Ionis Pharmaceuticals (IONS) 10-K21 Feb 242023 FY Annual reportFinancial data

Company Profile

Document and Entity Information

Document and Entity Information - USD ($)	12 Months Ended
Document and Entity Information - USD ($)	Dec. 31, 2023	Feb. 15, 2024	Jun. 30, 2023
Cover [Abstract]
Document Type	10-K
Amendment Flag	false
Document Annual Report	true
Document Period End Date	Dec. 31, 2023
Current Fiscal Year End Date	--12-31
Document Fiscal Year Focus	2023
Document Fiscal Period Focus	FY
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 Well-known Seasoned Issuer	Yes
Entity Voluntary Filers	No
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
ICFR Auditor Attestation Flag	true
Document Financial Statement Error Correction [Flag]	false
Entity Shell Company	false
Entity Public Float			$ 4,243,321,410
Entity Common Stock, Shares Outstanding		145,751,797
Auditor Firm ID	42
Auditor Name	Ernst & Young LLP
Auditor Location	San Diego, California

CONSOLIDATED BALANCE SHEETS

CONSOLIDATED BALANCE SHEETS - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Current assets:
Cash and cash equivalents	$ 399,266	$ 276,472
Short-term investments	1,931,935	1,710,397
Contracts receivable	97,778	25,538
Inventories	28,425	22,033
Other current assets	184,449	168,254
Total current assets	2,641,853	2,202,694
Property, plant and equipment, net	71,043	74,294
Right-of-use assets	171,896	181,544
Deposits and other assets	105,280	75,344
Total assets	2,990,072	2,533,876
Current liabilities:
Accounts payable	26,027	17,921
Accrued compensation	67,727	49,178
Accrued liabilities	147,894	140,101
Income taxes payable	2,151	6,249
0.125 percent convertible senior notes, net	44,332	0
Current portion of deferred contract revenue	151,128	90,577
Other current liabilities	8,831	7,535
Total current liabilities	448,090	311,561
Long-term deferred contract revenue	241,184	287,768
Liability related to sale of future royalties, net	513,736	0
Long-term lease liabilities	170,875	178,941
Long-term obligations	41,836	15,973
Total liabilities	2,603,386	1,960,989
Stockholders' equity:
Common stock, $0.001 par value; 300,000,000 shares authorized, 144,340,526 and 142,057,736 shares issued and outstanding at December 31, 2023 and December 31, 2022, respectively	144	142
Additional paid-in capital	2,215,098	2,059,850
Accumulated other comprehensive loss	(32,645)	(57,480)
Accumulated deficit	(1,795,911)	(1,429,625)
Total stockholders' equity	386,686	572,887
Total liabilities and stockholders' equity	2,990,072	2,533,876
1.75 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	562,285	0
0 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	625,380	622,242
0.125 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	$ 0	$ 544,504

CONSOLIDATED BALANCE SHEETS (Pa

CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares	Dec. 31, 2023	Dec. 31, 2022
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)	144,340,526	142,057,736
Common stock, shares outstanding (in shares)	144,340,526	142,057,736
1.75 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	1.75%	1.75%
0 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	0%	0%
0.125 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	0.125%	0.125%

CONSOLIDATED STATEMENTS OF OPER

CONSOLIDATED STATEMENTS OF OPERATIONS - USD ($) shares in Thousands, $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Revenue:
Revenue	$ 787,647	$ 587,367	$ 810,456
Expenses:
Cost of sales	9,133	14,116	10,842
Research, development and patent	899,625	833,147	643,453
Selling, general and administrative	232,619	150,295	186,347
Total operating expenses	1,141,377	997,558	840,642
Loss from operations	(353,730)	(410,191)	(30,186)
Other income (expense):
Investment income	89,041	25,331	10,044
Interest expense	(12,660)	(8,122)	(9,349)
Interest expense related to sale of future royalties	(68,797)	0	0
Gain (loss) on investments	(1,914)	(7,333)	10,103
Gain (loss) on sale of real estate assets	(161)	149,604	0
Other income (expense)	14,256	(7,274)	(9,760)
Loss before income tax benefit (expense)	(333,965)	(257,985)	(29,148)
Income tax benefit (expense)	(32,321)	(11,737)	551
Net loss	$ (366,286)	$ (269,722)	$ (28,597)
Basic net loss per share (in dollars per share)	$ (2.56)	$ (1.9)	$ (0.2)
Shares used in computing basic net loss per share (in shares)	143,190	141,848	141,021
Diluted net loss per share (in dollars per share)	$ (2.56)	$ (1.9)	$ (0.2)
Shares used in computing diluted net loss per share (in shares)	143,190	141,848	141,021
Commercial Revenue [Member]
Revenue:
Revenue	$ 308,591	$ 303,358	$ 342,395
SPINRAZA Royalties [Member]
Revenue:
Revenue	240,379	242,314	267,776
Other Commercial Revenue [Member]
Revenue:
Revenue	68,212	61,044	74,619
Research and Development Revenue [Member]
Revenue:
Revenue	479,056	284,009	468,061
Collaborative Agreement Revenue [Member]
Revenue:
Revenue	352,657	207,222	468,061
WAINUA Joint Development Revenue [Member]
Revenue:
Revenue	$ 126,399	$ 76,787	$ 0

CONSOLIDATED STATEMENTS OF COMP

CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS [Abstract]
Net loss	$ (366,286)	$ (269,722)	$ (28,597)
Unrealized gains (losses) on investments, net of tax	24,484	(24,395)	(11,486)
Currency translation adjustment	351	(417)	(111)
Comprehensive loss	$ (341,451)	$ (294,534)	$ (40,194)

CONSOLIDATED STATEMENTS OF STOC

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	(28,597)	(28,597)
Change in unrealized gains (losses), net of tax	0	0	(11,486)	0	(11,486)
Foreign currency translation	0	0	(111)	0	(111)
Issuance of common stock in connection with employee stock plans	$ 1	11,563	0	0	11,564
Issuance of common stock in connection with employee stock plans (in shares)	1,132
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	120,678	0	0	120,678
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	$ 0	(16,725)	0	0	(16,725)
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)	(288)
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	(269,722)	(269,722)
Change in unrealized gains (losses), net of tax	0	0	(24,395)	0	(24,395)
Foreign currency translation	0	0	(417)	0	(417)
Issuance of common stock in connection with employee stock plans	$ 1	6,372	0	0	6,373
Issuance of common stock in connection with employee stock plans (in shares)	1,194
Stock-based compensation expense	$ 0	100,264	0	0	100,264
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	$ 0	(10,953)	0	0	(10,953)
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)	(346)
Balance at Dec. 31, 2022	$ 142	2,059,850	(57,480)	(1,429,625)	572,887
Balance (in shares) at Dec. 31, 2022	142,058
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(366,286)	(366,286)
Change in unrealized gains (losses), net of tax	0	0	24,484	0	24,484
Foreign currency translation	0	0	351	0	351
Issuance of common stock in connection with employee stock plans	$ 2	49,439	0	0	49,441
Issuance of common stock in connection with employee stock plans (in shares)	2,283
Stock-based compensation expense	$ 0	105,809	0	0	105,809
Balance at Dec. 31, 2023	$ 144	$ 2,215,098	$ (32,645)	$ (1,795,911)	$ 386,686
Balance (in shares) at Dec. 31, 2023	144,341

CONSOLIDATED STATEMENTS OF CASH

CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Operating activities:
Net loss	$ (366,286)	$ (269,722)	$ (28,597)
Adjustments to reconcile net loss to net cash provided by (used in) operating activities:
Depreciation	10,292	14,328	15,487
Amortization of right-of-use operating lease assets	9,647	5,362	1,721
Amortization of other assets	2,559	2,415	2,352
Amortization of premium (discount) on investments, net	(28,885)	7,389	17,776
Amortization of debt issuance costs	6,330	5,373	4,958
Non-cash royalty revenue related to sale of royalties	(44,628)	0	0
Non-cash interest related to sale of future royalties	68,238	0	0
Stock-based compensation expense	105,809	100,264	120,678
Loss (gain) on early retirement of debt	(13,389)	0	8,627
Non-cash losses related to disposal of property, plant and equipment	16,649	531	0
Loss (gain) on sale of real estate assets	161	(150,135)	0
Loss (gain) on investments	1,589	224	(1,092)
Non-cash losses related to other assets	1,661	2,030	2,707
Changes in operating assets and liabilities:
Contracts receivable	(72,059)	36,358	14,308
Inventories	(6,392)	2,773	(2,841)
Other current and long-term assets	(29,840)	(24,682)	(877)
Accounts payable	8,119	1,094	(6,000)
Income taxes	(4,098)	6,213	(280)
Accrued compensation	18,549	10,368	(26,918)
Accrued liabilities and other current liabilities	(5,506)	46,695	(8,381)
Deferred contract revenue	13,967	(71,248)	(82,829)
Net cash provided by (used in) operating activities	(307,513)	(274,370)	30,799
Investing activities:
Purchases of short-term investments	(1,770,814)	(1,485,772)	(1,124,193)
Proceeds from sale of short-term investments	1,584,676	989,152	1,344,185
Purchases of property, plant and equipment	(23,805)	(15,721)	(11,955)
Proceeds from sale of real estate assets	22	254,083	0
Acquisition of licenses and other assets, net	(4,206)	(4,378)	(5,946)
Purchases of strategic investments	0	0	(7,185)
Net cash provided by (used in) investing activities	(214,127)	(262,636)	194,906
Financing activities:
Proceeds from equity, net	49,442	6,373	11,565
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	0	(10,953)	(16,725)
Proceeds from sale of future royalties	500,000	0	0
Payments of transaction costs related to sale of future royalties	(10,434)	(29)	0
Proceeds from real estate transaction	32,352	0	0
Repayment of remaining principal amount of 1 percent convertible senior notes at maturity	0	0	(61,967)
Proceeds from issuance of warrants	0	0	89,752
Purchase of note hedges	0	0	(136,620)
Principal payments on debt	(160)	(50,686)	0
Net cash provided by (used in) financing activities	644,082	(55,295)	245,933
Effects of exchange rates on cash	352	(418)	(111)
Net increase (decrease) in cash and cash equivalents	122,794	(592,719)	471,527
Cash and cash equivalents at beginning of year	276,472	869,191	397,664
Cash and cash equivalents at end of year	399,266	276,472	869,191
Supplemental disclosures of cash flow information:
Interest paid	6,512	2,898	4,778
Income taxes paid	48,334	5,010	38
Supplemental disclosures of non-cash investing and financing activities:
Right-of-use assets obtained in exchange for lease liabilities	0	168,931	6,641
Amounts accrued for capital and patent expenditures	172	4,767	705
1.75 Percent Convertible Senior Notes [Member]
Financing activities:
Proceeds from issuance of convertible senior notes	575,000	0	0
Convertible senior notes issuance costs	(14,175)	0	0
0.125 Percent Convertible Senior Notes [Member]
Financing activities:
Repurchase of convertible senior notes	(487,943)	0	0
Repayment of remaining principal amount of 1 percent convertible senior notes at maturity	(504,400)
0 Percent Convertible Senior Notes [Member]
Financing activities:
Proceeds from issuance of convertible senior notes	0	0	632,500
Convertible senior notes issuance costs	0	0	(15,609)
Proceeds from issuance of warrants			89,800
Purchase of note hedges			(136,700)
1 Percent Convertible Senior Notes [Member]
Financing activities:
Repurchase of convertible senior notes	$ 0	$ 0	(256,963)
Repayment of remaining principal amount of 1 percent convertible senior notes at maturity			$ (309,900)

CONSOLIDATED STATEMENTS OF CA_2

CONSOLIDATED STATEMENTS OF CASH FLOWS (Parenthetical) - USD ($) $ in Millions	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021	Apr. 30, 2021	Dec. 31, 2019
1.75 Percent Convertible Senior Notes [Member]
Financing activities:
Interest rate on convertible senior notes	1.75%	1.75%
0.125 Percent Convertible Senior Notes [Member]
Financing activities:
Interest rate on convertible senior notes	0.125%	0.125%	0.125%		0.125%
Principal amount repurchased	$ 504.4
0 Percent Convertible Senior Notes [Member]
Financing activities:
Interest rate on convertible senior notes	0%	0%	0%	0%
1 Percent Convertible Senior Notes [Member]
Financing activities:
Interest rate on convertible senior notes	1%		1%
Principal amount repurchased			$ 247.9		$ 375.6

Organization and Significant Ac

Organization and Significant Accounting Policies	12 Months Ended
Organization and Significant Accounting Policies	Dec. 31, 2023
Organization and Basis of Presentation [Abstract]
Organization and Significant Accounting Policies	1. Organization and Significant Accounting Policies Basis of Presentation In our 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”). Organization and Business Activity We incorporated in California on January 10, 1989. In conjunction with our IPO, we reorganized as a Delaware corporation in April 1991. We were organized principally to develop human therapeutic medicines using antisense technology. In December 2015, we changed our name from Isis Pharmaceuticals, Inc. to Ionis Pharmaceuticals, Inc. Use of Estimates We prepare our consolidated financial statements in conformity with accounting principles generally accepted in the United States, or U.S., that require us to make estimates and assumptions that affect the amounts reported in our consolidated financial statements and accompanying notes. Actual results could differ from our estimates. Revenue Recognition 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 within deferred revenue in our consolidated balance sheets. 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 ASC Topic 808, Collaborative Arrangements ASC 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 that contain multiple elements, we determine which elements of the collaboration reflect a vendor-customer relationship and therefore are within the scope of ASC , 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 We evaluate the income statement classification for presentation of amounts due from or owed to other participants associated with multiple activities in a collaboration arrangement based on the nature of each separate activity. For example, in our WAINUA collaboration with AstraZeneca, we recognize funding received from AstraZeneca for co-development activities as revenue; while we recognize cost sharing payments to and from AstraZeneca associated with co-commercialization activities and co-medical affairs activities as selling, general and administrative, or SG&A, expense and research and development, or R&D, expense, respectively. 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: 1. 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. 2. Identify the performance obligations We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the contract. We may 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. When a partner exercises its option to license a medicine that was not previously determined to be a material right at the inception of the agreement 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. 3. 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 that 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. 4. 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 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 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. 5. Recognize revenue We recognize revenue in of 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. We recognize royalty revenue 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. Under our distribution agreements with Swedish Orphan Biovitrum AB, or 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. 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: 1) If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and 2) 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-effect 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. Refer to Note 4, Collaborative Arrangements and Licensing Agreements 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 December 31, 2023, approximately 87.8 percent of our contracts receivables were from one significant customer. As of December 31, 2022, approximately 82.5 percent of our contracts receivables were from one significant customer. 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 in our consolidated balance sheets. 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 in our consolidated balance sheets. Cost of Sales Our cost of sales is comprised of costs related to our commercial revenue, including 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. Research, Development and Patent Expenses Our research, development and patent expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs, patents and other expenses that are directly related to our R&D operations. We expense R&D costs as we incur them. When we make payments for R&D services prior to the services being rendered, we record those amounts as prepaid assets in our consolidated balance sheets and we expense them as the services are provided. A portion of the costs included in R&D expenses are costs associated with our partner agreements. In 2023, 2022 and 2021, patent expenses were $4.3 million, $4.7 million and $5.3 million, respectively. 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. Basic and Diluted Net Loss per Share Basic net loss per share We compute basic net loss per share by dividing our net loss by our weighted-average number of common shares outstanding during the period. Diluted net loss per share For the years ended December 31, 2023, 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 Notes; ● Note hedges related to the Notes; ● 0.125 percent convertible senior notes, or Notes; ● Note hedges related to the 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 year ended December 31, 2023, common stock underlying the 1.75 percent convertible senior notes, or 1.75% Notes, would also have had an anti-dilutive effect on net loss per share. Additionally as of December 31, 2023, 2022 and 2021, we had warrants related to our 0% Notes 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. 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 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 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. Stock Options and Stock Purchase Rights: 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. The expected term of stock options granted represents the period of time that we expect them to be outstanding. Historically, we estimated the expected term of options granted based on historical exercise patterns. In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or 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 years ended December 31, 2023 and 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. 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 we granted to our board of directors after June 2020 fully vest after one year. 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 PRSUs we granted in 2020 through 2022, one third Under the terms of the PRSUs we granted in 2023, 100 percent of the PRSUs may vest at the end of the three-year performance period based on our relative TSR as compared to a peer group of companies and as measured at the end of the 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 to 200 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. Refer to Note 8, Stockholders’ Equity, Concentration of Credit Risk Financial instruments that potentially subject us to concentrations of credit risk consist primarily of cash equivalents, short-term investments and receivables. We place our cash equivalents and short-term investments with reputable financial institutions. We primarily invest our excess cash in commercial paper and debt instruments of the U.S. Treasury, financial institutions, corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody’s, Standard & Poor’s, or S&P, or Fitch, respectively. We have established guidelines relative to diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity. Fair Value Measurements We have estimated the fair value of our financial instruments. The amounts reported for cash, accounts receivable, accounts payable and accrued expenses approximate the fair value because of their short maturities. We report our investment securities at their estimated fair value based on quoted market prices for identical or similar instruments. 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 traded biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify most of our securities as Level 2. We obtain the fair value of our Level 2 investments from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value to the fair value based on observable market prices. 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 consolidated statements 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 public and private biotechnology companies that we received as part of a technology license or partner agreement. At December 31, 2023, we held equity investments in three publicly traded companies and seven 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 consolidated statements of operations. We account for our equity investments in publicly traded companies at their listed stock price. 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. Inventories We reflect our inventory in our consolidated balance sheets 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. Property, Plant and Equipment We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which we determine as the following (in years): Estimated Useful Lives Computer software, laboratory, manufacturing and other equipment 3 to 10 Building, building improvements and building systems 15 to 40 Land improvements 20 Leasehold improvements 5 to 15 Furniture and fixtures 5 to 10 We depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term. We evaluate long-lived assets, which include property, plant and equipment, 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. Accrued Liabilities 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. 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 815-15 and we did not issue our convertible debt instruments at a substantial premium. We record debt issuance costs as contra-liabilities in our consolidated balance sheets at i

Supplemental Financial Data

Supplemental Financial Data	12 Months Ended
Supplemental Financial Data	Dec. 31, 2023
Supplemental Financial Data [Abstract]
Supplemental Financial Data	2. Supplemental Financial Data Inventories Our inventory consisted of the following (in thousands): December 31, 2023 2022 Raw materials: Raw materials- clinical $ 20,985 $ 17,061 Raw materials- commercial 1,809 2,699 Total raw materials 22,794 19,760 Work in process 5,477 2,109 Finished goods 154 164 Total inventory $ 28,425 $ 22,033 Property, Plant and Equipment Our property, plant and equipment consisted of the following (in thousands): December 31, 2023 2022 Computer software, laboratory, manufacturing and other equipment $ 79,885 $ 74,351 Building, building improvements and building systems 41,228 41,158 Leasehold improvements 28,276 28,357 Furniture and fixtures 9,844 9,575 159,233 153,441 Less: Accumulated depreciation (96,759 ) (87,716 ) 62,474 65,725 Land 8,569 8,569 Total $ 71,043 $ 74,294 Accrued Liabilities Our accrued liabilities consisted of the following (in thousands): December 31, 2023 2022 Clinical expenses $ 105,967 $ 116,460 In-licensing expenses 7,454 7,945 Commercial expenses 4,875 3,498 Other miscellaneous expenses 29,598 12,198 Total accrued liabilities $ 147,894 $ 140,101

Revenues

Revenues	12 Months Ended
Revenues	Dec. 31, 2023
Revenues [Abstract]
Revenues	3. Revenues During the years ended December 31, , and Year Ended December 31, 2023 2022 2021 Revenue: Commercial revenue: SPINRAZA royalties $ 240,379 $ 242,314 $ 267,776 Other commercial revenue: TEGSEDI and WAYLIVRA revenue, net 34,913 30,051 55,500 Licensing and other royalty revenue 33,299 30,993 19,119 Total other commercial revenue 68,212 61,044 74,619 Total commercial revenue 308,591 303,358 342,395 Research and development revenue: Collaborative agreement revenue 352,657 207,222 468,061 WAINUA joint development revenue 126,399 76,787 — Total research and development revenue 479,056 284,009 468,061 Total revenue $ 787,647 $ 587,367 $ 810,456 Revenue Sources The following are sources of revenue and when we typically recognize revenue. 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 earn royalty revenue on net sales of QALSODY which is included in Licensing and other royalty revenue. Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net We earn commercial revenue from TEGSEDI and WAYLIVRA sales under our distribution agreements with . In addition, we receive royalties from Collaborative Arrangements and Licensing Agreements Research and development revenue under collaboration agreements We 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, R&D services and manufacturing services. 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. Milestone payments: We include variable 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, when we achieve a milestone payment from a partner for advancing a clinical study under a collaboration agreement, we add the milestone payment to the transaction price if the milestone relates to an ongoing R&D services performance obligation and recognize revenue related to the milestone payment over our estimated period of performance. If we have partially completed our performance obligation, then we record a cumulative-effect adjustment in the period we add the milestone payment to the transaction price. 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. License fees: We 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 who has full use of the license and we do not have any additional performance obligations related to the license after delivery. 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. WAINUA (Eplontersen) Collaboration with AstraZeneca In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize WAINUA for the treatment of transthyretin amyloidosis, or ATTR. We jointly developed and are preparing to commercialize WAINUA with AstraZeneca in the U.S. We initially granted AstraZeneca exclusive rights to commercialize WAINUA outside the U.S., except for certain Latin American countries. In July 2023, we expanded those rights to include Latin America. Under the terms of the agreement, we received a $200 million upfront payment in 2021. We evaluated our WAINUA 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 currently 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 WAINUA 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.

