0000874015-21-000166 | 10-Q | XBRL Viewer | Ionis Pharmaceuticals INC

Document and Entity Information - shares	9 Months Ended
Document and Entity Information - shares	Sep. 30, 2021	Oct. 27, 2021
Cover [Abstract]
Document Type	10-Q
Amendment Flag	false
Document Quarterly Report	true
Document Period End Date	Sep. 30, 2021
Current Fiscal Year End Date	--12-31
Document Fiscal Year Focus	2021
Document Fiscal Period Focus	Q3
Document Transition Report	false
Entity Registrant Name	Ionis Pharmaceuticals, Inc.
Entity Central Index Key	0000874015
Entity File Number	000-19125
Entity Incorporation, State or Country Code	DE
Entity Tax Identification Number	33-0336973
Entity Address, Address Line One	2855 Gazelle Court
Entity Address, City or Town	Carlsbad
Entity Address, State or Province	CA
Entity Address, Postal Zip Code	92010
City Area Code	760
Local Phone Number	931-9200
Title of 12(b) Security	Common Stock, $.001 Par Value
Trading Symbol	IONS
Security Exchange Name	NASDAQ
Entity Current Reporting Status	Yes
Entity Interactive Data Current	Yes
Entity Filer Category	Large Accelerated Filer
Entity Small Business	false
Entity Emerging Growth Company	false
Entity Shell Company	false
Entity Common Stock, Shares Outstanding		141,210,015

CONDENSED CONSOLIDATED BALANCE SHEETS - USD ($) $ in Thousands	Sep. 30, 2021	Dec. 31, 2020
Current assets:
Cash and cash equivalents	$ 632,953	$ 397,664
Short-term investments	1,354,146	1,494,711
Contracts receivable	9,068	76,204
Inventories	22,930	21,965
Other current assets	136,643	140,163
Total current assets	2,155,740	2,130,707
Property, plant and equipment, net	180,144	181,077
Patents, net	30,038	27,937
Deposits and other assets	48,971	50,034
Total assets	2,414,893	2,389,755
Current liabilities:
Accounts payable	8,357	17,199
Accrued compensation	32,320	65,728
Accrued liabilities	75,681	90,161
Income taxes payable	450	1,324
1 percent convertible senior notes, net	61,936	308,809
Current portion of long-term obligations	3,109	7,301
Current portion of deferred contract revenue	97,925	108,376
Total current liabilities	279,778	598,898
Long-term deferred contract revenue	362,887	424,046
Long-term obligations, less current portion	21,628	23,409
Long-term mortgage debt	59,955	59,984
Total liabilities	1,884,357	1,646,473
Stockholders' equity:
Common stock, $0.001 par value; 300,000,000 shares authorized, 141,184,026 and 140,365,594 shares issued and outstanding at September 30, 2021 (unaudited) and December 31, 2020, respectively	141	140
Additional paid-in capital	1,942,348	1,895,519
Accumulated other comprehensive loss	(27,437)	(21,071)
Accumulated deficit	(1,384,516)	(1,131,306)
Total stockholders' equity	530,536	743,282
Total liabilities and stockholders' equity	2,414,893	2,389,755
0 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	618,341	0
0.125 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	$ 541,768	$ 540,136

CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares	Sep. 30, 2021	Dec. 31, 2020
Stockholders' equity:
Common stock, par value (in dollars per share)	$ 0.001	$ 0.001
Common stock, shares authorized (in shares)	300,000,000	300,000,000
Common stock, shares issued (in shares)	141,184,026	140,365,594
Common stock, shares outstanding (in shares)	141,184,026	140,365,594
0 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	0.00%
0.125 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	0.125%	0.125%
1 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	1.00%	1.00%

CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS - USD ($) shares in Thousands, $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2021	Sep. 30, 2020	Sep. 30, 2021	Sep. 30, 2020
Revenue:
Revenue	$ 133,093	$ 160,079	$ 370,450	$ 438,983
Expenses:
Cost of sales	3,079	3,086	8,616	8,646
Research, development and patent	184,770	125,083	463,878	364,298
Selling, general and administrative	31,093	68,447	148,747	215,455
Total operating expenses	218,942	196,616	621,241	588,399
Loss from operations	(85,849)	(36,537)	(250,791)	(149,416)
Other income (expense):
Investment income	872	6,454	8,236	25,913
Interest expense	(2,340)	(2,428)	(7,111)	(7,076)
Gain on investments	4,013	835	4,885	10,722
Loss on early retirement of debt	0	0	(8,627)	0
Other income (expenses)	(469)	126	(656)	(122)
Loss before income tax benefit (expense)	(83,773)	(31,550)	(254,064)	(119,979)
Income tax benefit (expense)	1,307	(5,064)	854	(4,077)
Net loss	(82,466)	(36,614)	(253,210)	(124,056)
Net loss attributable to noncontrolling interest in Akcea Therapeutics, Inc.	0	12,147	0	34,325
Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders	$ (82,466)	$ (24,467)	$ (253,210)	$ (89,731)
Basic net loss per share (in dollars per share)	$ (0.58)	$ (0.18)	$ (1.80)	$ (0.64)
Diluted net loss per share (in dollars per share)	$ (0.58)	$ (0.18)	$ (1.80)	$ (0.64)
Shares used in computing basic net loss per share (in shares)	141,139	139,708	140,958	139,497
Shares used in computing diluted net loss per share (in shares)	141,139	139,708	140,958	139,497
Commercial Revenue [Member]
Revenue:
Revenue	$ 84,820	$ 95,340	$ 255,129	$ 269,035
SPINRAZA Royalties [Member]
Revenue:
Revenue	66,572	74,171	198,726	211,925
TEGSEDI and WAYLIVRA Revenue, Net [Member]
Revenue:
Revenue	15,519	19,040	46,901	50,562
Licensing and Other Royalty Revenue [Member]
Revenue:
Revenue	2,729	2,129	9,502	6,548
Research and Development Revenue Under Collaborative Agreements [Member]
Revenue:
Revenue	$ 48,273	$ 64,739	$ 115,321	$ 169,948

CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2021	Sep. 30, 2020	Sep. 30, 2021	Sep. 30, 2020
CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS [Abstract]
Net loss	$ (82,466)	$ (36,614)	$ (253,210)	$ (124,056)
Unrealized gains (losses) on debt securities, net of tax	(1,618)	(3,448)	(6,321)	5,803
Currency translation adjustment	(23)	275	(45)	357
Comprehensive loss	(84,107)	(39,787)	(259,576)	(117,896)
Comprehensive loss attributable to noncontrolling interest in Akcea Therapeutics, Inc.	0	(12,188)	0	(33,883)
Comprehensive loss attributable to Ionis Pharmaceuticals, Inc. common stockholders	$ (84,107)	$ (27,599)	$ (259,576)	$ (84,013)

- Definition

Amount after tax of increase (decrease) in equity from transactions and other events and circumstances from net income (loss) and other comprehensive income (loss), attributable to noncontrolling interests. Excludes changes in equity resulting from investments by owners and distributions to owners.

+ References + Details

- Definition

Amount after tax of increase (decrease) in equity from transactions and other events and circumstances from net income and other comprehensive income. Excludes changes in equity resulting from investments by owners and distributions to owners.

+ References + Details

- Definition

The consolidated profit or loss for the period, net of income taxes, including the portion attributable to the noncontrolling interest.

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+ Details

CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY - USD ($) shares in Thousands, $ in Thousands	Common Stock [Member]	Additional Paid In Capital [Member]	Accumulated Other Comprehensive Loss [Member]	Accumulated Deficit [Member]	Total Ionis Stockholders' Equity [Member]	Noncontrolling Interest in Akcea Therapeutics, Inc. [Member]	Total
Balance at Dec. 31, 2019	$ 140	$ 1,985,650	$ (25,290)	$ (596,495)	$ 1,364,005	$ 213,453	$ 1,577,458
Balance (in shares) at Dec. 31, 2019	140,340
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(89,731)	(89,731)	0	(89,731)
Change in unrealized gains (losses), net of tax	0	0	5,803	0	5,803	0	5,803
Foreign currency translation	0	0	357	0	357	0	357
Issuance of common stock in connection with employee stock plans	$ 1	29,449	0	0	29,450	0	29,450
Issuance of common stock in connection with employee stock plans (in shares)	1,141
Repurchases and retirements of common stock	$ (1)	0	0	(90,549)	(90,550)	0	(90,550)
Repurchases and retirements of common stock (in shares)	(1,478)
Stock-based compensation expense	$ 0	135,077	0	0	135,077	0	135,077
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	$ 0	(12,960)	0	0	(12,960)	0	(12,960)
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)	(209)
Noncontrolling interest in Akcea Therapeutics, Inc.	$ 0	(43,665)	(442)	0	(44,107)	9,782	(34,325)
Balance at Sep. 30, 2020	$ 140	2,093,551	(19,572)	(776,775)	1,297,344	223,235	1,520,579
Balance (in shares) at Sep. 30, 2020	139,794
Balance at Jun. 30, 2020	$ 139	2,053,502	(16,440)	(752,308)	1,284,893	217,620	1,502,513
Balance (in shares) at Jun. 30, 2020	139,489
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(24,467)	(24,467)	0	(24,467)
Change in unrealized gains (losses), net of tax	0	0	(3,448)	0	(3,448)	0	(3,448)
Foreign currency translation	0	0	275	0	275	0	275
Issuance of common stock in connection with employee stock plans	$ 1	12,997	0	0	12,998	0	12,998
Issuance of common stock in connection with employee stock plans (in shares)	321
Stock-based compensation expense	$ 0	45,845	0	0	45,845	0	45,845
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	$ 0	(990)	0	0	(990)	0	(990)
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)	(16)
Noncontrolling interest in Akcea Therapeutics, Inc.	$ 0	(17,803)	41	0	(17,762)	5,615	(12,147)
Balance at Sep. 30, 2020	$ 140	2,093,551	(19,572)	(776,775)	1,297,344	223,235	1,520,579
Balance (in shares) at Sep. 30, 2020	139,794
Balance at Dec. 31, 2020	$ 140	1,895,519	(21,071)	(1,131,306)	743,282	0	743,282
Balance (in shares) at Dec. 31, 2020	140,366
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(253,210)	(253,210)	0	(253,210)
Change in unrealized gains (losses), net of tax	0	0	(6,321)	0	(6,321)	0	(6,321)
Foreign currency translation	0	0	(45)	0	(45)	0	(45)
Issuance of common stock in connection with employee stock plans	$ 1	11,563	0	0	11,564	0	11,564
Issuance of common stock in connection with employee stock plans (in shares)	1,094
Issuance of warrants	$ 0	89,752	0	0	89,752	0	89,752
Purchase of note hedges	0	(136,620)	0	0	(136,620)	0	(136,620)
Stock-based compensation expense	0	98,419	0	0	98,419	0	98,419
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	$ 0	(16,285)	0	0	(16,285)	0	(16,285)
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)	(276)
Balance at Sep. 30, 2021	$ 141	1,942,348	(27,437)	(1,384,516)	530,536	0	530,536
Balance (in shares) at Sep. 30, 2021	141,184
Balance at Jun. 30, 2021	$ 141	1,910,379	(25,796)	(1,302,050)	582,674	0	582,674
Balance (in shares) at Jun. 30, 2021	141,022
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(82,466)	(82,466)	0	(82,466)
Change in unrealized gains (losses), net of tax	0	0	(1,618)	0	(1,618)	0	(1,618)
Foreign currency translation	0	0	(23)	0	(23)	0	(23)
Issuance of common stock in connection with employee stock plans	$ 0	1,922	0	0	1,922	0	1,922
Issuance of common stock in connection with employee stock plans (in shares)	176
Stock-based compensation expense	$ 0	30,537	0	0	30,537	0	30,537
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	$ 0	(490)	0	0	(490)	0	(490)
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)	(14)
Balance at Sep. 30, 2021	$ 141	$ 1,942,348	$ (27,437)	$ (1,384,516)	$ 530,536	$ 0	$ 530,536
Balance (in shares) at Sep. 30, 2021	141,184

CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	9 Months Ended
	Sep. 30, 2021	Sep. 30, 2020
Operating activities:
Net loss	$ (253,210)	$ (124,056)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation	11,665	9,713
Amortization of right-of-use operating lease assets	1,171	1,356
Amortization of patents	1,740	1,526
Amortization of premium on investments, net	13,515	7,812
Amortization of debt issuance costs	3,586	2,388
Stock-based compensation expense	98,419	135,077
Gain on investments	(933)	(10,722)
Loss on early retirement of debt	8,627	0
Non-cash losses related to patents	1,150	616
Provision for deferred income taxes	0	1,649
Changes in operating assets and liabilities:
Contracts receivable	67,136	24,057
Inventories	(965)	(1,468)
Other current and long-term assets	10,358	(5,647)
Income taxes (payable) receivable	134	(23,674)
Accounts payable	(10,737)	(10,970)
Accrued compensation	(33,408)	(8,967)
Accrued liabilities and other current liabilities	(19,526)	13,195
Deferred contract revenue	(71,610)	(73,970)
Net cash used in operating activities	(172,888)	(62,085)
Investing activities:
Purchases of short-term investments	(930,963)	(1,376,631)
Proceeds from sale of short-term investments	1,051,857	1,497,433
Purchases of property, plant and equipment	(9,453)	(29,971)
Acquisition of patents, net	(4,459)	(4,203)
Purchase of Bicycle Therapeutics plc common stock	(7,185)	0
Net cash provided by investing activities	99,797	86,628
Financing activities:
Proceeds from equity, net	11,564	29,450
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	(16,285)	(12,960)
Proceeds from issuance of 0 percent convertible senior notes	632,500	0
0 percent convertible senior notes issuance costs	(15,525)	0
Repurchase of $247.9 million principal amount of 1 percent convertible senior notes	(256,963)	0
Proceeds from issuance of warrants	89,752	0
Purchase of note hedges	(136,620)	0
Repurchases and retirements of common stock	0	(90,548)
Payments of transaction costs for Akcea merger	0	(1,071)
Net cash provided by (used in) financing activities	308,423	(75,129)
Effects of exchange rates on cash	(43)	358
Net increase (decrease) in cash and cash equivalents	235,289	(50,228)
Cash and cash equivalents at beginning of period	397,664	683,287
Cash and cash equivalents at end of period	632,953	633,059
Supplemental disclosures of cash flow information:
Interest paid	3,527	3,700
Income taxes paid	3	23,532
Supplemental disclosures of non-cash investing and financing activities:
Amounts accrued for capital and patent expenditures	1,811	6,576
Amounts accrued for Akcea merger transaction costs	$ 0	$ 8,103

CONSOLIDATED STATEMENTS OF CASH FLOWS (Parenthetical) - USD ($) $ in Millions	Sep. 30, 2021	Apr. 30, 2021	Dec. 31, 2020	Sep. 30, 2020
0 Percent Convertible Senior Notes [Member]
Financing activities:
Interest rate on convertible senior notes	0.00%
1 Percent Convertible Senior Notes [Member]
Financing activities:
Interest rate on convertible senior notes	1.00%		1.00%	1.00%
Principal amount repurchased	$ 247.9	$ 247.9

Basis of Presentation	9 Months Ended
Basis of Presentation	Sep. 30, 2021
Basis of Presentation [Abstract]
Basis of Presentation	1. Basis of Presentation We prepared the unaudited interim condensed consolidated financial statements for the three and nine months ended September 30, 2021 and 2020 on the same basis as the audited financial statements for the year ended December 31, 2020, with the exception of our retrospective adoption of Accounting Standards Update, or ASU, 2020-06, which simplifies the accounting for convertible debt instruments. See Note 2, Significant Accounting Polices, Convertible Debt, for details of our adoption of this guidance. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended December 31, 2020 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC. In our condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (“we”, “us” or “our”). We formed Akcea in December 2014. In July 2017, Akcea completed an initial public offering, or IPO, which reduced our ownership of Akcea’s common stock below 100 percent. In October 2020, we completed a merger transaction with Akcea such that following the completion of the merger, Akcea became our wholly owned subsidiary. We will refer to this transaction as the Akcea Merger throughout the remainder of this document. We reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the period the changes occurred.

Significant Accounting Policies

9 Months Ended

Sep. 30, 2021

Significant Accounting Policies [Abstract]

Significant Accounting Policies

2. Significant Accounting Policies

Revenue Recognition

Our Revenue Sources

We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include the amounts in deferred revenue on our condensed consolidated balance sheet.

Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue

We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. We will also recognize as commercial revenue sales milestone payments and royalties we earn under our other partnerships.

Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net

In April 2021, we began commercializing TEGSEDI in North America through a distribution agreement with Swedish Orphan Biovitrum AB, or Sobi. In January 2021, we began commercializing TEGSEDI and WAYLIVRA in Europe through a distribution agreement with Sobi. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.

Prior to the second quarter of 2021 in North America, we sold TEGSEDI through exclusive distribution agreements with third-party logistics companies, or 3PLs, that took title to TEGSEDI. The 3PLs then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In the United States, or U.S., we had a single 3PL as our sole customer and in Canada we also had a single 3PL as our sole customer. Prior to 2021 in Europe, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as distributors.

Under our collaboration agreement with PTC Therapeutics International Limited, or PTC, PTC is responsible for commercializing TEGSEDI and WAYLIVRA in Latin America and Caribbean countries. In the third quarter of 2021, we earned a $4 million milestone payment from PTC when WAYLIVRA was approved in Brazil, which we included in TEGSEDI and WAYLIVRA revenue in our condensed consolidated statement of operations.

Research and development revenue under collaborative agreements

We often enter into collaboration agreements to license and sell our technology on an exclusive or non-exclusive basis. Our collaboration agreements typically contain multiple elements, or performance obligations, including technology licenses or options to obtain technology licenses, research and development, or R&D, services, and manufacturing services.

See Note 5, Collaborative Arrangements and Licensing Agreements, for collaborations with substantive changes that occurred in 2021. Additionally, see Note 6, Collaborative Arrangements and Licensing Agreements, in our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2020 for a summary of each of our material collaborative agreements.

Steps to Recognize Revenue

We use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five-step process is as follows:

Identify the contract

Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:

●

We and our partner approved the contract and we are both committed to perform our obligations;

●

We have identified our rights, our partner’s rights and the payment terms;

●

We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and

●

We believe collectability of the consideration is probable.

Identify the performance obligations

We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the contract. We typically have only one performance obligation at the inception of a contract, which is to perform R&D services.

Often we enter into a collaboration agreement in which we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights because these items are contingent upon future events that may not occur and are not priced at a significant discount. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item.

In some cases, we deliver a license at the start of an agreement. If we determine that our partner has full use of the license and we do not have any additional material performance obligations related to the license after delivery, then we consider the license to be a separate performance obligation.

Determine the transaction price

We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration agreement, including any variable consideration. Under our collaboration agreements, consideration typically includes fixed consideration in the form of an upfront payment and variable consideration in the form of potential milestone payments, license fees and royalties. At the start of an agreement, our transaction price usually consists of only the upfront payment. We do not typically include any payments we may receive in the future in our initial transaction price because the payments are not probable and are contingent on certain future events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.

Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our milestone payments are contingent upon events that are not within our control and/or are usually based on scientific progress which is inherently uncertain. For example, in the third quarter of 2021, we earned a $25 million milestone payment from Novartis when Novartis achieved 50 percent enrollment in the Lp(a) HORIZON Phase 3 cardiovascular outcome study of pelacarsen. We did not consider the milestone payment probable until Novartis achieved the milestone event because it was contingent on Novartis’ enrollment of patients and was not within our control. We recognized the milestone payment in full in the period the milestone event was achieved because we did not have any remaining performance obligations related to the milestone payment.

Allocate the transaction price

Next, we allocate the transaction price to each of our performance obligations. When we have to allocate the transaction price to more than one performance obligation, we make estimates of the relative stand-alone selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price. We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.

We may engage a third party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present value. The significant inputs we use to determine the projected income of a license could include:

●

Estimated future product sales;

●

Estimated royalties we may receive from future product sales;

●

Estimated contractual milestone payments we may receive;

●

Estimated expenses we may incur;

●

Estimated income taxes; and

●

A discount rate.

We typically estimate the selling price of R&D services by using our internal estimates of the cost to perform the specific services. The significant inputs we use to determine the selling price of our R&D services include:

●

The estimated number of internal hours we will spend performing these services;

●

The estimated cost of work we will perform;

●

The estimated cost of work that we will contract with third parties to perform; and

●

The estimated cost of API we will use.

For purposes of determining the stand-alone selling price of the R&D services we perform and the API we will deliver, accounting guidance requires us to include a markup for a reasonable profit margin.

Recognize revenue

We recognize revenue in one of two ways, over time or at a point in time. We recognize revenue over time when we are executing on our performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&D services. We recognize revenue at a point in time when our partner receives full use of an item at a specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.

For R&D services that we recognize over time, we measure our progress using an input method. The input methods we use are based on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires us to make numerous estimates and use significant judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.

The following are examples of when we typically recognize revenue based on the types of payments we receive.

Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue

We recognize royalty revenue, including royalties from SPINRAZA sales, in the period in which the counterparty sells the related product and recognizes the related revenue, which in certain cases may require us to estimate our royalty revenue.

Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net

Under our distribution agreements with Sobi we concluded that our performance obligation is to provide services to Sobi over the term of the agreement, which includes supplying finished goods inventory to Sobi and because we retained the marketing authorization for TEGSEDI and WAYLIVRA we are responsible for leading the global commercial strategy for each medicine. We view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize distribution fee revenue based on Sobi’s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.

Prior to our distribution agreements with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as selling, general and administrative, or SG&A, expenses in our condensed consolidated statements of operations. We classified payments to customers or other parties in the distribution channel that did not meet those criteria as a reduction of revenue, as discussed further below. We excluded from revenues taxes collected from customers relating to TEGSEDI and WAYLIVRA commercial revenue and remitted these amounts to governmental authorities.

Reserves for TEGSEDI and WAYLIVRA commercial revenue

Under our distribution agreements with Sobi, Sobi is responsible for any applicable reserves.

Prior to our distribution agreements with Sobi, we recorded TEGSEDI and WAYLIVRA commercial revenue at our net sales price, or transaction price. We included in our transaction price estimated reserves for discounts, returns, chargebacks, rebates and other allowances that we offered within contracts between us and our customers, wholesalers, distributors, health care providers and other indirect customers. We estimated our reserves using the amounts we have earned or we could claim on the associated sales. We classified our reserves as a reduction of accounts receivable when we were not required to make a payment or as a current liability when we were required to make a payment. In certain cases, our estimates included a range of possible outcomes that were probability weighted for relevant factors such as our historical experience, current contractual and statutory requirements, specific known market events and trends, industry data and forecasted customer buying and payment patterns. Overall, our reserves reflected our best estimates under the terms of our respective contracts. When calculating our reserves and related TEGSEDI and WAYLIVRA commercial revenue, we only recognized amounts to the extent that we considered it probable that we would not have to reverse a significant amount of the cumulative sales we previously recognized in a future period. Under our agreements with Sobi, we transferred all reserves to Sobi. See our revenue recognition policy in Note 1, Organization and Significant Accounting Policies, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2020 for additional details regarding how we accounted for the reserves related to TEDSEDI and WAYLIVIRA product sales prior to our agreements with Sobi.

Research and development revenue under collaboration agreements:

Upfront payments

When we enter into a collaboration agreement and receive an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&D services. For example, under our collaboration agreement with Roche to develop IONIS-FB-L_Rx for the treatment of complement-mediated diseases, we received a $75 million upfront payment in the fourth quarter of 2018. We allocated the upfront payment to our single performance obligation, R&D services. We are amortizing the $75 million upfront payment using an input method over the estimated period of time we are providing R&D services.

Milestone payments

We are required to include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&D services in the transaction price when they are achieved. We include these milestone payments when they are achieved because typically there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include approval milestone payments in the transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting rules.

We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, in the fourth quarter of 2020, we achieved a $7.5 million milestone payment from Biogen when we advanced a target under our 2018 strategic collaboration. We added this payment to the transaction price and allocated it to our R&D services performance obligation. We are recognizing revenue related to this milestone payment over our estimated period of performance.

Conversely, we recognize in full those milestone payments that we earn based on our partners’ activities when our partner achieves the milestone event and we do not have a performance obligation. For example, in the third quarter of 2021, we recognized a $25 million milestone payment from Novartis when Novartis achieved 50 percent enrollment in the Lp(a) HORIZON Phase 3 cardiovascular outcome study of pelacarsen. We recognized the milestone payment in full in the third quarter of 2021 because we did not have any remaining performance obligations related to the milestone payment.

License fees

We generally recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner. This is because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. For example, in the fourth quarter of 2020, we earned a $30 million license fee from AstraZeneca when AstraZeneca licensed ION455, an investigational medicine in development to treat nonalcoholic steatohepatitis, or NASH.

Sublicense fees

We recognize sublicense fee revenue in the period in which a party, who has already licensed our technology, further licenses the technology to another party because we do not have any performance obligations related to the sublicense.

Amendments to Agreements

From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:

If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and

If the goods and/or services are sold at a stand-alone selling price.

If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated revenue as a cumulative adjustment.

For example, in May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI_Rx for the prevention of thrombosis. As part of the agreement, Bayer paid us a $100 million upfront payment. At the onset of the agreement, we were responsible for completing a Phase 2 study of IONIS-FXI_Rx in people with end-stage renal disease on hemodialysis and for providing an initial supply of API. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI_Rx and to initiate development of fesomersen (IONIS-FXI-L_Rx), which Bayer licensed. As part of the 2017 amendment, Bayer paid us $75 million. We are also eligible to receive milestone payments and tiered royalties on gross margins of IONIS-FXI_Rx and fesomersen. Under the 2017 amendment, we concluded we had a new agreement with three performance obligations. These performance obligations were to deliver the license of fesomersen, to provide R&D services and to deliver API. We allocated the $75 million transaction price to these performance obligations. Refer to Note 6, Collaborative Arrangements and Licensing Agreements, in our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2020 for further discussion of the Bayer collaboration.

Multiple agreements

From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:

●

Whether the agreements were negotiated together with a single objective;

●

Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or

●

Whether the goods and/or services promised under the agreements are a single performance obligation.

Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting guidance requires us to account for them as a combined arrangement.

For example, in the second quarter of 2018, we entered into two separate agreements with Biogen at the same time: a new strategic neurology collaboration agreement and a stock purchase agreement, or SPA. We evaluated the Biogen agreements to determine whether we should treat the agreements separately or combine them. We considered that the agreements were negotiated concurrently and in contemplation of one another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis.

Contracts Receivable

Our contracts receivable balance represents the amounts we have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contracts receivable to be unconditional. We typically receive payment within one quarter of billing our partner or customer.

As of September 30, 2021, approximately 58.3 percent of our contracts receivables were from three significant customers. As of December 31, 2020, approximately 99.5 percent of our contracts receivables were from two significant customers.

Unbilled SPINRAZA Royalties

Our unbilled SPINRAZA royalties represent our right to receive consideration from Biogen in advance of when we are eligible to bill Biogen for SPINRAZA royalties. We include these unbilled amounts in other current assets on our condensed consolidated balance sheet.

Deferred Revenue

We are often entitled to bill our customers and receive payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue on our condensed consolidated balance sheet. During the three months ended September 30, 2021 and 2020, we recognized $21.1 million and $22.5 million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. During the nine months ended September 30, 2021 and 2020, we recognized $71.9 million and $84.1 million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. For further discussion, refer to our revenue recognition policy above.

Cost of Sales

Our cost of sales includes manufacturing costs, transportation and freight costs and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of sales.

Cash, Cash Equivalents and Investments

We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as “available-for-sale” and carry them at fair market value based upon prices on the last day of the fiscal period for identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments in our condensed consolidated statement of operations. We use the specific identification method to determine the cost of securities sold.

We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we received as part of a technology license or partner agreement. At September 30, 2021, we held equity investments in three publicly held companies, Antisense Therapeutics Limited, or ATL, Bicycle Therapeutics plc, or Bicycle, and ProQR Therapeutics N.V., or ProQR. We also held equity investments in seven privately held companies, Aro Biotherapeutics, Atlantic Pharmaceuticals Limited, Dynacure SAS, Empirico, Inc., Flamingo Therapeutics BV, YourBio Health, Inc. (formerly Seventh Sense Biosystems) and Suzhou-Ribo Life Science Co, Ltd.

We are required to measure and record our equity investments at fair value and to recognize the changes in fair value in our condensed consolidated statement of operations. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer. For example, during the second and fourth quarters of 2020, we revalued our investments in three privately held companies, Dynacure, Suzhou-Ribo and Aro Biotherapeutics because the companies sold additional equity securities that were similar to the equity we own. These observable price changes resulted in us recognizing a $6.3 million gain on our investment in Dynacure, a $3.0 million gain on our investment in Suzhou-Ribo and a $5.5 million gain on our investment in Aro Biotherapeutics in our condensed consolidated statement of operations during 2020 because the sales were at higher prices compared to our recorded value.

Inventory Valuation

We reflect our inventory on our condensed consolidated balance sheet at the lower of cost or net realizable value under the first-in, first-out method, or FIFO. We capitalize the costs of raw materials that we purchase for use in producing our medicines because until we use these raw materials, they have alternative future uses, which we refer to as clinical raw materials. We include in inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and, as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We expense these costs as R&D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency. Our raw materials- commercial inventory includes API for our commercial medicines. We capitalize material, labor and overhead costs as part of our raw materials- commercial inventory.

We obtained the first regulatory approval for TEGSEDI in July 2018 and for WAYLIVRA in May 2019. At September 30, 2021, our physical inventory for TEGSEDI and WAYLIVRA included API that we produced prior to when we obtained regulatory approval. As such, this API has no cost basis as we had previously expensed the costs as R&D expenses.

We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical write-offs. For the nine months ended September 30, 2021 and 2020, we recorded an immaterial amount of inventory write-offs.

Our inventory consisted of the following (in thousands):

	September 30, 2021		December 31, 2020
Raw materials:
Raw materials- clinical	$	11,993	$	9,206
Raw materials- commercial		4,147		7,502
Total raw materials		16,140		16,708
Work in process		6,183		2,252
Finished goods		607		3,005
Total inventory	$	22,930	$	21,965

Leases

We determine if an arrangement contains a lease at inception. We currently only have operating leases. We recognize a right-of-use operating lease asset and associated short- and long-term operating lease liability on our condensed consolidated balance sheet for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we will pay over the lease term. We determine the lease term at the inception of each lease, and in certain cases our lease term could include renewal options if we concluded we were reasonably certain that we will exercise the renewal option. When we exercise a lease option that was not previously included in the initial lease term, we reassess our right-of-use asset and lease liabilities for the new lease term.

As our current leases do not provide an interest rate implicit in the lease, we used our incremental borrowing rate, based on the information available on the date we adopted Topic 842 (January 2019), as of the lease inception date or at the lease option extension date in determining the present value of future payments. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.

In September 2021, we entered into an operating lease agreement for office space located in Boston, Massachusetts. We determined that the lease commencement date is the date in which the space is ready for our occupancy, which we expect will be in the fourth quarter of 2021. We are leasing this space under a non-cancelable operating lease with an initial term ending 91 months following the lease commencement date and an option to extend the lease for an additional five-year term. Under the lease agreement, we will receive a seven-month free rent period, which will commence on the lease commencement date. Our lease payments over the initial term total $6.8 million. We will recognize a right-of-use lease asset and lease liability in the fourth quarter of 2021 upon the lease commencement date. Since we did not have the right to occupy the premises as of September 30, 2021, there was no accounting impact in the third quarter.

Research, Development and Patent Expenses

Our research and development expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the services being rendered, we record those amounts as prepaid assets on our condensed consolidated balance sheet and we expense them as the services are provided.

We capitalize costs consisting principally of outside legal costs and filing fees related to obtaining patents. We amortize patent costs over the useful life of the patent, beginning with the date the U.S. Patent and Trademark Office, or foreign equivalent, issues the patent. We review our capitalized patent costs regularly to ensure that they include costs for patents and patent applications that have future value. When we identify patents and patent applications that we are not actively pursuing, we write off any associated costs.

Income Taxes

We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount we expect to realize.

We evaluate our deferred tax assets regularly to determine whether adjustments to the valuation allowance are appropriate due to changes in facts or circumstances, such as changes in expected future pre-tax earnings, tax law, interactions with taxing authorities and developments in case law. In making this evaluation, we rely on our recent history of pre-tax earnings. Our material assumptions are our forecasts of future pre-tax earnings and the nature and timing of future deductions and income represented by the deferred tax assets and liabilities, all of which involve the exercise of significant judgment.

