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Stock-Based Compensation
 6 Months Ended
Jun. 30, 2022
Share-Based Payment Arrangement [Abstract]  
Stock-Based Compensation Stock-Based Compensation
Equity Plans
The 2015 Stock Incentive Plan, as amended (“2015 Plan”), was approved at the Company's annual meeting of stockholders in June 2015. Under the 2015 Plan, equity awards may be granted to officers, directors, employees, and consultants of and advisors to the Company and any present or future subsidiary.
The 2015 Plan authorizes the issuance of up to 14.8 million shares of common stock under equity awards granted under the 2015 Plan, which includes an increase of 2.4 million shares approved for issuance under the 2015 Plan at the Company's 2022 annual meeting of stockholders. All such shares authorized for issuance under the 2015 Plan have been reserved. The 2015 Plan will expire on March 4, 2025.
The Amended and Restated 2005 Stock Incentive Plan (“2005 Plan”) expired in February 2015 and no new awards may be made under such plan, although awards will continue to be outstanding in accordance with their terms.
The 2015 Plan permits and the 2005 Plan permitted the grant of stock options (including incentive stock options), restricted stock, stock appreciation rights (“SARs”), and restricted stock units (“RSUs”). In addition, under the 2015 Plan, unrestricted stock, stock units, and performance awards may be granted. Stock options and SARs generally have a maximum term of ten years and may be or were granted with an exercise price that is no less than 100% of the fair market value of the Company's common stock at the time of grant. Grants of stock options are generally subject to vesting over periods ranging from one to four years.
The Company recorded all stock-based compensation expense in the consolidated statements of operations as follows (in thousands):
Three Months Ended
June 30,		Six Months Ended
June 30,
2022202120222021
Research and development$19,695 $24,779 $36,582 $48,569 
General and administrative18,353 28,344 34,399 57,614 
Total stock-based compensation expense$38,048 $53,123 $70,981 $106,183 
As of June 30, 2022, there was approximately $212 million of total unrecognized compensation expense related to unvested stock options, SARs, RSUs, and the Company’s Employee Stock Purchase Plan, as amended (“ESPP”). This unrecognized non-cash compensation expense is expected to be recognized over a weighted-average period of approximately one year. This estimate does not include the impact of other possible stock-based awards that may be made during future periods.
The aggregate intrinsic value represents the total intrinsic value (the difference between the Company’s closing stock price on the last trading day of the period and the exercise price, multiplied by the number of in-the-money stock options and SARs) that would have been received by the holders had all stock option and SAR holders exercised their stock options and SARs on June 30, 2022. This amount is subject to change based on changes to the closing price of the Company's common stock. The aggregate intrinsic value of stock options and SARs exercises and vesting of RSUs for the six months ended June 30, 2022 and 2021 was approximately $8 million and $115 million, respectively.
Stock Options and Stock Appreciation Rights
The following is a summary of stock options and SARs activity under the 2015 Plan and 2005 Plan for the six months ended June 30, 2022:
2015 Plan2005 Plan
Stock
Options		Weighted-Average
Exercise
Price		Stock
Options		Weighted-Average
Exercise
Price
Outstanding at December 31, 20213,635,837 $42.60 68,225 $109.52 
Granted506,821 73.94 — 
Exercised(59,727)15.61 (3,000)31.10 
Canceled(35,195)78.51 (1,500)121.00 
Outstanding at June 30, 20224,047,736 $46.61 63,725 $112.94 
Shares exercisable at June 30, 20221,463,037 $55.28 63,725 $112.94 
Shares available for grant at June 30, 20224,834,171 
The fair value of stock options granted under the 2015 Plan was estimated at the date of grant using the Black-Scholes option-pricing model with the following assumptions:
Three Months Ended
June 30,		Six Months Ended
June 30,
2022202120222021
Weighted average Black-Scholes fair value of stock options granted
$43.21
$166.66
$62.52
$131.66
Risk-free interest rate
2.7%-3.2%
0.6%-1.1%
1.4%-3.2%
0.5%-1.1%
Dividend yield—%—%—%—%
Volatility
120.5%-136.7%
126.2%-142.0%
120.5%-136.7%
124.7%-142.0%
Expected term (in years)
4.0-6.2
4.1-6.1
4.0-6.2
4.1-6.1
The total aggregate intrinsic value and weighted-average remaining contractual term of stock options and SARs outstanding under the 2015 Plan and 2005 Plan as of June 30, 2022 was approximately $91 million and 7.5 years, respectively. The total aggregate intrinsic value and weighted-average remaining contractual term of stock options and SARs exercisable under the 2015 Plan and 2005 Plan as of June 30, 2022 was approximately $30 million and 6.5 years, respectively.
Restricted Stock Units
The following is a summary of RSU activity for the six months ended June 30, 2022:
Number of
Shares		Per Share
Weighted-
Average
Fair Value
Outstanding and unvested at December 31, 2021819,828 $116.70 
Granted882,828 74.34 
Vested(55,425)157.97 
Forfeited(71,989)110.57 
Outstanding and unvested at June 30, 20221,575,242 $91.79 
Employee Stock Purchase Plan
The ESPP was approved at the Company's annual meeting of stockholders in June 2013. The ESPP currently authorizes an aggregate of 1.1 million shares of common stock to be purchased, and the aggregate amount of shares will continue to increase 5% on each anniversary of its adoption up to a maximum of 1.65 million shares. The ESPP allows employees to purchase shares of common stock of the Company at each purchase date through payroll deductions of up to a maximum of 15% of their compensation, at 85% of the lesser of the market price of the shares at the time of purchase or the market price on the beginning date of an option period (or, if later, the date during the option period when the employee was first eligible to participate). No ESPP option periods commenced during the three months ended June 30, 2022 and 2021. As of June 30, 2022, there were 0.7 million shares available for issuance under the ESPP.
The ESPP is considered compensatory for financial reporting purposes. As such, the fair value of ESPP shares was estimated at the date of grant using the Black-Scholes option-pricing model with the following assumptions:
Six Months Ended
June 30,
20222021
Range of Black-Scholes fair values of ESPP shares granted
$44.67-$79.74
$128.70-$238.85
Risk-free interest rate
0.6%-1.4%
0.1%
Dividend yield—%—%
Volatility
116.2%-142.9%
120.4%-159.4%
Expected term (in years)
0.5-2
0.5-2.0