0000874015-22-000148 | 10-Q | XBRL Viewer | Ionis Pharmaceuticals INC

Document and Entity Information - shares	6 Months Ended
Document and Entity Information - shares	Jun. 30, 2022	Aug. 03, 2022
Cover [Abstract]
Document Type	10-Q
Amendment Flag	false
Document Quarterly Report	true
Document Period End Date	Jun. 30, 2022
Current Fiscal Year End Date	--12-31
Document Fiscal Year Focus	2022
Document Fiscal Period Focus	Q2
Document Transition Report	false
Entity File Number	000-19125
Entity Registrant Name	Ionis Pharmaceuticals, Inc.
Entity Central Index Key	0000874015
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		141,941,338

CONDENSED CONSOLIDATED BALANCE SHEETS - USD ($) $ in Thousands	Jun. 30, 2022	Dec. 31, 2021
Current assets:
Cash and cash equivalents	$ 521,917	$ 869,191
Short-term investments	1,499,910	1,245,782
Contracts receivable	6,751	61,896
Inventories	19,811	24,806
Other current assets	142,759	143,374
Total current assets	2,191,148	2,345,049
Property, plant and equipment, net	177,015	178,069
Patents, net	29,054	29,005
Deposits and other assets	58,916	59,567
Total assets	2,456,133	2,611,690
Current liabilities:
Accounts payable	10,351	11,904
Accrued compensation	24,985	38,810
Accrued liabilities	134,336	88,560
Income taxes payable	14	36
Current portion of long-term obligations	4,732	3,526
Current portion of deferred contract revenue	93,393	97,714
Total current liabilities	267,811	240,550
Long-term deferred contract revenue	315,196	351,879
Long-term obligations, less current portion	25,093	26,378
Long-term mortgage debt	59,222	59,713
Total liabilities	1,831,407	1,839,953
Stockholders' equity:
Common stock, $0.001 par value; 300,000,000 shares authorized, 141,830,659 and 141,210,015 shares issued and outstanding at June 30, 2022 (unaudited) and December 31, 2021, respectively	142	141
Additional paid-in capital	2,008,794	1,964,167
Accumulated other comprehensive loss	(54,007)	(32,668)
Accumulated deficit	(1,330,203)	(1,159,903)
Total stockholders' equity	624,726	771,737
Total liabilities and stockholders' equity	2,456,133	2,611,690
0 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	620,678	619,119
0.125 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	$ 543,407	$ 542,314

CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares	Jun. 30, 2022	Dec. 31, 2021
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)	141,830,659	141,210,015
Common stock, shares outstanding (in shares)	141,830,659	141,210,015
0 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	0.00%	0.00%
0.125 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	0.125%	0.125%

CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS - USD ($) shares in Thousands, $ in Thousands	3 Months Ended		6 Months Ended
	Jun. 30, 2022	Jun. 30, 2021	Jun. 30, 2022	Jun. 30, 2021
Revenue:
Revenue	$ 133,791	$ 125,750	$ 275,710	$ 237,357
Expenses:
Cost of sales	4,745	2,958	8,914	5,537
Research, development and patent	180,758	139,306	341,884	279,107
Selling, general and administrative	33,802	56,455	67,929	117,653
Total operating expenses	219,305	198,719	418,727	402,297
Loss from operations	(85,514)	(72,969)	(143,017)	(164,940)
Other income (expense):
Investment income	3,403	2,734	5,396	7,364
Interest expense	(2,130)	(2,357)	(4,252)	(4,771)
Gain (loss) on investments	(6,337)	860	(12,963)	873
Other expense	(12,297)	(8,816)	(12,110)	(8,813)
Loss before income tax expense	(102,875)	(80,548)	(166,946)	(170,287)
Income tax expense	(2,260)	(327)	(3,354)	(457)
Net loss	$ (105,135)	$ (80,875)	$ (170,300)	$ (170,744)
Basic net loss per share (in dollars per share)	$ (0.74)	$ (0.57)	$ (1.20)	$ (1.21)
Diluted net loss per share (in dollars per share)	$ (0.74)	$ (0.57)	$ (1.20)	$ (1.21)
Shares used in computing basic net loss per share (in shares)	141,794	140,962	141,697	140,866
Shares used in computing diluted net loss per share (in shares)	141,794	140,962	141,697	140,866
Commercial Revenue [Member]
Revenue:
Revenue	$ 78,184	$ 85,861	$ 150,468	$ 170,309
SPINRAZA Royalties [Member]
Revenue:
Revenue	59,627	72,168	113,444	132,154
TEGSEDI and WAYLIVRA Revenue, Net [Member]
Revenue:
Revenue	10,386	11,544	16,547	31,382
Licensing and Other Royalty Revenue [Member]
Revenue:
Revenue	8,171	2,149	20,477	6,773
Research and Development Revenue [Member]
Revenue:
Revenue	55,607	39,889	125,242	67,048
Collaborative Agreement Revenue [Member]
Revenue:
Revenue	38,247	39,889	88,032	67,048
Eplontersen Joint Development Revenue [Member]
Revenue:
Revenue	$ 17,360	$ 0	$ 37,210	$ 0

CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($) $ in Thousands	3 Months Ended		6 Months Ended
	Jun. 30, 2022	Jun. 30, 2021	Jun. 30, 2022	Jun. 30, 2021
CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS [Abstract]
Net loss	$ (105,135)	$ (80,875)	$ (170,300)	$ (170,744)
Unrealized losses on debt securities, net of tax	(5,018)	(1,697)	(20,774)	(4,703)
Currency translation adjustment	(411)	104	(565)	(22)
Comprehensive loss	$ (110,564)	$ (82,468)	$ (191,639)	$ (175,469)

- Definition

The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.

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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
Balance at Dec. 31, 2020	$ 140	$ 1,895,519	$ (21,071)	$ (1,131,306)	$ 743,282
Balance (in shares) at Dec. 31, 2020	140,366
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(170,744)	(170,744)
Change in unrealized losses, net of tax	0	0	(4,703)	0	(4,703)
Foreign currency translation	0	0	(22)	0	(22)
Issuance of common stock in connection with employee stock plans	$ 1	9,641	0	0	9,642
Issuance of common stock in connection with employee stock plans (in shares)	917
Issuance of warrants	$ 0	89,752	0	0	89,752
Purchase of note hedges	0	(136,620)	0	0	(136,620)
Stock-based compensation expense	0	67,882	0	0	67,882
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	$ 0	(15,795)	0	0	(15,795)
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)	(261)
Balance at Jun. 30, 2021	$ 141	1,910,379	(25,796)	(1,302,050)	582,674
Balance (in shares) at Jun. 30, 2021	141,022
Balance at Mar. 31, 2021	$ 141	1,925,801	(24,203)	(1,221,175)	680,564
Balance (in shares) at Mar. 31, 2021	140,924
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(80,875)	(80,875)
Change in unrealized losses, net of tax	0	0	(1,697)	0	(1,697)
Foreign currency translation	0	0	104	0	104
Issuance of common stock in connection with employee stock plans	$ 0	1,882	0	0	1,882
Issuance of common stock in connection with employee stock plans (in shares)	108
Issuance of warrants	$ 0	89,752	0	0	89,752
Purchase of note hedges	0	(136,620)	0	0	(136,620)
Stock-based compensation expense	0	30,022	0	0	30,022
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	$ 0	(458)	0	0	(458)
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)	(10)
Balance at Jun. 30, 2021	$ 141	1,910,379	(25,796)	(1,302,050)	582,674
Balance (in shares) at Jun. 30, 2021	141,022
Balance at Dec. 31, 2021	$ 141	1,964,167	(32,668)	(1,159,903)	771,737
Balance (in shares) at Dec. 31, 2021	141,210
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(170,300)	(170,300)
Change in unrealized losses, net of tax	0	0	(20,774)	0	(20,774)
Foreign currency translation	0	0	(565)	0	(565)
Issuance of common stock in connection with employee stock plans	$ 1	3,461	0	0	3,462
Issuance of common stock in connection with employee stock plans (in shares)	935
Stock-based compensation expense	$ 0	50,738	0	0	50,738
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	$ 0	(9,572)	0	0	(9,572)
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)	(314)
Balance at Jun. 30, 2022	$ 142	2,008,794	(54,007)	(1,330,203)	624,726
Balance (in shares) at Jun. 30, 2022	141,831
Balance at Mar. 31, 2022	$ 142	1,983,078	(48,578)	(1,225,068)	709,574
Balance (in shares) at Mar. 31, 2022	141,753
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(105,135)	(105,135)
Change in unrealized losses, net of tax	0	0	(5,018)	0	(5,018)
Foreign currency translation	0	0	(411)	0	(411)
Issuance of common stock in connection with employee stock plans	$ 0	1,614	0	0	1,614
Issuance of common stock in connection with employee stock plans (in shares)	87
Stock-based compensation expense	$ 0	24,502	0	0	24,502
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	$ 0	(400)	0	0	(400)
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)	(9)
Balance at Jun. 30, 2022	$ 142	$ 2,008,794	$ (54,007)	$ (1,330,203)	$ 624,726
Balance (in shares) at Jun. 30, 2022	141,831

CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	6 Months Ended
	Jun. 30, 2022	Jun. 30, 2021
Operating activities:
Net loss	$ (170,300)	$ (170,744)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation	7,484	7,951
Amortization of right-of-use operating lease assets	1,300	781
Amortization of patents	1,197	1,137
Amortization of premium on investments, net	7,867	8,824
Amortization of debt issuance costs	2,688	2,193
Stock-based compensation expense	50,738	67,882
Loss (gain) on investments	54	(873)
Loss on early retirement of debt	0	8,627
Non-cash losses related to disposal of property, plant and equipment	527	0
Non-cash losses related to patents	951	827
Changes in operating assets and liabilities:
Contracts receivable	55,145	52,200
Inventories	4,995	(2,134)
Other current and long-term assets	(39)	9,179
Income taxes payable	(22)	551
Accounts payable	(2,672)	(2,819)
Accrued compensation	(13,825)	(35,506)
Accrued liabilities and other current liabilities	45,170	(14,914)
Deferred contract revenue	(41,004)	(50,476)
Net cash used in operating activities	(49,746)	(117,314)
Investing activities:
Purchases of short-term investments	(663,195)	(740,721)
Proceeds from sale of short-term investments	380,375	727,859
Purchases of property, plant and equipment	(6,040)	(6,130)
Acquisition of licenses and other assets, net	(1,993)	(3,182)
Net cash used in nvesting activities	(290,853)	(22,174)
Financing activities:
Proceeds from equity, net	3,462	9,642
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	(9,572)	(15,795)
Proceeds from the issuance of 0 percent convertible notes	0	632,500
0 percent convertible senior notes issuance costs	0	(15,551)
Repurchase of $247.9 million principal amount of the 1 percent convertible senior notes	0	(256,963)
Proceeds from issuance of warrants	0	89,752
Purchase of note hedges	0	(136,620)
Net cash (used in) provided by financing activities	(6,110)	306,965
Effects of exchange rates on cash	(565)	(22)
Net (decrease) increase in cash and cash equivalents	(347,274)	167,455
Cash and cash equivalents at beginning of period	869,191	397,664
Cash and cash equivalents at end of period	521,917	565,119
Supplemental disclosures of cash flow information:
Interest paid	1,544	2,866
Income taxes paid	2	0
Supplemental disclosures of non-cash investing and financing activities:
Amounts accrued for capital and patent expenditures	$ 1,121	$ 278

CONSOLIDATED STATEMENTS OF CASH FLOWS (Parenthetical) - USD ($) $ in Millions	Jun. 30, 2022	Dec. 31, 2021	Jun. 30, 2021	Apr. 30, 2021
0 Percent Convertible Senior Notes [Member]
Financing activities:
Interest rate on convertible senior notes	0.00%	0.00%	0.00%
1 Percent Convertible Senior Notes [Member]
Financing activities:
Interest rate on convertible senior notes	1.00%		1.00%
Principal amount repurchased			$ 247.9	$ 247.9

Basis of Presentation	6 Months Ended
Basis of Presentation	Jun. 30, 2022
Basis of Presentation [Abstract]
Basis of Presentation	1. Basis of Presentation We prepared the unaudited interim condensed consolidated financial statements for the three and six months ended June 30, 2022 and 2021 on the same basis as the audited financial statements for the year ended December 31, 2021. 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, 2021 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”).

Significant Accounting Policies

6 Months Ended

Jun. 30, 2022

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.

At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of Accounting Standards Codification, or ASC, Topic 808, Collaborative Arrangements, or ASC 808. ASC 808 does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. For collaboration arrangements within the scope of ASC 808 that contain multiple elements, we first determine which elements of the collaboration reflect a vendor-customer relationship and therefore are within the scope of ASC 606, Revenue from Contracts with Customers. When we determine elements of a collaboration do not reflect a vendor-customer relationship, we consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature.

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 January 2021 and April 2021, we entered into distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, in which Sobi began commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. 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. Under our agreement, we started receiving royalties from PTC for TEGSEDI sales in December 2021.

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 6, Collaborative Arrangements and Licensing Agreements, for collaborations with substantive changes that occurred in 2022. 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, 2021 for a summary of each of our material collaborative agreements.

Steps to Recognize Revenue

For elements of our contractual relationships that we account for under ASC 606, 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.

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 first quarter of 2022, we earned a $10 million milestone payment from Biogen when Biogen advanced the Phase 1/2 study for ION859, an investigational antisense medicine targeting leucine rich repeat kinase 2, or LRRK2, in patients with Parkinson’s disease. We did not consider the milestone payment probable until Biogen achieved the milestone event because advancing ION859 was contingent on Biogen advancing a Phase 1/2 study 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. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and 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, 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, 2021 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 second quarter of 2022, we achieved a $20 million milestone payment from Roche when we advanced the Phase 2 study in patients with dry age-related macular degeneration, or AMD, under our collaboration agreement with Roche to develop IONIS-FB-L_Rx. We added this payment to the transaction price and allocated it to our R&D services performance obligation for IONIS-FB-L_Rx. We are recognizing revenue related to this milestone payment over our estimated period of performance. As a result, we recorded a cumulative catch-up adjustment of $13.8 million to increase revenue as of June 30, 2022 for this payment. We estimate we will satisfy our performance obligation in the fourth quarter of 2023.

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 first quarter of 2022, we recognized $18 million in milestone payments when Biogen advanced two targets under our 2013 strategic collaboration. We concluded that the milestone payments were not related to our R&D services performance obligation. Therefore, we recognized the milestone payments in full in the first quarter of 2022.

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 2021, we earned a $60 million license fee from Biogen when Biogen licensed ION306, an investigational medicine in development to treat SMA.

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. For example, in the fourth quarter of 2020, we earned a $41.2 million sublicense fee from Alnylam Pharmaceuticals for its sublicense of our technology to Sanofi Genzyme.

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.

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.

Eplontersen Collaboration with AstraZeneca

In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for the treatment of transthyretin amyloidosis, or ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the U.S., except certain countries in Latin America. Under the terms of the agreement, we received a $200 million upfront payment in 2021.

We evaluated our eplontersen collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.

We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a result we had one performance obligation. For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations after we delivered the license to AstraZeneca.

We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we made an accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca, net of our share of AstraZeneca’s development expenses, in the same period we incur the related development expenses. As AstraZeneca is responsible for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca related to commercial and medical affairs activities as reductions of our SG&A expense and R&D expense, respectively. Refer to Item 2, Management’s Discussion and Analysis of Financial Condition and Results of Operations, for further details on the financial statement impacts of our eplontersen collaboration with AstraZeneca.

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 June 30, 2022, approximately 69.9 percent of our contracts receivables were from three significant customers. As of December 31, 2021, approximately 93.8 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 June 30, 2022 and 2021, we recognized $22.6 million and $26.8 million of revenue from amounts that were in our beginning deferred revenue balance for each respective period. During the six months ended June 30, 2022 and 2021, we recognized $48.4 million and $51.4 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.

Accrued Liabilities

Our accrued liabilities consisted of the following (in thousands):

	June 30, 2022		December 31, 2021
Clinical expenses	$	89,007	$	65,730
In-licensing expenses		7,332		8,044
Commercial expenses		5,066		2,471
Other miscellaneous expenses		32,931		12,315
Total accrued liabilities	$	134,336	$	88,560

Estimated Liability for Clinical Development Costs

We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. On at least a quarterly basis, we estimate our liability for preclinical and clinical development costs we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these costs. These costs primarily relate to third-party clinical management costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities determined based on the contracted fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon settlement, these costs may differ materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.

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 June 30, 2022, we held equity investments in three publicly held companies and eight privately held companies.

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 publicly held companies based on observable inputs such as quoted prices in active markets for identical assets. 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. We recorded an immaterial amount of fair value adjustments related to our equity investments for the six months ended June 30, 2022 and 2021.

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 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.

Our inventory consisted of the following (in thousands):

	June 30, 2022		December 31, 2021
Raw materials:
Raw materials- clinical	$	14,686	$	14,507
Raw materials- commercial		889		4,139
Total raw materials		15,575		18,646
Work in process		3,927		5,770
Finished goods		309		390
Total inventory	$	19,811	$	24,806

Leases

We determine if an arrangement contains a lease at inception of the arrangement. As of June 30, 2022, we only had 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 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 January 2022, we entered into a sublease agreement for our office space located in Boston, Massachusetts. The sublease commenced in January 2022 when the office space was ready for our tenant’s occupancy. We are subleasing this space under a non-cancelable operating sublease with a sublease term ending in November 2028 with no option to extend the sublease. Under the sublease agreement we provided a seven-month free rent period, which commenced in January 2022. We will receive lease payments over the sublease term totaling $9.6 million. We are recognizing sublease payments as other income on a straight-line, gross basis over the term of our sublease.

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 expected to be realized.

We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.

We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes. Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the provision for income taxes in the period in which we make such determination.

We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be realized.

We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.

Long-lived Assets

We evaluate long-lived assets, which include property, plant and equipment, right-of-use assets 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 six months ended June 30, 2022 and 2021 by dividing our net loss by our weighted-average number of common shares outstanding during the period. Our basic net loss per share for the three months ended June 30, 2022 and 2021 were $0.74 and $0.57, respectively. Our basic net loss per share for the six months ended June 30, 2022 and 2021 were $1.20 and $1.21, respectively.

Diluted net loss per share

For the three and six months ended June 30, 2022 and 2021, 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 percent convertible senior notes, or 0% Notes;

●

Note hedges related to the 0% Notes;

●

0.125 percent convertible senior notes, or 0.125% Notes;

●

Note hedges related to the 0.125% 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 six months ended June 30, 2021, common stock that we could have issued from our 1 percent convertible senior notes, or 1% Notes, would also have had an anti-dilutive effect on net loss per share.

Additionally as of June 30, 2022, 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

We 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, Derivatives and Hedging, or ASC 815, and our convertible debt instruments were not issued at a substantial premium. We record the entire debt issuance costs as a contra-liability on our condensed consolidated balance sheet at issuance and we amortize them over the contractual term using an updated effective interest rate. As such, the ending balances for our 0% and 0.125% Notes represent the principal balance of each convertible debt instrument less debt issuance costs. We amortize debt issuance costs for our 0% and 0.125% Notes over the respective contractual term using an effective interest rate of 0.5 percent for each note. Refer to Note 7, Convertible Debt, for further details on our convertible debt instruments.

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 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

We operate 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.

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 six months ended June 30, 2022 and 2021, we used the following weighted-average assumptions in our Black-Scholes calculations:

Employee Stock Options:

	Six Months Ended June 30,
	2022			2021
Risk-free interest rate		1.8	%		0.5	%
Dividend yield		0.0	%		0.0	%
Volatility		55.1	%		54.8	%
Expected life*	6.3 years			4.9 years

In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and 2020 Plan, that increased the contractual term of stock options granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the six months ended June 30, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.

