Audentes Therapeutics 10-Q 7 May 19 2019 Q1 Quarterly report Financial data

Document and Entity Information

Document and Entity Information - shares	3 Months Ended
	Mar. 31, 2019	May 03, 2019
Document And Entity Information [Abstract]
Document Type	10-Q
Amendment Flag	false
Document Period End Date	Mar. 31, 2019
Document Fiscal Year Focus	2019
Document Fiscal Period Focus	Q1
Trading Symbol	BOLD
Entity Registrant Name	AUDENTES THERAPEUTICS, INC.
Entity Central Index Key	0001628738
Current Fiscal Year End Date	--12-31
Entity Filer Category	Large Accelerated Filer
Entity Small Business	false
Entity Emerging Growth Company	false
Entity Common Stock, Shares Outstanding		44,290,458

Condensed Consolidated Balance

Condensed Consolidated Balance Sheets - USD ($) $ in Thousands	Mar. 31, 2019	Dec. 31, 2018
Current assets:
Cash and cash equivalents	$ 133,160	$ 144,349
Short-term investments	236,344	269,958
Prepaid expenses and other current assets	3,651	5,465
Total current assets	373,155	419,772
Restricted cash - long-term	3,748	3,748
Long-term investments	5,517	0
Property and equipment, net	34,731	32,099
Right of use assets	21,089
Goodwill	3,631	3,631
Intangible assets	8,000	8,000
Other assets	5,305	5,305
Total assets	455,176	472,555
Current liabilities:
Accounts payable	11,811	8,123
Accrued liabilities	11,520	12,928
Operating lease liabilities	2,773
Contingent acquisition consideration payable	0	2,345
Deferred rent	0	456
Total current liabilities	26,104	23,852
Deferred rent - long-term	0	4,720
Asset retirement obligation - long-term	221	215
Operating lease liabilities - long-term	23,519
Contingent acquisition consideration payable - long-term	2,323	0
Deferred tax liability, net	1,014	1,014
Total liabilities	53,181	29,801
Stockholders' equity:
Preferred stock, $0.00001 par value, 10,000,000 shares authorized as of March 31, 2019 and December 31, 2018; 0 shares issued and outstanding as of March 31, 2019 and December 31, 2018, respectively	0	0
Common stock, $0.00001 par value, 300,000,000 shares authorized as of March 31, 2019 and December 31, 2018; 43,760,677 and 43,546,786 shares issued and outstanding as of March 31, 2019 and December 31, 2018, respectively	0	0
Additional paid-in capital	770,789	762,284
Accumulated deficit	(368,861)	(319,470)
Accumulated other comprehensive income (loss)	67	(60)
Total stockholders' equity	401,995	442,754
Total liabilities and stockholders' equity	$ 455,176	$ 472,555

Condensed Consolidated Balanc_2

Condensed Consolidated Balance Sheets (Parenthetical) - $ / shares	Mar. 31, 2019	Dec. 31, 2018
Statement of Financial Position [Abstract]
Preferred stock, par value (USD per share)	$ 0.00001	$ 0.00001
Preferred stock, shares authorized (shares)	10,000,000	10,000,000
Preferred stock, shares issued (shares)	0	0
Preferred stock, shares outstanding (shares)	0	0
Common stock, par value (USD per share)	$ 0.00001	$ 0.00001
Common stock, shares authorized (shares)	300,000,000	300,000,000
Common stock, shares issued (shares)	43,760,677	43,546,786
Common stock, shares outstanding (shares)	43,760,677	43,546,786

Condensed Consolidated Statemen

Condensed Consolidated Statements of Operations and Comprehensive Loss - USD ($) $ in Thousands	3 Months Ended
	Mar. 31, 2019	Mar. 31, 2018
Operating expenses:
Research and development	$ 39,837	$ 19,891
General and administrative	11,993	6,519
Total operating expenses	51,830	26,410
Loss from operations	(51,830)	(26,410)
Interest income, net	2,472	859
Other expense, net	(33)	(20)
Net loss	(49,391)	(25,571)
Unrealized gains (losses) on investments, net	127	(14)
Comprehensive loss	$ (49,264)	$ (25,585)
Net loss per share, basic and diluted (USD per share)	$ (1.13)	$ (0.74)
Weighted-average number of shares used in computing net loss per share, basic and diluted (shares)	43,625,316	34,582,071

Condensed Consolidated Statem_2

Condensed Consolidated Statements of Stockholders' Equity Statement - USD ($) $ in Thousands	Total	Common Stock	Additional Paid-in Capital	Accumulated Deficit	Accumulated Other Comprehensive Loss
Beginning balance (in shares) at Dec. 31, 2017		29,901,368
Beginning balance at Dec. 31, 2017	$ 156,598	$ 0	$ 347,327	$ (190,649)	$ (80)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Exercise of stock options (in shares)		183,692
Exercise of stock options	807		807
Stock-based compensation expense	3,385		3,385
Issuance of common stock, net of $14,201 in issuance costs (in shares)		6,612,500
Issuance of common stock, net of $14,201 in issuance costs	217,237		217,237
Net loss	(25,571)			(25,571)
Unrealized gain (loss) on investments, net	(14)				(14)
Ending balance (in shares) at Mar. 31, 2018		36,697,560
Ending balance at Mar. 31, 2018	$ 352,442	$ 0	568,756	(216,220)	(94)
Beginning balance (in shares) at Dec. 31, 2018	43,546,786	43,546,786
Beginning balance at Dec. 31, 2018	$ 442,754	$ 0	762,284	(319,470)	(60)
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Exercise of stock options (in shares)	213,891	213,891
Exercise of stock options	$ 3,005	$ 0	3,005	0	0
Stock-based compensation expense	5,500		5,500
Net loss	(49,391)			(49,391)
Unrealized gain (loss) on investments, net	$ 127				127
Ending balance (in shares) at Mar. 31, 2019	43,760,677	43,760,677
Ending balance at Mar. 31, 2019	$ 401,995	$ 0	$ 770,789	$ (368,861)	$ 67

Condensed Consolidated Statem_3

Condensed Consolidated Statements of Cash Flows - USD ($) $ in Thousands	3 Months Ended
	Mar. 31, 2019	Mar. 31, 2018
Cash flows from operating activities:
Net loss	$ (49,391)	$ (25,571)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation and amortization	1,728	1,149
Amortization of right-of-use assets	580
Stock-based compensation	5,500	3,385
Accretion of discount on marketable securities	(1,090)	(121)
Change in fair value of contingent acquisition consideration payable	(22)	(2,284)
Other	6	34
Changes in operating assets and liabilities:
Prepaid expenses and other current assets	1,814	275
Accounts payable	1,852	596
Accrued liabilities	(2,644)	(2,223)
Deferred rent	0	168
Operating lease liabilities	(553)
Net cash used in operating activities	(42,220)	(24,592)
Cash flows from investing activities:
Purchases of property and equipment	(1,288)	(921)
Proceeds from maturities of marketable securities	146,802	34,775
Purchases of marketable securities	(117,488)	(35,294)
Net cash provided by (used in) investing activities	28,026	(1,440)
Cash flows from financing activities:
Proceeds from exercise of stock options	3,005	807
Proceeds from issuance of common stock, net of issuance costs	0	217,122
Net cash provided by financing activities	3,005	217,929
Net (decrease) increase in cash, cash equivalents and restricted cash	(11,189)	191,897
Cash, cash equivalents and restricted cash at beginning of period	148,097	42,661
Cash, cash equivalents and restricted cash at end of period	136,908	234,558
Noncash investing and financing activities:
Change in accounts payable and accrued liabilities related to property and equipment purchases	3,072	2,293
Deferred financing costs for follow-on offering	0	$ 115
Cash paid for amounts included in the measurement of lease liabilities:
Operating leases	$ 1,323

Organization and Basis of Prese

Organization and Basis of Presentation	3 Months Ended
	Mar. 31, 2019
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Organization and Basis of Presentation	Organization and Basis of Presentation Audentes Therapeutics, Inc., or the Company, was incorporated in the State of Delaware on November 13, 2012. The Company is an AAV-based genetic medicines company focused on developing and commercializing innovative products for patients living with serious, rare neuromuscular diseases. The Company operates in one business segment, with its corporate headquarters located in San Francisco, California and its manufacturing and research operations located in South San Francisco, California. The accompanying consolidated financial statements include the accounts of Audentes Therapeutics, Inc., and its wholly owned subsidiaries. All intercompany balances and transactions have been eliminated in consolidation. Need for Additional Capital The Company has incurred net losses from operations since inception and as of March 31, 2019 , had an accumulated deficit of $368.9 million . The Company expects that its development activities will continue to generate operating losses over the next several years. Liquidity As of March 31, 2019 , the Company had approximately $375.0 million of cash, cash equivalents and marketable securities, consisting of $133.2 million of cash and cash equivalents and $241.9 million of marketable securities. The Company believes that its balance of cash, cash equivalents and investments as of March 31, 2019 is sufficient to fund its current operational plan for at least the next twelve months, though it may pursue additional capital through the issuance of additional equity and potentially through strategic alliances with partner companies. If financing is not available at adequate levels or on acceptable terms, the Company may need to reevaluate its operating plans. In addition, if the Company’s anticipated operating results are not achieved in future periods, planned expenditures may need to be reduced in order to extend the time period over which the then-available resources would be able to fund the Company’s operations.