We assessed our valuation allowance requirements and recorded a valuation allowance against all of Ionis’ U.S. federal net deferred tax assets in the fourth quarter of 2020, due to uncertainties related to our ability to realize the tax benefits associated with these assets. We based our determination largely on Akcea rejoining the Ionis U.S. consolidated federal tax group in the fourth quarter of 2020. Due to Akcea’s historical and projected financial statement losses, and the negative impact we expect this to have on Ionis’ consolidated taxable income, there is uncertainty of generating sufficient consolidated pre-tax income in future periods to realize the Ionis deferred tax benefits. We also expect that Ionis’ pre-tax income in future periods may be lower due to increased research and development expenses associated with our pipeline of wholly owned medicines. We continue to maintain a valuation allowance against all our consolidated U.S. federal and state net deferred tax assets.

Long-lived Assets

We evaluate long-lived assets, which include property, plant and equipment and patent costs, for impairment on at least a quarterly basis and whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.

Use of Estimates

We prepare our condensed consolidated financial statements in conformity with accounting principles generally accepted in the U.S. that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying notes. Actual results could differ from our estimates.

Basic and Diluted Net Loss Per Share

Basic net loss per share

We calculated our basic net loss per share for the three and nine months ended September 30, 2021 by dividing our net loss by our weighted-average number of common shares outstanding during the period. For the first nine months of 2021, we did not have to consider Akcea results separately in our calculation because we owned 100 percent of Akcea for the entire period. Our basic net loss per share for the three and nine months ended September 30, 2021 was $0.58 and $1.80, respectively.

In the third quarter of 2020, prior to the Akcea Merger, we calculated our basic net loss per share for the three and nine months ended September 30, 2020 by calculating our net loss for Ionis on a stand-alone basis plus our share of Akcea’s net loss for the period to determine our total net loss attributable to our common stockholders. To calculate the portion of Akcea’s net loss attributable to our ownership, we multiplied Akcea’s net loss per share by the weighted average shares we owned in Akcea during the period. As a result of this calculation, our total net loss available to Ionis common stockholders for the calculation of net loss per share is different than our net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders in the condensed consolidated statements of operations.

We calculated our basic net loss per share for the three months ended September 30, 2020 as follows (in thousands, except per share amounts):

Three months ended September 30, 2020	Weighted Average Shares Owned in Akcea		Akcea’s Net Loss Per Share			Basic Net Loss Per Share Calculation (as revised*)
Ionis’ portion of Akcea’s net loss		77,095	$	(0.49	)	$	(37,822	)
Akcea’s net loss attributable to our ownership						$	(37,822	)
Ionis’ stand-alone net income							13,251
Net loss available to Ionis common stockholders						$	(24,571	)
Weighted average shares outstanding							139,708
Basic net loss per share						$	(0.18	)

We calculated our basic net loss per share for the nine months ended September 30, 2020 as follows (in thousands, except per share amounts):

Nine months ended September 30, 2020	Weighted Average Shares Owned in Akcea		Akcea’s Net Loss Per Share			Basic Net Loss Per Share Calculation (as revised*)
Ionis’ portion of Akcea’s net loss		77,095	$	(1.40	)	$	(108,176	)
Akcea’s net loss attributable to our ownership						$	(108,176	)
Ionis’ stand-alone net income							18,235
Net loss available to Ionis common stockholders						$	(89,941	)
Weighted average shares outstanding							139,497
Basic net loss per share						$	(0.64	)

*	We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 2, Significant Accounting Policies, for further information.

Diluted net loss per share

For the three and nine months ended September 30, 2021 and 2020, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share:

●

0.125 percent convertible senior notes, or 0.125% Notes;

●

Note hedges related to the 0.125% Notes;

●

1 percent convertible senior notes, or 1% Notes;

●

Dilutive stock options;

●

Unvested restricted stock units, or RSUs;

●

Unvested performance restricted stock units, or PRSUs; and

●

Employee Stock Purchase Plan, or ESPP.

For the three and nine months ended September 30, 2021, common stock from the following would also have had an anti-dilutive effect on net loss per share:

●

0 percent convertible senior notes, or 0% Notes; and

●

Note hedges related to the 0% Notes.

Additionally as of September 30, 2021, we had warrants related to our 0% and 0.125% Notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.

Convertible Debt

Adoption of ASU 2020-06

In August 2020, the FASB issued ASU 2020-06, which simplifies the accounting for convertible debt instruments, amends the guidance on derivative scope exceptions for contracts in an entity’s own equity, and modifies the guidance on diluted earnings per share calculations. We adopted ASU 2020-06 on January 1, 2021 under the full retrospective approach, which required us to revise our prior period financial statements. This guidance impacted our accounting for outstanding convertible debt. At January 1, 2021, we had two outstanding convertible notes, our 0.125% Notes, which mature in December 2024, and our 1% Notes, which mature in November 2021. In April 2021, we completed a $632.5 million offering of 0% Notes primarily to repurchase a majority of our 1% Notes. We accounted for our 0% Notes under ASU 2020-06 at issuance. Refer to Note 6, Convertible Debt, for further information.

The updated guidance eliminates the cash conversion accounting model we previously followed in Accounting Standard Codification, or ASC, 470-20, which required us to separate each of our convertible debt instruments at issuance into two units of accounting, a liability component, based on our nonconvertible debt borrowing rate at issuance, and an equity component. Under ASU 2020-06, we now account for each of our convertible debt instruments as a single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and our convertible debt instruments were not issued at a substantial premium. Since we adopted ASU 2020-06 using the full retrospective approach, we were required to apply the guidance to all convertible debt instruments we had outstanding as of January 1, 2019. We recomputed the basis of each convertible debt instrument as if we accounted for each as a single unit of accounting at issuance. This update included recalculating the amortization of debt issuance costs using an updated effective interest rate. As a result of adopting ASU 2020-06, we recorded a cumulative adjustment to decrease our additional paid in capital and our accumulated deficit at January 1, 2019. We have updated these financial statements to reflect the cumulative adjustment for the periods presented. We have labeled our prior period financial statements “as revised” to indicate the change required under the new accounting guidance. Below is a summary of the change in our balance sheet at December 31, 2020 and statement of operations from the three and nine months ended September 30, 2020 under the ASC 470-20 legacy guidance compared to the new ASU 2020-06 guidance we adopted:

The following table summarizes the adjustments we made to the condensed 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	)

Under ASU 2020-06, our revised ending balances for our 1% Notes and 0.125% Notes as of December 31, 2020 represent the principal balance of each convertible debt instrument less debt issuance costs. Additionally, because we have deferred tax assets related to our convertible debt instruments, we also adjusted these amounts as part of our adoption of ASU 2020-06. However, because we have a full valuation allowance on our deferred tax assets, there was no impact to our condensed consolidated balance sheet related to our deferred tax assets.

The following tables summarize the adjustments we made to the condensed consolidated statement of operations we originally reported for the three and nine months ended September 30, 2020 to adopt ASU 2020-06 (in thousands):

	Three Months Ended September 30, 2020
	As Previously Reported			ASU 2020-06 Adjustment			As Revised
Interest expense	$	(11,321	)	$	8,893		$	(2,428	)
Loss before income tax expense	$	(40,443	)	$	8,893		$	(31,550	)
Income tax expense	$	(2,648	)	$	(2,416	)	$	(5,064	)
Net loss	$	(43,091	)	$	6,477		$	(36,614	)
Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders	$	(30,944	)	$	6,477		$	(24,467	)
Basic and diluted net loss per share	$	(0.22	)	$	0.04		$	(0.18	)

	Nine Months Ended September 30, 2020
	As Previously Reported			ASU 2020-06 Adjustment			As Revised
Interest expense	$	(33,484	)	$	26,408		$	(7,076	)
Loss before income tax benefit (expense)	$	(146,387	)	$	26,408		$	(119,979	)
Income tax benefit (expense)	$	1,047		$	(5,124	)	$	(4,077	)
Net loss	$	(145,340	)	$	21,284		$	(124,056	)
Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders	$	(111,015	)	$	21,284		$	(89,731	)
Basic and diluted net loss per share	$	(0.80	)	$	0.16		$	(0.64	)

Under ASU 2020-06, our revised interest expense is lower because we are no longer recording non-cash interest expense related to a debt discount. This decrease was partially offset by the increase in interest expense related to the amortization of debt issuance costs because we no longer allocate a portion of our debt issuance costs to stockholders’ equity at issuance. Instead, the entire debt issuance costs were recorded as a contra-liability on our condensed consolidated balance sheet at issuance and we are amortizing them over the contractual term using an updated effective interest rate. Our updated effective interest rates for our 1% Notes and 0.125% Notes were 1.4 percent and 0.5 percent, respectively.

The following tables summarize the adjustments we made to our condensed 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		$	(107,089	)	$	1,577,458

Call Spread

In conjunction with the issuance of our 0% Notes and 0.125% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not meet the definition of a liability using the guidance contained in ASC Topic 480, therefore we account for the note hedges and warrants using the Derivatives and Hedging – Contracts in Entity’s Own Equity accounting guidance contained in ASC Topic 815. We determined that the note hedges and warrants meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified in shareholders’ equity. We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants as additional paid-in capital in our condensed consolidated balance sheet. We reassess our ability to continue to classify the note hedges and warrants in shareholders’ equity at each reporting period.

Segment Information

In 2021, we began operating as a single segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment. Previously, we had operated as two operating segments, Ionis Core and Akcea Therapeutics. We completed the Akcea Merger in October 2020 and fully integrated Akcea’s operations into ours as of January 1, 2021.

Stock-based Compensation Expense

We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates. We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP.

On the grant date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the awards, and actual and projected employee stock option exercise behaviors.

We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award were in substance multiple awards, which results in the expense being front-loaded over the vesting period.

In December 2020, we amended and restated the Akcea 2015 equity plan, including renaming the plan as the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan, or 2020 Plan. As a result, all employees are now under an Ionis stock plan and subject to the same Black-Scholes assumptions.

For the nine months ended September 30, 2021 and 2020, we used the following weighted-average assumptions in our Black-Scholes calculations:

Employee Stock Options:

	Nine Months Ended September 30,
	2021			2020
Risk-free interest rate		0.5	%		1.5	%
Dividend yield		0.0	%		0.0	%
Volatility		54.3	%		58.8	%
Expected life	4.9 years			4.7 years

Ionis Board of Director Stock Options:

	Nine Months Ended September 30,
	2021			2020
Risk-free interest rate		1.2	%		0.5	%
Dividend yield		0.0	%		0.0	%
Volatility		55.9	%		57.6	%
Expected life	7.3 years			6.7 years

ESPP:

	Nine Months Ended September 30,
	2021			2020
Risk-free interest rate		0.1	%		0.8	%
Dividend yield		0.0	%		0.0	%
Volatility		42.4	%		47.9	%
Expected life	6 months			6 months

RSU’s:

The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest annually over a four-year period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a four-year period. RSUs granted after June 2020 to our board of directors fully vest after one year. The weighted-average grant date fair value of RSUs granted to employees and our board of directors for the nine months ended September 30, 2021 was $59.15 and $39.42 per share, respectively.

PRSU’s:

Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Under the terms of the grants, one third of the PRSUs may vest at the end of three separate performance periods spread over the three years following the date of grant (i.e., the one-year period commencing on the date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant and ending on the second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third anniversary of the date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants no number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero percentto 150 percent of the target number depending on our relative TSR.

We determined the fair value of Dr. Monia’s PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period. The weighted-average grant date fair value of PRSUs granted to Dr. Monia for the nine months ended September 30, 2021 was $77.17 per share.

The following table summarizes stock-based compensation expense for the three and nine months ended September 30, 2021 and 2020 (in thousands).

	Three Months Ended September 30,				Nine Months Ended September 30,
	2021		2020		2021		2020
Cost of sales	$	111	$	315	$	293	$	902
Research, development and patent expense		23,332		25,359		71,979		76,931
Selling, general and administrative expense		7,094		20,171		26,147		57,244
Total non-cash stock-based compensation expense	$	30,537	$	45,845	$	98,419	$	135,077

As of September 30, 2021, total unrecognized estimated non-cash stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $65.3 million, $72.2 million and $2.5 million, respectively. Our actual expenses may differ from these estimates because we will adjust our unrecognized non-cash stock-based compensation expense for future forfeitures. We expect to recognize the cost of non-cash stock-based compensation expense related to our non-vested stock options, RSUs and PRSUs over a weighted average amortization period of 1.2 years, 1.4 years and 1.2 years, respectively.

Amendments to Equity Plans

2020 Equity Incentive Plan

In the second quarter of 2021, our Compensation Committee approved an amendment to the 2020 Plan. The amendment decreased the total number of shares of common stock authorized for issuance under the 2020 Plan from approximately 2.6 million to 1.6 million. We assumed the 2020 Plan in connection with Ionis’ reacquisition of all of the outstanding shares of Akcea Therapeutics, Inc. as part of the Akcea Merger.

2011 Equity Incentive Plan

In the second quarter of 2021, after receiving approval from our stockholders, we amended our 2011 Equity Incentive Plan, or 2011 Plan. The amendment increased the total number of shares of common stock authorized for issuance under the 2011 Plan from 23.0 million to 29.7 million and added a fungible share counting ratio whereby the share reserve will be reduced by 1.7 shares for each share of common stock issued pursuant to a full value award (i.e., RSU or PRSU) and increased by 1.7 shares for each share of common stock returning from a full value award.

Impact of Recently Issued Accounting Standards

As disclosed in the “Convertible Debt” policy above within this footnote, we adopted the simplified accounting for convertible debt instrument guidance (ASU 2020-06) on January 1, 2021. Refer to the section above for the impact of adoption. We do not expect any other recently issued accounting standards to have a material impact to our financial results.

Investments

9 Months Ended

Sep. 30, 2021

Investments [Abstract]

Investments

3. Investments

The following table summarizes the contract maturity of the available-for-sale securities we held as of September 30, 2021:

One year or less	58	%
After one year but within two years	26	%
After two years but within three and a half years	16	%
Total	100	%

As illustrated above, at September 30, 2021, 84 percent of our available-for-sale securities had a maturity of less than two years.

All of our available-for-sale securities are available to us for use in our current operations. As a result, we categorize all of these securities as current assets even though the stated maturity of some individual securities may be one year or more beyond the balance sheet date.

We invest in available-for-sale securities with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Standard & Poor’s, or S&P, Moody’s or Fitch, respectively.

At September 30, 2021, we had an ownership interest of less than 20 percent in seven private companies and three public companies with which we conduct business. The privately held companies are Aro Biotherapeutics, Atlantic Pharmaceuticals Limited, Dynacure SAS, Empirico, Inc., Flamingo Therapeutics BV, YourBio Health, Inc. and Suzhou-Ribo Life Science Co, Ltd. The publicly traded companies are Antisense Therapeutics Ltd., Bicycle and ProQR.

The following is a summary of our investments (in thousands):

			Gross Unrealized					Estimated
September 30, 2021	Cost (1)		Gains		Losses			Fair Value
Available-for-sale securities:
Corporate debt securities (2)	$	447,173	$	1,338	$	(50	)	$	448,461
Debt securities issued by U.S. government agencies		83,630		96		(7	)		83,719
Debt securities issued by the U.S. Treasury (2)		89,267		10		(2	)		89,275
Debt securities issued by states of the U.S. and political subdivisions of the states		141,161		103		(30	)		141,234
Other municipal debt securities		5,028		—		(2	)		5,026
Total securities with a maturity of one year or less		766,259		1,547		(91	)		767,715
Corporate debt securities		366,907		1,181		(475	)		367,613
Debt securities issued by U.S. government agencies		73,028		1		(120	)		72,909
Debt securities issued by the U.S. Treasury		98,499		245		(88	)		98,656
Debt securities issued by states of the U.S. and political subdivisions of the states		41,167		8		(65	)		41,110
Other municipal debt		6,169		—		(26	)		6,143
Total securities with a maturity of more than one year		585,770		1,435		(774	)		586,431
Total available-for-sale securities	$	1,352,029	$	2,982	$	(865	)	$	1,354,146
Equity securities:
Total equity securities included in other current assets (3)	$	11,897	$	1,935	$	(663	)	$	13,169
Total equity securities included in deposits and other assets (4)		15,615		16,707		—			32,322
Total equity securities		27,512		18,642		(663	)		45,491
Total available-for-sale and equity securities	$	1,379,541	$	21,624	$	(1,528	)	$	1,399,637

			Gross Unrealized					Estimated
December 31, 2020	Cost (1)		Gains		Losses			Fair Value
Available-for-sale securities:
Corporate debt securities (2)	$	514,182	$	2,194	$	(41	)	$	516,335
Debt securities issued by U.S. government agencies		94,234		354		(2	)		94,586
Debt securities issued by the U.S. Treasury (2)		307,576		233		(9	)		307,800
Debt securities issued by states of the U.S. and political subdivisions of the states		104,271		196		(12	)		104,455
Other municipal debt securities		5,191		—		(7	)		5,184
Total securities with a maturity of one year or less		1,025,454		2,977		(71	)		1,028,360
Corporate debt securities		325,079		4,941		(40	)		329,980
Debt securities issued by U.S. government agencies		80,099		185		(9	)		80,275
Debt securities issued by the U.S. Treasury		50,318		383		(4	)		50,697
Debt securities issued by states of the U.S. and political subdivisions of the states		31,779		91		(16	)		31,854
Other municipal debt securities		1,041		—		—			1,041
Total securities with a maturity of more than one year		488,316		5,600		(69	)		493,847
Total available-for-sale securities	$	1,513,770	$	8,577	$	(140	)	$	1,522,207
Equity securities:
Total equity securities included in other current assets (3)	$	4,712	$	—	$	(2,681	)	$	2,031
Total equity securities included in deposits and other assets (4)		15,062		15,938		—			31,000
Total equity securities		19,774		15,938		(2,681	)		33,031
Total available-for-sale and equity securities	$	1,533,544	$	24,515	$	(2,821	)	$	1,555,238

(1)	We hold our available-for-sale securities at amortized cost.