ESPP:

	Six Months Ended June 30,
	2022			2021
Risk-free interest rate		0.6	%		0.1	%
Dividend yield		0.0	%		0.0	%
Volatility		50.2	%		39.1	%
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 for the six months ended June 30, 2022 was $34.38 per share.

PRSU’s:

Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added PRSU awards to the compensation for our other Section 16 officers. 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 the 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 our Section 16 officers for the six months ended June 30, 2022 and 2021 were $42.28 and $77.17 per share, respectively.

The following table summarizes stock-based compensation expense for the three and six months ended June 30, 2022 and 2021 (in thousands).

	Three Months Ended June 30,				Six Months Ended June 30,
	2022		2021		2022		2021
Cost of sales	$	53	$	—	$	213	$	182
Research, development and patent expense		18,500		22,748		37,582		48,647
Selling, general and administrative expense		5,949		7,274		12,943		19,053
Total stock-based compensation expense	$	24,502	$	30,022	$	50,738	$	67,882

As of June 30, 2022, total unrecognized estimated stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $54.3 million, $61.6 million and $4.4 million, respectively. Our actual expenses may differ from these estimates because we will adjust our unrecognized stock-based compensation expense for future forfeitures. We expect to recognize the cost of stock-based compensation expense related to our non-vested stock options, RSUs and PRSUs over a weighted average amortization period of 1.3 years, 1.6 years and 1.4 years, respectively. Our stock-based compensation expense related to equity awards decreased in the first half of 2022 compared to the same period in 2021 due to decreased headcount as a result of the Akcea Merger and restructuring our commercial operations for TEGSEDI and WAYLIVRA.

Impact of Recently Issued Accounting Standards

We do not expect any recently issued accounting standards to have a material impact to our financial results.

Investments

6 Months Ended

Jun. 30, 2022

Investments [Abstract]

Investments

3. Investments

The following table summarizes the contract maturity of the available-for-sale securities we held as of June 30, 2022:

One year or less	68	%
After one year but within two years	26	%
After two years but within three and a half years	6	%
Total	100	%

As illustrated above, at June 30, 2022, 94 percent of our available-for-sale securities had a maturity of less than two years.

All of our available-for-sale debt 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 June 30, 2022, we had an equity ownership interest of less than 20 percent in eight private companies and three public companies with which we conduct business.

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

	Amortized		Gross Unrealized					Estimated
June 30, 2022	Cost		Gains		Losses			Fair Value
Available-for-sale securities:
Corporate debt securities (1)	$	481,866	$	4	$	(3,749	)	$	478,121
Debt securities issued by U.S. government agencies		55,207		—		(927	)		54,280
Debt securities issued by the U.S. Treasury (1)		340,480		34		(1,829	)		338,685
Debt securities issued by states of the U.S. and political subdivisions of the states		148,750		1		(493	)		148,258
Other municipal debt securities		6,384		—		(90	)		6,294
Total securities with a maturity of one year or less		1,032,687		39		(7,088	)		1,025,638
Corporate debt securities		294,276		1		(11,542	)		282,735
Debt securities issued by U.S. government agencies		35,545		—		(1,451	)		34,094
Debt securities issued by the U.S. Treasury		158,476		61		(3,100	)		155,437
Debt securities issued by states of the U.S. and political subdivisions of the states		26,109		2		(748	)		25,363
Total securities with a maturity of more than one year		514,406		64		(16,841	)		497,629
Total available-for-sale securities	$	1,547,093	$	103	$	(23,929	)	$	1,523,267
Equity securities:
Publicly traded equity securities included in other current assets (2)	$	11,897	$	—	$	(7,159	)	$	4,738
Privately held equity securities included in deposits and other assets (3)		23,115		17,257		—			40,372
Total equity securities		35,012		17,257		(7,159	)		45,110
Total available-for-sale and equity securities	$	1,582,105	$	17,360	$	(31,088	)	$	1,568,377

	Amortized		Gross Unrealized					Estimated
December 31, 2021	Cost		Gains		Losses			Fair Value
Available-for-sale securities:
Corporate debt securities (1)	$	383,870	$	728	$	(226	)	$	384,372
Debt securities issued by U.S. government agencies		48,493		19		(18	)		48,494
Debt securities issued by the U.S. Treasury (1)		45,424		—		(64	)		45,360
Debt securities issued by states of the U.S. and political subdivisions of the states		134,770		45		(37	)		134,778
Total securities with a maturity of one year or less		612,557		792		(345	)		613,004
Corporate debt securities		382,000		331		(2,644	)		379,687
Debt securities issued by U.S. government agencies		72,935		—		(561	)		72,374
Debt securities issued by the U.S. Treasury		137,635		139		(500	)		137,274
Debt securities issued by states of the U.S. and political subdivisions of the states		39,909		1		(224	)		39,686
Other municipal debt securities		6,136		—		(37	)		6,099
Total securities with a maturity of more than one year		638,615		471		(3,966	)		635,120
Total available-for-sale securities	$	1,251,172	$	1,263	$	(4,311	)	$	1,248,124
Equity securities:
Publicly traded equity securities included in other current assets (2)	$	11,897	$	7,145	$	(837	)	$	18,205
Privately held equity securities included in deposits and other assets (3)		15,615		16,707		—			32,322
Total equity securities		27,512		23,852		(837	)		50,527
Total available-for-sale and equity securities	$	1,278,684	$	25,115	$	(5,148	)	$	1,298,651

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

(2)

Our equity securities included in other current assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value. In the six months ended June 30, 2022, we recognized a $13.5 million unrealized loss in our condensed consolidated statement of operations related to a decrease in the fair value of our investments in publicly traded companies.

(3)

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 June 30, 2022 (in thousands, except for number of investments). 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.

			Less than 12 Months of Temporary Impairment					More than 12 Months of Temporary Impairment					Total Temporary Impairment
	Number of Investments		Estimated Fair Value		Unrealized Losses			Estimated Fair Value		Unrealized Losses			Estimated Fair Value		Unrealized Losses
Corporate debt securities		380	$	703,643	$	(14,199	)	$	42,106	$	(1,092	)	$	745,749	$	(15,291	)
Debt securities issued by U.S. government agencies		11		65,974		(1,781	)		14,400		(597	)		80,374		(2,378	)
Debt securities issued by the U.S. Treasury		48		420,076		(4,767	)		4,837		(162	)		424,913		(4,929	)
Debt securities issued by states of the U.S. and political subdivisions of the states		403		119,174		(975	)		10,617		(266	)		129,791		(1,241	)
Other municipal debt securities		3		1,308		(14	)		4,986		(76	)		6,294		(90	)
Total temporarily impaired securities		845	$	1,310,175	$	(21,736	)	$	76,946	$	(2,193	)	$	1,387,121	$	(23,929	)

Fair Value Measurements

6 Months Ended

Jun. 30, 2022

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, which includes our investments in equity securities in privately held biotechnology companies. 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 June 30, 2022 and December 31, 2021 that we regularly measure and carry at fair value. As of June 30, 2022 and December 31, 2021, one of our investments in publicly held biotechnology companies 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. 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 June 30, 2022		Quoted Prices in Active Markets (Level 1)		Significant Other Observable Inputs (Level 2)		Significant Unobservable Inputs (Level 3)
Cash equivalents (1)	$	409,877	$	409,877	$	—	$	—
Corporate debt securities (2)		760,856		—		760,856		—
Debt securities issued by U.S. government agencies (2)		88,374		—		88,374		—
Debt securities issued by the U.S. Treasury (2)		494,122		494,122		—		—
Debt securities issued by states of the U.S. and political subdivisions of the states (3)		173,621		—		173,621		—
Other municipal debt securities (2)		6,294		—		6,294		—
Publicly traded equity securities included in other current assets		4,738		376		—		4,362
Privately held equity securities included in deposits and other assets		40,372		—		—		40,372
Total	$	1,978,254	$	904,375	$	1,029,145	$	44,734

	At December 31, 2021		Quoted Prices in Active Markets (Level 1)		Significant Other Observable Inputs (Level 2)		Significant Unobservable Inputs (Level 3)
Cash equivalents (1)	$	541,199	$	541,199	$	—	$	—
Corporate debt securities (2)		764,059		—		764,059		—
Debt securities issued by U.S. government agencies (2)		120,868		—		120,868		—
Debt securities issued by the U.S. Treasury (2)		182,634		182,634		—		—
Debt securities issued by states of the U.S. and political subdivisions of the states (4)		174,464		—		174,464		—
Other municipal debt securities (2)		6,099		—		6,099		—
Publicly traded equity securities included in other current assets		18,205		3,875		—		14,330
Privately held equity securities included in deposits and other assets		32,322		—		—		32,322
Total	$	1,839,850	$	727,708	$	1,065,490	$	46,652

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)	$23.4 million was 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.

(4)	$2.3 million was 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 0.125% Notes and 0% Notes had a fair value of $485.2 million and $577.0 million at June 30, 2022, 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

Income Taxes	6 Months Ended
Income Taxes	Jun. 30, 2022
Income Taxes [Abstract]
Income Taxes	5. Income Taxes Beginning in 2022, the Tax Cuts and Jobs Act of 2017, or TCJA, requires taxpayers to amortize research and development expenditures over five years pursuant to Internal Revenue Code, or IRC, Section 174. Although the U.S. Congress is considering legislation that would defer the amortization requirement to later years, we have no assurance that the provision will be repealed or otherwise modified. As a result, we recorded income tax expense of $2.3 million and $0.3 million for the three months ended June 30, 2022 and 2021, respectively, and income tax expense of $3.4 million and $0.5 million for the six months ended June 30, 2022 and 2021, respectively.

