Ionis Pharmaceuticals (IONS) 10-Q 6 Nov 24 2024 Q3 Quarterly report Financial data

Document and Entity Information

Document and Entity Information - shares	9 Months Ended
	Sep. 30, 2024	Oct. 31, 2024
Cover [Abstract]
Document Type	10-Q
Amendment Flag	false
Document Quarterly Report	true
Document Period End Date	Sep. 30, 2024
Current Fiscal Year End Date	--12-31
Document Fiscal Year Focus	2024
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		157,897,287

CONDENSED CONSOLIDATED BALANCE

CONDENSED CONSOLIDATED BALANCE SHEETS - USD ($) $ in Thousands	Sep. 30, 2024	Dec. 31, 2023
Current assets:
Cash and cash equivalents	$ 334,605	$ 399,266
Short-term investments	2,148,671	1,931,935
Contracts receivable	17,928	97,778
Inventories	28,452	28,425
Other current assets	184,194	184,449
Total current assets	2,713,850	2,641,853
Property, plant and equipment, net	82,502	71,043
Right-of-use assets	164,424	171,896
Deposits and other assets	120,323	105,280
Total assets	3,081,099	2,990,072
Current liabilities:
Accounts payable	9,052	26,027
Accrued compensation	40,558	67,727
Accrued liabilities	124,396	147,894
Income taxes payable	41	2,151
0.125 percent convertible senior notes, net	44,467	44,332
Current portion of deferred contract revenue	76,018	151,128
Other current liabilities	10,034	8,831
Total current liabilities	304,566	448,090
Long-term deferred contract revenue	173,776	241,184
Liability related to sale of future royalties, net	538,102	513,736
Long-term lease liabilities	168,372	170,875
Long-term obligations	41,735	41,836
Total liabilities	2,418,631	2,603,386
Stockholders' equity:
Common stock, $0.001 par value; 300,000,000 shares authorized, 157,813,136 and 144,340,526 shares issued and outstanding at September 30, 2024 (unaudited) and December 31, 2023, respectively	158	144
Additional paid-in capital	2,831,942	2,215,098
Accumulated other comprehensive loss	(24,173)	(32,645)
Accumulated deficit	(2,145,459)	(1,795,911)
Total stockholders' equity	662,468	386,686
Total liabilities and stockholders' equity	3,081,099	2,990,072
1.75 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	564,335	562,285
0 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	$ 627,745	$ 625,380

CONDENSED CONSOLIDATED BALANC_2

CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares	Sep. 30, 2024	Dec. 31, 2023
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)	157,813,136	144,340,526
Common stock, shares outstanding (in shares)	157,813,136	144,340,526
0.125 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	0.125%	0.125%
1.75 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	1.75%	1.75%
0 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	0%	0%

CONDENSED CONSOLIDATED STATEMEN

CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS - USD ($) shares in Thousands, $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2024	Sep. 30, 2023	Sep. 30, 2024	Sep. 30, 2023
Revenue:
Revenue	$ 133,814	$ 144,207	$ 478,562	$ 463,142
Expenses:
Cost of sales	1,071	2,191	7,385	6,071
Research, development and patent	219,761	215,330	656,040	643,070
Selling, general and administrative	61,638	69,951	179,395	161,608
Total operating expenses	282,470	287,472	842,820	810,749
Loss from operations	(148,656)	(143,265)	(364,258)	(347,607)
Other income (expense):
Investment income	26,228	23,935	78,112	63,355
Interest expense	(4,161)	(4,203)	(12,803)	(8,102)
Interest expense related to sale of future royalties	(18,533)	(17,779)	(54,788)	(50,948)
Gain (loss) on investments	879	(1,943)	(321)	(1,753)
Other income	142	2,447	1,029	13,857
Loss before income tax benefit (expense)	(144,101)	(140,808)	(353,029)	(331,198)
Income tax benefit (expense)	3,621	(6,602)	3,481	(25,825)
Net loss	$ (140,480)	$ (147,410)	$ (349,548)	$ (357,023)
Basic net loss per share (in dollars per share)	$ (0.95)	$ (1.03)	$ (2.38)	$ (2.5)
Diluted net loss per share (in dollars per share)	$ (0.95)	$ (1.03)	$ (2.38)	$ (2.5)
Shares used in computing basic net loss per share (in shares)	148,593	143,317	146,703	143,052
Shares used in computing diluted net loss per share (in shares)	148,593	143,317	146,703	143,052
Commercial Revenue [Member]
Revenue:
Revenue	$ 75,731	$ 84,081	$ 207,360	$ 229,746
SPINRAZA Royalties [Member]
Revenue:
Revenue	57,208	67,253	152,406	178,511
WAINUA Royalties [Member]
Revenue:
Revenue	5,371	0	10,278	0
Other Commercial Revenue [Member]
Revenue:
Revenue	13,152	16,828	44,676	51,235
Research and Development Revenue [Member]
Revenue:
Revenue	58,083	60,126	271,202	233,396
Collaborative Agreement Revenue [Member]
Revenue:
Revenue	44,883	44,167	235,753	173,513
WAINUA Joint Development Revenue [Member]
Revenue:
Revenue	$ 13,200	$ 15,959	$ 35,449	$ 59,883

CONDENSED CONSOLIDATED STATEM_2

CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2024	Sep. 30, 2023	Sep. 30, 2024	Sep. 30, 2023
CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS [Abstract]
Net loss	$ (140,480)	$ (147,410)	$ (349,548)	$ (357,023)
Unrealized gains on debt securities, net of tax	10,315	5,029	8,259	11,421
Currency translation adjustment	350	(153)	213	22
Comprehensive loss	$ (129,815)	$ (142,534)	$ (341,076)	$ (345,580)

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, 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, 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, net	$ 1	8,679	0	0	8,680
Issuance of common stock in connection with employee stock plans, net (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, 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, net	$ 0	3,729	0	0	3,729
Issuance of common stock in connection with employee stock plans, net (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
Balance at Dec. 31, 2023	$ 144	2,215,098	(32,645)	(1,795,911)	386,686
Balance (in shares) at Dec. 31, 2023	144,341
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(349,548)	(349,548)
Change in unrealized gains, net of tax	0	0	8,259	0	8,259
Foreign currency translation	0	0	213	0	213
Issuance of common stock in connection with employee stock plans, net	$ 2	33,205	0	0	33,207
Issuance of common stock in connection with employee stock plans, net (in shares)	1,972
Issuance of public common stock, net	$ 12	489,081	0	0	489,093
Issuance of public common stock, net (in shares)	11,500
Stock-based compensation expense	$ 0	94,558	0	0	94,558
Balance at Sep. 30, 2024	$ 158	2,831,942	(24,173)	(2,145,459)	662,468
Balance (in shares) at Sep. 30, 2024	157,813
Balance at Jun. 30, 2024	$ 146	2,303,369	(34,838)	(2,004,979)	263,698
Balance (in shares) at Jun. 30, 2024	146,025
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(140,480)	(140,480)
Change in unrealized gains, net of tax	0	0	10,315	0	10,315
Foreign currency translation	0	0	350	0	350
Issuance of common stock in connection with employee stock plans, net	$ 0	7,002	0	0	7,002
Issuance of common stock in connection with employee stock plans, net (in shares)	288
Issuance of public common stock, net	$ 12	489,081	0	0	489,093
Issuance of public common stock, net (in shares)	11,500
Stock-based compensation expense	$ 0	32,490	0	0	32,490
Balance at Sep. 30, 2024	$ 158	$ 2,831,942	$ (24,173)	$ (2,145,459)	$ 662,468
Balance (in shares) at Sep. 30, 2024	157,813

CONDENSED CONSOLIDATED STATEM_4

CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	1 Months Ended	3 Months Ended		9 Months Ended		12 Months Ended
	Sep. 30, 2024	Sep. 30, 2024	Sep. 30, 2023	Sep. 30, 2024	Sep. 30, 2023	Dec. 31, 2023
Operating activities:
Net loss		$ (140,480)	$ (147,410)	$ (349,548)	$ (357,023)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation				7,374	7,748
Amortization of right-of-use operating lease assets				7,472	7,234
Amortization of other assets				1,877	1,904
Amortization of discount on investments, net				(28,283)	(20,396)
Amortization of debt issuance costs				5,016	4,666
Non-cash royalty revenue related to sale of royalties				(30,422)	(27,814)
Non-cash interest related to sale of future royalties				54,330	50,541
Stock-based compensation expense				94,052	79,473
Loss on investments				320	1,429
Gain on early retirement of debt				0	(13,389)
Non-cash losses related to disposal of property, plant and equipment				114	14,646
Non-cash losses related to other assets				895	849
Changes in operating assets and liabilities:
Contracts receivable				79,850	(116,814)
Inventories				(27)	(3,601)
Other current and long-term assets				(8,155)	(18,325)
Income taxes				(2,110)	24,821
Accounts payable				(19,215)	(12,462)
Accrued compensation				(27,169)	(15,397)
Accrued liabilities and other current liabilities				(28,661)	(24,219)
Deferred contract revenue				(142,518)	75,751
Net cash used in operating activities				(384,808)	(340,378)
Investing activities:
Purchases of short-term investments				(1,519,227)	(1,353,100)
Proceeds from sale of short-term investments				1,339,284	1,193,724
Purchases of property, plant and equipment				(19,783)	(24,624)
Acquisition of licenses and other assets, net				(2,514)	(3,414)
Net cash used in investing activities				(202,240)	(187,414)
Financing activities:
Proceeds from issuance of common stock through equity plans, net				33,207	8,680
Proceeds from issuance of common stock in public offering, net	$ 489,100			489,093	0
Proceeds from issuance of 1.75 percent convertible senior notes				0	575,000
1.75 percent convertible senior notes issuance costs				0	(14,175)
Repurchase of $504.4 million principal amount of 0.125 percent convertible senior notes				0	(487,943)
Proceeds from sale of future royalties				0	500,000
Payments of transaction costs related to sale of future royalties				0	(10,434)
Proceeds from real estate transaction				0	32,352
Principal payments on mortgage debt				(126)	(122)
Net cash provided by financing activities				522,174	603,358
Effects of exchange rates on cash				213	22
Net increase (decrease) in cash and cash equivalents				(64,661)	75,588
Cash and cash equivalents at beginning of period				399,266	276,472	$ 276,472
Cash and cash equivalents at end of period	$ 334,605	$ 334,605	$ 352,060	334,605	352,060	$ 399,266
Supplemental disclosures of cash flow information:
Interest paid				5,714	952
Income taxes paid				2,072	714
Supplemental disclosures of non-cash investing and financing activities:
Amounts accrued for capital and patent expenditures				$ 2,240	$ 341

