Regulus Therapeutics (RGLS) 10-K 18 Mar 19 2018 FY Annual report Financial data

Document and Entity Information

Document and Entity Information - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2018	Mar. 08, 2019	Jun. 29, 2018
Document And Entity Information [Abstract]
Document Type	10-K
Amendment Flag	false
Document Period End Date	Dec. 31, 2018
Document Fiscal Year Focus	2018
Document Fiscal Period Focus	FY
Trading Symbol	RGLS
Entity Registrant Name	REGULUS THERAPEUTICS INC.
Entity Central Index Key	0001505512
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			$ 66.8
Entity Common Stock, Shares Outstanding		10,743,922
Entity Small Business	true
Entity Emerging Growth Company	false
Entity Shell Company	false

Balance Sheets

Balance Sheets - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Current assets:
Cash and cash equivalents	$ 13,935	$ 13,519
Short-term investments	0	46,555
Contract and other receivables	26	373
Prepaid materials, net	4,194	4,783
Prepaid expenses and other current assets	1,140	1,506
Total current assets	19,295	66,736
Property and equipment, net	7,806	9,708
Intangibles, net	500	775
Other assets	326	590
Total assets	27,927	77,809
Current liabilities:
Accounts payable	1,714	5,743
Accrued liabilities	4,184	4,941
Accrued compensation	1,601	1,985
Current portion of term loan, less debt issuance costs	16,575	19,859
Current portion of contract liabilities	2,572	72
Total current liabilities	26,646	32,600
Contract liabilities, less current portion	6	1,921
Deferred rent, less current portion	6,820	8,072
Other long-term liabilities	309	0
Total liabilities	33,781	42,593
Commitments and Contingencies (Note 8)
Stockholders’ equity:
Common stock, $0.001 par value; 200,000,000 shares authorized, 8,818,019 and 8,662,435 shares issued and outstanding at December 31, 2018 and 2017, respectively	9	9
Additional paid-in capital	386,860	381,199
Accumulated other comprehensive loss	0	(134)
Accumulated deficit	(392,723)	(345,858)
Total stockholders’ (deficit) equity	(5,854)	35,216
Total liabilities and stockholders’ (deficit) equity	$ 27,927	$ 77,809

Balance Sheets (Parenthetical)

Balance Sheets (Parenthetical) - $ / shares	Dec. 31, 2018	Dec. 31, 2017
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	8,818,019	8,662,435
Common stock, shares outstanding	8,818,019	8,662,435

Statements of Operations and Co

Statements of Operations and Comprehensive Loss - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Revenues:
Total revenues	$ 72	$ 72	$ 1,194
Operating expenses:
Research and development	33,975	53,192	64,305
General and administrative	12,860	17,011	18,391
Total operating expenses	46,835	70,203	82,696
Loss from operations	(46,763)	(70,131)	(81,502)
Other income (expense):
Interest and other income	459	752	844
Interest and other expense	(2,343)	(2,723)	(1,182)
Loss before income taxes	(48,647)	(72,102)	(81,840)
Income tax (expense) benefit	(62)	197	4
Net loss	(48,709)	(71,905)	(81,836)
Other comprehensive loss:
Unrealized (loss) gain on short-term investments, net	0	(11)	10
Comprehensive loss	$ (48,709)	$ (71,916)	$ (81,826)
Net loss per share - basic and diluted (in dollars per share)	$ (5.59)	$ (11.47)	$ (18.59)
Weighted average shares used to compute basic and diluted net loss per share (in shares)	8,718,563	6,269,758	4,401,701
Strategic Alliances and Collaborations
Revenues:
Total revenues	$ 72	$ 72	$ 1,194

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, 2015		4,388,625
Beginning balance at Dec. 31, 2015	$ 124,078	$ 4	$ 315,722	$ (133)	$ (191,515)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Issuance of common stock upon exercise of options (in shares)		7,478
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)		13,806
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		4,409,909
Ending balance at Dec. 31, 2016	56,075	$ 4	329,545	(123)	(273,351)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	(20,021)
Beginning balance (in shares) at Dec. 31, 2016		4,409,909
Beginning balance at Dec. 31, 2016	56,075	$ 4	329,545	(123)	(273,351)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Issuance of common stock upon exercise of options (in shares)		915
Issuance of common stock upon exercise of options	4		4
Stock-based compensation expense	7,642		7,642
Issuance of common stock under Employee Stock Purchase Plan (in shares)		34,945
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 $292 of offering costs (in shares)		4,216,666
Issuance of common stock, net of $292 of offering costs	42,992	$ 5	42,987
Net loss	(71,905)				(71,905)
Ending balance (in shares) at Dec. 31, 2017		8,662,435
Ending balance at Dec. 31, 2017	35,216	$ 9	381,199	(134)	(345,858)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Issuance of common stock upon exercise of options (in shares)		328
Issuance of common stock upon exercise of options	1		1
Issuance of common stock upon vesting of restricted stock units (in shares)		128,840
Stock-based compensation expense	5,441		5,441
Issuance of common stock under Employee Stock Purchase Plan (in shares)		26,416
Issuance of common stock under Employee Stock Purchase Plan	219		219
Unrealized gain (loss) on short-term investments	0
Unrealized gain on short-term investments	134			134
Net loss	(48,709)				(48,709)
Ending balance (in shares) at Dec. 31, 2018		8,818,019
Ending balance at Dec. 31, 2018	$ (5,854)	$ 9	$ 386,860	$ 0	$ (392,723)

Statements of Stockholders' E_2

Statements of Stockholders' Equity (Parentheticals) $ in Thousands	12 Months Ended
	Dec. 31, 2018USD ($)
Statement of Stockholders' Equity [Abstract]
Issuance of common stock, offering costs	$ 292
Reverse stock split ratio	0.08333

Statements of Cash Flows

Statements of Cash Flows - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Operating activities
Net loss	$ (48,709)	$ (71,905)	$ (81,836)
Adjustments to reconcile net loss to net cash used in operating activities
Depreciation and amortization expense	2,262	2,524	2,276
Stock-based compensation	5,441	7,642	12,872
Amortization of premium on investments, net	148	349	666
Other	756	600	1,043
Change in operating assets and liabilities:
Contracts and other receivables	347	1,284	8,364
Prepaid materials	134	394	(616)
Prepaid expenses and other assets	630	2,369	(778)
Accounts payable	(4,029)	(65)	3,123
Accrued liabilities	(1,370)	(492)	(871)
Accrued compensation	(384)	(333)	(74)
Contract liabilities	2,428	(72)	(1,194)
Deferred rent and other liabilities	(927)	(1,068)	143
Net cash used in operating activities	(43,273)	(58,773)	(56,882)
Investing activities
Purchases of short-term investments	0	(55,686)	(65,110)
Sales and maturities of short-term investments	46,541	69,941	101,387
Purchases of property and equipment	(22)	(303)	(913)
Acquisition of intangibles	0	(16)	(53)
Net cash provided by investing activities	46,519	13,936	35,311
Financing activities
Proceeds from issuance of common stock, net	219	43,411	641
Proceeds from borrowing under term loan, net	0	0	19,768
Proceeds from exercise of common stock options	1	4	310
Proceeds from capital lease financing	292	0	0
Principal payments on term loan	(3,342)	0	(167)
Net cash (used in) provided by financing activities	(2,830)	43,415	20,552
Net increase (decrease) in cash and cash equivalents	416	(1,422)	(1,019)
Cash and cash equivalents at beginning of period	13,519	14,941	15,960
Cash and cash equivalents at end of period	13,935	13,519	14,941
Supplemental disclosure of cash flow information
Net changes in restricted cash	0	0	(1,256)
Interest paid	(2,073)	(1,944)	(981)
Income taxes paid	(1)	(1)	(1)
Supplemental disclosure of non-cash investing and financing activities
Allowance for tenant improvements	0	0	6,653
Amounts accrued for property and equipment	$ 0	$ 11	$ 292