- Definition

The entire disclosure for income taxes. Disclosures may include net deferred tax liability or asset recognized in an enterprise's statement of financial position, net change during the year in the total valuation allowance, approximate tax effect of each type of temporary difference and carryforward that gives rise to a significant portion of deferred tax liabilities and deferred tax assets, utilization of a tax carryback, and tax uncertainties information.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-SubTopic 10
-Section 50
-Paragraph 21
-URI http://asc.fasb.org/extlink&oid=121826272&loc=d3e32857-109319

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-SubTopic 10
-Section S99
-Paragraph 2
-Subparagraph (SAB Topic 11.C)
-URI http://asc.fasb.org/extlink&oid=122134291&loc=d3e330215-122817

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-SubTopic 10
-Section 50
-Paragraph 17
-Subparagraph (b)
-URI http://asc.fasb.org/extlink&oid=121826272&loc=d3e32809-109319

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-SubTopic 10
-Section S99
-Paragraph 1
-Subparagraph (SAB TOPIC 6.I.5.Q1)
-URI http://asc.fasb.org/extlink&oid=122134291&loc=d3e330036-122817

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-SubTopic 10
-Section 50
-Paragraph 14
-URI http://asc.fasb.org/extlink&oid=121826272&loc=d3e32705-109319

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-SubTopic 270
-Section 50
-Paragraph 1
-URI http://asc.fasb.org/extlink&oid=6424409&loc=d3e44925-109338

Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-URI http://asc.fasb.org/topic&trid=2144680

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 740
-SubTopic 30
-Section 50
-Paragraph 2
-Subparagraph (a)
-URI http://asc.fasb.org/extlink&oid=6424122&loc=d3e41874-109331

Reference 9: http://www.xbrl.org/2003/role/disclosureRef
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-Topic 235
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-Paragraph 1
-Subparagraph (SX 210.4-08(h)(2))
-URI http://asc.fasb.org/extlink&oid=120395691&loc=d3e23780-122690

+ Details

Collaborative Arrangements and Licensing Agreements

6 Months Ended

Jun. 30, 2022

Collaborative Arrangements and Licensing Agreements [Abstract]

Collaborative Arrangements and Licensing Agreements

6. Collaborative Arrangements and Licensing Agreements

Below, we have included our Biogen and Roche collaborations, which are our only collaborations with substantive changes during 2022 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, 2021.

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 numerous investigational medicines to treat neurodegenerative diseases under these collaborations, including medicines in development to treat people with ALS, SMA, Angelman Syndrome, 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 June 30, 2022, we have received $3.3 billion from our Biogen collaborations.

During the three and six months ended June 30, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):

	Three Months Ended June 30,						Six Months Ended June 30,
	2022			2021			2022			2021
SPINRAZA royalties (commercial revenue)	$	59.6		$	72.2		$	113.4		$	132.2
R&D revenue		17.3			27.8			57.4			45.9
Total revenue from our relationship with Biogen	$	76.9		$	100.0		$	170.8		$	178.1
Percentage of total revenue		58	%		80	%		62	%		75	%

Our condensed consolidated balance sheet at June 30, 2022 and December 31, 2021 included deferred revenue of $368.3 million and $407.5 million, respectively, related to our relationship with Biogen.

During the first six months of 2022, we did not have any material changes to our performance obligations, transaction price or the timing in which we expect to recognize revenue under our Biogen collaborations.

In the first quarter of 2022, we earned $18 million in milestone payments from Biogen when Biogen advanced two targets under our 2013 strategic collaboration. We recognized the milestone payments in full in the first quarter of 2022 because we did not have any remaining performance obligations related to the milestone payments.

In July 2022, we earned a $9 million milestone payment from Biogen when the U.S. Food and Drug Administration, or FDA, accepted Biogen’s New Drug Application, or NDA, filing of tofersen, an investigational antisense medicine for the treatment of superoxide dismutase 1 amyotrophic lateral sclerosis, or SOD1-ALS. We will achieve the next payment of up to $10 million if Biogen advances another medicine under our 2013 strategic neurology collaboration.

Roche

We have two collaborations with Roche, one to develop IONIS-FB-L_Rx for the treatment of complement-mediated diseases, and one to develop treatments for Huntington's disease, or HD.

In October 2018, we entered into a collaboration agreement with Roche to develop IONIS-FB-L_Rx. We are currently conducting Phase 2 studies in two disease indications for IONIS-FB-L_Rx, one for the treatment of patients with geographic atrophy, or GA, the advanced stage of dry AMD, and a second for the treatment of patients with immunoglobulin A nephropathy, or IgAN. After positive data from a Phase 2 clinical study, Roche licensed IONIS-FB-L_Rx in July 2022 and plans to advance IONIS-FB-L_Rx into Phase 3 development for patients with IgAN. As a result, Roche is responsible for global development, regulatory and commercialization activities and costs for the Phase 3 IgAN study of IONIS-FB-L_Rx. We will continue to lead and conduct the open label Phase 2 study in patients with IgAN and the Phase 2 study in patients with GA. In July 2022, we amended our IONIS-FB-L_Rx collaboration agreement with Roche. Under our amended collaboration agreement, we are eligible to receive up to $145 million in development milestones, $279 million in regulatory milestones and $280 million in sales-related milestone payments. In addition, we are also eligible to receive tiered royalties from the high teens to 20 percent on net sales.

Under the collaboration agreement with Roche to develop treatments for HD, we discovered and developed tominersen, an investigational medicine targeting huntingtin, or HTT, protein, through completion of our Phase 1/2 clinical study in people with early stage HD. In the fourth quarter of 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. Roche is responsible for all global development, regulatory and commercialization activities and costs for tominersen. In March 2021, Roche decided to discontinue dosing in the Phase 3 GENERATION HD1 study of tominersen in patients with manifest HD based on the results of a pre-planned review of data from the Phase 3 study conducted by an unblinded iDMC. In January 2022, Roche announced it is actively preparing to initiate a new Phase 2 study of tominersen in patients with HD. Post-hoc analyses from the GENERATION HD1 study suggested tominersen may benefit younger adult patients with lower disease burden. From inception through June 30, 2022, we have received over $245 million from our Roche collaborations.

During the three and six months ended June 30, 2022 and 2021, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):

	Three Months Ended June 30,						Six Months Ended June 30,
	2022			2021			2022			2021
R&D revenue	$	19.5		$	3.6		$	23.9		$	7.5
Percentage of total revenue		15	%		3	%		9	%		3	%

Our condensed consolidated balance sheet at June 30, 2022 and December 31, 2021 included deferred revenue of $29.7 million and $31.6 million, respectively, related to our relationship with Roche.

In the second quarter of 2022, we achieved a $20 million milestone payment from Roche when we advanced the Phase 2 study in patients with dry AMD under our IONIS-FB-L_Rx collaboration. We added this payment to the transaction price and allocated it to our R&D services performance obligation for IONIS-FB-L_Rx. We are recognizing revenue for our R&D services performance obligation over our estimated period of performance.

In July 2022, we earned a $35 million payment from Roche when Roche licensed IONIS-FB-L_Rx. We will achieve the next payment of up to $90 million if Roche advances a medicine under our IONIS-FB-L_Rx collaboration.

Convertible Debt

6 Months Ended

Jun. 30, 2022

Convertible Debt [Abstract]

Convertible Debt

7. 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 June 30, 2022, 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	$	11.8
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 June 30, 2022, 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	$	5.4
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

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 loss on early retirement of debt in the second quarter of 2021, reflecting the early retirement of a significant portion of our 1% Notes. The 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. We paid the remaining principal balance of our 1% Notes with $62.0 million of cash at maturity in November 2021.

Other Terms of Convertible Senior Notes

The 0% and 0.125% 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. The 1% Notes were subject to similar terms.

- 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

Legal Proceedings	6 Months Ended
Legal Proceedings	Jun. 30, 2022
Legal Proceedings [Abstract]
Legal Proceedings	8. Legal Proceedings From time to time, we are involved in legal proceedings arising in the ordinary course of our business. Periodically, we evaluate the status of each legal matter and assess our potential financial exposure. If we consider the potential loss from any legal proceeding to be probable and we can reasonably estimate the amount, we accrue a liability for the estimated loss. The outcome of any proceeding is not determinable in advance. Therefore, we are required to use significant judgment to determine the probability of a loss and whether the amount of the loss is reasonably estimable. Our assessment of a potential liability and the amount of accruals we recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding and may revise our estimates. On August 5, 2021, four purported former stockholders of Akcea filed an action in the Delaware Court of Chancery captioned John Makris, et al. v. Ionis Pharmaceuticals, Inc., et al., C.A. No. 2021-0681, or the “Delaware Action.” The plaintiffs in the Delaware Action assert claims against (i) former members of Akcea’s board of directors; and (ii) Ionis, or collectively, the “Defendants.” The plaintiffs assert putatively direct claims on behalf of a purported class of former Akcea stockholders. The plaintiffs in the Delaware Action assert that the Defendants breached their fiduciary duties in connection with the October 2020 take-private transaction that Ionis and Akcea entered into, in which Akcea became a wholly-owned subsidiary of Ionis. Ionis believes this lawsuit is without merit. However, the outcome of this lawsuit or any other lawsuit that may be filed challenging the October 2020 take-private transaction is uncertain. Accordingly, on June 3, 2022, the parties reached an agreement in principle to settle the Delaware Action for $12.5 million, subject to the approval of the Delaware Court of Chancery. A Stipulation and Agreement of Compromise, Settlement and Release relating to this matter (the “Stipulation and Settlement Agreement”) has been executed and filed with the Delaware Court of Chancery, where it awaits Court approval. The terms of the Stipulation and Settlement Agreement include no finding of wrongdoing on the part of any of the Defendants. A hearing on the Stipulation and Settlement Agreement is scheduled for October 11, 2022. We recorded a legal reserve of $12.5 million as of June 30, 2022 for the proposed litigation settlement. We recorded the corresponding litigation settlement expense within other expense in the accompanying condensed consolidated statements of operations for the three and six months ended June 30, 2022. In July 2022, we entered into a settlement agreement with our insurance carrier wherein the insurance carrier agreed to contribute toward the settlement in the amount of $4.5 million. We will record the insurance contribution in the third quarter of 2022.