Summary of Significant Accounti

Summary of Significant Accounting Policies	3 Months Ended
	Mar. 31, 2019
Accounting Policies [Abstract]
Summary of Significant Accounting Policies	Summary of Significant Accounting Policies The Company's significant accounting policies are detailed in Note 2 of the “Notes to Consolidated Financial Statements” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2018 . Except as detailed below, there have been no material changes to the Company’s significant accounting policies during the three months ended March 31, 2019, as compared to the significant accounting policies disclosed in Note 2 - Significant Accounting Policies included in the Company’s Annual Report on Form 10-K for the year ended December 31, 2018. Leases The Company determines if an arrangement is or contains a lease at inception by assessing whether the arrangement contains an identified asset and whether it has the right to control the identified asset. Right-of-use (ROU) assets represent the Company's right to use an underlying asset for the lease term and lease liabilities represent the Company's obligation to make lease payments arising from the lease. ROU assets and lease liabilities are recognized at the lease commencement date based on the present value of future lease payments over the lease term. As the implicit rate in the Company's leases is unknown, the Company uses its incremental borrowing rate based on the information available at the lease commencement date in determining the present value of future lease payments. The Company gives consideration to its credit risk, term of the lease, total lease payments and adjust for the impacts of collateral, as necessary, when calculating its incremental borrowing rates. The ROU asset is based on the measurement of the lease liability and also includes any lease payments made prior to or on lease commencement and excludes lease incentives and initial direct costs incurred, as applicable. The lease terms may include options to extend or terminate the lease when it is reasonably certain the Company will exercise any such options. Rent expense for the Company's operating leases is recognized on a straight-line basis over the lease term. The Company has lease agreements with lease and non-lease components. The Company has elected to not separate lease and non-lease components for any leases within its existing classes of assets and, as a result, accounts for the lease and non-lease components as a single lease component. The Company has also elected to not apply the recognition requirement to any leases within its existing classes of assets with a term of 12 months or less. Basis of Preparation The accompanying unaudited interim condensed consolidated financial statements have been prepared in accordance with accounting principles generally accepted in the United States of America, or U.S. GAAP, and applicable rules and regulations of the SEC regarding interim financial reporting. As permitted under those rules, certain footnotes or other financial information that are normally required by U.S. GAAP have been condensed or omitted, and accordingly the balance sheet as of December 31, 2018 has been derived from audited financial statements at that date but does not include all of the information required by U.S. GAAP for complete financial statements. These unaudited interim condensed consolidated financial statements have been prepared on the same basis as the Company’s annual financial statements and, in the opinion of management, reflect all adjustments (consisting only of normal recurring adjustments) that are necessary for a fair presentation of the Company’s financial information. The results of operations for the three months ended March 31, 2019 are not necessarily indicative of the results to be expected for the year ending December 31, 2019 or for any other interim period or for any other future year. The accompanying unaudited interim condensed consolidated financial statements and related financial information should be read in conjunction with the audited financial statements and the related notes thereto for the year ended December 31, 2018 included in the Company’s audited financial statements filed in its Annual Report on Form 10-K for the year ended December 31, 2018 . Use of Estimates The accompanying unaudited interim condensed consolidated financial statements have been prepared in accordance with U.S. generally accepted accounting principles, or GAAP. The preparation of financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities, as of the date of the financial statements, and the reported amounts of any expenses during the reporting period. On an ongoing basis, management evaluates its estimates, including those related to accrued liabilities, acquisition contingent consideration, income taxes, and stock-based compensation. Management bases its estimates on historical experience, and on various other market-specific relevant assumptions that management believes to be reasonable, under the circumstances. Actual results may differ from those estimates. Concentration of Credit Risk Financial instruments that potentially subject the Company to a concentration of credit risk consist of cash and cash equivalents and marketable securities. The Company invests in a variety of financial instruments and in accordance with its investment policy, limits the amount of credit exposure with any one issuer, industry or geographic area for investments other than instruments backed by the U.S. federal government. Concentration of Manufacturing and Third-Party Services Risk The Company is subject to certain risks with respect to sources of supply of manufactured materials and drug product for use in its preclinical studies and clinical trials. Due to the technical aspects of manufacturing drug product for gene therapies, there exist few alternative sources of manufacturing. The Company is reliant upon its own internal manufacturing capability and a small number of third-party vendors to produce drug product in sufficient quantities and quality to conduct its research and development activities. Accounting Pronouncements Adopted in 2019 In June 2018, the FASB issued ASU 2018-07, Compensation - Stock Compensation (Topic 718), Improvements to Nonemployee Share-Based Payment Accounting , which expands the scope of Topic 718 to include share-based payment transactions for acquiring goods and services from nonemployees. An entity should apply the requirements of Topic 718 to nonemployee awards except for specific guidance on inputs to an option pricing model and the attribution of cost. The measurement of equity-classified nonemployee awards is fixed at the grant date, and entities would measure the cost of awards subject to a performance condition using the outcome that is probable at the balance sheet date. The Company adopted this standard on January 1, 2019. As a result of adopting this standard, the Company no longer remeasures equity-classified nonemployee awards. The adoption of this new standard did not result in material impact on the Company's condensed consolidated financial statements. In February 2016, the FASB issued ASU No. 2016-02, Leases (Topic 842) , which establishes a comprehensive new lease accounting model. Under the new guidance, at the commencement date, lessees are required to recognize a lease liability with a corresponding right-of-use (ROU) asset. Effective January 1, 2019, the Company adopted Topic 842 using the modified retrospective approach provided by ASU 2018-11. Results for reporting periods beginning January 1, 2019 are presented under Topic 842, while prior period amounts were not adjusted and continue to be presented in accordance with the Company’s historical accounting under Topic 840, Leases . The Company elected certain practical expedients permitted under the transition guidance, including the election to carryforward historical lease classification. The Company also elected the short-term lease practical expedient, which allowed the Company to not recognize leases with a term of less than twelve months on its consolidated balance sheets. In addition, the Company elected the lease and non-lease components practical expedient, which allowed the Company to calculate the present value of the fixed payments without performing an allocation of lease and non-lease components. The impact of the adoption of Topic 842 on the accompanying Condensed Consolidated Balance Sheet as of January 1, 2019 was as follows: December 31, 2018 Effect of Adoption January 1, 2019 (in thousands) Operating lease right-of-use assets $ — $ 21,669 $ 21,669 Liabilities: Operating leases $ — $ 2,541 $ 2,541 Deferred rent $ 456 $ (456 ) $ — Operating lease liabilities - long-term $ — $ 24,304 $ 24,304 Deferred rent and asset retirement obligation - long-term $ 4,935 $ (4,720 ) $ 215 Adoption of the new standard resulted in recording operating lease right-of-use assets and operating lease liabilities of approximately $21.1 million and $26.3 million , respectively, on the Company’s condensed consolidated balance sheets as of March 31, 2019 . However, the adoption of the new standard did not have an impact on the Company’s beginning accumulated deficit, statement of operations or cash flows. For additional information regarding the Company’s leases, see Note 9 in the notes to the condensed consolidated financial statements.