(2)	Includes investments classified as cash equivalents on our condensed consolidated balance sheet.

(3)

Our equity securities included in other current assets consisted of our investments in two publicly traded companies, ProQR and Bicycle, which we classify as Level 1 and Level 3 investments, respectively. We recognize publicly traded equity securities at fair value. In the nine months ended September 30, 2021, we recognized a $1.9 million unrealized gain and a $0.7 million unrealized loss on our condensed consolidated statement of operations related to our investments in Bicycle and ProQR, respectively. In the nine months ended September 30, 2020, our equity securities included in other current assets only consisted of ProQR.

(4)

Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer.

The following is a summary of our investments we consider to be temporarily impaired at September 30, 2021 (in thousands, except for number of investments). All of these investments have less than 12 months of temporary impairment. We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates since purchase. We believe it is more likely than not that we will be able to hold our debt securities to maturity. Therefore, we anticipate full recovery of our debt securities’ amortized cost basis at maturity.

	Number of Investments		Estimated Fair Value		Unrealized Losses
Corporate debt securities		158	$	334,828	$	(525	)
Debt securities issued by U.S. government agencies		13		103,460		(127	)
Debt securities issued by the U.S. Treasury		10		75,009		(90	)
Debt securities issued by states of the U.S. and political subdivisions of the states		432		123,489		(95	)
Other municipal debt securities		3		11,168		(28	)
Total temporarily impaired securities		616	$	647,954	$	(865	)

Fair Value Measurements

9 Months Ended

Sep. 30, 2021

Fair Value Measurements [Abstract]

Fair Value Measurements

4. Fair Value Measurements

We use a three-tier fair value hierarchy to prioritize the inputs used in our fair value measurements. These tiers include: Level 1, defined as observable inputs such as quoted prices in active markets for identical assets, which includes our money market funds and treasury securities classified as available-for-sale securities and our investment in equity securities in publicly held biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify most of our securities as Level 2. We obtain the fair value of our Level 2 investments from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value to the fair value based on observable market prices.

The following tables present the major security types we held at September 30, 2021 and December 31, 2020 that we regularly measure and carry at fair value. As of September 30, 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 September 30, 2021		Quoted Prices in Active Markets (Level 1)		Significant Other Observable Inputs (Level 2)		Significant Unobservable Inputs (Level 3)
Cash equivalents (1)	$	545,339	$	545,339	$	—	$	—
Corporate debt securities (2)		816,074		—		816,074		—
Debt securities issued by U.S. government agencies (2)		156,628		—		156,628		—
Debt securities issued by the U.S. Treasury (2)		187,931		187,931		—		—
Debt securities issued by states of the U.S. and political subdivisions of the states		182,344		—		182,344		—
Other municipal debt securities (2)		11,169		—		11,169		—
Investment in Bicycle Therapeutics plc (3)		9,120		—		—		9,120
Investment in ProQR Therapeutics N.V. (3)		4,049		4,049		—		—
Total	$	1,912,654	$	737,319	$	1,166,215	$	9,120

	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 (4)		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 (5)		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. (3)		2,031		2,031		—
Total	$	1,745,363	$	581,653	$	1,163,710

The following footnotes reference lines on our condensed consolidated balance sheet:

(1)	Included in cash and cash equivalents on our condensed consolidated balance sheet.

(2)	Included in short-term investments.

(3)	Included in other current assets on our condensed consolidated balance sheet.

(4)	$10.0 million was included in cash and cash equivalents, with the difference included in short-term investments.

(5)	$17.5 million included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.

Convertible Notes

Our 1% Notes, 0.125% Notes and 0% Notes had a fair value of $61.9 million, $504.3 million and $581.4 million at September 30, 2021, respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.

- Definition

The entire disclosure for the fair value of financial instruments (as defined), including financial assets and financial liabilities (collectively, as defined), and the measurements of those instruments as well as disclosures related to the fair value of non-financial assets and liabilities. Such disclosures about the financial instruments, assets, and liabilities would include: (1) the fair value of the required items together with their carrying amounts (as appropriate); (2) for items for which it is not practicable to estimate fair value, disclosure would include: (a) information pertinent to estimating fair value (including, carrying amount, effective interest rate, and maturity, and (b) the reasons why it is not practicable to estimate fair value; (3) significant concentrations of credit risk including: (a) information about the activity, region, or economic characteristics identifying a concentration, (b) the maximum amount of loss the entity is exposed to based on the gross fair value of the related item, (c) policy for requiring collateral or other security and information as to accessing such collateral or security, and (d) the nature and brief description of such collateral or security; (4) quantitative information about market risks and how such risks are managed; (5) for items measured on both a recurring and nonrecurring basis information regarding the inputs used to develop the fair value measurement; and (6) for items presented in the financial statement for which fair value measurement is elected: (a) information necessary to understand the reasons for the election, (b) discussion of the effect of fair value changes on earnings, (c) a description of [similar groups] items for which the election is made and the relation thereof to the balance sheet, the aggregate carrying value of items included in the balance sheet that are not eligible for the election; (7) all other required (as defined) and desired information.

+ References + Details

Collaborative Arrangements and Licensing Agreements

9 Months Ended

Sep. 30, 2021

Collaborative Arrangements and Licensing Agreements [Abstract]

Collaborative Arrangements and Licensing Agreements

5. Collaborative Arrangements and Licensing Agreements

Below, we have included our Biogen and Novartis collaborations, which are our only collaborations with substantive changes during 2021 from those included in Note 6 of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2020.

Strategic Partnership

Biogen

We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders. These collaborations combine our expertise in creating antisense medicines with Biogen’s expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. We and Biogen are currently developing eight investigational medicines to treat neurodegenerative diseases under these collaborations, including medicines in development to treat people with ALS, Alzheimer’s diseaseand Parkinson’s disease. In addition to these medicines, our collaborations with Biogen include a substantial research pipeline that addresses a broad range of neurological diseases. From inception through September 30, 2021, we have received more than $3.0 billion from our Biogen collaborations.

During the three and nine months ended September 30, 2021 and 2020, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):

	Three Months Ended September 30,						Nine Months Ended September 30,
	2021			2020			2021			2020
SPINRAZA royalties (commercial revenue)	$	66.6		$	74.2		$	198.7		$	211.9
R&D revenue		17.4			51.2			63.4			98.6
Total revenue from our relationship with Biogen	$	84.0		$	125.4		$	262.1		$	310.5
Percentage of total revenue		63	%		78	%		71	%		71	%

Our condensed consolidated balance sheet at September 30, 2021 and December 31, 2020 included deferred revenue of $412.5 million and $465.8 million, respectively, related to our relationship with Biogen.

During the first nine months of 2021, we did not have any changes to our performance obligations, transaction price or the timing in which we expect to recognize revenue under our Biogen collaborations.

In April 2021, we earned a $10 million milestone payment from Biogen when Biogen advanced ION541, an investigational medicine targeting ATXN2 to treat patients with ALS. We recognized the milestone payment in full in the second quarter of 2021 because we did not have any remaining performance obligations related to the milestone payment. We will achieve the next payment of $8 million if Biogen advances one of the medicines under our 2013 strategic neurology collaboration.

Research, Development and Commercialization Partner

Novartis

In January 2017, we initiated a collaboration with Novartis to develop and commercialize pelacarsen. In February 2019, Novartis licensed pelacarsen. Novartis is responsible for conducting and funding future development and regulatory activities for pelacarsen, including a global Phase 3 cardiovascular outcomes study that Novartis initiated in the fourth quarter 2019. In connection with Novartis’ license of pelacarsen, we and Novartis established a more definitive framework under which the companies would negotiate the co-commercialization of pelacarsen in selected markets. Included in this framework is an option by which Novartis could solely commercialize pelacarsen in exchange for Novartis paying us increased sales milestone payments based on sales of pelacarsen. From inception through September 30, 2021, we have received $425 million from our Novartis collaboration.

In August 2021, we earned a $25 million milestone payment from Novartis when Novartis achieved 50 percent enrollment in the Lp(a) HORIZON Phase 3 cardiovascular outcome study of pelacarsen. We recognized the milestone payment in full in the third quarter of 2021 because we did not have any remaining performance obligations related to the milestone payment. We will achieve the next payment of up to $75 million if Novartis advances regulatory activities for pelacarsen.

Technology Enhancement Collaboration

Bicycle License Agreement

In December 2020, we entered into a collaboration agreement with Bicycle and obtained an option to license its peptide technology to potentially increase the delivery capabilities of our LIgand Conjugated Antisense, or LICA, medicines. In July 2021, we paid $42 million when we exercised our option to license Bicycle’s technology, which included an equity investment in Bicycle. As part of our stock purchase, we entered into a lockup agreement with Bicycle that restricts our ability to trade our Bicycle shares for one year. In the third quarter of 2021, we recorded a $7.2 million equity investment for the shares we received in Bicycle. We recognized the remaining $34.8 million as R&D expense in the third quarter of 2021. From inception through September 30, 2021, we have paid $45 million under our collaboration agreement with Bicycle.

Convertible Debt

9 Months Ended

Sep. 30, 2021

Convertible Debt [Abstract]

Convertible Debt

6. Convertible Debt

0 Percent Convertible Senior Notes and Call Spread

In April 2021, we completed a $632.5 million offering of convertible senior notes. We used a portion of the net proceeds from the issuance of the 0% Notes to repurchase $247.9 million in principal of our 1% Notes for $257.0 million.

At September 30, 2021, we had the following 0% Notes outstanding (amounts in millions except interest rate and price per share data):

	0% Notes
Outstanding principal balance	$	632.5
Unamortized debt issuance costs	$	14.2
Maturity date	April 2026
Interest rate	0 percent
Effective interest rate	0.5 percent
Conversion price per share	$	57.84
Effective conversion price per share with call spread	$	76.39
Total shares of common stock subject to conversion		10.9

In conjunction with the April 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our 0% Notes by increasing the effective conversion price on our 0% Notes. We increased our effective conversion price to $76.39 with the same number of underlying shares as our 0% Notes. The call spread cost us $46.9 million, of which $136.7 million was for the note hedge purchase, offset by $89.8 million we received for selling the warrants. Similar to our 0% Notes, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the 0% Notes. The note hedges will expire upon maturity of the 0% Notes, or April 2026. The note hedges and warrants are separate transactions and are not part of the terms of our 0% Notes. The holders of the 0% Notes do not have any rights with respect to the note hedges and warrants.

We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our condensed consolidated balance sheet. See our Call Spread accounting policy in Note 2, Significant Accounting Policies, in the Notes to the Condensed Consolidated Financial Statements. We reassess our ability to continue to classify the note hedges and warrants in shareholders’ equity at each reporting period.

0.125 Percent Convertible Senior Notes and Call Spread

At September 30, 2021, we had the following 0.125% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):

	0.125% Notes
Outstanding principal balance	$	548.8
Unamortized debt issuance costs	$	7.1
Maturity date	December 2024
Interest rate	0.125 percent
Effective interest rate	0.5 percent
Conversion price per share	$	83.28
Effective conversion price per share with call spread	$	123.38
Total shares of common stock subject to conversion		6.6

In conjunction with the issuance of our 0.125% Notes in December 2019, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our 0.125% Notes by increasing the effective conversion price on our 0.125% Notes. We increased our effective conversion price to $123.38 with the same number of underlying shares as our 0.125% Notes. The call spread cost us $52.6 million, of which $108.7 million was for the note hedge purchase, offset by $56.1 million we received for selling the warrants. Similar to our 0.125% Notes, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the 0.125% Notes. The note hedges will expire upon maturity of the 0.125% Notes, or December 2024. The note hedges and warrants are separate transactions and are not part of the terms of our 0.125% Notes. The holders of the 0.125% Notes do not have any rights with respect to the note hedges and warrants.

1 Percent Convertible Senior Notes

At September 30, 2021, we had the following 1% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):

	1% Notes
Outstanding principal balance	$	62.0
Unamortized debt issuance costs	$	0.03
Maturity date	November 2021
Interest rate	1 percent
Effective interest rate	1.4 percent
Conversion price per share	$	66.81
Total shares of common stock subject to conversion		0.9

In April 2021, we repurchased $247.9 million in aggregate principal amount of our 1% Notes in privately negotiated transactions. As a result of the repurchase, we recognized an $8.6 million non-cash loss on early retirement of debt, reflecting the early retirement of a significant portion of our 1% Notes. The non-cash loss on the early retirement of our debt is the difference between the amount paid to retire our 1% Notes and the net carrying balance of the liability at the time that we retired the debt.

Other Terms of Convertible Senior Notes

The 0%, 0.125% and 1% Notes are convertible under certain conditions, at the option of the note holders. We can settle conversions of the notes, at our election, in cash, shares of our common stock or a combination of both. We may not redeem the notes prior to maturity, and we do not have to provide a sinking fund for them. Holders of the notes may require us to purchase some or all of their notes upon the occurrence of certain fundamental changes, as set forth in the indentures governing the notes, at a purchase price equal to 100 percent of the principal amount of the notes to be purchased, plus any accrued and unpaid interest.

- Definition

The entire disclosure for information about short-term and long-term debt arrangements, which includes amounts of borrowings under each line of credit, note payable, commercial paper issue, bonds indenture, debenture issue, own-share lending arrangements and any other contractual agreement to repay funds, and about the underlying arrangements, rationale for a classification as long-term, including repayment terms, interest rates, collateral provided, restrictions on use of assets and activities, whether or not in compliance with debt covenants, and other matters important to users of the financial statements, such as the effects of refinancing and noncompliance with debt covenants.

+ References

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+ Details

Severance and Retention Costs

9 Months Ended

Sep. 30, 2021

Severance and Retention Costs [Abstract]

Severance and Retention Costs

7. Severance and Retention Costs

Akcea Merger

As a result of the Akcea Merger in October 2020, we began recognizing severance and retention expenses in the fourth quarter of 2020. The following table summarizes our total estimated severance and retention expenses related to the Akcea Merger (in millions):

	Severance and Retention Expenses
Total estimated expenses	$	27.2
Expenses incurred from inception to September 30, 2021		27.0
Remaining estimated expenses to be recognized through October 2021	$	0.2

The following table summarizes our severance and retention expenses related to the Akcea Merger that we recognized during the three and nine months ended September 30, 2021 (in millions):

	Three Months Ended September 30, 2021		Nine Months Ended September 30, 2021
Research, development and patent expenses	$	1.3	$	5.1
Selling, general and administrative expenses		0.6		6.6
Total	$	1.9	$	11.7

The following table summarizes the severance and retention reserve amounts related to the Akcea Merger that we included in accrued compensation for the period indicated (in millions):

	Nine Months Ended September 30, 2021
Beginning balance as of January 1, 2021	$	14.7
Amounts expensed during the period		13.5
Reserve adjustments during the period		(1.8	)
Net amount expensed during the period		11.7
Amounts paid during the period		(20.6	)
Ending balance as of September 30, 2021	$	5.8

The reserve adjustments during the period primarily related to forfeitures of severance and retention payments as a result of employee terminations before they earned the amounts.