CONDENSED CONSOLIDATED STATEM_5

CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS (Parenthetical) - USD ($) $ in Millions	Sep. 30, 2024	Dec. 31, 2023	Sep. 30, 2023
1.75 Percent Convertible Senior Notes [Member]
Financing activities:
Interest rate on convertible senior notes	1.75%	1.75%	1.75%
0.125 Percent Convertible Senior Notes [Member]
Financing activities:
Principal amount repurchased			$ 504.4
Interest rate on convertible senior notes	0.125%	0.125%	0.125%

Organization and Basis of Prese

Organization and Basis of Presentation	9 Months Ended
	Sep. 30, 2024
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, 2024 and 2023 on the same basis as the audited financial statements for the year ended December 31, 2023. 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, 2023 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, 2024
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, 2023. Recently Issued Accounting Standards We do not expect any recently issued accounting standards other than those included in our Annual Report on Form 10-K for the year ended December 31, 2023 to have a material impact to our financial results.

Supplemental Financial Data

Supplemental Financial Data	9 Months Ended
	Sep. 30, 2024
Supplemental Financial Data [Abstract]
Supplemental Financial Data	3. Supplemental Financial Data Inventories Our inventory consisted of the following (in thousands): September 30, 2024 December 31, 2023 Raw materials: Raw materials - clinical $ 20,773 $ 20,985 Raw materials - commercial 963 1,809 Total raw materials 21,736 22,794 Work in process 6,653 5,477 Finished goods 63 154 Total inventories $ 28,452 $ 28,425 Accrued Liabilities Our accrued liabilities consisted of the following (in thousands): September 30, 2024 December 31, 2023 Clinical development expenses $ 90,239 $ 105,967 In-licensing expenses 7,082 7,454 Commercial expenses 5,016 4,875 Other miscellaneous expenses 22,059 29,598 Total accrued liabilities $ 124,396 $ 147,894

Revenues

Revenues	9 Months Ended
	Sep. 30, 2024
Revenues [Abstract]
Revenues	4. Revenues During the three and nine months ended September 30, 2024 and 2023, our revenues were comprised of the following (in thousands): Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Revenue: Commercial revenue: SPINRAZA royalties $ 57,208 $ 67,253 $ 152,406 $ 178,511 WAINUA royalties 5,371 — 10,278 — Other commercial revenue: TEGSEDI and WAYLIVRA revenue, net 8,924 8,286 25,744 25,420 Licensing and other royalty revenue 4,228 8,542 18,932 25,815 Total other commercial revenue 13,152 16,828 44,676 51,235 Total commercial revenue 75,731 84,081 207,360 229,746 Research and development revenue: Collaborative agreement revenue 44,883 44,167 235,753 173,513 WAINUA joint development revenue 13,200 15,959 35,449 59,883 Total research and development revenue 58,083 60,126 271,202 233,396 Total revenue $ 133,814 $ 144,207 $ 478,562 $ 463,142 Revenue Sources The following are sources of revenue and when we typically recognize revenue. Commercial Revenue: SPINRAZA royalties and WAINUA royalties We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA. In 2024, we began earning royalties on net sales of WAINUA. Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net We earn commercial revenue from TEGSEDI and WAYLIVRA sales under our distribution agreements with Sobi. In addition, we receive royalties from PTC Therapeutics International Limited, or PTC, for TEGSEDI and WAYLIVRA sales. Commercial Revenue: Licensing and other royalty revenue We also recognize as commercial revenue sales milestone payments and royalties we earn under our partnerships. For example, we earn royalty revenue on net sales of QALSODY, which is included in Licensing and other royalty revenue. Research and development revenue under collaboration agreements We enter into collaboration agreements to license and sell our technology on an exclusive or non-exclusive basis. Our collaboration agreements typically contain multiple elements, or performance obligations, including technology licenses or options to obtain technology licenses, research and development, or R&D, services and manufacturing services. Upfront payments: Milestone payments: We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, when we achieve a milestone payment from a partner for advancing a clinical study under a collaboration agreement, we add the milestone payment to the transaction price if the milestone relates to an ongoing R&D services performance obligation and recognize revenue related to the milestone payment over our estimated period of performance. If we have partially completed our performance obligation, then we record a cumulative-effect adjustment in the period we add the milestone payment to the transaction price. Conversely, we recognize in full those milestone payments that we earn based on our partners’ activities when our partner achieves the milestone event and we do not have a performance obligation. License fees: WAINUA (Eplontersen) Collaboration with AstraZeneca In 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize WAINUA for the treatment of transthyretin amyloidosis, or ATTR. We jointly developed and are commercializing WAINUA for the treatment of adults with polyneuropathy caused by hereditary ATTR, or ATTRv-PN. We evaluated our WAINUA collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing. We determined that we had a vendor-customer relationship within the scope of Accounting Standards Codification, or ASC, Topic 606, Revenue from Contracts with Customers We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within the scope of ASC Topic 808, Collaborative Arrangements

Collaborative Arrangements and

Collaborative Arrangements and Licensing Agreements	9 Months Ended
	Sep. 30, 2024
Collaborative Arrangements and Licensing Agreements [Abstract]
Collaborative Arrangements and Licensing Agreements	5. Collaborative Arrangements and Licensing Agreements Below, we have included our AstraZeneca, Biogen, Otsuka and Roche collaborations, which are the collaborations with substantive changes during 2024 from those included in Part IV, Item 15, Note 4, 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, 2023. AstraZeneca We have collaborations with AstraZeneca: focused on the joint development and commercialization of WAINUA and focused on the treatment of cardiovascular, renal and metabolic diseases. From inception through , we have received more than $ million from these collaborations. Over the term of our WAINUA collaboration, we are eligible to receive up to $3.6 billion, which is comprised of a $200 million upfront payment, up to $485 million in development and approval milestone payments and up to $2.9 billion in sales milestone payments. The agreement includes territory-specific development, commercial and medical affairs cost-sharing provisions. In addition, we are eligible to receive up to mid-20 percent royalties for sales in the U.S. and tiered royalties up to the high teens for sales outside the U.S. In January 2024, we and AstraZeneca launched WAINUA in the U.S. for the treatment of adults with ATTRv-PN. As a result, we began earning royalties from WAINUA sales, which we recognize as commercial revenue in our condensed consolidated statements of operations. During the three and nine months ended September 30, 2024 and 2023, we earned the following revenue from our relationship with AstraZeneca (in thousands, except percentage amounts): Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Revenue from our relationship with AstraZeneca $ 19,461 $ 15,959 $ 47,106 $ 99,885 Percentage of total revenue 15 % 11 % 10 % 22 % In October 2024, we earned a $30 million milestone payment from AstraZeneca when the Medicines and Healthcare products Regulatory Agency approved WAINUA for ATTRv-PN in the United Kingdom as WAINZUA. We will achieve the next payment of $ million or $ million upon regulatory approval of WAINUA for ATTR-CM in the U.S. or Europe, respectively, under this collaboration. Our condensed consolidated balance sheet at September 30, 2024 included deferred contract revenue of $1.0 million from our relationship with AstraZeneca. We did not have any deferred contract revenue from our relationship with AstraZeneca at December 31, 2023. 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. QALSODY, our medicine to treat patients with superoxide dismutase 1 amyotrophic lateral sclerosis, or SOD1-ALS, received accelerated approval from the U.S. Food and Drug Administration, or FDA, in April 2023 and marketing authorization under exceptional circumstances from the European Medicines Agency, or EMA, in May 2024. In addition, we and Biogen are currently developing numerous other investigational medicines to treat neurodegenerative diseases, including medicines in development to treat people with SOD1-ALS, SMA, Alzheimer’s disease, or AD, and Parkinson’s disease, or PD. From inception through September 30, 2024, we have received more than $4.0 billion in payments from our Biogen collaborations, including payments to purchase our stock. Under our 2013 strategic neurology collaboration, we earned a $20 million milestone payment from Biogen when the EMA approved Biogen’s Marketing Authorization Application, or MAA, filing of QALSODY in the second quarter of 2024. We recognized this milestone payment as R&D revenue in full in the second quarter of 2024 because we did not have any remaining performance obligations related to the milestone payment. We will achieve the next milestone payment for QALSODY of $10 million if the Ministry of Health, Labour and Welfare of Japan approves Biogen’s Japanese New Drug Application filing of QALSODY. In the second quarter of 2024, Biogen’s option to license ION582, an investigational antisense medicine for the potential treatment of Angelman Syndrome, expired unexercised. As a result, we recognized $30 million of R&D revenue from previously deferred milestone payments related to the ION582 study because we did not have any remaining performance obligations. We will achieve the next milestone payment of $25 million if Biogen advances IONIS-MAPT Rx In the third quarter of 2024, we earned a $7.5 million milestone payment from Biogen when Biogen advanced an investigational medicine under our 2018 strategic neurology collaboration. We recognized this milestone payment as R&D revenue in full in the third quarter of 2024 because we did not have any remaining performance obligations related to the milestone payment. We will achieve the next payment of up to $15 million if Biogen advances a medicine under this collaboration. During the three and nine months ended September 30, 2024 and 2023, we earned the following revenue from our relationship with Biogen (in thousands, except percentage amounts): Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Revenue from our relationship with Biogen $ 80,291 $ 94,695 $ 277,686 $ 262,599 Percentage of total revenue 60 % 66 % 58 % 57 % Our condensed consolidated balance sheets at September 30, 2024 and December 31, 2023 Otsuka In 2023, we entered into an agreement with Otsuka Pharmaceutical Co., Ltd., or Otsuka, to commercialize donidalorsen in Europe. In the second quarter of 2024, we expanded the agreement to include commercialization rights for donidalorsen in the Asia-Pacific region in addition to Europe. As a result, we received a $ million upfront payment from Otsuka. Under the amended agreement, we are eligible to receive up to $ million, which is comprised of $ million in upfront payments, up to $ million in regulatory milestone payments and up to $ million in sales milestone payments over the term of the collaboration. In addition, we are eligible to receive tiered royalties up to on net sales. We are responsible for completing the ongoing development of donidalorsen. We retained the rights to commercialize donidalorsen in the U.S. and in the rest of the world, assuming regulatory approvals. We identified two performance obligations under our amended agreement for the Asia-Pacific region, comprised of our license of donidalorsen to Otsuka and R&D services for donidalorsen. We allocated the transaction price of $20 million based on the estimated stand-alone selling price of each performance obligation as follows: ● $17.5 million for the license of donidalorsen; and ● $2.5 million for the R&D services for donidalorsen. In the second quarter of 2024, we recognized $17.5 million as revenue in full because Otsuka had full use of the license without any continuing involvement from us. We are recognizing revenue for our R&D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our R&D services performance obligation in March 2026. We will achieve the next payment of $15 million if the EMA accepts a MAA filing for donidalorsen in the European Union, or EU, under this collaboration. During the three and nine months ended September 30, 2024 and 2023, we earned the following revenue from our relationship with Otsuka (in thousands, except percentage amounts): Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Revenue from our relationship with Otsuka $ 1,083 $ — $ 20,773 $ — Percentage of total revenue 1 % 0 % 4 % 0 % Our condensed consolidated balance sheets at September 30, 2024 and December 31, 2023 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 July 2024, Roche discontinued development Rx Rx Over the term of the IONIS-FB-L Rx Rx During the three and nine months ended September 30, 2024 and 2023, 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, 2024 2023 2024 2023 Revenue from our relationship with Roche $ 11,084 $ 8,858 $ 33,679 $ 16,979 Percentage of total revenue 8 % 6 % 7 % 4 % Our condensed consolidated balance sheets at September 30, 2024 and December 31, 2023 included deferred contract revenue of $4.5 million and $36.7 million, respectively, from our relationship with Roche.