Basis of Presentation (Policies)	6 Months Ended
Basis of Presentation (Policies)	Jun. 30, 2022
Basis of Presentation [Abstract]
Basis of Presentation	We prepared the unaudited interim condensed consolidated financial statements for the three and six months ended June 30, 2022 and 2021 on the same basis as the audited financial statements for the year ended December 31, 2021. 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, 2021 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”).

Significant Accounting Policies (Policies)

6 Months Ended

Jun. 30, 2022

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

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.

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.

Eplontersen Collaboration with AstraZeneca

Contracts Receivable

Unbilled SPINRAZA Royalties

Deferred Revenue

Cost of Sales

Estimated Liability for Clinical Development Costs

Cash, Cash Equivalents and Investments

Inventory Valuation

Our inventory consisted of the following (in thousands):

	June 30, 2022		December 31, 2021
Raw materials:
Raw materials- clinical	$	14,686	$	14,507
Raw materials- commercial		889		4,139
Total raw materials		15,575		18,646
Work in process		3,927		5,770
Finished goods		309		390
Total inventory	$	19,811	$	24,806

Leases

Research and Development Expenses

Patent Expenses

Income Taxes

We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign subsidiaries.

Long-Lived Assets

Long-lived Assets

Use of Estimates

Basic and Diluted Net Loss per Share

Basic and Diluted Net Loss Per Share

Basic net loss per share

Diluted net loss per share

●

0 percent convertible senior notes, or 0% Notes;

●

Note hedges related to the 0% Notes;

●

0.125 percent convertible senior notes, or 0.125% Notes;

●

Note hedges related to the 0.125% Notes;

●

Dilutive stock options;

●

Unvested restricted stock units, or RSUs;

●

Unvested performance restricted stock units, or PRSUs; and

●

Employee Stock Purchase Plan, or ESPP.

Convertible Debt

Call Spread

Segment Information

We operate 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.

Stock-Based Compensation Expense

Stock-based Compensation Expense

For the six months ended June 30, 2022 and 2021, we used the following weighted-average assumptions in our Black-Scholes calculations:

Employee Stock Options:

	Six Months Ended June 30,
	2022			2021
Risk-free interest rate		1.8	%		0.5	%
Dividend yield		0.0	%		0.0	%
Volatility		55.1	%		54.8	%
Expected life*	6.3 years			4.9 years

ESPP:

	Six Months Ended June 30,
	2022			2021
Risk-free interest rate		0.6	%		0.1	%
Dividend yield		0.0	%		0.0	%
Volatility		50.2	%		39.1	%
Expected life	6 months			6 months

RSU’s:

PRSU’s:

The following table summarizes stock-based compensation expense for the three and six months ended June 30, 2022 and 2021 (in thousands).

	Three Months Ended June 30,				Six Months Ended June 30,
	2022		2021		2022		2021
Cost of sales	$	53	$	—	$	213	$	182
Research, development and patent expense		18,500		22,748		37,582		48,647
Selling, general and administrative expense		5,949		7,274		12,943		19,053
Total stock-based compensation expense	$	24,502	$	30,022	$	50,738	$	67,882

Impact of Recently Issued Accounting Standards

We do not expect any recently issued accounting standards to have a material impact to our financial results.

Significant Accounting Policies (Tables)

6 Months Ended

Jun. 30, 2022

Significant Accounting Policies [Abstract]

Inventory

Our inventory consisted of the following (in thousands):

	June 30, 2022		December 31, 2021
Raw materials:
Raw materials- clinical	$	14,686	$	14,507
Raw materials- commercial		889		4,139
Total raw materials		15,575		18,646
Work in process		3,927		5,770
Finished goods		309		390
Total inventory	$	19,811	$	24,806

Weighted-Average Assumptions for Stock Options

Employee Stock Options:

	Six Months Ended June 30,
	2022			2021
Risk-free interest rate		1.8	%		0.5	%
Dividend yield		0.0	%		0.0	%
Volatility		55.1	%		54.8	%
Expected life*	6.3 years			4.9 years

Weighted-Average Assumptions for ESPP

ESPP:

	Six Months Ended June 30,
	2022			2021
Risk-free interest rate		0.6	%		0.1	%
Dividend yield		0.0	%		0.0	%
Volatility		50.2	%		39.1	%
Expected life	6 months			6 months

Stock-Based Compensation Expense

The following table summarizes stock-based compensation expense for the three and six months ended June 30, 2022 and 2021 (in thousands).

	Three Months Ended June 30,				Six Months Ended June 30,
	2022		2021		2022		2021
Cost of sales	$	53	$	—	$	213	$	182
Research, development and patent expense		18,500		22,748		37,582		48,647
Selling, general and administrative expense		5,949		7,274		12,943		19,053
Total stock-based compensation expense	$	24,502	$	30,022	$	50,738	$	67,882

Investments (Tables)

6 Months Ended

Jun. 30, 2022

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 June 30, 2022:

One year or less	68	%
After one year but within two years	26	%
After two years but within three and a half years	6	%
Total	100	%

Summary of Investments

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

	Amortized		Gross Unrealized					Estimated
June 30, 2022	Cost		Gains		Losses			Fair Value
Available-for-sale securities:
Corporate debt securities (1)	$	481,866	$	4	$	(3,749	)	$	478,121
Debt securities issued by U.S. government agencies		55,207		—		(927	)		54,280
Debt securities issued by the U.S. Treasury (1)		340,480		34		(1,829	)		338,685
Debt securities issued by states of the U.S. and political subdivisions of the states		148,750		1		(493	)		148,258
Other municipal debt securities		6,384		—		(90	)		6,294
Total securities with a maturity of one year or less		1,032,687		39		(7,088	)		1,025,638
Corporate debt securities		294,276		1		(11,542	)		282,735
Debt securities issued by U.S. government agencies		35,545		—		(1,451	)		34,094
Debt securities issued by the U.S. Treasury		158,476		61		(3,100	)		155,437
Debt securities issued by states of the U.S. and political subdivisions of the states		26,109		2		(748	)		25,363
Total securities with a maturity of more than one year		514,406		64		(16,841	)		497,629
Total available-for-sale securities	$	1,547,093	$	103	$	(23,929	)	$	1,523,267
Equity securities:
Publicly traded equity securities included in other current assets (2)	$	11,897	$	—	$	(7,159	)	$	4,738
Privately held equity securities included in deposits and other assets (3)		23,115		17,257		—			40,372
Total equity securities		35,012		17,257		(7,159	)		45,110
Total available-for-sale and equity securities	$	1,582,105	$	17,360	$	(31,088	)	$	1,568,377

	Amortized		Gross Unrealized					Estimated
December 31, 2021	Cost		Gains		Losses			Fair Value
Available-for-sale securities:
Corporate debt securities (1)	$	383,870	$	728	$	(226	)	$	384,372
Debt securities issued by U.S. government agencies		48,493		19		(18	)		48,494
Debt securities issued by the U.S. Treasury (1)		45,424		—		(64	)		45,360
Debt securities issued by states of the U.S. and political subdivisions of the states		134,770		45		(37	)		134,778
Total securities with a maturity of one year or less		612,557		792		(345	)		613,004
Corporate debt securities		382,000		331		(2,644	)		379,687
Debt securities issued by U.S. government agencies		72,935		—		(561	)		72,374
Debt securities issued by the U.S. Treasury		137,635		139		(500	)		137,274
Debt securities issued by states of the U.S. and political subdivisions of the states		39,909		1		(224	)		39,686
Other municipal debt securities		6,136		—		(37	)		6,099
Total securities with a maturity of more than one year		638,615		471		(3,966	)		635,120
Total available-for-sale securities	$	1,251,172	$	1,263	$	(4,311	)	$	1,248,124
Equity securities:
Publicly traded equity securities included in other current assets (2)	$	11,897	$	7,145	$	(837	)	$	18,205
Privately held equity securities included in deposits and other assets (3)		15,615		16,707		—			32,322
Total equity securities		27,512		23,852		(837	)		50,527
Total available-for-sale and equity securities	$	1,278,684	$	25,115	$	(5,148	)	$	1,298,651

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

(2)

(3)

Temporarily Impaired Investments

			Less than 12 Months of Temporary Impairment					More than 12 Months of Temporary Impairment					Total Temporary Impairment
	Number of Investments		Estimated Fair Value		Unrealized Losses			Estimated Fair Value		Unrealized Losses			Estimated Fair Value		Unrealized Losses
Corporate debt securities		380	$	703,643	$	(14,199	)	$	42,106	$	(1,092	)	$	745,749	$	(15,291	)
Debt securities issued by U.S. government agencies		11		65,974		(1,781	)		14,400		(597	)		80,374		(2,378	)
Debt securities issued by the U.S. Treasury		48		420,076		(4,767	)		4,837		(162	)		424,913		(4,929	)
Debt securities issued by states of the U.S. and political subdivisions of the states		403		119,174		(975	)		10,617		(266	)		129,791		(1,241	)
Other municipal debt securities		3		1,308		(14	)		4,986		(76	)		6,294		(90	)
Total temporarily impaired securities		845	$	1,310,175	$	(21,736	)	$	76,946	$	(2,193	)	$	1,387,121	$	(23,929	)

Fair Value Measurements (Tables)

6 Months Ended

Jun. 30, 2022

Fair Value Measurements [Abstract]

Assets Measured at Fair Value on a Recurring Basis

	At June 30, 2022		Quoted Prices in Active Markets (Level 1)		Significant Other Observable Inputs (Level 2)		Significant Unobservable Inputs (Level 3)
Cash equivalents (1)	$	409,877	$	409,877	$	—	$	—
Corporate debt securities (2)		760,856		—		760,856		—
Debt securities issued by U.S. government agencies (2)		88,374		—		88,374		—
Debt securities issued by the U.S. Treasury (2)		494,122		494,122		—		—
Debt securities issued by states of the U.S. and political subdivisions of the states (3)		173,621		—		173,621		—
Other municipal debt securities (2)		6,294		—		6,294		—
Publicly traded equity securities included in other current assets		4,738		376		—		4,362
Privately held equity securities included in deposits and other assets		40,372		—		—		40,372
Total	$	1,978,254	$	904,375	$	1,029,145	$	44,734

	At December 31, 2021		Quoted Prices in Active Markets (Level 1)		Significant Other Observable Inputs (Level 2)		Significant Unobservable Inputs (Level 3)
Cash equivalents (1)	$	541,199	$	541,199	$	—	$	—
Corporate debt securities (2)		764,059		—		764,059		—
Debt securities issued by U.S. government agencies (2)		120,868		—		120,868		—
Debt securities issued by the U.S. Treasury (2)		182,634		182,634		—		—
Debt securities issued by states of the U.S. and political subdivisions of the states (4)		174,464		—		174,464		—
Other municipal debt securities (2)		6,099		—		6,099		—
Publicly traded equity securities included in other current assets		18,205		3,875		—		14,330
Privately held equity securities included in deposits and other assets		32,322		—		—		32,322
Total	$	1,839,850	$	727,708	$	1,065,490	$	46,652

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)	$23.4 million was 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.