Restructured European Operations

In December 2020, we entered into a distribution agreement with Sobi for TEGSEDI and WAYLIVRA in Europe. As a result, we restructured our European Operations, or Restructured European Operations. In the fourth quarter of 2020, we began recognizing severance and retention expenses related to our Restructured European Operations. The following table summarizes our total severance and retention expenses related to our Restructured European Operations (in millions):

	Severance and Retention Expenses
Total estimated expenses	$	14.2
Expenses incurred from inception to September 30, 2021		14.0
Remaining estimated expenses to be recognized through October 2021	$	0.2

The following table summarizes the severance and retention expenses related to our Restructured European Operations that we recognized during the three and nine months ended September 30, 2021 (in millions):

	Three Months Ended September 30, 2021		Nine Months Ended September 30, 2021
Research, development and patent expenses	$	0.5	$	0.6
Selling, general and administrative expenses		0.1		1.1
Total	$	0.6	$	1.7

The following table summarizes the severance and retention reserve amounts related to our Restructured European Operations that we included in accrued compensation for the period indicated (in millions):

	Nine Months Ended September 30, 2021
Beginning balance as of January 1, 2021	$	12.4
Amounts expensed during the period		2.5
Reserve adjustments during the period		(0.8	)
Net amount expensed during the period		1.7
Amounts paid during the period		(13.4	)
Ending balance as of September 30, 2021	$	0.7

The reserve adjustments during the period primarily related to tax expense adjustments.

Restructured North American TEGSEDI Operations

In April 2021, we entered into a distribution agreement with Sobi for TEGSEDI in North America. Under the terms of the distribution agreement, we will retain the marketing authorizations for TEGSEDI in the U.S. and Canada. We will continue to supply commercial product to Sobi and manage regulatory and manufacturing processes, as well as relationships with key opinion leaders. We will also continue to lead the TEGSEDI global commercial strategy. Sobi will otherwise have responsibility for commercializing TEGSEDI in the U.S. and Canada.

In connection with restructuring our North American TEGSEDI operations, or Restructured North American TEGSEDI Operations, we enacted a plan to reorganize our Akcea workforce in North America to better align with the needs of our business and to focus on our wholly owned pipeline.

The following table summarizes the severance expenses related to our Restructured North American TEGSEDI Operations that we recognized during the second quarter of 2021 (in millions):

	Three Months Ended June 30, 2021
Research, development and patent expenses	$	2.3
Selling, general and administrative expenses		7.1
Total	$	9.4

We recognized all severance expenses related to our Restructured North American TEGSEDI Operations during the three months ended June 30, 2021.

The following table summarizes the severance reserve amounts related to our Restructured North American TEGSEDI Operations that we included in accrued compensation for the period indicated (in millions):

	Nine Months Ended September 30, 2021
Beginning balance as of January 1, 2021	$	—
Amounts expensed during the period		9.4
Amounts paid during the period		(9.2	)
Ending balance as of September 30, 2021	$	0.2

Basis of Presentation (Policies)	9 Months Ended
Basis of Presentation (Policies)	Sep. 30, 2021
Basis of Presentation [Abstract]
Basis of Presentation	We prepared the unaudited interim condensed consolidated financial statements for the three and nine months ended September 30, 2021 and 2020 on the same basis as the audited financial statements for the year ended December 31, 2020, with the exception of our retrospective adoption of Accounting Standards Update, or ASU, 2020-06, which simplifies the accounting for convertible debt instruments. See Note 2, Significant Accounting Polices, Convertible Debt, for details of our adoption of this guidance. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended December 31, 2020 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.
Consolidation	In our condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (“we”, “us” or “our”). We formed Akcea in December 2014. In July 2017, Akcea completed an initial public offering, or IPO, which reduced our ownership of Akcea’s common stock below 100 percent. In October 2020, we completed a merger transaction with Akcea such that following the completion of the merger, Akcea became our wholly owned subsidiary. We will refer to this transaction as the Akcea Merger throughout the remainder of this document. We reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the period the changes occurred.

Significant Accounting Policies (Policies)

9 Months Ended

Sep. 30, 2021

Significant Accounting Policies [Abstract]

Revenue Recognition

Our Revenue Sources

Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue

Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net

Research and development revenue under collaborative agreements

Steps to Recognize Revenue

We use a five-step process to determine the amount of revenue we should recognize and when we should recognize it. The five-step process is as follows:

Identify the contract

Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:

●

We and our partner approved the contract and we are both committed to perform our obligations;

●

We have identified our rights, our partner’s rights and the payment terms;

●

We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and

●

We believe collectability of the consideration is probable.

Identify the performance obligations

Determine the transaction price

Allocate the transaction price

●

Estimated future product sales;

●

Estimated royalties we may receive from future product sales;

●

Estimated contractual milestone payments we may receive;

●

Estimated expenses we may incur;

●

Estimated income taxes; and

●

A discount rate.

●

The estimated number of internal hours we will spend performing these services;

●

The estimated cost of work we will perform;

●

The estimated cost of work that we will contract with third parties to perform; and

●

The estimated cost of API we will use.

Recognize revenue

The following are examples of when we typically recognize revenue based on the types of payments we receive.

Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue

Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net

Reserves for TEGSEDI and WAYLIVRA commercial revenue

Under our distribution agreements with Sobi, Sobi is responsible for any applicable reserves.

Research and development revenue under collaboration agreements:

Upfront payments

Milestone payments

License fees

Sublicense fees

Amendments to Agreements

From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:

If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and

If the goods and/or services are sold at a stand-alone selling price.

Multiple agreements

●

Whether the agreements were negotiated together with a single objective;

●

Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or

●

Whether the goods and/or services promised under the agreements are a single performance obligation.

Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting guidance requires us to account for them as a combined arrangement.

Contracts Receivable

Unbilled SPINRAZA Royalties

Deferred Revenue

Cost of Sales

Cash, Cash Equivalents and Investments

Inventory Valuation

Our inventory consisted of the following (in thousands):

	September 30, 2021		December 31, 2020
Raw materials:
Raw materials- clinical	$	11,993	$	9,206
Raw materials- commercial		4,147		7,502
Total raw materials		16,140		16,708
Work in process		6,183		2,252
Finished goods		607		3,005
Total inventory	$	22,930	$	21,965

Leases

Research and Development Expenses

Long-lived Assets

Basic and Diluted Net Loss per Share

Basic and Diluted Net Loss Per Share

Basic net loss per share

We calculated our basic net loss per share for the three months ended September 30, 2020 as follows (in thousands, except per share amounts):

Three months ended September 30, 2020	Weighted Average Shares Owned in Akcea		Akcea’s Net Loss Per Share			Basic Net Loss Per Share Calculation (as revised*)
Ionis’ portion of Akcea’s net loss		77,095	$	(0.49	)	$	(37,822	)
Akcea’s net loss attributable to our ownership						$	(37,822	)
Ionis’ stand-alone net income							13,251
Net loss available to Ionis common stockholders						$	(24,571	)
Weighted average shares outstanding							139,708
Basic net loss per share						$	(0.18	)

We calculated our basic net loss per share for the nine months ended September 30, 2020 as follows (in thousands, except per share amounts):

Nine months ended September 30, 2020	Weighted Average Shares Owned in Akcea		Akcea’s Net Loss Per Share			Basic Net Loss Per Share Calculation (as revised*)
Ionis’ portion of Akcea’s net loss		77,095	$	(1.40	)	$	(108,176	)
Akcea’s net loss attributable to our ownership						$	(108,176	)
Ionis’ stand-alone net income							18,235
Net loss available to Ionis common stockholders						$	(89,941	)
Weighted average shares outstanding							139,497
Basic net loss per share						$	(0.64	)

*	We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 2, Significant Accounting Policies, for further information.

Diluted net loss per share

●

0.125 percent convertible senior notes, or 0.125% Notes;

●

Note hedges related to the 0.125% Notes;

●

1 percent convertible senior notes, or 1% Notes;

●

Dilutive stock options;

●

Unvested restricted stock units, or RSUs;

●

Unvested performance restricted stock units, or PRSUs; and

●

Employee Stock Purchase Plan, or ESPP.

For the three and nine months ended September 30, 2021, common stock from the following would also have had an anti-dilutive effect on net loss per share:

●

0 percent convertible senior notes, or 0% Notes; and

●

Note hedges related to the 0% Notes.

Convertible Debt

Adoption of ASU 2020-06

The following table summarizes the adjustments we made to the condensed 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	)

	Three Months Ended September 30, 2020
	As Previously Reported			ASU 2020-06 Adjustment			As Revised
Interest expense	$	(11,321	)	$	8,893		$	(2,428	)
Loss before income tax expense	$	(40,443	)	$	8,893		$	(31,550	)
Income tax expense	$	(2,648	)	$	(2,416	)	$	(5,064	)
Net loss	$	(43,091	)	$	6,477		$	(36,614	)
Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders	$	(30,944	)	$	6,477		$	(24,467	)
Basic and diluted net loss per share	$	(0.22	)	$	0.04		$	(0.18	)

	Nine Months Ended September 30, 2020
	As Previously Reported			ASU 2020-06 Adjustment			As Revised
Interest expense	$	(33,484	)	$	26,408		$	(7,076	)
Loss before income tax benefit (expense)	$	(146,387	)	$	26,408		$	(119,979	)
Income tax benefit (expense)	$	1,047		$	(5,124	)	$	(4,077	)
Net loss	$	(145,340	)	$	21,284		$	(124,056	)
Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders	$	(111,015	)	$	21,284		$	(89,731	)
Basic and diluted net loss per share	$	(0.80	)	$	0.16		$	(0.64	)

	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		$	(107,089	)	$	1,577,458

Call Spread

Segment Information

Stock-Based Compensation Expense

Stock-based Compensation Expense

For the nine months ended September 30, 2021 and 2020, we used the following weighted-average assumptions in our Black-Scholes calculations:

Employee Stock Options:

	Nine Months Ended September 30,
	2021			2020
Risk-free interest rate		0.5	%		1.5	%
Dividend yield		0.0	%		0.0	%
Volatility		54.3	%		58.8	%
Expected life	4.9 years			4.7 years

Ionis Board of Director Stock Options:

	Nine Months Ended September 30,
	2021			2020
Risk-free interest rate		1.2	%		0.5	%
Dividend yield		0.0	%		0.0	%
Volatility		55.9	%		57.6	%
Expected life	7.3 years			6.7 years

ESPP:

	Nine Months Ended September 30,
	2021			2020
Risk-free interest rate		0.1	%		0.8	%
Dividend yield		0.0	%		0.0	%
Volatility		42.4	%		47.9	%
Expected life	6 months			6 months

RSU’s:

PRSU’s:

The following table summarizes stock-based compensation expense for the three and nine months ended September 30, 2021 and 2020 (in thousands).

	Three Months Ended September 30,				Nine Months Ended September 30,
	2021		2020		2021		2020
Cost of sales	$	111	$	315	$	293	$	902
Research, development and patent expense		23,332		25,359		71,979		76,931
Selling, general and administrative expense		7,094		20,171		26,147		57,244
Total non-cash stock-based compensation expense	$	30,537	$	45,845	$	98,419	$	135,077

Impact of Recently Issued Accounting Standards

Significant Accounting Policies (Tables)

9 Months Ended

Sep. 30, 2021

Significant Accounting Policies [Abstract]

Inventory

Our inventory consisted of the following (in thousands):

	September 30, 2021		December 31, 2020
Raw materials:
Raw materials- clinical	$	11,993	$	9,206
Raw materials- commercial		4,147		7,502
Total raw materials		16,140		16,708
Work in process		6,183		2,252
Finished goods		607		3,005
Total inventory	$	22,930	$	21,965

Basic Net Loss per Share

We calculated our basic net loss per share for the three months ended September 30, 2020 as follows (in thousands, except per share amounts):

Three months ended September 30, 2020	Weighted Average Shares Owned in Akcea		Akcea’s Net Loss Per Share			Basic Net Loss Per Share Calculation (as revised*)
Ionis’ portion of Akcea’s net loss		77,095	$	(0.49	)	$	(37,822	)
Akcea’s net loss attributable to our ownership						$	(37,822	)
Ionis’ stand-alone net income							13,251
Net loss available to Ionis common stockholders						$	(24,571	)
Weighted average shares outstanding							139,708
Basic net loss per share						$	(0.18	)

We calculated our basic net loss per share for the nine months ended September 30, 2020 as follows (in thousands, except per share amounts):

Nine months ended September 30, 2020	Weighted Average Shares Owned in Akcea		Akcea’s Net Loss Per Share			Basic Net Loss Per Share Calculation (as revised*)
Ionis’ portion of Akcea’s net loss		77,095	$	(1.40	)	$	(108,176	)
Akcea’s net loss attributable to our ownership						$	(108,176	)
Ionis’ stand-alone net income							18,235
Net loss available to Ionis common stockholders						$	(89,941	)
Weighted average shares outstanding							139,497
Basic net loss per share						$	(0.64	)

*	We revised our 2020 amounts to reflect the simplified convertible instruments accounting guidance, which we adopted retrospectively. Refer to Note 2, Significant Accounting Policies, for further information.

Adoption of ASU 2020-06

The following table summarizes the adjustments we made to the condensed 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	)

	Three Months Ended September 30, 2020
	As Previously Reported			ASU 2020-06 Adjustment			As Revised
Interest expense	$	(11,321	)	$	8,893		$	(2,428	)
Loss before income tax expense	$	(40,443	)	$	8,893		$	(31,550	)
Income tax expense	$	(2,648	)	$	(2,416	)	$	(5,064	)
Net loss	$	(43,091	)	$	6,477		$	(36,614	)
Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders	$	(30,944	)	$	6,477		$	(24,467	)
Basic and diluted net loss per share	$	(0.22	)	$	0.04		$	(0.18	)

	Nine Months Ended September 30, 2020
	As Previously Reported			ASU 2020-06 Adjustment			As Revised
Interest expense	$	(33,484	)	$	26,408		$	(7,076	)
Loss before income tax benefit (expense)	$	(146,387	)	$	26,408		$	(119,979	)
Income tax benefit (expense)	$	1,047		$	(5,124	)	$	(4,077	)
Net loss	$	(145,340	)	$	21,284		$	(124,056	)
Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders	$	(111,015	)	$	21,284		$	(89,731	)
Basic and diluted net loss per share	$	(0.80	)	$	0.16		$	(0.64	)

	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		$	(107,089	)	$	1,577,458

Weighted-Average Assumptions for Stock Options

Employee Stock Options:

	Nine Months Ended September 30,
	2021			2020
Risk-free interest rate		0.5	%		1.5	%
Dividend yield		0.0	%		0.0	%
Volatility		54.3	%		58.8	%
Expected life	4.9 years			4.7 years

Ionis Board of Director Stock Options:

	Nine Months Ended September 30,
	2021			2020
Risk-free interest rate		1.2	%		0.5	%
Dividend yield		0.0	%		0.0	%
Volatility		55.9	%		57.6	%
Expected life	7.3 years			6.7 years

Weighted-Average Assumptions for ESPP

ESPP:

	Nine Months Ended September 30,
	2021			2020
Risk-free interest rate		0.1	%		0.8	%
Dividend yield		0.0	%		0.0	%
Volatility		42.4	%		47.9	%
Expected life	6 months			6 months

Stock-Based Compensation Expense

The following table summarizes stock-based compensation expense for the three and nine months ended September 30, 2021 and 2020 (in thousands).

