Ionis Pharmaceuticals (IONS) 10-Q 2 Nov 23 2023 Q3 Quarterly report Financial data

Document and Entity Information

Document and Entity Information - shares	9 Months Ended
	Sep. 30, 2023	Oct. 27, 2023
Cover [Abstract]
Document Type	10-Q
Amendment Flag	false
Document Quarterly Report	true
Document Period End Date	Sep. 30, 2023
Current Fiscal Year End Date	--12-31
Document Fiscal Year Focus	2023
Document Fiscal Period Focus	Q3
Document Transition Report	false
Entity File Number	000-19125
Entity Registrant Name	Ionis Pharmaceuticals, Inc.
Entity Central Index Key	0000874015
Entity Incorporation, State or Country Code	DE
Entity Tax Identification Number	33-0336973
Entity Address, Address Line One	2855 Gazelle Court
Entity Address, City or Town	Carlsbad
Entity Address, State or Province	CA
Entity Address, Postal Zip Code	92010
City Area Code	760
Local Phone Number	931-9200
Title of 12(b) Security	Common Stock, $.001 Par Value
Trading Symbol	IONS
Security Exchange Name	NASDAQ
Entity Current Reporting Status	Yes
Entity Interactive Data Current	Yes
Entity Filer Category	Large Accelerated Filer
Entity Small Business	false
Entity Emerging Growth Company	false
Entity Shell Company	false
Entity Common Stock, Shares Outstanding		143,472,119

CONDENSED CONSOLIDATED BALANCE

CONDENSED CONSOLIDATED BALANCE SHEETS - USD ($) $ in Thousands	Sep. 30, 2023	Dec. 31, 2022
Current assets:
Cash and cash equivalents	$ 352,060	$ 276,472
Short-term investments	1,883,522	1,710,397
Contracts receivable	142,359	25,538
Inventories	25,634	22,033
Other current assets	181,075	168,254
Total current assets	2,584,650	2,202,694
Property, plant and equipment, net	70,928	74,294
Right-of-use assets	174,310	181,544
Deposits and other assets	104,083	75,344
Total assets	2,933,971	2,533,876
Current liabilities:
Accounts payable	5,615	17,921
Accrued compensation	33,781	49,178
Accrued liabilities	118,968	140,101
Income taxes payable	31,070	6,249
Current portion of deferred contract revenue	204,824	90,577
Other current liabilities	9,952	7,535
Total current liabilities	404,210	311,561
Long-term deferred contract revenue	249,272	287,768
Liability related to sale of future royalties, net	512,700	0
Long-term lease liabilities	173,038	178,941
Long-term obligations	48,801	15,973
Total liabilities	2,618,511	1,960,989
Stockholders' equity:
Common stock, $0.001 par value; 300,000,000 shares authorized, 143,393,493 and 142,057,736 shares issued and outstanding at September 30, 2023 (unaudited) and December 31, 2022, respectively	143	142
Additional paid-in capital	2,148,002	2,059,850
Accumulated other comprehensive loss	(46,037)	(57,480)
Accumulated deficit	(1,786,648)	(1,429,625)
Total stockholders' equity	315,460	572,887
Total liabilities and stockholders' equity	2,933,971	2,533,876
1.75 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	561,609	0
0 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	624,594	622,242
0.125 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	$ 44,287	$ 544,504

CONDENSED CONSOLIDATED BALANC_2

CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares	Sep. 30, 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)	143,393,493	142,057,736
Common stock, shares outstanding (in shares)	143,393,493	142,057,736
1.75 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	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%

CONDENSED CONSOLIDATED STATEMEN

CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS - USD ($) shares in Thousands, $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022
Revenue:
Revenue	$ 144,207	$ 159,767	$ 463,142	$ 435,478
Expenses:
Cost of sales	2,191	1,515	6,071	10,430
Research, development and patent	215,330	182,990	643,070	524,875
Selling, general and administrative	69,951	34,416	161,608	102,345
Total operating expenses	287,472	218,921	810,749	637,650
Loss from operations	(143,265)	(59,154)	(347,607)	(202,172)
Other income (expense):
Investment income	23,935	7,524	63,355	13,447
Interest expense	(4,203)	(2,139)	(8,102)	(6,391)
Interest expense related to sale of future royalties	(17,779)	0	(50,948)	0
Gain (loss) on investments	(1,943)	2,347	(1,753)	(10,616)
Other income (expense)	2,447	4,713	13,857	(7,923)
Loss before income tax expense	(140,808)	(46,709)	(331,198)	(213,655)
Income tax expense	(6,602)	(283)	(25,825)	(3,637)
Net loss	$ (147,410)	$ (46,992)	$ (357,023)	$ (217,292)
Basic net loss per share (in dollars per share)	$ (1.03)	$ (0.33)	$ (2.5)	$ (1.53)
Diluted net loss per share (in dollars per share)	$ (1.03)	$ (0.33)	$ (2.5)	$ (1.53)
Shares used in computing basic net loss per share (in shares)	143,317	141,950	143,052	141,782
Shares used in computing diluted net loss per share (in shares)	143,317	141,950	143,052	141,782
Commercial Revenue [Member]
Revenue:
Revenue	$ 84,081	$ 72,410	$ 229,746	$ 222,879
SPINRAZA Royalties [Member]
Revenue:
Revenue	67,253	61,647	178,511	175,092
Other Commercial Revenue [Member]
Revenue:
Revenue	16,828	10,763	51,235	47,787
Research and Development Revenue [Member]
Revenue:
Revenue	60,126	87,357	233,396	212,599
Collaborative Agreement Revenue [Member]
Revenue:
Revenue	44,167	69,250	173,513	157,282
Eplontersen Joint Development Revenue [Member]
Revenue:
Revenue	$ 15,959	$ 18,107	$ 59,883	$ 55,317

CONDENSED CONSOLIDATED STATEM_2

CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022
CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS [Abstract]
Net loss	$ (147,410)	$ (46,992)	$ (357,023)	$ (217,292)
Unrealized gains (losses) on debt securities, net of tax	5,029	(8,734)	11,421	(29,508)
Currency translation adjustment	(153)	(399)	22	(964)
Comprehensive loss	$ (142,534)	$ (56,125)	$ (345,580)	$ (247,764)

CONDENSED CONSOLIDATED STATEM_3

CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY - USD ($) shares in Thousands, $ in Thousands	Common Stock [Member]	Additional Paid in Capital [Member]	Accumulated Other Comprehensive Loss [Member]	Accumulated Deficit [Member]	Total
Balance at Dec. 31, 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	(217,292)	(217,292)
Change in unrealized gains (losses), net of tax	0	0	(29,508)	0	(29,508)
Foreign currency translation	0	0	(964)	0	(964)
Issuance of common stock in connection with employee stock plans	$ 1	6,029	0	0	6,030
Issuance of common stock in connection with employee stock plans (in shares)	1,138
Stock-based compensation expense	$ 0	74,575	0	0	74,575
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	$ 0	(10,217)	0	0	(10,217)
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)	(331)
Balance at Sep. 30, 2022	$ 142	2,034,554	(63,140)	(1,377,195)	594,361
Balance (in shares) at Sep. 30, 2022	142,017
Balance at Jun. 30, 2022	$ 142	2,008,794	(54,007)	(1,330,203)	624,726
Balance (in shares) at Jun. 30, 2022	141,831
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(46,992)	(46,992)
Change in unrealized gains (losses), net of tax	0	0	(8,734)	0	(8,734)
Foreign currency translation	0	0	(399)	0	(399)
Issuance of common stock in connection with employee stock plans	$ 0	2,567	0	0	2,567
Issuance of common stock in connection with employee stock plans (in shares)	203
Stock-based compensation expense	$ 0	23,837	0	0	23,837
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	$ 0	(644)	0	0	(644)
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)	(17)
Balance at Sep. 30, 2022	$ 142	2,034,554	(63,140)	(1,377,195)	594,361
Balance (in shares) at Sep. 30, 2022	142,017
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	(357,023)	(357,023)
Change in unrealized gains (losses), net of tax	0	0	11,421	0	11,421
Foreign currency translation	0	0	22	0	22
Issuance of common stock in connection with employee stock plans	$ 1	8,679	0	0	8,680
Issuance of common stock in connection with employee stock plans (in shares)	1,335
Stock-based compensation expense	$ 0	79,473	0	0	79,473
Balance at Sep. 30, 2023	$ 143	2,148,002	(46,037)	(1,786,648)	315,460
Balance (in shares) at Sep. 30, 2023	143,393
Balance at Jun. 30, 2023	$ 143	2,118,309	(50,913)	(1,639,238)	428,301
Balance (in shares) at Jun. 30, 2023	143,167
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(147,410)	(147,410)
Change in unrealized gains (losses), net of tax	0	0	5,029	0	5,029
Foreign currency translation	0	0	(153)	0	(153)
Issuance of common stock in connection with employee stock plans	$ 0	3,729	0	0	3,729
Issuance of common stock in connection with employee stock plans (in shares)	226
Stock-based compensation expense	$ 0	25,964	0	0	25,964
Balance at Sep. 30, 2023	$ 143	$ 2,148,002	$ (46,037)	$ (1,786,648)	$ 315,460
Balance (in shares) at Sep. 30, 2023	143,393