(4)	$2.3 million was 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)

6 Months Ended

Jun. 30, 2022

Biogen [Member]

Collaborative Arrangements and Licensing Agreements [Abstract]

Revenue from Collaborative Relationship

During the three and six months ended June 30, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):

	Three Months Ended June 30,						Six Months Ended June 30,
	2022			2021			2022			2021
SPINRAZA royalties (commercial revenue)	$	59.6		$	72.2		$	113.4		$	132.2
R&D revenue		17.3			27.8			57.4			45.9
Total revenue from our relationship with Biogen	$	76.9		$	100.0		$	170.8		$	178.1
Percentage of total revenue		58	%		80	%		62	%		75	%

Roche [Member]

Collaborative Arrangements and Licensing Agreements [Abstract]

Revenue from Collaborative Relationship

During the three and six months ended June 30, 2022 and 2021, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):

	Three Months Ended June 30,						Six Months Ended June 30,
	2022			2021			2022			2021
R&D revenue	$	19.5		$	3.6		$	23.9		$	7.5
Percentage of total revenue		15	%		3	%		9	%		3	%

Convertible Debt (Tables)

6 Months Ended

Jun. 30, 2022

0 Percent Convertible Senior Notes [Member]

Convertible Notes [Abstract]

Convertible Senior Notes

At June 30, 2022, 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	$	11.8
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 Senior Notes

At June 30, 2022, 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	$	5.4
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

Significant Accounting Policies, Revenue Recognition (Details) $ in Thousands	3 Months Ended							6 Months Ended		12 Months Ended
	Jun. 30, 2022 USD ($)	Mar. 31, 2022 USD ($) Target	Dec. 31, 2021 USD ($) Component PerformanceObligation	Jun. 30, 2021 USD ($)	Dec. 31, 2020 USD ($)	Dec. 31, 2018 USD ($)	Jun. 30, 2018 Agreement	Jun. 30, 2022 USD ($)	Jun. 30, 2021 USD ($)	Dec. 31, 2021 USD ($) Component PerformanceObligation
Revenue Recognition [Abstract]
Revenue	$ 133,791			$ 125,750				$ 275,710	$ 237,357
Biogen [Member]
Revenue Recognition [Abstract]
Number of agreements \| Agreement							2
Biogen 2013 Strategic Neurology [Member]
Revenue Recognition [Abstract]
Revenue		$ 18,000
Number of targets advanced \| Target		2
Biogen 2013 Strategic Neurology [Member] \| ION859 [Member]
Revenue Recognition [Abstract]
Revenue		$ 10,000
IONIS-FB-L for Complement-Mediated Diseases [Member]
Revenue Recognition [Abstract]
Revenue	13,800
Upfront payment received						$ 75,000
Milestone payment received and added to transaction price	$ 20,000
New Antisense Medicines for the Treatment of SMA [Member] \| ION306 [Member]
Revenue Recognition [Abstract]
Revenue			$ 60,000
Alnylam [Member]
Revenue Recognition [Abstract]
Revenue					$ 41,200
Eplontersen Collaboration with AstraZeneca [Member]
Revenue Recognition [Abstract]
Revenue										$ 200,000
Number of material components \| Component			4							4
Number of separate performance obligations \| PerformanceObligation			1							1
Transaction price			$ 200,000							$ 200,000
Percentage of costs associated with ongoing global Phase 3 development program paid by AstraZeneca								55.00%

Significant Accounting Policies, Contracts Receivable (Details) - Partner	6 Months Ended	12 Months Ended
	Jun. 30, 2022	Dec. 31, 2021
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	69.90%
Contracts Receivables [Member] \| Credit Concentration [Member] \| Two Significant Customers [Member]
Significant Partners [Abstract]
Concentration percentage		93.80%

Significant Accounting Policies, Deferred Revenue (Details) - USD ($) $ in Millions	3 Months Ended		6 Months Ended
	Jun. 30, 2022	Jun. 30, 2021	Jun. 30, 2022	Jun. 30, 2021
Deferred Revenue [Abstract]
Revenue recognized from amounts in beginning deferred revenue balance	$ 22.6	$ 26.8	$ 48.4	$ 51.4

Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)	Jun. 30, 2022 Company
Cash, Cash Equivalents and Investments [Abstract]
Number of publicly held companies in which there is an equity ownership interest of less than 20%	3
Number of privately held companies in which there is an equity ownership interest of less than 20%	8

Significant Accounting Policies, Inventory Valuation (Details) - USD ($) $ in Thousands	Jun. 30, 2022	Dec. 31, 2021
Inventory Valuation [Abstract]
Raw materials	$ 15,575	$ 18,646
Work in process	3,927	5,770
Finished goods	309	390
Total inventory	19,811	24,806
Clinical [Member]
Inventory Valuation [Abstract]
Raw materials	14,686	14,507
Commercial [Member]
Inventory Valuation [Abstract]
Raw materials	$ 889	$ 4,139

Significant Accounting Policies, Leases (Details) - Office Space in Boston, Massachusetts [Member] $ in Millions	6 Months Ended
	Jun. 30, 2022 USD ($)
Leases [Abstract]
Free rent period under sublease agreement	7 months
Lease payments to be received over sublease term	$ 9.6

Significant Accounting Policies, Basic and Diluted Net Loss per Share (Details) - $ / shares	3 Months Ended		6 Months Ended
	Jun. 30, 2022	Jun. 30, 2021	Jun. 30, 2022	Jun. 30, 2021	Dec. 31, 2021
Basic and Diluted Net Loss per Share [Abstract]
Basic net loss per share (in dollars per share)	$ (0.74)	$ (0.57)	$ (1.20)	$ (1.21)
0 Percent Convertible Senior Notes [Member]
Basic and Diluted Net Loss per Share [Abstract]
Interest rate on convertible senior notes	0.00%	0.00%	0.00%	0.00%	0.00%
0.125 Percent Convertible Senior Notes [Member]
Basic and Diluted 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 and Diluted Net Loss per Share [Abstract]
Interest rate on convertible senior notes	1.00%	1.00%	1.00%	1.00%

- Definition

The amount of net income (loss) for the period per each share of common stock or unit outstanding during the reporting period.

+ References

Reference 1: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 815
-SubTopic 40
-Section 65
-Paragraph 1
-Subparagraph (e)(4)
-URI http://asc.fasb.org/extlink&oid=123482062&loc=SL123482106-238011

Reference 2: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 250
-SubTopic 10
-Section 50
-Paragraph 3
-URI http://asc.fasb.org/extlink&oid=124431687&loc=d3e22583-107794

Reference 3: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 250
-SubTopic 10
-Section 50
-Paragraph 11
-Subparagraph (b)
-URI http://asc.fasb.org/extlink&oid=124431687&loc=d3e22694-107794

Reference 4: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 260
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-Section 45
-Paragraph 10
-URI http://asc.fasb.org/extlink&oid=125511455&loc=d3e1448-109256

Reference 5: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 250
-SubTopic 10
-Section 50
-Paragraph 4
-URI http://asc.fasb.org/extlink&oid=124431687&loc=d3e22595-107794

Reference 6: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
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-Subparagraph (a)
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Reference 7: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 260
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-URI http://asc.fasb.org/extlink&oid=125511455&loc=d3e1337-109256

Reference 8: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 815
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Reference 9: http://www.xbrl.org/2003/role/exampleRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 260
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-Section 55
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-URI http://asc.fasb.org/extlink&oid=125512782&loc=d3e4984-109258

Reference 10: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 944
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-Section S99
-Paragraph 1
-Subparagraph (SX 210.7-04(23))
-URI http://asc.fasb.org/extlink&oid=120400993&loc=SL114874131-224263

Reference 11: http://www.xbrl.org/2003/role/disclosureRef
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-Name Accounting Standards Codification
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-URI http://asc.fasb.org/extlink&oid=125512782&loc=d3e3842-109258

Reference 12: http://www.xbrl.org/2003/role/disclosureRef
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-Name Accounting Standards Codification
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Reference 13: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 260
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Reference 14: http://www.xbrl.org/2003/role/disclosureRef
-Publisher FASB
-Name Accounting Standards Codification
-Topic 220
-SubTopic 10
-Section S99
-Paragraph 2
-Subparagraph (SX 210.5-03(25))
-URI http://asc.fasb.org/extlink&oid=123367319&loc=SL114868664-224227

Reference 15: http://www.xbrl.org/2003/role/disclosureRef
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-Name Accounting Standards Codification
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+ Details

