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CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands | 12 Months Ended | 130 Months Ended
--- | --- | ---
Dec. 31, 2022 | Dec. 31, 2021 | Dec. 31, 2020 | Dec. 31, 2022
Cash flows from operating activities: |  |  |  |
Net loss | $ (368,198) | $ (523,837) | $ (444,440) |
Adjustments to reconcile net loss to net cash used in operating activities: |  |  |  |
Non-cash royalty revenue related to the sales of future royalties | (69,794) | (77,746) | (48,563) | $ (403,245)
Non-cash interest expense on liabilities related to sales of future royalties | 28,911 | 47,313 | 30,267 | 273,184
Loss on revaluation of liability related to the sale of future royalties | 0 | 24,410 | 0 |
Change in fair value of development derivative liability | (33,427) | 8,023 | 0 |
Non-cash research and development expense | 4,951 | 16,703 | 0 |
Stock-based compensation | 57,320 | 94,674 | 94,261 |
Depreciation and amortization | 13,030 | 14,146 | 14,182 |
Deferred income tax expense | 2,708 | (102) | (36) |
Impairment of right-of-use assets and property, plant and equipment | 65,761 | 0 | 0 |
(Gain) loss on sale or disposal of property, plant and equipment, net | (3,326) | 0 | 0 |
Impairment of advance payments to contract manufacturers and equipment for terminated program | 0 | 0 | 20,351 |
Amortization of premiums (discounts), net and other non-cash transactions | (2,435) | 6,730 | 3,943 |
Changes in operating assets and liabilities: |  |  |  |
Accounts receivable | 16,511 | 12,397 | 1,913 |
Inventory | (3,401) | (509) | (2,627) |
Operating leases, net | (2,680) | 2,340 | 2,743 |
Other assets | 6,906 | (2,586) | 4,512 |
Accounts payable | 3,103 | (11,690) | 2,382 |
Accrued compensation | (6,153) | 1,203 | 4,697 |
Other accrued expenses | (12,734) | (23,524) | 8,644 |
Deferred revenue | (1,060) | (605) | (5,516) |
Net cash used in operating activities | (304,007) | (412,660) | (313,287) |
Cash flows from investing activities: |  |  |  |
Purchases of investments | (467,914) | (960,689) | (987,533) |
Maturities of investments | 826,229 | 1,166,951 | 1,449,304 |
Sales of investments | 0 | 11,504 | 41,700 |
Purchases of property, plant and equipment | (5,676) | (14,989) | (7,258) |
Sales of property, plant and equipment | 13,196 | 0 | 0 |
Net cash provided by investing activities | 365,835 | 202,777 | 496,213 |
Cash flows from financing activities: |  |  |  |
Proceeds from sale of future royalties, net of $3.8 million of transaction costs | 0 | 0 | 146,250 |
Repayment of senior notes | 0 | 0 | (250,000) |
Cash receipts from development derivative liability | 750 | 3,000 | 0 |
Proceeds from shares issued under equity compensation plans | 758 | 33,238 | 23,396 |
Net cash provided by (used in) financing activities | 1,508 | 36,238 | (80,354) |
Effect of foreign exchange rates on cash and cash equivalents | (327) | (92) | 20 |
Net increase (decrease) in cash and cash equivalents | 63,009 | (173,737) | 102,592 |
Cash and cash equivalents at beginning of year | 25,218 | 198,955 | 96,363 |
Cash and cash equivalents at end of year | 88,227 | 25,218 | 198,955 | $ 88,227
Supplemental disclosure of cash flow information: |  |  |  |
Cash paid for interest | 0 | 0 | 9,742 |
Cash paid for income taxes | 272 | 325 | 539 |
Operating lease right-of-use assets recognized in exchange for lease liabilities | 0 | 1,057 | 2,133 |
Accounts receivable recognized in exchange for long-term liabilities | $ 0 | $ 0 | $ 4,000 |

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