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Consolidated Statements of Cash Flows - USD ($) | 12 Months Ended | 118 Months Ended
--- | --- | ---
Dec. 31, 2021 | Dec. 31, 2020 | Dec. 31, 2019 | Dec. 31, 2021
Cash flows from operating activities: |  |  |  |
Net loss | $ (523,837,000) | $ (444,440,000) | $ (440,667,000) |
Adjustments to reconcile net loss to net cash used in operating activities: |  |  |  |
Non-cash royalty revenue related to the sales of future royalties | (77,746,000) | (48,563,000) | (36,303,000) | $ (333,451,000)
Non-cash interest expense on liabilities related to sales of future royalties | 47,313,000 | 30,267,000 | 25,044,000 | 244,273,000
Loss on revaluation of liability related to the sale of future royalties | 24,410,000 | 0 | 0 |
Change in fair value of development derivative liability | 8,023,000 | 0 | 0 |
Non-cash research and development expense | 16,703,000 | 0 | 0 |
Stock-based compensation | 94,674,000 | 94,261,000 | 99,795,000 |
Depreciation and amortization | 14,146,000 | 14,182,000 | 13,156,000 |
Impairment of advance payments to contract manufacturers and equipment for terminated program | 0 | 20,351,000 | 0 |
Amortization of premiums (discounts), net and other non-cash transactions | (6,730,000) | (3,943,000) | 11,394,000 |
Changes in operating assets and liabilities |  |  |  |
Accounts receivable | 12,397,000 | 1,913,000 | 6,411,000 |
Inventory | (509,000) | (2,627,000) | (1,284,000) |
Operating leases, net | 2,340,000 | 2,743,000 | 13,090,000 |
Other assets | (2,688,000) | 4,476,000 | 1,190,000 |
Accounts payable | (11,690,000) | 2,382,000 | 12,967,000 |
Accrued compensation | 1,203,000 | 4,697,000 | 1,530,000 |
Other accrued expenses | (23,524,000) | 8,644,000 | 4,349,000 |
Deferred revenue | (605,000) | (5,516,000) | (16,565,000) |
Net cash used in operating activities | (412,660,000) | (313,287,000) | (328,681,000) |
Cash flows from investing activities: |  |  |  |
Purchases of investments | (960,689,000) | (987,533,000) | (1,380,865,000) |
Maturities of investments | 1,166,951,000 | 1,449,304,000 | 1,614,036,000 |
Sales of investments | 11,504,000 | 41,700,000 | 0 |
Purchases of property, plant and equipment | (14,989,000) | (7,258,000) | (26,285,000) |
Net cash provided by investing activities | 202,777,000 | 496,213,000 | 206,886,000 |
Cash flows from financing activities: |  |  |  |
Proceeds from sale of future royalties, net of $3.8 million of transaction costs | 0 | 146,250,000 | 0 |
Repayment of senior notes | 0 | (250,000,000) | 0 |
Cash receipts from development derivative liability | 3,000,000 | 0 | 0 |
Proceeds from shares issued under equity compensation plans | 33,238,000 | 23,396,000 | 23,355,000 |
Net cash provided by (used in) financing activities | 36,238,000 | (80,354,000) | 23,355,000 |
Effect of foreign exchange rates on cash and cash equivalents | (92,000) | 20,000 | (102,000) |
Net increase (decrease) in cash and cash equivalents | (173,737,000) | 102,592,000 | (98,542,000) |
Cash and cash equivalents at beginning of year | 198,955,000 | 96,363,000 | 194,905,000 |
Cash and cash equivalents at end of year | 25,218,000 | 198,955,000 | 96,363,000 | $ 25,218,000
Supplemental disclosure of cash flow information: |  |  |  |
Cash paid for interest | 0 | 9,742,000 | 19,199,000 |
Cash paid for income taxes | 325,000 | 539,000 | 555,000 |
Operating lease right-of-use assets recognized in exchange for lease liabilities | 1,057,000 | 2,133,000 | 57,691,000 |
Accounts receivable recognized in exchange for long-term liabilities | $ 0 | $ 4,000,000 | $ 0 |

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