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Income Taxes - Components of the Company's Deferred Tax Assets (Liabilities) (Details) - USD ($) $ in Thousands | Dec. 31, 2021 | Dec. 31, 2020
--- | --- | ---
Deferred income tax assets: |  |
Federal U.S. net operating loss carryforward | $ 175,802 | $ 136,086
State net operating loss carryforward | 49,965 | 37,465
Research and development credit, net | 60,514 | 50,271
Orphan drug credit, net | 24,858 | 23,409
Operating lease liabilities | 7,008 | 8,048
Deferred revenue | 1,245 | 3,132
Other | 16,727 | 14,285
Gross deferred income tax assets | 336,119 | 272,696
Valuation allowance | (327,595) | (263,403)
Net deferred income tax assets | 8,524 | 9,293
Deferred income tax liabilities: |  |
Depreciation | (1,688) | (2,123)
Operating lease ROU assets | (4,576) | (5,316)
Prepaid expenditures | (2,260) | (1,854)
Gross deferred income tax liabilities | (8,524) | (9,293)
Net deferred income tax asset/(liability) | $ 0 | $ 0

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