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Organization and Significant Accounting Policies (Tables) | 12 Months Ended
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Dec. 31, 2021
Organization and Significant Accounting Policies [Abstract] |
Basic Net Income (Loss) per Share | We calculated our basic net loss per share for the year ended December 31, 2020 as follows (in thousands, except per share amounts):
Year Ended December 31, 2020 |  | Weighted Average Shares Owned in Akcea |  |  | Akcea’s Net Loss Per Share |  |  | Basic Net Loss Per Share Calculation |
Akcea’s net loss in the pre-merger period attributable to our ownership |  |  | 77,095 |  |  | $ | (1.45 | ) |  | $ | (111,775 | )
Akcea’s net loss in the post-merger period attributable to our ownership |  |  |  |  |  |  |  |  |  |  | (85,987 | )
Akcea’s total net loss attributable to our ownership |  |  |  |  |  |  |  |  |  | $ | (197,762 | )
Ionis’ stand-alone net loss |  |  |  |  |  |  |  |  |  |  | (246,702 | )
Net loss available to Ionis common stockholders |  |  |  |  |  |  |  |  |  | $ | (444,464 | )
Weighted average shares outstanding |  |  |  |  |  |  |  |  |  |  | 139,612 |
Basic net loss per share |  |  |  |  |  |  |  |  |  | $ | (3.18 | )
We calculated our basic net income per share for the year ended December 31, 2019 as follows (in thousands, except per share amounts):
Year Ended December 31, 2019 |  | Weighted Average Shares Owned in Akcea |  |  | Akcea’s Net Income Per Share |  |  | Basic Net Income Per Share Calculation |
Common shares |  |  | 70,100 |  |  | $ | 0.49 |  |  | $ | 34,073 |
Akcea’s net income attributable to our ownership |  |  |  |  |  |  |  |  |  | $ | 34,073 |
Ionis’ stand-alone net income |  |  |  |  |  |  |  |  |  |  | 246,487 |
Net income available to Ionis common stockholders |  |  |  |  |  |  |  |  |  | $ | 280,560 |
Weighted average shares outstanding |  |  |  |  |  |  |  |  |  |  | 139,998 |
Basic net income per share |  |  |  |  |  |  |  |  |  | $ | 2.00 |
Basic and Diluted Net Income Per Share | For the year ended December 31, 2019, we reported net income available to Ionis common stockholders. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during each period. We calculated our diluted net income per share as follows (in thousands except per share amounts):
Year Ended December 31, 2019 |  | Net Income Available to Ionis Common Stockholders (Numerator) |  |  | Shares (Denominator) |  |  | Per-Share Amount |
Net income available to Ionis common stockholders |  | $ | 280,560 |  |  |  | 139,998 |  |  | $ | 2.00 |
Effect of dilutive securities: |  |  |  |  |  |  |  |  |  |  |  |
Shares issuable upon exercise of stock options |  |  | — |  |  |  | 2,090 |  |  |  |  |
Shares issuable upon restricted stock award issuance |  |  | — |  |  |  | 766 |  |  |  |  |
Shares issuable related to our ESPP |  |  | — |  |  |  | 18 |  |  |  |  |
Shares issuable related to our 0.125 percent convertible notes |  |  | 860 |  |  |  | 217 |  |  |  |  |
Shares issuable related to our 1 percent convertible notes |  |  | 9,527 |  |  |  | 10,075 |  |  |  |  |
|  | $ | 290,947 |  |  |  | 153,164 |  |  | $ | 1.90 |
Amortization Expense for Patents | Based on our existing patents, we estimate amortization expense related to patents in each of the next five years to be the following:
Year Ending December 31, |  | Amortization (in millions) |
2022 |  | $ | 2.2 |
2023 |  | $ | 2.1 |
2024 |  | $ | 1.9 |
2025 |  | $ | 1.8 |
2026 |  | $ | 1.8 |
Accrued Liabilities | Our accrued liabilities consisted of the following (in thousands):
|  | December 31, |
|  | 2021 |  |  | 2020 |
Clinical expenses |  | $ | 65,730 |  |  | $ | 39,477 |
In-licensing expenses |  |  | 8,044 |  |  |  | 8,264 |
Commercial expenses |  |  | 2,471 |  |  |  | 11,559 |
Other miscellaneous expenses |  |  | 12,315 |  |  |  | 30,861 |
Total accrued liabilities |  | $ | 88,560 |  |  | $ | 90,161 |
Inventory | Our inventory consisted of the following (in thousands):
|  | December 31, |
|  | 2021 |  |  | 2020 |
Raw materials: |  |  |  |  |  |
Raw materials- clinical |  | $ | 14,507 |  |  | $ | 9,206 |
Raw materials- commercial |  |  | 4,139 |  |  |  | 7,502 |
Total raw materials |  |  | 18,646 |  |  |  | 16,708 |
Work in process |  |  | 5,770 |  |  |  | 2,252 |
Finished goods |  |  | 390 |  |  |  | 3,005 |