Collaborative Arrangements and

Collaborative Arrangements and Licensing Agreements	12 Months Ended
Collaborative Arrangements and Licensing Agreements	Dec. 31, 2023
Collaborative Arrangements and Licensing Agreements [Abstract]
Collaborative Arrangements and Licensing Agreements	4. Collaborative Arrangements and Licensing Agreements Strategic Partnership Biogen We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. Under our 2013 strategic neurology collaboration, Biogen developed QALSODY (tofersen), our medicine that received accelerated approval in the U.S. to treat patients with superoxide dismutase 1 amyotrophic lateral sclerosis, or SOD1-ALS. In addition, we and Biogen are currently developing numerous other investigational medicines to treat neurodegenerative diseases, including medicines in development to treat people with amyotrophic lateral sclerosis, or ALS, SMA, Angelman Syndrome, or AS, Alzheimer’s disease, or AD, and Parkinson’s disease, or PD. 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 December 31, 2023, we have received nearly $3.8 billion from our Biogen collaborations, including payments to purchase our stock. Spinal Muscular Atrophy Collaborations SPINRAZA In 2012, we entered into a collaboration agreement with Biogen to develop and commercialize SPINRAZA. From inception through , we earned more than $ billion in total revenue under our SPINRAZA collaboration, including more than $ billion in revenue from SPINRAZA royalties and more than $ million in R&D revenue. We are receiving tiered royalties ranging from to on net sales of SPINRAZA. We have exclusively in-licensed patents related to SPINRAZA from Cold Spring Harbor Laboratory and the University of Massachusetts. We pay Cold Spring Harbor Laboratory and the University of Massachusetts a low single digit royalty on net sales of SPINRAZA. Biogen is responsible for all global development, regulatory and commercialization activities and costs for SPINRAZA. We completed our performance obligations under our collaboration in 2016 In 2023, we entered into a royalty purchase agreement with Royalty Pharma in which Royalty Pharma receives 25 percent of our SPINRAZA royalty payments from 2023 through 2027, increasing to 45 percent of royalty payments in 2028, on up to $1.5 billion in annual sales. Royalty Pharma’s royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma reach either $475 million or $550 million, depending on the timing and occurrence of the U.S. Food and Drug Administration, or FDA, approval of pelacarsen, which Novartis is developing. Refer to Note 7, Long-Term Obligations and Commitments New Antisense Medicines for the Treatment of SMA In 2017, we entered into a collaboration agreement with Biogen to new antisense medicines for the treatment of SMA . Biogen has the option to license therapies arising out of this collaboration following the completion of preclinical studies. Upon licensing, Biogen will be responsible for global development, regulatory and commercialization activities and costs for such therapies . At the commencement of this collaboration, we received a upfront payment from Biogen. In 2021 , Biogen exercised its option to license ION 306 , a drug we discovered under this collaboration, for which we earned a $ million license fee payment. We recognized this payment as revenue in full because We will receive development and regulatory milestone payments from Biogen if new medicines, including ION 306 , advance towards marketing approval. Over the term of the collaboration, we are eligible to receive up to $555 million if Biogen advances ION306, which is comprised of up to $45 million in development milestone payments, up to $110 million in regulatory milestone payments and up to $400 million in sales milestone payments. In addition, we are eligible to receive tiered royalties from the mid-teens to on net sales from any product that Biogen successfully commercializes under this collaboration. for the initiation of a Phase 3 trial under this collaboration. Neurology Collaborations 2018 Strategic Neurology In 2018, we and Biogen entered into a strategic collaboration to develop novel antisense medicines for a broad range of neurological diseases. We also entered into a Stock Purchase Agreement, or SPA. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for these diseases for years. We are responsible for the identification of antisense drug candidates based on selected targets Biogen has the option to license the selected medicine If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine. At the commencement of this collaboration, we received For each medicine under this collaboration, w e are eligible to receive up to $ million, which is comprised of a $ million license fee, up to $ million in development milestone payments and up to $ million in regulatory milestone payments. up to the on net sales from any product that Biogen successfully commercializes under this collaboration. W under this collaboration. We considered that the collaboration agreement and SPA 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. W We determined our transaction price to be $ million, comprised of $ million from the upfront payment and $ million for the premium paid by Biogen for its purchase of our common stock. From inception through December 31, 2023, we have included $623 million in upfront and milestone payments in the transaction price for our R&D services performance obligation under this collaboration, including a $ million milestone payment we achieved in the fourth quarter of 2023. This milestone payment did not create a new performance obligation because it is part of our original R&D services performance obligation. Therefore, we included this amount in our transaction price for our R&D services performance obligation in the period we achieved the milestone payment. We are recognizing revenue for our R&D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our performance obligation at the end of the contractual term in June 2028. 2013 Strategic Neurology In 2013, we and Biogen entered into a strategic relationship focused on applying antisense technology to advance the treatment of neurodegenerative diseases. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for neurological diseases and has the option to license medicines resulting from this collaboration. In most cases, we are responsible for drug discovery and early development of antisense medicines and Biogen has the option to license antisense medicines after Phase 2 proof-of-concept. In 2016, we expanded our collaboration to include additional research activities we will perform. If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine. We are currently advancing four investigational medicines in development under this collaboration, including a a Under the terms of the agreement, we received an upfront payment of $100 million and are eligible to receive milestone payments, license fees and royalty payments for all medicines developed under this collaboration, with the specific amounts dependent upon the modality of the molecule advanced by Biogen. Over the term of the collaboration for QALSODY, we are eligible to receive nearly $110 million, which is comprised of a $35 million license fee we received when Biogen licensed QALSODY from us in 2018, $18 million in development milestone payments and up to $55 million in regulatory milestone payments. In addition, we are eligible to receive tiered royalties ranging from 11 percent to 15 percent on net sales of QALSODY. We will achieve the next milestone payment for QALSODY of $20 million if the European Medicines Agency, or EMA, approves Biogen’s Marketing Authorization Application, or MAA, filing of QALSODY. For each of the other antisense molecules that are chosen for drug discovery and development under this collaboration, we are eligible to receive up to approximately $260 million, which is comprised of a $70 million license fee, up to $60 million in development milestone payments and up to $130 million in regulatory milestone payments. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales from any product that Biogen successfully commercializes under this collaboration. From inception through December 31, 2023, we have received more than $325 million in payments under our 2013 strategic neurology collaboration. We will achieve the next payment of $70 million if Biogen licenses a medicine under this collaboration. At the commencement of our 2013 strategic neurology collaboration, we identified one performance obligation, which was to perform R&D services for Biogen. At inception, we determined the transaction price to be the $100 million upfront payment we received and allocated it to our single performance obligation. As we achieve milestone payments for our R&D services, we include these amounts in our transaction price for our R&D services performance obligation. We recognized revenue for our R&D services performance obligation based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation . R&D services and recognized the remaining revenue related to this performance obligation. Under this collaboration, we have also generated additional payments that we concluded were not part of our R&D services performance obligation. We recognized each of these payments in full in the respective period we generated the payment because we did not have any performance obligations for the respective payment. For example, in 2023, we earned a million milestone payment from Biogen when the FDA approved Biogen’s New Drug Application, or NDA, for QALSODY, which we recognized in full because we did not have any remaining performance obligations related to this milestone payment. 2012 Neurology In 2012, we and Biogen entered into a collaboration agreement to develop and commercialize novel antisense medicines to treat neurodegenerative diseases. We are responsible for the development of each of the medicines through the completion of the initial Phase 2 clinical study for such medicine. Biogen has the option to license a medicine from each of the programs through the completion of the first Phase 2 study for each program. Under this collaboration, Biogen is conducting the IONIS-MAPT Rx Rx Rx Under the terms of the agreement, we received an upfront payment of $ million. For each program under this collaboration, we are eligible to receive up to $ million, which is comprised of a license fee of up to $ million, up to $ million in development milestone payments and up to $ million in regulatory milestone payments, plus a mark-up on the cost estimate of the Phase 1 and 2 studies. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales of any medicines resulting from each of the programs. From inception through , we have received more than $ million in payments under this collaboration, including $ million in milestone payments we received from Biogen for advancing ION582 during 2023 and a $ million milestone payment we received from Biogen when Biogen advanced Rx during 2022. We will achieve the next payment of $ When we commenced development for IONIS-MAPT Rx Rx Rx Rx During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in thousands, except percentage amounts): Year Ended December 31, 2023 2022 2021 Revenue from our relationship with Biogen $ 350,146 $ 366,696 $ 428,784 Percentage of total revenue 44 % 62 % 53 % Our , and included deferred revenue of $ million and $ million, respectively, related to our relationship with Biogen. Joint Development and Commercialization Arrangement AstraZeneca WAINUA (Eplontersen) Collaboration In 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize eplontersen for the treatment of ATTR. In December 2023, the FDA approved eplontersen with the brand name, WAINUA, in the U.S. for ATTRv-PN. We are jointly developing and commercializing WAINUA with AstraZeneca in the U.S. We initially granted AstraZeneca exclusive rights to commercialize WAINUA outside the U.S., except for certain Latin American countries. In July 2023, we expanded those rights to include Latin America. Over the term of the collaboration, we are eligible to receive up to $ billion, which is comprised of a $ million upfront payment, a $ million license fee, up to $ million in development and approval milestone payments and up to $ billion in sales milestone payments. The agreement includes territory-specific development, commercial and medical affairs cost-sharing provisions. In addition, we are eligible to receive up to mid- royalties for sales in the U.S. and tiered royalties ranging from mid to high teens for sales outside the U.S. From inception through , we have received nearly $ million in payments under this collaboration. We will achieve the next payment of $ million upon regulatory approval of WAINUA for ATTRv-PN in the EU under this collaboration. We evaluated our WAINUA 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 will perform, (iii) the co-commercialization activities that we and AstraZeneca will perform and (iv) the co-medical affairs activities that we and AstraZeneca will perform. 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 in 2021. In 2023, we earned a $20 million license fee payment when we licensed rights to Latin America for WAINUA to AstraZeneca. We recognized these payments in full because we did not have any remaining performance obligations after we delivered the licenses 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. AstraZeneca is currently 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 recognize as revenue the 55 percent of cost-share funding AstraZeneca is responsible for 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 WAINUA to market outside the U.S., we recognize cost-share funding we receive from AstraZeneca related to these activities as a reduction of our commercial and medical affairs expenses. In 2023, we earned a $50 million milestone payment when the FDA approved WAINUA for ATTRv-PN in the U.S. We recognized this milestone payment in full as joint development revenue because we did not have any remaining performance obligations related to the milestone payment. Research and Development Partners AstraZeneca In addition to our collaboration for WAINUA, we have a collaboration with AstraZeneca focused on discovering and developing treatments for cardiovascular, renal and metabolic diseases, which we formed in 2015. Under our collaboration, AstraZeneca has licensed multiple medicines from us. AstraZeneca is responsible for global development, regulatory and commercialization activities and costs for each of the medicines it has licensed from us. Over the term of the collaboration, we are eligible to receive up to $3.4 billion, which is comprised of a $65 million upfront payment, up to $290 million in license fees, up to $865 million in development milestone payments and up to $2.2 billion in regulatory milestone payments. In addition, we are eligible to receive tiered royalties up to the low teens on net sales from any product that AstraZeneca successfully commercializes under this collaboration agreement. From inception through December 31, 2023, we have received more than $300 million in payments under this collaboration. We will achieve the next payment of $10 million if AstraZeneca advances a medicine under this collaboration . At the commencement of this collaboration, we identified one performance obligation, which was to perform R&D services for AstraZeneca. We determined the transaction price to be the $65 million upfront payment we received and we allocated it to our single performance obligation. We recognized revenue for our R&D services performance obligation as we performed services based on our effort to satisfy this performance obligation relative to our total effort expected to satisfy our performance obligation. We completed our performance obligation in Under this collaboration, we have also generated additional payments that we concluded were not part of our R&D services performance obligation. We recognized each of these payments in full in the respective period we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. For example, in 2023, we earned a $36 million payment when AstraZeneca licensed ION826 from us. We recognized this payment in full in 2023 because we did not have any remaining performance obligations after we delivered the license to AstraZeneca. During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with AstraZeneca (in thousands, except percentage amounts): Year Ended December 31, 2023 2022 2021 Revenue from our relationship with AstraZeneca $ 202,236 $ 79,160 $ 254,591 Percentage of total revenue 26 % 13 % 31 % We did not have any deferred revenue from our relationship with AstraZeneca at December 31, 2023 and 2022. GSK In 2010, we entered into a collaboration with GSK using our antisense drug discovery platform to discover and develop new medicines against targets for serious and rare diseases, including infectious diseases. Upon initiating the collaboration, we received an upfront payment of $35 million. Under our collaboration, GSK is developing bepirovirsen for the treatment of chronic hepatitis B virus infection, or HBV, infection. In 2019, following positive Phase 2 results, GSK licensed our HBV program. GSK is responsible for all global development, regulatory and commercialization activities and costs for the HBV program. Over the term of the collaboration, we are eligible to receive nearly $260 million, which is comprised of a $25 million license fee, up to $42.5 million in development milestone payments, up to $120 million in regulatory milestone payments and up to $70 million in sales milestone payments if GSK successfully develops and commercializes bepirovirsen. In addition, we are eligible to receive tiered royalties up to the low-teens on net sales of bepirovirsen. From inception through December 31, 2023, we have received more than $105 million in an upfront payment and payments related to the HBV program. We completed our R&D services performance obligations in 2015, therefore we do not have any remaining performance obligations under our collaboration with GSK. However, we can still earn additional payments and royalties as GSK advances the HBV program. In 2023, we earned a $ million milestone payment when GSK initiated a Phase 3 program of bepirovirsen. We recognized this milestone payment as R&D revenue in full in 2023 because we did not have any remaining performance obligations related to the milestone payment. We will achieve the next payment of $ million if the FDA accepts an NDA filing of bepirovirsen for review. During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with GSK (in thousands, except percentage amounts): Year Ended December 31, 2023 2022 2021 Revenue from our relationship with GSK $ 15,000 $ — $ — Percentage of total revenue 2 % 0 % 0 % We did not have any deferred revenue from our relationship with GSK at December 31, 2023 and 2022. Novartis Pelacarsen Collaboration In 2017, we initiated a collaboration with Novartis to develop and commercialize pelacarsen. Over the term of the collaboration, we are eligible to receive up to $900 million, which is comprised of a $75 million upfront payment, a $150 million license fee, a $25 million development milestone payment, up to $290 million in regulatory milestone payments and up to $360 million in sales milestone payments. We are also eligible to receive tiered royalties in the mid-teens to low 20 percent range on net sales of pelacarsen. From inception through , we have received more than $ million in payments under this collaboration. We will achieve the next payment of $ million if the FDA accepts an NDA filing for pelacarsen. In conjunction with this collaboration, we entered into a SPA with Novartis. As part of the SPA, Novartis purchased 1.6 million shares of our common stock for $100 million in 2017. At the commencement of this collaboration, we identified four separate performance obligations: ● R&D services for pelacarsen; ● R&D services for olezarsen; ● API for pelacarsen; and ● API for olezarsen. We determined that the R&D services for each medicine and the API for each medicine were distinct performance obligations. We determined our transaction price to be $108.4 million, comprised of the following: ● $75 million from the upfront payment; ● $28.4 million for the premium paid by Novartis for its purchase of our common stock at a premium in 2017; and ● $5.0 million for the potential premium Novartis would have paid if they purchased our common stock in the future. We allocated the transaction price based on the estimated stand-alone selling price of each performance obligation as follows: ● $ million for the R&D services for pelacarsen; ● $40.1 million for the R&D services for olezarsen ● $1.5 ● $2.8 We completed our R&D services performance obligations for olezarsen and pelacarsen We recognized revenue related to the R&D services for pelacarsen and olezarsen performance obligations as we performed services . As described in the Biogen SPINRAZA Long-Term Obligations and Commitments New Medicine for the Treatment of Lp(a)-Driven Cardiovascular Disease In August 2023, we entered into a collaboration and license agreement with Novartis for the discovery, development and commercialization of a novel medicine for patients with Lp(a)-driven cardiovascular disease, or CVD. Novartis is solely responsible for the development, manufacturing and potential commercialization of the next generation Lp(a) therapy. Over the term of the collaboration, we are eligible to receive up to $730 million, which is comprised of a $60 million upfront payment, up to $155 million in development milestone payments, up to $105 million in regulatory milestone payments and up to $410 million in sales milestone payments. In addition, we are eligible to receive tiered royalties ranging from 10 percent to 20 percent on net sales. From inception through December 31, 2023, we have received $60 million from the upfront payment we received under this collaboration. We will achieve the next payment of $5 million if we designate a development candidate under this collaboration. At the commencement of this collaboration, we identified one performance obligation, which was to perform R&D services for Novartis. We determined the transaction price to be the $60 million upfront payment we received in the fourth quarter 2023. We allocated the transaction price to our single performance obligation. We are recognizing revenue for our R&D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our performance obligation at the end of the research term in June 2024. During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with Novartis (in thousands, except percentage amounts): Year Ended December 31, 2023 2022 2021 Revenue from our relationship with Novartis $ 30,194 $ 237 $ 25,526 Percentage of total revenue 4 % Less than 1% 3 % Our consolidated balance sheet at December 31, 2023 included deferred revenue of $30.0 million related to our relationship with Novartis. We did not have any deferred revenue from our relationship with Novartis at December 31, 2022. Roche Huntington’s Disease In 2013, we entered into an agreement with Hoffmann-La Roche Inc and F. Hoffmann-La Roche Ltd, collectively Roche, to develop treatments for HD based on our antisense technology. Under the agreement, we discovered and developed tominersen, an investigational medicine targeting HTT protein. We developed tominersen through completion of our Phase 1/2 clinical study in people with early-stage HD. In 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. As a result, Roche is responsible for all global development, regulatory and commercialization activities and costs for tominersen. Over the term of the collaboration, we are eligible to receive up to $395 million, which is comprised of a $30 million upfront payment, a $45 million license fee, up to $70 million in development milestone payments, up to $170 million in regulatory milestone payments and up to $80 million in sales milestone payments as tominersen advances. In addition, we are eligible to receive up to $136.5 million in milestone payments for each additional medicine successfully developed. We are also eligible to receive tiered royalties up to the mid-teens on net sales of any product resulting from this collaboration. From inception through December 31, 2023, we have received more than $150 million in payments under this collaboration. We will achieve the next payment of $17.5 million if Roche advances a medicine under this collaboration. At the commencement of this collaboration, we identified one performance obligation, which was to perform R&D services for Roche. We determined the transaction price to be the $30 million upfront payment we received and allocated it to our single performance obligation. As we achieved milestone payments for our R&D services, we included these amounts in our transaction price for our R&D services performance obligation. We recognized revenue for our R&D services performance obligation over our period of performance, which ended in 2017. Under this collaboration, we have also generated additional payments that we concluded were not part of our R&D services performance obligation. We recognized each of these payments in full in the respective period in which we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. In 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 independent data monitoring committee, or iDMC. In January 2023, Roche initiated the Phase 2, GENERATION HD2, study of tominersen in patients with prodromal or early manifest HD. Roche is focusing on early-stage and younger patients based on the post-hoc analyses from the GENERATION HD1 study that suggested tominersen may benefit these patient groups. We do not have any remaining performance obligations related to tominersen under this collaboration with Roche; however, we can still earn additional payments and royalties as Roche advances tominersen. IONIS-FB-L Rx for Complement-Mediated Diseases In 2018, we entered into a collaboration agreement with Roche to develop IONIS-FB-L Rx IONIS-FB-L Rx Rx After positive data from a Phase 2 clinical study in patients with IgAN, licensed IONIS-FB-L Rx in 2022 for $ million. As a result, Roche is responsible for global development, regulatory and commercialization activities, and costs for IONIS-FB-L Rx , except for the open label Phase 2 study in patients with IgAN and the Phase 2 study in patients with GA, both of which we are conducting and funding. In 2022, we amended our IONIS-FB-L Rx collaboration agreement with Roche. The amendment changed future potential milestone payments we could receive under the collaboration. We determined there were no changes that would require adjustments to revenue we previously recognized. Over the term of the collaboration, we are eligible to receive more than $ million, which is comprised of a $ million upfront payment, a $ million license fee, up to $ million in development milestone payments, up to $ million in regulatory milestone payments and up to $ million in sales milestone payments. In addition, we are also eligible to receive tiered royalties from the high teens to on net sales. We will achieve the next payment of up to $ million if Roche advances IONIS-FB-L Rx under this collaboration. At the commencement of this collaboration, we identified one performance obligation, which was to perform R&D services for Roche. From inception through December 31, 2023, we have included $97 million in upfront and milestone payments in the transaction price for our R&D services performance obligation under this collaboration, including $22 million of milestone payments we achieved in 2022. We are recognizing revenue for our R&D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. currently estimate we will satisfy our performance obligation in RNA-Targeting Medicines for Alzheimer's Disease and Huntington's Disease In September 2023, we entered into an agreement with Roche to develop two undisclosed early-stage programs for RNA-targeting investigational medicines for the treatment of AD and HD. Under the agreement, we are responsible for advancing the two programs through preclinical studies and Roche is responsible for clinical development, manufacturing and commercialization of the medicines if they receive regulatory approval. Over the term of the collaboration, we are eligible to receive up to $625 million, which is comprised of a $60 million upfront payment, up to $167 million in development milestone payments and up to $398 million in sales milestone payments. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales. From inception through December 31, 2023, we have received $60 million from the upfront payment we received under this collaboration. We will achieve the next payment of $7.5 million if we advance a medicine under this collaboration. We identified two performance obligations under this new agreement, comprised of R&D services for each of the two separate programs. We determined the transaction price to be the $60 million upfront payment we received in the fourth quarter 2023. We allocated the transaction price based on the estimated stand-alone selling price of each performance obligation as follows: ● $45 million for the R&D services for the investigational medicine for AD; and ● $ million for the R&D services for t We are recognizing revenue for our R&D services performance obligations as we perform services based on our effort to satisfy our performance obligations relative to our total effort expected to satisfy our performance obligations. We currently estimate we will satisfy our performance obligations at the end of the research terms of March 2024 and March 2025 for the investigational medicines for AD and H

Investments

Investments	12 Months Ended
Investments	Dec. 31, 2023
Investments [Abstract]
Investments	5. Investments The following table summarizes the contract maturity of the available-for-sale securities we held as of December 31, 2023: One year 68 % After one year two years 24 % After two years three and a half years 8 % Total 100 % As illustrated above, at December 31, 2023, 92 percent of our available-for-sale securities had a maturity of less than two years. All of our available-for-sale securities are available to us for use in our current operations. As a result, we categorize all of these securities as current assets even though the stated maturity of some individual securities may be one year or more beyond the balance sheet date. We invest in debt securities with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Standard & Poor’s, Moody’s or Fitch, respectively. At December 31, 2023, we had an ownership interest of less than 20 percent . The following is a summary of our investments (in thousands): Amortized Gross Unrealized Estimated December 31, 2023 Cost Gains Losses Fair Value Available-for-sale securities: Corporate debt securities (1) $ 559,967 $ 157 $ (2,625 ) $ 557,499 Debt securities issued by U.S. government agencies 224,711 64 (611 ) 224,164 Debt securities issued by the U.S. Treasury (1) 513,784 152 (1,889 ) 512,047 Debt securities issued by states of the U.S. and political subdivisions of the states 17,757 42 (113 ) 17,686 Total securities with a maturity of one year or less 1,316,219 415 (5,238 ) 1,311,396 Corporate debt securities 243,151 1,270 (692 ) 243,729 Debt securities issued by U.S. government agencies 110,138 547 (21 ) 110,664 Debt securities issued by the U.S. Treasury 294,873 1,239 (480 ) 295,632 Debt securities issued by states of the U.S. and political subdivisions of the states 3,466 7 (4 ) 3,469 Total securities with a maturity of more than one year 651,628 3,063 (1,197 ) 653,494 Total available-for-sale securities $ 1,967,847 $ 3,478 $ (6,435 ) $ 1,964,890 Equity securities: Publicly traded equity securities included in other current assets (2) $ 11,897 $ 236 $ (5,832 ) $ 6,301 Privately held securities included in deposits and other assets (3) 23,115 25,001 (5,125 ) 42,991 Total equity securities $ 35,012 $ 25,237 $ (10,957 ) $ 49,292 Total available-for-sale and equity securities $ 2,002,859 $ 28,715 $ (17,392 ) $ 2,014,182 Amortized Gross Unrealized Estimated December 31, 2022 Cost Gains Losses Fair Value Available-for-sale securities: Corporate debt securities (1) $ 513,790 $ 23 $ (4,365 ) $ 509,448 Debt securities issued by U.S. government agencies 133,585 — (1,829 ) 131,756 Debt securities issued by the U.S. Treasury (1) 512,655 23 (5,124 ) 507,554 Debt securities issued by states of the U.S. and political subdivisions of the states 57,484 18 (686 ) 56,816 Other municipal debt securities 6,008 — (14 ) 5,994 Total securities with a maturity of one year or less 1,223,522 64 (12,018 ) 1,211,568 Corporate debt securities 227,631 14 (10,143 ) 217,502 Debt securities issued by U.S. government agencies 34,339 — (1,040 ) 33,299 Debt securities issued by the U.S. Treasury 245,030 — (4,109 ) 240,921 Debt securities issued by states of the U.S. and political subdivisions of the states 18,314 116 (329 ) 18,101 Total securities with a maturity of more than one year 525,314 130 (15,621 ) 509,823 Total available-for-sale securities $ 1,748,836 $ 194 $ (27,639 ) $ 1,721,391 Equity securities: Publicly traded equity securities included in other current assets (2) $ 11,897 $ — $ (1,358 ) $ 10,539 Privately held equity securities included in deposits and other assets (3) 23,115 17,257 — 40,372 Total equity securities $ 35,012 $ 17,257 $ (1,358 ) $ 50,911 Total available-for-sale and equity securities $ 1,783,848 $ 17,451 $ (28,997 ) $ 1,772,302 ________________ (1) Includes investments classified as cash equivalents in our consolidated balance sheets. (2) Our publicly traded equity securities are included in other current assets. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2023, we recorded a $4.2 million net unrealized loss in our consolidated statements of operations related to changes in the fair value of our investments in publicly traded companies. (3) Our privately held equity securities are included in deposits and other assets. We recognize our privately held equity securities at , we recorded a $ million net unrealized gain in our consolidated statements of operations related to changes in the fair value of our investments in privately held companies. The following is a summary of our investments we considered to be temporarily impaired at (in thousands, except for number of 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 297 $ 323,708 $ (553 ) $ 178,183 $ (2,764 ) $ 501,891 $ (3,317 ) Debt securities issued by U.S. government agencies 63 199,372 (246 ) 14,777 (386 ) 214,149 (632 ) Debt securities issued by the U.S. Treasury 34 325,966 (1,031 ) 131,000 (1,338 ) 456,966 (2,369 ) Debt securities issued by states of the U.S. and political subdivisions of the states 61 8,352 (17 ) 7,888 (100 ) 16,240 (117 ) Total temporarily impaired securities 455 $ 857,398 $ (1,847 ) $ 331,848 $ (4,588 ) $ 1,189,246 $ (6,435 ) 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 rather than underlying credit deterioration for any of the issuers. We believe it is more likely than not that we will be able to hold our debt securities with declines in value to maturity. Therefore, we intend to hold these securities to maturity and anticipate full recovery of our debt securities’ amortized cost basis at maturity.