Basic and Diluted Net Loss Per

Basic and Diluted Net Loss Per Share	9 Months Ended
	Sep. 30, 2024
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, 2024 and 2023 by dividing our net loss by our weighted-average number of common shares outstanding during the period. In September 2024, we issued 11,500,000 shares of common stock through a public offering. Refer to Note 13, Public Common Stock Offering Diluted net loss per share For the three and nine months ended September 30, 2024 and 2023, 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, 2024 and 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, 2024
Investments [Abstract]
Investments	7. Investments The following table summarizes the contract maturity of the available-for-sale securities we held as of September 30, 2024: One year 70 % After one year two years 23 % After two years three and a half years 7 % Total 100 % As illustrated above, at September 30, 2024, 93 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, 2024, 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, 2024 Cost Gains Losses Fair Value Available-for-sale debt securities: Corporate debt securities (1) $ 653,028 $ 1,120 $ (213 ) $ 653,935 Debt securities issued by U.S. government agencies 149,658 464 (20 ) 150,102 Debt securities issued by the U.S. Treasury (1) 678,977 1,283 (114 ) 680,146 Debt securities issued by states of the U.S. and political subdivisions of the states 10,652 18 (2 ) 10,668 Total debt securities with a maturity of one year or less 1,492,315 2,885 (349 ) 1,494,851 Corporate debt securities 433,542 1,813 (312 ) 435,043 Debt securities issued by U.S. government agencies 78,241 526 (51 ) 78,716 Debt securities issued by the U.S. Treasury 175,390 847 (50 ) 176,187 Total debt securities with a maturity of more than one year 687,173 3,186 (413 ) 689,946 Total available-for-sale debt securities $ 2,179,488 $ 6,071 $ (762 ) $ 2,184,797 Equity securities: Publicly traded equity securities included in other current assets (2) $ 11,897 $ 426 $ (4,624 ) $ 7,699 Privately held equity securities included in deposits and other assets (3) 23,115 25,001 (7,093 ) 41,023 Total equity securities 35,012 25,427 (11,717 ) 48,722 Total available-for-sale debt and equity securities $ 2,214,500 $ 31,498 $ (12,479 ) $ 2,233,519 Amortized Gross Unrealized Estimated December 31, 2023 Cost Gains Losses Fair Value Available-for-sale debt securities: Corporate debt securities (1) $ 559,967 $ 157 $ (2,625 ) $ 557,499 Debt securities issued by U.S. government agencies 224,711 64 (611 ) 224,164 Debt securities issued by the U.S. Treasury (1) 513,784 152 (1,889 ) 512,047 Debt securities issued by states of the U.S. and political subdivisions of the states 17,757 42 (113 ) 17,686 Total debt securities with a maturity of one year or less 1,316,219 415 (5,238 ) 1,311,396 Corporate debt securities 243,151 1,270 (692 ) 243,729 Debt securities issued by U.S. government agencies 110,138 547 (21 ) 110,664 Debt securities issued by the U.S. Treasury 294,873 1,239 (480 ) 295,632 Debt securities issued by states of the U.S. and political subdivisions of the states 3,466 7 (4 ) 3,469 Total debt securities with a maturity of more than one year 651,628 3,063 (1,197 ) 653,494 Total available-for-sale debt securities $ 1,967,847 $ 3,478 $ (6,435 ) $ 1,964,890 Equity securities: Publicly traded equity securities included in other current assets (2) $ 11,897 $ 236 $ (5,832 ) $ 6,301 Privately held equity securities included in deposits and other assets (3) 23,115 25,001 (5,125 ) 42,991 Total equity securities 35,012 25,237 (10,957 ) 49,292 Total available-for-sale debt and equity securities $ 2,002,859 $ 28,715 $ (17,392 ) $ 2,014,182 (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, 2024, we recorded a $1.4 million net unrealized gain in our condensed consolidated statements of operations related to changes in the fair value of our investments in publicly traded companies. (3) Our privately held equity securities are included in deposits and other assets. We recognize our privately held equity securities at . In the , we recorded a loss of $ million in our condensed consolidated statements of operations related to observable price changes of our investments in privately held companies. The following is a summary of our investments we consider to be temporarily impaired at September 30, 2024 (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 209 $ 331,968 $ (351 ) $ 47,159 $ (174 ) $ 379,127 $ (525 ) Debt securities issued by U.S. government agencies 26 49,966 (70 ) 3,068 (1 ) 53,034 (71 ) Debt securities issued by the U.S. Treasury 12 48,664 (30 ) 59,416 (134 ) 108,080 (164 ) Debt securities issued by states of the U.S. and political subdivisions of the states 8 534 — 919 (2 ) 1,453 (2 ) Total temporarily impaired securities 255 $ 431,132 $ (451 ) $ 110,562 $ (311 ) $ 541,694 $ (762 ) 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, 2024
Fair Value Measurements [Abstract]
Fair Value Measurements	8. Fair Value Measurements The following tables present the major security types we held at September 30, 2024 and December 31, 2023 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, 2024 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 255,924 $ 255,924 $ — Corporate debt securities (2) 1,088,978 — 1,088,978 Debt securities issued by U.S. government agencies (3) 228,818 — 228,818 Debt securities issued by the U.S. Treasury (4) 856,333 856,333 — Debt securities issued by states of the U.S. and political subdivisions of the states (3) 10,668 — 10,668 Publicly traded equity securities included in other current assets (5) 7,699 7,699 — Total $ 2,448,420 $ 1,119,956 $ 1,328,464 At December 31, 2023 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 185,424 $ 185,424 $ — Corporate debt securities (6) 801,228 — 801,228 Debt securities issued by U.S. government agencies (3) 334,828 — 334,828 Debt securities issued by the U.S. Treasury (3) 807,679 807,679 — Debt securities issued by states of the U.S. and political subdivisions of the states (3) 21,155 — 21,155 Publicly traded equity securities included in other current assets (5) 6,301 6,301 — Total $ 2,156,615 $ 999,404 $ 1,157,211 The following footnotes reference lines in our condensed consolidated balance sheets: (1) Included in cash and cash equivalents. (2) $21.2 million was included in cash and cash equivalents, with the difference included in short-term investments. (3) Included in short-term investments. (4) $14.9 million was included in cash and cash equivalents, with the difference included in short-term investments. (5) Included in other current assets. (6) $33.0 million was included in cash and cash equivalents, with the difference included in short-term investments. Convertible Notes Our 1.75% Notes, 0% Notes and 0.125% Notes had a fair value of $589.8 million, $630.7 million and $44.0 million at September 30, 2024, respectively. Our 1.75% Notes, 0% Notes and 0.125% Notes had a fair value of $661.1 million, $667.8 million and $42.4 million at December 31, 2023, respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.