The Business, Basis of Presenta

The Business, Basis of Presentation and Summary of Significant Accounting Policies	12 Months Ended
	Dec. 31, 2018
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 $407.5 million . As of December 31, 2018, we had approximately $13.9 million of cash and cash equivalents. Based on our operating plans, we believe our cash and cash equivalents may not be sufficient to fund our operations for the period one year following the issuance of these financial statements. As a result, there is substantial doubt about our ability to continue as a going concern. All amounts due under the Term Loan (see note 9) have been classified as a current liability as of December 31, 2018 and 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. We have 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 we become unable to continue as a going concern, we may have to liquidate our 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. Effective January 1, 2018, we adopted Accounting Standards Update (“ASU”) 2014-09, Revenue from Contracts with Customers (Topic 606) (“Topic 606”) using the modified retrospective method which consisted of applying and recognizing the cumulative effect of Topic 606 at the date of initial application. Topic 606 supersedes the revenue recognition requirements in Accounting Standards Codification (“ASC”) Topic 605, Revenue Recognition (“Topic 605”). All periods prior to the adoption date of Topic 606 have not been restated to reflect the impact of the adoption of Topic 606, but are accounted for and presented under Topic 605. The following paragraphs in this section describe our revenue recognition accounting polices under Topic 606 upon adoption on January 1, 2018. Refer to Note 1 to the financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2017 for revenue recognition accounting policies under Topic 605. We recognize revenue when we transfer promised goods or services to customers in an amount that reflects the consideration to which we expect to be entitled in exchange for those goods or services. To determine revenue recognition for contracts with customers we perform the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligation(s) in the contract; (iii) determine the transaction price; (iv) allocate the transaction price to the performance obligation(s) in the contract; and (v) recognize revenue when (or as) we satisfy the performance obligation(s). At contract inception, we assess the goods or services promised within each contract, assess whether each promised good or service is distinct and identify those that are performance obligations. We recognize as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) the performance obligation is satisfied. Collaborative Arrangements We enter into collaborative arrangements with partners that typically include payment to us of one of more of the following: (i) license fees; (ii) payments related to the achievement of developmental, regulatory, or commercial milestones; and (iii) royalties on net sales of licensed products. Where a portion of non-refundable up-front fees or other payments received are allocated to continuing performance obligations under the terms of a collaborative arrangement, they are recorded as contract liabilities and recognized as revenue when (or as) the underlying performance obligation is satisfied. As part of the accounting for these arrangements, we must develop estimates and assumptions that require judgment to determine the underlying stand-alone selling price for each performance obligation which determines how the transaction price is allocated among the performance obligation(s). The stand-alone selling price may include items such as forecasted revenues, development timelines, discount rates, and probabilities of technical and regulatory success. We evaluate each performance obligation to determine if it can be satisfied at a point in time, or over time. In addition, variable consideration must be evaluated to determine if it is constrained and, therefore, excluded from the transaction price. License Fees If a license to our intellectual property is determined to be distinct from the other performance obligations identified in the arrangement, we recognize revenues from non-refundable, up-front fees allocated to the license when the license is transferred to the licensee and the licensee is able to use and benefit from the license. For licenses that are bundled with other performance obligations, we use judgment to assess the nature of the combined performance obligation to determine whether it is satisfied over time or at a point in time and, if over time, the appropriate method of measuring progress for purposes of recognizing revenue. We evaluate the measure of progress each reporting period and, if necessary, adjust the measure of performance and related revenue recognition. Milestone Payments At the inception of each arrangement that includes milestone payments (variable consideration), we evaluate whether the milestones are considered probable of being reached and estimate the amount to be included in the transaction price. If it is probable that a milestone event would occur at the inception of an arrangement, the associated milestone value is included in the transaction price. Milestone payments that are contingent upon the achievement of events that are uncertain or not controllable, such as regulatory approvals, are generally not considered probable of being achieved until those approvals are received, and therefore not included in the transaction price. The transaction price is then allocated to each performance obligation on a relative stand-alone selling price basis, for which we recognize revenue as or when the performance obligations under the contract are satisfied. At the end of each reporting period, we evaluate the probability of achievement of such milestones and any related constraint(s), and if necessary, may adjust our estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis, which could affect license, collaboration or other revenues and earnings in the period of adjustment. Royalties For arrangements that include sales-based royalties, including milestone payments based on the level of sales, and for which the license is deemed to be the predominant item to which the royalties relate, we recognize revenue at the later of (i) when the related sales occur, or (ii) when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied). To date, we have not recognized any royalty revenue resulting from any of our collaborative arrangements. 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. 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. 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 have historically consisted 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 for the years ended December 31, 2018 or 2017 . 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 have historically invested our excess cash primarily in 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 8 years at December 31, 2018 . 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. At December 31, 2018 we did not have any licenses capitalized in our balance sheet. 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, 2018 , 2017 or 2016 . 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 July 2018 and May 2017, respectively, we implemented corporate restructurings to streamline our operations, reduce our operating expenses, extend our cash runway and focus our resources on our most promising programs. In connection with our July 2018 restructuring, we reduced our workforce by approximately 60% . We recorded net charges of approximately $0.8 million for employee severance and other related termination benefits and less than $0.1 million in net one-time, non-cash stock-based compensation charges due to the acceleration of outstanding stock options, in accordance with executive employment agreements, partially offset by the reversal of expense previously recognized for stock options that were cancelled upon termination. All payments associated with the corporate restructuring were paid in full by the end of the third quarter of 2018. In connection with our May 2017 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 by the end of the second quarter of 2017. Recent Accounting Pronouncements As disclosed above, effective January 1, 2018, we adopted Topic 606. Since ASU 2014-09 was issued, several additional ASUs have been issued and incorporated within Topic 606 to clarify various elements of the guidance. As part of our adoption efforts, we have completed the assessment of our collaboration and license agreements under Topic 606. We adopted Topic 606 in the first quarter of 2018 using the modified retrospective method which consists of applying and recognizing the cumulative effect of Topic 606 at the date of initial application and providing certain additional disclosures as defined per Topic 606. On January 1, 2018, we recorded a cumulative adjustment to decrease deferred revenue and accumulated deficit by approximately $1.8 million to reflect the impact of the adoption of Topic 606. The cumulative adjustment relates primarily to our agreement with Sanofi which is described further in Note 5. Below is a summary of the affected line items of the condensed balance sheets upon adoption of Topic 606 (in thousands): Balance at December 31, 2017 Adjustments due to Topic 606 Balance at January 1, 2018 Balance Sheet Deferred revenue (contract liabilities), non-current 1,921 (1,844 ) 77 Accumulated deficit (345,858 ) 1,844 (344,014 ) There we no impact on revenue recognized in 2018 as a result of the adoption of Topic 606. 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. The adoption of this guidance had 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. Since ASU 2016-02 was issued, several additional ASUs have been issued to clarify various elements of the guidance. The standard is effective for annual reporting periods beginning after December 15, 2018, including interim periods within those annual reporting periods. We expect to elect the standard’s package of practical expedients on adoption, which allows us to carry forward our historical assessment of whether existing agreements contain a lease and the classification of our existing lease agreements. We anticipate the most significant impact from the standard will be the requirement to record a right-of-use asset and corresponding lease liability on the balance sheet for our operating lease. We are in the process of quantifying the impact to the financial statements once the standard is effective for the Company in the first quarter of 2019. 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 had 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. The adoption of this guidance had no impact on our financial statements. In May 2017, the FASB issued ASU No. 2017-09, Compensation - Stock Compensation: 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 had no impact on our financial statements and will continue to have no impact on our financial statements unless we have modification accounting in accordance with Topic 718. In December 2017, the SEC issued Staff Accounting Bulletin No. 118 (“SAB 118”), which provides guidance on accounting for the income tax effects of the Tax Act. SAB 118 provides a measurement period that should not extend beyond one year from the Tax Act enactment date for companies to complete the accounting relating to the Tax Act under ASC Topic 740 Income Taxes, or “ASC 740”. In accordance with SAB 118, a company must reflect the income tax effects of those aspects of the Tax Act for which the accounting under ASC 740 is complete. To the extent that a company’s accounting for Tax Act-related income tax effects is incomplete, but the company is able to determine a reasonable estimate, it must record a provisional estimate in its financial statements. If a company cannot determine a provisional estimate to be included in its financial statements, it should continue to apply ASC 740 on the basis of the provisions of the tax laws that were in effect immediately before the enactment of the Tax Act. We completed our evaluation and there is no impact to our December 31, 2018 financial statements. In June 2018, the FASB issued ASU No. 2018-07, Compensation - Stock Compensation: Improvements to Nonemployee Share-Based Payment Accounting , which aligns the measurement and classification guidance for share-based payment to non-employees with the guidance for share-based payments to employees. Under the new guidance, the measurement period for equity-classified non-employee awards will be fixed at the grant date. This update is effective for annual periods beginning after December 15, 2018, and interim periods within those periods and early adoption is permitted. The adoption of this guidance is not anticipated to have an impact on our financial statements. In August 2018, the FASB issued ASU No. 2018-13, Fair Value Measurement: Disclosure Framework - Changes to the Disclosure Requirements for Fair Value Measurement , which updates and modifies the disclosure requirements on fair value measurements in Topic 820, primarily in relation to Level 3 fair value measurements. This update is effective for annual periods beginning after December 15, 2019, and interim periods within those periods. Early adoption is permitted. The adoption of this guidance is not anticipated to have an impact on our financial statements. In November 2018, the FASB issued ASU No. 2018-18, Collaborative Arrangements , which clarifies the interaction between Topic 808 , Collaborative Arrangements and Topic 606, including clarification around certain transactions between collaborative arrangement participants and adding unit-of-account guidance to Topic 808. This update is effective for annual periods beginning after December 15, 2019, and interim periods within those periods. Early adoption is permitted. The adoption of this guidance is not anticipated to have an impact on our financial statements.

Net Loss Per Share

Net Loss Per Share	12 Months Ended
	Dec. 31, 2018
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 and restricted stock units outstanding under our equity 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 zero and 245,488 shares attributable to common stock options and restricted stock units for the years ended December 31, 2018 and 2017, respectively, and 462,628 shares attributable to common stock options for the year ended December 31, 2016.

Investments

Investments	12 Months Ended
	Dec. 31, 2018
Investments, Debt and Equity Securities [Abstract]
Investments	Investments Historically, we have invested our excess cash primarily in debt instruments of financial institutions, corporations, U.S. government-sponsored agencies and the U.S. treasury and have held such investments until we had recovered our amortized cost basis. As of December 31, 2018 , our cash balance was comprised entirely of cash and cash equivalents. The following table summarizes our short-term investments as of December 31, 2017 (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 U.S. government-sponsored enterprise securities 1 or less $ 1,498 $ — $ (4 ) $ 1,494 Total $ 46,632 $ — $ (77 ) $ 46,555

Fair Value Measurements

Fair Value Measurements	12 Months Ended
	Dec. 31, 2018
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, 2018 and December 31, 2017 (in thousands): Fair value as of December 31, 2018 Total Level 1 Level 2 Level 3 Assets: Cash equivalents $ 11,173 $ 11,173 $ — $ — $ 11,173 $ 11,173 $ — $ — 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 $ — 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, 2018
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, 2018 2017 2016 Sanofi $ 72 $ 72 $ 72 AstraZeneca — — 1,122 Total $ 72 $ 72 $ 1,194 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 was deferred as of December 31, 2017, and recorded as an adjustment to accumulated deficit upon our adoption of Topic 606 on January 1, 2018. 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 the 2014 Sanofi Amendment, Sanofi had 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 were responsible for developing each of these programs to proof-of-concept, at which time Sanofi had an exclusive option on each program. If Sanofi chose to exercise its option on any of these programs, Sanofi would reimburse us for a significant portion of our preclinical and clinical development costs and would 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 relating to our preclinical program targeting miR-221/222. As indicated below, we entered into an additional amendment with Sanofi in November 2018, under which Sanofi's opt-in rights to our miR-21 programs under the 2014 Sanofi Amendment were relinquished. Sanofi's opt-in rights with regard to our miR-221/222 preclinical program under the 2014 Sanofi Amendment remained unchanged. 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. 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, 2018 , contract liability 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 one year. In November 2018, we entered into an amendment to the 2014 Sanofi Amendment with Sanofi to modify the parties’ rights and obligations with respect to our miR-21 programs, including our RG-012 program (the “2018 Sanofi Amendment”). Under the terms of the 2018 Sanofi Amendment, we have granted Sanofi a worldwide, royalty-free, fee-bearing, exclusive license, with the right to grant sublicenses, under our know-how and patents to develop and commercialize miR-21 compounds and products for all indications, including Alport Syndrome. Sanofi will control and will assume all responsibilities and obligations for developing and commercializing each of our miR-21 programs, including our obligations regarding the administration and expense of clinical trials and all other costs, including in-license royalties and other in-license payments, related to our miR-21 programs. Under the terms of the 2018 Sanofi Amendment, we have assigned to Sanofi certain agreements, product-specific patents and all materials directed to miR-21 or to any miR-21 compound or product and are required to provide reasonable technical assistance to Sanofi for a period of 24 months after the date of the 2018 Sanofi Amendment. Under the terms of the 2018 Sanofi Amendment, we are eligible to receive approximately $6.8 million in upfront payments for the license and for miR-21 program-related materials (collectively, the “Upfront Amendment Payments”). We are also eligible to receive up to $40.0 million in development milestone payments. In addition, Sanofi has agreed to reimburse us for certain out-of-pocket transition activities and assume our upstream license royalty obligations. We and Sanofi also agreed to a general release of claims against each other for any claims that arose at any time prior to the date of the 2018 Sanofi Amendment, or that thereafter could arise based on anything that occurred prior to the date of the 2018 Sanofi Amendment. In November 2018, we received $2.5 million of the approximately $6.8 million in Upfront Amendment Payments under the 2018 Sanofi Amendment. We determined the amount constituted a contract liability as of December 31, 2018 under Topic 606, as the performance obligation conditions had not been satisfied as of that date. We are eligible to receive milestone payments of up to $38.8 million for proof-of-concept option exercise fees (net of $1.25 million creditable, as noted above), $40.0 million for clinical milestones and up to $130.0 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-221/222 program 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 miR-221/222 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. 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 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 was to become effective in June 2018, 12 months following the date of delivery of the notice by AstraZeneca. In May 2018, AstraZeneca requested to extend the termination effective date by an additional 12 months to allow AstraZeneca to complete all activities involving RG-125(AZD4076). The new termination effective date pursuant to the extension is June 2019.