Investments

Investments	3 Months Ended
	Mar. 31, 2019
Investments [Abstract]
Investments	Investments Investments consist of available-for-sale securities as follows: March 31, 2019 Amortized Cost Unrealized Gains Unrealized Losses Fair Value (in thousands) Money market funds $ 49,747 $ — $ — $ 49,747 Commercial paper 114,105 1 (12 ) 114,094 Corporate securities 78,231 70 (9 ) 78,292 U.S. treasury bills 51,288 7 — 51,295 U.S. government agency securities 27,867 3 (2 ) 27,868 U.S. agency bonds 32,732 9 — 32,741 U.S. agency discount securities 10,999 — — 10,999 Total available-for-sale securities $ 364,969 $ 90 $ (23 ) $ 365,036 December 31, 2018 Amortized Cost Unrealized Gains Unrealized Losses Fair Value (in thousands) Money market funds $ 33,399 $ — $ — $ 33,399 Commercial paper 144,578 — — 144,578 Corporate securities 82,670 8 (39 ) 82,639 U.S. treasury bills 60,573 — (8 ) 60,565 U.S. government agency securities 15,219 — — 15,219 U.S. agency bonds 51,411 — (22 ) 51,389 U.S. agency discount securities 18,716 — — 18,716 Total available-for-sale securities $ 406,566 $ 8 $ (69 ) $ 406,505 The Company does not intend to sell the investments that are in an unrealized loss position, and it is unlikely that it will be required to sell the investments before recovery of their amortized cost basis, which may be maturity. The Company determined that the gross unrealized losses on its marketable securities at March 31, 2019 were temporary in nature. Unrealized losses from all marketable securities at March 31, 2019 are not material. The Company’s long-term investments as of March 31, 2019 consist of corporate securities.

Fair Value Measurements

Fair Value Measurements	3 Months Ended
	Mar. 31, 2019
Fair Value Disclosures [Abstract]
Fair Value Measurements	Fair Value Measurements Fair value accounting is applied for all financial assets and liabilities that are recognized or disclosed at fair value in the financial statements on a recurring basis (at least annually). Financial instruments include cash and cash equivalents, restricted cash, accounts payable and accrued liabilities that approximate fair value due to their relatively short maturities. Assets and liabilities recorded at fair value on a recurring basis in the balance sheets are categorized based upon the level of judgment associated with the inputs used to measure their fair values. Fair value is defined as the exchange price that would be received for an asset or an exit price that would be paid to transfer a liability in the principal or most advantageous market for the asset or liability in an orderly transaction between market participants on the measurement date. The authoritative guidance on fair value measurements establishes a three-tier fair value hierarchy for disclosure of fair value measurements as follows: Level 1 – Inputs are unadjusted, quoted prices in active markets for identical assets or liabilities at the measurement date; Level 2 – Inputs are observable, unadjusted quoted prices in active markets for similar assets or liabilities, unadjusted quoted prices for identical or similar assets or liabilities in markets that are not active, or other inputs that are observable or can be corroborated by observable market data for substantially the full term of the related assets or liabilities; and Level 3 – Unobservable inputs that are significant to the measurement of the fair value of the assets or liabilities that are supported by little or no market data. Assets Measured at Fair Value Financial assets subject to fair value measurements on a recurring basis and the level of inputs used in such measurements are as follows: March 31, 2019 Fair Value Measurements Using Total Level 1 Level 2 Level 3 (in thousands) Money market funds $ 49,747 $ 49,747 $ — $ — Commercial paper 114,094 — 114,094 — Corporate securities 78,292 — 78,292 — U.S. treasury bills 51,295 — 51,295 — U.S. government agency securities 27,868 — 27,868 — U.S. agency bonds 32,741 — 32,741 — U.S. agency discount securities 10,999 — 10,999 — Total financial assets $ 365,036 $ 49,747 $ 315,289 $ — December 31, 2018 Fair Value Measurements Using Total Level 1 Level 2 Level 3 (in thousands) Money market funds $ 33,399 $ 33,399 $ — $ — Commercial paper 144,578 — 144,578 — Corporate securities 82,639 — 82,639 — U.S. treasury bills 60,565 — 60,565 — U.S. government agency securities 15,219 — 15,219 — U.S. agency bonds 51,389 — 51,389 — U.S. agency discount securities 18,716 — 18,716 — Total financial assets $ 406,505 $ 33,399 $ 373,106 $ — The financial assets listed above do not include cash held in the Company’s primary operating bank accounts of $10.0 million and $7.8 million as of March 31, 2019 and December 31, 2018 , respectively. Liabilities Measured at Fair Value The Company’s contingent acquisition consideration payable, resulting from the acquisition of Cardiogen Sciences, Inc., or Cardiogen, in August 2015, is estimated using a probability-based income approach utilizing an appropriate discount rate. Key assumptions used by management to estimate the fair value of contingent acquisition consideration payable include estimated probability of occurrence, the estimated timing of when the milestone may be attained and assumed discount period and discount rate, which are Level 3 inputs. Changes in the fair value of the contingent acquisition consideration payable, resulting from management’s revision of key assumptions are recorded in research and development expense in the consolidated statement of operations and comprehensive loss. The probability-based income approach used by management to estimate the fair value of the contingent acquisition consideration is most sensitive to changes in the estimated probability of occurrence. The following is a summary of the contingent acquisition consideration payable recorded in the accompanying consolidated balance sheets: Amount (in thousands) Balance, December 31, 2018 $ 2,345 Change in fair value of contingent acquisition consideration payable (22 ) Balance, March 31, 2019 $ 2,323

Balance Sheet Components

Balance Sheet Components	3 Months Ended
	Mar. 31, 2019
Disclosure Text Block Supplement [Abstract]
Balance Sheet Components	Balance Sheet Components Property and Equipment, Net Property and equipment, net, consist of the following: March 31, 2019 December 31, 2018 (in thousands) Furniture and office equipment $ 1,968 $ 1,898 Computer equipment 1,219 1,019 Software 513 513 Leasehold improvements 22,917 19,607 Laboratory equipment 10,007 9,570 Manufacturing equipment 6,723 6,619 Construction in progress and deposits on equipment 3,559 3,320 Total property and equipment 46,906 42,546 Less accumulated depreciation and amortization (12,175 ) (10,447 ) Property and equipment, net $ 34,731 $ 32,099 Property and equipment depreciation and amortization expense for the three months ended March 31, 2019 and 2018 was $1.7 million and $1.1 million , respectively. Accrued Liabilities Accrued liabilities consist of the following: March 31, 2019 December 31, 2018 (in thousands) Accrued payroll and related expenses $ 5,034 $ 8,581 Accrued research and development expenses 4,877 3,317 Accrued property and equipment 623 71 Accrued professional services 680 783 Other 306 176 Total accrued liabilities $ 11,520 $ 12,928

Commitments and Contingencies

Commitments and Contingencies	3 Months Ended
	Mar. 31, 2019
Organization, Consolidation and Presentation of Financial Statements [Abstract]
License Agreements	Commitments and Contingencies During the three months ended March 31, 2019 , the Company entered into an exclusive license agreement with Nationwide Children's Hospital related the Company's AT702 program. Pursuant to the agreement, the Company paid an upfront fee of $7.0 million and will be obligated to make certain milestone and royalty payments upon the achievement of developmental, regulatory and net sales milestones. As of March 31, 2019 , the Company is subject to contingent payments upon the achievement of certain development, regulatory and commercial milestones, totaling up to approximately $275.1 million across all of its licensing agreements. Of this amount, $77.9 million relates to the Company’s Crigler-Najjar and CASQ2 -CPVT programs, for which the Company announced plans to explore outlicensing opportunities to continue development activities .