Stock-based Compensation Expens

Stock-based Compensation Expense	9 Months Ended
	Sep. 30, 2024
Stock-based Compensation Expense [Abstract]
Stock-based Compensation Expense	9. Stock-based Compensation Expense The following table summarizes stock-based compensation expense for the three and nine months ended September 30, 2024 and 2023 (in thousands): Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Cost of sales $ 159 $ 118 $ 609 $ 355 Research, development and patent expense 22,120 18,727 67,111 57,543 Selling, general and administrative expense 9,705 7,119 26,332 21,575 Stock-based compensation expense, net of amounts capitalized $ 31,984 $ 25,964 $ 94,052 $ 79,473 Capitalized stock-based compensation expense 506 — 506 — Total stock-based compensation expense $ 32,490 $ 25,964 $ 94,558 $ 79,473 As of September 30, 2024, total unrecognized estimated stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $54.1 million, $87.2 million and $12.1 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, 1.5 years and 1.7 years, respectively. Refer to Part IV, Item 15, Note 1, Organization and Significant Accounting Policies For the nine months ended September 30, 2024 and 2023, we used the following weighted-average assumptions in our Black-Scholes calculations: Employee Stock Options: Nine Months Ended September 30, 2024 2023 Risk-free interest rate 4.1 % 3.7 % Dividend yield 0.0 % 0.0 % Volatility 43.8 % 47.1 % Expected life 6.3 years 6.3 years Board of Director Stock Options: Nine Months Ended September 30, 2024 2023 Risk-free interest rate 4.5 % 3.8 % Dividend yield 0.0 % 0.0 % Volatility 49.8 % 53.0 % Expected life 7.5 years 7.7 years ESPP: Nine Months Ended September 30, 2024 2023 Risk-free interest rate 5.2 % 5.3 % Dividend yield 0.0 % 0.0 % Volatility 37.8 % 36.0 % Expected life 6 months 6 months RSUs: The weighted-average grant date fair value of RSUs granted to employees for the nine months ended September 30, 2024 and 2023 was $52.08 and $39.78 per share, respectively. PRSUs: Under the terms of the PRSUs we granted in 2024 and 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. The weighted-average grant date fair value of PRSUs we granted to our executive officers for the nine months ended September 30, 2024 and 2023 was $78.41 and $58.99 per share, respectively.

Income Taxes

Income Taxes	9 Months Ended
	Sep. 30, 2024
Income Taxes [Abstract]
Income Taxes	10. Income Taxes We recorded income tax benefit of $3.6 million and $3.5 million for the three and nine months ended September 30, 2024, respectively, compared to income tax expense of $6.6 million and $25.8 million for the same periods in 2023, respectively. The benefit for the three and nine months ended September 30, 2024 primarily relates to the 2023 tax return position for the royalty purchase agreement with Royalty Pharma that we finalized during the third quarter of 2024. We reflected the Royalty Pharma transaction as a taxable sale, which required us to include the proceeds from the sale, net of currently deductible issuance costs, as taxable income in 2023. The decrease in income tax expense for the three and nine months ended September 30, 2024 compared to the same periods in 2023 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, 2024
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, 2024 and 2023, the estimated effective interest rate under the agreement was 13.5 percent. The following table sets forth information on our liability related to sale of future royalties (in thousands): Proceeds from sale of future royalties in January 2023 $ 500,000 Issuance costs related to sale of future royalties (10,434 ) Royalty payments to Royalty Pharma (44,628 ) Interest expense related to sale of future royalties 68,238 Amortization of issuance costs related to sale of future royalties 560 Net liability related to sale of future royalties as of December 31, 2023 513,736 Royalty payments to Royalty Pharma (30,422 ) Interest expense related to sale of future royalties 54,330 Amortization of issuance costs related to sale of future royalties 458 Net liability related to sale of future royalties as of September 30, 2024 $ 538,102 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, 2024
Convertible Debt [Abstract]
Convertible Debt	12. Convertible Debt 1.75 Percent Convertible Senior Notes In 2023, we completed a $575.0 million offering of our 1.75% Notes and used $488.2 million of the net proceeds from the issuance of our 1.75% Notes to repurchase $504.4 million in principal of our 0.125% Notes. We expect to use the remaining net proceeds to settle the 0.125% Notes that remain outstanding and for general corporate and working capital purposes. At September 30, 2024, 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 $ 10.7 Maturity date June 2028 Interest rate 1.75 % Effective interest rate 2.3 % Conversion price per share $ 53.73 Total shares of common stock subject to conversion 10.7 0 Percent Convertible Senior Notes and Call Spread In 2021, we completed a $632.5 million offering of our 0% Notes. We used $319.0 million of the net proceeds from the issuance of our 0% Notes to pay the remaining $309.9 million principal balance of our 1 percent convertible senior notes, or 1% Notes, in 2021. At September 30, 2024, we had the following 0% 0% Notes Outstanding principal balance $ 632.5 Unamortized debt issuance costs $ 4.8 Maturity date April 2026 Interest rate 0 % Effective interest rate 0.5 % Conversion price per share $ 57.84 Effective conversion price per share with call spread $ 76.39 Total shares of common stock subject to conversion 10.9 In conjunction with the 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our 0% 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 In 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain holders of our 1% Notes to exchange $375.6 million of our 1% Notes for $439.3 million of our 0.125% Notes, and to issue $109.5 million of our 0.125% Notes. As discussed above, in 2023, we repurchased $504.4 million of our 0.125% Notes. At September 30, 2024, 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 $ 0.1 Maturity date December 2024 Interest rate 0.125 % Effective interest rate 0.5 % Conversion price per share $ 83.28 Effective conversion price per share with call spread $ 123.38 Total shares of common stock subject to conversion, excluding shares related to 0.125 0.5 In conjunction with the issuance of our Notes in 2019, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our . We increased our effective conversion price to $ with the same number of underlying shares as our Notes. The call spread cost us $ million, of which $ million was for the note hedge purchase, offset by $ million we received for selling the warrants. Similar to our , our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the . The note hedges will expire upon maturity of the , or December 2024. The note hedges and warrants are separate transactions and are not part of the terms of our . The holders of the do not have any rights with respect to the note hedges and warrants. 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.

Public Common Stock Offering

Public Common Stock Offering	9 Months Ended
	Sep. 30, 2024
Public Common Stock Offering [Abstract]
Public Common Stock Offering	13. Public Common Stock Offering In September 2024, we completed the sale of 11,500,000 shares of our common stock through a public offering at a price of $43.50 per share. We received net proceeds of $489.1 million from the sale of these shares net of underwriting discounts and commissions and other offering expenses of $11.2 million.

Legal Proceedings

Legal Proceedings	9 Months Ended
	Sep. 30, 2024
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	3 Months Ended
	Sep. 30, 2024 shares
Trading Arrangements, by Individual
Material Terms of Trading Arrangement	During the quarter ended September 30, 2024, 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** Eric Swayze EVP, Research Termination August 12, 2024 X 85,614 Upon the execution of all instructions provided in the plan Brian Birchler EVP, Corporate and Development Operations Adoption August 12, 2024 X 71,400 The earlier to occur of (i) January 2, 2026, and (ii) upon the execution of all instructions provided in the plan Brett P. Monia Chief Executive Officer Adoption August 12, 2024 X 431,245 The earlier to occur of (i) May 7, 2026, and (ii) upon the execution of all instructions provided in the plan C. Frank Bennett EVP, Chief Scientific Officer Adoption August 12, 2024 X 111,149 The earlier to occur of (i) January 2, 2026, and (ii) upon the execution of all instructions provided in the plan Joseph Loscalzo Board Member Adoption August 12, 2024 X 62,677 The earlier to occur of (i) November 10, 2025, and (ii) upon the execution of all instructions provided in the plan Eric Swayze EVP, Research Adoption August 14, 2024 X 177,770 The earlier to occur of (i) December 31, 2027, and (ii) upon the execution of all instructions provided in the plan Shannon L. Devers EVP, Chief Human Resources Officer Adoption September 3, 2024 X 123,508 The earlier to occur of (i) January 31, 2026, and (ii) upon the execution of all instructions provided in the plan Spencer Berthelsen Director Adoption September 11, 2024 X 16,000 The earlier to occur of (i) June 30, 2025, and (ii) upon the execution of all instructions provided in the plan
Termination [Member] | Eric Swayze [Member]
Trading Arrangements, by Individual
Name	Eric Swayze
Title	EVP, Research
Rule 10b5-1 Arrangement Terminated	true
Non-Rule 10b5-1 Arrangement Terminated	false
Termination Date	August 12, 2024
Expiration Date
Aggregate Available	85,614
Adoption [Member] | 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	August 14, 2024
Expiration Date	December 31, 2027
Arrangement Duration	1235 days
Aggregate Available	177,770
Adoption [Member] | Brian Birchler [Member]
Trading Arrangements, by Individual
Name	Brian Birchler
Title	EVP, Corporate and Development Operations
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	August 12, 2024
Expiration Date	January 2, 2026
Arrangement Duration	509 days
Aggregate Available	71,400
Adoption [Member] | Brett Monia [Member]
Trading Arrangements, by Individual
Name	Brett P. Monia
Title	Chief Executive Officer
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	August 12, 2024
Expiration Date	May 7, 2026
Arrangement Duration	634 days
Aggregate Available	431,245
Adoption [Member] | C. Frank Bennett [Member]
Trading Arrangements, by Individual
Name	C. Frank Bennett
Title	EVP, Chief Scientific Officer
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	August 12, 2024
Expiration Date	January 2, 2026
Arrangement Duration	509 days
Aggregate Available	111,149
Adoption [Member] | Joseph Loscalzo [Member]
Trading Arrangements, by Individual
Name	Joseph Loscalzo
Title	Board Member
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	August 12, 2024
Expiration Date	November 10, 2025
Arrangement Duration	456 days
Aggregate Available	62,677
Adoption [Member] | Shannon L. Devers [Member]
Trading Arrangements, by Individual
Name	Shannon L. Devers
Title	EVP, Chief Human Resources Officer
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	September 3, 2024
Expiration Date	January 31, 2026
Arrangement Duration	516 days
Aggregate Available	123,508
Adoption [Member] | Spencer Berthelsen [Member]
Trading Arrangements, by Individual
Name	Spencer Berthelsen
Title	Director
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	September 11, 2024
Expiration Date	June 30, 2025
Arrangement Duration	293 days
Aggregate Available	16,000

