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Income Taxes (Tables) | 12 Months Ended
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Dec. 31, 2021
Income Tax Disclosure [Abstract] |
Components of the Company's Deferred Income Tax Assets (Liabilities) | The significant components of the Company's deferred income tax assets (liabilities) were as follows (in thousands):
| December 31,
| 2021 |  | 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) | $ | — |  |  | $ | — |
Reconciliation of Reported Estimated Income Tax Benefit | The reconciliation of the reported estimated income tax benefit to the amount that would result by applying the U.S. federal statutory tax rate to the net income is as follows (in thousands):
| Year Ended December 31,
| 2021 |  | 2020 |  | 2019
United States federal tax at statutory rate | $ | (42,445) |  |  | $ | (27,245) |  |  | $ | (31,880) |
State taxes (net of federal benefit) | (12,806) |  |  | (8,100) |  |  | (9,524) |
Deferred income tax adjustments | 473 |  |  | 344 |  |  | 2,004 |
Research credit, net | (10,243) |  |  | (14,691) |  |  | (5,830) |
Orphan drug credit, net | (1,449) |  |  | (528) |  |  | (301) |
Other permanent items | 1,199 |  |  | 1,156 |  |  | 1,206 |
Equity-based compensation | 1,079 |  |  | 554 |  |  | 1,889 |
Change in valuation allowance | 64,192 |  |  | 48,510 |  |  | 42,436 |
Income tax expense/(benefit) | $ | — |  |  | $ | — |  |  | $ | — |
Reconciliation of the Beginning and Ending Amount of Gross Unrecognized Tax Benefits | A reconciliation of the beginning and ending amount of gross unrecognized tax benefits is as follows (in thousands):
| Year Ended December 31,
| 2021 |  | 2020 |  | 2019
Beginning balance | $ | 6,126 |  |  | $ | 4,950 |  |  | $ | 4,318 |
Increases for current year tax positions | 965 |  |  | 839 |  |  | 637 |
Increases/(decreases) for prior year tax positions | 106 |  |  | 337 |  |  | (5) |
Ending balance | $ | 7,197 |  |  | $ | 6,126 |  |  | $ | 4,950 |

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