	Three Months Ended September 30,				Nine Months Ended September 30,
	2021		2020		2021		2020
Cost of sales	$	111	$	315	$	293	$	902
Research, development and patent expense		23,332		25,359		71,979		76,931
Selling, general and administrative expense		7,094		20,171		26,147		57,244
Total non-cash stock-based compensation expense	$	30,537	$	45,845	$	98,419	$	135,077

Investments (Tables)

9 Months Ended

Sep. 30, 2021

Investments [Abstract]

Contract Maturity of Available-for-Sale Securities

The following table summarizes the contract maturity of the available-for-sale securities we held as of September 30, 2021:

One year or less	58	%
After one year but within two years	26	%
After two years but within three and a half years	16	%
Total	100	%

Summary of Investments

The following is a summary of our investments (in thousands):

			Gross Unrealized					Estimated
September 30, 2021	Cost (1)		Gains		Losses			Fair Value
Available-for-sale securities:
Corporate debt securities (2)	$	447,173	$	1,338	$	(50	)	$	448,461
Debt securities issued by U.S. government agencies		83,630		96		(7	)		83,719
Debt securities issued by the U.S. Treasury (2)		89,267		10		(2	)		89,275
Debt securities issued by states of the U.S. and political subdivisions of the states		141,161		103		(30	)		141,234
Other municipal debt securities		5,028		—		(2	)		5,026
Total securities with a maturity of one year or less		766,259		1,547		(91	)		767,715
Corporate debt securities		366,907		1,181		(475	)		367,613
Debt securities issued by U.S. government agencies		73,028		1		(120	)		72,909
Debt securities issued by the U.S. Treasury		98,499		245		(88	)		98,656
Debt securities issued by states of the U.S. and political subdivisions of the states		41,167		8		(65	)		41,110
Other municipal debt		6,169		—		(26	)		6,143
Total securities with a maturity of more than one year		585,770		1,435		(774	)		586,431
Total available-for-sale securities	$	1,352,029	$	2,982	$	(865	)	$	1,354,146
Equity securities:
Total equity securities included in other current assets (3)	$	11,897	$	1,935	$	(663	)	$	13,169
Total equity securities included in deposits and other assets (4)		15,615		16,707		—			32,322
Total equity securities		27,512		18,642		(663	)		45,491
Total available-for-sale and equity securities	$	1,379,541	$	21,624	$	(1,528	)	$	1,399,637

			Gross Unrealized					Estimated
December 31, 2020	Cost (1)		Gains		Losses			Fair Value
Available-for-sale securities:
Corporate debt securities (2)	$	514,182	$	2,194	$	(41	)	$	516,335
Debt securities issued by U.S. government agencies		94,234		354		(2	)		94,586
Debt securities issued by the U.S. Treasury (2)		307,576		233		(9	)		307,800
Debt securities issued by states of the U.S. and political subdivisions of the states		104,271		196		(12	)		104,455
Other municipal debt securities		5,191		—		(7	)		5,184
Total securities with a maturity of one year or less		1,025,454		2,977		(71	)		1,028,360
Corporate debt securities		325,079		4,941		(40	)		329,980
Debt securities issued by U.S. government agencies		80,099		185		(9	)		80,275
Debt securities issued by the U.S. Treasury		50,318		383		(4	)		50,697
Debt securities issued by states of the U.S. and political subdivisions of the states		31,779		91		(16	)		31,854
Other municipal debt securities		1,041		—		—			1,041
Total securities with a maturity of more than one year		488,316		5,600		(69	)		493,847
Total available-for-sale securities	$	1,513,770	$	8,577	$	(140	)	$	1,522,207
Equity securities:
Total equity securities included in other current assets (3)	$	4,712	$	—	$	(2,681	)	$	2,031
Total equity securities included in deposits and other assets (4)		15,062		15,938		—			31,000
Total equity securities		19,774		15,938		(2,681	)		33,031
Total available-for-sale and equity securities	$	1,533,544	$	24,515	$	(2,821	)	$	1,555,238

(1)	We hold our available-for-sale securities at amortized cost.

(2)	Includes investments classified as cash equivalents on our condensed consolidated balance sheet.

(3)

(4)

Temporarily Impaired Investments

	Number of Investments		Estimated Fair Value		Unrealized Losses
Corporate debt securities		158	$	334,828	$	(525	)
Debt securities issued by U.S. government agencies		13		103,460		(127	)
Debt securities issued by the U.S. Treasury		10		75,009		(90	)
Debt securities issued by states of the U.S. and political subdivisions of the states		432		123,489		(95	)
Other municipal debt securities		3		11,168		(28	)
Total temporarily impaired securities		616	$	647,954	$	(865	)

Fair Value Measurements (Tables)

9 Months Ended

Sep. 30, 2021

Fair Value Measurements [Abstract]

Assets Measured at Fair Value on a Recurring Basis

	At September 30, 2021		Quoted Prices in Active Markets (Level 1)		Significant Other Observable Inputs (Level 2)		Significant Unobservable Inputs (Level 3)
Cash equivalents (1)	$	545,339	$	545,339	$	—	$	—
Corporate debt securities (2)		816,074		—		816,074		—
Debt securities issued by U.S. government agencies (2)		156,628		—		156,628		—
Debt securities issued by the U.S. Treasury (2)		187,931		187,931		—		—
Debt securities issued by states of the U.S. and political subdivisions of the states		182,344		—		182,344		—
Other municipal debt securities (2)		11,169		—		11,169		—
Investment in Bicycle Therapeutics plc (3)		9,120		—		—		9,120
Investment in ProQR Therapeutics N.V. (3)		4,049		4,049		—		—
Total	$	1,912,654	$	737,319	$	1,166,215	$	9,120

	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 (4)		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 (5)		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. (3)		2,031		2,031		—
Total	$	1,745,363	$	581,653	$	1,163,710

The following footnotes reference lines on our condensed consolidated balance sheet:

(1)	Included in cash and cash equivalents on our condensed consolidated balance sheet.

(2)	Included in short-term investments.

(3)	Included in other current assets on our condensed consolidated balance sheet.

(4)	$10.0 million was included in cash and cash equivalents, with the difference included in short-term investments.

(5)	$17.5 million included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.

Collaborative Arrangements and Licensing Agreements (Tables)

9 Months Ended

Sep. 30, 2021

Biogen [Member]

Collaborative Arrangements and Licensing Agreements [Abstract]

Revenue from Collaborative Relationship

During the three and nine months ended September 30, 2021 and 2020, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):

	Three Months Ended September 30,						Nine Months Ended September 30,
	2021			2020			2021			2020
SPINRAZA royalties (commercial revenue)	$	66.6		$	74.2		$	198.7		$	211.9
R&D revenue		17.4			51.2			63.4			98.6
Total revenue from our relationship with Biogen	$	84.0		$	125.4		$	262.1		$	310.5
Percentage of total revenue		63	%		78	%		71	%		71	%

Convertible Debt (Tables)

9 Months Ended

Sep. 30, 2021

0 Percent Convertible Senior Notes [Member]

Convertible Notes [Abstract]

Convertible Notes

At September 30, 2021, we had the following 0% Notes outstanding (amounts in millions except interest rate and price per share data):

	0% Notes
Outstanding principal balance	$	632.5
Unamortized debt issuance costs	$	14.2
Maturity date	April 2026
Interest rate	0 percent
Effective interest rate	0.5 percent
Conversion price per share	$	57.84
Effective conversion price per share with call spread	$	76.39
Total shares of common stock subject to conversion		10.9

0.125 Percent Convertible Senior Notes [Member]

Convertible Notes [Abstract]

Convertible Notes

At September 30, 2021, we had the following 0.125% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):

	0.125% Notes
Outstanding principal balance	$	548.8
Unamortized debt issuance costs	$	7.1
Maturity date	December 2024
Interest rate	0.125 percent
Effective interest rate	0.5 percent
Conversion price per share	$	83.28
Effective conversion price per share with call spread	$	123.38
Total shares of common stock subject to conversion		6.6

1 Percent Convertible Senior Notes [Member]

Convertible Notes [Abstract]

Convertible Notes

At September 30, 2021, we had the following 1% Notes outstanding with interest payable semi-annually (amounts in millions except interest rate and price per share data):

	1% Notes
Outstanding principal balance	$	62.0
Unamortized debt issuance costs	$	0.03
Maturity date	November 2021
Interest rate	1 percent
Effective interest rate	1.4 percent
Conversion price per share	$	66.81
Total shares of common stock subject to conversion		0.9

Severance and Retention Costs (Tables)

9 Months Ended

Sep. 30, 2021

Akcea Merger [Member]

Severance and Retention Costs [Abstract]

Severance and Retention Costs

	Severance and Retention Expenses
Total estimated expenses	$	27.2
Expenses incurred from inception to September 30, 2021		27.0
Remaining estimated expenses to be recognized through October 2021	$	0.2

The following table summarizes our severance and retention expenses related to the Akcea Merger that we recognized during the three and nine months ended September 30, 2021 (in millions):

	Three Months Ended September 30, 2021		Nine Months Ended September 30, 2021
Research, development and patent expenses	$	1.3	$	5.1
Selling, general and administrative expenses		0.6		6.6
Total	$	1.9	$	11.7

The following table summarizes the severance and retention reserve amounts related to the Akcea Merger that we included in accrued compensation for the period indicated (in millions):

	Nine Months Ended September 30, 2021
Beginning balance as of January 1, 2021	$	14.7
Amounts expensed during the period		13.5
Reserve adjustments during the period		(1.8	)
Net amount expensed during the period		11.7
Amounts paid during the period		(20.6	)
Ending balance as of September 30, 2021	$	5.8

Restructured European Operations [Member]

Severance and Retention Costs [Abstract]

Severance and Retention Costs

	Severance and Retention Expenses
Total estimated expenses	$	14.2
Expenses incurred from inception to September 30, 2021		14.0
Remaining estimated expenses to be recognized through October 2021	$	0.2

	Three Months Ended September 30, 2021		Nine Months Ended September 30, 2021
Research, development and patent expenses	$	0.5	$	0.6
Selling, general and administrative expenses		0.1		1.1
Total	$	0.6	$	1.7

	Nine Months Ended September 30, 2021
Beginning balance as of January 1, 2021	$	12.4
Amounts expensed during the period		2.5
Reserve adjustments during the period		(0.8	)
Net amount expensed during the period		1.7
Amounts paid during the period		(13.4	)
Ending balance as of September 30, 2021	$	0.7

Restructured North American TEGSEDI Operations [Member]

Severance and Retention Costs [Abstract]

Severance and Retention Costs

The following table summarizes the severance expenses related to our Restructured North American TEGSEDI Operations that we recognized during the second quarter of 2021 (in millions):

	Three Months Ended June 30, 2021
Research, development and patent expenses	$	2.3
Selling, general and administrative expenses		7.1
Total	$	9.4

	Nine Months Ended September 30, 2021
Beginning balance as of January 1, 2021	$	—
Amounts expensed during the period		9.4
Amounts paid during the period		(9.2	)
Ending balance as of September 30, 2021	$	0.2

Basis of Presentation (Details) - Akcea [Member]	Sep. 30, 2021	Jul. 31, 2017
Basis of Presentation [Abstract]
Percentage ownership	100.00%
Maximum [Member]
Basis of Presentation [Abstract]
Percentage ownership		100.00%

Significant Accounting Policies, Revenue Recognition (Details) $ in Thousands	1 Months Ended			3 Months Ended					9 Months Ended
	Aug. 31, 2021 USD ($)	Feb. 28, 2017 USD ($) PerformanceObligation	May 31, 2015 USD ($)	Sep. 30, 2021 USD ($)	Dec. 31, 2020 USD ($)	Sep. 30, 2020 USD ($)	Dec. 31, 2018 USD ($)	Jun. 30, 2018 Agreement	Sep. 30, 2021 USD ($) PerformanceObligation	Sep. 30, 2020 USD ($)
Revenue Recognition [Abstract]
Revenue				$ 133,093		$ 160,079			$ 370,450	$ 438,983
Number of performance obligations at inception of contract \| PerformanceObligation									1
Biogen [Member]
Revenue Recognition [Abstract]
Number of agreements \| Agreement								2
TEGSEDI and WAYLIVRA [Member]
Revenue Recognition [Abstract]
Revenue				15,519		$ 19,040			$ 46,901	$ 50,562
PTC [Member] \| TEGSEDI and WAYLIVRA [Member]
Revenue Recognition [Abstract]
Revenue				4,000
Novartis [Member] \| Pelacarsen [Member]
Revenue Recognition [Abstract]
Revenue	$ 25,000			$ 25,000
Percentage enrollment in Lp(a) HORIZON Phase 3 cardiovascular outcome study	50.00%			50.00%					50.00%
IONIS-FB-L for Complement-Mediated Diseases [Member]
Revenue Recognition [Abstract]
Upfront payment received							$ 75,000
Biogen 2018 Strategic Neurology [Member]
Revenue Recognition [Abstract]
Milestone payment received and added to transaction price					$ 7,500
AstraZeneca [Member] \| ION455 [Member]
Revenue Recognition [Abstract]
Revenue					$ 30,000
Bayer [Member]
Revenue Recognition [Abstract]
Upfront payment received			$ 100,000
Bayer [Member]
Revenue Recognition [Abstract]
Upfront payment received		$ 75,000
Number of separate performance obligations \| PerformanceObligation		3
Transaction price		$ 75,000

Significant Accounting Policies, Contracts Receivable (Details) - Partner	9 Months Ended	12 Months Ended
	Sep. 30, 2021	Dec. 31, 2020
Contracts Receivable [Abstract]
Period of time after billing when payment is received	3 months
Significant Partners [Abstract]
Number of significant customers	3	2
Contracts Receivables [Member] \| Credit Concentration [Member] \| Three Significant Customers [Member]
Significant Partners [Abstract]
Concentration percentage	58.30%
Contracts Receivables [Member] \| Credit Concentration [Member] \| Two Significant Customers [Member]
Significant Partners [Abstract]
Concentration percentage		99.50%

Significant Accounting Policies, Deferred Revenue (Details) - USD ($) $ in Millions	3 Months Ended		9 Months Ended
	Sep. 30, 2021	Sep. 30, 2020	Sep. 30, 2021	Sep. 30, 2020
Deferred Revenue [Abstract]
Revenue recognized from amounts in beginning deferred revenue balance	$ 21.1	$ 22.5	$ 71.9	$ 84.1

Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2021 USD ($) Company	Sep. 30, 2020 USD ($)	Sep. 30, 2021 USD ($) Company	Dec. 31, 2020 USD ($) Investment	Sep. 30, 2020 USD ($)
Cash, Cash Equivalents and Investments [Abstract]
Number of publicly held companies in which there is an equity ownership interest of less than 20% \| Company	3		3
Number of privately held companies in which there is an equity ownership interest of less than 20% \| Company	7		7
Number of investments in privately held companies that were revalued \| Investment				3
Gain on investment	$ 4,013	$ 835	$ 4,885		$ 10,722
Dynacure [Member]
Cash, Cash Equivalents and Investments [Abstract]
Gain on investment				$ 6,300
Suzhou-Ribo [Member]
Cash, Cash Equivalents and Investments [Abstract]
Gain on investment				3,000
Aro Biotherapeutics [Member]
Cash, Cash Equivalents and Investments [Abstract]
Gain on investment				$ 5,500

Significant Accounting Policies, Inventory Valuation (Details) - USD ($) $ in Thousands	Sep. 30, 2021	Dec. 31, 2020
Inventory Valuation [Abstract]
Raw materials	$ 16,140	$ 16,708
Work in process	6,183	2,252
Finished goods	607	3,005
Total inventory	22,930	21,965
Clinical [Member]
Inventory Valuation [Abstract]
Raw materials	11,993	9,206
Commercial [Member]
Inventory Valuation [Abstract]
Raw materials	$ 4,147	$ 7,502

Significant Accounting Policies, Leases (Details) - Office Space in Boston, Massachusetts [Member] $ in Millions	9 Months Ended
	Sep. 30, 2021 USD ($)
Operating Leases [Abstract]
Initial term of operating lease	91 months
Term of operating lease extension	5 years
Free rent period	7 months
Lease payments over initial term of lease	$ 6.8

Significant Accounting Policies, Basic and Diluted Net Loss per Share (Details) - USD ($) $ / shares in Units, shares in Thousands, $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2021	Sep. 30, 2020	Sep. 30, 2021	Sep. 30, 2020	Dec. 31, 2020
Basic Net Loss per Share [Abstract]
Basic net loss per share (in dollars per share)	$ (0.58)	$ (0.18)	$ (1.80)	$ (0.64)
Net income (loss)	$ (82,466)	$ (24,467)	$ (253,210)	$ (89,731)
Net loss available to Ionis common shareholders		$ (24,571)		$ (89,941)
Weighted average shares outstanding (in shares)	141,139	139,708	140,958	139,497
0.125 Percent Convertible Senior Notes [Member]
Basic Net Loss per Share [Abstract]
Interest rate on convertible senior notes	0.125%	0.125%	0.125%	0.125%	0.125%
1 Percent Convertible Senior Notes [Member]
Basic Net Loss per Share [Abstract]
Interest rate on convertible senior notes	1.00%	1.00%	1.00%	1.00%	1.00%
0 Percent Convertible Senior Notes [Member]
Basic Net Loss per Share [Abstract]
Interest rate on convertible senior notes	0.00%		0.00%
Ionis [Member]
Basic Net Loss per Share [Abstract]
Net income (loss)		$ 13,251		$ 18,235
Akcea [Member]
Basic Net Loss per Share [Abstract]
Percentage ownership	100.00%		100.00%
Net income (loss)		$ (37,822)		$ (108,176)
Akcea [Member] \| Common Stock [Member]
Basic Net Loss per Share [Abstract]
Weighted average shares owned in Akcea (in shares)		77,095		77,095
Basic net loss per share (in dollars per share)		$ (0.49)		$ (1.40)
Net income (loss)		$ (37,822)		$ (108,176)