Organization and Basis of Pre_2

Organization and Basis of Presentation (Policies)	9 Months Ended
	Sep. 30, 2024
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, 2024 and 2023 on the same basis as the audited financial statements for the year ended December 31, 2023. 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, 2023 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, 2024
Significant Accounting Policies [Abstract]
Recently Issued Accounting Standards	Recently Issued Accounting Standards We do not expect any recently issued accounting standards other than those included in our Annual Report on Form 10-K for the year ended December 31, 2023 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, 2024
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, 2024 and 2023 by dividing our net loss by our weighted-average number of common shares outstanding during the period. In September 2024, we issued 11,500,000 shares of common stock through a public offering. Refer to Note 13, Public Common Stock Offering Diluted net loss per share For the three and nine months ended September 30, 2024 and 2023, 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, 2024 and 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.

Supplemental Financial Data (Ta

Supplemental Financial Data (Tables)	9 Months Ended
	Sep. 30, 2024
Supplemental Financial Data [Abstract]
Inventories	Inventories Our inventory consisted of the following (in thousands): September 30, 2024 December 31, 2023 Raw materials: Raw materials - clinical $ 20,773 $ 20,985 Raw materials - commercial 963 1,809 Total raw materials 21,736 22,794 Work in process 6,653 5,477 Finished goods 63 154 Total inventories $ 28,452 $ 28,425
Accrued Liabilities	Accrued Liabilities Our accrued liabilities consisted of the following (in thousands): September 30, 2024 December 31, 2023 Clinical development expenses $ 90,239 $ 105,967 In-licensing expenses 7,082 7,454 Commercial expenses 5,016 4,875 Other miscellaneous expenses 22,059 29,598 Total accrued liabilities $ 124,396 $ 147,894

Revenues (Tables)

Revenues (Tables)	9 Months Ended
	Sep. 30, 2024
Revenues [Abstract]
Revenues	During the three and nine months ended September 30, 2024 and 2023, our revenues were comprised of the following (in thousands): Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Revenue: Commercial revenue: SPINRAZA royalties $ 57,208 $ 67,253 $ 152,406 $ 178,511 WAINUA royalties 5,371 — 10,278 — Other commercial revenue: TEGSEDI and WAYLIVRA revenue, net 8,924 8,286 25,744 25,420 Licensing and other royalty revenue 4,228 8,542 18,932 25,815 Total other commercial revenue 13,152 16,828 44,676 51,235 Total commercial revenue 75,731 84,081 207,360 229,746 Research and development revenue: Collaborative agreement revenue 44,883 44,167 235,753 173,513 WAINUA joint development revenue 13,200 15,959 35,449 59,883 Total research and development revenue 58,083 60,126 271,202 233,396 Total revenue $ 133,814 $ 144,207 $ 478,562 $ 463,142

Collaborative Arrangements an_2

Collaborative Arrangements and Licensing Agreements (Tables)	9 Months Ended
	Sep. 30, 2024
AstraZeneca [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the three and nine months ended September 30, 2024 and 2023, we earned the following revenue from our relationship with AstraZeneca (in thousands, except percentage amounts): Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Revenue from our relationship with AstraZeneca $ 19,461 $ 15,959 $ 47,106 $ 99,885 Percentage of total revenue 15 % 11 % 10 % 22 %
Biogen [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the three and nine months ended September 30, 2024 and 2023, we earned the following revenue from our relationship with Biogen (in thousands, except percentage amounts): Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Revenue from our relationship with Biogen $ 80,291 $ 94,695 $ 277,686 $ 262,599 Percentage of total revenue 60 % 66 % 58 % 57 %
Otsuka [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the three and nine months ended September 30, 2024 and 2023, we earned the following revenue from our relationship with Otsuka (in thousands, except percentage amounts): Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Revenue from our relationship with Otsuka $ 1,083 $ — $ 20,773 $ — Percentage of total revenue 1 % 0 % 4 % 0 %
Roche [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the three and nine months ended September 30, 2024 and 2023, 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, 2024 2023 2024 2023 Revenue from our relationship with Roche $ 11,084 $ 8,858 $ 33,679 $ 16,979 Percentage of total revenue 8 % 6 % 7 % 4 %

Investments (Tables)

Investments (Tables)	9 Months Ended
	Sep. 30, 2024
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, 2024: One year 70 % After one year two years 23 % After two years three and a half years 7 % Total 100 %
Summary of Investments	The following is a summary of our investments (in thousands): Amortized Gross Unrealized Estimated September 30, 2024 Cost Gains Losses Fair Value Available-for-sale debt securities: Corporate debt securities (1) $ 653,028 $ 1,120 $ (213 ) $ 653,935 Debt securities issued by U.S. government agencies 149,658 464 (20 ) 150,102 Debt securities issued by the U.S. Treasury (1) 678,977 1,283 (114 ) 680,146 Debt securities issued by states of the U.S. and political subdivisions of the states 10,652 18 (2 ) 10,668 Total debt securities with a maturity of one year or less 1,492,315 2,885 (349 ) 1,494,851 Corporate debt securities 433,542 1,813 (312 ) 435,043 Debt securities issued by U.S. government agencies 78,241 526 (51 ) 78,716 Debt securities issued by the U.S. Treasury 175,390 847 (50 ) 176,187 Total debt securities with a maturity of more than one year 687,173 3,186 (413 ) 689,946 Total available-for-sale debt securities $ 2,179,488 $ 6,071 $ (762 ) $ 2,184,797 Equity securities: Publicly traded equity securities included in other current assets (2) $ 11,897 $ 426 $ (4,624 ) $ 7,699 Privately held equity securities included in deposits and other assets (3) 23,115 25,001 (7,093 ) 41,023 Total equity securities 35,012 25,427 (11,717 ) 48,722 Total available-for-sale debt and equity securities $ 2,214,500 $ 31,498 $ (12,479 ) $ 2,233,519 Amortized Gross Unrealized Estimated December 31, 2023 Cost Gains Losses Fair Value Available-for-sale debt securities: Corporate debt securities (1) $ 559,967 $ 157 $ (2,625 ) $ 557,499 Debt securities issued by U.S. government agencies 224,711 64 (611 ) 224,164 Debt securities issued by the U.S. Treasury (1) 513,784 152 (1,889 ) 512,047 Debt securities issued by states of the U.S. and political subdivisions of the states 17,757 42 (113 ) 17,686 Total debt securities with a maturity of one year or less 1,316,219 415 (5,238 ) 1,311,396 Corporate debt securities 243,151 1,270 (692 ) 243,729 Debt securities issued by U.S. government agencies 110,138 547 (21 ) 110,664 Debt securities issued by the U.S. Treasury 294,873 1,239 (480 ) 295,632 Debt securities issued by states of the U.S. and political subdivisions of the states 3,466 7 (4 ) 3,469 Total debt securities with a maturity of more than one year 651,628 3,063 (1,197 ) 653,494 Total available-for-sale debt securities $ 1,967,847 $ 3,478 $ (6,435 ) $ 1,964,890 Equity securities: Publicly traded equity securities included in other current assets (2) $ 11,897 $ 236 $ (5,832 ) $ 6,301 Privately held equity securities included in deposits and other assets (3) 23,115 25,001 (5,125 ) 42,991 Total equity securities 35,012 25,237 (10,957 ) 49,292 Total available-for-sale debt and equity securities $ 2,002,859 $ 28,715 $ (17,392 ) $ 2,014,182 (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, 2024, we recorded a $1.4 million net unrealized gain in our condensed consolidated statements of operations related to changes in the fair value of our investments in publicly traded companies. (3) Our privately held equity securities are included in deposits and other assets. We recognize our privately held equity securities at . In the , we recorded a loss of $ million in our condensed consolidated statements of operations related to observable price changes 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, 2024 (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 209 $ 331,968 $ (351 ) $ 47,159 $ (174 ) $ 379,127 $ (525 ) Debt securities issued by U.S. government agencies 26 49,966 (70 ) 3,068 (1 ) 53,034 (71 ) Debt securities issued by the U.S. Treasury 12 48,664 (30 ) 59,416 (134 ) 108,080 (164 ) Debt securities issued by states of the U.S. and political subdivisions of the states 8 534 — 919 (2 ) 1,453 (2 ) Total temporarily impaired securities 255 $ 431,132 $ (451 ) $ 110,562 $ (311 ) $ 541,694 $ (762 )

Fair Value Measurements (Tables

Fair Value Measurements (Tables)	9 Months Ended
	Sep. 30, 2024
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, 2024 and December 31, 2023 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, 2024 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 255,924 $ 255,924 $ — Corporate debt securities (2) 1,088,978 — 1,088,978 Debt securities issued by U.S. government agencies (3) 228,818 — 228,818 Debt securities issued by the U.S. Treasury (4) 856,333 856,333 — Debt securities issued by states of the U.S. and political subdivisions of the states (3) 10,668 — 10,668 Publicly traded equity securities included in other current assets (5) 7,699 7,699 — Total $ 2,448,420 $ 1,119,956 $ 1,328,464 At December 31, 2023 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 185,424 $ 185,424 $ — Corporate debt securities (6) 801,228 — 801,228 Debt securities issued by U.S. government agencies (3) 334,828 — 334,828 Debt securities issued by the U.S. Treasury (3) 807,679 807,679 — Debt securities issued by states of the U.S. and political subdivisions of the states (3) 21,155 — 21,155 Publicly traded equity securities included in other current assets (5) 6,301 6,301 — Total $ 2,156,615 $ 999,404 $ 1,157,211 The following footnotes reference lines in our condensed consolidated balance sheets: (1) Included in cash and cash equivalents. (2) $21.2 million was included in cash and cash equivalents, with the difference included in short-term investments. (3) Included in short-term investments. (4) $14.9 million was included in cash and cash equivalents, with the difference included in short-term investments. (5) Included in other current assets. (6) $33.0 million was included in cash and cash equivalents, with the difference included in short-term investments.

