Income Taxes (Tables)

12 Months Ended

Dec. 31, 2021

Income Tax Disclosure [Abstract]

Reconciliation of U.S. Federal Statutory Income Tax Rate to Effective Income Tax Rate

A reconciliation of the U.S. federal statutory income tax rate to the Company's effective income tax rate is as follows:

	Year Ended December 31,
	2021		2020		2019
Federal statutory income tax rate	21.0	%	21.0	%	21.0	%
State taxes, including credits, net of federal benefit	3.2		2.4		7.0
Federal research and orphan drug credit	2.5		2.1		5.4
Stock-based compensation	0.1		5.4		4.7
Permanent adjustments and other	(0.3)		0.5		(0.9)
Increase in deferred tax asset valuation allowance	(26.5)		(31.4)		(37.2)
Effective income tax rate	—	%	—	%	—	%

Schedule of Net Deferred Tax Assets

Net deferred tax assets consisted of the following:

	December 31,
(in thousands)	2021		2020
Deferred tax assets (liabilities):
Net operating loss carryforwards	$	216,377	$	159,192
Research and orphan drug credit carryforwards	40,077		31,142
Stock-based compensation	15,701		8,928
Accrued expenses	9,560		3,779
Operating lease liabilities	9,019		9,321
Property and equipment	(322)		(387)
Operating lease assets	(8,904)		(8,811)
Other	1,028		16
Total gross deferred tax assets	282,536		203,180
Valuation allowance	(282,536)		(203,180)
Net deferred tax assets	$	—	$	—

Schedule of Changes in Valuation Allowance for Deferred Tax Assets

The change in the valuation allowance was as follows:

	Year Ended December 31,
(in thousands)	2021		2020
Valuation allowance as of beginning of year	$	(203,180)	$	(119,647)
Net increases recorded to income tax provision	(79,356)		(83,533)
Valuation allowance as of end of year	$	(282,536)	$	(203,180)

Schedule of Income before Income Tax, Domestic and Foreign

Net loss by jurisdiction is as follows:

	Year Ended December 31,
(in thousands)	2021		2020		2019
U.S.	$	(281,129)	$	(266,483)	$	(192,256)
Foreign	(18,835)		(6)		—
Net loss	$	(299,964)	$	(266,489)	$	(192,256)