Property and Equipment, net

Property and Equipment, net	12 Months Ended
	Dec. 31, 2018
Property, Plant and Equipment [Abstract]
Property and Equipment, net	Property and Equipment, net The following table summarizes our major classes of property and equipment (in thousands): December 31, 2018 2017 Laboratory equipment $ 8,163 $ 8,430 Computer equipment and software 281 281 Furniture and fixtures 706 706 Leasehold improvements 8,550 8,550 17,700 17,967 Less accumulated depreciation and amortization (9,894 ) (8,259 ) Property and equipment, net $ 7,806 $ 9,708 Depreciation and amortization of property and equipment of $2.2 million , $2.4 million and $2.2 million was recorded for the years ended December 31, 2018 , 2017 and 2016 , respectively.

Intangible Assets, net

Intangible Assets, net	12 Months Ended
	Dec. 31, 2018
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, 2018 2017 Patents $ 721 $ 871 Licenses — 379 721 1,250 Accumulated amortization (221 ) (475 ) Intangibles, net $ 500 $ 775 Intangible asset amortization of $0.1 million was recorded for each of the years ended December 31, 2018 , 2017 and 2016 , respectively. Amortization of these intangible assets over the next five years is expected to be less than $0.1 million per year.

Commitments and Contingencies

Commitments and Contingencies	12 Months Ended
	Dec. 31, 2018
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, 2018 and 2017. 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, 2018 , 2017 and 2016 was $1.3 million , $1.4 million and $1.2 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 was $8.0 million and $9.3 million as of December 31, 2018 and 2017 , 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, 2018 , aggregate future annual minimum lease payments for the Lease are as follows (in thousands): 2019 $ 2,654 2020 2,733 2021 2,815 2022 2,901 2023 2,986 Thereafter 1,005 $ 15,094 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.

Term Loan

Term Loan	12 Months Ended
	Dec. 31, 2018
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" or sometimes referred to as the “ Lender ” ), 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 bears 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% . Under the original Loan Agreement, we were required to make interest-only payments through June 1, 2018, followed by 24 equal monthly payments of principal and unpaid accrued interest. In August 2018, we and Oxford entered into an amendment to our Loan Agreement, providing for a modification of the loan amortization period. Under the terms of the amendment, principal amortization and repayment was deferred between August 2018 through October 2018, and during this period, we were required to make payments of interest-only. Amortization payments recommenced in November 2018. There were no changes to the maturity date of the Term Loan, which is June 2020. Pursuant to the amendment, we granted the Lender a security interest in our intellectual property as additional collateral for the repayment of the Term Loan. In November 2018, and in connection with the 2018 Sanofi Amendment, we entered into a fourth amendment to the Term Loan with the Lender (the "Fourth Amendment"). Under the terms of the Fourth Amendment, the Lender has consented to the 2018 Sanofi Amendment and our license, assignment and transfer to Sanofi of certain of our intellectual property, as required to be delivered to Sanofi under the 2018 Sanofi Amendment (the “Assigned Assets”), which previously served as collateral under the loan and security agreement, and has released its liens in the Assigned Assets, provided that the Lender will continue to have liens on all proceeds received by us pursuant to the Sanofi License. Under the terms of the Fourth Amendment, we now have the option to prepay part of the Term Loan at any time and in any amount after 10 days’ prior written notice. We are also required to prepay part of the Term Loan with 25% of certain payments we receive under the 2018 Sanofi Amendment, which payments consist of the Upfront Amendment Payments and the first development milestone payment in the amount of $10.0 million . In accordance with this term, we prepaid $0.6 million in November 2018 pursuant to our receipt of $2.5 million in Upfront Amendment Payments in November 2018. We will be required to pay the applicable 5.5% final payment fee related to each such 2018 Sanofi Amendment prepayment. Under the Fourth Amendment, we are required to maintain cash in a collateral account controlled by the Lender of (i) $10.0 million , if we have not received net proceeds of at least $15.0 million from (a) the issuance and sale of our unsecured subordinated convertible debt and/or equity securities or (b) upfront or milestone payments in connection with a joint venture, collaboration or other partnering transaction, other than pursuant to the Sanofi License (the receipt of such net proceeds, a “Capital Event”), or (ii) $5.0 million if a Capital Event has occurred. The maturity date of the Term Loan remains unchanged and the Term Loan is required to be paid in full on June 1, 2020. 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 and certain assets under capital lease obligations. 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. All amounts due under the Term Loan have been classified as a current liability as of December 31, 2018 and 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 our control. We have not been notified of an event of default by the Lender as of the date of the filing of this Form 10-K and as of December 31, 2018 we were in compliance with all covenants under the Loan Agreement. As of December 31, 2018 , $16.6 million was 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 fees are being accrued over the life of the Term Loan through interest expense. Future principal payments for the Term Loan due under the Loan Agreement are as follows (in thousands): 2019 $ 10,540 2020 6,118 $ 16,658

Common Stock and Stockholders'

Common Stock and Stockholders' Equity	12 Months Ended
	Dec. 31, 2018
Equity [Abstract]
Common Stock and Stockholders’ Equity	Common Stock and Stockholders’ Equity Common Stock As of December 31, 2018 , there were 8,818,019 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. Reverse Stock Split On October 2, 2018, we filed a Certificate of Amendment of Amended and Restated Certificate of Incorporation with the Secretary of State of the state of Delaware to effect a 1-for-12 reverse stock split of our issued and outstanding common stock. The primary purpose of the reverse stock split was to raise the per share trading price of our common stock to seek to maintain the listing of our common stock on The Nasdaq Global Market. At the effective time of the reverse stock split, 5:00 p.m. on October 3, 2018, each 12 shares of our issued and outstanding common stock were automatically combined and converted into one issued and outstanding share of common stock. All of our stock options and RSUs outstanding immediately prior to the reverse stock split were proportionately adjusted. All issued and outstanding common stock, options exercisable for common stock, restricted stock units, and per share amounts contained in these financial statements have been retrospectively adjusted. Exchange Offer On October 15, 2018, we filed a tender offer statement on Schedule TO with the Securities and Exchange Commission related to an offer by us to certain eligible optionholders, subject to specified conditions, to exchange some or all of their outstanding options to purchase shares of our common stock for new RSUs (the "Exchange Offer"). The Exchange Offer expired at 5:00 p.m., U.S. Pacific Time, on November 11, 2018. An option holder was eligible to exchange their options (an “Eligible Holder”) if: • on the date the Exchange Offer commenced, either an optionholder was employed by us (each, an “Employee”) or is a non-employee member (each, a “Non-Employee Director”) of our board of directors and has not been notified by us that such optionholder’s employment or service relationship with us is being terminated; and • such optionholder continued to be an Employee or serve as a Non-Employee Director and had not submitted a notice of resignation or received a notice of termination, as of the first business day following the Expiration Time (as defined in the Exchange Offer). An option was eligible for exchange (an “Eligible Option”) if it: • was held by an Eligible Holder; • had an exercise price equal to or greater than $4.56 (and an exercise price greater than the closing price of our common stock on the last business day before the Expiration Time); and • was granted under our 2009 Equity Incentive Plan, 2012 Equity Incentive Plan or 2015 Inducement Plan. The exchange ratio for each Eligible Option was determined using the Black-Scholes option pricing model and was based on, among other things, the fair market value of a share of our common stock, the volatility of our common stock, U.S. treasury rates, the exercise prices of the Eligible Options, the remaining terms of the Eligible Options and the term of the new RSUs. For purposes of determining the fair value of Eligible Options, the fair market value of a share of our common stock was determined based on the trailing 20-day volume weighted average price (the “20-Day VWAP”). The 20-Day VWAP represents the simple arithmetic average of the daily VWAPs over the 20 consecutive trading days beginning on October 15, 2018 and ending on the last business day prior to the Expiration Time. For purposes of determining the fair value of the new RSUs, the fair market value of a share of our common stock was determined based on the closing trading price of a share of our common stock on Nasdaq on the last business day prior to the Expiration Time. In no event was an Eligible Optionholder be eligible to receive more new RSUs than the number of shares underlying the number of Eligible Options. There were a total of 915,009 options eligible for exchange in the Exchange Offer by 31 eligible optionholders, all of which were exchanged for 603,058 RSUs. Of the 603,058 RSUs issued in the Exchange Offer, 514,955 contain certain performance conditions requisite for vesting commencement. Incremental stock-based compensation cost associated with the Exchange Offer was $0.4 million . Shares Reserved for Future Issuance The following shares of common stock were reserved for future issuance as of December 31, 2018 : Common stock options outstanding 59 Restricted stock units outstanding 601 Common stock available for future grant under the 2012 Plan 454 Common stock available for future grant under the Inducement Plan 83 Employee Stock Purchase Plan 156 Total common shares reserved for future issuance 1,353 The following table summarizes our stock option activity under all equity incentive plans for the year ended December 31, 2018 (shares in thousands): Number of options Weighted average exercise price Weighted average remaining contractual term Aggregate intrinsic value Options outstanding at December 31, 2017 887 $ 53.24 Granted 603 $ 11.70 Exercised (1 ) $ 4.56 Canceled/forfeited/expired (1,430 ) $ 36.06 Options outstanding at December 31, 2018 59 $ 45.60 6.3 $ — Exercisable at December 31, 2018 35 $ 63.39 4.6 $ — The weighted average grant date fair value per share of employee stock options granted during the years ended December 31, 2018 , 2017 and 2016 was $8.63 , $11.73 and $39.54 , respectively. The total intrinsic value of stock options exercised was less than $0.1 million during the years ended December 31, 2018 and 2017, and $0.2 million during the year ended December 31, 2016 . Cash received from the exercise of stock options was less than $0.1 million for the years ended December 31, 2018 and 2017 and approximately $0.3 million for the year ended December 31, 2016 . The total compensation cost related to stock options not yet recognized was $0.1 million as of December 31, 2018 . The weighted-average period over which this expense is expected to be recognized is approximately 1.4 years . The following table summarizes our RSU activity under all equity incentive plans for the year ended December 31, 2018 (shares and aggregate intrinsic value in thousands): Number of options Weighted average grant date fair value Weighted average remaining contractual term Aggregate intrinsic value RSUs outstanding at December 31, 2017 35 $ 10.68 Granted 705 $ 1.84 Vested (128 ) $ 5.49 Canceled/forfeited/expired (11 ) $ 6.32 RSUs outstanding at December 31, 2018 601 $ 1.50 3.4 $ 559 The total compensation cost related to non-vested RSUs not yet recognized was $3.8 million as of December 31, 2018 . The weighted-average period over which this expense is expected to be recognized is approximately 3.4 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, 2018 2017 2016 Stock options Risk-free interest rate 2.7 % 2.0 % 1.5 % Volatility 87.8 % 89.4 % 82.7 % Dividend yield — — — Expected term (years) 6.1 6.1 6.0 Performance stock options Risk-free interest rate 2.7 % 2.1 % 1.4 % Volatility 87.4 % 89.2 % 82.4 % Dividend yield — — — Expected term (years) 5.7 5.7 5.9 Employee stock purchase plan shares Risk-free interest rate 1.9 % 0.9 % 0.5 % Volatility 100.6 % 105.6 % 93.7 % 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 account for forfeitures as they occur. 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 July 2018 and May 2017 corporate restructuring (in thousands): Year ended December 31, 2018 2017 2016 Research and development $ 2,225 $ 2,862 $ 5,458 Research and development-restructuring related adjustments 31 (1,399 ) — General and administrative 3,199 3,500 7,414 General and administrative-restructuring related adjustments (15 ) 2,679 — Total $ 5,440 $ 7,642 $ 12,872 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. Net amounts recorded in connection with our July 2018 corporate restructuring were less than $0.1 million . 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, 2018 , 87,913 shares of our common stock had been issued under the 2012 Purchase Plan, with 26,417 shares of common stock issued for the year ended December 31, 2018 . Under the 2012 Purchase Plan, 155,056 shares of our common stock were reserved for future issuance and have been authorized for purchase as of December 31, 2018 . 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 vested 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. One hundred percent of options issued under the Inducement Plan were exchanged by eligible optionholders in the Exchange Offer. As of December 31, 2018, 83,333 shares were reserved for future issuance under the Inducement Plan.