Stock-based Compensation Expe_2

Stock-based Compensation Expense (Tables)	9 Months Ended
	Sep. 30, 2024
Stock-based Compensation Expense [Abstract]
Stock-Based Compensation Expense	The following table summarizes stock-based compensation expense for the three and nine months ended September 30, 2024 and 2023 (in thousands): Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Cost of sales $ 159 $ 118 $ 609 $ 355 Research, development and patent expense 22,120 18,727 67,111 57,543 Selling, general and administrative expense 9,705 7,119 26,332 21,575 Stock-based compensation expense, net of amounts capitalized $ 31,984 $ 25,964 $ 94,052 $ 79,473 Capitalized stock-based compensation expense 506 — 506 — Total stock-based compensation expense $ 32,490 $ 25,964 $ 94,558 $ 79,473
Weighted-Average Assumptions for Stock Options	Employee Stock Options: Nine Months Ended September 30, 2024 2023 Risk-free interest rate 4.1 % 3.7 % Dividend yield 0.0 % 0.0 % Volatility 43.8 % 47.1 % Expected life 6.3 years 6.3 years Board of Director Stock Options: Nine Months Ended September 30, 2024 2023 Risk-free interest rate 4.5 % 3.8 % Dividend yield 0.0 % 0.0 % Volatility 49.8 % 53.0 % Expected life 7.5 years 7.7 years
Weighted-Average Assumptions for ESPP	ESPP: Nine Months Ended September 30, 2024 2023 Risk-free interest rate 5.2 % 5.3 % Dividend yield 0.0 % 0.0 % Volatility 37.8 % 36.0 % Expected life 6 months 6 months

Liability Related to Sale of _2

Liability Related to Sale of Future Royalties (Tables)	9 Months Ended
	Sep. 30, 2024
Liability Related to Sale of Future Royalties [Abstract]
Liability Related to Sale of Future Royalties	The following table sets forth information on our liability related to sale of future royalties (in thousands): Proceeds from sale of future royalties in January 2023 $ 500,000 Issuance costs related to sale of future royalties (10,434 ) Royalty payments to Royalty Pharma (44,628 ) Interest expense related to sale of future royalties 68,238 Amortization of issuance costs related to sale of future royalties 560 Net liability related to sale of future royalties as of December 31, 2023 513,736 Royalty payments to Royalty Pharma (30,422 ) Interest expense related to sale of future royalties 54,330 Amortization of issuance costs related to sale of future royalties 458 Net liability related to sale of future royalties as of September 30, 2024 $ 538,102

Convertible Debt (Tables)

Convertible Debt (Tables)	9 Months Ended
	Sep. 30, 2024
1.75% Notes [Member]
Convertible Debt [Abstract]
Convertible Senior Notes	At September 30, 2024, 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 $ 10.7 Maturity date June 2028 Interest rate 1.75 % Effective interest rate 2.3 % Conversion price per share $ 53.73 Total shares of common stock subject to conversion 10.7
0% Notes [Member]
Convertible Debt [Abstract]
Convertible Senior Notes	At September 30, 2024, we had the following 0% 0% Notes Outstanding principal balance $ 632.5 Unamortized debt issuance costs $ 4.8 Maturity date April 2026 Interest rate 0 % Effective interest rate 0.5 % Conversion price per share $ 57.84 Effective conversion price per share with call spread $ 76.39 Total shares of common stock subject to conversion 10.9
0.125% Notes [Member]
Convertible Debt [Abstract]
Convertible Senior Notes	At September 30, 2024, 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 $ 0.1 Maturity date December 2024 Interest rate 0.125 % Effective interest rate 0.5 % Conversion price per share $ 83.28 Effective conversion price per share with call spread $ 123.38 Total shares of common stock subject to conversion, excluding shares related to 0.125 0.5

Organization and Basis of Pre_3

Organization and Basis of Presentation (Details)	9 Months Ended
	Sep. 30, 2024 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, 2024	Dec. 31, 2023
Inventory [Abstract]
Raw materials	$ 21,736	$ 22,794
Work in process	6,653	5,477
Finished goods	63	154
Total inventories	28,452	28,425
Clinical [Member]
Inventory [Abstract]
Raw materials	20,773	20,985
Commercial [Member]
Inventory [Abstract]
Raw materials	$ 963	$ 1,809

Supplemental Financial Data, Ac

Supplemental Financial Data, Accrued Liabilities (Details) - USD ($) $ in Thousands	Sep. 30, 2024	Dec. 31, 2023
Accrued Liabilities [Abstract]
Clinical development expenses	$ 90,239	$ 105,967
In-licensing expenses	7,082	7,454
Commercial expenses	5,016	4,875
Other miscellaneous expenses	22,059	29,598
Total accrued liabilities	$ 124,396	$ 147,894

Revenues (Details)

Revenues (Details) $ in Thousands	3 Months Ended		9 Months Ended		12 Months Ended
	Sep. 30, 2024 USD ($)	Sep. 30, 2023 USD ($)	Sep. 30, 2024 USD ($)	Sep. 30, 2023 USD ($)	Dec. 31, 2021 USD ($) PerformanceObligation Component
Revenues [Abstract]
Revenue	$ 133,814	$ 144,207	$ 478,562	$ 463,142
WAINUA (Eplontersen) Collaboration with AstraZeneca [Member]
Revenues [Abstract]
Upfront payment received					$ 200,000
Number of material components | Component					4
Number of performance obligations | PerformanceObligation					1
Transaction price					$ 200,000
Percentage of costs associated with ongoing global Phase 3 development program paid by AstraZeneca			55%
Commercial Revenue [Member]
Revenues [Abstract]
Revenue	75,731	84,081	$ 207,360	229,746
SPINRAZA Royalties [Member]
Revenues [Abstract]
Revenue	57,208	67,253	152,406	178,511
WAINUA Royalties [Member]
Revenues [Abstract]
Revenue	5,371	0	10,278	0
Other Commercial Revenue [Member]
Revenues [Abstract]
Revenue	13,152	16,828	44,676	51,235
TEGSEDI and WAYLIVRA Revenue, Net [Member]
Revenues [Abstract]
Revenue	8,924	8,286	25,744	25,420
Licensing and Other Royalty Revenue [Member]
Revenues [Abstract]
Revenue	4,228	8,542	18,932	25,815
Research and Development Revenue [Member]
Revenues [Abstract]
Revenue	58,083	60,126	271,202	233,396
Collaborative Agreement Revenue [Member]
Revenues [Abstract]
Revenue	44,883	44,167	235,753	173,513
WAINUA Joint Development Revenue [Member]
Revenues [Abstract]
Revenue	$ 13,200	$ 15,959	$ 35,449	$ 59,883

Collaborative Arrangements an_3

Collaborative Arrangements and Licensing Agreements, AstraZeneca (Details) $ in Thousands	1 Months Ended	3 Months Ended		9 Months Ended
	Oct. 31, 2024 USD ($)	Sep. 30, 2024 USD ($) Agreement	Sep. 30, 2023 USD ($)	Sep. 30, 2024 USD ($) Agreement	Sep. 30, 2023 USD ($)	Dec. 31, 2023 USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		$ 133,814	$ 144,207	$ 478,562	$ 463,142
AstraZeneca [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement		2		2
Revenue		$ 19,461	$ 15,959	$ 47,106	$ 99,885
Deferred contract revenue		$ 1,000		$ 1,000		$ 0
AstraZeneca [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage		15%	11%	10%	22%
AstraZeneca [Member] | Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received		$ 935,000		$ 935,000
WAINUA [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement		1		1
Maximum amount of payments receivable over term of collaboration		$ 3,600,000		$ 3,600,000
Maximum amount of upfront payments over term of collaboration		200,000		200,000
Maximum amount of development milestone payments over term of collaboration		485,000		485,000
Maximum amount of sales milestone payments over term of collaboration		$ 2,900,000		$ 2,900,000
WAINUA [Member] | Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 30,000
WAINUA [Member] | Maximum [Member] | Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next payment to be achieved	200,000
WAINUA [Member] | Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Royalty percentage received on net sales of medicine				20%
WAINUA [Member] | Minimum [Member] | Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next payment to be achieved	$ 115,000
Cardiovascular, Renal and Metabolic Diseases [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement		1		1