Stock Compensation

Stock Compensation	3 Months Ended
	Mar. 31, 2019
Disclosure of Compensation Related Costs, Share-based Payments [Abstract]
Stock Compensation	Stock Compensation Stock-based Compensation Expense Stock-based compensation expense by category was as follows for the three months ended March 31, 2019 and 2018 : Three Months Ended March 31, 2019 2018 (in thousands) Research and development $ 3,215 $ 2,055 General and administrative 2,285 1,330 Total stock-based compensation expense $ 5,500 $ 3,385 The following table summarizes option activity for the three months ended March 31, 2019 : Number of Options Outstanding Weighted- Average Exercise Price Per Option Weighted- Average Remaining Contract Term (Years) Aggregate Intrinsic Value (in thousands) Balance, December 31, 2018 4,894,201 $ 18.79 7.97 $ 30,235 Options granted 1,248,000 $ 25.66 Options exercised (213,891 ) $ 14.05 Options forfeited (69,456 ) $ 26.37 Balance, March 31, 2019 5,858,854 $ 20.34 8.15 $ 109,622 Exercisable, March 31, 2019 2,316,213 $ 13.08 7.17 $ 60,086 Vested and expected to vest, March 31, 2019 5,483,592 $ 19.89 8.09 $ 105,047 The aggregate intrinsic values of options outstanding, exercisable, vested and expected to vest were calculated as the difference between the exercise price of the options and the fair value of the Company’s common stock as of March 31, 2019 . During the three months ended March 31, 2019 , options to purchase 213,891 shares of common stock with an intrinsic value of approximately $3.8 million were exercised, generating approximately $3.0 million of cash received. The weighted average grant date fair value of employee options granted during the three months ended March 31, 2019 and 2018 was $16.03 and $21.81 per share, respectively. As of March 31, 2019 , the total unrecognized compensation expense related to unvested employee options, net of estimated forfeitures, was approximately $55.8 million , which the Company expects to recognize over an estimated weighted average period of 2.67 years . To the extent the actual forfeiture rate is different from what the Company has estimated, stock-based compensation related to these awards will be different from its expectations. The fair value of stock options granted to employees was estimated using a Black-Scholes option pricing model with the following assumptions: Three Months Ended March 31, 2019 2018 Expected term (in years) 5.5-6.1 5.8-6.1 Expected volatility 68 % 75-76% Risk-free interest rate 2.3-2.6% 2.3-2.7% Expected dividend yield — % — % Restricted Stock Units In January 2019, the Company's compensation committee of the board of directors approved the commencement of granting restricted stock units, or RSUs, to our employees. RSUs are share awards that entitle the holder to receive freely tradable shares of the Company's common stock upon the completion of a specific period of continued service. RSUs are generally subject to forfeiture if employment terminates prior to the release of vesting restrictions. RSUs granted are valued at the market price of the Company's common stock on the date of grant. The Company recognizes stock-based compensation expense for the fair value of RSUs on a straight-line basis over the requisite service period of these awards. The following table summarizes activity of RSUs granted to employees with service-based vesting during the three months ended March 31, 2019 : Number of RSUs Outstanding Weighted- Average Grant Date Fair Value Per RSU Balance, December 31, 2018 — RSUs granted 418,819 $ 25.66 RSUs vested — RSUs forfeited (3,825 ) $ 24.74 Balance, March 31, 2019 414,994 $ 25.67 2016 Employee Stock Purchase Plan On July 19, 2016, the 2016 Employee Stock Purchase Plan, or the 2016 ESPP was adopted. The Company initially reserved 210,000 shares of common stock for issuance under the 2016 ESPP. The number of shares reserved for issuance under the 2016 ESPP will increase automatically on January 1 of each calendar year beginning after the first offering date and continuing through the first ten calendar years by the number of shares equal to 1% of the total outstanding shares of the Company’s common stock as of the immediately preceding December 31 . The 2016 ESPP commenced on May 1, 2018. Under the 2016 ESPP, employees may purchase common stock through payroll deductions at a price equal to 85% of the lower of the fair market value at the beginning of the offering period or at the end of each applicable purchase period. The 2016 ESPP generally provides for offering periods of six months in duration with purchase periods ending on either May 15 or November 15. Contributions under the 2016 ESPP are limited to a maximum of 15% of an employee’s eligible compensation and purchases are settled with common stock from the ESPP’s previously authorized and available pool of shares. The expense for the three months ended March 31, 2019 was based on the fair value of rights granted upon the commencement of an offering and calculated using the following assumptions: expected term in years is 0.5 ; volatility is 62.2% ; the risk-free interest rate is 2.50% ; and no dividend yield.

Income Taxes

Income Taxes	3 Months Ended
	Mar. 31, 2019
Income Tax Disclosure [Abstract]
Income Taxes	Income Taxes The Company did not record a federal or state income tax provision or benefit for the three months ended March 31, 2019 and 2018 as it has incurred net losses since inception. In addition, the net deferred tax assets generated from net operating losses have been fully reserved as the Company believes it is not more likely than not that the benefit will be realized.

Leases

Leases	3 Months Ended
	Mar. 31, 2019
Leases [Abstract]
Leases	Leases Under Topic 842, operating lease expense is generally recognized evenly over the term of the lease. The Company has various non-cancelable lease agreements for our office and manufacturing spaces with lease periods expiring between 2023 and 2027. The Company’s lease terms may include options to extend or terminate the leases. The lease term represents the period up to the early termination date unless it is reasonably certain that the Company will not exercise the early termination option. For certain leases, the Company has options to extend the lease term for additional periods ranging from five to eight years. These renewal options are not considered in the remaining lease term unless it is reasonably certain that the Company will exercise such options. Certain leases include rental payments that are adjusted periodically based on changes in consumer price and other indices. Leases with an initial term of twelve months or less are not recorded on the condensed consolidated balance sheets. For lease agreements entered into or reassessed after the adoption of Topic 842, the Company combined the lease and non-lease components in determining the lease liabilities and ROU assets. The Company’s lease agreements generally do not provide an implicit borrowing rate, therefore an internal incremental borrowing rate is determined based on information available at lease commencement date for purposes of determining the present value of lease payments. The Company used the incremental borrowing rate on January 1, 2019 for all leases that commenced prior to that date. For the three months ended March 31, 2019 , the Company recorded operating lease costs of $1.4 million . As of March 31, 2019 , maturities of lease liabilities for the following five fiscal years and thereafter were as follows (in thousands except lease term and discount rate): Amount Remainder of 2019 $ 4,214 2020 5,791 2021 5,973 2022 6,174 2023 4,863 Thereafter 10,086 Total lease payments 37,101 Less: Imputed interest (10,633 ) Tenant improvement not yet received (176 ) Present value of operating lease liabilities $ 26,292 Current operating lease liabilities $ 2,773 Operating lease liabilities - long-term $ 23,519 Weighted-average remaining lease term ( in years) 6.4 Weighted-average discount rate 10.9 % Additional lease not yet commenced (undiscounted) Operating lease liability to commence May 2019 $ 7,854 As the Company elected to apply the provisions of Topic 842 on a prospective basis, the following comparative period disclosure is being presented in accordance with Topic 840. The future minimum commitments under the Company's leases as of December 31, 2018, were as follows: Amount (in thousands) 2019 $ 6,073 2020 6,692 2021 6,901 2022 7,130 2023 5,847 Thereafter 13,024 Total minimum lease payments $ 45,667

Net Loss per Share

Net Loss per Share	3 Months Ended
	Mar. 31, 2019
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 during the period and excludes any potential dilutive effects of common stock equivalents. Diluted net loss per share is computed giving effect to all potential dilutive common shares, including common stock issuable upon exercise of stock options, convertible preferred stock, and unvested restricted common stock. As the Company had net losses for the three months ended March 31, 2019 and 2018 , all potential common shares were determined to be anti-dilutive and were therefore excluded from the calculation of diluted net loss per share. The following table sets forth the computation of basic and diluted net loss per share of common stock during the three months ended March 31, 2019 and 2018 : Three Months Ended March 31, 2019 2018 (in thousands, except per share data) Net loss $ (49,391 ) $ (25,571 ) Weighted-average number of shares used in computing net loss per share 43,625,316 34,582,071 Net loss per share, basic and diluted $ (1.13 ) $ (0.74 ) The following outstanding shares of common stock equivalents were excluded from the computation of diluted net loss per share of common stock for the periods presented because including them would have been anti-dilutive: Three Months Ended March 31, 2019 2018 Stock options to purchase common stock 5,858,854 4,902,872 Restricted stock units 414,994 — Common stock warrants — 9,914 6,273,848 4,912,786

Related Party Transactions

Related Party Transactions	3 Months Ended
	Mar. 31, 2019
Related Party Transactions [Abstract]
Related Party Transactions	Related Party Transactions There were no material related party transactions during the three months ended March 31, 2019 and 2018 .