Defined Contribution Plan

Defined Contribution Plan	12 Months Ended
	Dec. 31, 2018
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 , $0.1 million and $0.2 million for the years ended December 31, 2018 , 2017 , and 2016 , respectively.

Income Taxes

Income Taxes	12 Months Ended
	Dec. 31, 2018
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, 2018 2017 2016 Current: Federal $ (26 ) $ (143 ) $ — State 1 1 1 (25 ) (142 ) 1 Deferred: Federal 87 (55 ) (5 ) State — — — 87 (55 ) (5 ) Income tax expense (benefit) $ 62 $ (197 ) $ (4 ) 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, 2018 2017 2016 Expected income tax benefit at federal statutory tax rate $ (10,216 ) $ (24,515 ) $ (27,826 ) State income taxes, net of federal benefit (3,005 ) 1 (1,152 ) Tax credits (3,666 ) (5,151 ) (5,447 ) Change in valuation allowance 12,706 (8,705 ) 31,990 Adjustments related to prior year 441 1 (1,320 ) Stock compensation 251 1,135 2,458 Reserve for uncertain tax positions 3,596 311 1,314 Tax Cuts and Jobs Act rate change — 36,249 — Other (45 ) 477 (21 ) Income tax expense (benefit) $ 62 $ (197 ) $ (4 ) The following table summarizes the significant components of our deferred tax assets and liabilities (in thousands): December 31, 2018 2017 Deferred tax assets: Net operating loss carryovers $ 74,965 $ 66,549 Research and development and other tax credits 33,121 29,702 Deferred revenue 16 419 Stock compensation expense 5,033 4,238 Other 2,027 2,196 Total deferred tax assets 115,162 103,104 Total deferred tax liabilities (176 ) (408 ) Net deferred tax asset 114,986 102,696 Valuation allowance (114,960 ) (102,641 ) Net deferred tax asset $ 26 $ 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 $115.0 million . As of December 31, 2018, we had federal and California tax NOL carryforwards of $305.3 million and $255.5 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, 2018, we also had federal and California research and development tax credit carryforwards of $30.9 million and $8.8 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. The future utilization of our research and development credit carryforwards and NOL 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 NOL carryforwards in the event of a cumulative change in ownerships in excess of 50% as defined in the Act. On December 22, 2017, the Tax Act was enacted into law. The Tax Act made significant changes to U.S tax laws, including, but not limited to, the following: (a) reducing the federal corporate income tax rate from 35% to 21%, effective January 1, 2018; (b) eliminating the federal corporate alternative minimum tax, or "AMT" and changing how existing AMT credits can be realized; and (c) eliminating several business deductions and credits, including deductions for certain executive compensation in excess of $1.0 million. As a result of the rate reduction, we have 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 our valuation allowance by the same amount. 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, 2018 2017 2016 Beginning balance of unrecognized tax benefits $ 4,421 $ 5,632 $ 2,298 Increase (decrease) for prior year tax positions 5,961 (2,466 ) 1,991 Increase for current year tax positions 4,318 1,255 1,343 Total $ 14,700 $ 4,421 $ 5,632 Included in unrecognized tax benefits of $14.7 million at December 31, 2018 was $11.8 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 state jurisdictions where applicable. Our tax years for 2009 and forward are subject to examination by the U.S. tax authorities and our tax years for 2010 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, 2018 , 2017 and 2016 , we have not recognized any interest or penalties related to income taxes.

Related Party Transactions

Related Party Transactions	12 Months Ended
	Dec. 31, 2018
Related Party Transactions [Abstract]
Related Party Transactions	Related Party Transactions We have entered into certain agreements with related parties in the ordinary course of business to license intellectual property and to procure research and development support services. 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 for the years ended December 31, 2018 and 2017, respectively, and $0.9 million for the year ended December 31, 2016.

Selected Quarterly Financial Da

Selected Quarterly Financial Data (Unaudited)	12 Months Ended
	Dec. 31, 2018
Quarterly Financial Information Disclosure [Abstract]
Selected Quarterly Financial Data (Unaudited)	Selected Quarterly Financial Data (Unaudited) The following 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 2018 and 2017 are as follows (in thousands, except per share data): For the quarters ending March 31 June 30 September 30 December 31 2018 Total revenues $ 18 $ 18 $ 18 $ 18 Total operating expenses (15,601 ) (13,362 ) (9,872 ) (8,000 ) Net loss (16,025 ) (13,847 ) (10,273 ) (8,563 ) Net loss per share, basic and diluted (1) $ (1.85 ) $ (1.59 ) $ (1.18 ) $ (0.98 ) 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) $ (4.53 ) $ (4.87 ) $ (2.11 ) $ (1.67 ) (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.

Subsequent Events

Subsequent Events	12 Months Ended
	Dec. 31, 2018
Subsequent Events [Abstract]
Subsequent Events	Subsequent Events Fifth Amendment to Loan and Security Agreement On January 31, 2019, we entered into a fifth amendment to our Loan and Security Agreement (the "Fifth Amendment") with Oxford Finance LLC, as the collateral agent and a Lender, dated June 17, 2016, as amended, pursuant to which the Lender lent us $20.0 million in a term loan. Under the terms of the Fifth Amendment, our required monthly payment to the Lender for the month of February 2019 was comprised of interest only. The maturity date of the Term Loan remains unchanged and the Term Loan is required to be paid in full on June 1, 2020. Sixth Amendment to Loan and Security Agreement On March 7, 2019 we entered into a sixth amendment to our Loan and Security Agreement (the "Sixth Amendment") with Oxford Finance LLC, as the collateral agent and a Lender, dated June 17, 2016, as amended, pursuant to which the Lender lent us $20.0 million in a term loan. Under the terms of the Sixth Amendment, our required monthly payment to the Lender for the month of March 2019 was comprised of interest only. Amortization payments will recommence in April 2019. The maturity date of the Term Loan remains unchanged and the Term Loan is required to be paid in full on June 1, 2020. Corporate Headquarters Lease Agreements On February 25, 2019, we entered into a lease agreement (the "Lease") with ARE-SD Region No. 44 LLC ("Landlord"), for the lease of approximately 24,562 square feet of rentable area of the building located at 10628 Science Center Drive, San Diego, California, 92121 (the "Premises"), which Premises are currently occupied by Nitto Biopharma, Inc. ("Nitto"). The commencement date of the Lease is expected to be on or before April 1, 2019 (the “Commencement Date”). We expect to use the Premises as our new principal executive offices and as a laboratory for research and development, manufacturing and other related uses. The term of the Lease (“Initial Term”) is 51 months , ending June 30, 2023 (assuming an April 1, 2019 Commencement Date). The aggregate base rent due over the Initial Term is approximately $4.8 million (without giving effect to certain rent abatement terms). We will also be responsible for the payment of additional rent to cover our share of the annual operating expenses of the building, the annual tax expenses of the building and the annual utilities costs for the building. On February 25, 2019, we and Landlord entered into a second amendment (the “Lease Amendment”) to the lease dated July 31, 2015, as amended, between us and Landlord (the “Prior Lease”) for the lease of approximately 59,248 square feet located at 10614 Science Center Drive, San Diego, California 92121. Under the terms of the Lease Amendment, the expiration date of the Prior Lease will be accelerated from April 30, 2024 to April 1, 2019 and the Prior Lease will terminate upon the Commencement Date of the Lease. The Lease Amendment will eliminate all further rents due under the Prior Lease, including aggregate base rent over its remaining term of approximately $14.4 million . On February 19, 2019, we entered into an agreement, the “Space Swap Agreement", with Nitto, pursuant to which we agreed, contingent upon the execution of the Lease and the termination of the Prior Lease, to, among other things, (i) swap buildings with Nitto on or about the Commencement Date, and (ii) sell, convey and transfer all right, title and interest in certain furniture, fixtures and equipment to Nitto, as set forth in the Space Swap Agreement. Under the Space Swap Agreement, we will pay to Nitto (a) a relocation assistance payment in the amount of $0.1 million ; (b) $0.2 million representing the difference between the security deposits under the Prior Lease and Nitto’s prior lease, and (c) $1.3 million as reimbursement for the six monthly installments of base monthly rent due pursuant to the new lease between Nitto and Landlord, subject to certain adjustments, which reimbursements are to be paid as rent comes due for Nitto under its new lease.