Fair Value Measurements

Fair Value Measurements	12 Months Ended
Fair Value Measurements	Dec. 31, 2023
Fair Value Measurements [Abstract]
Fair Value Measurements	6. Fair Value Measurements The following tables present the major security types we held at December 31, 2023 and 2022 that we regularly measure and carry at fair value At December 31, 2023 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 185,424 $ 185,424 $ — Corporate debt securities (2) 801,228 — 801,228 Debt securities issued by U.S. government agencies (3) 334,828 — 334,828 Debt securities issued by the U.S. Treasury (3) 807,679 807,679 — Debt securities issued by states of the U.S. and political subdivisions of the states (3) 21,155 — 21,155 Publicly traded equity securities included in other current assets (5) 6,301 6,301 — Total $ 2,156,615 $ 999,404 $ 1,157,211 At December 31, 2022 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 211,655 $ 211,655 $ — Corporate debt securities (4) 726,950 — 726,950 Debt securities issued by U.S. government agencies (3) 165,055 — 165,055 Debt securities issued by the U.S. Treasury (3) 748,475 748,475 — Debt securities issued by states of the U.S. and political subdivisions of the states (3) 74,917 — 74,917 Other municipal debt securities (3) 5,994 — 5,994 Publicly traded equity securities included in other current assets (5) 10,539 10,539 — Total $ 1,943,585 $ 970,669 $ 972,916 ________________ (1) Included in cash and cash equivalents in our consolidated balance sheets. (2) $33.0 million was included in cash and cash equivalents, with the difference included in short-term investments in our consolidated balance sheets. (3) Included in short-term investments in our consolidated balance sheets. (4) $11.0 million was included in cash and cash equivalents, with the difference included in short-term investments in our consolidated balance sheets. (5) Included in other current assets in our consolidated balance sheets. Convertible Notes Our 1.75% Notes, 0% Notes and 0.125% Notes had a fair value of $661.1 million, $667.8 million and $42.4 million at December 31, 2023, 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.

Long-Term Obligations and Commi

Long-Term Obligations and Commitments	12 Months Ended
Long-Term Obligations and Commitments	Dec. 31, 2023
Long-Term Obligations and Commitments [Abstract]
Long-Term Obligations and Commitments	7. Long-Term Obligations and Commitments The carrying value of our long-term obligations was as follows (in thousands): December 31, 2023 2022 1.75 $ 562,285 $ — 0 625,380 622,242 0.125 — 544,504 Liability related to sale of future royalties 513,736 — Lease liabilities 178,969 186,156 Mortgage debt 8,859 8,998 Other obligations 33,714 7,295 Total $ 1,922,943 $ 1,369,195 Less: current portion (8,831 ) (7,535 ) Total Long-Term Obligations $ 1,914,112 $ 1,361,660 As of December 31, 2023, our 0.125% Notes was classified as a current liability because it matures in December 2024. Convertible Debt and Call Spread 1.75% Convertible Senior Notes In 2023, we completed a $575.0 million offering of convertible senior notes and used $488.2 million of the net proceeds from the issuance of the 1.75% Notes to repurchase $504.4 million in principal of our 0.125% Notes. We expect to use the remaining net proceeds to settle the 0.125% Notes that remain outstanding. At December 31, 2023, we had the following 1.75% Notes outstanding (in millions, except interest rate and price per share data): 1.75% Notes Outstanding principal balance $ 575.0 Unamortized debt issuance costs $ 12.7 Maturity date June 2028 Interest rate 1.75 % Effective interest rate 2.3 % Conversion price per share $ 53.73 Total shares of common stock subject to conversion 10.7 0% Convertible Senior Notes and Call Spread In 2021, we completed a $632.5 million offering of convertible senior notes. We used $319.0 million of the net proceeds from the issuance of the 0% Notes to pay the remaining $309.9 million principal balance of our 1% Notes in 2021. At December 31, 2023, we had the following 0% Notes outstanding (in millions, except interest rate and price per share data): 0% Notes Outstanding principal balance $ 632.5 Unamortized debt issuance costs $ 7.2 Maturity date April 2026 Interest rate 0 % Effective interest rate 0.5 % 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 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 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 consolidated balance sheets. Refer to Note 1, Organization and Significant Accounting Policies 0.125% Convertible Senior Notes and Call Spread In 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain holders of our 1% Notes to exchange $375.6 million of our 1% Notes for $439.3 million of our 0.125% Notes, and to issue $109.5 million of our 0.125% Notes. As discussed above, in 2023, we repurchased $504.4 million of our 0.125% Notes. We are holding the repurchased 0.125% Notes in treasury until maturity. As a result, the remaining principal balance of our 0.125% Notes was $44.5 million as of December 31, 2023. Additionally, during the year ended December 31, 2023, we recorded a $13.4 million gain on the early retirement of debt, which we recorded as other income in our consolidated statements of operations. The gain on the early retirement of our debt is the difference between the amounts paid to repurchase our 0.125% Notes and the net carrying balance of the liability at the time that we completed the repurchases. At December 31, 2023, we had the following 0.125% Notes outstanding with interest payable semi-annually (in millions, except interest rate and price per share data): 0.125% Notes Outstanding principal balance $ 44.5 Unamortized debt issuance costs $ 0.2 Maturity date December 2024 Interest rate 0.125 % Effective interest rate 0.5 % Conversion price per share $ 83.28 Effective conversion price per share with call spread $ 123.38 Total shares of common stock subject to conversion, excluding shares related to 0.125 0.5 In conjunction with the issuance of our Notes in 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 . We increased our effective conversion price to $ with the same number of underlying shares as our Notes. The call spread cost us $ million, of which $ million was for the note hedge purchase, offset by $ million we received for selling the warrants. Similar to our , our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the . The note hedges will expire upon maturity of the , or December 2024 . The note hedges and warrants are separate transactions and are not part of the terms of our . The holders of the 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 consolidated balance sheets. Refer to Note 1, Organization and Significant Accounting Policies Other Terms of Convertible Senior Notes The 1.75%, 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. Our total interest expense for our outstanding senior convertible notes for the years ended December 31, 2023, 2022 and 2021 included $5.9 million, $5.3 million and $4.9 million, respectively, of non-cash interest expense related to the amortization of debt issuance costs for our convertible notes. Financing Arrangements Operating Facilities In 2017, we purchased the building that houses our primary R&D facility for $79.4 million and our manufacturing facility for $14.0 million. We financed the purchase of these two facilities with mortgage debt of $60.4 million in total. Our primary R&D facility mortgage had an interest rate of 3.88 percent. Our manufacturing facility mortgage has an interest rate of 4.20 percent. During the first five years of both mortgages, we were only required to make interest payments. We began making principal payments in 2022. Our manufacturing facility mortgage matures in August 2027. We repaid our primary R&D facility mortgage in 2022 in conjunction with a sale and leaseback transaction. In 2022, we concurrently entered into two purchase and sale agreements with a real estate investor. In the same period, we closed the first transaction in which we sold the facilities at our headquarters in Carlsbad, California, which includes our primary R&D facility, for a purchase price of $263.4 million. As a result, we de-recognized the related land and improvements, building and building improvements, which resulted in a net gain of $150.1 million that we reported in other income in our consolidated statements of operations. We used a portion of the sale proceeds to extinguish our outstanding mortgage debt on our primary R&D facility of $51.3 million. In connection with this transaction, we leased back our headquarters facilities for an initial lease term of 15 years with options to extend the lease for two additional terms of five years each. In August 2023, we closed the second transaction and transferred legal ownership of two lots of undeveloped land adjacent to our headquarters to the real estate investor for a purchase price of $33 million. In connection with this transaction, we entered into a build-to-suit lease agreement with the same real estate investor to lease a new R&D facility. The lessor will develop and construct a new building composed of R&D and office space. We will design and construct tenant improvements to customize the facility’s interior space. We will lease the facility for an initial term of 15 years with options to extend the lease for two additional terms of five years each. The lease will commence once the structure of this new facility is completed. Since the building is under construction and unavailable to lease, we are unable to complete the sale-leaseback evaluation under ASC 842, Leases. As a result, the land remains in our consolidated balance sheets and we accounted for the proceeds as a financial liability. We will reassess the transaction under the sale-leaseback accounting guidance when the facilities are available for lease commencement. Debt Maturity Schedules Annual convertible and mortgage debt maturities, including fixed and determinable interest, at December 31, 2023 are as follows (in thousands): 2024 $ 55,298 2025 10,657 2026 643,157 2027 10,509 2028 580,277 Thereafter 8,462 Total debt and mortgage maturities $ 1,308,360 Less: Current portion included in other current liabilities (157 ) Less: Fixed and determinable interest (47,138 ) Less: Debt issuance costs (20,061 ) Total debt $ 1,241,004 Royalty Revenue Monetization In January 2023, we entered into a royalty purchase agreement with Royalty Pharma Investments, or Royalty Pharma, to monetize a portion of our future SPINRAZA and pelacarsen royalties we are entitled to under our agreements with Biogen and Novartis, respectively. As a result, we received an upfront payment of $500 million and we are eligible to receive up to $625 million in additional milestone payments. Under the terms of the agreement, Royalty Pharma will receive 25 percent of our SPINRAZA royalty payments from 2023 through 2027, increasing to 45 percent of royalty payments in 2028, on up to $1.5 billion in annual sales. In addition, Royalty Pharma will receive 25 percent of any future royalty payments on pelacarsen. Royalty Pharma’s royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma reach either $475 million or $550 million, depending on the timing and occurrence of FDA approval of pelacarsen. We recorded the upfront payment of $500 million as a liability related to the sale of future royalties, net of transaction costs of $10.4 million, which we are amortizing over the estimated life of the arrangement using the effective interest rate method. We recognize royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue. We record royalty payments made to Royalty Pharma as a reduction of the liability. We determine the effective interest rate used to record interest expense under this agreement based on an estimate of future royalty payments to Royalty Pharma. As of , the estimated effective interest rate under the agreement was . The following is a summary of our liability related to sale of future royalties for the year ended (in thousands): Proceeds from sale of future royalties $ 500,000 Royalty payments to Royalty Pharma (44,628 ) Interest expense related to sale of future royalties 68,238 Liability related to sale of future royalties as of December 31, 2023 523,610 Issuance costs related to sale of future royalties (10,434 ) Amortization of issuance costs related to sale of future royalties as of December 31, 2023 560 Net liability related to sale of future royalties as of December 31, 2023 $ 513,736 There are numerous factors, most of which are not within our control, that could materially impact the amount and timing of royalty payments from Biogen and Novartis, and result in changes to our estimate of future royalty payments to Royalty Pharma. Such factors include, but are not limited to, the commercial sales of SPINRAZA, the regulatory approval and commercial sales of pelacarsen, competing products or other significant events.
Long-Term Obligations and Commitments	Operating Leases Carlsbad Leases We lease a facility adjacent to our manufacturing facility that has laboratory and office space that we use to support our manufacturing facility. We lease this space under a non-cancelable operating lease. In 2020, we exercised our option to extend our lease, extending our lease term from June 2021 to August 2026. We have one remaining option to extend the lease for an additional five-year period. We also lease an additional office space and warehouse space in Carlsbad. We lease these spaces under non-cancelable operating leases. In 2022, we exercised our option to extend the office space lease, extending our term from January 2023 to May 2027. We have no remaining options to extend this lease. Our warehouse space lease in Carlsbad has an initial term ending in 2028 with no options to extend the lease. As discussed above in the section titled, Financing Arrangements Oceanside Lease In 2022, we entered into a build-to-suit lease agreement to lease a development chemistry and manufacturing facility to be constructed by the lessor in Oceanside, California. We capitalized costs that we incurred related to the design and development of tenant improvements as construction-in-progress in our consolidated balance sheets. In August 2023, we reached a mutual agreement with the lessor to terminate the lease agreement. As a result, we recorded a charge of $20 million, primarily associated with the impairment of construction-in-progress assets, within SG&A expense Boston Leases We entered into an operating lease agreement for office space located in Boston, Massachusetts which commenced in August 2018. We are leasing this space under a non-cancelable operating lease with an initial term ending after 123 months and an option to extend the lease for an additional five-year term. Under the lease agreement, we received a three-month free rent period. In 2022, we entered into a sublease agreement for our office space located in Boston, Massachusetts. The sublease commencement date was 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 83 months following the sublease commencement date 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 entered into an operating lease agreement for another office space located in Boston, Massachusetts which commenced in 2021. We are leasing this space under a non-cancelable operating lease with an initial term ending 91 months following the lease commencement date and an option to extend the lease for an When we determined our lease term for our operating lease right-of-use assets and lease liabilities for these leases, we did not include the extension options for these leases in the original lease term because it was not reasonably certain we would exercise those extension options. Amounts related to our operating leases were as follows (dollar amounts in millions): At December 31, 2023 Right-of-use operating lease assets $ 171.9 Operating lease liabilities $ 179.0 Weighted average remaining lease term 13.0 years Weighted average discount rate 6.9 % During the years ended December 31, 2023, 2022, and 2021 we paid $20.1 million, $4.0 million and $3.3 million of lease payments, which were included in operating activities in our consolidated statements of cash flows. As of December 31, 2023, the future payments for our operating lease liabilities are as follows (in thousands): Operating Leases Year ending December 31, 2024 $ 20,398 2025 20,645 2026 20,781 2027 20,800 2028 20,774 Thereafter 176,138 Total minimum lease payments 279,536 Less: Imputed interest (100,567 ) Less: Current portion (included in other current liabilities (8,094 ) Total long-term lease liabilities $ 170,875 Rent expense was $23.1 million, $8.3 million and $3.4 million for the years ended December 31, 2023, 2022 and 2021, respectively.

Stockholders' Equity

Stockholders' Equity	12 Months Ended
Stockholders' Equity	Dec. 31, 2023
Stockholders' Equity [Abstract]
Stockholders' Equity	8. Stockholders Equity Preferred Stock We are authorized to issue up to 15 million shares of “blank check” Preferred Stock. As of December 31, 2023, there were no shares of Preferred Stock outstanding. We have designated Series C Junior Participating Preferred Stock but have no issued or outstanding shares as of December 31, 2023. Common Stock At December 31, 2023 and 2022, we had 300 million shares of common stock authorized, of which 144.3 million and 142.1 million were issued and outstanding, respectively. As of December 31, 2023, total common shares reserved for future issuance were 49.7 million. During the years ended December 31, 2023, 2022 and 2021, we issued 2.3 million, 1.2 million and 1.1 million shares of common stock, respectively, for stock option exercises, vesting of restricted stock units, and ESPP purchases. We received net proceeds from these transactions of $49.4 million, $6.4 million and $11.6 million in 2023, 2022 and 2021, respectively. Stock Plans 1989 Stock Option Plan In 1989, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that, as amended, provides for the issuance of non-qualified and incentive stock options for the purchase of up to 20.0 million shares of common stock to our employees, directors, and consultants. The plan expires in January 2024. The 1989 Stock Option Plan, or 1989 Plan, does not allow us to grant stock bonuses or restricted stock awards and prohibits us from repricing any options outstanding under the plan unless our stockholders approve the repricing. Options vest over a four-year period, with 25 percent exercisable at the end of one year from the date of the grant and the balance vesting ratably, on a monthly basis, thereafter and have a term of seven years. At December 31, 2023, no options were outstanding and 68,000 shares were available for future grant under the 1989 Plan. 2011 Equity Incentive Plan In 2011, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that provides for the issuance of stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards, and performance cash awards to our employees, directors, and consultants. In June 2015, May 2017 and June 2019, after receiving approval from our stockholders, we amended our 2011 Equity Incentive Plan, or 2011 Plan, 2011 Plan. The amendment increased the total number of shares of common stock authorized for issuance under the 2011 Plan from million to million and added a fungible share counting ratio whereby the share reserve will be reduced by shares for each share of common stock issued pursuant to a full value award (i.e., RSU or PRSU) and increased by shares for each share of common stock returning from a full value award. 2011 Plan to increase the total number of shares of common stock authorized for issuance under the 2011 Plan from million to million. The plan expires in June 2031. The 2011 Plan does not allow us to reduce the exercise price of any outstanding stock options or stock appreciation rights or cancel any outstanding stock options or stock appreciation rights that have an exercise price or strike price greater than the current fair market value of the common stock in exchange for cash or other stock awards unless our stockholders approve such action. Currently we anticipate awarding only stock options, RSU and PRSU awards to our employees, directors and consultants. Options vest over a four-year period, with 25 percent exercisable at the end of one year from the date of the grant and the balance vesting ratably, on a monthly basis, thereafter and have a term of seven years. Options granted after December 31, 2021 have a term of ten years. We have granted restricted stock unit awards to our employees under the 2011 Plan which vest annually over a four-year period. At December 31, 2023, a total of 12.8 million options were outstanding, of which 8.7 million were exercisable, 3.3 million restricted stock unit awards were outstanding, and 8.0 million shares were available for future grant under the 2011 Plan. Under the 2011 Plan, we may issue a stock award with additional acceleration of vesting and exercisability upon or after a change in control. In the absence of such provisions, no such acceleration will occur. In addition, we implemented a change of control and severance benefit plan that provides for change of control and severance benefits to our executive officers, including our chief executive officer and chief financial officer, and vice presidents. If one of our executive officers or vice presidents is terminated or resigns for good reason during the period that begins three months before and ends twelve months following a change in control of the company, the impacted employee’s stock options and RSUs vesting will accelerate for options and RSUs outstanding as of the termination date. 2020 Equity Incentive Plan In connection with the Akcea Merger in 2020, we assumed the unallocated portion of the available share reserve under the Akcea 2015 Equity Incentive Plan. In 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. The 2020 Plan provided for the issuance of up to million shares of our Common Stock to our employees, directors and consultants who were employees of Akcea prior to the Akcea Merger. In the second quarter of 2021, our Compensation Committee approved an amendment to the 2020 Plan. The amendment decreased the total number of shares of common stock authorized for issuance under the 2020 Plan from approximately million to million. We assumed the 2020 Plan in connection with Ionis’ reacquisition of all of the outstanding shares of Akcea Therapeutics, Inc. as part of the Akcea Merger. The plan expires in December 2025. The 2020 Plan does not allow us to reduce the exercise price of any outstanding stock options or stock appreciation rights or cancel any outstanding stock options or stock appreciation rights that have an exercise price or strike price greater than the current fair market value of the common stock in exchange for cash or other stock awards unless our stockholders approve such action. Currently we anticipate awarding only stock options and RSU awards to our eligible employees, directors and consultants. Options vest over a four-year period, with 25 percent exercisable at the end of one year from the date of the grant and the balance vesting ratably, on a monthly basis, thereafter and have a term of seven years. Options granted after December 31, 2021 have a term of ten years. We have granted restricted stock unit awards to our employees under the 2020 Plan which vest annually over a four-year period. At December 31, 2023, a total of 0.4 million options were outstanding, of which 0.1 million were exercisable, 0.2 million restricted stock unit awards were outstanding, and 1.0 million shares were available for future grant under the 2020 Plan. Under the 2020 Plan, we may issue a stock award with additional acceleration of vesting and exercisability upon or after a change in control. In the absence of such provisions, no such acceleration will occur. Corporate Transactions and Change in Control under 2011 and 2020 Plans In the event of certain significant corporate transactions, our Board of Directors has the discretion to take one or more of the following actions with respect to outstanding stock awards under the 2011 and 2020 Plans: ● arrange for assumption, continuation, or substitution of a stock award by a surviving or acquiring entity (or its parent company); ● arrange for the assignment of any reacquisition or repurchase rights applicable to any shares of our common stock issued pursuant to a stock award to the surviving or acquiring corporation (or its parent company); ● accelerate the vesting and exercisability of a stock award followed by the termination of the stock award; ● arrange for the lapse of any reacquisition or repurchase rights applicable to any shares of our common stock issued pursuant to a stock award; ● cancel or arrange for the cancellation of a stock award, to the extent not vested or not exercised prior to the effective date of the corporate transaction, in exchange for cash consideration, if any, as the Board, in its sole discretion, may consider appropriate; and ● arrange for the surrender of a stock award in exchange for a payment equal to the excess of (a) the value of the property the holder of the stock award would have received upon the exercise of the stock award, over (b) any exercise price payable by such holder in connection with such exercise. 2002 Non-Employee Directors’ Stock Option Plan In 2001, our Board of Directors adopted, and the stockholders subsequently approved, an amendment and restatement of the 1992 Non-Employee Directors’ Stock Option Plan, which provides for the issuance of non-qualified stock options and restricted stock units to our non-employee directors. The name of the resulting plan is the 2002 Non-Employee Directors’ Stock Option Plan, or the 2002 Plan. In 2015, after receiving approval from our stockholders, we amended our 2002 Plan to increase the total number of shares reserved for issuance from 1.2 million to 2.0 million. In 2020, after receiving approval from our stockholders, we further amended our 2002 Plan. The amendments included: ● An increase to the total number of shares reserved for issuance under the plan from million to million shares; ● A reduction to the amount of the automatic awards under the plan; ● A revision to the vesting schedule of new awards granted; and ● An extension of the term of the plan. Options under this plan expire 10 years from the date of grant. At December 31, 2023, a total of 0.9 million options were outstanding, of which 0.9 million were exercisable, 40,000 restricted stock unit awards were outstanding, and 0.5 million shares were available for future grant under the 2002 Plan. Employee Stock Purchase Plan In 2009, our Board of Directors adopted, and the stockholders subsequently approved, the amendment and restatement of the ESPP and we reserved an additional 150,000 shares of common stock for issuance thereunder. In each of the subsequent years until 2019, we reserved an additional 150,000 shares of common stock for the ESPP resulting in a total of 3.2 million shares authorized under the plan as of December 31, 2023. The ESPP permits full-time employees to purchase common stock through payroll deductions (which cannot exceed 10 percent of each employee’s compensation) at the lower of 85 percent of fair market value at the beginning of the purchase period or the end of each purchase period. Under the amended and restated ESPP, employees must hold the stock they purchase for a minimum of six months from the date of purchase. During 2023, employees purchased and we issued to employees 0.1 million shares under the ESPP at a weighted average price of $30.53 per share. At December 31, 2023, there were 0.4 million shares available for purchase under the ESPP. Stock Option Activity The following table summarizes the stock option activity under our stock plans for the year ended December 31, 2023 (in thousands, except per share and contractual life data): Number of Shares Weighted Average Exercise Price Per Share Average Remaining Contractual Term (Years) Aggregate Intrinsic Value Outstanding at December 31, 2022 14,970 $ 50.57 Granted 2,407 $ 38.80 Exercised (1,444 ) $ 45.06 Cancelled/forfeited/expired (1,842 ) $ 55.90 Outstanding at December 31, 2023 14,091 $ 48.43 4.74 $ 78,542 Exercisable at December 31, 2023 9,703 $ 52.24 3.20 $ 28,349 The weighted-average estimated fair values of options granted were $19.72, $18.66 and $24.35 for the years ended December 31, 2023, 2022 and 2021, respectively. The total intrinsic value of options exercised during the years ended December 31, 2023, 2022 and 2021 were $6.0 million, $1.4 million and $2.5 million, respectively, which we determined as of the date of exercise. The amount of cash received from the exercise of stock options was $65.1 million, $3.6 million and $8.5 million for the years ended December 31, 2023, 2022 and 2021, respectively. For the year ended December 31, 2023, the weighted-average fair value of options exercised was $49.23. As of December 31, 2023, total unrecognized compensation cost related to non-vested stock options was $36.6 million. We expect to recognize this cost over a weighted average period of 1.1 years. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures. Restricted Stock Unit Activity The following table summarizes the RSU activity for the year ended December 31, 2023 (in thousands, except per share data): Number of Shares Weighted Average Grant Date Fair Value Per Share Non-vested at December 31, 2022 2,766 $ 48.30 Granted 1,707 $ 40.51 Vested (1,055 ) $ 51.64 Cancelled/forfeited (179 ) $ 42.90 Non-vested at December 31, 2023 3,239 $ 43.40 For the years ended December 31, 2023, 2022 and 2021, the weighted-average grant date fair value of RSUs granted was $40.51, $36.14 and $57.02 per RSU, respectively. As of December 31, 2023, total unrecognized compensation cost related to RSUs was $53.7 million. We expect to recognize this cost over a weighted average period of 1.3 years. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures. Performance Restricted Stock Unit Activity The following table summarizes the PRSU activity for the year ended December 31, 2023 (in thousands, except per share data): Number of Shares Weighted Average Grant Date Fair Value Per Share Non-vested at December 31, 2022 143 $ 52.59 Granted 158 $ 57.43 Vested (75 ) $ 52.43 Non-vested at December 31, 2023 226 $ 56.04 For the years ended December 31, 2023, 2022 and 2021, the weighted-average grant date fair value of PRSUs granted was $57.43, $42.28 and $77.17 per PRSU, respectively. As of December 31, 2023, total unrecognized compensation cost related to PRSUs was $4.4 million. We expect to recognize this cost over a weighted average period of 1.4 years. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures. Stock-based Compensation Expense and Valuation Information The following table summarizes stock-based compensation expense for the years ended December 31, 2023, 2022 and 2021 (in thousands): Year Ended December 31, 2023 2022 2021 Cost of sales $ 499 $ 533 $ 456 Research, development and patent 77,826 73,704 87,522 Selling, general and administrative 27,484 26,027 32,700 Total $ 105,809 $ 100,264 $ 120,678 Refer to Note 1, Organization and Significant Accounting Policies For the years ended December 31, 2023, 2022 and 2021, we used the following weighted-average assumptions in our Black-Scholes calculations: Employee Stock Options: Year Ended December 31, 2023 2022 2021 Risk-free interest rate 3.8 % 2.1 % 0.6 % Dividend yield 0.0 % 0.0 % 0.0 % Volatility 46.8 % 54.5 % 54.0 % Expected life 6.3 years 6.3 years 4.9 years Board of Director Stock Options: Year Ended December 31, 2023 2022 2021 Risk-free interest rate 3.8 % 2.9 % 1.2 % Dividend yield 0.0 % 0.0 % 0.0 % Volatility 52.7 % 56.2 % 55.9 % Expected life 7.7 years 7.4 years 7.3 years ESPP: Year Ended December 31, 2023 2022 2021 Risk-free interest rate 5.3 % 1.2 % 0.1 % Dividend yield 0.0 % 0.0 % 0.0 % Volatility 36.0 % 50.1 % 42.4 % Expected life 6 months 6 months 6 months Risk-Free Interest Rate. Dividend Yield. Volatility. Expected Life. seven Forfeitures.

