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Income Taxes
12 Months Ended
Dec. 31, 2021
Income Tax Disclosure [Abstract]  
Income Taxes Income Taxes
    Income (loss) before provision for income taxes includes the following components (in thousands):
Year Ended December 31,
202120202019
Domestic
$(524,440)$(445,370)$(441,494)
Foreign
1,160 1,423 1,440 
Loss before provision for income taxes$(523,280)$(443,947)$(440,054)
Provision for Income Taxes
    The provision for income taxes consists of the following (in thousands):
Year Ended December 31,
202120202019
Current:
Federal
$— $— $— 
State
50 165 139 
Foreign
609 364 495 
Total current income tax expense659 529 634 
Deferred:
Federal
— — — 
State
— — — 
Foreign
(102)(36)(21)
Total deferred income tax expense(102)(36)(21)
Provision for income taxes
$557 $493 $613 
    
Our income tax provision related to continuing operations differs from the amount computed by applying the statutory income tax rate of 21% to our pretax loss as follows (in thousands):
Year Ended December 31,
202120202019
Income tax benefit at federal statutory rate$(109,889)$(93,229)$(92,411)
Research credits
(4,727)(3,081)(10,511)
Change in valuation allowance
97,914 87,060 104,440 
Non-cash interest expense on liability related to sales of future royalties9,936 6,356 5,259 
Non-cash royalty revenue related to sales of future royalties(7,891)(7,967)(7,624)
Loss on revaluation of liability related to the sale of future royalties4,940 — — 
Stock-based compensation
6,627 7,929 (672)
Other
3,647 3,425 2,132 
Provision for income taxes$557 $493 $613 
Deferred Tax Assets and Liabilities
    Deferred income taxes reflect the net tax effects of loss and credit carryforwards and temporary differences between the carrying amount of assets and liabilities for financial reporting purposes and the amounts used for income tax purposes. We measure deferred tax assets and liabilities based on the rates at which they are expected to reverse in the future. Significant components of our deferred tax assets for federal and state income taxes are as follows (in thousands):
December 31,
20212020
Deferred tax assets:
Net operating loss carryforwards$564,712 $456,284 
Research and other credits139,996 132,994 
Operating lease liabilities34,680 35,672 
Stock-based compensation33,408 32,517 
Liability related to the sale of future royalties23,757 32,737 
Development derivative liability6,639 — 
Other10,651 11,688 
Deferred tax assets before valuation allowance813,843 701,892 
Valuation allowance for deferred tax assets(785,748)(670,103)
Total deferred tax assets28,095 31,789 
Deferred tax liabilities:
Operating lease right-of-use assets(27,204)(29,707)
Other(564)(1,856)
Total deferred tax liabilities(27,768)(31,563)
Net deferred tax assets$327 $226 
    Realization of our deferred tax assets is dependent upon future earnings, if any, the timing and amount of which are uncertain. Because of our lack of U.S. earnings history, other than income resulting from revenue recognized from the BMS Collaboration Agreement, and projected future losses, we have fully reserved our net U.S. deferred tax assets with a valuation allowance. The valuation allowance increased by $115.6 million and $95.0 million during the years ended December 31, 2021 and 2020, respectively. The increase in the valuation allowance is consistent with the increase in net operating loss carryforwards in the respective periods.
    Net Operating Loss and Tax Credit Carryforwards
    As of December 31, 2021, we had a net operating loss carryforward for federal income tax purposes of approximately $2.4 billion, portions of which will begin to expire in 2022 and a total state net operating loss carryforward of approximately $1.5 billion, portions of which will begin to expire in 2026. We have federal research credits of approximately $103.3 million, which will begin to expire in 2023 and state research credits of approximately $47.0 million which have no expiration date. We have federal orphan drug credits of $19.4 million which will begin to expire in 2026. Utilization of some of the federal and state
net operating loss and credit carryforwards are subject to annual limitations due to the “change in ownership” provisions of the Internal Revenue Code of 1986 and similar state provisions.
Unrecognized tax benefits
    We have the following activity relating to unrecognized tax benefits (in thousands):
Year Ended December 31,
202120202019
Beginning balance
$78,665 $77,410 $27,419 
Tax positions related to current year:
Additions2,371 2,512 49,858 
Reductions— — — 
Tax positions related to prior years:
Additions58 193 277 
Reductions(490)(1,450)(144)
Settlements— — — 
Lapses in statute of limitations— — — 
Ending balance
$80,604 $78,665 $77,410 
    If we are eventually able to recognize our uncertain tax positions, our effective tax rate may be reduced. We currently have a full valuation allowance against our U.S. net deferred tax asset which would impact the timing of the effective tax rate benefit should any of these uncertain tax positions be favorably settled in the future. Adjustments to the substantial majority of our uncertain tax positions would result in an adjustment of our net operating loss or tax credit carryforwards rather than resulting in a cash outlay.
    We file income tax returns in the U.S., California, Alabama, certain other states and India. As a result of our net operating loss and research credit carryforwards, substantially all of our domestic tax years remain open and subject to examination. We may be subject to examination in India from time to time, but we do not believe that any liability resulting from such an examination would have a material effect on our financial position or results of operations.
Our policy is to include interest and penalties related to unrecognized tax benefits, if any, within the provision for income taxes in the consolidated statements of operations. During the years ended December 31, 2021, 2020 and 2019, no significant interest or penalties were recognized relating to unrecognized tax benefits. Although it is reasonably possible that certain unrecognized tax benefits could change in the future, we do not anticipate any significant changes over the next twelve months.