Summary of Significant Accoun_2

Summary of Significant Accounting Policies (Policies)	3 Months Ended
	Mar. 31, 2019
Accounting Policies [Abstract]
Leases	Leases The Company determines if an arrangement is or contains a lease at inception by assessing whether the arrangement contains an identified asset and whether it has the right to control the identified asset. Right-of-use (ROU) assets represent the Company's right to use an underlying asset for the lease term and lease liabilities represent the Company's obligation to make lease payments arising from the lease. ROU assets and lease liabilities are recognized at the lease commencement date based on the present value of future lease payments over the lease term. As the implicit rate in the Company's leases is unknown, the Company uses its incremental borrowing rate based on the information available at the lease commencement date in determining the present value of future lease payments. The Company gives consideration to its credit risk, term of the lease, total lease payments and adjust for the impacts of collateral, as necessary, when calculating its incremental borrowing rates. The ROU asset is based on the measurement of the lease liability and also includes any lease payments made prior to or on lease commencement and excludes lease incentives and initial direct costs incurred, as applicable. The lease terms may include options to extend or terminate the lease when it is reasonably certain the Company will exercise any such options. Rent expense for the Company's operating leases is recognized on a straight-line basis over the lease term. The Company has lease agreements with lease and non-lease components. The Company has elected to not separate lease and non-lease components for any leases within its existing classes of assets and, as a result, accounts for the lease and non-lease components as a single lease component. The Company has also elected to not apply the recognition requirement to any leases within its existing classes of assets with a term of 12 months or less.
Basis of Presentation	Basis of Preparation The accompanying unaudited interim condensed consolidated financial statements have been prepared in accordance with accounting principles generally accepted in the United States of America, or U.S. GAAP, and applicable rules and regulations of the SEC regarding interim financial reporting. As permitted under those rules, certain footnotes or other financial information that are normally required by U.S. GAAP have been condensed or omitted, and accordingly the balance sheet as of December 31, 2018 has been derived from audited financial statements at that date but does not include all of the information required by U.S. GAAP for complete financial statements. These unaudited interim condensed consolidated financial statements have been prepared on the same basis as the Company’s annual financial statements and, in the opinion of management, reflect all adjustments (consisting only of normal recurring adjustments) that are necessary for a fair presentation of the Company’s financial information. The results of operations for the three months ended March 31, 2019 are not necessarily indicative of the results to be expected for the year ending December 31, 2019 or for any other interim period or for any other future year. The accompanying unaudited interim condensed consolidated financial statements and related financial information should be read in conjunction with the audited financial statements and the related notes thereto for the year ended December 31, 2018 included in the Company’s audited financial statements filed in its Annual Report on Form 10-K for the year ended December 31, 2018 .
Use of Estimates	Use of Estimates The accompanying unaudited interim condensed consolidated financial statements have been prepared in accordance with U.S. generally accepted accounting principles, or GAAP. The preparation of financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities, as of the date of the financial statements, and the reported amounts of any expenses during the reporting period. On an ongoing basis, management evaluates its estimates, including those related to accrued liabilities, acquisition contingent consideration, income taxes, and stock-based compensation. Management bases its estimates on historical experience, and on various other market-specific relevant assumptions that management believes to be reasonable, under the circumstances. Actual results may differ from those estimates.
Concentration of Credit Risk	Concentration of Credit Risk Financial instruments that potentially subject the Company to a concentration of credit risk consist of cash and cash equivalents and marketable securities. The Company invests in a variety of financial instruments and in accordance with its investment policy, limits the amount of credit exposure with any one issuer, industry or geographic area for investments other than instruments backed by the U.S. federal government.
Concentration of Manufacturing and Third-Party Services Risk	Concentration of Manufacturing and Third-Party Services Risk The Company is subject to certain risks with respect to sources of supply of manufactured materials and drug product for use in its preclinical studies and clinical trials. Due to the technical aspects of manufacturing drug product for gene therapies, there exist few alternative sources of manufacturing. The Company is reliant upon its own internal manufacturing capability and a small number of third-party vendors to produce drug product in sufficient quantities and quality to conduct its research and development activities.
Recent Accounting Pronouncements	Accounting Pronouncements Adopted in 2019 In June 2018, the FASB issued ASU 2018-07, Compensation - Stock Compensation (Topic 718), Improvements to Nonemployee Share-Based Payment Accounting , which expands the scope of Topic 718 to include share-based payment transactions for acquiring goods and services from nonemployees. An entity should apply the requirements of Topic 718 to nonemployee awards except for specific guidance on inputs to an option pricing model and the attribution of cost. The measurement of equity-classified nonemployee awards is fixed at the grant date, and entities would measure the cost of awards subject to a performance condition using the outcome that is probable at the balance sheet date. The Company adopted this standard on January 1, 2019. As a result of adopting this standard, the Company no longer remeasures equity-classified nonemployee awards. The adoption of this new standard did not result in material impact on the Company's condensed consolidated financial statements. In February 2016, the FASB issued ASU No. 2016-02, Leases (Topic 842) , which establishes a comprehensive new lease accounting model. Under the new guidance, at the commencement date, lessees are required to recognize a lease liability with a corresponding right-of-use (ROU) asset. Effective January 1, 2019, the Company adopted Topic 842 using the modified retrospective approach provided by ASU 2018-11. Results for reporting periods beginning January 1, 2019 are presented under Topic 842, while prior period amounts were not adjusted and continue to be presented in accordance with the Company’s historical accounting under Topic 840, Leases . The Company elected certain practical expedients permitted under the transition guidance, including the election to carryforward historical lease classification. The Company also elected the short-term lease practical expedient, which allowed the Company to not recognize leases with a term of less than twelve months on its consolidated balance sheets. In addition, the Company elected the lease and non-lease components practical expedient, which allowed the Company to calculate the present value of the fixed payments without performing an allocation of lease and non-lease components. The impact of the adoption of Topic 842 on the accompanying Condensed Consolidated Balance Sheet as of January 1, 2019 was as follows: December 31, 2018 Effect of Adoption January 1, 2019 (in thousands) Operating lease right-of-use assets $ — $ 21,669 $ 21,669 Liabilities: Operating leases $ — $ 2,541 $ 2,541 Deferred rent $ 456 $ (456 ) $ — Operating lease liabilities - long-term $ — $ 24,304 $ 24,304 Deferred rent and asset retirement obligation - long-term $ 4,935 $ (4,720 ) $ 215 Adoption of the new standard resulted in recording operating lease right-of-use assets and operating lease liabilities of approximately $21.1 million and $26.3 million , respectively, on the Company’s condensed consolidated balance sheets as of March 31, 2019 . However, the adoption of the new standard did not have an impact on the Company’s beginning accumulated deficit, statement of operations or cash flows. For additional information regarding the Company’s leases, see Note 9 in the notes to the condensed consolidated financial statements.