Income Taxes

Income Taxes	12 Months Ended
Income Taxes	Dec. 31, 2023
Income Taxes [Abstract]
Income Taxes	9. Income Taxes Loss before income taxes is comprised of (in thousands): Year Ended December 31, 2023 2022 2021 United States $ (334,707 ) $ (258,493 ) $ (29,966 ) Foreign 742 508 818 Loss before income taxes $ (333,965 ) $ (257,985 ) $ (29,148 ) Our income tax expense (benefit) was as follows (in thousands): Year Ended December 31, 2023 2022 2021 Current: Federal $ 35,861 $ 10,522 $ (200 ) State (3,687 ) 1,129 (690 ) Foreign 147 86 339 Total current income tax expense (benefit) 32,321 11,737 (551 ) Deferred: Federal — — — State — — — Total deferred income tax benefit — — — Total income tax expense (benefit) $ 32,321 $ 11,737 $ (551 ) Our expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to loss before income taxes. The sources and tax effects of the differences are as follows (in thousands): Year Ended December 31, 2023 2022 2021 Pre-tax loss $ (333,965 ) $ (257,985 ) $ (29,148 ) Statutory rate (70,133 ) 21.0 % (54,177 ) 21.0 % (6,121 ) 21.0 % State income tax net of federal benefit (22,597 ) 6.8 % (13,622 ) 5.3 % 4,278 (14.7 )% Foreign (22 ) 0.0 % (49 ) 0.0 % 143 (0.5 )% Net change in valuation allowance 175,388 (52.5 )% 104,951 (40.7 )% 2,885 (9.9 )% Loss on debt transactions — — — — 262 (0.9 )% Tax credits (67,131 ) 20.1 % (39,729 ) 15.4 % (23,198 ) 79.6 % Deferred tax true-up 4 0.0 % (20 ) 0.0 % (24 ) 0.1 % Tax rate change 1,023 (0.3 )% (3,091 ) 1.2 % 12,838 (44.0 )% Non-deductible compensation 3,814 (1.1 )% 3,023 (1.2 )% 5,085 (17.4 )% Other non-deductible items 327 (0.1 )% 57 0.0 % 84 (0.3 )% Foreign-derived intangible income benefit (7,493 ) 2.2 % — — — — Stock-based compensation 19,546 (5.9 )% 14,030 (5.4 )% 4,720 (16.2 )% Other (405 ) 0.1 % 364 (0.1 )% (1,503 ) 5.1 % Effective rate $ 32,321 (9.7 )% $ 11,737 (4.5 )% $ (551 ) 1.9 % Deferred income taxes reflect the net tax effects of temporary differences between the carrying amounts of assets and liabilities for financial reporting purposes and the amounts used for income tax purposes. Significant components of our deferred tax assets and liabilities as of December 31, 2023 and 2022 are as follows (in thousands): Year Ended December 31, 2023 2022 Deferred Tax Assets: Net operating loss carryovers $ 77,964 $ 87,802 Tax credits 239,962 277,436 Deferred revenue 71,683 85,700 Stock-based compensation 77,468 86,983 Intangible and capital assets 104,380 104,649 Convertible debt 16,849 34,384 Capitalized research and development expenses 238,738 119,635 Long-term lease liabilities 43,718 45,612 Sale of future royalties 144,608 — Other 10,343 15,813 Total deferred tax assets $ 1,025,713 $ 858,014 Deferred Tax Liabilities: Fixed assets (4,166 ) (4,475 ) Right-of-use assets (42,007 ) (44,504 ) Other (1,910 ) (313 ) Net deferred tax asset $ 977,630 $ 808,722 Valuation allowance (977,630 ) (808,722 ) Total net deferred tax assets and liabilities $ — $ — We evaluate our deferred tax assets regularly to determine whether adjustments to the valuation allowance are appropriate due to changes in facts or circumstances, such as changes in expected future pre-tax earnings, tax law, interactions with taxing authorities and developments in case law. In making this evaluation, we rely on our recent history of pre-tax earnings. Our material assumptions are our forecasts of future pre-tax earnings and the nature and timing of future deductions and income represented by the deferred tax assets and liabilities, all of which involve the exercise of significant judgment. Although we believe our estimates are reasonable, we are required to use significant judgment in determining the appropriate amount of valuation allowance recorded against our deferred tax assets. Our valuation allowance increased by $169 million from December 31, 2022 to December 31, 2023. The increase was primarily related to increases in our deferred tax assets for capitalized research and development expenses and sale of future royalties. At December 31, 2023, we had federal and state, primarily California, tax net operating loss carryforwards of $242.8 million and $398.8 million, respectively. Our federal tax loss carryforwards are available indefinitely. Our California tax loss carryforwards will begin to expire in 2032. At December 31, 2023, we also had federal and California research and development tax credit carryforwards of $169.7 million and $124.4 million, respectively. Our federal research and development tax credit carryforwards will begin to expire in 2038. Our California research and development tax credit carryforwards are available indefinitely. Our 2023 current tax expense includes a benefit of approximately $3.2 million related to utilization of state tax loss carryforwards, primarily California. Utilization of the net operating loss and tax credit carryforwards may be subject to an annual limitation due to the ownership change limitations provided by the Internal Revenue Code of 1986, as amended, and similar state provisions. The annual limitation may result in the expiration of net operating losses and credits before utilization. We analyze filing positions in all U.S. federal, state and foreign jurisdictions where we file income tax returns, and all open tax years in these jurisdictions to determine if we have any uncertain tax positions on any of our income tax returns. We recognize the impact of an uncertain tax position on an income tax return at the largest amount that the relevant taxing authority is more-likely-than not to sustain upon audit. We do not recognize uncertain income tax positions if they have less than 50 percent likelihood of the applicable tax authority sustaining our position. The following table summarizes our gross unrecognized tax benefits (in thousands): Year Ended December 31, 2023 2022 2021 Beginning balance of unrecognized tax benefits $ 56,567 $ 55,085 $ 54,163 Decrease for lapse of statute of limitations (14,993 ) — — Decrease for prior period tax positions (737 ) (267 ) (695 ) Increase for prior period tax positions 429 259 263 Increase for current period tax positions 2,032 1,490 1,354 Ending balance of unrecognized tax benefits $ 43,298 $ 56,567 $ 55,085 Included in the balance of unrecognized tax benefits at December 31, 2023, 2022 and 2021 was $0.3 million, $6.2 million and $6.2 million respectively, that if we recognized, could impact our effective tax rate, subject to our remaining valuation allowance. We estimate that it is reasonably possible that the balance of our gross unrecognized tax benefits may decrease by approximately $7.6 million within the next 12 months due to the lapse of statute of limitations on underlying tax positions primarily related to amortization of certain capitalized state research and development expenditures. We recognize interest and/or penalties related to income tax matters in income tax expense. During the years ended December 31, 2023, 2022 and 2021, we recognized $0.1 million, $0.8 million and $0.5 million, respectively, of accrued interest and penalties related to gross unrecognized tax benefits. We are subject to taxation in the U.S. and various state and foreign jurisdictions. U.S. tax years 2020 through 2022 remain open to examination and tax years 2019 through 2022 remain open to examination by major state taxing jurisdictions, primarily California, although net operating loss and credit carryforwards generated prior to these periods may still be adjusted upon examination by the Internal Revenue Service or state tax authorities if they have been used in an open period or are used in a future period

Employment Benefits

Employment Benefits	12 Months Ended
Employment Benefits	Dec. 31, 2023
Employment Benefits [Abstract]
Employment Benefits	10. Employment Benefits We have employee 401(k) salary deferral plans covering all employees. Employees could make contributions by withholding a percentage of their salary up to the IRS annual limits of $22,500 and $30,000 in 2023 for employees under 50 years old and employees 50 years old or over, respectively. We made approximately $7.1 million, $5.6 million and $5.5 million in matching contributions for the years ended December 31, 2023, 2022 and 2021, respectively.

Legal Proceedings

Legal Proceedings	12 Months Ended
Legal Proceedings	Dec. 31, 2023
Legal Proceedings [Abstract]
Legal Proceedings	11. 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. There are no pending material legal proceedings to which we are a party or of which our property is the subject.

Fourth Quarter Financial Data (

Fourth Quarter Financial Data (Unaudited)	12 Months Ended
Fourth Quarter Financial Data (Unaudited)	Dec. 31, 2023
Fourth Quarter Financial Data (Unaudited) [Abstract]
Fourth Quarter Financial Data (Unaudited)	12. Fourth Quarter Financial Data (Unaudited) The following financial information reflects all normal recurring adjustments, which are, in the opinion of management, necessary for a fair statement of the results of the interim periods. Summarized fourth quarter data for 2023 and 2022 are as follows (in thousands, except per share data). Three Months Ended December 31, 2023 2022 Revenue (1) $ 324,505 $ 151,890 Operating expenses (2) $ 330,627 $ 359,909 Loss from operations $ (6,122 ) $ (208,019 ) Net loss (3) $ (9,263 ) $ (52,430 ) Basic net loss per share (4) (5) $ (0.06 ) $ (0.37 ) Diluted net loss per share (4) (6) $ (0.06 ) $ (0.37 ) ________________ (1) Revenue was higher in the three months ended December 31, 2023 compared to the same period in 2022 primarily due to the $50 million milestone payment we earned from AstraZeneca when the FDA approved WAINUA for ATTRv-PN in the U.S., $36 million payment we earned when AstraZeneca licensed ION826 and revenue we recognized in the fourth quarter of 2023 from the upfront payments we received from our new collaborations with Otsuka, Roche and Novartis. (2) Operating expenses were lower in the three months ended December 31, 2023 compared to the same period in 2022 primarily due to the $80 million upfront payment we made for our collaboration with Metagenomi in the fourth quarter of 2022. (3) Our net loss for the three months ended December 31, 2022 includes the $150.1 million gain we recognized from the sale and leaseback transaction for our headquarters in Carlsbad, California. (4) We the year. (5) As discussed in Note 1, Organization and Significant Accounting Policies, (6) We incurred a net loss for the fourth quarter of 2023 and 2022. As a result, 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.

Insider Trading Arrangements

Insider Trading Arrangements	3 Months Ended	12 Months Ended
Insider Trading Arrangements	Dec. 31, 2023 shares	Dec. 31, 2023 shares
Insider Trading Arrangements [Line Items]
Material Terms of Trading Arrangement		During the quarter ended December 31, 2023, our officers and directors (as defined in Rule 16a-1(f) under the Exchange Act), or Section 16 officers and directors, adopted or terminated contracts, instructions or written plans for the purchase or sale of our securities as noted in the table below. * Contract, instruction or written plan intended to satisfy the affirmative defense conditions of Rule 10b5-1(c) under the Exchange Act. ** “Non-Rule 10b5-1 trading arrangement” as defined in item 408(c) of Regulation S-K under the Exchange Act. Action Date Trading Arrangement Total Shares to be Sold Expiration Date Rule 10b5-1* Non-Rule 10b5-1** Joseph Wender, Board Member Adoption November 30, 2023 X 104,079 February 28, 2025
Name	Joseph Wender
Title	Board Member
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	November 30, 2023
Arrangement Duration	15 months
Aggregate Available	104,079	104,079

Organization and Significant _2

Organization and Significant Accounting Policies (Policies)	12 Months Ended
Organization and Significant Accounting Policies (Policies)	Dec. 31, 2023
Organization and Basis of Presentation [Abstract]
Basis of Presentation	Basis of Presentation In our 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”).
Use of Estimates	Use of Estimates We prepare our consolidated financial statements in conformity with accounting principles generally accepted in the United States, or U.S., that require us to make estimates and assumptions that affect the amounts reported in our consolidated financial statements and accompanying notes. Actual results could differ from our estimates.
Revenue Recognition	Revenue Recognition 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 within deferred revenue in our consolidated balance sheets. 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 ASC Topic 808, Collaborative Arrangements ASC 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 that contain multiple elements, we determine which elements of the collaboration reflect a vendor-customer relationship and therefore are within the scope of ASC , 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 We evaluate the income statement classification for presentation of amounts due from or owed to other participants associated with multiple activities in a collaboration arrangement based on the nature of each separate activity. For example, in our WAINUA collaboration with AstraZeneca, we recognize funding received from AstraZeneca for co-development activities as revenue; while we recognize cost sharing payments to and from AstraZeneca associated with co-commercialization activities and co-medical affairs activities as selling, general and administrative, or SG&A, expense and research and development, or R&D, expense, respectively. 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: 1. 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. 2. Identify the performance obligations We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the contract. We may 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. When a partner exercises its option to license a medicine that was not previously determined to be a material right at the inception of the agreement 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. 3. 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 that 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. 4. 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 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 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. 5. Recognize revenue We recognize revenue in of 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. We recognize royalty revenue 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. Under our distribution agreements with Swedish Orphan Biovitrum AB, or 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. 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: 1) If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and 2) 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-effect 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. Refer to Note 4, Collaborative Arrangements and Licensing Agreements
Contracts Receivable	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 December 31, 2023, approximately 87.8 percent of our contracts receivables were from one significant customer. As of December 31, 2022, approximately 82.5 percent of our contracts receivables were from one significant customer.
Unbilled SPINRAZA Royalties	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 in our consolidated balance sheets.
Deferred Revenue	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 in our consolidated balance sheets.
Cost of Sales	Cost of Sales Our cost of sales is comprised of costs related to our commercial revenue, including 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.
Research, Development and Patent Expenses	Research, Development and Patent Expenses Our research, development and patent expenses include wages, benefits, facilities, supplies, external services, clinical trial and manufacturing costs, patents and other expenses that are directly related to our R&D operations. We expense R&D costs as we incur them. When we make payments for R&D services prior to the services being rendered, we record those amounts as prepaid assets in our consolidated balance sheets and we expense them as the services are provided. A portion of the costs included in R&D expenses are costs associated with our partner agreements. In 2023, 2022 and 2021, patent expenses were $4.3 million, $4.7 million and $5.3 million, respectively.
Income Taxes	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.
Basic and Diluted Net Loss Per Share	Basic and Diluted Net Loss per Share Basic net loss per share We compute basic net loss per share by dividing our net loss by our weighted-average number of common shares outstanding during the period. Diluted net loss per share For the years ended December 31, 2023, 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 Notes; ● Note hedges related to the Notes; ● 0.125 percent convertible senior notes, or Notes; ● Note hedges related to the 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 year ended December 31, 2023, common stock underlying the 1.75 percent convertible senior notes, or 1.75% Notes, would also have had an anti-dilutive effect on net loss per share. Additionally as of December 31, 2023, 2022 and 2021, we had warrants related to our 0% Notes 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.
Stock-Based Compensation Expense	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 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 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. Stock Options and Stock Purchase Rights: 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. The expected term of stock options granted represents the period of time that we expect them to be outstanding. Historically, we estimated the expected term of options granted based on historical exercise patterns. In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or 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 years ended December 31, 2023 and 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. 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 we granted to our board of directors after June 2020 fully vest after one year. 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 PRSUs we granted in 2020 through 2022, one third Under the terms of the PRSUs we granted in 2023, 100 percent of the PRSUs may vest at the end of the three-year performance period based on our relative TSR as compared to a peer group of companies and as measured at the end of the 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 to 200 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. Refer to Note 8, Stockholders’ Equity,
Concentration of Credit Risk	Concentration of Credit Risk Financial instruments that potentially subject us to concentrations of credit risk consist primarily of cash equivalents, short-term investments and receivables. We place our cash equivalents and short-term investments with reputable financial institutions. We primarily invest our excess cash in commercial paper and debt instruments of the U.S. Treasury, financial institutions, corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody’s, Standard & Poor’s, or S&P, or Fitch, respectively. We have established guidelines relative to diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity.
Fair Value Measurements	Fair Value Measurements We have estimated the fair value of our financial instruments. The amounts reported for cash, accounts receivable, accounts payable and accrued expenses approximate the fair value because of their short maturities. We report our investment securities at their estimated fair value based on quoted market prices for identical or similar instruments. 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 traded biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify most of our securities as Level 2. We obtain the fair value of our Level 2 investments from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value to the fair value based on observable market prices.
Cash, Cash Equivalents and Investments	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 consolidated statements 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 public and private biotechnology companies that we received as part of a technology license or partner agreement. At December 31, 2023, we held equity investments in three publicly traded companies and seven 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 consolidated statements of operations. We account for our equity investments in publicly traded companies at their listed stock price. 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.
Inventories	Inventories We reflect our inventory in our consolidated balance sheets 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.
Property, Plant and Equipment	Property, Plant and Equipment We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which we determine as the following (in years): Estimated Useful Lives Computer software, laboratory, manufacturing and other equipment 3 to 10 Building, building improvements and building systems 15 to 40 Land improvements 20 Leasehold improvements 5 to 15 Furniture and fixtures 5 to 10 We depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term. We evaluate long-lived assets, which include property, plant and equipment, 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.
Accrued Liabilities	Accrued Liabilities 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.
Convertible Debt	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 815-15 and we did not issue our convertible debt instruments at a substantial premium. We record debt issuance costs as contra-liabilities in our consolidated balance sheets at issuance and amortize them over the contractual term of the convertible debt instrument using the effective interest rate. balances of our convertible senior notes presented in our consolidated balance sheets represent the principal balance of each convertible debt instrument less debt issuance costs. As of December 31, 2023, we had three outstanding convertible senior notes, our 1.75% Notes, which mature in June 2028, our 0% Notes, which mature in April 2026, and our 0.125% Notes, which mature in December 2024. Refer to Note 7, Long-Term Obligations and Commitments
Call Spread	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
Liability Related to Sale of Future Royalties	Liability Related to Sale of Future Royalties In January 2023, we entered into a royalty purchase agreement with Royalty Pharma Investments, or Royalty Pharma, to monetize a portion of our future SPINRAZA and pelacarsen royalties we are entitled to under our arrangements with Biogen and Novartis, respectively. Refer to Note 7, Long-Term Obligations and Commitments Under our agreement with Royalty Pharma, we record upfront payments and milestone payments we receive from the sale of future royalties as a liability, net of transaction costs. We record royalty payments made to Royalty Pharma as a reduction of the liability or accrued interest and amortize the transaction costs over the estimated life of the royalty stream. We account for the associated interest expense under the effective interest rate method, while continuing to recognize the full amount of royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue. We calculate the liability related to the sale of future royalties, effective interest rate and the related interest expense using our current estimate of anticipated future royalty payments under the arrangement, which we periodically reassess based on internal projections and information from our partners who are responsible for commercializing the medicines. If there is a material change in our estimate, we will prospectively adjust the effective interest rate and the related interest expense.
Leases	Leases We determine if an arrangement contains a lease at inception. We currently only have operating leases. We recognize a right-of-use operating lease asset and associated short- and long-term operating lease liability in our consolidated balance sheets 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. As our leases do not provide an interest rate implicit in the lease, we use our incremental borrowing rate, based on the information available 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. Our leases do not include material variable or contingent lease payments. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.
Segment Information	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
Recently Issued Accounting Standards	Recently Issued Accounting Standards In November 2023, the Financial Accounting Standards Board, or FASB, issued updated guidance on segment reporting. The guidance requires public companies with a single reportable segment to provide all disclosures required under ASC 280, Segment Reporting In December 2023, the FASB issued updated guidance on income tax disclosures. The new guidance requires companies to provide additional disaggregation of information related to the income tax rate reconciliation and income tax payments. In addition, the guidance eliminates certain existing disclosure requirements related to uncertain tax positions and unrecognized deferred tax liabilities. This update is effective for annual periods beginning after December 15, 2024. Early adoption of this guidance is permitted. We currently plan to adopt this guidance in our 2025 Annual Report on Form 10-K. We do not expect any other recently issued accounting standards to have a material impact to our financial results.