The Business, Basis of Presen_2

The Business, Basis of Presentation and Summary of Significant Accounting Policies (Policies)	12 Months Ended
	Dec. 31, 2018
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. Effective January 1, 2018, we adopted Accounting Standards Update (“ASU”) 2014-09, Revenue from Contracts with Customers (Topic 606) (“Topic 606”) using the modified retrospective method which consisted of applying and recognizing the cumulative effect of Topic 606 at the date of initial application. Topic 606 supersedes the revenue recognition requirements in Accounting Standards Codification (“ASC”) Topic 605, Revenue Recognition (“Topic 605”). All periods prior to the adoption date of Topic 606 have not been restated to reflect the impact of the adoption of Topic 606, but are accounted for and presented under Topic 605. The following paragraphs in this section describe our revenue recognition accounting polices under Topic 606 upon adoption on January 1, 2018. Refer to Note 1 to the financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2017 for revenue recognition accounting policies under Topic 605. We recognize revenue when we transfer promised goods or services to customers in an amount that reflects the consideration to which we expect to be entitled in exchange for those goods or services. To determine revenue recognition for contracts with customers we perform the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligation(s) in the contract; (iii) determine the transaction price; (iv) allocate the transaction price to the performance obligation(s) in the contract; and (v) recognize revenue when (or as) we satisfy the performance obligation(s). At contract inception, we assess the goods or services promised within each contract, assess whether each promised good or service is distinct and identify those that are performance obligations. We recognize as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) the performance obligation is satisfied. Collaborative Arrangements We enter into collaborative arrangements with partners that typically include payment to us of one of more of the following: (i) license fees; (ii) payments related to the achievement of developmental, regulatory, or commercial milestones; and (iii) royalties on net sales of licensed products. Where a portion of non-refundable up-front fees or other payments received are allocated to continuing performance obligations under the terms of a collaborative arrangement, they are recorded as contract liabilities and recognized as revenue when (or as) the underlying performance obligation is satisfied. As part of the accounting for these arrangements, we must develop estimates and assumptions that require judgment to determine the underlying stand-alone selling price for each performance obligation which determines how the transaction price is allocated among the performance obligation(s). The stand-alone selling price may include items such as forecasted revenues, development timelines, discount rates, and probabilities of technical and regulatory success. We evaluate each performance obligation to determine if it can be satisfied at a point in time, or over time. In addition, variable consideration must be evaluated to determine if it is constrained and, therefore, excluded from the transaction price. License Fees If a license to our intellectual property is determined to be distinct from the other performance obligations identified in the arrangement, we recognize revenues from non-refundable, up-front fees allocated to the license when the license is transferred to the licensee and the licensee is able to use and benefit from the license. For licenses that are bundled with other performance obligations, we use judgment to assess the nature of the combined performance obligation to determine whether it is satisfied over time or at a point in time and, if over time, the appropriate method of measuring progress for purposes of recognizing revenue. We evaluate the measure of progress each reporting period and, if necessary, adjust the measure of performance and related revenue recognition. Milestone Payments At the inception of each arrangement that includes milestone payments (variable consideration), we evaluate whether the milestones are considered probable of being reached and estimate the amount to be included in the transaction price. If it is probable that a milestone event would occur at the inception of an arrangement, the associated milestone value is included in the transaction price. Milestone payments that are contingent upon the achievement of events that are uncertain or not controllable, such as regulatory approvals, are generally not considered probable of being achieved until those approvals are received, and therefore not included in the transaction price. The transaction price is then allocated to each performance obligation on a relative stand-alone selling price basis, for which we recognize revenue as or when the performance obligations under the contract are satisfied. At the end of each reporting period, we evaluate the probability of achievement of such milestones and any related constraint(s), and if necessary, may adjust our estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis, which could affect license, collaboration or other revenues and earnings in the period of adjustment. Royalties For arrangements that include sales-based royalties, including milestone payments based on the level of sales, and for which the license is deemed to be the predominant item to which the royalties relate, we recognize revenue at the later of (i) when the related sales occur, or (ii) when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied). To date, we have not recognized any royalty revenue resulting from any of our collaborative arrangements.
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. 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	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 Taxes	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.
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 have historically consisted 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 for the years ended December 31, 2018 or 2017 .
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 have historically invested our excess cash primarily in 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 8 years at December 31, 2018 . 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. At December 31, 2018 we did not have any licenses capitalized in our balance sheet.
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 As disclosed above, effective January 1, 2018, we adopted Topic 606. Since ASU 2014-09 was issued, several additional ASUs have been issued and incorporated within Topic 606 to clarify various elements of the guidance. As part of our adoption efforts, we have completed the assessment of our collaboration and license agreements under Topic 606. We adopted Topic 606 in the first quarter of 2018 using the modified retrospective method which consists of applying and recognizing the cumulative effect of Topic 606 at the date of initial application and providing certain additional disclosures as defined per Topic 606. On January 1, 2018, we recorded a cumulative adjustment to decrease deferred revenue and accumulated deficit by approximately $1.8 million to reflect the impact of the adoption of Topic 606. The cumulative adjustment relates primarily to our agreement with Sanofi which is described further in Note 5. Below is a summary of the affected line items of the condensed balance sheets upon adoption of Topic 606 (in thousands): Balance at December 31, 2017 Adjustments due to Topic 606 Balance at January 1, 2018 Balance Sheet Deferred revenue (contract liabilities), non-current 1,921 (1,844 ) 77 Accumulated deficit (345,858 ) 1,844 (344,014 ) There we no impact on revenue recognized in 2018 as a result of the adoption of Topic 606. 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. The adoption of this guidance had 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. Since ASU 2016-02 was issued, several additional ASUs have been issued to clarify various elements of the guidance. The standard is effective for annual reporting periods beginning after December 15, 2018, including interim periods within those annual reporting periods. We expect to elect the standard’s package of practical expedients on adoption, which allows us to carry forward our historical assessment of whether existing agreements contain a lease and the classification of our existing lease agreements. We anticipate the most significant impact from the standard will be the requirement to record a right-of-use asset and corresponding lease liability on the balance sheet for our operating lease. We are in the process of quantifying the impact to the financial statements once the standard is effective for the Company in the first quarter of 2019. 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 had 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. The adoption of this guidance had no impact on our financial statements. In May 2017, the FASB issued ASU No. 2017-09, Compensation - Stock Compensation: 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 had no impact on our financial statements and will continue to have no impact on our financial statements unless we have modification accounting in accordance with Topic 718. In December 2017, the SEC issued Staff Accounting Bulletin No. 118 (“SAB 118”), which provides guidance on accounting for the income tax effects of the Tax Act. SAB 118 provides a measurement period that should not extend beyond one year from the Tax Act enactment date for companies to complete the accounting relating to the Tax Act under ASC Topic 740 Income Taxes, or “ASC 740”. In accordance with SAB 118, a company must reflect the income tax effects of those aspects of the Tax Act for which the accounting under ASC 740 is complete. To the extent that a company’s accounting for Tax Act-related income tax effects is incomplete, but the company is able to determine a reasonable estimate, it must record a provisional estimate in its financial statements. If a company cannot determine a provisional estimate to be included in its financial statements, it should continue to apply ASC 740 on the basis of the provisions of the tax laws that were in effect immediately before the enactment of the Tax Act. We completed our evaluation and there is no impact to our December 31, 2018 financial statements. In June 2018, the FASB issued ASU No. 2018-07, Compensation - Stock Compensation: Improvements to Nonemployee Share-Based Payment Accounting , which aligns the measurement and classification guidance for share-based payment to non-employees with the guidance for share-based payments to employees. Under the new guidance, the measurement period for equity-classified non-employee awards will be fixed at the grant date. This update is effective for annual periods beginning after December 15, 2018, and interim periods within those periods and early adoption is permitted. The adoption of this guidance is not anticipated to have an impact on our financial statements. In August 2018, the FASB issued ASU No. 2018-13, Fair Value Measurement: Disclosure Framework - Changes to the Disclosure Requirements for Fair Value Measurement , which updates and modifies the disclosure requirements on fair value measurements in Topic 820, primarily in relation to Level 3 fair value measurements. This update is effective for annual periods beginning after December 15, 2019, and interim periods within those periods. Early adoption is permitted. The adoption of this guidance is not anticipated to have an impact on our financial statements. In November 2018, the FASB issued ASU No. 2018-18, Collaborative Arrangements , which clarifies the interaction between Topic 808 , Collaborative Arrangements and Topic 606, including clarification around certain transactions between collaborative arrangement participants and adding unit-of-account guidance to Topic 808. This update is effective for annual periods beginning after December 15, 2019, and interim periods within those periods. Early adoption is permitted. The adoption of this guidance is not anticipated to have an impact on our financial statements.
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 Business, Basis of Presen_3

The Business, Basis of Presentation and Summary of Significant Accounting Policies (Tables)	12 Months Ended
	Dec. 31, 2018
Accounting Policies [Abstract]
Schedule of New Accounting Pronouncements and Changes in Accounting Principles [Table Text Block]	Below is a summary of the affected line items of the condensed balance sheets upon adoption of Topic 606 (in thousands): Balance at December 31, 2017 Adjustments due to Topic 606 Balance at January 1, 2018 Balance Sheet Deferred revenue (contract liabilities), non-current 1,921 (1,844 ) 77 Accumulated deficit (345,858 ) 1,844 (344,014 )

Investments (Tables)

Investments (Tables)	12 Months Ended
	Dec. 31, 2018
Investments, Debt and Equity Securities [Abstract]
Summary of Short-Term Investments	The following table summarizes our short-term investments as of December 31, 2017 (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 U.S. government-sponsored enterprise securities 1 or less $ 1,498 $ — $ (4 ) $ 1,494 Total $ 46,632 $ — $ (77 ) $ 46,555

Fair Value Measurements (Tables

Fair Value Measurements (Tables)	12 Months Ended
	Dec. 31, 2018
Fair Value Disclosures [Abstract]
Fair Value Hierarchy for Assets	The following table presents our fair value hierarchy for assets measured at fair value on a recurring basis as of December 31, 2018 and December 31, 2017 (in thousands): Fair value as of December 31, 2018 Total Level 1 Level 2 Level 3 Assets: Cash equivalents $ 11,173 $ 11,173 $ — $ — $ 11,173 $ 11,173 $ — $ — 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 $ —

Strategic Alliances and Colla_2

Strategic Alliances and Collaborations (Tables)	12 Months Ended
	Dec. 31, 2018
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, 2018 2017 2016 Sanofi $ 72 $ 72 $ 72 AstraZeneca — — 1,122 Total $ 72 $ 72 $ 1,194

Property and Equipment, net (Ta

Property and Equipment, net (Tables)	12 Months Ended
	Dec. 31, 2018
Property, Plant and Equipment [Abstract]
Property, Plant and Equipment	The following table summarizes our major classes of property and equipment (in thousands): December 31, 2018 2017 Laboratory equipment $ 8,163 $ 8,430 Computer equipment and software 281 281 Furniture and fixtures 706 706 Leasehold improvements 8,550 8,550 17,700 17,967 Less accumulated depreciation and amortization (9,894 ) (8,259 ) Property and equipment, net $ 7,806 $ 9,708

Intangible Assets, net (Tables)

Intangible Assets, net (Tables)	12 Months Ended
	Dec. 31, 2018
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, 2018 2017 Patents $ 721 $ 871 Licenses — 379 721 1,250 Accumulated amortization (221 ) (475 ) Intangibles, net $ 500 $ 775

Commitments and Contingencies (

Commitments and Contingencies (Tables)	12 Months Ended
	Dec. 31, 2018
Commitments and Contingencies Disclosure [Abstract]
Schedule of Future Minimum Rental Payments for Operating Leases	As of December 31, 2018 , aggregate future annual minimum lease payments for the Lease are as follows (in thousands): 2019 $ 2,654 2020 2,733 2021 2,815 2022 2,901 2023 2,986 Thereafter 1,005 $ 15,094

Term Loan (Tables)

Term Loan (Tables)	12 Months Ended
	Dec. 31, 2018
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): 2019 $ 10,540 2020 6,118 $ 16,658