CONDENSED CONSOLIDATED STATEM_4

CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	9 Months Ended
	Sep. 30, 2023	Sep. 30, 2022
Operating activities:
Net loss	$ (357,023)	$ (217,292)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation	7,748	11,301
Amortization of right-of-use operating lease assets	7,234	1,970
Amortization of other assets	1,904	1,805
Amortization of premium (discount) on investments, net	(20,396)	9,072
Amortization of debt issuance costs	4,666	4,035
Non-cash royalty revenue related to sale of royalties	(27,814)	0
Non-cash interest related to sale of future royalties	50,541	0
Stock-based compensation expense	79,473	74,575
Loss on investments	1,429	228
Gain on early retirement of debt	(13,389)	0
Non-cash losses related to disposal of property, plant and equipment	14,646	528
Non-cash losses related to other assets	849	1,155
Changes in operating assets and liabilities:
Contracts receivable	(116,814)	55,251
Inventories	(3,601)	4,161
Other current and long-term assets	(18,325)	(988)
Income taxes payable	24,821	(20)
Accounts payable	(12,462)	5,607
Accrued compensation	(15,397)	(8,400)
Accrued liabilities and other current liabilities	(24,219)	38,263
Deferred contract revenue	75,751	(55,426)
Net cash used in operating activities	(340,378)	(74,175)
Investing activities:
Purchases of short-term investments	(1,353,100)	(1,223,791)
Proceeds from sale of short-term investments	1,193,724	764,101
Purchases of property, plant and equipment	(24,624)	(11,582)
Acquisition of licenses and other assets, net	(3,414)	(3,511)
Net cash used in investing activities	(187,414)	(474,783)
Financing activities:
Proceeds from equity, net	8,680	6,030
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	0	(10,217)
Proceeds from issuance of 1.75 percent convertible senior notes	575,000	0
1.75 percent convertible senior notes issuance costs	(14,175)	0
Repurchase of $504.4 million principal amount of 0.125 percent convertible senior notes	(487,943)	0
Proceeds from sale of future royalties	500,000	0
Payments of transaction costs related to sale of future royalties	(10,434)	0
Proceeds from real estate transaction	32,352	0
Principal payments on mortgage debt	(122)	(89)
Net cash provided by (used in) financing activities	603,358	(4,276)
Effects of exchange rates on cash	22	(964)
Net increase (decrease) in cash and cash equivalents	75,588	(554,198)
Cash and cash equivalents at beginning of period	276,472	869,191
Cash and cash equivalents at end of period	352,060	314,993
Supplemental disclosures of cash flow information:
Interest paid	952	2,204
Income taxes paid	714	2
Supplemental disclosures of non-cash investing and financing activities:
Amounts accrued for capital and patent expenditures	341	3,032
Right-of-use assets obtained in exchange for lease liabilities	$ 0	$ 657

CONDENSED CONSOLIDATED STATEM_5

CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS (Parenthetical) - USD ($) $ in Millions	Sep. 30, 2023	Jun. 30, 2023	Dec. 31, 2022	Sep. 30, 2022
1.75 Percent Convertible Senior Notes [Member]
Financing activities:
Interest rate on convertible senior notes	1.75%
0.125 Percent Convertible Senior Notes [Member]
Financing activities:
Interest rate on convertible senior notes	0.125%		0.125%	0.125%
Principal amount repurchased	$ 504.4	$ 434.1

Organization and Basis of Prese

Organization and Basis of Presentation	9 Months Ended
	Sep. 30, 2023
Organization and Basis of Presentation [Abstract]
Organization and Basis of Presentation	1. Organization and Basis of Presentation Organization and Business Activity We incorporated in California on January 10, 1989. In conjunction with our initial public offering, we reorganized as a Delaware corporation in April 1991. We are a leader in the discovery and development of RNA-targeted therapeutics. Basis of Presentation We prepared the unaudited interim condensed consolidated financial statements for the three and nine months ended September 30, 2023 and 2022 on the same basis as the audited financial statements for the year ended December 31, 2022. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended December 31, 2022 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC. In our condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (“we”, “us” or “our”). We operate as a single single Use of Estimates We prepare our condensed consolidated financial statements in conformity with accounting principles generally accepted in the United States, or

Significant Accounting Policies

Significant Accounting Policies	9 Months Ended
	Sep. 30, 2023
Significant Accounting Policies [Abstract]
Significant Accounting Policies	2. Significant Accounting Policies Our significant accounting policies have not changed substantially from those included in our Annual Report on Form 10-K for the year ended December 31, 2022, other than as discussed below. 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 11, Liability Related to Sale of Future Royalties 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 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 liability related to the sale of future royalties, effective interest rate and the related interest expense. Recently Adopted Accounting Standards We do not expect any recently issued accounting standards to have a material impact to our financial results.

Supplemental Financial Data

Supplemental Financial Data	9 Months Ended
	Sep. 30, 2023
Supplemental Financial Data [Abstract]
Supplemental Financial Data	3. Supplemental Financial Data Inventories Our inventory consisted of the following (in thousands): September 30, 2023 December 31, 2022 Raw materials: Raw materials - clinical $ 18,427 $ 17,061 Raw materials - commercial 4,380 2,699 Total raw materials 22,807 19,760 Work in process 2,651 2,109 Finished goods 176 164 Total inventory $ 25,634 $ 22,033 Accrued Liabilities Our accrued liabilities consisted of the following (in thousands): September 30, 2023 December 31, 2022 Clinical development expenses $ 89,217 $ 116,460 In-licensing expenses 7,560 7,945 Commercial expenses 8,575 3,498 Other miscellaneous expenses 13,616 12,198 Total accrued liabilities $ 118,968 $ 140,101

Revenues

Revenues	9 Months Ended
	Sep. 30, 2023
Revenues [Abstract]
Revenues	4. Revenues During the three and nine months ended September 30, 2023 and 2022, our revenues were comprised of the following (in thousands): Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Revenue: Commercial revenue: SPINRAZA royalties $ 67,253 $ 61,647 $ 178,511 $ 175,092 Other commercial revenue: TEGSEDI and WAYLIVRA revenue, net 8,286 5,920 25,420 22,467 Licensing and other royalty revenue 8,542 4,843 25,815 25,320 Total other commercial revenue 16,828 10,763 51,235 47,787 Total commercial revenue 84,081 72,410 229,746 222,879 Research and development revenue: Collaborative agreement revenue 44,167 69,250 173,513 157,282 Eplontersen joint development revenue 15,959 18,107 59,883 55,317 Total research and development revenue 60,126 87,357 233,396 212,599 Total revenue $ 144,207 $ 159,767 $ 463,142 $ 435,478 Refer to Note 5, Collaborative Arrangements and Licensing Agreements

Collaborative Arrangements and

Collaborative Arrangements and Licensing Agreements	9 Months Ended
	Sep. 30, 2023
Collaborative Arrangements and Licensing Agreements [Abstract]
Collaborative Arrangements and Licensing Agreements	5. Collaborative Arrangements and Licensing Agreements Below, we have included our AstraZeneca, Biogen, GSK, Novartis, Roche and Sobi collaborations, which are the collaborations with substantive changes during 2023 from those included in Part IV, Item 15, Note 7, Collaborative Arrangements and Licensing Agreements , of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2022. AstraZeneca We have collaborations with AstraZeneca, focused on the joint development and commercialization of eplontersen for the treatment of transthyretin amyloidosis, or ATTR, and focused on the treatment of cardiovascular, renal and metabolic diseases. From inception through , we have received nearly $ million from these collaborations. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. In addition, we granted AstraZeneca exclusive rights to commercialize eplontersen outside the U.S. In the second quarter of 2023, we earned a $ million license fee payment when we licensed rights to Latin America for eplontersen to AstraZeneca. We recognized the upfront payment in full in the second quarter of 2023 because AstraZeneca had full use of the license without any continuing involvement from us. Under our collaboration for cardiovascular, renal and metabolic diseases, 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. In the second quarter of 2023, . During the three and nine months ended September 30, 2023 and 2022, we earned the following revenue from our relationship with AstraZeneca (in thousands, except percentages): Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Revenue from our relationship with AstraZeneca $ 15,959 $ 18,107 $ 99,885 $ 55,718 Percentage of total revenue 11 % 11 % 22 % 13 % We did not have any deferred contract revenue from our relationship with AstraZeneca at September 30, 2023 or December 31, 2022. 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 recently approved medicine in the U.S. to treat patients with superoxide dismutase 1 amyotrophic lateral sclerosis, or SOD1-ALS. Under our collaborations, we and Biogen are currently developing numerous investigational medicines to treat neurodegenerative diseases in addition to SMA and SOD1-ALS, including medicines in development to treat people with , 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 , we have received more than $ billion in payments from our Biogen collaborations. Under our 2013 strategic neurology collaboration, we earned a $16 million milestone payment from Biogen when the U.S. Food and Drug Administration, or FDA, approved Biogen’s New Drug Application, or NDA, for QALSODY in the second quarter of 2023. We recognized this milestone payment as R&D revenue in full in the second quarter of 2023 because we did not have any remaining performance obligations related to the milestone payment. Under our collaboration agreement with Biogen, we are eligible to receive tiered royalties ranging from 11 percent to 15 percent on sales of QALSODY. Following the NDA approval in April 2023, we began earning royalties from QALSODY sales, which we recognize as other commercial revenue in our condensed consolidated statements of operations. We will achieve the next milestone payment for QALSODY of $20 million if the European Medicines Agency approves Biogen’s Marketing Authorization Application, filing of QALSODY. Under our 2012 neurology collaboration, we achieved $21 million in milestone payments from Biogen when Biogen advanced ION582, our investigational antisense medicine for the potential treatment of AS, in the third quarter of 2023. We are recognizing these milestone payments as revenue as we perform services based on our effort to satisfy our R&D services performance obligation relative to the total effort expected to satisfy our performance obligation for ION582. During the three and nine months ended September 30, 2023 and 2022, we earned the following revenue from our relationship with Biogen (in thousands, except percentages): Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Revenue from our relationship with Biogen $ 94,695 $ 88,959 $ 262,599 $ 259,713 Percentage of total revenue 66 % 56 % 57 % 60 % In October 2023, we earned a milestone payment of $9 million from Biogen when we advanced ION582 under our 2012 neurology collaboration. We will achieve the next payment of $70 million if Biogen licenses ION582 under this collaboration. Our condensed consolidated balance sheets at September 30, 2023 and December 31, 2022 GSK In March 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 and some conditions causing blindness. Our collaboration with GSK currently includes bepirovirsen, our medicine in development for the treatment of hepatitis B virus, or HBV, infection. In the third quarter of 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 In the first quarter of 2023, we earned a $15 million milestone payment when GSK initiated a Phase 3 program of bepirovirsen. We recognized this milestone payment as R&D revenue in full in the first quarter of 2023 because we did not have any remaining performance obligations related to the milestone payment. We will achieve the next payment of $15 million if the FDA accepts an NDA filing of bepirovirsen for review. During the three and nine months ended September 30, 2023 and 2022, we earned the following revenue from our relationship with GSK (in thousands, except percentages): Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Revenue from our relationship with GSK $ — $ — $ 15,000 $ — Percentage of total revenue 0 % 0 % 3 % 0 % We did not have any deferred contract revenue from our relationship with GSK at September 30, 2023 or December 31, 2022. Novartis In January 2017, we initiated a collaboration with Novartis to develop and commercialize pelacarsen, an investigational medicine for patients with elevated lipoprotein(a), or Lp(a)-driven cardiovascular disease, or CVD. Novartis is responsible for conducting and funding development and regulatory activities for pelacarsen, including a global Phase 3 cardiovascular outcomes study, which Novartis initiated in December 2019. 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 CVD. Novartis is solely responsible for the development, manufacturing and potential commercialization of the next generation Lp(a) therapy. In September 2023, this agreement received clearance under the Hart-Scott-Rodino Antitrust Improvements Act of 1976. Novartis paid us a $ million upfront payment in October 2023 and we are eligible to receive development, regulatory and commercial milestone payments and tiered royalties ranging from to . At the commencement of this collaboration, we identified one performance obligation, which was to perform R&D services for Novartis. We included the upfront payment in our transaction price for our R&D services 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 will achieve the next payment of $5 million if we designate a development candidate under this collaboration. From inception through September 30, 2023, we have received more than $275 million in payments from our Novartis collaborations. During the three and nine months ended September 30, 2023 and 2022, we earned the following revenue from our relationship with Novartis (in thousands, except percentages): Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Revenue from our relationship with Novartis $ 1,908 $ — $ 2,023 $ — Percentage of total revenue 1 % 0 % 0 % 0 % Our condensed consolidated balance sheet at September 30, 2023 included deferred contract revenue of $58.1 million from our relationship with Novartis. We did not have any deferred contract revenue from our relationship with Novartis at December 31, 2022. Roche We have three collaborations with Hoffmann-La Roche Inc and F. Hoffmann-La Roche Ltd, collectively Roche: one to develop IONIS-FB-L Rx 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. Roche paid us a $60 million upfront payment in October 2023 and we are eligible to receive development, regulatory and commercial milestone payments and tiered royalties up to the mid-teens on net sales of any product resulting from this collaboration. We identified two performance obligations under this new agreement, comprised of R&D services for each of the two From inception through September 30, 2023, we have received more than $285 million in payments from our Roche collaborations. During the three and nine months ended September 30, 2023 and 2022, we earned the following revenue from our relationship with Roche (in thousands, except percentage amounts): Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 R&D revenue $ 8,858 $ 41,504 $ 16,979 $ 65,360 Percentage of total revenue 6 % 26 % 4 % 15 % Our condensed consolidated balance sheets at September 30, 2023 and December 31, 2022 included deferred contract revenue of $68.0 million and $22.4 million, respectively, from our relationship with Roche. Swedish Orphan Biovitrum AB (Sobi) We began commercializing TEGSEDI and WAYLIVRA in Europe in January 2021 and TEGSEDI in North America in April 2021 through distribution agreements with Swedish Orphan Biovitrum AB, or Sobi. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. In exchange, we earn a distribution fee on net sales from Sobi for each medicine. In October 2023, our distribution agreement for TEGSEDI in North America was terminated. During the three and nine months ended September 30, 2023 and 2022, we earned the following revenue from our distribution agreement with Sobi for TEGSEDI in North America (in thousands, except percentage amounts). Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 TEGSEDI revenue from our distribution agreement with Sobi in North America $ 794 $ 1,008 $ 2,189 $ 3,443 Percentage of total revenue 1 % 1 % 2 % 1 %