Organization and Significant _3

Organization and Significant Accounting Policies (Tables)	12 Months Ended
Organization and Significant Accounting Policies (Tables)	Dec. 31, 2023
Organization and Basis of Presentation [Abstract]
Property, Plant and Equipment	We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its estimated useful life, which we determine as the following (in years): Estimated Useful Lives Computer software, laboratory, manufacturing and other equipment 3 to 10 Building, building improvements and building systems 15 to 40 Land improvements 20 Leasehold improvements 5 to 15 Furniture and fixtures 5 to 10

Supplemental Financial Data (Ta

Supplemental Financial Data (Tables)	12 Months Ended
Supplemental Financial Data (Tables)	Dec. 31, 2023
Supplemental Financial Data [Abstract]
Inventories	Our inventory consisted of the following (in thousands): December 31, 2023 2022 Raw materials: Raw materials- clinical $ 20,985 $ 17,061 Raw materials- commercial 1,809 2,699 Total raw materials 22,794 19,760 Work in process 5,477 2,109 Finished goods 154 164 Total inventory $ 28,425 $ 22,033
Property, Plant and Equipment	Our property, plant and equipment consisted of the following (in thousands): December 31, 2023 2022 Computer software, laboratory, manufacturing and other equipment $ 79,885 $ 74,351 Building, building improvements and building systems 41,228 41,158 Leasehold improvements 28,276 28,357 Furniture and fixtures 9,844 9,575 159,233 153,441 Less: Accumulated depreciation (96,759 ) (87,716 ) 62,474 65,725 Land 8,569 8,569 Total $ 71,043 $ 74,294
Accrued Liabilities	Our accrued liabilities consisted of the following (in thousands): December 31, 2023 2022 Clinical expenses $ 105,967 $ 116,460 In-licensing expenses 7,454 7,945 Commercial expenses 4,875 3,498 Other miscellaneous expenses 29,598 12,198 Total accrued liabilities $ 147,894 $ 140,101

Revenues (Tables)

Revenues (Tables)	12 Months Ended
Revenues (Tables)	Dec. 31, 2023
Revenues [Abstract]
Revenues	During the years ended December 31, , and Year Ended December 31, 2023 2022 2021 Revenue: Commercial revenue: SPINRAZA royalties $ 240,379 $ 242,314 $ 267,776 Other commercial revenue: TEGSEDI and WAYLIVRA revenue, net 34,913 30,051 55,500 Licensing and other royalty revenue 33,299 30,993 19,119 Total other commercial revenue 68,212 61,044 74,619 Total commercial revenue 308,591 303,358 342,395 Research and development revenue: Collaborative agreement revenue 352,657 207,222 468,061 WAINUA joint development revenue 126,399 76,787 — Total research and development revenue 479,056 284,009 468,061 Total revenue $ 787,647 $ 587,367 $ 810,456

Collaborative Arrangements an_2

Collaborative Arrangements and Licensing Agreements (Tables)	12 Months Ended
	Dec. 31, 2023
Biogen [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in thousands, except percentage amounts): Year Ended December 31, 2023 2022 2021 Revenue from our relationship with Biogen $ 350,146 $ 366,696 $ 428,784 Percentage of total revenue 44 % 62 % 53 %
AstraZeneca [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with AstraZeneca (in thousands, except percentage amounts): Year Ended December 31, 2023 2022 2021 Revenue from our relationship with AstraZeneca $ 202,236 $ 79,160 $ 254,591 Percentage of total revenue 26 % 13 % 31 %
GSK [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with GSK (in thousands, except percentage amounts): Year Ended December 31, 2023 2022 2021 Revenue from our relationship with GSK $ 15,000 $ — $ — Percentage of total revenue 2 % 0 % 0 %
Novartis [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with Novartis (in thousands, except percentage amounts): Year Ended December 31, 2023 2022 2021 Revenue from our relationship with Novartis $ 30,194 $ 237 $ 25,526 Percentage of total revenue 4 % Less than 1% 3 %
Otsuka [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the year ended December 31, 2023, we earned the following revenue from our relationship with Otsuka (in thousands, except percentage amount): Year Ended December 31, 2023 Revenue from our relationship with Otsuka $ 56,480 Percentage of total revenue 7 %
Roche [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with Roche (in thousands, except percentage amounts): Year Ended December 31, 2023 2022 2021 Revenue from our relationship with Roche $ 48,838 $ 67,202 $ 17,241 Percentage of total revenue 6 % 11 % 2 %
Sobi [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our distribution agreement with Sobi for TEGSEDI in North America (in thousands, except percentage amounts): Year Ended December 31, 2023 2022 2021 TEGSEDI revenue from our distribution agreement with Sobi in North America $ 2,646 $ 4,004 $ 7,443 Percentage of total revenue Less than 1% 1 % 1 %
Alnylam [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the years ended December 31, 2023, 2022 and 2021, we earned the following revenue from our relationship with Alnylam (in thousands, except percentage amounts): Year Ended December 31, 2023 2022 2021 Revenue from our relationship with Alnylam $ 28,426 $ 21,389 $ — Percentage of total revenue 4 % 4 % 0 %

Investments (Tables)

Investments (Tables)	12 Months Ended
Investments (Tables)	Dec. 31, 2023
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 December 31, 2023: One year 68 % After one year two years 24 % After two years three and a half years 8 % Total 100 %
Summary of Investments	The following is a summary of our investments (in thousands): Amortized Gross Unrealized Estimated December 31, 2023 Cost Gains Losses Fair Value Available-for-sale securities: Corporate debt securities (1) $ 559,967 $ 157 $ (2,625 ) $ 557,499 Debt securities issued by U.S. government agencies 224,711 64 (611 ) 224,164 Debt securities issued by the U.S. Treasury (1) 513,784 152 (1,889 ) 512,047 Debt securities issued by states of the U.S. and political subdivisions of the states 17,757 42 (113 ) 17,686 Total securities with a maturity of one year or less 1,316,219 415 (5,238 ) 1,311,396 Corporate debt securities 243,151 1,270 (692 ) 243,729 Debt securities issued by U.S. government agencies 110,138 547 (21 ) 110,664 Debt securities issued by the U.S. Treasury 294,873 1,239 (480 ) 295,632 Debt securities issued by states of the U.S. and political subdivisions of the states 3,466 7 (4 ) 3,469 Total securities with a maturity of more than one year 651,628 3,063 (1,197 ) 653,494 Total available-for-sale securities $ 1,967,847 $ 3,478 $ (6,435 ) $ 1,964,890 Equity securities: Publicly traded equity securities included in other current assets (2) $ 11,897 $ 236 $ (5,832 ) $ 6,301 Privately held securities included in deposits and other assets (3) 23,115 25,001 (5,125 ) 42,991 Total equity securities $ 35,012 $ 25,237 $ (10,957 ) $ 49,292 Total available-for-sale and equity securities $ 2,002,859 $ 28,715 $ (17,392 ) $ 2,014,182 Amortized Gross Unrealized Estimated December 31, 2022 Cost Gains Losses Fair Value Available-for-sale securities: Corporate debt securities (1) $ 513,790 $ 23 $ (4,365 ) $ 509,448 Debt securities issued by U.S. government agencies 133,585 — (1,829 ) 131,756 Debt securities issued by the U.S. Treasury (1) 512,655 23 (5,124 ) 507,554 Debt securities issued by states of the U.S. and political subdivisions of the states 57,484 18 (686 ) 56,816 Other municipal debt securities 6,008 — (14 ) 5,994 Total securities with a maturity of one year or less 1,223,522 64 (12,018 ) 1,211,568 Corporate debt securities 227,631 14 (10,143 ) 217,502 Debt securities issued by U.S. government agencies 34,339 — (1,040 ) 33,299 Debt securities issued by the U.S. Treasury 245,030 — (4,109 ) 240,921 Debt securities issued by states of the U.S. and political subdivisions of the states 18,314 116 (329 ) 18,101 Total securities with a maturity of more than one year 525,314 130 (15,621 ) 509,823 Total available-for-sale securities $ 1,748,836 $ 194 $ (27,639 ) $ 1,721,391 Equity securities: Publicly traded equity securities included in other current assets (2) $ 11,897 $ — $ (1,358 ) $ 10,539 Privately held equity securities included in deposits and other assets (3) 23,115 17,257 — 40,372 Total equity securities $ 35,012 $ 17,257 $ (1,358 ) $ 50,911 Total available-for-sale and equity securities $ 1,783,848 $ 17,451 $ (28,997 ) $ 1,772,302 ________________ (1) Includes investments classified as cash equivalents in our consolidated balance sheets. (2) Our publicly traded equity securities are included in other current assets. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2023, we recorded a $4.2 million net unrealized loss in our consolidated statements of operations related to changes in the fair value of our investments in publicly traded companies. (3) Our privately held equity securities are included in deposits and other assets. We recognize our privately held equity securities at , we recorded a $ million net unrealized gain in our consolidated statements of operations related to changes in the fair value of our investments in privately held companies.
Temporarily Impaired Investments	The following is a summary of our investments we considered to be temporarily impaired at (in thousands, except for number of 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 297 $ 323,708 $ (553 ) $ 178,183 $ (2,764 ) $ 501,891 $ (3,317 ) Debt securities issued by U.S. government agencies 63 199,372 (246 ) 14,777 (386 ) 214,149 (632 ) Debt securities issued by the U.S. Treasury 34 325,966 (1,031 ) 131,000 (1,338 ) 456,966 (2,369 ) Debt securities issued by states of the U.S. and political subdivisions of the states 61 8,352 (17 ) 7,888 (100 ) 16,240 (117 ) Total temporarily impaired securities 455 $ 857,398 $ (1,847 ) $ 331,848 $ (4,588 ) $ 1,189,246 $ (6,435 )

Fair Value Measurements (Tables

Fair Value Measurements (Tables)	12 Months Ended
Fair Value Measurements (Tables)	Dec. 31, 2023
Fair Value Measurements [Abstract]
Assets Measured at Fair Value on a Recurring Basis	The following tables present the major security types we held at December 31, 2023 and 2022 that we regularly measure and carry at fair value At December 31, 2023 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 185,424 $ 185,424 $ — Corporate debt securities (2) 801,228 — 801,228 Debt securities issued by U.S. government agencies (3) 334,828 — 334,828 Debt securities issued by the U.S. Treasury (3) 807,679 807,679 — Debt securities issued by states of the U.S. and political subdivisions of the states (3) 21,155 — 21,155 Publicly traded equity securities included in other current assets (5) 6,301 6,301 — Total $ 2,156,615 $ 999,404 $ 1,157,211 At December 31, 2022 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 211,655 $ 211,655 $ — Corporate debt securities (4) 726,950 — 726,950 Debt securities issued by U.S. government agencies (3) 165,055 — 165,055 Debt securities issued by the U.S. Treasury (3) 748,475 748,475 — Debt securities issued by states of the U.S. and political subdivisions of the states (3) 74,917 — 74,917 Other municipal debt securities (3) 5,994 — 5,994 Publicly traded equity securities included in other current assets (5) 10,539 10,539 — Total $ 1,943,585 $ 970,669 $ 972,916 ________________ (1) Included in cash and cash equivalents in our consolidated balance sheets. (2) $33.0 million was included in cash and cash equivalents, with the difference included in short-term investments in our consolidated balance sheets. (3) Included in short-term investments in our consolidated balance sheets. (4) $11.0 million was included in cash and cash equivalents, with the difference included in short-term investments in our consolidated balance sheets. (5) Included in other current assets in our consolidated balance sheets.

Long-Term Obligations and Com_2

Long-Term Obligations and Commitments (Tables)	12 Months Ended
Long-Term Obligations and Commitments (Tables)	Dec. 31, 2023
Long-Term Obligations and Commitments [Abstract]
Long-Term Obligations	The carrying value of our long-term obligations was as follows (in thousands): December 31, 2023 2022 1.75 $ 562,285 $ — 0 625,380 622,242 0.125 — 544,504 Liability related to sale of future royalties 513,736 — Lease liabilities 178,969 186,156 Mortgage debt 8,859 8,998 Other obligations 33,714 7,295 Total $ 1,922,943 $ 1,369,195 Less: current portion (8,831 ) (7,535 ) Total Long-Term Obligations $ 1,914,112 $ 1,361,660
Convertible Notes [Abstract]
Debt Maturity Schedules	Annual convertible and mortgage debt maturities, including fixed and determinable interest, at December 31, 2023 are as follows (in thousands): 2024 $ 55,298 2025 10,657 2026 643,157 2027 10,509 2028 580,277 Thereafter 8,462 Total debt and mortgage maturities $ 1,308,360 Less: Current portion included in other current liabilities (157 ) Less: Fixed and determinable interest (47,138 ) Less: Debt issuance costs (20,061 ) Total debt $ 1,241,004
Amounts Related to Operating Leases	Amounts related to our operating leases were as follows (dollar amounts in millions): At December 31, 2023 Right-of-use operating lease assets $ 171.9 Operating lease liabilities $ 179.0 Weighted average remaining lease term 13.0 years Weighted average discount rate 6.9 %
Future Payments for Operating Lease Liabilities	As of December 31, 2023, the future payments for our operating lease liabilities are as follows (in thousands): Operating Leases Year ending December 31, 2024 $ 20,398 2025 20,645 2026 20,781 2027 20,800 2028 20,774 Thereafter 176,138 Total minimum lease payments 279,536 Less: Imputed interest (100,567 ) Less: Current portion (included in other current liabilities (8,094 ) Total long-term lease liabilities $ 170,875
Liability Related to Sale of Future Royalties	The following is a summary of our liability related to sale of future royalties for the year ended (in thousands): Proceeds from sale of future royalties $ 500,000 Royalty payments to Royalty Pharma (44,628 ) Interest expense related to sale of future royalties 68,238 Liability related to sale of future royalties as of December 31, 2023 523,610 Issuance costs related to sale of future royalties (10,434 ) Amortization of issuance costs related to sale of future royalties as of December 31, 2023 560 Net liability related to sale of future royalties as of December 31, 2023 $ 513,736
1.75% Notes [Member]
Convertible Notes [Abstract]
Convertible Senior Notes	At December 31, 2023, we had the following 1.75% Notes outstanding (in millions, except interest rate and price per share data): 1.75% Notes Outstanding principal balance $ 575.0 Unamortized debt issuance costs $ 12.7 Maturity date June 2028 Interest rate 1.75 % Effective interest rate 2.3 % Conversion price per share $ 53.73 Total shares of common stock subject to conversion 10.7
0% Notes [Member]
Convertible Notes [Abstract]
Convertible Senior Notes	At December 31, 2023, we had the following 0% Notes outstanding (in millions, except interest rate and price per share data): 0% Notes Outstanding principal balance $ 632.5 Unamortized debt issuance costs $ 7.2 Maturity date April 2026 Interest rate 0 % Effective interest rate 0.5 % 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% Notes [Member]
Convertible Notes [Abstract]
Convertible Senior Notes	At December 31, 2023, we had the following 0.125% Notes outstanding with interest payable semi-annually (in millions, except interest rate and price per share data): 0.125% Notes Outstanding principal balance $ 44.5 Unamortized debt issuance costs $ 0.2 Maturity date December 2024 Interest rate 0.125 % Effective interest rate 0.5 % Conversion price per share $ 83.28 Effective conversion price per share with call spread $ 123.38 Total shares of common stock subject to conversion, excluding shares related to 0.125 0.5

Stockholders' Equity (Tables)

Stockholders' Equity (Tables)	12 Months Ended
Stockholders' Equity (Tables)	Dec. 31, 2023
Stockholders' Equity [Abstract]
Stock Option Activity	The following table summarizes the stock option activity under our stock plans for the year ended December 31, 2023 (in thousands, except per share and contractual life data): Number of Shares Weighted Average Exercise Price Per Share Average Remaining Contractual Term (Years) Aggregate Intrinsic Value Outstanding at December 31, 2022 14,970 $ 50.57 Granted 2,407 $ 38.80 Exercised (1,444 ) $ 45.06 Cancelled/forfeited/expired (1,842 ) $ 55.90 Outstanding at December 31, 2023 14,091 $ 48.43 4.74 $ 78,542 Exercisable at December 31, 2023 9,703 $ 52.24 3.20 $ 28,349
Restricted Stock Unit Activity	The following table summarizes the RSU activity for the year ended December 31, 2023 (in thousands, except per share data): Number of Shares Weighted Average Grant Date Fair Value Per Share Non-vested at December 31, 2022 2,766 $ 48.30 Granted 1,707 $ 40.51 Vested (1,055 ) $ 51.64 Cancelled/forfeited (179 ) $ 42.90 Non-vested at December 31, 2023 3,239 $ 43.40
Performance Restricted Stock Unit Activity	The following table summarizes the PRSU activity for the year ended December 31, 2023 (in thousands, except per share data): Number of Shares Weighted Average Grant Date Fair Value Per Share Non-vested at December 31, 2022 143 $ 52.59 Granted 158 $ 57.43 Vested (75 ) $ 52.43 Non-vested at December 31, 2023 226 $ 56.04
Stock-Based Compensation Expense	The following table summarizes stock-based compensation expense for the years ended December 31, 2023, 2022 and 2021 (in thousands): Year Ended December 31, 2023 2022 2021 Cost of sales $ 499 $ 533 $ 456 Research, development and patent 77,826 73,704 87,522 Selling, general and administrative 27,484 26,027 32,700 Total $ 105,809 $ 100,264 $ 120,678
Weighted-Average Assumptions for Stock Options	Employee Stock Options: Year Ended December 31, 2023 2022 2021 Risk-free interest rate 3.8 % 2.1 % 0.6 % Dividend yield 0.0 % 0.0 % 0.0 % Volatility 46.8 % 54.5 % 54.0 % Expected life 6.3 years 6.3 years 4.9 years Board of Director Stock Options: Year Ended December 31, 2023 2022 2021 Risk-free interest rate 3.8 % 2.9 % 1.2 % Dividend yield 0.0 % 0.0 % 0.0 % Volatility 52.7 % 56.2 % 55.9 % Expected life 7.7 years 7.4 years 7.3 years
Weighted-Average Assumptions for ESPP	ESPP: Year Ended December 31, 2023 2022 2021 Risk-free interest rate 5.3 % 1.2 % 0.1 % Dividend yield 0.0 % 0.0 % 0.0 % Volatility 36.0 % 50.1 % 42.4 % Expected life 6 months 6 months 6 months

Income Taxes (Tables)

Income Taxes (Tables)	12 Months Ended
Income Taxes (Tables)	Dec. 31, 2023
Income Taxes [Abstract]
Loss Before Income Taxes	Loss before income taxes is comprised of (in thousands): Year Ended December 31, 2023 2022 2021 United States $ (334,707 ) $ (258,493 ) $ (29,966 ) Foreign 742 508 818 Loss before income taxes $ (333,965 ) $ (257,985 ) $ (29,148 )
Income Tax Expense (Benefit)	Our income tax expense (benefit) was as follows (in thousands): Year Ended December 31, 2023 2022 2021 Current: Federal $ 35,861 $ 10,522 $ (200 ) State (3,687 ) 1,129 (690 ) Foreign 147 86 339 Total current income tax expense (benefit) 32,321 11,737 (551 ) Deferred: Federal — — — State — — — Total deferred income tax benefit — — — Total income tax expense (benefit) $ 32,321 $ 11,737 $ (551 )
Reconciliation of Statutory to Effective Tax Rate	Our expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to loss before income taxes. The sources and tax effects of the differences are as follows (in thousands): Year Ended December 31, 2023 2022 2021 Pre-tax loss $ (333,965 ) $ (257,985 ) $ (29,148 ) Statutory rate (70,133 ) 21.0 % (54,177 ) 21.0 % (6,121 ) 21.0 % State income tax net of federal benefit (22,597 ) 6.8 % (13,622 ) 5.3 % 4,278 (14.7 )% Foreign (22 ) 0.0 % (49 ) 0.0 % 143 (0.5 )% Net change in valuation allowance 175,388 (52.5 )% 104,951 (40.7 )% 2,885 (9.9 )% Loss on debt transactions — — — — 262 (0.9 )% Tax credits (67,131 ) 20.1 % (39,729 ) 15.4 % (23,198 ) 79.6 % Deferred tax true-up 4 0.0 % (20 ) 0.0 % (24 ) 0.1 % Tax rate change 1,023 (0.3 )% (3,091 ) 1.2 % 12,838 (44.0 )% Non-deductible compensation 3,814 (1.1 )% 3,023 (1.2 )% 5,085 (17.4 )% Other non-deductible items 327 (0.1 )% 57 0.0 % 84 (0.3 )% Foreign-derived intangible income benefit (7,493 ) 2.2 % — — — — Stock-based compensation 19,546 (5.9 )% 14,030 (5.4 )% 4,720 (16.2 )% Other (405 ) 0.1 % 364 (0.1 )% (1,503 ) 5.1 % Effective rate $ 32,321 (9.7 )% $ 11,737 (4.5 )% $ (551 ) 1.9 %
Deferred Tax Assets and Liabilities	Significant components of our deferred tax assets and liabilities as of December 31, 2023 and 2022 are as follows (in thousands): Year Ended December 31, 2023 2022 Deferred Tax Assets: Net operating loss carryovers $ 77,964 $ 87,802 Tax credits 239,962 277,436 Deferred revenue 71,683 85,700 Stock-based compensation 77,468 86,983 Intangible and capital assets 104,380 104,649 Convertible debt 16,849 34,384 Capitalized research and development expenses 238,738 119,635 Long-term lease liabilities 43,718 45,612 Sale of future royalties 144,608 — Other 10,343 15,813 Total deferred tax assets $ 1,025,713 $ 858,014 Deferred Tax Liabilities: Fixed assets (4,166 ) (4,475 ) Right-of-use assets (42,007 ) (44,504 ) Other (1,910 ) (313 ) Net deferred tax asset $ 977,630 $ 808,722 Valuation allowance (977,630 ) (808,722 ) Total net deferred tax assets and liabilities $ — $ —
Gross Unrecognized Tax Benefits	The following table summarizes our gross unrecognized tax benefits (in thousands): Year Ended December 31, 2023 2022 2021 Beginning balance of unrecognized tax benefits $ 56,567 $ 55,085 $ 54,163 Decrease for lapse of statute of limitations (14,993 ) — — Decrease for prior period tax positions (737 ) (267 ) (695 ) Increase for prior period tax positions 429 259 263 Increase for current period tax positions 2,032 1,490 1,354 Ending balance of unrecognized tax benefits $ 43,298 $ 56,567 $ 55,085

Fourth Quarter Financial Data_2

Fourth Quarter Financial Data (Unaudited) (Tables)	12 Months Ended
Fourth Quarter Financial Data (Unaudited) (Tables)	Dec. 31, 2023
Fourth Quarter Financial Data (Unaudited) [Abstract]
Fourth Quarter Financial Data (Unaudited)	The following financial information reflects all normal recurring adjustments, which are, in the opinion of management, necessary for a fair statement of the results of the interim periods. Summarized fourth quarter data for 2023 and 2022 are as follows (in thousands, except per share data). Three Months Ended December 31, 2023 2022 Revenue (1) $ 324,505 $ 151,890 Operating expenses (2) $ 330,627 $ 359,909 Loss from operations $ (6,122 ) $ (208,019 ) Net loss (3) $ (9,263 ) $ (52,430 ) Basic net loss per share (4) (5) $ (0.06 ) $ (0.37 ) Diluted net loss per share (4) (6) $ (0.06 ) $ (0.37 ) ________________ (1) Revenue was higher in the three months ended December 31, 2023 compared to the same period in 2022 primarily due to the $50 million milestone payment we earned from AstraZeneca when the FDA approved WAINUA for ATTRv-PN in the U.S., $36 million payment we earned when AstraZeneca licensed ION826 and revenue we recognized in the fourth quarter of 2023 from the upfront payments we received from our new collaborations with Otsuka, Roche and Novartis. (2) Operating expenses were lower in the three months ended December 31, 2023 compared to the same period in 2022 primarily due to the $80 million upfront payment we made for our collaboration with Metagenomi in the fourth quarter of 2022. (3) Our net loss for the three months ended December 31, 2022 includes the $150.1 million gain we recognized from the sale and leaseback transaction for our headquarters in Carlsbad, California. (4) We the year. (5) As discussed in Note 1, Organization and Significant Accounting Policies, (6) We incurred a net loss for the fourth quarter of 2023 and 2022. As a result, 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.

