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Stock-Based Compensation - Employee expense (Details) - USD ($) $ in Thousands | 12 Months Ended
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Dec. 31, 2021 | Dec. 31, 2020 | Dec. 31, 2019
Stock-based compensation |  |  |
Total employee, director and non-employee stock-based compensation expense | $ 36,975 | $ 31,619 | $ 31,851
Options to purchase common stock |  |  |
Stock-based compensation |  |  |
Total employee, director and non-employee stock-based compensation expense | 27,909 | 26,045 | 30,502
Employee stock purchase plan |  |  |
Stock-based compensation |  |  |
Total employee, director and non-employee stock-based compensation expense | 992 | 804 | 687
Restricted stock units |  |  |
Stock-based compensation |  |  |
Total employee, director and non-employee stock-based compensation expense | 8,074 | 4,770 | 662
General and administrative |  |  |
Stock-based compensation |  |  |
Total employee, director and non-employee stock-based compensation expense | 12,813 | 10,769 | 8,854
Research and development |  |  |
Stock-based compensation |  |  |
Total employee, director and non-employee stock-based compensation expense | $ 24,162 | $ 20,850 | $ 22,997

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- Definition Amount of noncash expense for share-based payment arrangement. + References Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef -Publisher FASB -Name Accounting Standards Codification -Topic 230 -SubTopic 10 -Section 45 -Paragraph 28 -Subparagraph (a) -URI http://asc.fasb.org/extlink&oid=123570139&loc=d3e3602-108585 + Details
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