Basic and Diluted Net Loss Per

Basic and Diluted Net Loss Per Share	9 Months Ended
	Sep. 30, 2023
Basic and Diluted Net Loss Per Share [Abstract]
Basic and Diluted Net Loss Per Share	6. Basic and Diluted Net Loss Per Share Basic net loss per share We calculated our basic net loss per share for the three and nine months ended September 30, 2023 and 2022 by dividing our net loss by our weighted-average number of common shares outstanding during the period. Diluted net loss per share For the three and nine months ended September 30, 2023 and 2022, 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: ● 1.75 percent convertible senior notes, or 1.75% Notes; ● 0 percent convertible senior notes, or 0% Notes; ● Note hedges related to the 0% Notes; ● 0.125 percent convertible senior notes, or 0.125% Notes; ● Note hedges related to the 0.125% Notes; ● Dilutive stock options; ● Unvested restricted stock units, or RSUs; ● Unvested performance restricted stock units, or PRSUs; and ● Employee Stock Purchase Plan, or ESPP. Additionally as of September 30, 2023, we had warrants related to our 0% and 0.125% Notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.

Investments

Investments	9 Months Ended
	Sep. 30, 2023
Investments [Abstract]
Investments	7. Investments The following table summarizes the contract maturity of the available-for-sale securities we held as of September 30, 2023: One year 72 % After one year two years 20 % After two years three and a half years 8 % Total 100 % As illustrated above, at September 30, 2023, 92 percent of our available-for-sale securities had a maturity of less than two years. All of our available-for-sale debt securities are available to us for use in our current operations. As a result, we categorize all of these securities as current assets even though the stated maturity of some individual securities may be one year or more beyond the balance sheet date. We invest in debt securities At September 30, 2023, we had an equity ownership interest of less than 20 percent in seven private companies and three public companies with which we conduct business. The following is a summary of our investments (in thousands): Amortized Gross Unrealized Estimated September 30, 2023 Cost Gains Losses Fair Value Available-for-sale debt securities: Corporate debt securities (1) $ 535,408 $ 13 $ (4,492 ) $ 530,929 Debt securities issued by U.S. government agencies 267,503 — (1,429 ) 266,074 Debt securities issued by the U.S. Treasury (1) 520,013 1 (3,027 ) 516,987 Debt securities issued by states of the U.S. and political subdivisions of the states 23,906 — (242 ) 23,664 Total debt securities with a maturity of one year or less 1,346,830 14 (9,190 ) 1,337,654 Corporate debt securities 195,674 183 (3,160 ) 192,697 Debt securities issued by U.S. government agencies 56,365 — (507 ) 55,858 Debt securities issued by the U.S. Treasury 297,501 — (3,364 ) 294,137 Debt securities issued by states of the U.S. and political subdivisions of the states 4,164 53 (51 ) 4,166 Total debt securities with a maturity of more than one year 553,704 236 (7,082 ) 546,858 Total available-for-sale debt securities $ 1,900,534 $ 250 $ (16,272 ) $ 1,884,512 Equity securities: Publicly traded equity securities included in other current assets (2) $ 11,897 $ (1,252 ) $ (4,083 ) $ 6,562 Privately held equity securities included in deposits and other assets (3) 23,115 25,001 (5,125 ) 42,991 Total equity securities 35,012 23,749 (9,208 ) 49,553 Total available-for-sale debt and equity securities $ 1,935,546 $ 23,999 $ (25,480 ) $ 1,934,065 Amortized Gross Unrealized Estimated December 31, 2022 Cost Gains Losses Fair Value Available-for-sale debt 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 debt 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 debt securities with a maturity of more than one year 525,314 130 (15,621 ) 509,823 Total available-for-sale debt 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 debt and equity securities $ 1,783,848 $ 17,451 $ (28,997 ) $ 1,772,302 (1) Includes investments classified as cash equivalents in our condensed 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 nine months ended September 30, 2023, we recognized a $4.0 million unrealized loss in our condensed consolidated statements of operations related to a decrease 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 . In the , we recorded a net gain of $ million in our condensed 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 consider to be temporarily impaired at September 30, 2023 (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 370 $ 469,095 $ (2,390 ) $ 207,073 $ (5,262 ) $ 676,168 $ (7,652 ) Debt securities issued by U.S. government agencies 98 293,408 (1,242 ) 24,531 (694 ) 317,939 (1,936 ) Debt securities issued by the U.S. Treasury 68 557,489 (3,420 ) 225,634 (2,971 ) 783,123 (6,391 ) Debt securities issued by states of the U.S. and political subdivisions of the states 85 11,644 (73 ) 12,973 (220 ) 24,617 (293 ) Total temporarily impaired securities 621 $ 1,331,636 $ (7,125 ) $ 470,211 $ (9,147 ) $ 1,801,847 $ (16,272 ) 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	9 Months Ended
	Sep. 30, 2023
Fair Value Measurements [Abstract]
Fair Value Measurements	8. Fair Value Measurements The following tables present the major security types we held at September 30, 2023 and December 31, 2022 that we regularly measure and carry at fair value. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective security’s fair value (in thousands): At September 30, 2023 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 269,255 $ 269,255 $ — Corporate debt securities (2) 723,626 — 723,626 Debt securities issued by U.S. government agencies (3) 321,932 — 321,932 Debt securities issued by the U.S. Treasury (2) 811,124 811,124 — Debt securities issued by states of the U.S. and political subdivisions of the states (2) 27,830 — 27,830 Publicly traded equity securities included in other current assets (4) 6,562 6,562 — Total $ 2,160,329 $ 1,086,941 $ 1,073,388 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 (5) 726,950 — 726,950 Debt securities issued by U.S. government agencies (2) 165,055 — 165,055 Debt securities issued by the U.S. Treasury (2) 748,475 748,475 — Debt securities issued by states of the U.S. and political subdivisions of the states (2) 74,917 — 74,917 Other municipal debt securities (2) 5,994 — 5,994 Publicly traded equity securities included in other current assets (4) 10,539 10,539 — Total $ 1,943,585 $ 970,669 $ 972,916 The following footnotes reference lines in our condensed consolidated balance sheets: (1) Included in cash and cash equivalents in our condensed consolidated balance sheets. (2) Included in short-term investments in our condensed consolidated balance sheets. (3) $1.0 million was included in cash and cash equivalents, with the difference included in short-term investments, in our condensed consolidated balance sheets. (4) Included in other current assets in our condensed consolidated balance sheets. (5) $11.0 million was included in cash and cash equivalents, with the difference included in short-term investments, in our condensed consolidated balance sheets. Convertible Notes Our 1.75% Notes, 0% Notes and 0.125% Notes had a fair value of $605.3 million, $620.1 million and $42.4 million at September 30, 2023, respectively. Our 0% Notes and 0.125% Notes had a fair value of $587.3 million and $498.9 million at December 31, 2022, respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.