Collaborative Arrangements an_4

Collaborative Arrangements and Licensing Agreements, Biogen (Details) - USD ($) $ in Thousands	3 Months Ended			9 Months Ended
	Sep. 30, 2024	Jun. 30, 2024	Sep. 30, 2023	Sep. 30, 2024	Sep. 30, 2023	Dec. 31, 2023
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 133,814		$ 144,207	$ 478,562	$ 463,142
Biogen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	80,291		$ 94,695	277,686	$ 262,599
Deferred contract revenue	$ 226,400			$ 226,400		$ 307,400
Biogen [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage	60%		66%	58%	57%
Biogen [Member] | Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	$ 4,000,000			$ 4,000,000
2013 Strategic Neurology [Member] | QALSODY [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next payment to be achieved	10,000			10,000
Revenue		$ 20,000
2012 Neurology [Member] | ION582 [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		$ 30,000
2012 Neurology [Member] | IONIS-MAPT [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next payment to be achieved	25,000			25,000
2018 Strategic Neurology [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next payment to be achieved	15,000			$ 15,000
Revenue	$ 7,500

Collaborative Arrangements an_5

Collaborative Arrangements and Licensing Agreements, Otsuka (Details) $ in Thousands	3 Months Ended			9 Months Ended
	Sep. 30, 2024 USD ($)	Jun. 30, 2024 USD ($) PerformanceObligation	Sep. 30, 2023 USD ($)	Sep. 30, 2024 USD ($)	Sep. 30, 2023 USD ($)	Dec. 31, 2023 USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 133,814		$ 144,207	$ 478,562	$ 463,142
Otsuka [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Upfront payment received		$ 20,000
Maximum amount of payments receivable over term of collaboration	290,000			290,000
Maximum amount of upfront payments over term of collaboration	85,000			85,000
Maximum amount of regulatory milestone payments over term of collaboration	65,000			65,000
Maximum amount of sales milestone payments over term of collaboration	140,000			140,000
Cumulative payments received	85,000			85,000
Number of separate performance obligations | PerformanceObligation		2
Transaction price		$ 20,000
Revenue	1,083		$ 0	20,773	$ 0
Deferred contract revenue	$ 7,700			$ 7,700		$ 8,500
Otsuka [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage	1%		0%	4%	0%
Otsuka [Member] | Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Royalty percentage received on net sales of medicine				30%
Otsuka [Member] | Donidalorsen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next payment to be achieved	$ 15,000			$ 15,000
Otsuka [Member] | License of Donidalorsen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Transaction price		17,500
Revenue	$ 17,500
Otsuka [Member] | R&D Services for Donidalorsen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Transaction price		$ 2,500

Collaborative Arrangements an_6

Collaborative Arrangements and Licensing Agreements, Roche (Details) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2024 USD ($) Agreement	Sep. 30, 2023 USD ($)	Sep. 30, 2024 USD ($) Agreement	Sep. 30, 2023 USD ($)	Dec. 31, 2023 USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 133,814	$ 144,207	$ 478,562	$ 463,142
Roche [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement	3		3
Revenue	$ 11,084	$ 8,858	$ 33,679	$ 16,979
Deferred contract revenue	$ 4,500		$ 4,500		$ 36,700
Roche [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage	8%	6%	7%	4%
Roche [Member] | Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	$ 345,000		$ 345,000
HD [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement	1		1
IONIS-FB-L for Complement-Mediated Diseases [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement	1		1
Maximum amount of payments receivable over term of collaboration	$ 430,000		$ 430,000
Maximum amount of license fees over term of collaboration	35,000		35,000
Maximum amount of development milestone payments over term of collaboration	25,000		25,000
Maximum amount of regulatory milestone payments over term of collaboration	90,000		90,000
Maximum amount of sales milestone payments over term of collaboration	280,000		280,000
Next payment to be achieved	23,500		$ 23,500
Revenue	$ 8,500
RNA-targeted Programs for AD and HD [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement	1		1

Basic and Diluted Net Loss Pe_3

Basic and Diluted Net Loss Per Share (Details) - shares	1 Months Ended
	Sep. 30, 2024	Dec. 31, 2023	Sep. 30, 2023
Basic Net Loss per Share [Abstract]
Issuance of public common stock, net (in shares)	11,500,000
1.75% Notes [Member]
Diluted Net Loss per Share [Abstract]
Interest rate on convertible senior notes	1.75%	1.75%	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, 2024
Contract Maturity of Available-for-Sale Securities [Abstract]
One year or less	70%
After one year but within two years	23%
After two years but within three and a half years	7%
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	93%

Investments, Summary of Investm

Investments, Summary of Investments (Details) $ in Thousands		9 Months Ended
		Sep. 30, 2024 USD ($) Company	Dec. 31, 2023 USD ($)
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		$ 1,492,315	$ 1,316,219
Gross unrealized gains		2,885	415
Gross unrealized losses		(349)	(5,238)
Estimated fair value		1,494,851	1,311,396
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		687,173	651,628
Gross unrealized gains		3,186	3,063
Gross unrealized losses		(413)	(1,197)
Estimated fair value		689,946	653,494
Available-for-sale Debt Securities [Abstract]
Amortized cost		2,179,488	1,967,847
Gross unrealized gains		6,071	3,478
Gross unrealized losses		(762)	(6,435)
Estimated fair value		2,184,797	1,964,890
Equity Securities [Abstract]
Amortized cost		35,012	35,012
Gross unrealized gains		25,427	25,237
Gross unrealized losses		(11,717)	(10,957)
Estimated fair value		48,722	49,292
Available-for-sale Debt and Equity Securities [Abstract]
Amortized cost		2,214,500	2,002,859
Gross unrealized gains		31,498	28,715
Gross unrealized losses		(12,479)	(17,392)
Estimated fair value		2,233,519	2,014,182
Corporate Debt Securities [Member]
Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]
Amortized cost	[1]	653,028	559,967
Gross unrealized gains		1,120	157
Gross unrealized losses		(213)	(2,625)
Estimated fair value		653,935	557,499
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		433,542	243,151
Gross unrealized gains		1,813	1,270
Gross unrealized losses		(312)	(692)
Estimated fair value		435,043	243,729
Debt Securities Issued by U.S. Government Agencies [Member]
Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]
Amortized cost		149,658	224,711
Gross unrealized gains		464	64
Gross unrealized losses		(20)	(611)
Estimated fair value		150,102	224,164
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		78,241	110,138
Gross unrealized gains		526	547
Gross unrealized losses		(51)	(21)
Estimated fair value		78,716	110,664
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]	678,977	513,784
Gross unrealized gains		1,283	152
Gross unrealized losses		(114)	(1,889)
Estimated fair value		680,146	512,047
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		175,390	294,873
Gross unrealized gains		847	1,239
Gross unrealized losses		(50)	(480)
Estimated fair value		176,187	295,632
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		10,652	17,757
Gross unrealized gains		18	42
Gross unrealized losses		(2)	(113)
Estimated fair value		10,668	17,686
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost			3,466
Gross unrealized gains			7
Gross unrealized losses			(4)
Estimated fair value			3,469
Publicly Traded Equity Securities [Member]
Equity Securities [Abstract]
Amortized cost	[2]	11,897	11,897
Gross unrealized gains		426	236
Gross unrealized losses		(4,624)	(5,832)
Estimated fair value		7,699	6,301
Available-for-sale Debt and Equity Securities [Abstract]
Unrealized gain on equity securities		1,400
Privately Held Equity Securities [Member]
Equity Securities [Abstract]
Amortized cost	[3]	23,115	23,115
Gross unrealized gains		25,001	25,001
Gross unrealized losses		(7,093)	(5,125)
Estimated fair value		41,023	$ 42,991
Available-for-sale Debt and Equity Securities [Abstract]
Unrealized loss on equity securities		$ (2,000)
[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, 2024, we recorded a $1.4 million net unrealized gain in our condensed consolidated statements of operations related to changes in the fair value of our investments in publicly traded companies.[3] Our privately held equity securities are included in deposits and other assets. We recognize our privately held equity securities at . In the , we recorded a loss of $ million in our condensed consolidated statements of operations related to observable price changes of our investments in privately held companies.

Investments, Investments Tempor

Investments, Investments Temporarily Impaired (Details) $ in Thousands	Sep. 30, 2024 USD ($) Investment
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	255
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 431,132
More than 12 months of temporary impairment	110,562
Total temporary impairment	541,694
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(451)
More than 12 months of temporary impairment	(311)
Total temporary impairment	$ (762)
Corporate Debt Securities [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	209
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 331,968
More than 12 months of temporary impairment	47,159
Total temporary impairment	379,127
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(351)
More than 12 months of temporary impairment	(174)
Total temporary impairment	$ (525)
Debt Securities Issued by U.S. Government Agencies [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	26
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 49,966
More than 12 months of temporary impairment	3,068
Total temporary impairment	53,034
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(70)
More than 12 months of temporary impairment	(1)
Total temporary impairment	$ (71)
Debt Securities Issued by the U.S. Treasury [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	12
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 48,664
More than 12 months of temporary impairment	59,416
Total temporary impairment	108,080
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(30)
More than 12 months of temporary impairment	(134)
Total temporary impairment	$ (164)
Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	8
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 534
More than 12 months of temporary impairment	919
Total temporary impairment	1,453
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	0
More than 12 months of temporary impairment	(2)
Total temporary impairment	$ (2)