Summary of Significant Accoun_3

Summary of Significant Accounting Policies Schedule of New Accounting Pronouncements and Changes in Accounting Principles (Tables)	3 Months Ended
	Mar. 31, 2019
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Schedule of New Accounting Pronouncements and Changes in Accounting Principles [Table Text Block]	The impact of the adoption of Topic 842 on the accompanying Condensed Consolidated Balance Sheet as of January 1, 2019 was as follows: December 31, 2018 Effect of Adoption January 1, 2019 (in thousands) Operating lease right-of-use assets $ — $ 21,669 $ 21,669 Liabilities: Operating leases $ — $ 2,541 $ 2,541 Deferred rent $ 456 $ (456 ) $ — Operating lease liabilities - long-term $ — $ 24,304 $ 24,304 Deferred rent and asset retirement obligation - long-term $ 4,935 $ (4,720 ) $ 215

Investments (Tables)

Investments (Tables)	3 Months Ended
	Mar. 31, 2019
Investments [Abstract]
Schedule of Available-for-Sale Securities	Investments consist of available-for-sale securities as follows: March 31, 2019 Amortized Cost Unrealized Gains Unrealized Losses Fair Value (in thousands) Money market funds $ 49,747 $ — $ — $ 49,747 Commercial paper 114,105 1 (12 ) 114,094 Corporate securities 78,231 70 (9 ) 78,292 U.S. treasury bills 51,288 7 — 51,295 U.S. government agency securities 27,867 3 (2 ) 27,868 U.S. agency bonds 32,732 9 — 32,741 U.S. agency discount securities 10,999 — — 10,999 Total available-for-sale securities $ 364,969 $ 90 $ (23 ) $ 365,036 December 31, 2018 Amortized Cost Unrealized Gains Unrealized Losses Fair Value (in thousands) Money market funds $ 33,399 $ — $ — $ 33,399 Commercial paper 144,578 — — 144,578 Corporate securities 82,670 8 (39 ) 82,639 U.S. treasury bills 60,573 — (8 ) 60,565 U.S. government agency securities 15,219 — — 15,219 U.S. agency bonds 51,411 — (22 ) 51,389 U.S. agency discount securities 18,716 — — 18,716 Total available-for-sale securities $ 406,566 $ 8 $ (69 ) $ 406,505

Fair Value Measurements (Tables

Fair Value Measurements (Tables)	3 Months Ended
	Mar. 31, 2019
Fair Value Disclosures [Abstract]
Fair Value of Financial Assets	Financial assets subject to fair value measurements on a recurring basis and the level of inputs used in such measurements are as follows: March 31, 2019 Fair Value Measurements Using Total Level 1 Level 2 Level 3 (in thousands) Money market funds $ 49,747 $ 49,747 $ — $ — Commercial paper 114,094 — 114,094 — Corporate securities 78,292 — 78,292 — U.S. treasury bills 51,295 — 51,295 — U.S. government agency securities 27,868 — 27,868 — U.S. agency bonds 32,741 — 32,741 — U.S. agency discount securities 10,999 — 10,999 — Total financial assets $ 365,036 $ 49,747 $ 315,289 $ — December 31, 2018 Fair Value Measurements Using Total Level 1 Level 2 Level 3 (in thousands) Money market funds $ 33,399 $ 33,399 $ — $ — Commercial paper 144,578 — 144,578 — Corporate securities 82,639 — 82,639 — U.S. treasury bills 60,565 — 60,565 — U.S. government agency securities 15,219 — 15,219 — U.S. agency bonds 51,389 — 51,389 — U.S. agency discount securities 18,716 — 18,716 — Total financial assets $ 406,505 $ 33,399 $ 373,106 $ —
Summary of Contingent Acquisition Consideration Payable Recorded in Accompanying Consolidated Balance Sheets	The following is a summary of the contingent acquisition consideration payable recorded in the accompanying consolidated balance sheets: Amount (in thousands) Balance, December 31, 2018 $ 2,345 Change in fair value of contingent acquisition consideration payable (22 ) Balance, March 31, 2019 $ 2,323

Balance Sheet Components (Table

Balance Sheet Components (Tables)	3 Months Ended
	Mar. 31, 2019
Disclosure Text Block Supplement [Abstract]
Property and Equipment, Net	Property and equipment, net, consist of the following: March 31, 2019 December 31, 2018 (in thousands) Furniture and office equipment $ 1,968 $ 1,898 Computer equipment 1,219 1,019 Software 513 513 Leasehold improvements 22,917 19,607 Laboratory equipment 10,007 9,570 Manufacturing equipment 6,723 6,619 Construction in progress and deposits on equipment 3,559 3,320 Total property and equipment 46,906 42,546 Less accumulated depreciation and amortization (12,175 ) (10,447 ) Property and equipment, net $ 34,731 $ 32,099
Accrued Liabilities	Accrued liabilities consist of the following: March 31, 2019 December 31, 2018 (in thousands) Accrued payroll and related expenses $ 5,034 $ 8,581 Accrued research and development expenses 4,877 3,317 Accrued property and equipment 623 71 Accrued professional services 680 783 Other 306 176 Total accrued liabilities $ 11,520 $ 12,928

Stock Compensation (Tables)

Stock Compensation (Tables)	3 Months Ended
	Mar. 31, 2019
Disclosure of Compensation Related Costs, Share-based Payments [Abstract]
Stock-based Compensation Expense by Category	Stock-based compensation expense by category was as follows for the three months ended March 31, 2019 and 2018 : Three Months Ended March 31, 2019 2018 (in thousands) Research and development $ 3,215 $ 2,055 General and administrative 2,285 1,330 Total stock-based compensation expense $ 5,500 $ 3,385
Summary of Option Activity	The following table summarizes option activity for the three months ended March 31, 2019 : Number of Options Outstanding Weighted- Average Exercise Price Per Option Weighted- Average Remaining Contract Term (Years) Aggregate Intrinsic Value (in thousands) Balance, December 31, 2018 4,894,201 $ 18.79 7.97 $ 30,235 Options granted 1,248,000 $ 25.66 Options exercised (213,891 ) $ 14.05 Options forfeited (69,456 ) $ 26.37 Balance, March 31, 2019 5,858,854 $ 20.34 8.15 $ 109,622 Exercisable, March 31, 2019 2,316,213 $ 13.08 7.17 $ 60,086 Vested and expected to vest, March 31, 2019 5,483,592 $ 19.89 8.09 $ 105,047
Fair Value of Stock Options, Valuation Assumptions	The fair value of stock options granted to employees was estimated using a Black-Scholes option pricing model with the following assumptions: Three Months Ended March 31, 2019 2018 Expected term (in years) 5.5-6.1 5.8-6.1 Expected volatility 68 % 75-76% Risk-free interest rate 2.3-2.6% 2.3-2.7% Expected dividend yield — % — %
Schedule of RSU Activity	The following table summarizes activity of RSUs granted to employees with service-based vesting during the three months ended March 31, 2019 : Number of RSUs Outstanding Weighted- Average Grant Date Fair Value Per RSU Balance, December 31, 2018 — RSUs granted 418,819 $ 25.66 RSUs vested — RSUs forfeited (3,825 ) $ 24.74 Balance, March 31, 2019 414,994 $ 25.67

Leases (Tables)

Leases (Tables)	3 Months Ended
	Mar. 31, 2019
Leases [Abstract]
Future Minimum Lease Payments - Topic 842	As of March 31, 2019 , maturities of lease liabilities for the following five fiscal years and thereafter were as follows (in thousands except lease term and discount rate): Amount Remainder of 2019 $ 4,214 2020 5,791 2021 5,973 2022 6,174 2023 4,863 Thereafter 10,086 Total lease payments 37,101 Less: Imputed interest (10,633 ) Tenant improvement not yet received (176 ) Present value of operating lease liabilities $ 26,292 Current operating lease liabilities $ 2,773 Operating lease liabilities - long-term $ 23,519 Weighted-average remaining lease term ( in years) 6.4 Weighted-average discount rate 10.9 % Additional lease not yet commenced (undiscounted) Operating lease liability to commence May 2019 $ 7,854
Future Minimum Lease Payments - Topic 840	As the Company elected to apply the provisions of Topic 842 on a prospective basis, the following comparative period disclosure is being presented in accordance with Topic 840. The future minimum commitments under the Company's leases as of December 31, 2018, were as follows: Amount (in thousands) 2019 $ 6,073 2020 6,692 2021 6,901 2022 7,130 2023 5,847 Thereafter 13,024 Total minimum lease payments $ 45,667

Net Loss per Share (Tables)

Net Loss per Share (Tables)	3 Months Ended
	Mar. 31, 2019
Earnings Per Share [Abstract]
Computation of Basic and Diluted Net Loss per Share of Common Stock	The following table sets forth the computation of basic and diluted net loss per share of common stock during the three months ended March 31, 2019 and 2018 : Three Months Ended March 31, 2019 2018 (in thousands, except per share data) Net loss $ (49,391 ) $ (25,571 ) Weighted-average number of shares used in computing net loss per share 43,625,316 34,582,071 Net loss per share, basic and diluted $ (1.13 ) $ (0.74 )
Anti-Dilutive Common Stock Equivalents Excluded from Computation of Diluted Net Loss per Share	The following outstanding shares of common stock equivalents were excluded from the computation of diluted net loss per share of common stock for the periods presented because including them would have been anti-dilutive: Three Months Ended March 31, 2019 2018 Stock options to purchase common stock 5,858,854 4,902,872 Restricted stock units 414,994 — Common stock warrants — 9,914 6,273,848 4,912,786