Stock-based Compensation Expens

Stock-based Compensation Expense	9 Months Ended
	Sep. 30, 2023
Stock-based Compensation Expense [Abstract]
Stock-based Compensation Expense	9. Stock-based Compensation Expense We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates. We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. On the grant date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the awards, and actual and projected employee stock option exercise behaviors. We recognize compensation expense for stock options, 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. For the nine months ended September 30, 2023 and 2022, we used the following weighted-average assumptions in our Black-Scholes calculations: Employee Stock Options: Nine Months Ended September 30, 2023 2022 Risk-free interest rate 3.7 % 1.9 % Dividend yield 0.0 % 0.0 % Volatility 47.1 % 54.9 % Expected life 6.3 years 6.3 years Ionis Board of Director Stock Options: Nine Months Ended September 30, 2023 2022 Risk-free interest rate 3.8 % 2.9 % Dividend yield 0.0 % 0.0 % Volatility 53.0 % 56.2 % Expected life 7.7 years 7.4 years ESPP: Nine Months Ended September 30, 2023 2022 Risk-free interest rate 5.3 % 1.2 % Dividend yield 0.0 % 0.0 % Volatility 36.0 % 50.1 % Expected life 6 months 6 months RSUs: 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. The RSUs we granted after June 2020 to our board of directors fully vest after one year. The weighted-average grant date fair value of RSUs granted to employees for the nine months ended September 30, 2023 and 2022 was $39.78 and $34.88 per share, respectively. PRSUs: Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. In 2022, we added PRSU awards to the compensation for our other Section 16 officers. Beginning in 2023, we added PRSU awards to the compensation for all executive 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. The weighted-average grant date fair value of PRSUs granted to our executive officers for the nine months ended September 30, 2023 and 2022 were $58.99 and $42.28 per share, respectively. The following table summarizes stock-based compensation expense for the three and nine months ended September 30, 2023 and 2022 (in thousands): Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Cost of sales $ 118 $ 163 $ 355 $ 376 Research, development and patent expense 18,727 17,733 57,543 55,315 Selling, general and administrative expense 7,119 5,941 21,575 18,884 Total stock-based compensation expense $ 25,964 $ 23,837 $ 79,473 $ 74,575 As of September 30, 2023, total unrecognized estimated stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $44.1 million, $62.2 million and $7.3 million, respectively. Our actual expenses may differ from these estimates because we will adjust our unrecognized stock-based compensation expense for future forfeitures, including any PRSUs that do not vest. We expect to recognize the cost of stock-based compensation expense related to our non-vested stock options, RSUs and PRSUs over a weighted average amortization period of 1.2 years, 1.4 years and 1.7 years, respectively.

Income Taxes

Income Taxes	9 Months Ended
	Sep. 30, 2023
Income Taxes [Abstract]
Income Taxes	10. Income Taxes Beginning in 2022, the Tax Cuts and Jobs Act of 2017, or TCJA, requires taxpayers to amortize research and development expenditures over five years pursuant to Internal Revenue Code, or IRC, Section 174. Additionally, we expect to reflect the royalty purchase agreement with Royalty Pharma as a taxable sale, requiring us to include the proceeds from the sale, net of currently deductible issuance costs, as taxable income in 2023. The resulting tax liability is partially offset by the utilization of our R&D tax credits. We recorded income tax expense of $6.6 million and $25.8 million for the three and nine months ended September 30, 2023, respectively, compared to $0.3 million and $3.6 million for the same periods in 2022, respectively. The increase in income tax expense for the three and nine months ended September 30, 2023, compared to the same periods in 2022, relates primarily to the impact of the Royalty Pharma transaction. We continue to maintain a full valuation allowance on all our net deferred tax assets.

Liability Related to Sale of Fu

Liability Related to Sale of Future Royalties	9 Months Ended
	Sep. 30, 2023
Liability Related to Sale of Future Royalties [Abstract]
Liability Related to Sale of Future Royalties	11. Liability Related to Sale of Future Royalties In January 2023, we entered into a royalty purchase agreement with 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. 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 September 30, 2023, the estimated effective interest rate under the agreement was 13.5 percent. The following is a summary of our liability related to sale of future royalties for the nine months ended September 30, 2023 (in thousands): Proceeds from sale of future royalties $ 500,000 Royalty payments to Royalty Pharma (27,814 ) Interest expense related to sale of future royalties 50,541 Liability related to sale of future royalties as of September 30, 2023 522,727 Issuance costs related to sale of future royalties (10,434 ) Amortization of issuance costs related to sale of future royalties as of September 30, 2023 407 Net liability related to sale of future royalties as of September 30, 2023 $ 512,700 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.

Convertible Debt

Convertible Debt	9 Months Ended
	Sep. 30, 2023
Convertible Debt [Abstract]
Convertible Debt	12. Convertible Debt 1.75 Percent Convertible Senior Notes In June 2023, we completed a $575.0 million offering of convertible senior notes and used $420.4 million of the net proceeds from the issuance of the 1.75% Notes to repurchase $434.1 million in principal of our 0.125% Notes. In the third quarter of 2023, we used $67.8 million of the residual proceeds to repurchase an additional $70.3 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 September 30, 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 $ 13.4 Maturity date June 2028 Interest rate 1.75 percent Effective interest rate 2.3 percent Conversion price per share $ 53.73 Total shares of common stock subject to conversion 10.7 0 Percent Convertible Senior Notes and Call Spread In April 2021, we completed a $632.5 million offering of convertible senior notes. We used $257.0 million of the net proceeds from the issuance of the 0% Notes to repurchase $247.9 million in principal of our 1% convertible senior notes, or 1% Notes. At September 30, 2023, we had the following 0% 0% Notes Outstanding principal balance $ 632.5 Unamortized debt issuance costs $ 7.9 Maturity date April 2026 Interest rate 0 percent Effective interest rate 0.5 percent Conversion price per share $ 57.84 Effective conversion price per share with call spread $ 76.39 Total shares of common stock subject to conversion 10.9 In conjunction with the April 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our 0% 0% 0% 0% 0% 0% 0% 0% We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our condensed consolidated balance sheets. Refer to Part IV, Item 15, Note 1, Organization and Significant Accounting Policies 0.125 Percent Convertible Senior Notes and Call Spread As discussed above, in June 2023, we repurchased $434.1 million of our 0.125% Notes. In the third quarter of 2023, we used $67.8 million of residual net proceeds from the issuance of the 1.75% Notes to repurchase an additional $70.3 million of our 0.125% Notes. As a result, the remaining principal balance of our 0.125% Notes was $44.5 million as of September 30, 2023. Additionally, in the three and nine months ended September 30, 2023, we recorded a $2.1 million and $13.4 million gain on the early retirement of debt, respectively, which we recorded as other income in our condensed 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 September 30, 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 percent Effective interest rate 0.5 percent Conversion price per share $ 83.28 Effective conversion price per share with call spread $ 123.38 Total shares of common stock subject to conversion 0.5 In conjunction with the issuance of our Notes in December 2019, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our . 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. As of , the note hedges and warrants remain outstanding. We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our condensed consolidated balance sheets. We reassess our ability to continue to classify the note hedges and warrants in shareholders’ equity at each reporting period. Other Terms of Convertible Senior Notes The , 0% and 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 of the principal amount of the notes to be purchased, plus any accrued and unpaid interest.

Real Estate Transactions

Real Estate Transactions	9 Months Ended
	Sep. 30, 2023
Real Estate Transactions [Abstract]
Real Estate Transactions	13. Real Estate Transactions In October 2022, we concurrently entered into two purchase and sale agreements with a real estate investor. In the same month, 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. 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 In October 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 condensed 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 $18 million, primarily associated with the impairment of construction-in-progress assets, within selling, general and administrative

Legal Proceedings

Legal Proceedings	9 Months Ended
	Sep. 30, 2023
Legal Proceedings [Abstract]
Legal Proceedings	14. 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.

Insider Trading Arrangements

Insider Trading Arrangements	9 Months Ended
	Sep. 30, 2023 shares
Trading Arrangements, by Individual
Material Terms of Trading Arrangement	During the quarter ended September 30, 2023, our 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** Brett Monia, CEO and Board Member Termination July 12, 2023 X 30,023 Upon the execution of all instructions provided in the plan Brett Monia, CEO and Board Member Adoption July 13, 2023 X 54,442 Upon the execution of all instructions provided in the plan Eric Swayze, EVP, Research Adoption July 13, 2023 X 85,614 Upon the execution of all instructions provided in the plan Spencer Berthelsen, Board Member Adoption September 7, 2023 X 16,000 Upon the execution of all instructions provided in the plan B. Lynne Parshall, Board Member Adoption September 27, 2023 X 122,638 Upon the execution of all instructions provided in the plan
Brett Monia [Member]
Trading Arrangements, by Individual
Name	Brett Monia
Title	CEO and Board Member
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	July 13, 2023
Rule 10b5-1 Arrangement Terminated	true
Non-Rule 10b5-1 Arrangement Terminated	false
Termination Date	July 12, 2023
Eric Swayze [Member]
Trading Arrangements, by Individual
Name	Eric Swayze
Title	EVP, Research
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	July 13, 2023
Arrangement Duration
Aggregate Available	85,614
Spencer Berthelsen [Member]
Trading Arrangements, by Individual
Name	Spencer Berthelsen
Title	Board Member
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	September 7, 2023
Arrangement Duration
Aggregate Available	16,000
B. Lynne Parshall [Member]
Trading Arrangements, by Individual
Name	B. Lynne Parshall
Title	Board Member
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	September 27, 2023
Arrangement Duration
Aggregate Available	122,638
Termination [Member] | Brett Monia [Member]
Trading Arrangements, by Individual
Arrangement Duration
Aggregate Available	30,023
Adoption [Member] | Brett Monia [Member]
Trading Arrangements, by Individual
Arrangement Duration
Aggregate Available	54,442

Organization and Basis of Pre_2

Organization and Basis of Presentation (Policies)	9 Months Ended
	Sep. 30, 2023
Organization and Basis of Presentation [Abstract]
Basis of Presentation	We prepared the unaudited interim condensed consolidated financial statements for the three and nine months ended September 30, 2023 and 2022 on the same basis as the audited financial statements for the year ended December 31, 2022. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended December 31, 2022 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.
Consolidation	In our condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (“we”, “us” or “our”).
Segment Information	We operate as a single single
Use of Estimates	Use of Estimates We prepare our condensed consolidated financial statements in conformity with accounting principles generally accepted in the United States, or

Significant Accounting Polici_2

Significant Accounting Policies (Policies)	9 Months Ended
	Sep. 30, 2023
Significant Accounting Policies [Abstract]
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 11, Liability Related to Sale of Future Royalties 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 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 liability related to the sale of future royalties, effective interest rate and the related interest expense.
Recently Adopted Accounting Standards	Recently Adopted Accounting Standards We do not expect any recently issued accounting standards to have a material impact to our financial results.