Organization and Significant _4

Organization and Significant Accounting Policies, Contracts Receivable (Details) - Partner	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022
Contracts Receivable [Abstract]
Period of time after billing when payment is received	3 months
Contracts Receivable [Abstract]
Number of significant customers	1	1
Contracts Receivables [Member] \| Credit Concentration [Member] \| One Significant Customer [Member]
Contracts Receivable [Abstract]
Concentration percentage	87.80%
Contracts Receivables [Member] \| Credit Concentration [Member] \| Two Significant Customers [Member]
Contracts Receivable [Abstract]
Concentration percentage		82.50%

Organization and Significant _5

Organization and Significant Accounting Policies, Deferred Revenue (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022
Deferred Revenue [Abstract]
Revenue recognized from amounts in beginning deferred revenue balance	$ 78.2	$ 73.5

Organization and Significant _6

Organization and Significant Accounting Policies, Research, Development and Patent Expenses (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Research, Development and Patent Expenses [Abstract]
Patent expenses	$ 4.3	$ 4.7	$ 5.3

Organization and Significant _7

Organization and Significant Accounting Policies, Basic and Diluted Net Loss per Share (Details)	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021	Apr. 30, 2021	Dec. 31, 2019
0% Notes [Member]
Basic and Diluted Net Loss Per Share [Abstract]
Interest rate on convertible senior notes	0%	0%	0%	0%
0.125% Notes [Member]
Basic and Diluted Net Loss Per Share [Abstract]
Interest rate on convertible senior notes	0.125%	0.125%	0.125%		0.125%
1.75% Notes [Member]
Basic and Diluted Net Loss Per Share [Abstract]
Interest rate on convertible senior notes	1.75%	1.75%

Organization and Significant _8

Organization and Significant Accounting Policies, Stock-Based Compensation Expense (Details)	12 Months Ended
	Dec. 31, 2023 Period shares
Stock Options Granted Prior to January 1, 2022 [Member]
Stock-Based Compensation Expense [Abstract]
Award term	7 years
Stock Options Granted on January 1, 2022 and Thereafter [Member]
Stock-Based Compensation Expense [Abstract]
Award term	10 years
RSUs [Member] \| Employees [Member]
Stock-Based Compensation Expense [Abstract]
Vesting period	4 years
RSUs [Member] \| Board of Directors [Member] \| Granted Prior to June 2020 [Member]
Stock-Based Compensation Expense [Abstract]
Vesting period	4 years
RSUs [Member] \| Board of Directors [Member] \| Granted After June 2020 [Member]
Stock-Based Compensation Expense [Abstract]
Vesting period	1 year
PRSUs [Member]
Stock-Based Compensation Expense [Abstract]
Term of Alternative Calculation	3 years
Measurement period for Alternative Calculation	3 years
PRSUs [Member] \| Executive Officers [Member]
Stock-Based Compensation Expense [Abstract]
Number of performance periods \| Period	3
Vesting period	3 years
PRSUs [Member] \| Executive Officers [Member] \| One-Year Period [Member]
Stock-Based Compensation Expense [Abstract]
Vesting period	1 year
PRSUs [Member] \| Executive Officers [Member] \| Two-Year Period [Member]
Stock-Based Compensation Expense [Abstract]
Vesting period	2 years
PRSUs [Member] \| Executive Officers [Member] \| Three-Year Period [Member]
Stock-Based Compensation Expense [Abstract]
Vesting period	3 years
PRSUs [Member] \| Executive Officers [Member] \| Granted 2020 through 2022 [Member]
Stock-Based Compensation Expense [Abstract]
Number of units guaranteed to vest (in shares)	0
PRSUs [Member] \| Executive Officers [Member] \| Granted 2020 through 2022 [Member] \| Minimum [Member]
Stock-Based Compensation Expense [Abstract]
Percentage of units guaranteed to vest	0%
PRSUs [Member] \| Executive Officers [Member] \| Granted 2020 through 2022 [Member] \| Maximum [Member]
Stock-Based Compensation Expense [Abstract]
Percentage of units guaranteed to vest	150%
PRSUs [Member] \| Executive Officers [Member] \| Granted 2020 through 2022 [Member] \| One-Year Period [Member]
Stock-Based Compensation Expense [Abstract]
Vesting percentage	33.30%
PRSUs [Member] \| Executive Officers [Member] \| Granted 2020 through 2022 [Member] \| Two-Year Period [Member]
Stock-Based Compensation Expense [Abstract]
Vesting percentage	33.30%
PRSUs [Member] \| Executive Officers [Member] \| Granted 2020 through 2022 [Member] \| Three-Year Period [Member]
Stock-Based Compensation Expense [Abstract]
Vesting percentage	33.30%
PRSUs [Member] \| Executive Officers [Member] \| Granted in 2023 [Member]
Stock-Based Compensation Expense [Abstract]
Vesting percentage	100%
Number of units guaranteed to vest (in shares)	0
PRSUs [Member] \| Executive Officers [Member] \| Granted in 2023 [Member] \| Minimum [Member]
Stock-Based Compensation Expense [Abstract]
Percentage of units guaranteed to vest	0%
PRSUs [Member] \| Executive Officers [Member] \| Granted in 2023 [Member] \| Maximum [Member]
Stock-Based Compensation Expense [Abstract]
Percentage of units guaranteed to vest	200%

Organization and Significant _9

Organization and Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)	Dec. 31, 2023 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%	7

Organization and Significant_10

Organization and Significant Accounting Policies, Property, Plant and Equipment (Details)	Dec. 31, 2023
Computer Software, Laboratory, Manufacturing and Other Equipment [Member] \| Minimum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful life	3 years
Computer Software, Laboratory, Manufacturing and Other Equipment [Member] \| Maximum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful life	10 years
Building, Building Improvements and Building Systems [Member] \| Minimum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful life	15 years
Building, Building Improvements and Building Systems [Member] \| Maximum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful life	40 years
Land Improvements [Member]
Property, Plant and Equipment [Abstract]
Estimated useful life	20 years
Leasehold Improvements [Member] \| Minimum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful life	5 years
Leasehold Improvements [Member] \| Maximum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful life	15 years
Furniture and Fixtures [Member] \| Minimum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful life	5 years
Furniture and Fixtures [Member] \| Maximum [Member]
Property, Plant and Equipment [Abstract]
Estimated useful life	10 years

Organization and Significant_11

Organization and Significant Accounting Policies, Convertible Debt (Details) - Note	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021	Apr. 30, 2021	Dec. 31, 2019
Convertible Debt [Abstract]
Number of outstanding convertible notes	3
1.75% Notes [Member]
Convertible Debt [Abstract]
Interest rate on convertible senior notes	1.75%	1.75%
0% Notes [Member]
Convertible Debt [Abstract]
Interest rate on convertible senior notes	0%	0%	0%	0%
0.125% Notes [Member]
Convertible Debt [Abstract]
Interest rate on convertible senior notes	0.125%	0.125%	0.125%		0.125%

Organization and Significant_12

Organization and Significant Accounting Policies, Call Spread (Details)	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021	Apr. 30, 2021	Dec. 31, 2019
0% Notes [Member]
Call Spread [Abstract]
Interest rate on convertible senior notes	0%	0%	0%	0%
0.125% Notes [Member]
Call Spread [Abstract]
Interest rate on convertible senior notes	0.125%	0.125%	0.125%		0.125%

Organization and Significant_13

Organization and Significant Accounting Policies, Segment Information (Details)	12 Months Ended
	Dec. 31, 2023 Segment
Segment Information [Abstract]
Number of operating segments	1

Supplemental Financial Data, In

Supplemental Financial Data, Inventories (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Inventory [Abstract]
Raw materials	$ 22,794	$ 19,760
Work in process	5,477	2,109
Finished goods	154	164
Total inventory	28,425	22,033
Clinical [Member]
Inventory [Abstract]
Raw materials	20,985	17,061
Commercial [Member]
Inventory [Abstract]
Raw materials	$ 1,809	$ 2,699

Supplemental Financial Data, Pr

Supplemental Financial Data, Property, Plant and Equipment (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Property, Plant and Equipment [Abstract]
Less accumulated depreciation	$ (96,759)	$ (87,716)
Property, plant and equipment, net	71,043	74,294
Property, Plant and Equipment, Excluding Land [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	159,233	153,441
Property, plant and equipment, net	62,474	65,725
Computer Software, Laboratory, Manufacturing and Other Equipment [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	79,885	74,351
Building, Building Improvements and Building Systems [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	41,228	41,158
Leasehold Improvements [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	28,276	28,357
Furniture and Fixtures [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	9,844	9,575
Land [Member]
Property, Plant and Equipment [Abstract]
Property, plant and equipment	$ 8,569	$ 8,569

Supplemental Financial Data, Ac

Supplemental Financial Data, Accrued Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022
Accrued Liabilities [Abstract]
Clinical expenses	$ 105,967	$ 116,460
In-licensing expenses	7,454	7,945
Commercial expenses	4,875	3,498
Other miscellaneous expenses	29,598	12,198
Total accrued liabilities	$ 147,894	$ 140,101

Revenues (Details)

Revenues (Details) $ in Thousands	12 Months Ended
Revenues (Details) $ in Thousands	Dec. 31, 2023 USD ($)	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($) Component PerformanceObligation
Revenues [Abstract]
Revenue	$ 787,647	$ 587,367	$ 810,456
WAINUA (Eplontersen) Collaboration with AstraZeneca [Member]
Revenues [Abstract]
Revenue	$ 20,000		$ 200,000
Number of material components \| Component			4
Number of separate performance obligations \| PerformanceObligation			1
Transaction price			$ 200,000
Percentage of costs associated with ongoing global Phase 3 development program paid by AstraZeneca	55%
Commercial Revenue [Member]
Revenues [Abstract]
Revenue	$ 308,591	303,358	342,395
SPINRAZA Royalties [Member]
Revenues [Abstract]
Revenue	240,379	242,314	267,776
Other Commercial Revenue [Member]
Revenues [Abstract]
Revenue	68,212	61,044	74,619
TEGSEDI and WAYLIVRA Revenue, Net [Member]
Revenues [Abstract]
Revenue	34,913	30,051	55,500
Licensing and Other Royalty Revenue [Member]
Revenues [Abstract]
Revenue	33,299	30,993	19,119
Research and Development Revenue [Member]
Revenues [Abstract]
Revenue	479,056	284,009	468,061
Collaborative Agreement Revenue [Member]
Revenues [Abstract]
Revenue	352,657	207,222	468,061
WAINUA Joint Development Revenue [Member]
Revenues [Abstract]
Revenue	$ 126,399	$ 76,787	$ 0

Collaborative Arrangements an_3

Collaborative Arrangements and Licensing Agreements, Biogen (Details) $ in Thousands	3 Months Ended		12 Months Ended
	Dec. 31, 2023 USD ($) Medicine	Jun. 30, 2018 USD ($)	Dec. 31, 2023 USD ($) Medicine	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)	Dec. 31, 2020 USD ($)	Dec. 31, 2017 USD ($)	Dec. 31, 2013 USD ($)	Dec. 31, 2012 USD ($) PerformanceObligation Program	Jan. 31, 2023 USD ($)	Apr. 30, 2018 USD ($) PerformanceObligation	Sep. 30, 2013 USD ($) PerformanceObligation
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue			$ 787,647	$ 587,367	$ 810,456
SPINRAZA Royalties [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue			240,379	242,314	267,776
R&D Revenue [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue			479,056	284,009	468,061
SPINRAZA [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of annual sales on which royalty payments are paid	$ 1,500,000		$ 1,500,000							$ 1,500,000
SPINRAZA [Member] \| Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Percentage of royalty payments paid to Royalty Pharma on annual sales of medicine	25%		25%							25%
Maximum royalty payments made before royalty interest reverts back	$ 475,000		$ 475,000							$ 475,000
SPINRAZA [Member] \| Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Percentage of royalty payments paid to Royalty Pharma on annual sales of medicine	45%		45%							45%
Maximum royalty payments made before royalty interest reverts back	$ 550,000		$ 550,000							$ 550,000
Biogen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue			350,146	366,696	$ 428,784
Deferred revenue	307,400		$ 307,400	$ 351,200
Biogen [Member] \| Revenue [Member] \| Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage			44%	62%	53%
Biogen [Member] \| Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	3,800,000		$ 3,800,000
SPINRAZA [Member] \| Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative revenue earned	2,100,000		$ 2,100,000
Royalty percentage received on net sales of medicine			11%
SPINRAZA [Member] \| Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Royalty percentage received on net sales of medicine			15%
SPINRAZA [Member] \| SPINRAZA Royalties [Member] \| Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative revenue earned	1,600,000		$ 1,600,000
SPINRAZA [Member] \| R&D Revenue [Member] \| Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative revenue earned	425,000		425,000
New Antisense Medicines for the Treatment of SMA [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	85,000		$ 85,000
Royalty percentage received on net sales of medicine			20%
Upfront payment received							$ 25,000
Next payment to be achieved	45,000		$ 45,000
New Antisense Medicines for the Treatment of SMA [Member] \| ION306 [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable over term of collaboration	555,000		555,000
Maximum amount of development milestone payments over term of collaboration	45,000		45,000
Maximum amount of regulatory milestone payments over term of collaboration	110,000		110,000
Maximum amount of sales milestone payments over term of collaboration	400,000		400,000
Revenue					$ 60,000
2018 Strategic Neurology [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	1,100,000		$ 1,100,000
Royalty percentage received on net sales of medicine			20%
Upfront payment received		$ 375,000
Number of separate performance obligations \| PerformanceObligation											1
Transaction price											$ 552,000
Term of collaboration agreement			10 years
Upfront payment received, including purchase of stock		1,000,000
Proceeds from issuance of common stock		$ 625,000
Percentage cash premium paid on shares purchased		25%
Maximum amount of payments receivable per medicine over term of collaboration	270,000		$ 270,000
Maximum amount of license fees per medicine over term of collaboration	15,000		15,000
Maximum amount of development milestone payments per medicine over term of collaboration	105,000		105,000
Maximum amount of regulatory milestone payments per medicine over term of collaboration	150,000		150,000
Next payment to be achieved	15,000		15,000
Premium paid on shares purchased		$ 177,000
Cumulative payments included in transaction price for performance obligation	623,000		623,000
Milestone payments achieved and included in transaction price for performance obligation	7,500
2013 Strategic Neurology [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	325,000		325,000
Upfront payment received								$ 100,000
Number of separate performance obligations \| PerformanceObligation												1
Transaction price												$ 100,000
Next payment to be achieved	$ 70,000		$ 70,000
Cumulative payments included in transaction price for performance obligation						$ 145,000
Number of medicines currently being advanced \| Medicine	4		4
Maximum amount of payments receivable per antisense molecule over term of collaboration	$ 260,000		$ 260,000
Maximum amount of license fees per antisense molecule over term of collaboration	70,000		70,000
Maximum amount of development milestone payments per antisense molecule over term of collaboration	60,000		60,000
Maximum amount of regulatory milestone payments per antisense molecule over term of collaboration	$ 130,000		130,000
Revenue			$ 16,000
2013 Strategic Neurology [Member] \| Medicines for Parkinson's Disease [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of medicines currently being advanced \| Medicine	1		1
2013 Strategic Neurology [Member] \| Medicines for ALS [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of medicines currently being advanced \| Medicine	2		2
2013 Strategic Neurology [Member] \| Medicines for Multiple System Atrophy [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of medicines currently being advanced \| Medicine	1		1
2013 Strategic Neurology [Member] \| QALSODY [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable over term of collaboration	$ 110,000		$ 110,000
Maximum amount of license fees over term of collaboration	35,000		35,000
Maximum amount of development milestone payments over term of collaboration	18,000		18,000
Maximum amount of regulatory milestone payments over term of collaboration	55,000		55,000
Next payment to be achieved	20,000		$ 20,000
2013 Strategic Neurology [Member] \| QALSODY [Member] \| Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Royalty percentage received on net sales of medicine			11%
2013 Strategic Neurology [Member] \| QALSODY [Member] \| Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Royalty percentage received on net sales of medicine			15%
2012 Neurology [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront payment received									$ 30,000
Maximum amount of payments receivable over term of collaboration	210,000		$ 210,000
Maximum amount of license fees over term of collaboration	70,000		70,000
Maximum amount of development milestone payments over term of collaboration	10,000		10,000
Maximum amount of regulatory milestone payments over term of collaboration	130,000		130,000
Number of separate performance obligations \| PerformanceObligation									2
Next payment to be achieved	70,000		70,000
Number of programs under which medicines are to be developed and commercialized \| Program									2
2012 Neurology [Member] \| Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	230,000		230,000
2012 Neurology [Member] \| IONIS-MAPT [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments included in transaction price for performance obligation	57,000		57,000
Milestone payments achieved and included in transaction price for performance obligation						$ 19,500
Revenue				$ 10,000
2012 Neurology [Member] \| ION582 [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments included in transaction price for performance obligation	$ 68,000		68,000
Milestone payments achieved and included in transaction price for performance obligation			$ 39,000

Collaborative Arrangements an_4

Collaborative Arrangements and Licensing Agreements, AstraZeneca (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2023 USD ($)	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($) Component PerformanceObligation	Dec. 31, 2015 USD ($)	Jul. 31, 2015 USD ($) PerformanceObligation
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 787,647	$ 587,367	$ 810,456
AstraZeneca [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	202,236	79,160	$ 254,591
Deferred revenue	$ 0	$ 0
AstraZeneca [Member] \| Revenue [Member] \| Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage	26%	13%	31%
WAINUA (Eplontersen) [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable over term of collaboration	$ 3,600,000
Upfront payment received			$ 200,000
Maximum amount of license fees over term of collaboration	20,000
Maximum amount of development milestone payments over term of collaboration	485,000
Maximum amount of sales milestone payments over term of collaboration	$ 2,900,000
Royalty percentage received on sales of medicine in U.S.	20%
Number of material components \| Component			4
Number of separate performance obligations \| PerformanceObligation			1
Transaction price			$ 200,000
Percentage of costs associated with ongoing global Phase 3 development program paid by AstraZeneca	55%
Next payment to be achieved	$ 30,000
Revenue	20,000		$ 200,000
WAINUA (Eplontersen) [Member] \| Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	360,000
WAINUA (Eplontersen) [Member] \| ATTRv-PN [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	50,000
Cardiovascular, Renal and Metabolic Diseases [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable over term of collaboration	3,400,000
Upfront payment received				$ 65,000
Maximum amount of license fees over term of collaboration	290,000
Maximum amount of development milestone payments over term of collaboration	865,000
Maximum amount of regulatory milestone payments over term of collaboration	2,200,000
Number of separate performance obligations \| PerformanceObligation					1
Transaction price					$ 65,000
Next payment to be achieved	10,000
Cumulative payments included in transaction price for performance obligation	90,000
Revenue	36,000
Cardiovascular, Renal and Metabolic Diseases [Member] \| Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	$ 300,000

Collaborative Arrangements an_5

Collaborative Arrangements and Licensing Agreements, GSK (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2010
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 787,647	$ 587,367	$ 810,456
GSK [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront payment received				$ 35,000
Maximum amount of payments receivable over term of collaboration	260,000
Maximum amount of license fees over term of collaboration	25,000
Maximum amount of development milestone payments over term of collaboration	42,500
Maximum amount of regulatory milestone payments over term of collaboration	120,000
Maximum amount of sales milestone payments over term of collaboration	70,000
Next payment to be achieved	15,000
Revenue	15,000	0	$ 0
Deferred revenue	$ 0	$ 0
GSK [Member] \| Revenue [Member] \| Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage	2%	0%	0%
GSK [Member] \| Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	$ 105,000

Collaborative Arrangements an_6

Collaborative Arrangements and Licensing Agreements, Novartis (Details) $ in Thousands, shares in Millions	3 Months Ended	12 Months Ended
	Dec. 31, 2023 USD ($)	Dec. 31, 2023 USD ($)	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)	Dec. 31, 2017 USD ($) shares	Aug. 31, 2023 PerformanceObligation	Mar. 31, 2017 PerformanceObligation
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		$ 787,647	$ 587,367	$ 810,456
Pelacarsen API [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Percentage of royalty payments paid to Royalty Pharma on annual sales of medicine	25%	25%
Pelacarsen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable over term of collaboration	$ 900,000	$ 900,000
Upfront payment received					$ 75,000
Maximum amount of license fees over term of collaboration	150,000	150,000
Maximum amount of development milestone payments over term of collaboration	25,000	25,000
Maximum amount of regulatory milestone payments over term of collaboration	290,000	290,000
Maximum amount of sales milestone payments over term of collaboration	360,000	360,000
Cumulative payments received	275,000	275,000
Next payment to be achieved	50,000	50,000
Shares issued (in shares) \| shares					1.6
Proceeds from sale of common stock					$ 100,000
Number of separate performance obligations \| PerformanceObligation							4
Transaction price					108,400
Premium received on shares issued					28,400
Potential premium received if common stock was purchased in the future					5,000
Revenue		30,194	237	$ 25,526
Deferred revenue	30,000	$ 30,000	$ 0
Pelacarsen [Member] \| Revenue [Member] \| Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage		4%		3%
Pelacarsen [Member] \| Maximum [Member] \| Revenue [Member] \| Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage			1%
Pelacarsen [Member] \| R&D Services for Pelacarsen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Transaction price					64,000
Pelacarsen [Member] \| R&D Services for Olezarsen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Transaction price					40,100
Pelacarsen [Member] \| Pelacarsen API [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Royalty percentage received on net sales of medicine		20%
Transaction price					1,500
Pelacarsen [Member] \| Olezarsen API [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Transaction price					$ 2,800
Lp(a)-Driven Cardiovascular Disease [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable over term of collaboration	730,000	$ 730,000
Upfront payment received	60,000
Maximum amount of development milestone payments over term of collaboration	155,000	155,000
Maximum amount of regulatory milestone payments over term of collaboration	105,000	105,000
Maximum amount of sales milestone payments over term of collaboration	410,000	410,000
Cumulative payments received	60,000	60,000
Next payment to be achieved	5,000	5,000
Number of separate performance obligations \| PerformanceObligation						1
Transaction price	$ 60,000	$ 60,000
Lp(a)-Driven Cardiovascular Disease [Member] \| Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Royalty percentage received on net sales of medicine		10%
Lp(a)-Driven Cardiovascular Disease [Member] \| Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Royalty percentage received on net sales of medicine		20%