Organization and Basis of Pre_2

Organization and Basis of Presentation (Details) $ in Thousands	3 Months Ended
	Mar. 31, 2019USD ($)segment	Dec. 31, 2018USD ($)
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Number of operating business segment | segment	1
Accumulated deficit	$ 368,861	$ 319,470
Cash, cash equivalents and marketable securities	375,000
Cash and cash equivalents	133,160	$ 144,349
Investments	$ 241,900

Summary of Significant Accoun_4

Summary of Significant Accounting Policies Adjustment for Adoption (Details) - USD ($) $ in Thousands	Mar. 31, 2019	Jan. 01, 2019	Dec. 31, 2018
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Right of use assets	$ 21,089	$ 21,669
Liabilities:
Operating lease liabilities	2,773	2,541
Deferred rent	0	0	$ 456
Operating lease liabilities - long-term	23,519	24,304
Deferred rent - long-term		215	$ 4,935
Operating lease liability	$ 26,292
Accounting Standards Update 2016-02
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Right of use assets		21,669
Liabilities:
Operating lease liabilities		2,541
Deferred rent		(456)
Operating lease liabilities - long-term		24,304
Deferred rent - long-term		$ (4,720)

Investments - Schedule of Avail

Investments - Schedule of Available-for-Sale Securities (Details) - USD ($) $ in Thousands	Mar. 31, 2019	Dec. 31, 2018
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	$ 364,969	$ 406,566
Unrealized Gains	90	8
Unrealized Losses	(23)	(69)
Fair Value	365,036	406,505
Money market funds
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	49,747	33,399
Unrealized Gains	0	0
Unrealized Losses	0	0
Fair Value	49,747	33,399
Commercial paper
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	114,105	144,578
Unrealized Gains	1	0
Unrealized Losses	(12)	0
Fair Value	114,094	144,578
Corporate securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	78,231	82,670
Unrealized Gains	70	8
Unrealized Losses	(9)	(39)
Fair Value	78,292	82,639
U.S. treasury bills
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	51,288	60,573
Unrealized Gains	7	0
Unrealized Losses	0	(8)
Fair Value	51,295	60,565
U.S. government agency securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	27,867	15,219
Unrealized Gains	3	0
Unrealized Losses	(2)	0
Fair Value	27,868	15,219
U.S. agency bonds
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	32,732	51,411
Unrealized Gains	9	0
Unrealized Losses	0	(22)
Fair Value	32,741	51,389
U.S. agency discount securities
Debt Securities, Available-for-sale [Line Items]
Amortized Cost	10,999	18,716
Unrealized Gains	0	0
Unrealized Losses	0	0
Fair Value	$ 10,999	$ 18,716

Fair Value Measurements - Fair

Fair Value Measurements - Fair Value of Financial Assets (Details) - USD ($) $ in Thousands	Mar. 31, 2019	Dec. 31, 2018
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	$ 365,036	$ 406,505
Fair Value Measurements Using Level 1
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	49,747	33,399
Fair Value Measurements Using Level 2
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	315,289	373,106
Fair Value Measurements Using Level 3
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	0	0
Money market funds
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	49,747	33,399
Money market funds | Fair Value Measurements Using Level 1
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	49,747	33,399
Money market funds | Fair Value Measurements Using Level 2
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	0	0
Money market funds | Fair Value Measurements Using Level 3
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	0	0
Commercial paper
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	114,094	144,578
Commercial paper | Fair Value Measurements Using Level 1
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	0	0
Commercial paper | Fair Value Measurements Using Level 2
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	114,094	144,578
Commercial paper | Fair Value Measurements Using Level 3
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	0	0
Corporate securities
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	78,292	82,639
Corporate securities | Fair Value Measurements Using Level 1
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	0	0
Corporate securities | Fair Value Measurements Using Level 2
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	78,292	82,639
Corporate securities | Fair Value Measurements Using Level 3
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	0	0
U.S. treasury bills
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	51,295	60,565
U.S. treasury bills | Fair Value Measurements Using Level 1
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	0	0
U.S. treasury bills | Fair Value Measurements Using Level 2
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	51,295	60,565
U.S. treasury bills | Fair Value Measurements Using Level 3
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	0	0
U.S. government agency securities
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	27,868	15,219
U.S. government agency securities | Fair Value Measurements Using Level 1
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	0	0
U.S. government agency securities | Fair Value Measurements Using Level 2
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	27,868	15,219
U.S. government agency securities | Fair Value Measurements Using Level 3
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	0	0
U.S. agency bonds
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	32,741	51,389
U.S. agency bonds | Fair Value Measurements Using Level 1
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	0	0
U.S. agency bonds | Fair Value Measurements Using Level 2
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	32,741	51,389
U.S. agency bonds | Fair Value Measurements Using Level 3
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	0	0
U.S. agency discount securities
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	10,999	18,716
U.S. agency discount securities | Fair Value Measurements Using Level 1
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	0	0
U.S. agency discount securities | Fair Value Measurements Using Level 2
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	10,999	18,716
U.S. agency discount securities | Fair Value Measurements Using Level 3
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Financial assets	$ 0	$ 0

Fair Value Measurements - Addit

Fair Value Measurements - Additional Information (Details) - USD ($) $ in Millions	Mar. 31, 2019	Dec. 31, 2018
Fair Value Disclosures [Abstract]
Cash held in primary operating bank accounts	$ 10	$ 7.8

Fair Value Measurements - Summa

Fair Value Measurements - Summary of Contingent Acquisition Consideration Payable Recorded in Accompanying Consolidated Balance Sheets (Details) - USD ($) $ in Thousands	3 Months Ended
	Mar. 31, 2019	Mar. 31, 2018
Contingent Consideration [Roll Forward]
Beginning balance	$ 2,345
Change in fair value of contingent acquisition consideration payable	(22)	$ (2,284)
Ending balance	$ 2,323

Balance Sheet Components - Prop

Balance Sheet Components - Property and Equipment, Net (Details) - USD ($) $ in Thousands	Mar. 31, 2019	Dec. 31, 2018
Property, Plant and Equipment [Line Items]
Property and equipment	$ 46,906	$ 42,546
Less accumulated depreciation and amortization	(12,175)	(10,447)
Property and equipment, net	34,731	32,099
Furniture and office equipment
Property, Plant and Equipment [Line Items]
Property and equipment	1,968	1,898
Computer equipment
Property, Plant and Equipment [Line Items]
Property and equipment	1,219	1,019
Software
Property, Plant and Equipment [Line Items]
Property and equipment	513	513
Leasehold improvements
Property, Plant and Equipment [Line Items]
Property and equipment	22,917	19,607
Laboratory equipment
Property, Plant and Equipment [Line Items]
Property and equipment	10,007	9,570
Manufacturing equipment
Property, Plant and Equipment [Line Items]
Property and equipment	6,723	6,619
Construction in progress and deposits on equipment
Property, Plant and Equipment [Line Items]
Property and equipment	$ 3,559	$ 3,320

Balance Sheet Components - Addi

Balance Sheet Components - Additional Information (Details) - USD ($) $ in Thousands	3 Months Ended
	Mar. 31, 2019	Mar. 31, 2018
Property, Plant and Equipment [Abstract]
Depreciation and amortization expense	$ 1,728	$ 1,149

Balance Sheet Components - Accr

Balance Sheet Components - Accrued Liabilities (Details) - USD ($) $ in Thousands	Mar. 31, 2019	Dec. 31, 2018
Payables and Accruals [Abstract]
Accrued payroll and related expenses	$ 5,034	$ 8,581
Accrued research and development expenses	4,877	3,317
Accrued property and equipment	623	71
Accrued professional services	680	783
Other	306	176
Total accrued liabilities	$ 11,520	$ 12,928

Commitments and Contingencies -

Commitments and Contingencies - Additional Information (Details) $ in Millions	3 Months Ended
	Mar. 31, 2019USD ($)
Organization, Consolidation and Presentation of Financial Statements [Abstract]
Upfront fee consideration for licensed rights	$ 7
Contingent payments (up to)	275.1
Contingent payments, Crigler-Najjar and CASQ2-CPVT Programs (up to)	$ 77.9

