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Income Taxes - Reconciliation of Reported Estimated Income Tax Benefit (Details) - USD ($)
$ in Thousands
12 Months Ended
Dec. 31, 2021
Dec. 31, 2020
Dec. 31, 2019
Income Tax Disclosure [Abstract]      
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) $ 0 $ 0 $ 0