD ($)	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Sanofi
Related Party Transaction [Line Items]
Expenses incurred for services performed or out-of-pocket expenses (less than in 2017)	$ 100,000	$ 900,000	$ 400,000
Alnylam
Related Party Transaction [Line Items]
Potential milestone payments to related party	$ 33,000,000

Selected Quarterly Financial 65

Selected Quarterly Financial Data (Unaudited) (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2016	Sep. 30, 2016	Jun. 30, 2016	Mar. 31, 2016	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Quarterly Financial Information Disclosure [Abstract]
Total revenues	$ 18	$ 18	$ 18	$ 18	$ 18	$ 204	$ 483	$ 489	$ 72	$ 1,194	$ 20,759
Total operating expenses	13,724	15,433	21,335	19,711	19,762	19,396	21,671	21,867	70,203	82,696	75,517
Net loss	$ (14,448)	$ (15,828)	$ (21,608)	$ (20,021)	$ (20,020)	$ (19,519)	$ (21,090)	$ (21,207)	$ (71,905)	$ (81,836)	$ (55,748)
Basic and diluted net loss per share (dollars per share)	$ (0.14)	$ (0.18)	$ (0.41)	$ (0.38)					$ (0.96)	$ (1.55)	$ (1.08)
Basic net loss per share (dollars per share)					$ (0.38)	$ (0.37)	$ (0.40)	$ (0.40)