During the years ended December 31, 2019, 2018 and 2017, the Company recorded no income tax benefits for the net operating losses incurred in each year or interim period, due to its uncertainty of realizing a benefit from those items.

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,
	2019			2018			2017
Federal statutory income tax rate		(21.0	)%		(21.0	)%		(34.0	)%
Research and development tax credits		(5.8	)		(7.2	)		(7.7	)
State taxes, net of federal benefit		(6.8	)		(7.2	)		(4.8	)
Stock-based compensation		(1.7	)		2.0			1.2
Revaluation of preferred stock warrant liability		—			—			33.1
Other		(0.7	)		0.8			(0.3	)
Change in deferred tax asset valuation allowance		36.0			32.6			12.5
Effective income tax rate		—	%		—	%		—	%

Net deferred tax assets as of December 31, 2019 and 2018 consisted of the following:

	December 31,
	2019			2018
Deferred tax assets:
Net operating loss carryforwards	$	72,752		$	50,723
Research and development tax credit carryforwards		36,602			32,522
Capitalized organization costs		244			275
Stock-based compensation expense		12,783			9,178
Lease Liability		5,500			—
Charitable Contributions		13			11
Deferred Revenue		32,713			37,499
Accrued expenses		1,251			4,279
Capitalized research and development expenses		58			66
Total deferred tax assets	$	161,916		$	134,553
Deferred tax liabilities:
Depreciation and amortization		(1,467	)		(2,544	)
Right of use assets		(3,103	)		—
Total deferred tax liabilities		(4,570	)		(2,544	)
Valuation allowance	$	(157,346	)	$	(132,009	)
Net deferred tax assets	$	—		$	—

As of December 31, 2019, the Company had net operating loss carryforwards (“NOLs”) for federal and state income tax purposes of $266,485 and $265,671, respectively. Federal NOLs of $119,781, generated before 2018, will begin expiring in varying amounts in 2035 unless utilized. The remaining federal NOLs of $146,704, generated after 2017, will be carried forward indefinitely and could be used to offset up to 80% of taxable income of each future tax year. Massachusetts does not follow federal time periods for NOLs and as such the Company’s Massachusetts NOLs of $265,671 will expire in at various times starting in 2035. As of December 31, 2019, the Company also had available research and development tax credit carryforwards for federal and state income tax purposes of $31,828 and $6,043, respectively, which begin to expire in 2031 and 2028, respectively. The federal research and development tax credits include an orphan drug credit carryforward of $18,817. Utilization of the NOLs and research and development tax credit carryforwards may be subject to a substantial annual limitation under Sections 382 and 383 of the Internal Revenue Code of 1986 due to ownership changes that have occurred previously or that could occur in the future. These ownership changes may limit the amount of carryforwards that can be utilized annually to offset future taxable income. In general, an ownership change, as defined by Section 382, results from transactions increasing the ownership of certain shareholders or public groups in the stock of a corporation by more than 50% over a three-year period. Since its formation, the Company has raised capital through the issuance of capital stock on several occasions. These financings, combined with the purchasing shareholders' subsequent disposition of those shares, may have resulted in a change of control or could result in a change of control in the future upon subsequent disposition. The Company conducted an analysis to determine if historical changes in ownership through August 31, 2015 would limit or otherwise restrict its ability to utilize these NOLs and research and development credit carryforwards. As a result of this analysis, the Company does not believe there are any significant limitations on its ability to utilize these carryforwards. However, future changes in ownership after August 31, 2015 could affect the limitation in future years. Any limitation may result in expiration of a portion of the NOLs or research and development credit carryforwards before utilization.

The Company has evaluated the positive and negative evidence bearing upon its ability to realize the deferred tax assets. Management has considered the Company’s history of cumulative net losses incurred since inception and its lack of commercialization of any products or generation of any revenue from product sales since inception and has concluded that it is more likely than not that the Company will not realize the benefits of the deferred tax assets. Accordingly, a full valuation allowance has been established against the deferred tax assets as of December 31, 2019 and 2018. Management reevaluates the positive and negative evidence at each reporting period.

Changes in the valuation allowance for deferred tax assets during the years ended December 31, 2019, 2018 and 2017 related primarily to the increases in NOLs, research and development tax credit carryforwards, stock-based compensation and decrease of the deferred rate due to tax reform were as follows:

	Year Ended December 31,
	2019			2018			2017
Valuation allowance at beginning of year	$	(132,009	)	$	(94,126	)	$	(82,994	)
Decreases recorded as benefit to income tax provision		—			—			29,546
Increases recorded to income tax provision		(25,337	)		(37,883	)		(40,678	)
Valuation allowance as of end of year	$	(157,346	)	$	(132,009	)	$	(94,126	)

As of December 31, 2019, 2018, and 2017, the Company had no unrecognized tax benefits. Interest and penalty charges, if any, related to unrecognized tax benefits would be classified as income tax expense. The Company does not expect any significant change in its uncertain tax positions in the next 12 months.