	Years Ended December 31,
	2018			2017 *			2016 *
Domestic	$	(38,472	)	$	(80,735	)	$	(25,342	)
Foreign		(47,644	)		(39,819	)		(32,797	)
Loss before provision for income taxes	$	(86,116	)	$	(120,554	)	$	(58,139	)

The provision for (benefit from) income taxes consists of the following (in thousands):

	Years Ended December 31,
	2018		2017		2016
Current:
Federal	$	—	$	—	$	—
State		2		2		2
Foreign		302		319		139
Total current		304		321		141
Deferred:
Federal		—		—		(212	)
State		—		—		—
Foreign		—		—		—
Total deferred		—		—		(212	)
Total provision for (benefit from) income taxes	$	304	$	321	$	(71	)

The following is the reconciliation between the statutory federal income tax rate and the Company’s effective tax rate:

	Years Ended December 31,
	2018			2017			2016
Tax at statutory federal rate		21.0	%		34.0	%		34.0	%
State tax		—	%		—	%		—	%
Stock-based compensation expense		14.5	%		18.5	%		(7.9	)%
Change in deferred tax assets due to rate change		—	%		43.9	%		—	%
Change in valuation allowance due to rate change		—	%		(43.9	)%		—	%
Net operating losses not benefitted		(23.2	)%		(43.8	)%		(12.9	)%
Foreign net operating losses not benefitted		(11.6	)%		(6.7	)%		(13.0	)%
Orphan drug credit		0.0	%		(2.0	)%		—	%
Other		(1.1	)%		(0.3	)%		(0.1	)%
Total		(0.4	)%		(0.3	)%		0.1	%

Significant components of the Company’s deferred tax assets are as follows (in thousands):

	December 31,
	2018			2017
Federal and state net operating loss carryforwards	$	91,683		$	71,256
Tax credit carryforwards		45,885			39,488
Foreign net operating loss carryforwards		21,295			15,052
Stock-based compensation		9,281			7,835
Lease obligations		2,511			2,737
Reserves and accruals		6,072			4,851
Deferred revenue		16,454			18,103
Fixed assets		356			—
Other		450			420
Subtotal		193,987			159,742
Less: Valuation allowance		(193,987	)		(159,540	)
Net deferred tax assets		—			202

Fixed assets		—			(181	)
Other		—			(21	)
Net deferred tax liabilities		—			(202	)
Total net deferred tax assets	$	—		$	—

A valuation allowance has been provided to reduce the deferred tax assets to an amount management believes is more likely than not to be realized. Expected realization of the deferred tax assets for which a valuation allowance has not been recognized is based on upon the reversal of existing temporary differences and future taxable income.

The valuation allowance increased by $34.4 million, $30.5 million and $12.3 million for the years ended December 31, 2018, 2017 and 2016, respectively. Due to uncertainty surrounding the realization of the favorable tax attributes in the future tax returns, the Company has established a valuation allowance against its otherwise recognizable net deferred tax assets.

At December 31, 2018, the Company had net operating loss carryforwards available to offset future taxable income of approximately $400.3 million and $148.1 million for federal and state tax purposes, respectively. These carryforwards will begin to expire in 2026 for federal and 2019 for state purposes, if not utilized before these dates. The Company also had foreign net operating loss carryforwards of approximately $86.3 million which expire between 2019 and 2028 if not utilized.

At December 31, 2018, the Company had approximately $46.4 million of federal and $26.3 million of California research and development tax credit and other tax credit carryforwards available to offset future taxable income. The federal credits begin to expire in 2019 and the California research credits have no expiration dates.

On December 22, 2017, the Tax Cuts and Jobs Act (“Tax Act”) was signed into law making significant changes to the Internal Revenue Code. Changes include, but are not limited to, a corporate tax rate decrease from 35% to 21% effective for tax years beginning after December 31, 2017, the transition of U.S international taxation from a worldwide tax system to a territorial system, and a one-time transition tax on the mandatory deemed repatriation of cumulative foreign earnings as. In the fourth quarter of 2018, the Company completed its analysis to determine the effect of the Tax Act and no material adjustments were recognized as of December 31, 2018. Developing interpretations of the provisions of the Tax Act, changes to U.S. Treasury regulations, administrative interpretations or court decisions interpreting the Tax Act in the future periods may require further adjustments to the Company’s analysis.

Due to the adoption of ASU 2016-09 in 2017, the Company recorded a retrospective increase of $19.5 million in the deferred tax assets for previously unrecognized excess tax benefits that existed as of December 31, 2016, and a corresponding increase of $19.5 million in the valuation allowance against these deferred tax assets. In addition, all excess tax benefits and deficiencies are recognized as income tax expense and will result in increased volatility in the Company’s income tax.

Federal and state tax laws impose substantial restrictions on the utilization of net operating loss and credit carryforwards in the event of an “ownership change” for tax purposes, as defined in IRC Section 382. The Company reviewed its stock ownership for year ended December 31, 2018 and concluded no ownership changes occurred which would result in a reduction of its net operating loss or in its research and development credits expiring unused. If additional ownership change occurs, the utilization of net operating loss and credit carryforwards could be significantly reduced.

The Company had unrecognized tax benefits of approximately $28.0 million as of December 31, 2018. Approximately $0.5 million of unrecognized tax benefits, if recognized, would affect the effective tax rate. The interest accrued as of December 31, 2018 and 2017 was immaterial.

A reconciliation of the beginning and ending amounts of unrecognized income tax benefits during the three years ended December 31, 2018 is as follows (in thousands):

	Federal and State
Balance as of December 31, 2015	$	24,213
Decrease due to prior positions		(7,109	)
Increase due to current year position		2,550
Balance as of December 31, 2016		19,654
Increase due to prior positions		303
Increase due to current year position		5,448
Decrease due to U.S. tax rate change		(2,044	)
Balance as of December 31, 2017		23,361
Increase due to prior positions		379
Increase due to current year position		4,216
Balance as of December 31, 2018	$	27,956

Unrecognized tax benefits may change during the next twelve months for items that arise in the ordinary course of business. The Company does not anticipate a material change to its unrecognized tax benefits over the next twelve months that would affect the Company’s effective tax rate.

The Company classifies interest and penalties as a component of tax expense, if any.

The Company files income tax returns in the U.S. federal jurisdiction, U.S. state and other foreign jurisdictions. The U.S. federal and U.S. state taxing authorities may choose to audit tax returns for tax years beyond the statute of limitation period due to significant tax attribute carryforwards from prior years, making adjustments only to carryforward attributes. The foreign statute of limitation generally remains open from 2009 to 2018. The Company is not currently under audit in any tax jurisdiction.