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Stockholders' Equity (Tables) | 12 Months Ended
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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,
| 2021 |  | 2020 |  | 2019
Share-based compensation expense as a component of: |  |  |  |  |
Research and development expenses | $ | 17,436 |  |  | $ | 13,497 |  |  | $ | 9,641 |
General and administrative expenses | 21,347 |  |  | 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, 2019 | 1,736,304 |  |  | $ | 66.71 |  |  | 5.47 |  | $ | 125,858 |
Granted | 338,617 |  |  | $ | 116.69 |  |  |  |  |
Exercised | (112,011) |  |  | $ | 23.65 |  |  |  |  |
Forfeited | (6,531) |  |  | $ | 139.37 |  |  |  |  |
Balance at December 31, 2019 | 1,956,379 |  |  | $ | 77.54 |  |  | 5.45 |  | 72,002 |
Exercisable at December 31, 2019 | 1,454,726 |  |  | $ | 61.82 |  |  | 4.42 |  | 70,345 |
Options vested and expected to vest as of December 31, 2019 | 1,956,379 |  |  | $ | 77.54 |  |  | 5.45 |  | $ | 72,002 |
Granted | 806,300 |  |  | $ | 92.93 |  |  |  |  |
Exercised | (156,845) |  |  | $ | 21.26 |  |  |  |  |
Forfeited | (44,012) |  |  | $ | 91.30 |  |  |  |  |
Balance at December 31, 2020 | 2,561,822 |  |  | $ | 85.59 |  |  | 6.09 |  | 59,033 |
Exercisable at December 31, 2020 | 1,611,830 |  |  | $ | 76.05 |  |  | 4.54 |  | 53,286 |
Options vested and expected to vest as of December 31, 2020 | 2,561,822 |  |  | $ | 85.59 |  |  | 6.09 |  | $ | 59,033 |
Granted | 393,589 |  |  | $ | 159.12 |  |  |  |  |
Exercised | (619,731) |  |  | $ | 54.28 |  |  |  |  |
Forfeited | (136,082) |  |  | $ | 110.83 |  |  |  |  |
Balance at December 31, 2021 | 2,199,598 |  |  | $ | 106.00 |  |  | 6.34 |  | 113,302 |
Exercisable at December 31, 2021 | 1,391,952 |  |  | $ | 98.16 |  |  | 5.12 |  | 80,849 |
Options vested and expected to vest as of December 31, 2021 | 2,199,598 |  |  | $ | 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 |
$117.97 | 237,292 |  |  | 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,
| 2021 |  | 2020 |  | 2019 |
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, 2019 | 132,273 |  |  | $ | 130.63 |
Granted | 118,498 |  |  | $ | 115.90 |
Vested | (102,846) |  |  | $ | 121.55 |
Forfeited | (666) |  |  | $ | 134.36 |
Outstanding at December 31, 2019 | 147,259 |  |  | $ | 125.11 |
Granted | 111,306 |  |  | $ | 89.73 |
Vested | (52,363) |  |  | $ | 121.69 |
Forfeited | — |  |  | $ | — |
Outstanding at December 31, 2020 | 206,202 |  |  | $ | 106.88 |
Granted | 167,292 |  |  | $ | 169.63 |
Vested | (98,501) |  |  | $ | 125.59 |
Forfeited | (10,850) |  |  | $ | 141.85 |
Outstanding at December 31, 2021 | 264,143 |  |  | $ | 138.21 |

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