Significant Accounting Policies, Convertible Debt (Details) $ / shares in Units, $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2021 USD ($) Note $ / shares	Sep. 30, 2020 USD ($) $ / shares	Sep. 30, 2021 USD ($) Note $ / shares	Sep. 30, 2020 USD ($) $ / shares	Jun. 30, 2021 USD ($)	Apr. 30, 2021 USD ($)	Dec. 31, 2020 USD ($)	Jun. 30, 2020 USD ($)	Dec. 31, 2019 USD ($)
Convertible Debt [Abstract]
Number of outstanding convertible notes \| Note	2		2
Condensed Consolidated Balance Sheet [Abstract]
1 percent convertible senior notes, net	$ 61,936		$ 61,936				$ 308,809
Additional paid-in capital	1,942,348		1,942,348				1,895,519
Accumulated deficit	(1,384,516)		(1,384,516)				(1,131,306)
Condensed Consolidated Statement of Operations [Abstract]
Interest expense	(2,340)	$ (2,428)	(7,111)	$ (7,076)
Loss before income tax benefit (expense)	(83,773)	(31,550)	(254,064)	(119,979)
Income tax benefit (expense)	1,307	(5,064)	854	(4,077)
Net loss	(82,466)	(36,614)	(253,210)	(124,056)
Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders	$ (82,466)	$ (24,467)	$ (253,210)	$ (89,731)
Basic net loss per share (in dollars per share) \| $ / shares	$ (0.58)	$ (0.18)	$ (1.80)	$ (0.64)
Diluted net loss per share (in dollars per share) \| $ / shares	$ (0.58)	$ (0.18)	$ (1.80)	$ (0.64)
Condensed Consolidated Statements of Stockholders' Equity [Abstract]
Balance	$ 530,536	$ 1,520,579	$ 530,536	$ 1,520,579	$ 582,674		743,282	$ 1,502,513	$ 1,577,458
Additional Paid In Capital [Member]
Condensed Consolidated Statement of Operations [Abstract]
Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders	0	0	0	0
Condensed Consolidated Statements of Stockholders' Equity [Abstract]
Balance	1,942,348	2,093,551	1,942,348	2,093,551	1,910,379		1,895,519	2,053,502	1,985,650
Accumulated Deficit [Member]
Condensed Consolidated Statement of Operations [Abstract]
Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders	(82,466)	(24,467)	(253,210)	(89,731)
Condensed Consolidated Statements of Stockholders' Equity [Abstract]
Balance	(1,384,516)	(776,775)	(1,384,516)	(776,775)	(1,302,050)		(1,131,306)	(752,308)	(596,495)
Total Ionis Stockholders' Equity [Member]
Condensed Consolidated Statement of Operations [Abstract]
Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders	(82,466)	(24,467)	(253,210)	(89,731)
Condensed Consolidated Statements of Stockholders' Equity [Abstract]
Balance	$ 530,536	$ 1,297,344	$ 530,536	$ 1,297,344	$ 582,674		$ 743,282	$ 1,284,893	1,364,005
0.125 Percent Convertible Senior Notes [Member]
Convertible Debt [Abstract]
Interest rate on convertible senior notes	0.125%	0.125%	0.125%	0.125%			0.125%
Condensed Consolidated Balance Sheet [Abstract]
Convertible senior notes	$ 541,768		$ 541,768				$ 540,136
Condensed Consolidated Statement of Operations [Abstract]
Effective interest rate	0.50%		0.50%
1 Percent Convertible Senior Notes [Member]
Convertible Debt [Abstract]
Interest rate on convertible senior notes	1.00%	1.00%	1.00%	1.00%			1.00%
Condensed Consolidated Statement of Operations [Abstract]
Effective interest rate	1.40%		1.40%
0 Percent Convertible Senior Notes [Member]
Convertible Debt [Abstract]
Interest rate on convertible senior notes	0.00%		0.00%
Face amount of offering						$ 632,500
Condensed Consolidated Balance Sheet [Abstract]
Convertible senior notes	$ 618,341		$ 618,341				$ 0
Condensed Consolidated Statement of Operations [Abstract]
Effective interest rate	0.50%		0.50%
As Previously Reported [Member]
Condensed Consolidated Balance Sheet [Abstract]
1 percent convertible senior notes, net							293,161
Additional paid-in capital							2,113,646
Accumulated deficit							(1,249,368)
Condensed Consolidated Statement of Operations [Abstract]
Interest expense		$ (11,321)		$ (33,484)
Loss before income tax benefit (expense)		(40,443)		(146,387)
Income tax benefit (expense)		(2,648)		1,047
Net loss		(43,091)		(145,340)
Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders		$ (30,944)		$ (111,015)
Basic net loss per share (in dollars per share) \| $ / shares		$ (0.22)		$ (0.80)
Diluted net loss per share (in dollars per share) \| $ / shares		$ (0.22)		$ (0.80)
Condensed Consolidated Statements of Stockholders' Equity [Abstract]
Balance							843,347		1,684,547
As Previously Reported [Member] \| Additional Paid In Capital [Member]
Condensed Consolidated Statements of Stockholders' Equity [Abstract]
Balance							2,113,646		2,203,778
As Previously Reported [Member] \| Accumulated Deficit [Member]
Condensed Consolidated Statements of Stockholders' Equity [Abstract]
Balance							(1,249,368)		(707,534)
As Previously Reported [Member] \| 0.125 Percent Convertible Senior Notes [Member]
Condensed Consolidated Balance Sheet [Abstract]
Convertible senior notes							455,719
Adjustment [Member] \| ASU 2020-06 [Member]
Condensed Consolidated Balance Sheet [Abstract]
1 percent convertible senior notes, net							15,648
Additional paid-in capital							(218,127)
Accumulated deficit							118,062
Net deferred tax assets							0
Condensed Consolidated Statement of Operations [Abstract]
Interest expense		$ 8,893		$ 26,408
Loss before income tax benefit (expense)		8,893		26,408
Income tax benefit (expense)		(2,416)		(5,124)
Net loss		6,477		21,284
Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders		$ 6,477		$ 21,284
Basic net loss per share (in dollars per share) \| $ / shares		$ 0.04		$ 0.16
Diluted net loss per share (in dollars per share) \| $ / shares		$ 0.04		$ 0.16
Condensed Consolidated Statements of Stockholders' Equity [Abstract]
Balance							(100,065)		(107,089)
Adjustment [Member] \| ASU 2020-06 [Member] \| Additional Paid In Capital [Member]
Condensed Consolidated Statements of Stockholders' Equity [Abstract]
Balance							(218,127)		(218,128)
Adjustment [Member] \| ASU 2020-06 [Member] \| Accumulated Deficit [Member]
Condensed Consolidated Statements of Stockholders' Equity [Abstract]
Balance							118,062		$ 111,039
Adjustment [Member] \| ASU 2020-06 [Member] \| 0.125 Percent Convertible Senior Notes [Member]
Condensed Consolidated Balance Sheet [Abstract]
Convertible senior notes							$ 84,417

Significant Accounting Policies, Segment Information (Details)	9 Months Ended
	Sep. 30, 2021 Segment
Segment Information [Abstract]
Number of operating segments	2

Significant Accounting Policies, Stock-Based Compensation Expense (Details) $ / shares in Units, $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2021 USD ($)	Sep. 30, 2020 USD ($)	Sep. 30, 2021 USD ($) Period $ / shares shares	Sep. 30, 2020 USD ($)
Stock-based Compensation Expense [Abstract]
Non-cash stock-based compensation expense	$ 30,537	$ 45,845	$ 98,419	$ 135,077
Cost of Sales [Member]
Stock-based Compensation Expense [Abstract]
Non-cash stock-based compensation expense	111	315	293	902
Research, Development and Patent Expense [Member]
Stock-based Compensation Expense [Abstract]
Non-cash stock-based compensation expense	23,332	25,359	71,979	76,931
Selling, General and Administrative Expense [Member]
Stock-based Compensation Expense [Abstract]
Non-cash stock-based compensation expense	7,094	$ 20,171	26,147	$ 57,244
Stock Options [Member]
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation expense related to non-vested stock options	65,300		$ 65,300
Weighted average period for recognition			1 year 2 months 12 days
Stock Options [Member] \| Board of Directors [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate			1.20%	0.50%
Dividend yield			0.00%	0.00%
Volatility			55.90%	57.60%
Expected life			7 years 3 months 18 days	6 years 8 months 12 days
Stock Options [Member] \| Employees [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate			0.50%	1.50%
Dividend yield			0.00%	0.00%
Volatility			54.30%	58.80%
Expected life			4 years 10 months 24 days	4 years 8 months 12 days
ESPP [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate			0.10%	0.80%
Dividend yield			0.00%	0.00%
Volatility			42.40%	47.90%
Expected life			6 months	6 months
RSUs [Member]
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation cost related to non-vested units	72,200		$ 72,200
Weighted average period for recognition			1 year 4 months 24 days
RSUs [Member] \| Board of Directors [Member]
RSUs and PRSUs [Abstract]
Weighted-average grant date fair value (in dollars per share) \| $ / shares			$ 39.42
RSUs [Member] \| Board of Directors [Member] \| Maximum [Member]
RSUs and PRSUs [Abstract]
Vesting period			4 years
RSUs [Member] \| Board of Directors [Member] \| Minimum [Member]
RSUs and PRSUs [Abstract]
Vesting period			1 year
RSUs [Member] \| Employees [Member]
RSUs and PRSUs [Abstract]
Vesting period			4 years
Weighted-average grant date fair value (in dollars per share) \| $ / shares			$ 59.15
PRSUs [Member]
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation cost related to non-vested units	$ 2,500		$ 2,500
Weighted average period for recognition			1 year 2 months 12 days
PRSUs [Member] \| Chief Executive Officer, Dr. Brett Monia [Member]
RSUs and PRSUs [Abstract]
Number of performance periods \| Period			3
Vesting period			3 years
Number of units guaranteed to vest \| shares			0
Weighted-average grant date fair value (in dollars per share) \| $ / shares			$ 77.17
PRSUs [Member] \| Chief Executive Officer, Dr. Brett Monia [Member] \| Maximum [Member]
RSUs and PRSUs [Abstract]
Percentage of units guaranteed to vest			150.00%
PRSUs [Member] \| Chief Executive Officer, Dr. Brett Monia [Member] \| Minimum [Member]
RSUs and PRSUs [Abstract]
Percentage of units guaranteed to vest			0.00%
PRSUs [Member] \| Chief Executive Officer, Dr. Brett Monia [Member] \| One-Year Period [Member]
RSUs and PRSUs [Abstract]
Vesting percentage			33.30%
PRSUs [Member] \| Chief Executive Officer, Dr. Brett Monia [Member] \| Two-Year Period [Member]
RSUs and PRSUs [Abstract]
Vesting percentage			33.30%
PRSUs [Member] \| Chief Executive Officer, Dr. Brett Monia [Member] \| Three-Year Period [Member]
RSUs and PRSUs [Abstract]
Vesting percentage			33.30%

Significant Accounting Policies, Amendments to Equity Plan (Details) - shares	Jun. 30, 2021	Mar. 31, 2021
2020 Equity Incentive Plan [Member]
Amendments to Equity Plans [Abstract]
Number of shares authorized for issuance under the Plan (in shares)	1,600,000	2,600,000
2011 Equity Incentive Plan [Member]
Amendments to Equity Plans [Abstract]
Number of shares authorized for issuance under the Plan (in shares)	29,700,000	23,000,000.0
Reduction in fungible share reserve for each share issued pursuant to full value award (n shares)	(1.7)
Increase in fungible share reserve for each share returning from a full value award (in shares)	1.7

Investments, Contract Maturity of Available-for-Sale Securities (Details)	9 Months Ended
	Sep. 30, 2021
Contract Maturity of Available-for-Sale Securities [Abstract]
One year or less	58.00%
After one year but within two years	26.00%
After two years but within three and a half years	16.00%
Total	100.00%
Percentage of available-for-sale securities with a maturity of less than two years	84.00%
Maximum contract maturity period, range 1	1 year
Maximum contract maturity period, range 2	2 years
Maximum contract maturity period, range 3	3 years 6 months

Investments, Summary of Investments (Details)
$ in Thousands

9 Months Ended

12 Months Ended

Sep. 30, 2021

USD ($)

Company

Dec. 31, 2020

USD ($)

Ownership Interests in Private and Public Companies [Abstract]

Number of private companies in which there is an equity ownership interest of less than 20% | Company

Number of public companies in which there is an equity ownership interest of less than 20% | Company

Summary of Investments [Abstract]

Cost

$ 1,379,541

$ 1,533,544

Gross unrealized gains

21,624

24,515

Gross unrealized losses

(1,528)

(2,821)

Estimated fair value

$ 1,399,637

1,555,238

Number of publicly traded companies in which there is an investment included in other current assets | Company

Bicycle [Member]

Summary of Investments [Abstract]

Gross unrealized gains

$ 1,900

ProQR [Member]

Summary of Investments [Abstract]

Gross unrealized losses

(700)

Available-for-sale Securities [Member]

Summary of Investments [Abstract]

Cost

^[1]

1,352,029

1,513,770

Gross unrealized gains

2,982

8,577

Gross unrealized losses

(865)

(140)

Estimated fair value

1,354,146

1,522,207

Available-for-sale Securities [Member] | Securities with Maturity of One Year or Less [Member]

Summary of Investments [Abstract]

Cost

^[1]

766,259

1,025,454

Gross unrealized gains

1,547

2,977

Gross unrealized losses

(91)

(71)

Estimated fair value

767,715

1,028,360

Available-for-sale Securities [Member] | Securities with Maturity of More than One Year [Member]

Summary of Investments [Abstract]

Cost

^[1]

585,770

488,316

Gross unrealized gains

1,435

5,600

Gross unrealized losses

(774)

(69)

Estimated fair value

586,431

493,847

Corporate Debt Securities [Member] | Securities with Maturity of One Year or Less [Member]

Summary of Investments [Abstract]

Cost

^[1],[2]

447,173

514,182

Gross unrealized gains

1,338

2,194

Gross unrealized losses

(50)

(41)

Estimated fair value

448,461

516,335

Corporate Debt Securities [Member] | Securities with Maturity of More than One Year [Member]

Summary of Investments [Abstract]

Cost

^[1]

366,907

325,079

Gross unrealized gains

1,181

4,941

Gross unrealized losses

(475)

(40)

Estimated fair value

367,613

329,980

Debt Securities Issued by U.S. Government Agencies [Member] | Securities with Maturity of One Year or Less [Member]

Summary of Investments [Abstract]

Cost

^[1]

83,630

94,234

Gross unrealized gains

354

Gross unrealized losses

(7)

(2)

Estimated fair value

83,719

94,586

Debt Securities Issued by U.S. Government Agencies [Member] | Securities with Maturity of More than One Year [Member]

Summary of Investments [Abstract]

Cost

^[1]

73,028

80,099

Gross unrealized gains

185

Gross unrealized losses

(120)

(9)

Estimated fair value

72,909

80,275

Debt Securities Issued by the U.S. Treasury [Member] | Securities with Maturity of One Year or Less [Member]

Summary of Investments [Abstract]

Cost

^[1],[2]

89,267

307,576

Gross unrealized gains

233

Gross unrealized losses

(2)

(9)

Estimated fair value

89,275

307,800

Debt Securities Issued by the U.S. Treasury [Member] | Securities with Maturity of More than One Year [Member]

Summary of Investments [Abstract]

Cost

^[1]

98,499

50,318

Gross unrealized gains

245

383

Gross unrealized losses

(88)

(4)

Estimated fair value

98,656

50,697

Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member] | Securities with Maturity of One Year or Less [Member]

Summary of Investments [Abstract]

Cost

^[1]

141,161

104,271

Gross unrealized gains

103

196

Gross unrealized losses

(30)

(12)

Estimated fair value

141,234

104,455

Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member] | Securities with Maturity of More than One Year [Member]

Summary of Investments [Abstract]

Cost

^[1]

41,167

31,779

Gross unrealized gains

Gross unrealized losses

(65)

(16)

Estimated fair value

41,110

31,854

Other Municipal Debt Securities [Member] | Securities with Maturity of One Year or Less [Member]

Summary of Investments [Abstract]

Cost

^[1]

5,028

5,191

Gross unrealized gains

Gross unrealized losses

(2)

(7)

Estimated fair value

5,026

5,184

Other Municipal Debt Securities [Member] | Securities with Maturity of More than One Year [Member]

Summary of Investments [Abstract]

Cost

^[1]

6,169

1,041

Gross unrealized gains

Gross unrealized losses

(26)

Estimated fair value

6,143

1,041

Equity Securities [Member]

Summary of Investments [Abstract]

Cost

27,512

19,774

Gross unrealized gains

18,642

15,938

Gross unrealized losses

(663)

(2,681)

Estimated fair value

45,491

33,031

Equity Securities in Publicly Traded Company [Member]

Summary of Investments [Abstract]

Cost

^[3]

11,897

4,712

Gross unrealized gains

1,935

Gross unrealized losses

(663)

(2,681)

Estimated fair value

13,169

2,031

Equity Securities in Private Companies [Member]

Summary of Investments [Abstract]

Cost

^[4]

15,615

15,062

Gross unrealized gains

16,707

15,938

Gross unrealized losses

Estimated fair value

$ 32,322

$ 31,000

[1]	We hold our available-for-sale securities at amortized cost.
[2]	Includes investments classified as cash equivalents on our condensed consolidated balance sheet.
[3]	Our equity securities included in other current assets consisted of our investments in two publicly traded companies, ProQR and Bicycle, which we classify as Level 1 and Level 3 investments, respectively. We recognize publicly traded equity securities at fair value. In the nine months ended September 30, 2021, we recognized a $1.9 million unrealized gain and a $0.7 million unrealized loss on our condensed consolidated statement of operations related to our investments in Bicycle and ProQR, respectively. In the nine months ended September 30, 2020, our equity securities included in other current assets only consisted of ProQR.
[4]	Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer.