Collaborative Arrangements an_7

Collaborative Arrangements and Licensing Agreements, Roche (Details) $ in Thousands	3 Months Ended	12 Months Ended
	Dec. 31, 2023 USD ($) PerformanceObligation Program Indication	Dec. 31, 2023 USD ($) PerformanceObligation Program Indication	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)	Oct. 31, 2018 PerformanceObligation	Dec. 31, 2013 USD ($) PerformanceObligation
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		$ 787,647	$ 587,367	$ 810,456
Roche [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		48,838	67,202	$ 17,241
Deferred revenue	$ 36,700	$ 36,700	$ 22,400
Roche [Member] \| Revenue [Member] \| Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage		6%	11%	2%
HD [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable over term of collaboration	395,000	$ 395,000
Maximum amount of upfront payments over term of collaboration	30,000	30,000
Maximum amount of license fees over term of collaboration	45,000	45,000
Maximum amount of development milestone payments over term of collaboration	70,000	70,000
Maximum amount of regulatory milestone payments over term of collaboration	170,000	170,000
Maximum amount of sales milestone payments over term of collaboration	80,000	80,000
Maximum amount of milestone payments for each additional medicine successfully developed over term of collaboration	136,500	136,500
Cumulative payments received	150,000	150,000
Next payment to be achieved	17,500	17,500
Number of separate performance obligations \| PerformanceObligation						1
Transaction price						$ 30,000
IONIS-FB-L for Complement-Mediated Diseases [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable over term of collaboration	810,000	810,000
Maximum amount of upfront payments over term of collaboration	75,000	75,000
Maximum amount of license fees over term of collaboration	35,000	35,000
Maximum amount of development milestone payments over term of collaboration	145,000	145,000
Maximum amount of regulatory milestone payments over term of collaboration	279,000	279,000
Maximum amount of sales milestone payments over term of collaboration	280,000	280,000
Cumulative payments received	135,000	135,000
Next payment to be achieved	90,000	90,000
Number of separate performance obligations \| PerformanceObligation					1
Cumulative payments included in transaction price for performance obligation	$ 97,000	$ 97,000
Milestone payments achieved and included in transaction price for performance obligation			$ 22,000
Number of disease indications \| Indication	2	2
Royalty percentage received on net sales of medicine		20%
Revenue			$ 35,000
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
RNA-targeted Programs for AD and HD [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable over term of collaboration	$ 625,000	$ 625,000
Upfront payment received	60,000
Maximum amount of development milestone payments over term of collaboration	167,000	167,000
Maximum amount of sales milestone payments over term of collaboration	398,000	398,000
Cumulative payments received	60,000	60,000
Next payment to be achieved	$ 7,500	$ 7,500
Number of early-stage programs \| Program	2	2
Number of separate performance obligations \| PerformanceObligation	2	2
Transaction price	$ 60,000	$ 60,000
RNA-targeted Programs for AD and HD [Member] \| R&D Services for Investigational Medicine for AD [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Transaction price	45,000	45,000
RNA-targeted Programs for AD and HD [Member] \| R&D Services for Investigational Medicine for HD [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Transaction price	$ 15,000	$ 15,000

Collaborative Arrangements an_8

Collaborative Arrangements and Licensing Agreements, Otsuka (Details) $ in Thousands	3 Months Ended	12 Months Ended
	Dec. 31, 2023 USD ($) PerformanceObligation	Dec. 31, 2023 USD ($) PerformanceObligation	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		$ 787,647	$ 587,367	$ 810,456
Otsuka [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Maximum amount of payments receivable over term of collaboration	$ 185,000	185,000
Upfront payment received	65,000
Maximum amount of regulatory milestone payments over term of collaboration	50,000	50,000
Maximum amount of sales milestone payments over term of collaboration	70,000	70,000
Cumulative payments received	65,000	65,000
Next payment to be achieved	$ 15,000	$ 15,000
Number of separate performance obligations \| PerformanceObligation	2	2
Transaction price	$ 65,000	$ 65,000
Revenue		56,480
Deferred revenue	8,500	$ 8,500
Otsuka [Member] \| Revenue [Member] \| Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage		7%
Otsuka [Member] \| Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Royalty percentage received on net sales of medicine		20%
Otsuka [Member] \| Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Royalty percentage received on net sales of medicine		30%
Otsuka [Member] \| License of Donidalorsen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Transaction price	56,000	$ 56,000
Otsuka [Member] \| R&D Services for Donidalorsen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Transaction price	$ 9,000	$ 9,000

Collaborative Arrangements an_9

Collaborative Arrangements and Licensing Agreements, PTC Therapeutics (Details)	12 Months Ended
	Dec. 31, 2023
PTC Therapeutics [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Royalty percentage received on net sales of medicine	20%

Collaborative Arrangements a_10

Collaborative Arrangements and Licensing Agreements, Sobi (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 787,647	$ 587,367	$ 810,456
Sobi [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 2,646	$ 4,004	$ 7,443
Sobi [Member] \| Revenue [Member] \| Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage		1%	1%
Sobi [Member] \| Maximum [Member] \| Revenue [Member] \| Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage	1%

Collaborative Arrangements a_11

Collaborative Arrangements and Licensing Agreements, Bicycle Therapeutics (Details) - Bicycle License Agreement [Member] - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2021
Collaborative Arrangement and Licensing Agreement [Abstract]
Payment of license fee		$ 42
Trading restriction period under lock up agreement	1 year
Equity investment		7.2
R&D expense		$ 34.8

Collaborative Arrangements a_12

Collaborative Arrangements and Licensing Agreements, Metagenomi (Details) - Metagenomi [Member] $ in Millions	12 Months Ended
	Dec. 31, 2022 USD ($) Target
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of targets to be researched, developed and commercialized \| Target	4
Number of additional targets to be researched, developed and commercialized \| Target	4
Payment to license technology \| $	$ 80
Research and development expense \| $	$ 80

Collaborative Arrangements a_13

Collaborative Arrangements and Licensing Agreements, Alnylam Pharmaceuticals, Inc. (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2023 USD ($)	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)	Dec. 31, 2015 Program Target
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 787,647	$ 587,367	$ 810,456
R&D Revenue [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	479,056	284,009	$ 468,061
Alnylam [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of therapeutic programs \| Program				4
Number of therapeutic targets granted to Ionis \| Target				4
Number of unnamed therapeutic targets granted to Ionis \| Target				2
Number of therapeutic targets granted by Ionis \| Target				4
Deferred revenue	$ 0	$ 0
Alnylam [Member] \| Revenue [Member] \| Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage	4%	4%	0%
Alnylam [Member] \| R&D Revenue [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 28,426	$ 21,389	$ 0

Investments, Contract Maturity

Investments, Contract Maturity of Available-for-Sale Securities (Details)	12 Months Ended
	Dec. 31, 2023
Contract Maturity of Available-for-Sale Securities [Abstract]
One year or less	68%
After one year but within two years	24%
After two years but within three and a half years	8%
Total	100%
Percentage of available-for-sale securities with a maturity of less than two years	92%
Maximum contract maturity period, range 1	1 year
Maximum contract maturity period, range 2	2 years
Maximum contract maturity period, range 3	3 years 6 months

Investments, Summary of Investm

Investments, Summary of Investments (Details) $ in Thousands		12 Months Ended
		Dec. 31, 2023 USD ($) Company	Dec. 31, 2022 USD ($)
Ownership Interests in Private and Public Companies [Abstract]
Number of privately held companies in which there is an equity ownership interest of less than 20% \| Company		7
Number of publicly held companies in which there is an equity ownership interest of less than 20% \| Company		3
Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]
Amortized cost		$ 1,316,219	$ 1,223,522
Gross unrealized gains		415	64
Gross unrealized losses		(5,238)	(12,018)
Estimated fair value		1,311,396	1,211,568
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		651,628	525,314
Gross unrealized gains		3,063	130
Gross unrealized losses		(1,197)	(15,621)
Estimated fair value		653,494	509,823
Available-for-sale Debt Securities [Abstract]
Amortized cost		1,967,847	1,748,836
Gross unrealized gains		3,478	194
Gross unrealized losses		(6,435)	(27,639)
Estimated fair value		1,964,890	1,721,391
Equity Securities [Abstract]
Amortized cost		35,012	35,012
Gross unrealized gains		25,237	17,257
Gross unrealized losses		(10,957)	(1,358)
Estimated fair value		49,292	50,911
Available-for-sale Debt and Equity Securities [Abstract]
Amortized cost		2,002,859	1,783,848
Gross unrealized gains		28,715	17,451
Gross unrealized losses		(17,392)	(28,997)
Estimated fair value		2,014,182	1,772,302
Corporate Debt Securities [Member]
Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]
Amortized cost	[1]	559,967	513,790
Gross unrealized gains		157	23
Gross unrealized losses		(2,625)	(4,365)
Estimated fair value		557,499	509,448
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		243,151	227,631
Gross unrealized gains		1,270	14
Gross unrealized losses		(692)	(10,143)
Estimated fair value		243,729	217,502
Debt Securities Issued by U.S. Government Agencies [Member]
Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]
Amortized cost		224,711	133,585
Gross unrealized gains		64	0
Gross unrealized losses		(611)	(1,829)
Estimated fair value		224,164	131,756
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		110,138	34,339
Gross unrealized gains		547	0
Gross unrealized losses		(21)	(1,040)
Estimated fair value		110,664	33,299
Debt Securities Issued by the U.S. Treasury [Member]
Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]
Amortized cost	[1]	513,784	512,655
Gross unrealized gains		152	23
Gross unrealized losses		(1,889)	(5,124)
Estimated fair value		512,047	507,554
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		294,873	245,030
Gross unrealized gains		1,239	0
Gross unrealized losses		(480)	(4,109)
Estimated fair value		295,632	240,921
Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]
Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]
Amortized cost		17,757	57,484
Gross unrealized gains		42	18
Gross unrealized losses		(113)	(686)
Estimated fair value		17,686	56,816
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		3,466	18,314
Gross unrealized gains		7	116
Gross unrealized losses		(4)	(329)
Estimated fair value		3,469	18,101
Other Municipal Debt Securities [Member]
Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]
Amortized cost			6,008
Gross unrealized gains			0
Gross unrealized losses			(14)
Estimated fair value			5,994
Publicly Traded Equity Securities [Member]
Equity Securities [Abstract]
Amortized cost	[2]	11,897	11,897
Gross unrealized gains		236	0
Gross unrealized losses		(5,832)	(1,358)
Estimated fair value		6,301	10,539
Available-for-sale Debt and Equity Securities [Abstract]
Unrealized loss on equity securities		(4,200)
Privately Held Equity Securities [Member]
Equity Securities [Abstract]
Amortized cost	[3]	23,115	23,115
Gross unrealized gains		25,001	17,257
Gross unrealized losses		(5,125)	0
Estimated fair value		42,991	$ 40,372
Available-for-sale Debt and Equity Securities [Abstract]
Unrealized gain on equity securities		$ 2,600

[1]Includes investments classified as cash equivalents in our consolidated balance sheets.[2]Our publicly traded equity securities are included in other current assets. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2023, we recorded a $4.2 million net unrealized loss in our consolidated statements of operations related to changes in the fair value of our investments in publicly traded companies. Our privately held equity securities are included in deposits and other assets. We recognize our privately held equity securities at , we recorded a $ million net unrealized gain in our consolidated statements of operations related to changes in the fair value of our investments in privately held companies.

Investments, Investments Tempor

Investments, Investments Temporarily Impaired (Details) $ in Thousands	Dec. 31, 2023 USD ($) Investment
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	455
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 857,398
More than 12 months of temporary impairment	331,848
Total temporary impairment	1,189,246
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(1,847)
More than 12 months of temporary impairment	(4,588)
Total temporary impairment	$ (6,435)
Corporate Debt Securities [Member]
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	297
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 323,708
More than 12 months of temporary impairment	178,183
Total temporary impairment	501,891
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(553)
More than 12 months of temporary impairment	(2,764)
Total temporary impairment	$ (3,317)
Debt Securities Issued by U.S. Government Agencies [Member]
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	63
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 199,372
More than 12 months of temporary impairment	14,777
Total temporary impairment	214,149
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(246)
More than 12 months of temporary impairment	(386)
Total temporary impairment	$ (632)
Debt Securities Issued by the U.S. Treasury [Member]
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	34
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 325,966
More than 12 months of temporary impairment	131,000
Total temporary impairment	456,966
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(1,031)
More than 12 months of temporary impairment	(1,338)
Total temporary impairment	$ (2,369)
Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	61
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 8,352
More than 12 months of temporary impairment	7,888
Total temporary impairment	16,240
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(17)
More than 12 months of temporary impairment	(100)
Total temporary impairment	$ (117)

Fair Value Measurements (Detail

Fair Value Measurements (Details) - USD ($) $ in Thousands		Dec. 31, 2023		Dec. 31, 2022		Dec. 31, 2021	Apr. 30, 2021	Dec. 31, 2019
Fair Value Measurements [Abstract]
Available-for-sale securities		$ 1,964,890		$ 1,721,391
Equity securities		$ 49,292		$ 50,911
1.75% Notes [Member]
Fair Value Measurements [Abstract]
Interest rate on convertible senior notes		1.75%		1.75%
0.125% Notes [Member]
Fair Value Measurements [Abstract]
Interest rate on convertible senior notes		0.125%		0.125%		0.125%		0.125%
0% Notes [Member]
Fair Value Measurements [Abstract]
Interest rate on convertible senior notes		0%		0%		0%	0%
Publicly Traded Equity Securities [Member]
Fair Value Measurements [Abstract]
Equity securities		$ 6,301		$ 10,539
Recurring Basis [Member]
Fair Value Measurements [Abstract]
Cash equivalents	[1]	185,424		211,655
Total		2,156,615		1,943,585
Recurring Basis [Member] \| Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		801,228	[2]	726,950	[3]
Recurring Basis [Member] \| Corporate Debt Securities [Member] \| Cash and Cash Equivalents [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		33,000		11,000
Recurring Basis [Member] \| Debt Securities Issued by U.S. Government Agencies [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities	[4]	334,828		165,055
Recurring Basis [Member] \| Debt Securities Issued by the U.S. Treasury [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities	[4]	807,679		748,475
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	[4]	21,155		74,917
Recurring Basis [Member] \| Other Municipal Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities	[4]			5,994
Recurring Basis [Member] \| Publicly Traded Equity Securities [Member] \| Other Current Assets [Member]
Fair Value Measurements [Abstract]
Equity securities	[5]	6,301		10,539
Recurring Basis [Member] \| Quoted Prices in Active Markets (Level 1) [Member]
Fair Value Measurements [Abstract]
Cash equivalents		185,424		211,655
Total		999,404		970,669
Recurring Basis [Member] \| Quoted Prices in Active Markets (Level 1) [Member] \| Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		0		0
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		0		0
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		807,679		748,475
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		0		0
Recurring Basis [Member] \| Quoted Prices in Active Markets (Level 1) [Member] \| Other Municipal Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities				0
Recurring Basis [Member] \| Quoted Prices in Active Markets (Level 1) [Member] \| Publicly Traded Equity Securities [Member] \| Other Current Assets [Member]
Fair Value Measurements [Abstract]
Equity securities		6,301		10,539
Recurring Basis [Member] \| Significant Other Observable Inputs (Level 2) [Member]
Fair Value Measurements [Abstract]
Cash equivalents		0		0
Total		1,157,211		972,916
Recurring Basis [Member] \| Significant Other Observable Inputs (Level 2) [Member] \| 1.75% Notes [Member]
Fair Value Measurements [Abstract]
Convertible notes		661,100
Recurring Basis [Member] \| Significant Other Observable Inputs (Level 2) [Member] \| 0.125% Notes [Member]
Fair Value Measurements [Abstract]
Convertible notes		42,400
Recurring Basis [Member] \| Significant Other Observable Inputs (Level 2) [Member] \| 0% Notes [Member]
Fair Value Measurements [Abstract]
Convertible notes		667,800
Recurring Basis [Member] \| Significant Other Observable Inputs (Level 2) [Member] \| Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		801,228		726,950
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		334,828		165,055
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		0		0
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		21,155		74,917
Recurring Basis [Member] \| Significant Other Observable Inputs (Level 2) [Member] \| Other Municipal Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities				5,994
Recurring Basis [Member] \| Significant Other Observable Inputs (Level 2) [Member] \| Publicly Traded Equity Securities [Member] \| Other Current Assets [Member]
Fair Value Measurements [Abstract]
Equity securities		$ 0		$ 0

[1]Included in cash and cash equivalents in our consolidated balance sheets.[2]$33.0 million was included in cash and cash equivalents, with the difference included in short-term investments in our consolidated balance sheets.[3]$11.0 million was included in cash and cash equivalents, with the difference included in short-term investments in our consolidated balance sheets.[4]Included in short-term investments in our consolidated balance sheets.[5]Included in other current assets in our consolidated balance sheets.

Long-Term Obligations and Com_3

Long-Term Obligations and Commitments, Long-Term Obligations (Details) - USD ($) $ in Thousands	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021	Apr. 30, 2021	Dec. 31, 2019
Long-Term Obligations [Abstract]
Liability related to sale of future royalties	$ 513,736	$ 0
Lease liabilities	178,969	186,156
Mortgage debt	8,859	8,998
Other obligations	33,714	7,295
Total	1,922,943	1,369,195
Less: current portion	(8,831)	(7,535)
Total Long-Term Obligations	1,914,112	1,361,660
1.75 Percent Convertible Senior Notes [Member]
Long-Term Obligations [Abstract]
Convertible senior notes	$ 562,285	$ 0
Interest rate on convertible senior notes	1.75%	1.75%
0 Percent Convertible Senior Notes [Member]
Long-Term Obligations [Abstract]
Convertible senior notes	$ 625,380	$ 622,242
Interest rate on convertible senior notes	0%	0%	0%	0%
0.125 Percent Convertible Senior Notes [Member]
Long-Term Obligations [Abstract]
Convertible senior notes	$ 0	$ 544,504
Interest rate on convertible senior notes	0.125%	0.125%	0.125%		0.125%

Long-Term Obligations and Com_4

Long-Term Obligations and Commitments, Convertible Debt and Call Spread (Details) - USD ($) $ / shares in Units, $ in Thousands, shares in Millions	3 Months Ended	12 Months Ended
	Dec. 31, 2019	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2019	Apr. 30, 2021
Convertible Debt [Abstract]
Repurchase of convertible senior notes		$ 0	$ 0	$ 61,967
Gain (loss) on early retirement of debt		13,389	0	(8,627)
Unamortized debt issuance costs		20,061
Purchase of note hedges		0	0	136,620
Proceeds from issuance of warrants		0	0	89,752
Amortization of debt issuance costs		6,330	5,373	4,958
Convertible Senior Notes [Member]
Convertible Debt [Abstract]
Amortization of debt issuance costs		5,900	5,300	4,900
1.75% Notes [Member]
Convertible Debt [Abstract]
Face amount of offering		575,000
Proceeds from issuance of convertible senior notes		575,000	$ 0	0
Outstanding principal balance		575,000
Unamortized debt issuance costs		$ 12,700
Maturity date		Jun. 30, 2028
Interest rate		1.75%	1.75%
Effective interest rate		2.30%
Conversion price per share (in dollars per share)		$ 53.73
Total shares of common stock subject to conversion (in shares)		10.7
Percentage of principal amount used as purchase price upon occurrence of fundamental change		100%
1.75% Notes [Member]
Convertible Debt [Abstract]
Proceeds from issuance of convertible senior notes		$ 488,200
0% Notes [Member]
Convertible Debt [Abstract]
Face amount of offering				632,500
Proceeds from issuance of convertible senior notes		0	$ 0	$ 632,500
Outstanding principal balance		632,500
Unamortized debt issuance costs		$ 7,200
Maturity date		Apr. 30, 2026
Interest rate		0%	0%	0%		0%
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
Cost of call spread				$ 46,900
Purchase of note hedges				136,700
Proceeds from issuance of warrants				89,800
Percentage of principal amount used as purchase price upon occurrence of fundamental change		100%
0% Notes [Member]
Convertible Debt [Abstract]
Proceeds from issuance of convertible senior notes				$ 319,000
0.125% Notes [Member]
Convertible Debt [Abstract]
Repurchase of convertible senior notes		$ 504,400
Principal amount repurchased		504,400
Outstanding principal balance		44,500
Unamortized debt issuance costs		$ 200
Maturity date		Dec. 31, 2024
Interest rate	0.125%	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)		0.5
Cost of call spread					$ 52,600
Purchase of note hedges					108,700
Proceeds from issuance of warrants	$ 56,100
Percentage of principal amount used as purchase price upon occurrence of fundamental change		100%
0.125% Notes [Member] \| Other Income [Member]
Convertible Debt [Abstract]
Gain (loss) on early retirement of debt		$ 13,400
0.125% Convertible Senior Notes Issued in Exchange for 1 Percent Notes [Member]
Convertible Debt [Abstract]
Face amount of offering	439,300				439,300
0.125% Convertible Senior Notes Issued under Subscription Agreements [Member]
Convertible Debt [Abstract]
Face amount of offering	109,500				109,500
1% Notes [Member]
Convertible Debt [Abstract]
Repurchase of convertible senior notes				$ 309,900
Principal amount repurchased	$ 375,600			$ 247,900	$ 375,600
Interest rate		1%		1%

Long-Term Obligations and Com_5

Long-Term Obligations and Commitments, Financing Arrangements (Details) $ in Thousands	1 Months Ended	12 Months Ended
	Aug. 31, 2023 USD ($) Lot	Dec. 31, 2023 USD ($) Option	Dec. 31, 2022 USD ($) Agreement	Dec. 31, 2021 USD ($)	Dec. 31, 2017 USD ($) Facility
Operating Facilities [Abstract]
Number of purchased facilities financed with mortgage debt \| Facility					2
Number of purchase and sale agreements entered into with real estate investor \| Agreement			2
Gain on sale of real estate assets		$ (161)	$ 149,604	$ 0
Proceeds from sale of real estate assets		22	254,083	0
Payment of mortgage debt		$ 160	50,686	$ 0
Long-term Mortgage Debt [Member]
Operating Facilities [Abstract]
Face amount					$ 60,400
Primary R&D Facility Mortgage [Member]
Operating Facilities [Abstract]
Period to make interest only payments on mortgage loan		5 years
Payment of mortgage debt			51,300
Manufacturing Facility Mortgage [Member]
Operating Facilities [Abstract]
Period to make interest only payments on mortgage loan		5 years
Primary R&D Facility [Member]
Operating Facilities [Abstract]
Payment to acquire building					$ 79,400
Interest rate					3.88%
Manufacturing Facility [Member]
Operating Facilities [Abstract]
Payment to acquire building					$ 14,000
Interest rate					4.20%
Headquarters Location in Carlsbad, California [Member]
Operating Facilities [Abstract]
Gain on sale of real estate assets			150,100
Number of lots of undeveloped land transferred to real estate investor \| Lot	2
Proceeds from sale of real estate assets			$ 263,400
Initial term of lease		15 years
Number of options to extend lease \| Option		2
Term of lease extension		5 years
Undeveloped Land in Carlsbad, California [Member]
Operating Facilities [Abstract]
Number of lots of undeveloped land transferred to real estate investor \| Lot	2
Proceeds from sale of real estate assets	$ 33,000
New R&D Facility in Carlsbad, CA [Member]
Operating Facilities [Abstract]
Initial term of lease		15 years
Number of options to extend lease \| Option		2
Term of lease extension		5 years

Long-Term Obligations and Com_6

Long-Term Obligations and Commitments, Debt Maturity Schedules (Details) $ in Thousands	Dec. 31, 2023 USD ($)
Debt Maturities [Abstract]
2024	$ 55,298
2025	10,657
2026	643,157
2027	10,509
2028	580,277
Thereafter	8,462
Total debt and mortgage maturities	1,308,360
Less: Current portion included in other current liabilities	(157)
Less: Fixed and determinable interest	(47,138)
Less: Debt issuance costs	(20,061)
Total long-term debt	$ 1,241,004

Long-Term Obligations and Com_7

Long-Term Obligations and Commitments, Operating Leases (Details) $ in Thousands	1 Months Ended	12 Months Ended
	Aug. 31, 2023 USD ($) Lot	Dec. 31, 2023 USD ($) Option	Dec. 31, 2022 USD ($)	Dec. 31, 2021 USD ($)
Operating Leases [Abstract]
Lease payments to be made over initial term of lease		$ 279,536
Right-of-use operating lease assets		171,896	$ 181,544
Operating lease liabilities		$ 178,969	186,156
Weighted average remaining lease term		13 years
Weighted average discount rate		6.90%
Operating lease cash payments		$ 20,100	$ 4,000	$ 3,300
Carlsbad Facility [Member]
Operating Leases [Abstract]
Number of options to extend lease \| Option		1
Term of lease extension		5 years
Carlsbad Office Space [Member]
Operating Leases [Abstract]
Number of options to extend lease \| Option		0
Carlsbad Warehouse Space [Member]
Operating Leases [Abstract]
Number of options to extend lease \| Option		0
Headquarters Location in Carlsbad, California [Member]
Operating Leases [Abstract]
Initial term of lease		15 years
Number of options to extend lease \| Option		2
Term of lease extension		5 years
Lease payments to be made over initial term of lease		$ 280,000
Number of lots of undeveloped land transferred to real estate investor \| Lot	2
Development Chemistry and Manufacturing Facility in Oceanside, California [Member]
Operating Leases [Abstract]
Impairment charge	$ 20,000
Impairment, Long-Lived Asset, Held-for-Use, Statement of Income [Extensible Enumeration]	Selling, General and Administrative Expense
Boston Office Space [Member]
Operating Leases [Abstract]
Initial term of lease		123 months
Term of lease extension		5 years
Period of free rent under lease		3 months
Subleased Office Space in Boston [Member]
Operating Leases [Abstract]
Term of sublease		83 months
Number of options to extend sublease \| Option		0
Period of free rent under sublease		7 months
Lease payments to be received over term of sublease		$ 9,600
Another Office Space in Boston [Member]
Operating Leases [Abstract]
Initial term of lease		91 months
Number of options to extend lease \| Option		1
Term of lease extension		5 years
Period of free rent under lease		7 months
Lease payments to be made over initial term of lease		$ 6,800