Common Stock and Stockholders_2

Common Stock and Stockholders' Equity (Tables)	12 Months Ended
	Dec. 31, 2018
Equity [Abstract]
Common Stock Reserved for Future Issuance	The following shares of common stock were reserved for future issuance as of December 31, 2018 : Common stock options outstanding 59 Restricted stock units outstanding 601 Common stock available for future grant under the 2012 Plan 454 Common stock available for future grant under the Inducement Plan 83 Employee Stock Purchase Plan 156 Total common shares reserved for future issuance 1,353
Stock Option Activity	The following table summarizes our stock option activity under all equity incentive plans for the year ended December 31, 2018 (shares in thousands): Number of options Weighted average exercise price Weighted average remaining contractual term Aggregate intrinsic value Options outstanding at December 31, 2017 887 $ 53.24 Granted 603 $ 11.70 Exercised (1 ) $ 4.56 Canceled/forfeited/expired (1,430 ) $ 36.06 Options outstanding at December 31, 2018 59 $ 45.60 6.3 $ — Exercisable at December 31, 2018 35 $ 63.39 4.6 $ —
Schedule of Restricted Stock Units Activity	The following table summarizes our RSU activity under all equity incentive plans for the year ended December 31, 2018 (shares and aggregate intrinsic value in thousands): Number of options Weighted average grant date fair value Weighted average remaining contractual term Aggregate intrinsic value RSUs outstanding at December 31, 2017 35 $ 10.68 Granted 705 $ 1.84 Vested (128 ) $ 5.49 Canceled/forfeited/expired (11 ) $ 6.32 RSUs outstanding at December 31, 2018 601 $ 1.50 3.4 $ 559
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, 2018 2017 2016 Stock options Risk-free interest rate 2.7 % 2.0 % 1.5 % Volatility 87.8 % 89.4 % 82.7 % Dividend yield — — — Expected term (years) 6.1 6.1 6.0 Performance stock options Risk-free interest rate 2.7 % 2.1 % 1.4 % Volatility 87.4 % 89.2 % 82.4 % Dividend yield — — — Expected term (years) 5.7 5.7 5.9 Employee stock purchase plan shares Risk-free interest rate 1.9 % 0.9 % 0.5 % Volatility 100.6 % 105.6 % 93.7 % 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 July 2018 and May 2017 corporate restructuring (in thousands): Year ended December 31, 2018 2017 2016 Research and development $ 2,225 $ 2,862 $ 5,458 Research and development-restructuring related adjustments 31 (1,399 ) — General and administrative 3,199 3,500 7,414 General and administrative-restructuring related adjustments (15 ) 2,679 — Total $ 5,440 $ 7,642 $ 12,872

Income Taxes (Tables)

Income Taxes (Tables)	12 Months Ended
	Dec. 31, 2018
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, 2018 2017 2016 Current: Federal $ (26 ) $ (143 ) $ — State 1 1 1 (25 ) (142 ) 1 Deferred: Federal 87 (55 ) (5 ) State — — — 87 (55 ) (5 ) Income tax expense (benefit) $ 62 $ (197 ) $ (4 )
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, 2018 2017 2016 Expected income tax benefit at federal statutory tax rate $ (10,216 ) $ (24,515 ) $ (27,826 ) State income taxes, net of federal benefit (3,005 ) 1 (1,152 ) Tax credits (3,666 ) (5,151 ) (5,447 ) Change in valuation allowance 12,706 (8,705 ) 31,990 Adjustments related to prior year 441 1 (1,320 ) Stock compensation 251 1,135 2,458 Reserve for uncertain tax positions 3,596 311 1,314 Tax Cuts and Jobs Act rate change — 36,249 — Other (45 ) 477 (21 ) Income tax expense (benefit) $ 62 $ (197 ) $ (4 )
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, 2018 2017 Deferred tax assets: Net operating loss carryovers $ 74,965 $ 66,549 Research and development and other tax credits 33,121 29,702 Deferred revenue 16 419 Stock compensation expense 5,033 4,238 Other 2,027 2,196 Total deferred tax assets 115,162 103,104 Total deferred tax liabilities (176 ) (408 ) Net deferred tax asset 114,986 102,696 Valuation allowance (114,960 ) (102,641 ) Net deferred tax asset $ 26 $ 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, 2018 2017 2016 Beginning balance of unrecognized tax benefits $ 4,421 $ 5,632 $ 2,298 Increase (decrease) for prior year tax positions 5,961 (2,466 ) 1,991 Increase for current year tax positions 4,318 1,255 1,343 Total $ 14,700 $ 4,421 $ 5,632

Selected Quarterly Financial _2

Selected Quarterly Financial Data (Unaudited) (Tables)	12 Months Ended
	Dec. 31, 2018
Quarterly Financial Information Disclosure [Abstract]
Schedule of Quarterly Financial Information	Summarized quarterly data for 2018 and 2017 are as follows (in thousands, except per share data): For the quarters ending March 31 June 30 September 30 December 31 2018 Total revenues $ 18 $ 18 $ 18 $ 18 Total operating expenses (15,601 ) (13,362 ) (9,872 ) (8,000 ) Net loss (16,025 ) (13,847 ) (10,273 ) (8,563 ) Net loss per share, basic and diluted (1) $ (1.85 ) $ (1.59 ) $ (1.18 ) $ (0.98 ) 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) $ (4.53 ) $ (4.87 ) $ (2.11 ) $ (1.67 ) (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 Presen_4

The Business, Basis of Presentation and Summary of Significant Accounting Policies - Liquidity (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Accounting Policies [Abstract]
Financing from sale proceeds, debt, and agreement revenues	$ 407,500
Cash and cash equivalents	$ 13,935	$ 13,519	$ 14,941	$ 15,960

The Business, Basis of Presen_5

The Business, Basis of Presentation and Summary of Significant Accounting Policies - Property and Equipment (Details)	12 Months Ended
	Dec. 31, 2018
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 Presen_6

The Business, Basis of Presentation and Summary of Significant Accounting Policies - Intangibles (Details)	12 Months Ended
	Dec. 31, 2018
Weighted Average | Patents
Finite-Lived Intangible Assets [Line Items]
Finite-lived intangible asset, useful life	8 years

The Business, Basis of Presen_7

The Business, Basis of Presentation and Summary of Significant Accounting Policies - Impairment of Long-Lived Assets (Details) - USD ($)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Accounting Policies [Abstract]
Asset impairment charges	$ 0	$ 0	$ 0

The Business, Basis of Presen_8

The Business, Basis of Presentation and Summary of Significant Accounting Policies - Segment Reporting (Details)	12 Months Ended
	Dec. 31, 2018segment
Accounting Policies [Abstract]
Number of operating segments	1

The Business, Basis of Presen_9

The Business, Basis of Presentation and Summary of Significant Accounting Policies - Corporate Restructuring (Details) - USD ($) $ in Millions	1 Months Ended
	Jul. 31, 2018	Jun. 30, 2017	May 31, 2017
Accounting Policies [Abstract]
Reduction of workforce	60.00%
Severance costs	$ 0.8	$ 3.2
Non-cash stock-based compensation charges	$ 0.1
Workforce reduction, commitment, rate			30.00%
Employee benefits and share-based compensation, noncash		$ 1.3

The Business, Basis of Prese_10

The Business, Basis of Presentation and Summary of Significant Accounting Policies - Balance Sheet, Topic 606 Adoption (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Jan. 01, 2018	Dec. 31, 2017
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Deferred revenue (contract liabilities), non-current		$ 77
Accumulated deficit	$ (392,723)	(344,014)	$ (345,858)
Calculated under Revenue Guidance in Effect before Topic 606
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Deferred revenue (contract liabilities), non-current			1,921
Accumulated deficit			$ (345,858)
Accounting Standards Update 2014-09 | Difference between Revenue Guidance in Effect before and after Topic 606
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Deferred revenue (contract liabilities), non-current		(1,844)
Accumulated deficit		$ 1,844

The Business, Basis of Prese_11

The Business, Basis of Presentation and Summary of Significant Accounting Policies - Recent Accounting Pronouncements (Details) - USD ($) $ in Thousands	Oct. 15, 2018	Mar. 31, 2018	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016	Jan. 01, 2018	Mar. 31, 2017	Jan. 01, 2017
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Excess tax benefit amount			$ (7,700)
Cumulative effect of accounting change						$ 1,844
Stock-based compensation expenses	$ 400		$ 5,440	$ 7,642	$ 12,872
Accounting Standards Update 2016-09
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Stock-based compensation expenses		$ 600
Additional paid-in capital
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Cumulative effect of accounting change								$ 602
Additional paid-in capital | Accounting Standards Update 2016-09
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Cumulative effect of accounting change							$ 600

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, 2018	Dec. 31, 2017	Dec. 31, 2016
Earnings Per Share [Abstract]
Potentially dilutive securities not included in calculation of diluted net loss per share (in shares)	0	245,488	462,628

Investments - Summary of Short-

Investments - Summary of Short-Term Investments (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2017USD ($)
Investment [Line Items]
Amortized cost	$ 46,632
Gains	0
Losses	77
Estimated fair value	$ 46,555
Corporate debt securities
Investment [Line Items]
Maturity (or less) (in years)	1 year
Amortized cost	$ 32,922
Gains	0
Losses	55
Estimated fair value	$ 32,867
Certificates of deposit
Investment [Line Items]
Maturity (or less) (in years)	1 year
Amortized cost	$ 8,216
Gains	0
Losses	0
Estimated fair value	$ 8,216
U.S. treasury securities
Investment [Line Items]
Maturity (or less) (in years)	1 year
Amortized cost	$ 3,996
Gains	0
Losses	18
Estimated fair value	$ 3,978
Debt securities of U.S. government-sponsored agencies
Investment [Line Items]
Maturity (or less) (in years)	1 year
Amortized cost	$ 1,498
Gains	0
Losses	4
Estimated fair value	$ 1,494

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, 2018	Dec. 31, 2017
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure	$ 11,173	$ 57,402
Cash equivalents
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure	11,173	10,847
Corporate debt securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure		32,867
Certificates of deposit
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure		8,216
U.S. treasury securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure		3,978
Debt securities of U.S. government-sponsored agencies
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure		1,494
Fair Value, Inputs, Level 1
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure	11,173	10,847
Fair Value, Inputs, Level 1 | Cash equivalents
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure	11,173	10,847
Fair Value, Inputs, Level 1 | Corporate debt securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure		0
Fair Value, Inputs, Level 1 | Certificates of deposit
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure		0
Fair Value, Inputs, Level 1 | U.S. treasury securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure		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, Fair Value Disclosure		0
Fair Value, Inputs, Level 2
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure	0	46,555
Fair Value, Inputs, Level 2 | Cash equivalents
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure	0	0
Fair Value, Inputs, Level 2 | Corporate debt securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure		32,867
Fair Value, Inputs, Level 2 | Certificates of deposit
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure		8,216
Fair Value, Inputs, Level 2 | U.S. treasury securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure		3,978
Fair Value, Inputs, Level 2 | Debt securities of U.S. government-sponsored agencies
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure		1,494
Fair Value, Inputs, Level 3
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure	0	0
Fair Value, Inputs, Level 3 | Cash equivalents
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure	$ 0	0
Fair Value, Inputs, Level 3 | Corporate debt securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure		0
Fair Value, Inputs, Level 3 | Certificates of deposit
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure		0
Fair Value, Inputs, Level 3 | U.S. treasury securities
Fair Value, Balance Sheet Grouping, Financial Statement Captions [Line Items]
Assets, Fair Value Disclosure		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, Fair Value Disclosure		$ 0