Total inventory |  | $ | 24,806 |  |  | $ | 21,965 |
Property, Plant and Equipment | We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which consists of the following (in thousands):
|  | Estimated Useful |  |  | December 31, |
|  | Lives (in years) |  |  | 2021 |  |  | 2020 |
Computer software, laboratory, manufacturing and other equipment |  | 3 to 10 |  |  | $ | 72,802 |  |  | $ | 68,990 |
Building, building improvements and building systems |  | 15 to 40 |  |  |  | 144,046 |  |  |  | 137,879 |
Land improvements |  | 20 |  |  |  | 10,077 |  |  |  | 8,391 |
Leasehold improvements |  | 5 to 15 |  |  |  | 20,144 |  |  |  | 17,263 |
Furniture and fixtures |  | 5 to 10 |  |  |  | 10,591 |  |  |  | 12,871 |
|  |  |  |  |  |  | 257,660 |  |  |  | 245,394 |
Less accumulated depreciation |  |  |  |  |  |  | (102,653 | ) |  |  | (87,379 | )
|  |  |  |  |  |  | 155,007 |  |  |  | 158,015 |
Land |  |  |  |  |  |  | 23,062 |  |  |  | 23,062 |
Total |  |  |  |  |  | $ | 178,069 |  |  | $ | 181,077 |
Changes in Accumulated Other Comprehensive Loss | Accumulated other comprehensive loss is comprised of unrealized gains and losses on investments, net of taxes and currency translation adjustments. The following table summarizes changes in accumulated other comprehensive loss for the years ended December 31, 2021, 2020 and 2019 (in thousands):
|  | Year Ended December 31, |
|  | 2021 |  |  | 2020 |  |  | 2019 |
Beginning balance accumulated other comprehensive loss |  | $ | (21,071 | ) |  | $ | (25,290 | ) |  | $ | (32,016 | )
Unrealized gains (losses) on securities, net of tax (1) |  |  | (11,486 | ) |  |  | 3,729 |  |  |  | 6,633 |
Currency translation adjustment |  |  | (111 | ) |  |  | 617 |  |  |  | 93 |
Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc. |  |  | — |  |  |  | (127 | ) |  |  | — |
Net other comprehensive loss for the period |  |  | (11,597 | ) |  |  | 4,219 |  |  |  | 6,726 |
Ending balance accumulated other comprehensive loss |  | $ | (32,668 | ) |  | $ | (21,071 | ) |  | $ | (25,290 | )
________________
(1) | We did not have tax expense included in our other comprehensive loss for the years ended December 31, 2021 and 2020. For the year ended December 31, 2019, we had a tax benefit of $1.4 million included in other comprehensive loss.
Adoption of ASU 2020-06 | The following table summarizes the adjustments we made to the consolidated balance sheet we originally reported at December 31, 2020 to adopt ASU 2020-06 (in thousands):
|  | December 31, 2020 |
|  | As Previously Reported |  |  | ASU 2020-06 Adjustment |  |  | As Revised |
1 percent convertible senior notes |  | $ | 293,161 |  |  | $ | 15,648 |  |  | $ | 308,809 |
0.125 percent convertible senior notes |  | $ | 455,719 |  |  | $ | 84,417 |  |  | $ | 540,136 |
Additional paid-in-capital |  | $ | 2,113,646 |  |  | $ | (218,127 | ) |  | $ | 1,895,519 |
Accumulated deficit |  | $ | (1,249,368 | ) |  | $ | 118,062 |  |  | $ | (1,131,306 | )
The following tables summarize the adjustments we made to the consolidated statement of operations we originally reported for the years ended December 31, 2020 and 2019 to adopt ASU 2020-06 (in thousands):
|  | Year Ended December 31, 2020 |
|  | As Previously Reported |  |  | ASU 2020-06 Adjustment |  |  | As Revised |
Interest expense |  | $ | (44,990 | ) |  | $ | 35,480 |  |  | $ | (9,510 | )
Loss before income tax expense |  | $ | (170,032 | ) |  | $ | 35,480 |  |  | $ | (134,552 | )
Income tax expense |  | $ | (316,734 | ) |  | $ | (28,457 | ) |  | $ | (345,191 | )
Net loss |  | $ | (486,766 | ) |  | $ | 7,023 |  |  | $ | (479,743 | )
Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders |  | $ | (451,286 | ) |  | $ | 7,023 |  |  | $ | (444,263 | )
Basic and diluted net loss per share |  | $ | (3.23 | ) |  | $ | 0.05 |  |  | $ | (3.18 | )
|  | Year Ended December 31, 2019 |
|  | As Previously Reported |  |  | ASU 2020-06 Adjustment |  |  | As Revised |
Interest expense |  | $ | (48,768 | ) |  | $ | 36,328 |  |  | $ | (12,440 | )
Loss on early retirement of debt |  |  | (21,865 | ) |  |  | (44,331 | ) |  |  | (66,196 | )
Income before income tax benefit (expense) |  | $ | 346,769 |  |  | $ | (8,003 | ) |  | $ | 338,766 |
Income tax expense |  | $ | (43,507 | ) |  | $ | (8,000 | ) |  | $ | (51,507 | )
Net income |  | $ | 303,262 |  |  | $ | (16,003 | ) |  | $ | 287,259 |