Long-Term Obligations and Com_8

Long-Term Obligations and Commitments, Future Payments for Operating Lease Liabilities (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Future Payments for Operating Lease Liabilities [Abstract]
2024	$ 20,398
2025	20,645
2026	20,781
2027	20,800
2028	20,774
Thereafter	176,138
Total minimum lease payments	279,536
Less: Imputed interest	(100,567)
Less: Current portion (included in other current liabilities)	(8,094)
Total long-term lease liabilities	$ 170,875	$ 178,941
Operating Lease, Liability, Current, Statement of Financial Position [Extensible Enumeration]	Other current liabilities
Rent expense	$ 23,100	$ 8,300	$ 3,400

Long-Term Obligations and Com_9

Long-Term Obligations and Commitments, Royalty Revenue Monetization (Details) - USD ($) $ in Thousands	1 Months Ended	12 Months Ended
	Jan. 31, 2023	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Royalty Revenue Monetization [Abstract]
Upfront payment received	$ 500,000
Maximum amount of payments receivable for additional milestones	625,000
Transaction costs		$ 10,434	$ 29	$ 0
Proceeds from sale of future royalties		500,000	0	0
Royalty payments to Royalty Pharma		(44,628)	0	0
Interest expense related to sale of future royalties		68,238	0	0
Issuance costs related to sale of future royalties		(10,434)	(29)	$ 0
Net liability related to sale of future royalties		513,736	$ 0
SPINRAZA [Member]
Royalty Revenue Monetization [Abstract]
Maximum amount of annual sales on which royalty payments are paid	$ 1,500,000	$ 1,500,000
SPINRAZA [Member] \| Minimum [Member]
Royalty Revenue Monetization [Abstract]
Percentage of royalty payments paid on annual sales of medicine	25%	25%
Maximum royalty payments made before royalty interest reverts back	$ 475,000	$ 475,000
SPINRAZA [Member] \| Maximum [Member]
Royalty Revenue Monetization [Abstract]
Percentage of royalty payments paid on annual sales of medicine	45%	45%
Maximum royalty payments made before royalty interest reverts back	$ 550,000	$ 550,000
Pelacarsen [Member]
Royalty Revenue Monetization [Abstract]
Percentage of royalty payments paid on annual sales of medicine	25%
Royalty Purchase Agreement [Member]
Royalty Revenue Monetization [Abstract]
Transaction costs		$ 10,434
Effective interest rate		13.50%
Proceeds from sale of future royalties		$ 500,000
Royalty payments to Royalty Pharma		(44,628)
Interest expense related to sale of future royalties		68,238
Liability related to sale of future royalties		523,610
Issuance costs related to sale of future royalties		(10,434)
Amortization of issuance costs related to sale of future royalties		560
Net liability related to sale of future royalties		$ 513,736

Stockholders' Equity, Preferred

Stockholders' Equity, Preferred and Common Stock (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Common Stock [Abstract]
Common stock, shares authorized to issue (in shares)	300,000,000	300,000,000
Common stock, shares issued (in shares)	144,340,526	142,057,736
Common stock, shares outstanding (in shares)	144,340,526	142,057,736
Net proceeds from stock option exercises, vesting of restricted stock units, and ESPP purchases	$ 49,442	$ 6,373	$ 11,565
Preferred Stock [Member]
Preferred Stock [Abstract]
Preferred stock, shares authorized (in shares)	15,000,000
Preferred stock, shares outstanding (in shares)	0
Series C Junior Participating Preferred Stock [Member]
Preferred Stock [Abstract]
Preferred stock, shares issued (in shares)	0
Preferred stock, shares outstanding (in shares)	0
Common Stock [Member]
Common Stock [Abstract]
Common stock, shares authorized to issue (in shares)	300,000,000	300,000,000
Common stock, shares issued (in shares)	144,300,000	142,100,000
Common stock, shares outstanding (in shares)	144,300,000	142,100,000
Common shares reserved for future issuance (in shares)	49,700,000
Number of shares issued for stock option exercises, vesting of restricted stock units, and ESPP purchases (in shares)	2,300,000	1,200,000	1,100,000
Net proceeds from stock option exercises, vesting of restricted stock units, and ESPP purchases	$ 49,400	$ 6,400	$ 11,600

Stockholders' Equity, Stock Pla

Stockholders' Equity, Stock Plans (Details)

12 Months Ended

Dec. 31, 2023 Officer $ / shares shares

Dec. 31, 2019 shares

Dec. 31, 2018 shares

Dec. 31, 2017 shares

Dec. 31, 2016 shares

Dec. 31, 2015 shares

Dec. 31, 2014 shares

Dec. 31, 2013 shares

Dec. 31, 2012 shares

Dec. 31, 2011 shares

Dec. 31, 2010 shares

Dec. 31, 2009 shares

Jun. 30, 2023 shares

Dec. 31, 2022 shares

Jun. 30, 2021 shares

Dec. 31, 2020 shares

Jun. 30, 2019 shares

May 31, 2017 shares

Jun. 30, 2015 shares

May 31, 2015 shares

Stock Options [Member]

Stock Plans [Abstract]

Number of options outstanding (in shares)

14,091,000

14,970,000

Number of options exercisable (in shares)

9,703,000

1989 Stock Option Plan [Member]

Stock Plans [Abstract]

Number of shares authorized for issuance under the Plan (in shares)

20,000,000

Number of options outstanding (in shares)

Number of shares available for grant (in shares)

68,000

1989 Stock Option Plan [Member] | Stock Options [Member]

Stock Plans [Abstract]

Vesting period

4 years

Award term

7 years

1989 Stock Option Plan [Member] | Stock Options [Member] | One Year from Date of Grant [Member]

Stock Plans [Abstract]

Vesting percentage

25%

Period before options are exercisable

1 year

2011 Equity Incentive Plan [Member]

Stock Plans [Abstract]

Number of shares authorized for issuance under the Plan (in shares)

35,200,000

29,700,000

23,000,000

16,000,000

11,000,000

5,500,000

Reduction in fungible share reserve for each share issued pursuant to full value award (n shares)

(1.7)

Increase in fungible share reserve for each share returning from a full value award (in shares)

1.7

Number of options outstanding (in shares)

12,800,000

Number of options exercisable (in shares)

8,700,000

Number of shares available for grant (in shares)

8,000,000

Number of executive officers terminated before change in control when vesting will accelerate for executive officers | Officer

Period before change in control when vesting will accelerate for executive officers

3 months

Period after change in control when vesting will accelerate for executive officers

12 months

2011 Equity Incentive Plan [Member] | Stock Options [Member]

Stock Plans [Abstract]

Vesting period

4 years

Award term

7 years

2011 Equity Incentive Plan [Member] | Stock Options [Member] | Issued after December 31, 2021 [Member]

Stock Plans [Abstract]

Award term

10 years

2011 Equity Incentive Plan [Member] | Stock Options [Member] | One Year from Date of Grant [Member]

Stock Plans [Abstract]

Vesting percentage

25%

Period before options are exercisable

1 year

2011 Equity Incentive Plan [Member] | Restricted Stock Units [Member]

Stock Plans [Abstract]

Vesting period

4 years

Number of awards outstanding (in shares)

3,300,000

2020 Equity Incentive Plan [Member]

Stock Plans [Abstract]

Number of shares authorized for issuance under the Plan (in shares)

1,600,000

2,600,000

Number of options outstanding (in shares)

400,000

Number of options exercisable (in shares)

100,000

Number of shares available for grant (in shares)

1,000,000

2020 Equity Incentive Plan [Member] | Stock Options [Member]

Stock Plans [Abstract]

Vesting period

4 years

Award term

7 years

2020 Equity Incentive Plan [Member] | Stock Options [Member] | Issued after December 31, 2021 [Member]

Stock Plans [Abstract]

Award term

10 years

2020 Equity Incentive Plan [Member] | Stock Options [Member] | One Year from Date of Grant [Member]

Stock Plans [Abstract]

Vesting percentage

25%

Period before options are exercisable

1 year

2020 Equity Incentive Plan [Member] | Restricted Stock Units [Member]

Stock Plans [Abstract]

Vesting period

4 years

Number of awards outstanding (in shares)

200,000

2002 Non-Employee Directors' Stock Option Plan [Member]

Stock Plans [Abstract]

Number of shares authorized for issuance under the Plan (in shares)

2,000,000

1,200,000

2,800,000

Number of options outstanding (in shares)

900,000

Number of options exercisable (in shares)

900,000

Number of shares available for grant (in shares)

500,000

2002 Non-Employee Directors' Stock Option Plan [Member] | Stock Options [Member]

Stock Plans [Abstract]

Award term

10 years

2002 Non-Employee Directors' Stock Option Plan [Member] | Restricted Stock Units [Member]

Stock Plans [Abstract]

Number of awards outstanding (in shares)

40,000

Employee Stock Purchase Plan [Member]

Stock Plans [Abstract]

Number of shares authorized for issuance under the Plan (in shares)

3,200,000

Number of additional shares reserved for issuance (in shares)

150,000

Maximum percentage of employee compensation used to purchase shares

10%

Percentage of fair market value used to determine purchase price of stock

85%

Holding period for purchased stock

6 months

Shares purchased and issued under ESPP (in shares)

100,000

Weighted average purchase price (in dollars per share) | $ / shares

$ 30.53

Shares available for purchase under ESPP (in shares)

400,000

Stockholders' Equity, Stock Opt

Stockholders' Equity, Stock Option Activity (Details) - Stock Options [Member] - USD ($) $ / shares in Units, shares in Thousands, $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Number of Shares [Abstract]
Outstanding at beginning of period (in shares)	14,970
Granted (in shares)	2,407
Exercised (in shares)	(1,444)
Cancelled/forfeited/expired (in shares)	(1,842)
Outstanding at end of period (in shares)	14,091	14,970
Exercisable at end of period (in shares)	9,703
Weighted Average Exercise Price Per Share [Abstract]
Outstanding at beginning of period (in dollars per share)	$ 50.57
Granted (in dollars per share)	38.8
Exercised (in dollars per share)	45.06
Cancelled/forfeited/expired (in dollars per share)	55.9
Outstanding at end of period (in dollars per share)	48.43	$ 50.57
Exercisable at end of period (in dollars per share)	$ 52.24
Average Remaining Contractual Term, Aggregate Intrinsic Value and Other [Abstract]
Average remaining contractual term, outstanding at end of period	4 years 8 months 26 days
Average remaining contractual term, exercisable at end of period	3 years 2 months 12 days
Aggregate intrinsic value, outstanding at end of period	$ 78,542
Aggregate intrinsic value, exercisable at end of period	$ 28,349
Weighted average fair value of options granted (in dollars per share)	$ 19.72	$ 18.66	$ 24.35
Intrinsic value of options exercised	$ 6,000	$ 1,400	$ 2,500
Cash received from exercise of stock options	$ 65,100	$ 3,600	$ 8,500
Weighted-average fair value of options exercised (in dollars per share)	$ 49.23
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation cost related to non-vested stock options	$ 36,600
Weighted average period for recognition	1 year 1 month 6 days

Stockholders' Equity, Restricte

Stockholders' Equity, Restricted Stock Unit Activity (Details) - Restricted Stock Units [Member] - USD ($) $ / shares in Units, shares in Thousands, $ in Millions	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Number of Shares [Abstract]
Non-vested at beginning of period (in shares)	2,766
Granted (in shares)	1,707
Vested (in shares)	(1,055)
Cancelled/forfeited (in shares)	(179)
Non-vested at end of period (in shares)	3,239	2,766
Weighted Average Grant Date Fair Value per Share [Abstract]
Non-vested at beginning of period (in dollars per share)	$ 48.3
Granted (in dollars per share)	40.51	$ 36.14	$ 57.02
Vested (in dollars per share)	51.64
Cancelled/forfeited (in dollars per share)	42.9
Non-vested at end of period (in dollars per share)	$ 43.4	$ 48.3
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation cost related to non-vested units	$ 53.7
Weighted average period for recognition	1 year 3 months 18 days

Stockholders' Equity, Performan

Stockholders' Equity, Performance Restricted Stock Unit Activity (Details) - Performance Restricted Stock Units [Member] - USD ($) $ / shares in Units, shares in Thousands, $ in Millions	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Number of Shares [Abstract]
Non-vested at beginning of period (in shares)	143
Granted (in shares)	158
Vested (in shares)	(75)
Non-vested at end of period (in shares)	226	143
Weighted Average Grant Date Fair Value per Share [Abstract]
Non-vested at beginning of period (in dollars per share)	$ 52.59
Granted (in dollars per share)	57.43	$ 42.28	$ 77.17
Vested (in dollars per share)	52.43
Non-vested at end of period (in dollars per share)	$ 56.04	$ 52.59
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation cost related to non-vested units	$ 4.4
Weighted average period for recognition	1 year 4 months 24 days

Stockholders' Equity, Stock-bas

Stockholders' Equity, Stock-based Compensation Expense (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Stock-Based Compensation [Abstract]
Stock-based compensation expense	$ 105,809	$ 100,264	$ 120,678
Cost of Sales [Member]
Stock-Based Compensation [Abstract]
Stock-based compensation expense	499	533	456
Research, Development and Patent [Member]
Stock-Based Compensation [Abstract]
Stock-based compensation expense	77,826	73,704	87,522
Selling, General and Administrative [Member]
Stock-Based Compensation [Abstract]
Stock-based compensation expense	$ 27,484	$ 26,027	$ 32,700

Stockholders' Equity, Stock-b_2

Stockholders' Equity, Stock-based Valuation Information (Details)	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Employee Stock Options [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate	3.80%	2.10%	0.60%
Dividend yield	0%	0%	0%
Volatility	46.80%	54.50%	54%
Expected life	6 years 3 months 18 days	6 years 3 months 18 days	4 years 10 months 24 days
Employee Stock Options [Member] \| 2011 Equity Incentive Plan [Member]
Weighted-Average Assumptions [Abstract]
Award term	7 years
Employee Stock Options [Member] \| 2011 Equity Incentive Plan [Member] \| Issued after December 31, 2021 [Member]
Weighted-Average Assumptions [Abstract]
Award term	10 years
Employee Stock Options [Member] \| 2020 Equity Incentive Plan [Member]
Weighted-Average Assumptions [Abstract]
Award term	7 years
Employee Stock Options [Member] \| 2020 Equity Incentive Plan [Member] \| Issued after December 31, 2021 [Member]
Weighted-Average Assumptions [Abstract]
Award term	10 years
Board of Director Stock Options [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate	3.80%	2.90%	1.20%
Dividend yield	0%	0%	0%
Volatility	52.70%	56.20%	55.90%
Expected life	7 years 8 months 12 days	7 years 4 months 24 days	7 years 3 months 18 days
ESPP [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate	5.30%	1.20%	0.10%
Dividend yield	0%	0%	0%
Volatility	36%	50.10%	42.40%
Expected life	6 months	6 months	6 months

Income Taxes, Loss Before Incom

Income Taxes, Loss Before Income Taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Income Taxes [Abstract]
United States	$ (334,707)	$ (258,493)	$ (29,966)
Foreign	742	508	818
Loss before income tax benefit (expense)	$ (333,965)	$ (257,985)	$ (29,148)

Income Taxes, Income Tax Expens

Income Taxes, Income Tax Expense (Benefit) (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Current [Abstract]
Federal	$ 35,861	$ 10,522	$ (200)
State	(3,687)	1,129	(690)
Foreign	147	86	339
Total current income tax expense (benefit)	32,321	11,737	(551)
Deferred [Abstract]
Federal	0	0	0
State	0	0	0
Total deferred income tax benefit	0	0	0
Total income tax expense (benefit)	$ 32,321	$ 11,737	$ (551)

Income Taxes, Reconciliation of

Income Taxes, Reconciliation of Statutory to Effective Tax Rate (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Reconciliation Between Effective and Statutory Tax Rate [Abstract]
Pre-tax income (loss)	$ (333,965)	$ (257,985)	$ (29,148)
Statutory rate	(70,133)	(54,177)	(6,121)
State income tax net of federal benefit	(22,597)	(13,622)	4,278
Foreign	(22)	(49)	143
Net change in valuation allowance	175,388	104,951	2,885
Loss on debt transactions	0	0	262
Tax credits	(67,131)	(39,729)	(23,198)
Deferred tax true-up	4	(20)	(24)
Tax rate change	1,023	(3,091)	12,838
Non-deductible compensation	3,814	3,023	5,085
Other non-deductible items	327	57	84
Foreign-derived intangible income benefit	(7,493)	0	0
Stock-based compensation	19,546	14,030	4,720
Other	(405)	364	(1,503)
Total income tax expense (benefit)	$ 32,321	$ 11,737	$ (551)
Reconciliation Between Effective and Statutory Tax Rate Percentage [Abstract]
Statutory rate	21%	21%	21%
State income tax net of federal benefit	6.80%	5.30%	(14.70%)
Foreign	0%	0%	(0.50%)
Net change in valuation allowance	(52.50%)	(40.70%)	(9.90%)
Loss on debt transactions	0%	0%	(0.90%)
Tax credits	20.10%	15.40%	79.60%
Deferred tax true-up	0%	0%	0.10%
Tax rate change	(0.30%)	1.20%	(44.00%)
Non-deductible compensation	(1.10%)	(1.20%)	(17.40%)
Other non-deductible items	(0.10%)	0%	(0.30%)
Foreign-derived intangible income benefit	2.20%	0%	0%
Stock-based compensation	(5.90%)	(5.40%)	(16.20%)
Other	0.10%	(0.10%)	5.10%
Effective rate	(9.70%)	(4.50%)	1.90%

Income Taxes, Deferred Tax Asse

Income Taxes, Deferred Tax Assets and Liabilities (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022
Deferred Tax Assets [Abstract]
Net operating loss carryovers	$ 77,964	$ 87,802
Tax credits	239,962	277,436
Deferred revenue	71,683	85,700
Stock-based compensation	77,468	86,983
Intangible and capital assets	104,380	104,649
Convertible debt	16,849	34,384
Capitalized research and development expenses	238,738	119,635
Long-term lease liabilities	43,718	45,612
Sale of future royalties	144,608	0
Other	10,343	15,813
Total deferred tax assets	1,025,713	858,014
Deferred Tax Liabilities [Abstract]
Fixed assets	(4,166)	(4,475)
Right-of-use assets	(42,007)	(44,504)
Other	(1,910)	(313)
Net deferred tax asset	977,630	808,722
Valuation allowance	(977,630)	(808,722)
Total net deferred tax assets and liabilities	0	$ 0
Increase in valuation allowance	$ 169,000

Income Taxes, Tax Credit Carryf

Income Taxes, Tax Credit Carryforwards (Details) $ in Millions	12 Months Ended
	Dec. 31, 2023 USD ($)
Federal [Member]
Operating Loss Carryforwards [Abstract]
Net operating loss carryforwards	$ 242.8
California [Member]
Operating Loss Carryforwards [Abstract]
Net operating loss carryforwards	398.8
Research and Development [Member] \| Federal [Member]
Tax Credit Carryforwards [Abstract]
Tax credit carryforwards	169.7
Research and Development [Member] \| California [Member]
Tax Credit Carryforwards [Abstract]
Tax credit carryforwards	124.4
State [Member]
Operating Loss Carryforwards [Abstract]
Operating loss carryforwards utilized	$ 3.2

Income Taxes, Gross Unrecognize

Income Taxes, Gross Unrecognized Tax Benefits (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Gross Unrecognized Tax Benefits [Roll Forward]
Beginning balance of unrecognized tax benefits	$ 56,567	$ 55,085	$ 54,163
Decrease for lapse of statute of limitations	(14,993)	0	0
Decrease for prior period tax positions	(737)	(267)	(695)
Increase for prior period tax positions	429	259	263
Increase for current period tax positions	2,032	1,490	1,354
Ending balance of unrecognized tax benefits	43,298	56,567	55,085
Unrecognized tax benefits that could impact effective tax rate, if recognized	300	6,200	6,200
Decrease in unrecognized tax benefits that is reasonably possible	7,600
Interest and penalties on gross unrecognized tax benefits	$ 100	$ 800	$ 500

Employment Benefits (Details)

Employment Benefits (Details) - USD ($)	12 Months Ended
Employment Benefits (Details) - USD ($)	Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Employee Benefits [Abstract]
Matching contributions	$ 7,100,000	$ 5,600,000	$ 5,500,000
Minimum [Member]
Employee Benefits [Abstract]
Employee contribution limit per calendar year	22,500
Maximum [Member]
Employee Benefits [Abstract]
Employee contribution limit per calendar year	$ 30,000

Fourth Quarter Financial Data_3

Fourth Quarter Financial Data (Unaudited) (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended				12 Months Ended
	Dec. 31, 2023		Dec. 31, 2022		Dec. 31, 2023	Dec. 31, 2022	Dec. 31, 2021
Fourth Quarter Financial Data (Unaudited) [Abstract]
Revenue	$ 324,505	[1]	$ 151,890
Operating expenses	330,627	[2]	359,909		$ 1,141,377	$ 997,558	$ 840,642
Loss from operations	(6,122)		(208,019)		(353,730)	(410,191)	(30,186)
Net loss	$ (9,263)		$ (52,430)	[3]	$ (366,286)	$ (269,722)	$ (28,597)
Basic net loss per share (in dollars per share)	$ (0.06)	[4],[5]	$ (0.37)	[4],[5]	$ (2.56)	$ (1.9)	$ (0.2)
Diluted net loss per share (in dollars per share)	$ (0.06)	[4]	$ (0.37)	[4],[6]	$ (2.56)	$ (1.9)	$ (0.2)
Gain on sale of real estate assets			$ 150,100		$ (161)	$ 150,135	$ 0
WAINUA (Eplontersen) [Member]
Fourth Quarter Financial Data (Unaudited) [Abstract]
Revenue	$ 50,000
Cardiovascular, Renal and Metabolic Diseases [Member]
Fourth Quarter Financial Data (Unaudited) [Abstract]
Revenue	$ 36,000
Metagenomi License Agreement [Member]
Fourth Quarter Financial Data (Unaudited) [Abstract]
Upfront payment			$ 80,000

[1]Revenue was higher in the three months ended December 31, 2023 compared to the same period in 2022 primarily due to the $50 million milestone payment we earned from AstraZeneca when the FDA approved WAINUA for ATTRv-PN in the U.S., $36 million payment we earned when AstraZeneca licensed ION826 and revenue we recognized in the fourth quarter of 2023 from the upfront payments we received from our new collaborations with Otsuka, Roche and Novartis.[2]Operating expenses were lower in the three months ended December 31, 2023 compared to the same period in 2022 primarily due to the $80 million upfront payment we made for our collaboration with Metagenomi in the fourth quarter of 2022.[3]Our net loss for the three months ended December 31, 2022 includes the $150.1 million gain we recognized from the sale and leaseback transaction for our headquarters in Carlsbad, California.[4] We the year. Organization and Significant Accounting Policies,