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Consolidated Statements of Cash Flows - USD ($) | 12 Months Ended
--- | ---
Dec. 31, 2021 | Dec. 31, 2020 | Dec. 31, 2019
Cash flows from operating activities: |  |  |
Net loss | $ (303,658,710) | $ (167,474,914) | $ (120,551,777)
Adjustments to reconcile net loss to net cash used in operating activities: |  |  |
Depreciation | 3,040,096 | 3,038,996 | 3,598,388
Amortization of intangible assets | 520,415 | 547,081 | 1,066,294
Amortization of operating lease right-of-use assets | 1,170,270 | 1,041,713 | 851,760
Change in fair value of derivative liability | 0 | 75,670,977 | 1,763,652
Stock-based compensation | 26,336,764 | 15,647,523 | 10,901,320
Non-cash interest expense | 858,644 | 4,077,686 | 5,230,954
Amortization of premiums on investments | 1,633,286 | 0 | 1,962
Deferred taxes | 0 | 0 | 5,397
Loss (gain) on short-term investments | 5,397 | 588,270 | (476,368)
Settlement of receivable with shares of common stock from affiliated entity (PLS) | 0 | (1,713,770) | 0
Gain on deconsolidation of Geneos | 0 | (4,121,075) | 0
Loss on disposal of fixed assets | 0 | 26,913 | 5,889
Loss (gain) on equity investment in affiliated entities | 553,570 | (36,556,658) | 3,090,557
Share of net loss in Geneos | 434,387 | 4,584,610 | 0
Net unrealized loss (gain) on available-for-sale equity securities | 3,222,838 | (1,695,497) | 0
Tax benefit from other unrealized gains on short-term investments | 0 | 0 | (266,215)
Unrealized transaction (gain) loss on foreign-currency denominated debt | (176,927) | 15,902 | 471,172
Changes in operating assets and liabilities: |  |  |
Accounts receivable | 13,093,117 | (17,859,894) | 2,616,288
Accounts receivable from affiliated entities | (2,061,412) | 844,423 | (593,461)
Prepaid expenses and other current assets | (6,188,872) | (38,849,572) | (178,008)
Prepaid expenses and other current assets from affiliated entities | (154,760) | 374,107 | 70,665
Other assets | 24,531,654 | (23,285,424) | (2,026)
Accounts payable and accrued expenses | 26,235,907 | 3,115,828 | (4,337,829)
Accrued clinical trial expenses | 375,921 | 5,962,381 | (1,622,037)
Accounts payable and accrued expenses due to affiliated entities | (94,937) | 135,650 | (248,063)
Deferred revenue | (39,853) | (68,078) | (180,450)
Deferred revenue from affiliated entities | 0 | 5,725 | (1,800)
Operating lease right-of-use assets and liabilities, net | (2,329,394) | (2,091,855) | (1,733,599)
Grant funding liability | (2,914,589) | 1,409,098 | 1,899,364
Grant funding liability from affiliated entities | (58,500) | (784,925) | 816,342
Other liabilities | (42,837) | 20,720 | (48,507)
Net cash used in operating activities | (215,708,525) | (177,979,046) | (97,850,136)
Cash flows from investing activities: |  |  |
Purchases of investments | (348,953,236) | (156,216,677) | (100,950,301)
Proceeds from sale of or maturity of investments | 174,839,758 | 62,991,023 | 92,893,232
Purchases of capital assets | (1,231,006) | (1,520,665) | (987,926)
Proceeds from sale of investment of GeneOne | 0 | 40,125,418 | 0
Decrease in cash resulting from the deconsolidation of Geneos | 0 | (2,774,851) | 0
Investment in Geneos | 0 | (1,399,999) | 0
Net cash used in investing activities | (175,344,484) | (58,795,751) | (9,044,995)
Cash flows from financing activities: |  |  |
Proceeds from issuances of convertible senior notes and convertible bonds | 0 | 0 | 97,443,617
Costs related to issuances of convertible senior notes and convertible bonds | 0 | 0 | (3,314,757)
Proceeds from issuance of common stock, net of issuance costs | 209,441,410 | 454,486,400 | 9,089,010
Proceeds from stock option exercises, net of tax payments | 6,668,741 | 12,269,801 | 112,522
Taxes paid related to net share settlement of equity awards, net of proceeds from option exercises | (4,611,348) | (4,028,177) | (892,928)
Acquisition of non-controlling interest | 0 | 2,379,969 | 2,960,131
Proceeds from Geneos issuance of note payable | 0 | 171,620 | 0
Net cash provided by financing activities | 211,498,803 | 465,279,613 | 105,397,595
Effect of exchange rate changes on cash and cash equivalents | (30,134) | 27,205 | 0
Increase (decrease) in cash and cash equivalents | (179,584,340) | 228,532,021 | (1,497,536)
Cash and cash equivalents, beginning of period | 250,728,118 | 22,196,097 | 23,693,633
Cash and cash equivalents, end of period | 71,143,778 | 250,728,118 | 22,196,097
Supplemental disclosure: |  |  |
Amounts accrued for purchases of property and equipment | 204,815 | 136,711 | 0
Interest paid | 1,077,803 | 4,624,764 | 2,717,585
Change in prepaid expenses and other current assets included in fixed assets | 7,709,337 | 0 | 0
Equity component of issuance of convertible notes | 0 | 0 | 15,752,698
Right-of-use assets obtained in exchange for lease obligations | 0 | 0 | 14,634,769
August 2019 Bonds |  |  |
Adjustments to reconcile net loss to net cash used in operating activities: |  |  |
Gain (loss) on extinguishment of debt | 0 | 8,177,043 | 0
6.50% Convertible Senior Notes Due 2024 |  |  |
Adjustments to reconcile net loss to net cash used in operating activities: |  |  |
Gain (loss) on extinguishment of debt | $ 0 | $ (8,762,030) | $ 0

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