Strategic Alliances and Colla_3

Strategic Alliances and Collaborations - Revenue from Strategic Alliances (Details) - USD ($) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2018	Sep. 30, 2018	Jun. 30, 2018	Mar. 31, 2018	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Revenue from External Customer [Line Items]
Total revenues	$ 18	$ 18	$ 18	$ 18	$ 18	$ 18	$ 18	$ 18	$ 72	$ 72	$ 1,194
Strategic Alliances and Collaborations
Revenue from External Customer [Line Items]
Total revenues									72	72	1,194
Strategic Alliances and Collaborations | Sanofi
Revenue from External Customer [Line Items]
Total revenues									72	72	72
Strategic Alliances and Collaborations | AstraZeneca
Revenue from External Customer [Line Items]
Total revenues									$ 0	$ 0	$ 1,122

Strategic Alliances and Colla_4

Strategic Alliances and Collaborations (Details)

1 Months Ended

8 Months Ended

12 Months Ended

Nov. 30, 2018USD ($)

Jul. 31, 2017USD ($)

Jun. 30, 2017

Dec. 31, 2015USD ($)

Mar. 31, 2015USD ($)

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

Jul. 31, 2013USD ($)

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

Aug. 31, 2012agreement

Jul. 31, 2010target

Jan. 31, 2014USD ($)

Dec. 31, 2018USD ($)shares

Jan. 01, 2018USD ($)

Dec. 31, 2017USD ($)shares

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

Common stock, shares issued | shares

8,818,019

8,662,435

Common stock value

$ 9,000

$ 9,000

Upfront payment received

$ 2,500,000

Deferred revenue

$ 77,000

Sanofi

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

Number of collaborative areas granted | target

4

Upfront payment received

2,500,000

$ 400,000

Deferred revenue

$ 6,800,000

Agreement period

24 months

Expected revenue through milestone payments

$ 6,800,000

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

$ 10,000,000

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

$ 2,500,000

$ 2,500,000

Deferred revenue creditable against future milestones

$ 1,250,000

$ 1,250,000

$ 1,250,000

Milestone payments, earned

$ 1,250,000

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 | Common Stock Purchase Agreement

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

Deferred revenue

$ 100,000

Deferred revenue recognition period

1 year

Sanofi | Development Milestones

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

Expected revenue through milestone payments

$ 40,000,000

Sanofi | Proof-of-Concept Trial

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

Expected revenue through milestone payments

$ 38,800,000

Sanofi | Clinical

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

Expected revenue through milestone payments

40,000,000

Sanofi | Regulatory and Commercialization Milestones

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

Expected revenue through milestone payments

$ 130,000,000

AstraZeneca

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

Number of collaborative areas granted | agreement

3

Initial upfront option payment

$ 3,000,000

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

$ 4,300,000

Expected term of research and development plan

4 years

Termination grace period

12 months

Termination grace period extension

12 months

AstraZeneca | Clinical

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

Milestone payments, earned

$ 10,000,000

AstraZeneca | Preclinical

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

Milestone payments, earned

$ 2,500,000

Property and Equipment, net (De

Property and Equipment, net (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Property, Plant and Equipment [Line Items]
Property, Plant and Equipment, Gross	$ 17,700	$ 17,967
Less accumulated depreciation and amortization	(9,894)	(8,259)
Property and equipment, net	7,806	9,708
Depreciation and amortization expense	2,262	2,524	$ 2,276
Laboratory equipment
Property, Plant and Equipment [Line Items]
Property, Plant and Equipment, Gross	8,163	8,430
Computer equipment and software
Property, Plant and Equipment [Line Items]
Property, Plant and Equipment, Gross	281	281
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	$ 8,550

Intangible Assets, net (Details

Intangible Assets, net (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Finite-Lived Intangible Assets [Line Items]
Finite-lived intangible assets, gross	$ 721	$ 1,250
Accumulated amortization	(221)	(475)
Intangibles, net	500	775
Intangible asset amortization	100	100	$ 100
Finite-lived intangible assets, amortization expense, next 12 months (less than $1 million)	100
Finite-lived intangible assets, amortization expense, year two (less than $1 million)	100
Finite-lived intangible assets, amortization expense, year three (less than $1 million)	100
Finite-lived intangible assets, amortization expense, year four (less than $1 million)	100
Finite-lived intangible assets, amortization expense, year five (less than $1 million)	100
Patents
Finite-Lived Intangible Assets [Line Items]
Finite-lived intangible assets, gross	721	871
Licenses
Finite-Lived Intangible Assets [Line Items]
Finite-lived intangible assets, gross	$ 0	$ 379

Commitments and Contingencies_2

Commitments and Contingencies (Details) - USD ($)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016	Aug. 31, 2015	Jul. 31, 2015
Other Commitments [Line Items]
Term of lease					96 months
Tenant incentive				$ 1,400,000
Restricted cash	$ 0	$ 0
Tenant improvement allowance used	8,200,000		$ 8,200,000		$ 8,500,000
Unused tenant improvement	300,000
Rent expense	$ 1,300,000	1,400,000	$ 1,200,000
Renewal term	5 years
Other Noncurrent Liabilities
Other Commitments [Line Items]
Deferred rent, less current portion	$ 8,000,000	$ 9,300,000

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, 2018	Dec. 31, 2017	Dec. 31, 2016
Commitments and Contingencies Disclosure [Abstract]
Rent expense	$ 1,300	$ 1,400	$ 1,200
Operating Leases, Future Minimum Payments Due, Fiscal Year Maturity [Abstract]
Operating Leases, Future Minimum Payments Due in 2019	2,654
Operating Leases, Future Minimum Payments, Due in 2020	2,733
Operating Leases, Future Minimum Payments, Due in 2021	2,815
Operating Leases, Future Minimum Payments, Due in 2022	2,901
Operating Leases, Future Minimum Payments, Due in 2023	2,986
Operating Leases, Future Minimum Payments, Due Thereafter	1,005
Operating Leases, Future Minimum Payments Due	$ 15,094

Term Loan (Details)

Term Loan (Details)	Jun. 22, 2016USD ($)	Jun. 17, 2016USD ($)loan	Nov. 30, 2018USD ($)	Dec. 31, 2018USD ($)	Dec. 31, 2017USD ($)	Dec. 31, 2016USD ($)	Nov. 05, 2018USD ($)	Mar. 31, 2017USD ($)
Debt Instrument [Line Items]
Proceeds from borrowing under term loan				$ 0	$ 0	$ 19,768,000
Upfront payment received			$ 2,500,000
Debt Financing Agreement
Debt Instrument [Line Items]
Maximum borrowing capacity		$ 30,000,000
Number of term loans | loan		2
Stated interest rate, percentage		8.51%
Term loan, less current portion and debt issuance costs				16,600,000
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%
Fourth Amendment
Debt Instrument [Line Items]
Prepayment requirement of loan from license fees							25.00%
Expected revenue through milestone payments							$ 10,000,000
Prepayment required for loan			$ 600,000
Payment fee							5.50%
Minimum cash, debt covenant							$ 10,000,000
Proceeds debt covenant, conditional minimum amount							15,000,000
Conditional amount, capital event, debt covenant							$ 5,000,000
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				$ 16,658,000
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) - Debt Financing Agreement Tranche A $ in Thousands	Dec. 31, 2018USD ($)
Debt Instrument [Line Items]
Future Repayments of Principal, 2019	$ 10,540
Future Repayments of Principal, 2020	6,118
Long-term Debt	$ 16,658

Common Stock and Stockholders_3

Common Stock and Stockholders' Equity - Narrative 1 (Details) $ / shares in Units, $ in Thousands	Oct. 15, 2018USD ($)optionholder$ / sharesshares	Dec. 31, 2018USD ($)voteshares	Dec. 31, 2017USD ($)shares	Dec. 31, 2016USD ($)shares	Dec. 31, 2015shares
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Common stock voting rights per share (vote) | vote		1
Reverse stock split ratio		0.08333
Weighted average exercise price, Exercisable (in dollars per share) | $ / shares	$ 4.56
Exchange Offer shares available for exchange (in shares)	915,009
Number of Optionholders | optionholder	31
Restricted shares issued (in shares)	603,058
Stock-based compensation expenses | $	$ 400	$ 5,440	$ 7,642	$ 12,872
Common stock
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares outstanding (in shares)		8,818,019	8,662,435	4,409,909	4,388,625
Performance Shares
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Restricted shares issued (in shares)	514,955

Common Stock and Stockholders_4

Common Stock and Stockholders' Equity - Shares Reserved for Future Issuance (Details) shares in Thousands	Dec. 31, 2018shares
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Common stock options outstanding	59
Total common shares reserved for future issuance	1,353
Restricted Stock Units (RSUs)
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Restricted stock units outstanding	601
Common stock available for future grant under the 2012 Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares available for future grant	454
Common stock available for future grant under the Inducement Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares available for future grant	83
Employee Stock Purchase Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares available for future grant	156

Common Stock and Stockholders_5

Common Stock and Stockholders' Equity - Stock Option Activity (Details) - USD ($) $ / shares in Units, shares in Thousands, $ in Thousands	12 Months Ended
	Dec. 31, 2018	Oct. 15, 2018
Number of options
End number of options (in shares), outstanding	59
Weighted average exercise price
Weighted average exercise price, Exercisable (in dollars per share)		$ 4.56
Stock options
Number of options
Beginning number of options (in shares), outstanding	887
Number of options, Granted (in shares)	603
Number of options, Exercised (in shares)	(1)
Number of options, Canceled/forfeited/expired (in shares)	(1,430)
End number of options (in shares), outstanding	59
Number of options, Exercisable (in shares)	35
Weighted average exercise price
Beginning, Weighted average exercise price, Options outstanding (in dollars per share)	$ 53.24
Weighted average exercise price, Granted (in dollars per share)	11.70
Weighted average exercise price, Exercised (in dollars per share)	4.56
Weighted average exercise price, Canceled/forfeited/expired (in dollars per share)	36.06
Ending, Weighted average exercise price, Options outstanding (in dollars per share)	45.60
Weighted average exercise price, Exercisable (in dollars per share)	$ 63.39
Weighted average remaining contractual term
Weighted average remaining contractual term, Options outstanding	6 years 3 months 18 days
Weighted average remaining contractual term, Exercisable	4 years 7 months 6 days
Aggregate intrinsic value
Aggregate intrinsic value, Options outstanding	$ 0
Aggregate intrinsic value, Exercisable	$ 0