Basic and Diluted Net Loss Pe_2

Basic and Diluted Net Loss Per Share (Policies)	9 Months Ended
	Sep. 30, 2023
Basic and Diluted Net Loss Per Share [Abstract]
Basic and Diluted Net Loss Per Share	Basic net loss per share We calculated our basic net loss per share for the three and nine months ended September 30, 2023 and 2022 by dividing our net loss by our weighted-average number of common shares outstanding during the period. Diluted net loss per share For the three and nine months ended September 30, 2023 and 2022, 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: ● 1.75 percent convertible senior notes, or 1.75% Notes; ● 0 percent convertible senior notes, or 0% Notes; ● Note hedges related to the 0% Notes; ● 0.125 percent convertible senior notes, or 0.125% Notes; ● Note hedges related to the 0.125% Notes; ● Dilutive stock options; ● Unvested restricted stock units, or RSUs; ● Unvested performance restricted stock units, or PRSUs; and ● Employee Stock Purchase Plan, or ESPP. Additionally as of September 30, 2023, we had warrants related to our 0% and 0.125% Notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.

Stock-based Compensation Expe_2

Stock-based Compensation Expense (Policies)	9 Months Ended
	Sep. 30, 2023
Stock-based Compensation Expense [Abstract]
Stock-Based Compensation Expense	We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates. We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. On the grant date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the awards, and actual and projected employee stock option exercise behaviors. We recognize compensation expense for stock options, 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.

Supplemental Financial Data (Ta

Supplemental Financial Data (Tables)	9 Months Ended
	Sep. 30, 2023
Supplemental Financial Data [Abstract]
Inventories	Inventories Our inventory consisted of the following (in thousands): September 30, 2023 December 31, 2022 Raw materials: Raw materials - clinical $ 18,427 $ 17,061 Raw materials - commercial 4,380 2,699 Total raw materials 22,807 19,760 Work in process 2,651 2,109 Finished goods 176 164 Total inventory $ 25,634 $ 22,033
Accrued Liabilities	Accrued Liabilities Our accrued liabilities consisted of the following (in thousands): September 30, 2023 December 31, 2022 Clinical development expenses $ 89,217 $ 116,460 In-licensing expenses 7,560 7,945 Commercial expenses 8,575 3,498 Other miscellaneous expenses 13,616 12,198 Total accrued liabilities $ 118,968 $ 140,101

Revenues (Tables)

Revenues (Tables)	9 Months Ended
	Sep. 30, 2023
Revenues [Abstract]
Revenues	During the three and nine months ended September 30, 2023 and 2022, our revenues were comprised of the following (in thousands): Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Revenue: Commercial revenue: SPINRAZA royalties $ 67,253 $ 61,647 $ 178,511 $ 175,092 Other commercial revenue: TEGSEDI and WAYLIVRA revenue, net 8,286 5,920 25,420 22,467 Licensing and other royalty revenue 8,542 4,843 25,815 25,320 Total other commercial revenue 16,828 10,763 51,235 47,787 Total commercial revenue 84,081 72,410 229,746 222,879 Research and development revenue: Collaborative agreement revenue 44,167 69,250 173,513 157,282 Eplontersen joint development revenue 15,959 18,107 59,883 55,317 Total research and development revenue 60,126 87,357 233,396 212,599 Total revenue $ 144,207 $ 159,767 $ 463,142 $ 435,478

Collaborative Arrangements an_2

Collaborative Arrangements and Licensing Agreements (Tables)	9 Months Ended
	Sep. 30, 2023
AstraZeneca [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the three and nine months ended September 30, 2023 and 2022, we earned the following revenue from our relationship with AstraZeneca (in thousands, except percentages): Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Revenue from our relationship with AstraZeneca $ 15,959 $ 18,107 $ 99,885 $ 55,718 Percentage of total revenue 11 % 11 % 22 % 13 %
Biogen [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the three and nine months ended September 30, 2023 and 2022, we earned the following revenue from our relationship with Biogen (in thousands, except percentages): Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Revenue from our relationship with Biogen $ 94,695 $ 88,959 $ 262,599 $ 259,713 Percentage of total revenue 66 % 56 % 57 % 60 %
GSK [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the three and nine months ended September 30, 2023 and 2022, we earned the following revenue from our relationship with GSK (in thousands, except percentages): Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Revenue from our relationship with GSK $ — $ — $ 15,000 $ — Percentage of total revenue 0 % 0 % 3 % 0 %
Novartis [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the three and nine months ended September 30, 2023 and 2022, we earned the following revenue from our relationship with Novartis (in thousands, except percentages): Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Revenue from our relationship with Novartis $ 1,908 $ — $ 2,023 $ — Percentage of total revenue 1 % 0 % 0 % 0 %
Roche [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the three and nine months ended September 30, 2023 and 2022, we earned the following revenue from our relationship with Roche (in thousands, except percentage amounts): Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 R&D revenue $ 8,858 $ 41,504 $ 16,979 $ 65,360 Percentage of total revenue 6 % 26 % 4 % 15 %
Sobi [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the three and nine months ended September 30, 2023 and 2022, we earned the following revenue from our distribution agreement with Sobi for TEGSEDI in North America (in thousands, except percentage amounts). Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 TEGSEDI revenue from our distribution agreement with Sobi in North America $ 794 $ 1,008 $ 2,189 $ 3,443 Percentage of total revenue 1 % 1 % 2 % 1 %

Investments (Tables)

Investments (Tables)	9 Months Ended
	Sep. 30, 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 September 30, 2023: One year 72 % After one year two years 20 % 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 September 30, 2023 Cost Gains Losses Fair Value Available-for-sale debt securities: Corporate debt securities (1) $ 535,408 $ 13 $ (4,492 ) $ 530,929 Debt securities issued by U.S. government agencies 267,503 — (1,429 ) 266,074 Debt securities issued by the U.S. Treasury (1) 520,013 1 (3,027 ) 516,987 Debt securities issued by states of the U.S. and political subdivisions of the states 23,906 — (242 ) 23,664 Total debt securities with a maturity of one year or less 1,346,830 14 (9,190 ) 1,337,654 Corporate debt securities 195,674 183 (3,160 ) 192,697 Debt securities issued by U.S. government agencies 56,365 — (507 ) 55,858 Debt securities issued by the U.S. Treasury 297,501 — (3,364 ) 294,137 Debt securities issued by states of the U.S. and political subdivisions of the states 4,164 53 (51 ) 4,166 Total debt securities with a maturity of more than one year 553,704 236 (7,082 ) 546,858 Total available-for-sale debt securities $ 1,900,534 $ 250 $ (16,272 ) $ 1,884,512 Equity securities: Publicly traded equity securities included in other current assets (2) $ 11,897 $ (1,252 ) $ (4,083 ) $ 6,562 Privately held equity securities included in deposits and other assets (3) 23,115 25,001 (5,125 ) 42,991 Total equity securities 35,012 23,749 (9,208 ) 49,553 Total available-for-sale debt and equity securities $ 1,935,546 $ 23,999 $ (25,480 ) $ 1,934,065 Amortized Gross Unrealized Estimated December 31, 2022 Cost Gains Losses Fair Value Available-for-sale debt 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 debt 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 debt securities with a maturity of more than one year 525,314 130 (15,621 ) 509,823 Total available-for-sale debt 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 debt and equity securities $ 1,783,848 $ 17,451 $ (28,997 ) $ 1,772,302 (1) Includes investments classified as cash equivalents in our condensed 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 nine months ended September 30, 2023, we recognized a $4.0 million unrealized loss in our condensed consolidated statements of operations related to a decrease 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 . In the , we recorded a net gain of $ million in our condensed 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 consider to be temporarily impaired at September 30, 2023 (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 370 $ 469,095 $ (2,390 ) $ 207,073 $ (5,262 ) $ 676,168 $ (7,652 ) Debt securities issued by U.S. government agencies 98 293,408 (1,242 ) 24,531 (694 ) 317,939 (1,936 ) Debt securities issued by the U.S. Treasury 68 557,489 (3,420 ) 225,634 (2,971 ) 783,123 (6,391 ) Debt securities issued by states of the U.S. and political subdivisions of the states 85 11,644 (73 ) 12,973 (220 ) 24,617 (293 ) Total temporarily impaired securities 621 $ 1,331,636 $ (7,125 ) $ 470,211 $ (9,147 ) $ 1,801,847 $ (16,272 )

Fair Value Measurements (Tables

Fair Value Measurements (Tables)	9 Months Ended
	Sep. 30, 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 September 30, 2023 and December 31, 2022 that we regularly measure and carry at fair value. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective security’s fair value (in thousands): At September 30, 2023 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 269,255 $ 269,255 $ — Corporate debt securities (2) 723,626 — 723,626 Debt securities issued by U.S. government agencies (3) 321,932 — 321,932 Debt securities issued by the U.S. Treasury (2) 811,124 811,124 — Debt securities issued by states of the U.S. and political subdivisions of the states (2) 27,830 — 27,830 Publicly traded equity securities included in other current assets (4) 6,562 6,562 — Total $ 2,160,329 $ 1,086,941 $ 1,073,388 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 (5) 726,950 — 726,950 Debt securities issued by U.S. government agencies (2) 165,055 — 165,055 Debt securities issued by the U.S. Treasury (2) 748,475 748,475 — Debt securities issued by states of the U.S. and political subdivisions of the states (2) 74,917 — 74,917 Other municipal debt securities (2) 5,994 — 5,994 Publicly traded equity securities included in other current assets (4) 10,539 10,539 — Total $ 1,943,585 $ 970,669 $ 972,916 The following footnotes reference lines in our condensed consolidated balance sheets: (1) Included in cash and cash equivalents in our condensed consolidated balance sheets. (2) Included in short-term investments in our condensed consolidated balance sheets. (3) $1.0 million was included in cash and cash equivalents, with the difference included in short-term investments, in our condensed consolidated balance sheets. (4) Included in other current assets in our condensed consolidated balance sheets. (5) $11.0 million was included in cash and cash equivalents, with the difference included in short-term investments, in our condensed consolidated balance sheets.

