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Stockholders' Equity (Tables)
 12 Months Ended
Dec. 31, 2021
Equity [Abstract]  
Schedule of Share-Based Compensation Expense The following table summarizes non-cash share-based compensation expense (in thousands):
December 31,
202120202019
Share-based compensation expense as a component of:
Research and development expenses$17,436 $13,497 $9,641 
General and administrative expenses21,347 17,230 14,874 
$38,783 $30,727 $24,515 
Schedule of Stock Option Plan Activity
Following is a summary of our stock option plan activity and related information:
 
Shares
Weighted
Average
Exercise
Price
Weighted
Average
Remaining
Contractual
Term in
Years
Aggregate
Intrinsic
Value
(In thousands)
Balance at January 1, 20191,736,304 $66.71 5.47$125,858 
Granted338,617 $116.69 
Exercised(112,011)$23.65 
Forfeited(6,531)$139.37 
Balance at December 31, 20191,956,379 $77.54 5.4572,002 
Exercisable at December 31, 20191,454,726 $61.82 4.4270,345 
Options vested and expected to vest as of December 31, 20191,956,379 $77.54 5.45$72,002 
Granted806,300 $92.93 
Exercised(156,845)$21.26 
Forfeited(44,012)$91.30 
Balance at December 31, 20202,561,822 $85.59 6.0959,033 
Exercisable at December 31, 20201,611,830 $76.05 4.5453,286 
Options vested and expected to vest as of December 31, 20202,561,822 $85.59 6.09$59,033 
Granted393,589 $159.12 
Exercised(619,731)$54.28 
Forfeited(136,082)$110.83 
Balance at December 31, 2021 2,199,598 $106.00 6.34113,302 
Exercisable at December 31, 20211,391,952 $98.16 5.1280,849 
Options vested and expected to vest as of December 31, 20212,199,598 $106.00 6.34$113,302 
Schedule of Stock Option Plan Activity by Exercise Price Range
Following is a further breakdown of the options outstanding as of December 31, 2021:
 
Range of exercise prices
Options
outstanding
Weighted
average
remaining  life
in years
Weighted average
exercise price
Options
exercisable
Weighted average
exercise price
$12.53-$56.26
253,824 1.94$37.55 239,824 $38.90 
$67.53-$74.42
278,281 4.04$72.10 217,587 $73.17 
$82.90-$95.35
159,988 5.06$86.11 132,963 $86.24 
$95.68
266,263 8.12$95.68 109,154 $95.68 
$98.20-$100.38
294,772 7.33$99.10 160,120 $99.79 
$101.07-$117.58
159,204 7.45$111.26 99,488 $111.18 
$117.97237,292 7.12$117.97 158,958 $117.97 
$119.08-$159.01
299,585 7.00$149.40 205,098 $152.50 
$159.81-$171.28
6,881 6.51$166.28 5,828 $165.62 
$177.50-$195.91
243,508 8.91$178.62 62,932 $181.84 
2,199,598 6.34$106.00 1,391,952 $98.16 
Schedule of Stock Option Weighted-Average Assumptions
The assumptions used for the specified reporting periods and the resulting estimates of weighted-average grant date fair value per share of options granted:
 Year Ended December 31,
 202120202019
Risk-free interest rate
0.4%-1.2%
0.2%-1.4%
1.4%-2.6%
Expected volatility
47%-63%
47%-71%
40%-49%
Expected term
4.7 to 6.3 years
4.7 to 5.1 years
4.6 to 5.9 years
Schedule of Restricted Stock Activity
The following is a summary of our restricted stock activity and related information: 
Shares
Weighted-Average
Grant Date Fair
Value
Outstanding at January 1, 2019132,273 $130.63 
Granted118,498 $115.90 
Vested(102,846)$121.55 
Forfeited(666)$134.36 
Outstanding at December 31, 2019147,259 $125.11 
Granted111,306 $89.73 
Vested(52,363)$121.69 
Forfeited— $— 
Outstanding at December 31, 2020206,202 $106.88 
Granted167,292 $169.63 
Vested(98,501)$125.59 
Forfeited(10,850)$141.85 
Outstanding at December 31, 2021264,143 $138.21