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Consolidated Statements of Cash Flows - USD ($) | 12 Months Ended
--- | ---
Dec. 31, 2022 | Dec. 31, 2021 | Dec. 31, 2020
Cash flows from operating activities: |  |  |
Net loss | $ (279,818,065) | $ (303,658,710) | $ (167,474,914)
Adjustments to reconcile net loss to net cash used in operating activities: |  |  |
Depreciation | 3,656,713 | 3,040,096 | 3,038,996
Amortization of intangible assets | 496,494 | 520,415 | 547,081
Amortization of operating lease right-of-use assets | 1,342,819 | 1,170,270 | 1,041,713
Change in fair value of derivative liability | 0 | 0 | 75,670,977
Non-cash stock-based compensation | 22,555,419 | 26,336,764 | 15,647,523
Non-cash interest expense | 186,977 | 858,644 | 4,077,686
Amortization of (discounts) premiums on investments | (1,320,546) | 1,633,286 | 0
Loss on short-term investments | 4,029,961 | 5,397 | 588,270
Settlement of receivable with shares of common stock from affiliated entity (PLS) | 0 | 0 | (1,713,770)
Gain on deconsolidation of Geneos | 0 | 0 | (4,121,075)
Gain on remeasurement of investment in Geneos | (165,215) | 0 | 0
Loss on disposal of fixed assets | 1,074,830 | 0 | 26,913
Loss (gain) on equity investment in affiliated entities | 1,899,654 | 553,570 | (36,556,658)
Share of net loss in Geneos | 2,165,213 | 434,387 | 4,584,610
Net unrealized loss (gain) on available-for-sale equity securities | 7,846,172 | 3,222,838 | (1,695,497)
Unrealized transaction (gain) loss on foreign-currency denominated debt | 0 | (176,927) | 15,902
Changes in operating assets and liabilities: |  |  |
Accounts receivable, including from affiliated entities | (3,706,172) | 11,031,705 | (17,015,471)
Prepaid expenses and other current assets, including from affiliated entities | (5,336,525) | (6,343,632) | (38,475,465)
Other assets | 741,750 | 24,531,654 | (23,285,424)
Accounts payable and accrued expenses, including from affiliated entities | 32,606,581 | 26,140,970 | 3,251,478
Accrued clinical trial expenses | 267,807 | 375,921 | 5,962,381
Deferred revenue, including from affiliated entity | (85,989) | (39,853) | (62,353)
Operating lease right-of-use assets and liabilities, net | (2,603,956) | (2,329,394) | (2,091,855)
Grant funding liability, including from affiliated entity | (2,034,517) | (2,973,089) | 624,173
Other liabilities | (14,826) | (42,837) | 20,720
Net cash used in operating activities | (216,215,421) | (215,708,525) | (177,979,046)
Cash flows from investing activities: |  |  |
Purchases of investments | (248,528,843) | (348,953,236) | (156,216,677)
Proceeds from sale of or maturity of investments | 361,083,850 | 174,839,758 | 62,991,023
Purchases of capital assets | (969,153) | (1,231,006) | (1,520,665)
Proceeds from sale of investment of GeneOne | 0 | 0 | 40,125,418
Decrease in cash resulting from the deconsolidation of Geneos | 0 | 0 | (2,774,851)
Investment in Geneos | (1,999,998) | 0 | (1,399,999)
Net cash provided by (used in) investing activities | 109,585,856 | (175,344,484) | (58,795,751)
Cash flows from financing activities: |  |  |
Proceeds from issuance of common stock, net of issuance costs | 82,955,311 | 209,441,410 | 454,486,400
Proceeds from stock option exercises | 283,022 | 6,668,741 | 12,269,801
Taxes paid related to net share settlement of equity awards | (1,397,631) | (4,611,348) | (4,028,177)
Acquisition of non-controlling interest | 0 | 0 | 2,379,969
Proceeds from Geneos issuance of note payable | 0 | 0 | 171,620
Net cash provided by financing activities | 81,840,702 | 211,498,803 | 465,279,613
Effect of exchange rate changes on cash and cash equivalents | (25,556) | (30,134) | 27,205
(Decrease) increase in cash and cash equivalents | (24,814,419) | (179,584,340) | 228,532,021
Cash and cash equivalents, beginning of period | 71,143,778 | 250,728,118 | 22,196,097
Cash and cash equivalents, end of period | 46,329,359 | 71,143,778 | 250,728,118
Supplemental disclosure: |  |  |
Amounts accrued for purchases of property and equipment | 108,181 | 204,815 | 136,711
Interest paid | 1,066,975 | 1,077,803 | 4,624,764
Change in prepaid expenses and other current assets related to fixed assets | 6,071,000 | 7,709,337 | 0
August 2019 Bonds |  |  |
Adjustments to reconcile net loss to net cash used in operating activities: |  |  |
Gain (loss) on extinguishment of convertible bonds and senior notes | 0 | 0 | 8,177,043
6.50% Convertible Senior Notes Due 2024 |  |  |
Adjustments to reconcile net loss to net cash used in operating activities: |  |  |
Gain (loss) on extinguishment of convertible bonds and senior notes | $ 0 | $ 0 | $ (8,762,030)

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