Stock-based Compensation Expe_3

Stock-based Compensation Expense (Tables)	9 Months Ended
	Sep. 30, 2023
Stock-based Compensation Expense [Abstract]
Weighted-Average Assumptions for Stock Options	Employee Stock Options: Nine Months Ended September 30, 2023 2022 Risk-free interest rate 3.7 % 1.9 % Dividend yield 0.0 % 0.0 % Volatility 47.1 % 54.9 % Expected life 6.3 years 6.3 years Ionis Board of Director Stock Options: Nine Months Ended September 30, 2023 2022 Risk-free interest rate 3.8 % 2.9 % Dividend yield 0.0 % 0.0 % Volatility 53.0 % 56.2 % Expected life 7.7 years 7.4 years
Weighted-Average Assumptions for ESPP	ESPP: Nine Months Ended September 30, 2023 2022 Risk-free interest rate 5.3 % 1.2 % Dividend yield 0.0 % 0.0 % Volatility 36.0 % 50.1 % Expected life 6 months 6 months
Stock-Based Compensation Expense	The following table summarizes stock-based compensation expense for the three and nine months ended September 30, 2023 and 2022 (in thousands): Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Cost of sales $ 118 $ 163 $ 355 $ 376 Research, development and patent expense 18,727 17,733 57,543 55,315 Selling, general and administrative expense 7,119 5,941 21,575 18,884 Total stock-based compensation expense $ 25,964 $ 23,837 $ 79,473 $ 74,575

Liability Related to Sale of _2

Liability Related to Sale of Future Royalties (Tables)	9 Months Ended
	Sep. 30, 2023
Liability Related to Sale of Future Royalties [Abstract]
Liability Related to Sale of Future Royalties	The following is a summary of our liability related to sale of future royalties for the nine months ended September 30, 2023 (in thousands): Proceeds from sale of future royalties $ 500,000 Royalty payments to Royalty Pharma (27,814 ) Interest expense related to sale of future royalties 50,541 Liability related to sale of future royalties as of September 30, 2023 522,727 Issuance costs related to sale of future royalties (10,434 ) Amortization of issuance costs related to sale of future royalties as of September 30, 2023 407 Net liability related to sale of future royalties as of September 30, 2023 $ 512,700

Convertible Debt (Tables)

Convertible Debt (Tables)	9 Months Ended
	Sep. 30, 2023
1.75% Notes [Member]
Convertible Notes [Abstract]
Convertible Senior Notes	At September 30, 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 $ 13.4 Maturity date June 2028 Interest rate 1.75 percent Effective interest rate 2.3 percent 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 September 30, 2023, we had the following 0% 0% Notes Outstanding principal balance $ 632.5 Unamortized debt issuance costs $ 7.9 Maturity date April 2026 Interest rate 0 percent Effective interest rate 0.5 percent Conversion price per share $ 57.84 Effective conversion price per share with call spread $ 76.39 Total shares of common stock subject to conversion 10.9
0.125% Notes [Member]
Convertible Notes [Abstract]
Convertible Senior Notes	At September 30, 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 percent Effective interest rate 0.5 percent Conversion price per share $ 83.28 Effective conversion price per share with call spread $ 123.38 Total shares of common stock subject to conversion 0.5

Organization and Basis of Pre_3

Organization and Basis of Presentation (Details)	9 Months Ended
	Sep. 30, 2023 Segment
Organization and Basis of Presentation [Abstract]
Number of operating segments	1

Supplemental Financial Data, In

Supplemental Financial Data, Inventories (Details) - USD ($) $ in Thousands	Sep. 30, 2023	Dec. 31, 2022
Inventory [Abstract]
Raw materials	$ 22,807	$ 19,760
Work in process	2,651	2,109
Finished goods	176	164
Total inventory	25,634	22,033
Clinical [Member]
Inventory [Abstract]
Raw materials	18,427	17,061
Commercial [Member]
Inventory [Abstract]
Raw materials	$ 4,380	$ 2,699

Supplemental Financial Data, Ac

Supplemental Financial Data, Accrued Liabilities (Details) - USD ($) $ in Thousands	Sep. 30, 2023	Dec. 31, 2022
Accrued Liabilities [Abstract]
Clinical development expenses	$ 89,217	$ 116,460
In-licensing expenses	7,560	7,945
Commercial expenses	8,575	3,498
Other miscellaneous expenses	13,616	12,198
Total accrued liabilities	$ 118,968	$ 140,101

Revenues (Details)

Revenues (Details) - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022
Revenues [Abstract]
Revenue	$ 144,207	$ 159,767	$ 463,142	$ 435,478
Commercial Revenue [Member]
Revenues [Abstract]
Revenue	84,081	72,410	229,746	222,879
SPINRAZA Royalties [Member]
Revenues [Abstract]
Revenue	67,253	61,647	178,511	175,092
Other Commercial Revenue [Member]
Revenues [Abstract]
Revenue	16,828	10,763	51,235	47,787
TEGSEDI and WAYLIVRA Revenue, Net [Member]
Revenues [Abstract]
Revenue	8,286	5,920	25,420	22,467
Licensing and Other Royalty Revenue [Member]
Revenues [Abstract]
Revenue	8,542	4,843	25,815	25,320
Research and Development Revenue [Member]
Revenues [Abstract]
Revenue	60,126	87,357	233,396	212,599
Collaborative Agreement Revenue [Member]
Revenues [Abstract]
Revenue	44,167	69,250	173,513	157,282
Eplontersen Joint Development Revenue [Member]
Revenues [Abstract]
Revenue	$ 15,959	$ 18,107	$ 59,883	$ 55,317

Collaborative Arrangements an_3

Collaborative Arrangements and Licensing Agreements, AstraZeneca (Details) $ in Thousands	3 Months Ended			9 Months Ended
	Sep. 30, 2023 USD ($) Agreement	Jun. 30, 2023 USD ($)	Sep. 30, 2022 USD ($)	Sep. 30, 2023 USD ($) Agreement	Sep. 30, 2022 USD ($)	Dec. 31, 2022 USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 144,207		$ 159,767	$ 463,142	$ 435,478
AstraZeneca [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement	2			2
Revenue	$ 15,959		$ 18,107	$ 99,885	$ 55,718
Deferred contract revenue	$ 0			$ 0		$ 0
AstraZeneca [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage	11%		11%	22%	13%
AstraZeneca [Member] | Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	$ 650,000			$ 650,000
Eplontersen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement	1			1
Next payment to be achieved	$ 50,000			$ 50,000
Revenue		$ 20,000
Cardiovascular, Renal and Metabolic Diseases [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement	1			1
Cardiovascular, Renal and Metabolic Diseases [Member] | Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next payment to be achieved	$ 30,000			$ 30,000
Cardiovascular, Renal and Metabolic Diseases [Member] | ION839 [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		$ 20,000

Collaborative Arrangements an_4

Collaborative Arrangements and Licensing Agreements, Biogen (Details) - USD ($) $ in Thousands	1 Months Ended	3 Months Ended			9 Months Ended
	Oct. 31, 2023	Sep. 30, 2023	Jun. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022	Dec. 31, 2022
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		$ 144,207		$ 159,767	$ 463,142	$ 435,478
Biogen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		94,695		$ 88,959	262,599	$ 259,713
Deferred contract revenue		$ 316,800			$ 316,800		$ 351,200
Biogen [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage		66%		56%	57%	60%
Biogen [Member] | Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received		$ 3,600,000			$ 3,600,000
2013 Strategic Neurology [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue			$ 16,000
2013 Strategic Neurology [Member] | QALSODY [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
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 sales of medicine					11%
2013 Strategic Neurology [Member] | QALSODY [Member] | Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Royalty percentage received on sales of medicine					15%
2012 Neurology [Member] | Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next payment to be achieved	$ 70,000
2012 Neurology [Member] | ION582 [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Milestone payments achieved and included in transaction price for performance obligation		$ 21,000
2012 Neurology [Member] | ION582 [Member] | Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Milestone payments achieved and included in transaction price for performance obligation	$ 9,000

Collaborative Arrangements an_5

Collaborative Arrangements and Licensing Agreements, GSK (Details) - USD ($) $ in Thousands	3 Months Ended			9 Months Ended
	Sep. 30, 2023	Mar. 31, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022	Dec. 31, 2022
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 144,207		$ 159,767	$ 463,142	$ 435,478
GSK [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next payment to be achieved	15,000			15,000
Revenue	0		$ 0	15,000	$ 0
Deferred contract revenue	$ 0			$ 0		$ 0
GSK [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage	0%		0%	3%	0%
GSK [Member] | Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	$ 105,000			$ 105,000
GSK [Member] | Bepirovirsen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		$ 15,000

Collaborative Arrangements an_6

Collaborative Arrangements and Licensing Agreements, Novartis (Details) $ in Thousands	1 Months Ended		3 Months Ended		9 Months Ended
	Oct. 31, 2023 USD ($)	Aug. 31, 2023 PerformanceObligation	Sep. 30, 2023 USD ($)	Sep. 30, 2022 USD ($)	Sep. 30, 2023 USD ($)	Sep. 30, 2022 USD ($)	Dec. 31, 2022 USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue			$ 144,207	$ 159,767	$ 463,142	$ 435,478
Novartis [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received			275,000		275,000
Revenue			1,908	$ 0	2,023	$ 0
Deferred contract revenue			$ 58,100		$ 58,100		$ 0
Novartis [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage			1%	0%	0%	0%
Lp(a)-Driven Cardiovascular Disease [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of identified performance obligations | PerformanceObligation		1
Next payment to be achieved			$ 5,000		$ 5,000
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%
Lp(a)-Driven Cardiovascular Disease [Member] | Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront payment received	$ 60,000
Upfront payment achieved and included in transaction price for performance obligation	$ 60,000