Stock Compensation - Additional

Stock Compensation - Additional Information (Details) - USD ($) $ / shares in Units, $ in Thousands	May 01, 2018	Jul. 19, 2016	Mar. 31, 2019	Mar. 31, 2018
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Options exercised (in shares)			213,891
Intrinsic value of options exercised			$ 3,800
Options exercised, cash received			$ 3,005	$ 807
Employee Stock Option
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Weighted average grant date fair value of options granted (in USD per share)			$ 16.03	$ 21.81
Unrecognized compensation expense related to unvested options, net of estimated forfeitures			$ 55,800
Unrecognized compensation expense, estimated weighted average period			2 years 8 months 1 day
Fair values of rights granted, expected volatility			68.00%
Fair values of rights granted, expected dividend yield			0.00%	0.00%
2016 Employee Stock Purchase Plan
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Shares reserved for issuance (in shares)		210,000
Proportion of outstanding shares of common stock		1.00%
Common stock offering period	6 months
Purchase of common stock through payroll deductions expressed in percentage of fair market value	85.00%
Maximum percentage of an employee's eligible compensation	15.00%
Fair values of rights granted, expected term			6 months
Fair values of rights granted, expected volatility			62.20%
Fair values of rights granted, risk-free interest rate			2.50%
Fair values of rights granted, expected dividend yield			0.00%

Stock Compensation - Stock-base

Stock Compensation - Stock-based Compensation Expense by Category (Details) - USD ($) $ in Thousands	3 Months Ended
	Mar. 31, 2019	Mar. 31, 2018
Share-based Compensation Arrangement by Share-based Payment Award, Compensation Cost [Line Items]
Stock-based compensation expense	$ 5,500	$ 3,385
Research and development
Share-based Compensation Arrangement by Share-based Payment Award, Compensation Cost [Line Items]
Stock-based compensation expense	3,215	2,055
General and administrative
Share-based Compensation Arrangement by Share-based Payment Award, Compensation Cost [Line Items]
Stock-based compensation expense	$ 2,285	$ 1,330

Stock Compensation - Summary of

Stock Compensation - Summary of Option Activity (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended
	Mar. 31, 2019	Mar. 31, 2018	Dec. 31, 2018
Number of Options Outstanding
Beginning Balance (in shares)	4,894,201
Options granted (in shares)	1,248,000
Options exercised (in shares)	(213,891)
Options forfeited (in shares)	(69,456)
Ending Balance (in shares)	5,858,854
Number of Options Outstanding, Exercisable (in shares)	2,316,213
Number of Options Outstanding, Vested and expected to vest (in shares)	5,483,592
Weighted- Average Exercise Price Per Option
Beginning Balance (in USD per share)	$ 18.79
Options granted (in USD per share)	25.66
Options exercised (in USD per share)	14.05
Options forfeited (in USD per share)	26.37
Ending Balance (in USD per share)	20.34
Weighted-Average Exercise Price Per Option, Exercisable (in USD per share)	13.08
Weighted-Average Exercise Price Per Options, Vested and expected to vest (in USD per share)	$ 19.89
Weighted-Average Remaining Contract Term (Years)	8 years 1 month 24 days	7 years 11 months 19 days
Weighted-Average Remaining Contract Term (Years), Exercisable	7 years 2 months 1 day
Weighted-Average Remaining Contract Term (Years), Vested and expected to vest	8 years 1 month 2 days
Aggregate Intrinsic Value, Balance	$ 109,622		$ 30,235
Aggregate Intrinsic Value, Exercisable	60,086
Aggregate Intrinsic Value, Vested and expected to vest	$ 105,047

Stock Compensation - Fair Value

Stock Compensation - Fair Value of Stock Options, Valuation Assumptions (Details) - Employee Stock Option	3 Months Ended
	Mar. 31, 2019	Mar. 31, 2018
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Expected volatility	68.00%
Expected volatility, minimum		75.00%
Expected volatility, maximum		76.00%
Risk-free interest rate, minimum	2.30%	2.30%
Risk-free interest rate, maximum	2.60%	2.70%
Expected dividend yield	0.00%	0.00%
Minimum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Expected term	5 years 6 months	5 years 9 months 18 days
Maximum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Expected term	6 years 1 month 6 days	6 years 1 month 6 days

Stock Compensation - RSU Activi

Stock Compensation - RSU Activity (Details) - Restricted stock units - $ / shares	3 Months Ended
	Mar. 31, 2019	Mar. 31, 2018
Number of RSUs Outstanding
Beginning balance (in shares)	0
RSUs granted (in shares)	418,819
RSUs vested (in shares)	0
RSUs forfeited (in shares)	(3,825)
Ending balance (in shares)	414,994
Share-based Compensation Arrangement by Share-based Payment Award, Equity Instruments Other than Options, Nonvested, Weighted Average Grant Date Fair Value [Abstract]
RSUs granted (in USD per share)	$ 25.66
RSUs forfeited (in USD per share)		$ 24.74
Ending balance (in USD per share)	$ 25.67

Income taxes - Additional Infor

Income taxes - Additional Information (Details) - USD ($)	3 Months Ended
	Mar. 31, 2019	Mar. 31, 2018
Income Tax Disclosure [Abstract]
Federal income tax provision (benefit)	$ 0	$ 0
State income tax provision (benefit)	$ 0	$ 0

Leases - Maturities of Lease Li

Leases - Maturities of Lease Liabilities (Details) - USD ($) $ in Thousands	Mar. 31, 2019	Jan. 01, 2019	Dec. 31, 2018
Future Minimum Lease Payments - Topic 842
Remainder of 2019	$ 4,214
2020	5,791
2021	5,973
2022	6,174
2023	4,863
Thereafter	10,086
Total lease payments	37,101
Imputed interest	(10,633)
Tenant improvement not yet received	(176)
Present value of operating lease liabilities	26,292
Current operating lease liabilities	2,773	$ 2,541
Operating lease liabilities - long-term	$ 23,519	$ 24,304
Weighted-average remaining lease term	6 years 4 months 24 days
Weighted-average discount rate	10.90%
Operating lease liability to commence May 2019	$ 7,854
Future Minimum Lease Payments - Topic 840
2019			$ 6,073
2020			6,692
2020			6,901
2021			7,130
2022			5,847
Thereafter			13,024
Total minimum lease payments			$ 45,667

Leases - Lease Cost (Details)

Leases - Lease Cost (Details) $ in Millions	3 Months Ended
	Mar. 31, 2019USD ($)
Leases [Abstract]
Total lease cost	$ 1.4

Net Loss per Share - Computatio

Net Loss per Share - Computation of Basic and Diluted Net Loss Per Share of Common Stock (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended
	Mar. 31, 2019	Mar. 31, 2018
Earnings Per Share [Abstract]
Net loss	$ (49,391)	$ (25,571)
Weighted-average number of shares used in computing net loss per share	43,625,316	34,582,071
Net loss per share, basic and diluted	$ (1.13)	$ (0.74)

Net Loss per Share - Anti-Dilut

Net Loss per Share - Anti-Dilutive Common Stock Equivalents Excluded from Computation of Diluted Net Loss Per Share (Details) - shares	3 Months Ended
	Mar. 31, 2019	Mar. 31, 2018
Earnings Per Share, Basic, by Common Class, Including Two Class Method [Line Items]
Anti-dilutive common stock equivalents excluded from computation of diluted net loss per share	6,273,848	4,912,786
Stock options to purchase common stock
Earnings Per Share, Basic, by Common Class, Including Two Class Method [Line Items]
Anti-dilutive common stock equivalents excluded from computation of diluted net loss per share	5,858,854	4,902,872
Restricted stock units
Earnings Per Share, Basic, by Common Class, Including Two Class Method [Line Items]
Anti-dilutive common stock equivalents excluded from computation of diluted net loss per share	414,994	0
Common stock warrants
Earnings Per Share, Basic, by Common Class, Including Two Class Method [Line Items]
Anti-dilutive common stock equivalents excluded from computation of diluted net loss per share	0	9,914