Fair Value Measurements (Detail

Fair Value Measurements (Details) - USD ($) $ in Thousands		Sep. 30, 2024		Dec. 31, 2023		Sep. 30, 2023
Fair Value Measurements [Abstract]
Available-for-sale securities		$ 2,184,797		$ 1,964,890
Equity securities		$ 48,722		$ 49,292
1.75% Notes [Member]
Fair Value Measurements [Abstract]
Interest rate on convertible senior notes		1.75%		1.75%		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		$ 7,699		$ 6,301
Recurring Basis [Member]
Fair Value Measurements [Abstract]
Cash equivalents	[1]	255,924		185,424
Total		2,448,420		2,156,615
Recurring Basis [Member] | Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		1,088,978	[2]	801,228	[3]
Recurring Basis [Member] | Corporate Debt Securities [Member] | Cash and Cash Equivalents [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		21,200		33,000
Recurring Basis [Member] | Debt Securities Issued by U.S. Government Agencies [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities	[4]	228,818		334,828
Recurring Basis [Member] | Debt Securities Issued by the U.S. Treasury [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		856,333	[5]	807,679	[4]
Recurring Basis [Member] | Debt Securities Issued by the U.S. Treasury [Member] | Cash and Cash Equivalents [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		14,900
Recurring Basis [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities	[4]	10,668		21,155
Recurring Basis [Member] | Publicly Traded Equity Securities [Member] | Other Current Assets [Member]
Fair Value Measurements [Abstract]
Equity securities	[6]	7,699		6,301
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member]
Fair Value Measurements [Abstract]
Cash equivalents		255,924		185,424
Total		1,119,956		999,404
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		856,333		807,679
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] | Publicly Traded Equity Securities [Member]
Fair Value Measurements [Abstract]
Equity securities		7,699		6,301
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member]
Fair Value Measurements [Abstract]
Cash equivalents		0		0
Total		1,328,464		1,157,211
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 1.75% Notes [Member]
Fair Value Measurements [Abstract]
Convertible notes		589,800		661,100
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 0% Notes [Member]
Fair Value Measurements [Abstract]
Convertible notes		630,700		667,800
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 0.125% Notes [Member]
Fair Value Measurements [Abstract]
Convertible notes		44,000		42,400
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		1,088,978		801,228
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		228,818		334,828
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		10,668		21,155
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.[2]$21.2 million was included in cash and cash equivalents, with the difference included in short-term investments.[3]$33.0 million was included in cash and cash equivalents, with the difference included in short-term investments.[4]Included in short-term investments.[5]$14.9 million was included in cash and cash equivalents, with the difference included in short-term investments.[6]Included in other current assets.

Stock-based Compensation Expe_3

Stock-based Compensation Expense (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2024	Sep. 30, 2023	Sep. 30, 2024	Sep. 30, 2023
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense, net of amounts capitalized	$ 31,984	$ 25,964	$ 94,052	$ 79,473
Capitalized stock-based compensation expense	506	0	506	0
Total stock-based compensation expense	32,490	25,964	94,558	79,473
Cost of Sales [Member]
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense, net of amounts capitalized	159	118	609	355
Research, Development and Patent Expense [Member]
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense, net of amounts capitalized	22,120	18,727	67,111	57,543
Selling, General and Administrative Expense [Member]
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense, net of amounts capitalized	9,705	$ 7,119	26,332	$ 21,575
Stock Options [Member]
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation expense related to non-vested stock options	54,100		$ 54,100
Weighted average period for recognition			1 year 2 months 12 days
Stock Options [Member] | Employees [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate			4.10%	3.70%
Dividend yield			0%	0%
Volatility			43.80%	47.10%
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			4.50%	3.80%
Dividend yield			0%	0%
Volatility			49.80%	53%
Expected life			7 years 6 months	7 years 8 months 12 days
ESPP [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate			5.20%	5.30%
Dividend yield			0%	0%
Volatility			37.80%	36%
Expected life			6 months	6 months
RSUs [Member]
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation cost related to non-vested units	87,200		$ 87,200
Weighted average period for recognition			1 year 6 months
RSUs [Member] | Employees [Member]
RSUs and PRSUs [Abstract]
Weighted-average grant date fair value (in dollars per share)			$ 52.08	$ 39.78
PRSUs [Member]
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation cost related to non-vested units	$ 12,100		$ 12,100
Weighted average period for recognition			1 year 8 months 12 days
PRSUs [Member] | Executive Officers [Member]
RSUs and PRSUs [Abstract]
Weighted-average grant date fair value (in dollars per share)			$ 78.41	$ 58.99
PRSUs [Member] | Granted in 2024 [Member]
RSUs and PRSUs [Abstract]
Vesting percentage			100%
Vesting period			3 years
Number of units guaranteed to vest (in shares)			0
PRSUs [Member] | Granted in 2024 [Member] | Minimum [Member]
RSUs and PRSUs [Abstract]
Percentage of units guaranteed to vest			0%
PRSUs [Member] | Granted in 2024 [Member] | Maximum [Member]
RSUs and PRSUs [Abstract]
Percentage of units guaranteed to vest			200%
PRSUs [Member] | Granted in 2023 [Member] | Executive Officers [Member]
RSUs and PRSUs [Abstract]
Vesting percentage			100%
Vesting period			3 years
Number of units guaranteed to vest (in shares)			0
PRSUs [Member] | Granted in 2023 [Member] | Executive Officers [Member] | Minimum [Member]
RSUs and PRSUs [Abstract]
Percentage of units guaranteed to vest			0%
PRSUs [Member] | Granted in 2023 [Member] | Executive 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, 2024	Sep. 30, 2023	Sep. 30, 2024	Sep. 30, 2023
Income Taxes [Abstract]
Income tax (benefit) expense	$ (3,621)	$ 6,602	$ (3,481)	$ 25,825

Liability Related to Sale of _3

Liability Related to Sale of Future Royalties (Details) - USD ($) $ in Thousands	1 Months Ended	9 Months Ended		12 Months Ended
	Jan. 31, 2023	Sep. 30, 2024	Sep. 30, 2023	Dec. 31, 2023
Royalty Revenue Monetization [Abstract]
Proceeds from sale of future royalties in January 2023		$ 0	$ 500,000
Issuance costs related to sale of future royalties		0	(10,434)
Royalty payments to Royalty Pharma		(30,422)	(27,814)
Interest expense related to sale of future royalties		54,330	$ 50,541
Net liability related to sale of future royalties		538,102		$ 513,736
Royalty Purchase Agreement [Member]
Royalty Revenue Monetization [Abstract]
Upfront payment received	$ 500,000
Maximum amount of payments receivable for additional milestones		$ 625,000
Effective interest rate		13.50%	13.50%
Proceeds from sale of future royalties in January 2023	$ 500,000
Issuance costs related to sale of future royalties				(10,434)
Royalty payments to Royalty Pharma		$ (30,422)		(44,628)
Interest expense related to sale of future royalties		54,330		68,238
Amortization of issuance costs related to sale of future royalties		458		560
Net liability related to sale of future royalties		538,102		$ 513,736
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	9 Months Ended		12 Months Ended
	Sep. 30, 2024	Sep. 30, 2023	Dec. 31, 2023	Dec. 31, 2021	Dec. 31, 2019
Convertible Debt [Abstract]
Proceeds from issuance of convertible senior notes	$ 0	$ 575,000
Repurchase of convertible senior notes	0	$ 487,943
1.75% Notes [Member]
Convertible Debt [Abstract]
Face amount of offering			$ 575,000
Proceeds from issuance of convertible senior notes			$ 488,200
Outstanding principal balance	575,000
Unamortized debt issuance costs	$ 10,700
Maturity date	Jun. 30, 2028
Interest rate	1.75%	1.75%	1.75%
Effective interest rate	2.30%
Conversion price per share (in dollars per share)	$ 53.73
Total shares of common stock subject to conversion (in shares)	10.7
Percentage of principal amount used as purchase price upon occurrence of fundamental change	100%
0% Notes [Member]
Convertible Debt [Abstract]
Face amount of offering				$ 632,500
Proceeds from issuance of convertible senior notes				319,000
Outstanding principal balance	$ 632,500
Unamortized debt issuance costs	$ 4,800
Maturity date	Apr. 30, 2026
Interest rate	0%	0%	0%
Effective interest rate	0.50%
Conversion price per share (in dollars per share)	$ 57.84
Effective conversion price per share with call spread (in dollars per share)	$ 76.39
Total shares of common stock subject to conversion (in shares)	10.9
Cost of call spread				46,900
Purchase of note hedges				136,700
Proceeds from issuance of warrants				89,800
Percentage of principal amount used as purchase price upon occurrence of fundamental change	100%
1% Notes [Member]
Convertible Debt [Abstract]
Repurchase of convertible senior notes				$ 309,900	$ 375,600
Interest rate				1%
0.125% Notes [Member]
Convertible Debt [Abstract]
Repurchase of convertible senior notes			$ 504,400
Principal amount repurchased		$ 504,400
Outstanding principal balance	$ 44,500
Unamortized debt issuance costs	$ 100
Maturity date	Dec. 31, 2024
Interest rate	0.125%	0.125%	0.125%
Effective interest rate	0.50%
Conversion price per share (in dollars per share)	$ 83.28
Effective conversion price per share with call spread (in dollars per share)	$ 123.38
Total shares of common stock subject to conversion (in shares)	0.5
Cost of call spread					52,600
Purchase of note hedges					108,700
Proceeds from issuance of warrants					56,100
Percentage of principal amount used as purchase price upon occurrence of fundamental change	100%
0.125% Notes Issued in Exchange for 1% Notes [Member]
Convertible Debt [Abstract]
Face amount of offering					439,300
0.125% Notes Issued under Subscription Agreements [Member]
Convertible Debt [Abstract]
Face amount of offering					$ 109,500

Public Common Stock Offering (D

Public Common Stock Offering (Details) - USD ($) $ / shares in Units, $ in Thousands	1 Months Ended	9 Months Ended
	Sep. 30, 2024	Sep. 30, 2024	Sep. 30, 2023
Public Common Stock Offering [Abstract]
Issuance of public common stock, net (in shares)	11,500,000
Share price (in dollars per share)	$ 43.5	$ 43.5
Net proceeds	$ 489,100	$ 489,093	$ 0
Underwriting discounts and commissions and other offering expenses	$ 11,200