Net income attributable to Ionis Pharmaceuticals, Inc. common stockholders |  | $ | 294,146 |  |  | $ | (16,003 | ) |  | $ | 278,143 |
Basic net income per share |  |  | 2.12 |  |  |  | (0.12 | ) |  |  | 2.00 |
Diluted net income per share |  | $ | 2.08 |  |  | $ | (0.18 | ) |  | $ | 1.90 |
The following tables summarize the adjustments we made to our consolidated statements of stockholders’ equity we originally reported at December 31, 2020 and 2019 to adopt ASU 2020-06 (in thousands):
|  | December 31, 2020 |
|  | As Previously Reported |  |  | ASU 2020-06 Adjustment |  |  | As Revised |
Additional paid-in-capital |  | $ | 2,113,646 |  |  | $ | (218,127 | ) |  | $ | 1,895,519 |
Accumulated deficit |  | $ | (1,249,368 | ) |  | $ | 118,062 |  |  | $ | (1,131,306 | )
Total stockholders’ equity |  | $ | 843,347 |  |  | $ | (100,065 | ) |  | $ | 743,282 |
|  | December 31, 2019 |
|  | As Previously Reported |  |  | ASU 2020-06 Adjustment |  |  | As Revised |
Additional paid-in-capital |  | $ | 2,203,778 |  |  | $ | (218,128 | ) |  | $ | 1,985,650 |
Accumulated deficit |  | $ | (707,534 | ) |  | $ | 111,039 |  |  | $ | (596,495 | )
Total stockholders’ equity |  | $ | 1,684,547 |  |  | $ | (107,088 | ) |  | $ | 1,577,459 |
Assets Measured at Fair Value on a Recurring Basis | The following tables present the major security types we held at December 31, 2021 and 2020 that we regularly measure and carry at fair value. As of December 31, 2021, our Bicycle investment was subject to trading restrictions that extend to the third quarter of 2022; as a result, we included a lack of marketability discount in valuing this investment, which is a Level 3 input. As of December 31, 2020, we did not have any investments that we valued using Level 3 inputs. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities’ fair value (in thousands):
|  | At December 31, 2021 |  |  | Quoted Prices in Active Markets (Level 1) |  |  | Significant Other Observable Inputs (Level 2) |  |  | Significant Unobservable Inputs (Level 3) |
Cash equivalents (1) |  | $ | 541,199 |  |  | $ | 541,199 |  |  | $ | — |  |  | $ | — |
Corporate debt securities (2) |  |  | 764,059 |  |  |  | — |  |  |  | 764,059 |  |  |  | — |
Debt securities issued by U.S. government agencies (2) |  |  | 120,868 |  |  |  | — |  |  |  | 120,868 |  |  |  | — |
Debt securities issued by the U.S. Treasury (2) |  |  | 182,634 |  |  |  | 182,634 |  |  |  | — |  |  |  | — |
Debt securities issued by states of the U.S. and political subdivisions of the states (3) |  |  | 174,464 |  |  |  | — |  |  |  | 174,464 |  |  |  | — |
Other municipal debt securities (2) |  |  | 6,099 |  |  |  | — |  |  |  | 6,099 |  |  |  | — |
Investment in Bicycle Therapeutics plc (4) |  |  | 14,330 |  |  |  | — |  |  |  | — |  |  |  | 14,330 |
Investment in ProQR Therapeutics N.V. (4) |  |  | 3,875 |  |  |  | 3,875 |  |  |  | — |  |  |  | — |
Total |  | $ | 1,807,528 |  |  | $ | 727,708 |  |  | $ | 1,065,490 |  |  | $ | 14,330 |
|  | At December 31, 2020 |  |  | Quoted Prices in Active Markets (Level 1) |  |  | Significant Other Observable Inputs (Level 2) |
Cash equivalents (1) |  | $ | 221,125 |  |  | $ | 221,125 |  |  | $ | — |
Corporate debt securities (5) |  |  | 846,315 |  |  |  | — |  |  |  | 846,315 |
Debt securities issued by U.S. government agencies (2) |  |  | 174,861 |  |  |  | — |  |  |  | 174,861 |
Debt securities issued by the U.S. Treasury (6) |  |  | 358,497 |  |  |  | 358,497 |  |  |  | — |
Debt securities issued by states of the U.S. and political subdivisions of the states (2) |  |  | 136,309 |  |  |  | — |  |  |  | 136,309 |
Other municipal debt securities (2) |  |  | 6,225 |  |  |  | — |  |  |  | 6,225 |
Investment in ProQR Therapeutics N.V. (4) |  |  | 2,031 |  |  |  | 2,031 |  |  |  | — |
Total |  | $ | 1,745,363 |  |  | $ | 581,653 |  |  | $ | 1,163,710 |
________________
(1) | Included in cash and cash equivalents on our consolidated balance sheet.
(2) | Included in short-term investments.
(3) | $2.3 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.
(4) | Included in other current assets on our consolidated balance sheet.
(5) | $10.0 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.
(6) | $17.5 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.

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