Significant Accounting Policies, Convertible Debt (Details)	Jun. 30, 2022	Dec. 31, 2021	Jun. 30, 2021
0 Percent Convertible Senior Notes [Member]
Convertible Debt [Abstract]
Interest rate on convertible senior notes	0.00%	0.00%	0.00%
Effective interest rate	0.50%
0.125 Percent Convertible Senior Notes [Member]
Convertible Debt [Abstract]
Interest rate on convertible senior notes	0.125%	0.125%	0.125%
Effective interest rate	0.50%

Significant Accounting Policies, Segment Information (Details)	6 Months Ended
	Jun. 30, 2022 Segment
Segment Information [Abstract]
Number of operating segments	1

Significant Accounting Policies, Stock-Based Compensation Expense (Details)
$ / shares in Units, $ in Thousands

3 Months Ended

6 Months Ended

Jun. 30, 2022

USD ($)

Jun. 30, 2021

USD ($)

Jun. 30, 2022

USD ($)

Period

$ / shares

Jun. 30, 2021

USD ($)

$ / shares

Stock-based Compensation Expense [Abstract]

Stock-based compensation expense

$ 24,502

$ 30,022

$ 50,738

$ 67,882

Cost of Sales [Member]

Stock-based Compensation Expense [Abstract]

Stock-based compensation expense

213

182

Research, Development and Patent Expense [Member]

Stock-based Compensation Expense [Abstract]

Stock-based compensation expense

18,500

22,748

37,582

48,647

Selling, General and Administrative Expense [Member]

Stock-based Compensation Expense [Abstract]

Stock-based compensation expense

5,949

$ 7,274

12,943

$ 19,053

Stock Options [Member]

Unrecognized Compensation Expense [Abstract]

Unrecognized compensation expense related to non-vested stock options

54,300

$ 54,300

Weighted average period for recognition

1 year 3 months 18 days

Stock Options [Member] | Employees [Member]

Weighted-Average Assumptions [Abstract]

Risk-free interest rate

1.80%

0.50%

Dividend yield

0.00%

Volatility

55.10%

54.80%

Expected life

^[1]

6 years 3 months 18 days

4 years 10 months 24 days

Stock Options Granted Prior to January 1, 2022 [Member]

Weighted-Average Assumptions [Abstract]

Award term

7 years

Stock Options Granted on January 1, 2022 and Thereafter [Member]

Weighted-Average Assumptions [Abstract]

Award term

10 years

ESPP [Member]

Weighted-Average Assumptions [Abstract]

Risk-free interest rate

0.60%

0.10%

Dividend yield

0.00%

Volatility

50.20%

39.10%

Expected life

6 months

RSUs [Member]

Unrecognized Compensation Expense [Abstract]

Unrecognized compensation cost related to non-vested units

61,600

$ 61,600

Weighted average period for recognition

1 year 7 months 6 days

RSUs [Member] | Board of Directors [Member] | Minimum [Member]

RSUs and PRSUs [Abstract]

Vesting period

1 year

RSUs [Member] | Board of Directors [Member] | Maximum [Member]

RSUs and PRSUs [Abstract]

Vesting period

4 years

RSUs [Member] | Employees [Member]

RSUs and PRSUs [Abstract]

Vesting period

4 years

Weighted-average grant date fair value (in dollars per share) | $ / shares

$ 34.38

PRSUs [Member]

Unrecognized Compensation Expense [Abstract]

Unrecognized compensation cost related to non-vested units

$ 4,400

Weighted average period for recognition

1 year 4 months 24 days

PRSUs [Member] | Section 16 Officers [Member]

RSUs and PRSUs [Abstract]

Number of performance periods | Period

Vesting period

3 years

Number of units guaranteed to vest (in shares) | shares

Weighted-average grant date fair value (in dollars per share) | $ / shares

$ 42.28

$ 77.17

PRSUs [Member] | Section 16 Officers [Member] | Minimum [Member]

RSUs and PRSUs [Abstract]

Percentage of units guaranteed to vest

0.00%

PRSUs [Member] | Section 16 Officers [Member] | Maximum [Member]

RSUs and PRSUs [Abstract]

Percentage of units guaranteed to vest

150.00%

PRSUs [Member] | Section 16 Officers [Member] | One-Year Period [Member]

RSUs and PRSUs [Abstract]

Vesting percentage

33.30%

PRSUs [Member] | Section 16 Officers [Member] | Two-Year Period [Member]

RSUs and PRSUs [Abstract]

Vesting percentage

33.30%

PRSUs [Member] | Section 16 Officers [Member] | Three-Year Period [Member]

RSUs and PRSUs [Abstract]

Vesting percentage

33.30%

[1]

Investments, Contract Maturity of Available-for-Sale Securities (Details)	6 Months Ended
	Jun. 30, 2022
Contract Maturity of Available-for-Sale Securities [Abstract]
One year or less	68.00%
After one year but within two years	26.00%
After two years but within three and a half years	6.00%
Total	100.00%
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
Percentage of available-for-sale securities with a maturity of less than two years	94.00%

Investments, Summary of Investments (Details)
$ in Thousands

6 Months Ended

Jun. 30, 2022

USD ($)

Company

Dec. 31, 2021

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

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

Amortized cost

$ 1,032,687

$ 612,557

Gross unrealized gains

792

Gross unrealized losses

(7,088)

(345)

Estimated fair value

1,025,638

613,004

Available-for-sale Securities with Maturity of More Than One Year [Abstract]

Amortized cost

514,406

638,615

Gross unrealized gains

471

Gross unrealized losses

(16,841)

(3,966)

Estimated fair value

497,629

635,120

Available-for-sale Securities [Abstract]

Amortized cost

1,547,093

1,251,172

Gross unrealized gains

103

1,263

Gross unrealized losses

(23,929)

(4,311)

Estimated fair value

1,523,267

1,248,124

Equity Securities [Abstract]

Amortized cost

35,012

27,512

Gross unrealized gains

17,257

23,852

Gross unrealized losses

(7,159)

(837)

Estimated fair value

45,110

50,527

Available-for-sale and Equity Securities [Abstract]

Amortized cost

1,582,105

1,278,684

Gross unrealized gains

17,360

25,115

Gross unrealized losses

(31,088)

(5,148)

Estimated fair value

1,568,377

1,298,651

Corporate Debt Securities [Member]

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

Amortized cost

^[1]

481,866

383,870

Gross unrealized gains

728

Gross unrealized losses

(3,749)

(226)

Estimated fair value

478,121

384,372

Available-for-sale Securities with Maturity of More Than One Year [Abstract]

Amortized cost

294,276

382,000

Gross unrealized gains

331

Gross unrealized losses

(11,542)

(2,644)

Estimated fair value

282,735

379,687

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

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

Amortized cost

55,207

48,493

Gross unrealized gains

Gross unrealized losses

(927)

(18)

Estimated fair value

54,280

48,494

Available-for-sale Securities with Maturity of More Than One Year [Abstract]

Amortized cost

35,545

72,935

Gross unrealized gains

Gross unrealized losses

(1,451)

(561)

Estimated fair value

34,094

72,374

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

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

Amortized cost

^[1]

340,480

45,424

Gross unrealized gains

Gross unrealized losses

(1,829)

(64)

Estimated fair value

338,685

45,360

Available-for-sale Securities with Maturity of More Than One Year [Abstract]

Amortized cost

158,476

137,635

Gross unrealized gains

139

Gross unrealized losses

(3,100)

(500)

Estimated fair value

155,437

137,274

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

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

Amortized cost

148,750

134,770

Gross unrealized gains

Gross unrealized losses

(493)

(37)

Estimated fair value

148,258

134,778

Available-for-sale Securities with Maturity of More Than One Year [Abstract]

Amortized cost

26,109

39,909

Gross unrealized gains

Gross unrealized losses

(748)

(224)

Estimated fair value

25,363

39,686

Other Municipal Debt Securities [Member]

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

Amortized cost

6,384

Gross unrealized gains

Gross unrealized losses

(90)

Estimated fair value

6,294

Available-for-sale Securities with Maturity of More Than One Year [Abstract]

Amortized cost

6,136

Gross unrealized gains

Gross unrealized losses

(37)

Estimated fair value

6,099

Publicly Traded Equity Securities [Member]

Equity Securities [Abstract]

Amortized cost

^[2]

11,897

Gross unrealized gains

7,145

Gross unrealized losses

(7,159)

(837)

Estimated fair value

4,738

18,205

Available-for-sale and Equity Securities [Abstract]

Unrealized loss on equity investment

(13,500)

Privately Held Equity Securities [Member]

Equity Securities [Abstract]

Amortized cost

^[3]

23,115

15,615

Gross unrealized gains

17,257

16,707

Gross unrealized losses

Estimated fair value

$ 40,372

$ 32,322

[1]	Includes investments classified as cash equivalents on our condensed consolidated balance sheet.
[2]	Our equity securities included in other current assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value. In the six months ended June 30, 2022, we recognized a $13.5 million unrealized loss in our condensed consolidated statement of operations related to a decrease in the fair value of our investments in publicly traded companies.
[3]	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	Jun. 30, 2022 USD ($) Investment
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	845
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 1,310,175
More than 12 months of temporary impairment	76,946
Total temporary impairment	1,387,121
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(21,736)
More than 12 months of temporary impairment	(2,193)
Total temporary impairment	$ (23,929)
Corporate Debt Securities [Member]
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	380
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 703,643
More than 12 months of temporary impairment	42,106
Total temporary impairment	745,749
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(14,199)
More than 12 months of temporary impairment	(1,092)
Total temporary impairment	$ (15,291)
Debt Securities Issued by U.S. Government Agencies [Member]
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	11
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 65,974
More than 12 months of temporary impairment	14,400
Total temporary impairment	80,374
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(1,781)
More than 12 months of temporary impairment	(597)
Total temporary impairment	$ (2,378)
Debt Securities Issued by the U.S. Treasury [Member]
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	48
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 420,076
More than 12 months of temporary impairment	4,837
Total temporary impairment	424,913
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(4,767)
More than 12 months of temporary impairment	(162)
Total temporary impairment	$ (4,929)
Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	403
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 119,174
More than 12 months of temporary impairment	10,617
Total temporary impairment	129,791
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(975)
More than 12 months of temporary impairment	(266)
Total temporary impairment	$ (1,241)
Other Municipal Debt Securities [Member]
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	3
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 1,308
More than 12 months of temporary impairment	4,986
Total temporary impairment	6,294
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(14)
More than 12 months of temporary impairment	(76)
Total temporary impairment	$ (90)