Common Stock and Stockholders_6

Common Stock and Stockholders' Equity - Narrative 2 (Details) - USD ($) $ / shares in Units, $ in Thousands	Jul. 17, 2015	Oct. 31, 2012	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2018
Class of Stock [Line Items]
Proceeds from stock options exercised (less than in 2018 and 2017)			$ 1	$ 4	$ 310
Stock options
Class of Stock [Line Items]
Weighted average grant date fair value of employee stock options (in dollars per share)			$ 8.63	$ 11.73	$ 39.54
Total intrinsic value of stock options exercised (less than in 2018 and 2017)			$ 100		$ 200
Proceeds from stock options exercised (less than in 2018 and 2017)			100	$ 100	$ 300
Compensation cost related to non-vested awards not yet recognized			$ 100			$ 100
Weighted-average recognition period of compensation cost related to non-vested awards not yet recognized			1 year 4 months 24 days
Restricted Stock Units (RSUs)
Class of Stock [Line Items]
Share granted (in shares)			705,000
Compensation cost related to non-vested awards not yet recognized			$ 3,800			$ 3,800
Weighted-average recognition period of compensation cost related to non-vested awards not yet recognized			3 years 5 months
Employee Stock Purchase Plan 2012
Class of Stock [Line Items]
Percentage of participants eligible compensation		15.00%
Shares issued (in shares)			26,417			87,913
Common stock shares reserved for future issuance and authorized for purchase			155,056			155,056
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		83,333			83,333
Vesting period	4 years
Awards vesting, first anniversary	25.00%
Remaining vesting period after initial 25%, on a monthly basis (months)	36 months

Common Stock and Stockholders_7

Common Stock and Stockholders' Equity - RSU Activity (Details) - Restricted Stock Units (RSUs) - USD ($) $ / shares in Units, shares in Thousands, $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2018
Share-based Compensation Arrangement by Share-based Payment Award, Non-Option Equity Instruments, Outstanding [Roll Forward]
RSUs outstanding at December 31, 2017 (in shares)	35
Granted (in shares)	705
Vested (in shares)	(128)
Canceled/forfeited/expired (in shares)	(11)
RSUs outstanding at December 31, 2018 (in shares)	601
Share-based Compensation Arrangement by Share-based Payment Award, Equity Instruments Other than Options, Nonvested, Weighted Average Grant Date Fair Value [Abstract]
RSUs outstanding at December 31, 2017 (usd per share)	$ 10.68
Granted (usd per share)	1.84
Vested (usd per share)	5.49
Forfeited (usd per share)	6.32
RSUs outstanding at December 31, 2018 (usd per share)	$ 10.68	$ 1.50
Weighted average remaining contractual term	3 years 5 months
Aggregate intrinsic value		$ 559
Compensation cost related to non-vested awards not yet recognized		$ 3,800
Weighted-average recognition period of compensation cost related to non-vested awards not yet recognized	3 years 5 months

Common Stock and Stockholders_8

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 Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016	Jan. 01, 2018	Mar. 31, 2017	Jan. 01, 2017
Weighted average assumptions
Cumulative effect of accounting change				$ 1,844
Stock options
Weighted average assumptions
Risk-free interest rate	2.70%	2.00%	1.50%
Volatility	87.80%	89.40%	82.70%
Dividend yield	0.00%	0.00%	0.00%
Expected term (years)	6 years 1 month 6 days	6 years 1 month 6 days	6 years
Performance stock options
Weighted average assumptions
Risk-free interest rate	2.70%	2.10%	1.40%
Volatility	87.40%	89.20%	82.40%
Dividend yield	0.00%	0.00%	0.00%
Expected term (years)	5 years 7 months 28 days	5 years 8 months 12 days	5 years 10 months 24 days
Employee Stock Purchase Plan
Weighted average assumptions
Risk-free interest rate	1.90%	0.90%	0.50%
Volatility	100.60%	105.60%	93.70%
Dividend yield	0.00%	0.00%	0.00%
Expected term (years)	6 months	6 months	6 months
Additional paid-in capital
Weighted average assumptions
Cumulative effect of accounting change						$ 602
Accounting Standards Update 2016-09 | Additional paid-in capital
Weighted average assumptions
Cumulative effect of accounting change					$ 600

Common Stock and Stockholders_9

Common Stock and Stockholders' Equity - Schedule of Compensation Expense (Details) - USD ($) $ in Thousands	Oct. 15, 2018	May 31, 2017	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Employee Service Share-based Compensation, Allocation of Recognized Period Costs [Line Items]
Stock-based compensation expenses	$ 400		$ 5,440	$ 7,642	$ 12,872
Research and development
Employee Service Share-based Compensation, Allocation of Recognized Period Costs [Line Items]
Stock-based compensation expenses			2,225	2,862	5,458
Research and development-restructuring related adjustments
Employee Service Share-based Compensation, Allocation of Recognized Period Costs [Line Items]
Stock-based compensation expenses		$ (1,400)	31	(1,399)	0
General and administrative
Employee Service Share-based Compensation, Allocation of Recognized Period Costs [Line Items]
Stock-based compensation expenses			3,199	3,500	7,414
General and administrative-restructuring related adjustments
Employee Service Share-based Compensation, Allocation of Recognized Period Costs [Line Items]
Stock-based compensation expenses		2,700	$ (15)	$ 2,679	$ 0
Restructuring Charges
Employee Service Share-based Compensation, Allocation of Recognized Period Costs [Line Items]
Stock-based compensation expenses		$ 100

Defined Contribution Plan (Deta

Defined Contribution Plan (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
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	$ 0.1	$ 0.2

Income Taxes - Components of In

Income Taxes - Components of Income Tax (Benefit) Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Current:
Federal	$ (26)	$ (143)	$ 0
State	1	1	1
Current Income Tax Expense (Benefit), total	(25)	(142)	1
Deferred:
Federal	87	(55)	(5)
State	0	0	0
Deferred Income Tax Expense (Benefit), total	87	(55)	(5)
Income tax expense (benefit)	$ 62	$ (197)	$ (4)

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, 2018	Dec. 31, 2017	Dec. 31, 2016
Effective Income Tax Rate Reconciliation, Amount [Abstract]
Expected income tax benefit at federal statutory tax rate	$ (10,216)	$ (24,515)	$ (27,826)
State income taxes, net of federal benefit	(3,005)	1	(1,152)
Tax credits	(3,666)	(5,151)	(5,447)
Change in valuation allowance	12,706	(8,705)	31,990
Adjustments related to prior year	441	1	(1,320)
Stock compensation	251	1,135	2,458
Reserve for uncertain tax positions	3,596	311	1,314
Tax Cuts and Jobs Act rate change	0	36,249	0
Other	(45)	477	(21)
Income tax expense (benefit)	$ 62	$ (197)	$ (4)

Income Taxes - Components of De

Income Taxes - Components of Deferred Tax Assets and Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Deferred tax assets:
Net operating loss carryovers	$ 74,965	$ 66,549
Research and development and other tax credits	33,121	29,702
Deferred revenue	16	419
Stock compensation expense	5,033	4,238
Other	2,027	2,196
Total deferred tax assets	115,162	103,104
Total deferred tax liabilities	(176)	(408)
Net deferred tax asset	114,986	102,696
Valuation allowance	(114,960)	(102,641)
Net deferred tax asset	$ 26	$ 55

Income Taxes - Narrative (Detai

Income Taxes - Narrative (Details) - USD ($)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Operating Loss Carryforwards [Line Items]
Valuation allowance	$ 114,960,000	$ 102,641,000
Net operating loss carryovers	74,965,000	66,549,000
Excess tax benefit amount	$ (7,700,000)
Net operating loss carryforward limitation on use percentage ownership change minimum	50.00%
Decrease in deferred tax asset		36,200,000
Unrecognized tax benefits	$ 14,700,000	4,421,000	$ 5,632,000	$ 2,298,000
Unrecognized tax benefits that would impact effective tax rate	11,800,000
Income tax penalties and interest accrued	0	$ 0	$ 0
Internal Revenue Service (IRS)
Operating Loss Carryforwards [Line Items]
Net operating loss carryovers	305,300,000
Internal Revenue Service (IRS) | Research Tax Credit Carryforward
Operating Loss Carryforwards [Line Items]
Research and development tax credits carryforward	30,900,000
California
Operating Loss Carryforwards [Line Items]
Net operating loss carryovers	255,500,000
California | Research Tax Credit Carryforward
Operating Loss Carryforwards [Line Items]
Research and development tax credits carryforward	$ 8,800,000

Income Taxes - Changes in Amoun

Income Taxes - Changes in Amount of Unrecognized Tax Benefits (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Reconciliation of Unrecognized Tax Benefits, Excluding Amounts Pertaining to Examined Tax Returns [Roll Forward]
Beginning balance of unrecognized tax benefits	$ 4,421	$ 5,632	$ 2,298
Increase (decrease) for prior year tax positions	5,961	(2,466)	1,991
Increase for current year tax positions	4,318	1,255	1,343
Total	$ 14,700	$ 4,421	$ 5,632

Related Party Transactions (Det

Related Party Transactions (Details) - USD ($)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Sanofi
Related Party Transaction [Line Items]
Expenses incurred for services performed or out-of-pocket expenses (less than in 2018 and 2017)	$ 100,000	$ 100,000	$ 900,000

Selected Quarterly Financial _3

Selected Quarterly Financial Data (Unaudited) (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2018	Sep. 30, 2018	Jun. 30, 2018	Mar. 31, 2018	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Quarterly Financial Information Disclosure [Abstract]
Total revenues	$ 18	$ 18	$ 18	$ 18	$ 18	$ 18	$ 18	$ 18	$ 72	$ 72	$ 1,194
Total operating expenses	(8,000)	(9,872)	(13,362)	(15,601)	(13,724)	(15,433)	(21,335)	(19,711)	(46,835)	(70,203)	(82,696)
Net loss	$ (8,563)	$ (10,273)	$ (13,847)	$ (16,025)	$ (14,448)	$ (15,828)	$ (21,608)	$ (20,021)	$ (48,709)	$ (71,905)	$ (81,836)
Basic and diluted net loss per share (dollars per share)	$ (0.98)	$ (1.18)	$ (1.59)	$ (1.85)	$ (1.67)	$ (2.11)	$ (4.87)	$ (4.53)	$ (5.59)	$ (11.47)	$ (18.59)

Subsequent Events (Details)

Subsequent Events (Details)	Feb. 19, 2019USD ($)	Feb. 25, 2019USD ($)ft²	Jan. 31, 2019USD ($)	Dec. 31, 2018USD ($)	Jul. 31, 2015
Subsequent Event [Line Items]
Term of lease					96 months
Future lease payments				$ 15,094,000
Fifth Amendment | Subsequent Event
Subsequent Event [Line Items]
Term loan			$ 20,000,000
New Lease | Subsequent Event
Subsequent Event [Line Items]
Net rentable area | ft²		24,562
Term of lease		51 months
Future lease payments		$ 4,800,000
Prior Lease | Subsequent Event
Subsequent Event [Line Items]
Net rentable area | ft²		59,248
Future lease payments		$ 14,400,000
Nitto | Space Swap Agreement | Subsequent Event
Subsequent Event [Line Items]
Relocation assistance payment	$ 100,000
Difference between the security deposits under the Prior Lease and Nitto’s prior lease	200,000
Rent reimbursement	$ 1,300,000

Uncategorized Items - rgls-2018

Label	Element	Value
Retained Earnings [Member]
Cumulative Effect of New Accounting Principle in Period of Adoption	us-gaap_CumulativeEffectOfNewAccountingPrincipleInPeriodOfAdoption	$ (602,000)
Cumulative Effect of New Accounting Principle in Period of Adoption	us-gaap_CumulativeEffectOfNewAccountingPrincipleInPeriodOfAdoption	$ 1,844,000