Collaborative Arrangements an_7

Collaborative Arrangements and Licensing Agreements, Roche (Details) $ in Thousands	1 Months Ended		3 Months Ended		9 Months Ended
	Oct. 31, 2023 USD ($)	Sep. 30, 2023 USD ($) Agreement PerformanceObligation Program	Sep. 30, 2023 USD ($) Agreement Program	Sep. 30, 2022 USD ($)	Sep. 30, 2023 USD ($) Agreement Program	Sep. 30, 2022 USD ($)	Dec. 31, 2022 USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue			$ 144,207	$ 159,767	$ 463,142	$ 435,478
R&D Revenue [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue			$ 60,126	$ 87,357	$ 233,396	$ 212,599
Roche [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement		3	3		3
Deferred contract revenue		$ 68,000	$ 68,000		$ 68,000		$ 22,400
Roche [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage			6%	26%	4%	15%
Roche [Member] | Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received		$ 285,000	$ 285,000		$ 285,000
Roche [Member] | R&D Revenue [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue			$ 8,858	$ 41,504	$ 16,979	$ 65,360
HD [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement		1	1		1
IONIS-FB-L for Complement-Mediated Diseases [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement		1	1		1
RNA-targeted Programs for AD and HD [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement		1	1		1
Number of early-stage programs | Program		2	2		2
Number of identified performance obligations | PerformanceObligation		2
Next payment to be achieved		$ 7,500	$ 7,500		$ 7,500
RNA-targeted Programs for AD and HD [Member] | Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront payment received	$ 60,000

Collaborative Arrangements an_8

Collaborative Arrangements and Licensing Agreements, Sobi (Details) - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 144,207	$ 159,767	$ 463,142	$ 435,478
Sobi [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage	1%	1%	2%	1%
Sobi [Member] | TEGSEDI Revenue [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 794	$ 1,008	$ 2,189	$ 3,443

Basic and Diluted Net Loss Pe_3

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

Investments, Contract Maturity

Investments, Contract Maturity of Available-for-Sale Securities (Details)	9 Months Ended
	Sep. 30, 2023
Contract Maturity of Available-for-Sale Securities [Abstract]
One year or less	72%
After one year but within two years	20%
After two years but within three and a half years	8%
Total	100%
Maximum contract maturity period, range 1	1 year
Maximum contract maturity period, range 2	2 years
Maximum contract maturity period, range 3	3 years 6 months
Percentage of available-for-sale securities with a maturity of less than two years	92%

Investments, Summary of Investm

Investments, Summary of Investments (Details) $ in Thousands		9 Months Ended
		Sep. 30, 2023 USD ($) Company	Dec. 31, 2022 USD ($)
Ownership Interests in Private and Public Companies [Abstract]
Number of private companies in which there is an equity ownership interest of less than 20% | Company		7
Number of public 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		$ 1,346,830	$ 1,223,522
Gross unrealized gains		14	64
Gross unrealized losses		(9,190)	(12,018)
Estimated fair value		1,337,654	1,211,568
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		553,704	525,314
Gross unrealized gains		236	130
Gross unrealized losses		(7,082)	(15,621)
Estimated fair value		546,858	509,823
Available-for-sale Debt Securities [Abstract]
Amortized cost		1,900,534	1,748,836
Gross unrealized gains		250	194
Gross unrealized losses		(16,272)	(27,639)
Estimated fair value		1,884,512	1,721,391
Equity Securities [Abstract]
Amortized cost		35,012	35,012
Gross unrealized gains		23,749	17,257
Gross unrealized losses		(9,208)	(1,358)
Estimated fair value		49,553	50,911
Available-for-sale Debt and Equity Securities [Abstract]
Amortized cost		1,935,546	1,783,848
Gross unrealized gains		23,999	17,451
Gross unrealized losses		(25,480)	(28,997)
Estimated fair value		1,934,065	1,772,302
Corporate Debt Securities [Member]
Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]
Amortized cost	[1]	535,408	513,790
Gross unrealized gains		13	23
Gross unrealized losses		(4,492)	(4,365)
Estimated fair value		530,929	509,448
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		195,674	227,631
Gross unrealized gains		183	14
Gross unrealized losses		(3,160)	(10,143)
Estimated fair value		192,697	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		267,503	133,585
Gross unrealized gains		0	0
Gross unrealized losses		(1,429)	(1,829)
Estimated fair value		266,074	131,756
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		56,365	34,339
Gross unrealized gains		0	0
Gross unrealized losses		(507)	(1,040)
Estimated fair value		55,858	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]	520,013	512,655
Gross unrealized gains		1	23
Gross unrealized losses		(3,027)	(5,124)
Estimated fair value		516,987	507,554
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		297,501	245,030
Gross unrealized gains		0	0
Gross unrealized losses		(3,364)	(4,109)
Estimated fair value		294,137	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		23,906	57,484
Gross unrealized gains		0	18
Gross unrealized losses		(242)	(686)
Estimated fair value		23,664	56,816
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		4,164	18,314
Gross unrealized gains		53	116
Gross unrealized losses		(51)	(329)
Estimated fair value		4,166	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		(1,252)	0
Gross unrealized losses		(4,083)	(1,358)
Estimated fair value		6,562	10,539
Available-for-sale Debt and Equity Securities [Abstract]
Unrealized loss on equity securities		(4,000)
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 condensed 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 nine months ended September 30, 2023, we recognized a $4.0 million unrealized loss in our condensed consolidated statements of operations related to a decrease 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 . In the , we recorded a net gain of $ million in our condensed 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	Sep. 30, 2023 USD ($) Investment
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	621
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 1,331,636
More than 12 months of temporary impairment	470,211
Total temporary impairment	1,801,847
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(7,125)
More than 12 months of temporary impairment	(9,147)
Total temporary impairment	$ (16,272)
Corporate Debt Securities [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	370
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 469,095
More than 12 months of temporary impairment	207,073
Total temporary impairment	676,168
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(2,390)
More than 12 months of temporary impairment	(5,262)
Total temporary impairment	$ (7,652)
Debt Securities Issued by U.S. Government Agencies [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	98
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 293,408
More than 12 months of temporary impairment	24,531
Total temporary impairment	317,939
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(1,242)
More than 12 months of temporary impairment	(694)
Total temporary impairment	$ (1,936)
Debt Securities Issued by the U.S. Treasury [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	68
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 557,489
More than 12 months of temporary impairment	225,634
Total temporary impairment	783,123
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(3,420)
More than 12 months of temporary impairment	(2,971)
Total temporary impairment	$ (6,391)
Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	85
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 11,644
More than 12 months of temporary impairment	12,973
Total temporary impairment	24,617
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(73)
More than 12 months of temporary impairment	(220)
Total temporary impairment	$ (293)

Fair Value Measurements (Detail

Fair Value Measurements (Details) - USD ($) $ in Thousands		Sep. 30, 2023		Dec. 31, 2022		Sep. 30, 2022
Fair Value Measurements [Abstract]
Available-for-sale securities		$ 1,884,512		$ 1,721,391
Equity securities		$ 49,553		$ 50,911
1.75% Notes [Member]
Fair Value Measurements [Abstract]
Interest rate on convertible senior notes		1.75%
0% Notes [Member]
Fair Value Measurements [Abstract]
Interest rate on convertible senior notes		0%		0%		0%
0.125% Notes [Member]
Fair Value Measurements [Abstract]
Interest rate on convertible senior notes		0.125%		0.125%		0.125%
Publicly Traded Equity Securities [Member]
Fair Value Measurements [Abstract]
Equity securities		$ 6,562		$ 10,539
Recurring Basis [Member]
Fair Value Measurements [Abstract]
Cash equivalents	[1]	269,255		211,655
Total		2,160,329		1,943,585
Recurring Basis [Member] | Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		723,626	[2]	726,950	[3]
Recurring Basis [Member] | Corporate Debt Securities [Member] | Cash and Cash Equivalents [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities				11,000
Recurring Basis [Member] | Debt Securities Issued by U.S. Government Agencies [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		321,932	[4]	165,055	[2]
Recurring Basis [Member] | Debt Securities Issued by U.S. Government Agencies [Member] | Cash and Cash Equivalents [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		1,000
Recurring Basis [Member] | Debt Securities Issued by the U.S. Treasury [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities	[2]	811,124		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	[2]	27,830		74,917
Recurring Basis [Member] | Other Municipal Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities	[2]			5,994
Recurring Basis [Member] | Publicly Traded Equity Securities [Member] | Other Current Assets [Member]
Fair Value Measurements [Abstract]
Equity securities	[5]	6,562		10,539
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member]
Fair Value Measurements [Abstract]
Cash equivalents		269,255		211,655
Total		1,086,941		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		811,124		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]
Fair Value Measurements [Abstract]
Equity securities		6,562		10,539
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member]
Fair Value Measurements [Abstract]
Cash equivalents		0		0
Total		1,073,388		972,916
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 1.75% Notes [Member]
Fair Value Measurements [Abstract]
Convertible notes		605,300
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 0% Notes [Member]
Fair Value Measurements [Abstract]
Convertible notes		620,100		587,300
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 0.125% Notes [Member]
Fair Value Measurements [Abstract]
Convertible notes		42,400		498,900
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		723,626		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		321,932		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		27,830		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]
Fair Value Measurements [Abstract]
Equity securities		$ 0		$ 0
[1]Included in cash and cash equivalents in our condensed consolidated balance sheets.[2]Included in short-term investments in our condensed consolidated balance sheets.[3]$11.0 million was included in cash and cash equivalents, with the difference included in short-term investments, in our condensed consolidated balance sheets.[4]$1.0 million was included in cash and cash equivalents, with the difference included in short-term investments, in our condensed consolidated balance sheets.[5]Included in other current assets in our condensed consolidated balance sheets.