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

Jun. 30, 2022

Dec. 31, 2021

Jun. 30, 2021

Fair Value Measurements [Abstract]

Available-for-sale securities

$ 1,523,267

$ 1,248,124

Equity securities

$ 45,110

$ 50,527

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%

Publicly Traded Equity Securities [Member]

Fair Value Measurements [Abstract]

Equity securities

$ 4,738

$ 18,205

Privately Held Equity Securities [Member]

Fair Value Measurements [Abstract]

Equity securities

40,372

32,322

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

Fair Value Measurements [Abstract]

Fair value of convertible notes

485,200

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

Fair Value Measurements [Abstract]

Fair value of convertible notes

577,000

Recurring Basis [Member]

Fair Value Measurements [Abstract]

Cash equivalents

^[1]

409,877

541,199

Total

1,978,254

1,839,850

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

Fair Value Measurements [Abstract]

Available-for-sale securities

^[2]

760,856

764,059

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

Fair Value Measurements [Abstract]

Available-for-sale securities

^[2]

88,374

120,868

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

Fair Value Measurements [Abstract]

Available-for-sale securities

^[2]

494,122

182,634

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

173,621

^[3]

174,464

^[4]

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

Fair Value Measurements [Abstract]

Available-for-sale securities

23,400

2,300

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

Fair Value Measurements [Abstract]

Available-for-sale securities

^[2]

6,294

6,099

Recurring Basis [Member] | Publicly Traded Equity Securities [Member]

Fair Value Measurements [Abstract]

Equity securities

4,738

18,205

Recurring Basis [Member] | Privately Held Equity Securities [Member]

Fair Value Measurements [Abstract]

Equity securities

40,372

32,322

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

Fair Value Measurements [Abstract]

Cash equivalents

409,877

541,199

Total

904,375

727,708

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

494,122

182,634

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] | Quoted Prices in Active Markets (Level 1) [Member] | Publicly Traded Equity Securities [Member]

Fair Value Measurements [Abstract]

Equity securities

376

3,875

Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Privately Held Equity Securities [Member]

Fair Value Measurements [Abstract]

Equity securities

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

Fair Value Measurements [Abstract]

Cash equivalents

Total

1,029,145

1,065,490

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

Fair Value Measurements [Abstract]

Available-for-sale securities

760,856

764,059

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

88,374

120,868

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

173,621

174,464

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

Fair Value Measurements [Abstract]

Available-for-sale securities

6,294

6,099

Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Publicly Traded Equity Securities [Member]

Fair Value Measurements [Abstract]

Equity securities

Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Privately Held Equity Securities [Member]

Fair Value Measurements [Abstract]

Equity securities

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

Fair Value Measurements [Abstract]

Cash equivalents

Total

44,734

46,652

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

Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Publicly Traded Equity Securities [Member]

Fair Value Measurements [Abstract]

Equity securities

4,362

14,330

Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Privately Held Equity Securities [Member]

Fair Value Measurements [Abstract]

Equity securities

$ 40,372

$ 32,322

[1]	Included in cash and cash equivalents on our condensed consolidated balance sheet.
[2]	Included in short-term investments.
[3]	$23.4 million was 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.
[4]	$2.3 million was 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.

Income Taxes (Details) - USD ($) $ in Thousands	3 Months Ended		6 Months Ended
Income Taxes (Details) - USD ($) $ in Thousands	Jun. 30, 2022	Jun. 30, 2021	Jun. 30, 2022	Jun. 30, 2021
Income Taxes [Abstract]
Amortization period for research and development expenditures under IRC Section 174			5 years
Income tax expense	$ 2,260	$ 327	$ 3,354	$ 457

- Definition

Amount of current income tax expense (benefit) and deferred income tax expense (benefit) pertaining to continuing operations.

+ References + Details

Collaborative Arrangements and Licensing Agreements, Biogen (Details) $ in Thousands	1 Months Ended	3 Months Ended			6 Months Ended
	Jul. 31, 2022 USD ($)	Jun. 30, 2022 USD ($)	Mar. 31, 2022 USD ($) Target	Jun. 30, 2021 USD ($)	Jun. 30, 2022 USD ($)	Jun. 30, 2021 USD ($)	Dec. 31, 2021 USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		$ 133,791		$ 125,750	$ 275,710	$ 237,357
SPINRAZA Royalties [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		59,627		72,168	113,444	132,154
R&D Revenue [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		55,607		39,889	125,242	67,048
Biogen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received		3,300,000			3,300,000
Revenue		76,900		$ 100,000	170,800	$ 178,100
Deferred revenue		$ 368,300			$ 368,300		$ 407,500
Biogen [Member] \| Revenue [Member] \| Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage		58.00%		80.00%	62.00%	75.00%
Biogen [Member] \| SPINRAZA Royalties [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		$ 59,600		$ 72,200	$ 113,400	$ 132,200
Biogen [Member] \| R&D Revenue [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		$ 17,300		$ 27,800	$ 57,400	$ 45,900
2013 Strategic Neurology [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue			$ 18,000
Number of targets advanced \| Target			2
2013 Strategic Neurology [Member] \| Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 9,000
2013 Strategic Neurology [Member] \| Maximum [Member] \| Plan [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next prospective payment	$ 10,000

Collaborative Arrangements and Licensing Agreements, Roche (Details) $ in Thousands	1 Months Ended	3 Months Ended		6 Months Ended
	Jul. 31, 2022 USD ($)	Jun. 30, 2022 USD ($) Agreement Indication	Jun. 30, 2021 USD ($)	Jun. 30, 2022 USD ($) Agreement Indication	Jun. 30, 2021 USD ($)	Dec. 31, 2021 USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		$ 133,791	$ 125,750	$ 275,710	$ 237,357
R&D Revenue [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		$ 55,607	39,889	$ 125,242	67,048
Roche [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements \| Agreement		2		2
Revenue		$ 19,500	$ 3,600	$ 23,900	$ 7,500
Deferred revenue		29,700		29,700		$ 31,600
Roche [Member] \| Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received		$ 245,000		$ 245,000
Roche [Member] \| Revenue [Member] \| Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage		15.00%	3.00%	9.00%	3.00%
IONIS-FB-L for Complement-Mediated Diseases [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements \| Agreement		1		1
Number of disease indications \| Indication		2		2
Revenue		$ 13,800
Milestone payment received and added to transaction price		$ 20,000
IONIS-FB-L for Complement-Mediated Diseases [Member] \| Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable for development milestones	$ 145,000
Maximum amount of payments receivable for regulatory milestones	279,000
Maximum amount of payments receivable for sales-related milestones	280,000
Revenue	35,000
IONIS-FB-L for Complement-Mediated Diseases [Member] \| Maximum [Member] \| Plan [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next prospective milestone	$ 90,000
IONIS-FB-L for Complement-Mediated Diseases [Member] \| Maximum [Member] \| Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Royalty percentage received on net sales of medicine	20.00%
IONIS-FB-L for Complement-Mediated Diseases [Member] \| GA [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of disease indications \| Indication		1		1
IONIS-FB-L for Complement-Mediated Diseases [Member] \| IgAN [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of disease indications \| Indication		1		1
Huntington's Disease [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements \| Agreement		1		1

Convertible Debt (Details) - USD ($) $ / shares in Units, $ in Thousands, shares in Millions	1 Months Ended			3 Months Ended	6 Months Ended
	Nov. 30, 2021	Apr. 30, 2021	Dec. 31, 2019	Jun. 30, 2021	Jun. 30, 2022	Jun. 30, 2021	Dec. 31, 2021
Convertible Debt [Abstract]
Repurchase of convertible notes					$ 0	$ 256,963
Cost of call spread		$ 46,900	$ 52,600
Purchase of note hedges		136,700	108,700		0	136,620
Proceeds from issuance of warrants		89,800	$ 56,100		0	89,752
Loss on early retirement of debt					0	$ (8,627)
0% Notes [Member]
Convertible Debt [Abstract]
Face amount of offering		632,500
Outstanding principal balance					632,500
Unamortized debt issuance costs					$ 11,800
Maturity date					Apr. 30, 2026
Interest rate				0.00%	0.00%	0.00%	0.00%
Effective interest rate					0.50%
Conversion price per share (in dollars per share)					$ 57.84
Effective conversion price per share with call spread (in dollars per share)					$ 76.39
Total shares of common stock subject to conversion (in shares)					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
Unamortized debt issuance costs					$ 5,400
Maturity date					Dec. 31, 2024
Interest rate				0.125%	0.125%	0.125%	0.125%
Effective interest rate					0.50%
Conversion price per share (in dollars per share)					$ 83.28
Effective conversion price per share with call spread (in dollars per share)					$ 123.38
Total shares of common stock subject to conversion (in shares)					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	$ 62,000	$ 257,000
Interest rate				1.00%	1.00%	1.00%
Loss on early retirement of debt				$ 8,600

Legal Proceedings (Details) - John Makris, et al. v. Ionis Pharmaceuticals, Inc., et al. [Member] $ in Millions		1 Months Ended	3 Months Ended	6 Months Ended
	Aug. 05, 2021 Plaintiff	Jul. 31, 2022 USD ($)	Jun. 30, 2022 USD ($)	Jun. 30, 2022 USD ($)
Legal Procedings [Abstract]
Number of plaintiffs \| Plaintiff	4
Legal reserve for proposed litigation settlement			$ 12.5	$ 12.5
Subsequent Event [Member]
Legal Procedings [Abstract]
Contribution to settlement agreement by insurance carrier		$ 4.5
Other Expense [Member]
Legal Procedings [Abstract]
Litigation settlement expense			$ 12.5	$ 12.5