Investments, Investments Temporarily Impaired (Details) $ in Thousands	Sep. 30, 2021 USD ($) Investment
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	616
Estimated fair value, less than 12 months of temporary impairment	$ 647,954
Unrealized losses, less than 12 months of temporary impairment	$ (865)
Corporate Debt Securities [Member]
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	158
Estimated fair value, less than 12 months of temporary impairment	$ 334,828
Unrealized losses, less than 12 months of temporary impairment	$ (525)
Debt Securities Issued by U.S. Government Agencies [Member]
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	13
Estimated fair value, less than 12 months of temporary impairment	$ 103,460
Unrealized losses, less than 12 months of temporary impairment	$ (127)
Debt Securities Issued by the U.S. Treasury [Member]
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	10
Estimated fair value, less than 12 months of temporary impairment	$ 75,009
Unrealized losses, less than 12 months of temporary impairment	$ (90)
Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	432
Estimated fair value, less than 12 months of temporary impairment	$ 123,489
Unrealized losses, less than 12 months of temporary impairment	$ (95)
Other Municipal Debt Securities [Member]
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	3
Estimated fair value, less than 12 months of temporary impairment	$ 11,168
Unrealized losses, less than 12 months of temporary impairment	$ (28)

Fair Value Measurements (Details) - USD ($)
$ in Thousands

Sep. 30, 2021

Dec. 31, 2020

Sep. 30, 2020

1% Notes [Member]

Fair Value Measurements [Abstract]

Interest rate on convertible senior notes

1.00%

0.125% Notes [Member]

Fair Value Measurements [Abstract]

Interest rate on convertible senior notes

0.125%

0% Notes [Member]

Fair Value Measurements [Abstract]

Interest rate on convertible senior notes

0.00%

Significant Other Observable Inputs (Level 2) [Member] | 1% Notes [Member]

Fair Value Measurements [Abstract]

Fair value of convertible notes

$ 61,900

Significant Other Observable Inputs (Level 2) [Member] | 0.125% Notes [Member]

Fair Value Measurements [Abstract]

Fair value of convertible notes

504,300

Significant Other Observable Inputs (Level 2) [Member] | 0% Notes [Member]

Fair Value Measurements [Abstract]

Fair value of convertible notes

581,400

Recurring Basis [Member]

Fair Value Measurements [Abstract]

Cash equivalents

^[1]

545,339

$ 221,125

Total

1,912,654

1,745,363

Recurring Basis [Member] | Bicycle Therapeutics plc [Member]

Fair Value Measurements [Abstract]

Investment

^[2]

9,120

Recurring Basis [Member] | ProQR Therapeutics N.V. [Member]

Fair Value Measurements [Abstract]

Investment

^[2]

4,049

2,031

Recurring Basis [Member] | Corporate Debt Securities [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

816,074

^[3]

846,315

^[4]

Recurring Basis [Member] | Corporate Debt Securities [Member] | Cash and Cash Equivalents [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

10,000

Recurring Basis [Member] | Debt Securities Issued by U.S. Government Agencies [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

^[3]

156,628

174,861

Recurring Basis [Member] | Debt Securities Issued by the U.S. Treasury [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

187,931

^[3]

358,497

^[5]

Recurring Basis [Member] | Debt Securities Issued by the U.S. Treasury [Member] | Cash and Cash Equivalents [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

17,500

Recurring Basis [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

182,344

136,309

^[3]

Recurring Basis [Member] | Other Municipal Debt Securities [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

^[3]

11,169

6,225

Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member]

Fair Value Measurements [Abstract]

Cash equivalents

545,339

221,125

Total

737,319

581,653

Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Bicycle Therapeutics plc [Member]

Fair Value Measurements [Abstract]

Investment

Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | ProQR Therapeutics N.V. [Member]

Fair Value Measurements [Abstract]

Investment

4,049

2,031

Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Corporate Debt Securities [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by U.S. Government Agencies [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by the U.S. Treasury [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

187,931

358,497

Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Other Municipal Debt Securities [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member]

Fair Value Measurements [Abstract]

Cash equivalents

Total

1,166,215

1,163,710

Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Bicycle Therapeutics plc [Member]

Fair Value Measurements [Abstract]

Investment

Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | ProQR Therapeutics N.V. [Member]

Fair Value Measurements [Abstract]

Investment

Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Corporate Debt Securities [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

816,074

846,315

Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by U.S. Government Agencies [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

156,628

174,861

Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by the U.S. Treasury [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

182,344

136,309

Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Other Municipal Debt Securities [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

11,169

6,225

Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member]

Fair Value Measurements [Abstract]

Cash equivalents

Total

9,120

$ 0

Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Bicycle Therapeutics plc [Member]

Fair Value Measurements [Abstract]

Investment

9,120

Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | ProQR Therapeutics N.V. [Member]

Fair Value Measurements [Abstract]

Investment

Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Corporate Debt Securities [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Debt Securities Issued by U.S. Government Agencies [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Debt Securities Issued by the U.S. Treasury [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Other Municipal Debt Securities [Member]

Fair Value Measurements [Abstract]

Available-for-sale securities

$ 0

[1]	Included in cash and cash equivalents on our condensed consolidated balance sheet.
[2]	Included in other current assets on our condensed consolidated balance sheet.
[3]	Included in short-term investments.
[4]	$10.0 million was included in cash and cash equivalents, with the difference included in short-term investments.
[5]	$17.5 million included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.

Collaborative Arrangements and Licensing Agreements, Biogen (Details) $ in Thousands	3 Months Ended			9 Months Ended
	Sep. 30, 2021 USD ($) Medicine	Jun. 30, 2021 USD ($)	Sep. 30, 2020 USD ($)	Sep. 30, 2021 USD ($) Medicine	Sep. 30, 2020 USD ($)	Dec. 31, 2020 USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 133,093		$ 160,079	$ 370,450	$ 438,983
SPINRAZA Royalties [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	66,572		74,171	198,726	211,925
R&D Revenue [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 48,273		64,739	$ 115,321	169,948
Biogen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of medicines currently being developed \| Medicine	8			8
Revenue	$ 84,000		$ 125,400	$ 262,100	$ 310,500
Deferred revenue	$ 412,500			$ 412,500		$ 465,800
Biogen [Member] \| Revenue [Member] \| Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage	63.00%		78.00%	71.00%	71.00%
Biogen [Member] \| SPINRAZA Royalties [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 66,600		$ 74,200	$ 198,700	$ 211,900
Biogen [Member] \| R&D Revenue [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	17,400		$ 51,200	63,400	$ 98,600
Biogen [Member] \| Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	3,000,000			3,000,000
2013 Strategic Neurology [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next prospective payment	$ 8,000			$ 8,000
2013 Strategic Neurology [Member] \| ION541 [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		$ 10,000

Collaborative Arrangements and Licensing Agreements, Novartis (Details) - USD ($) $ in Thousands	1 Months Ended	3 Months Ended		9 Months Ended
	Aug. 31, 2021	Sep. 30, 2021	Sep. 30, 2020	Sep. 30, 2021	Sep. 30, 2020
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		$ 133,093	$ 160,079	$ 370,450	$ 438,983
Novartis [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received		425,000		425,000
Novartis [Member] \| Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next prospective milestone		75,000		$ 75,000
Novartis [Member] \| Pelacarsen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 25,000	$ 25,000
Percentage enrollment in Lp(a) HORIZON Phase 3 cardiovascular outcome study	50.00%	50.00%		50.00%

- Definition

Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 30
-Subparagraph (a)
-URI http://asc.fasb.org/extlink&oid=123359005&loc=d3e8906-108599

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 40
-URI http://asc.fasb.org/extlink&oid=123359005&loc=d3e9031-108599

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 41
-Subparagraph (a)
-URI http://asc.fasb.org/extlink&oid=123359005&loc=d3e9038-108599

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 32
-Subparagraph (b)
-URI http://asc.fasb.org/extlink&oid=123359005&loc=d3e8933-108599

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 32
-Subparagraph (a)
-URI http://asc.fasb.org/extlink&oid=123359005&loc=d3e8933-108599

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 4
-Subparagraph (a)
-URI http://asc.fasb.org/extlink&oid=123351226&loc=SL49130543-203045

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 22
-Subparagraph (b)
-URI http://asc.fasb.org/extlink&oid=123359005&loc=d3e8736-108599

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 22
-Subparagraph (a)
-URI http://asc.fasb.org/extlink&oid=123359005&loc=d3e8736-108599

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 280
-SubTopic 10
-Section 50
-Paragraph 42
-URI http://asc.fasb.org/extlink&oid=123359005&loc=d3e9054-108599

Reference 10: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 606
-SubTopic 10
-Section 50
-Paragraph 5
-URI http://asc.fasb.org/extlink&oid=123351226&loc=SL49130545-203045

Reference 11: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 924
-SubTopic 10
-Section S99
-Paragraph 1
-Subparagraph (SAB Topic 11.L)
-URI http://asc.fasb.org/extlink&oid=6472922&loc=d3e499488-122856

+ Details

Collaborative Arrangements and Licensing Agreements, Bicycle License Agreement (Details) - Bicycle License Agreement [Member] - USD ($) $ in Millions	1 Months Ended	3 Months Ended	9 Months Ended
	Jul. 31, 2021	Sep. 30, 2021	Sep. 30, 2021
Collaborative Arrangement and Licensing Agreement [Abstract]
Payment of license fee	$ 42.0
Trading restriction period under lock up agreement			1 year
Equity investment		$ 7.2
R&D expense		34.8
Cumulative payments made		$ 45.0	$ 45.0

Convertible Debt (Details) - USD ($) $ / shares in Units, $ in Thousands, shares in Millions	1 Months Ended		3 Months Ended		9 Months Ended
	Apr. 30, 2021	Dec. 31, 2019	Sep. 30, 2021	Sep. 30, 2020	Sep. 30, 2021	Sep. 30, 2020	Dec. 31, 2020
Convertible Debt [Abstract]
Repurchase of convertible notes					$ 256,963	$ 0
Cost of call spread	$ 46,900	$ 52,600
Purchase of note hedges	136,700	108,700			136,620	0
Proceeds from issuance of warrants	89,800	$ 56,100			89,752	0
Loss on early retirement of debt			$ 0	$ 0	(8,627)	$ 0
0% Notes [Member]
Convertible Debt [Abstract]
Face amount of offering	632,500
Outstanding principal balance			632,500		632,500
Unamortized debt issuance costs			$ 14,200		$ 14,200
Maturity date					Apr. 30, 2026
Interest rate			0.00%		0.00%
Effective interest rate			0.50%		0.50%
Conversion price per share (in dollars per share)			$ 57.84		$ 57.84
Effective conversion price per share with call spread (in dollars per share)			$ 76.39		$ 76.39
Total shares of common stock subject to conversion (in shares)			10.9		10.9
Percentage of principal amount used as purchase price upon occurrence of fundamental change					100.00%
0.125% Notes [Member]
Convertible Debt [Abstract]
Outstanding principal balance			$ 548,800		$ 548,800
Unamortized debt issuance costs			$ 7,100		$ 7,100
Maturity date					Dec. 31, 2024
Interest rate			0.125%	0.125%	0.125%	0.125%	0.125%
Effective interest rate			0.50%		0.50%
Conversion price per share (in dollars per share)			$ 83.28		$ 83.28
Effective conversion price per share with call spread (in dollars per share)			$ 123.38		$ 123.38
Total shares of common stock subject to conversion (in shares)			6.6		6.6
Percentage of principal amount used as purchase price upon occurrence of fundamental change					100.00%
1% Notes [Member]
Convertible Debt [Abstract]
Principal amount repurchased	247,900		$ 247,900		$ 247,900
Repurchase of convertible notes	257,000
Outstanding principal balance			62,000		62,000
Unamortized debt issuance costs			$ 30		$ 30
Maturity date					Nov. 30, 2021
Interest rate			1.00%	1.00%	1.00%	1.00%	1.00%
Effective interest rate			1.40%		1.40%
Conversion price per share (in dollars per share)			$ 66.81		$ 66.81
Total shares of common stock subject to conversion (in shares)			0.9		0.9
Loss on early retirement of debt	$ 8,600
Percentage of principal amount used as purchase price upon occurrence of fundamental change					100.00%

Severance and Retention Costs, Akcea Merger (Details) - Akcea Merger [Member] $ in Millions	3 Months Ended	9 Months Ended
	Sep. 30, 2021 USD ($)	Sep. 30, 2021 USD ($)
Severance and Retention Costs [Abstract]
Total estimated expenses	$ 27.2	$ 27.2
Expenses incurred from inception to September 30, 2021	27.0	27.0
Remaining estimated expenses to be recognized through October 2021	0.2	0.2
Beginning balance		14.7
Amounts expensed during the period		13.5
Reserve adjustments during the period		(1.8)
Net amount expensed during the period	1.9	11.7
Amounts paid during the period		(20.6)
Ending balance	5.8	5.8
Research, Development and Patent Expenses [Member]
Severance and Retention Costs [Abstract]
Net amount expensed during the period	1.3	5.1
Selling, General and Administrative Expenses [Member]
Severance and Retention Costs [Abstract]
Net amount expensed during the period	$ 0.6	$ 6.6

Severance and Retention Costs, Restructured European Operations (Details) - Restructured European Operations [Member] $ in Millions	3 Months Ended	9 Months Ended
	Sep. 30, 2021 USD ($)	Sep. 30, 2021 USD ($)
Severance and Retention Costs [Abstract]
Total estimated expenses	$ 14.2	$ 14.2
Expenses incurred from inception to September 30, 2021	14.0	14.0
Remaining estimated expenses to be recognized through October 2021	0.2	0.2
Beginning balance		12.4
Amounts expensed during the period		2.5
Reserve adjustments during the period		(0.8)
Net amount expensed during the period	0.6	1.7
Amounts paid during the period		(13.4)
Ending balance	0.7	0.7
Research, Development and Patent Expenses [Member]
Severance and Retention Costs [Abstract]
Net amount expensed during the period	0.5	0.6
Selling, General and Administrative Expenses [Member]
Severance and Retention Costs [Abstract]
Net amount expensed during the period	$ 0.1	$ 1.1

Severance and Retention Costs, Restructured North American TEGSEDI Operations (Details) - Restructured North American TEGSEDI Operations [Member] - USD ($) $ in Millions	3 Months Ended	9 Months Ended
	Jun. 30, 2021	Sep. 30, 2021
Severance and Retention Costs [Abstract]
Beginning balance		$ 0.0
Amounts expensed during the period	$ 9.4	9.4
Amounts paid during the period		(9.2)
Ending balance		$ 0.2
Research, Development and Patent Expenses [Member]
Severance and Retention Costs [Abstract]
Amounts expensed during the period	2.3
Selling, General and Administrative Expenses [Member]
Severance and Retention Costs [Abstract]
Amounts expensed during the period	$ 7.1