Stock-based Compensation Expe_4

Stock-based Compensation Expense (Details) $ / shares in Units, $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2023 USD ($)	Sep. 30, 2022 USD ($)	Sep. 30, 2023 USD ($) Period $ / shares shares	Sep. 30, 2022 USD ($) $ / shares
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense	$ 25,964	$ 23,837	$ 79,473	$ 74,575
Cost of Sales [Member]
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense	118	163	355	376
Research, Development and Patent Expense [Member]
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense	18,727	17,733	57,543	55,315
Selling, General and Administrative Expense [Member]
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense	7,119	$ 5,941	21,575	$ 18,884
Stock Options [Member]
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation expense related to non-vested stock options	44,100		$ 44,100
Weighted average period for recognition			1 year 2 months 12 days
Stock Options [Member] | Employees [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate			3.70%	1.90%
Dividend yield			0%	0%
Volatility			47.10%	54.90%
Expected life			6 years 3 months 18 days	6 years 3 months 18 days
Stock Options [Member] | Board of Directors [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate			3.80%	2.90%
Dividend yield			0%	0%
Volatility			53%	56.20%
Expected life			7 years 8 months 12 days	7 years 4 months 24 days
ESPP [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate			5.30%	1.20%
Dividend yield			0%	0%
Volatility			36%	50.10%
Expected life			6 months	6 months
RSUs [Member]
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation cost related to non-vested units	62,200		$ 62,200
Weighted average period for recognition			1 year 4 months 24 days
RSUs [Member] | Employees [Member]
RSUs and PRSUs [Abstract]
Vesting period			4 years
Weighted-average grant date fair value (in dollars per share) | $ / shares			$ 39.78	$ 34.88
RSUs [Member] | Board of Directors [Member] | Minimum [Member]
RSUs and PRSUs [Abstract]
Vesting period			1 year
RSUs [Member] | Board of Directors [Member] | Maximum [Member]
RSUs and PRSUs [Abstract]
Vesting period			4 years
PRSUs [Member]
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation cost related to non-vested units	$ 7,300		$ 7,300
Weighted average period for recognition			1 year 8 months 12 days
PRSUs [Member] | Section 16 Officers [Member]
RSUs and PRSUs [Abstract]
Weighted-average grant date fair value (in dollars per share) | $ / shares			$ 58.99	$ 42.28
PRSUs [Member] | Granted in 2020 - 2022 [Member] | Section 16 Officers [Member]
RSUs and PRSUs [Abstract]
Number of performance periods | Period			3
Vesting period			3 years
Number of units guaranteed to vest (in shares) | shares			0
PRSUs [Member] | Granted in 2020 - 2022 [Member] | Section 16 Officers [Member] | Minimum [Member]
RSUs and PRSUs [Abstract]
Percentage of units guaranteed to vest			0%
PRSUs [Member] | Granted in 2020 - 2022 [Member] | Section 16 Officers [Member] | Maximum [Member]
RSUs and PRSUs [Abstract]
Percentage of units guaranteed to vest			150%
PRSUs [Member] | Granted in 2020 - 2022 [Member] | Section 16 Officers [Member] | One-Year Period [Member]
RSUs and PRSUs [Abstract]
Vesting percentage			33.30%
Vesting period			1 year
PRSUs [Member] | Granted in 2020 - 2022 [Member] | Section 16 Officers [Member] | Two-Year Period [Member]
RSUs and PRSUs [Abstract]
Vesting percentage			33.30%
Vesting period			2 years
PRSUs [Member] | Granted in 2020 - 2022 [Member] | Section 16 Officers [Member] | Three-Year Period [Member]
RSUs and PRSUs [Abstract]
Vesting percentage			33.30%
Vesting period			3 years
PRSUs [Member] | Granted in 2023 [Member] | Section 16 Officers [Member]
RSUs and PRSUs [Abstract]
Vesting percentage			100%
Vesting period			3 years
Number of units guaranteed to vest (in shares) | shares			0
PRSUs [Member] | Granted in 2023 [Member] | Section 16 Officers [Member] | Minimum [Member]
RSUs and PRSUs [Abstract]
Percentage of units guaranteed to vest			0%
PRSUs [Member] | Granted in 2023 [Member] | Section 16 Officers [Member] | Maximum [Member]
RSUs and PRSUs [Abstract]
Percentage of units guaranteed to vest			200%

Income Taxes (Details)

Income Taxes (Details) - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2023	Sep. 30, 2022	Sep. 30, 2023	Sep. 30, 2022
Income Taxes [Abstract]
Income tax expense	$ 6,602	$ 283	$ 25,825	$ 3,637

Liability Related to Sale of _3

Liability Related to Sale of Future Royalties (Details) - USD ($) $ in Thousands	1 Months Ended	9 Months Ended
	Jan. 31, 2023	Sep. 30, 2023	Sep. 30, 2022
Royalty Revenue Monetization [Abstract]
Transaction costs		$ 10,434	$ 0
Proceeds from sale of future royalties		500,000	0
Royalty payments to Royalty Pharma		(27,814)	0
Interest expense related to sale of future royalties		50,541	0
Issuance costs related to sale of future royalties		(10,434)	$ 0
Net liability related to sale of future royalties		512,700
Royalty Purchase Agreement [Member]
Royalty Revenue Monetization [Abstract]
Upfront payment received	$ 500,000
Maximum amount of payments receivable for additional milestones		625,000
Transaction costs		$ 10,434
Effective interest rate		13.50%
Proceeds from sale of future royalties		$ 500,000
Royalty payments to Royalty Pharma		(27,814)
Interest expense related to sale of future royalties		50,541
Liability related to sale of future royalties		522,727
Issuance costs related to sale of future royalties		(10,434)
Amortization of issuance costs related to sale of future royalties		407
Net liability related to sale of future royalties		512,700
Royalty Purchase Agreement [Member] | SPINRAZA [Member]
Royalty Revenue Monetization [Abstract]
Maximum amount of annual sales on which royalty payments are paid		$ 1,500,000
Royalty Purchase Agreement [Member] | SPINRAZA [Member] | Minimum [Member]
Royalty Revenue Monetization [Abstract]
Percentage of royalty payments paid on annual sales of medicine		25%
Maximum royalty payments made before royalty interest reverts back		$ 475,000
Royalty Purchase Agreement [Member] | SPINRAZA [Member] | Maximum [Member]
Royalty Revenue Monetization [Abstract]
Percentage of royalty payments paid on annual sales of medicine		45%
Maximum royalty payments made before royalty interest reverts back		$ 550,000
Royalty Purchase Agreement [Member] | Pelacarsen [Member]
Royalty Revenue Monetization [Abstract]
Percentage of royalty payments paid on annual sales of medicine		25%

Convertible Debt (Details)

Convertible Debt (Details) - USD ($) $ / shares in Units, $ in Thousands, shares in Millions	1 Months Ended			3 Months Ended	9 Months Ended
	Jun. 30, 2023	Apr. 30, 2021	Dec. 31, 2019	Sep. 30, 2023	Sep. 30, 2023	Sep. 30, 2022	Dec. 31, 2022
Convertible Debt [Abstract]
Proceeds from issuance of convertible senior notes					$ 575,000	$ 0
Repurchase of convertible senior notes					487,943	0
Gain on early retirement of debt					13,389	$ 0
1.75% Notes [Member]
Convertible Debt [Abstract]
Face amount of offering	$ 575,000
Repurchase of convertible senior notes				$ 67,800
Outstanding principal balance				575,000	575,000
Unamortized debt issuance costs				$ 13,400	$ 13,400
Maturity date					Jun. 30, 2028
Interest rate				1.75%	1.75%
Effective interest rate				2.30%	2.30%
Conversion price per share (in dollars per share)				$ 53.73	$ 53.73
Total shares of common stock subject to conversion (in shares)				10.7	10.7
Percentage of principal amount used as purchase price upon occurrence of fundamental change					100%
0% Notes [Member]
Convertible Debt [Abstract]
Face amount of offering		$ 632,500
Outstanding principal balance				$ 632,500	$ 632,500
Unamortized debt issuance costs				$ 7,900	$ 7,900
Maturity date					Apr. 30, 2026
Interest rate				0%	0%	0%	0%
Effective interest rate				0.50%	0.50%
Conversion price per share (in dollars per share)				$ 57.84	$ 57.84
Effective conversion price per share with call spread (in dollars per share)				$ 76.39	$ 76.39
Total shares of common stock subject to conversion (in shares)				10.9	10.9
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%
1% Notes [Member]
Convertible Debt [Abstract]
Repurchase of convertible senior notes		257,000
Principal amount repurchased		$ 247,900
Interest rate				1%	1%
0.125% Notes [Member]
Convertible Debt [Abstract]
Proceeds from issuance of convertible senior notes	420,400
Repurchase of convertible senior notes				$ 70,300
Principal amount repurchased	$ 434,100			504,400	$ 504,400
Outstanding principal balance				44,500	44,500
Unamortized debt issuance costs				$ 200	$ 200
Maturity date					Dec. 31, 2024
Interest rate				0.125%	0.125%	0.125%	0.125%
Effective interest rate				0.50%	0.50%
Conversion price per share (in dollars per share)				$ 83.28	$ 83.28
Effective conversion price per share with call spread (in dollars per share)				$ 123.38	$ 123.38
Total shares of common stock subject to conversion (in shares)				0.5	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 on early retirement of debt				$ 2,100	$ 13,400

Real Estate Transactions (Detai

Real Estate Transactions (Details) $ in Millions	1 Months Ended		9 Months Ended
	Aug. 31, 2023 USD ($) Lot	Oct. 31, 2022 USD ($) Agreement	Sep. 30, 2023 Option
Headquarters Location in Carlsbad, California [Member]
Real Estate Transactions [Abstract]
Number of purchase and sale agreements entered into with real estate investor | Agreement		2
Proceeds from sale of real estate assets		$ 263.4
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]
Real Estate Transactions [Abstract]
Number of lots of undeveloped land included in purchase and sale agreement | Lot	2
Proceeds from sale of real estate assets	$ 33
Initial term of lease			15 years
Number of options to extend lease | Option			2
Term of lease extension			5 years
Development Chemistry and Manufacturing Facility in Oceanside, California [Member]
Real Estate Transactions [Abstract]
Impairment charge	$ 18
Impairment, Long-Lived Asset, Held-for-Use, Statement of Income [Extensible Enumeration]	Selling, general and administrative