IONS Ionis Pharmaceuticals Inc

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QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

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TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF SECURITIES EXCHANGE ACT OF 1934

Delaware		33-0336973
(State or other jurisdiction of incorporation or organization)		(IRS Employer Identification No.)

2855 Gazelle Court, Carlsbad, California		92010
(Address of Principal Executive Offices)		(Zip Code)

Title of each class		Trading symbol		Name of each exchange on which registered
Common Stock, $.001 Par Value		“IONS”		The Nasdaq Stock Market LLC

Large Accelerated Filer ☒	Accelerated Filer ☐
Non-accelerated Filer ☐	Smaller Reporting Company ☐
	Emerging Growth Company ☐

PART I	FINANCIAL INFORMATION
ITEM 1:	Financial Statements:
	Condensed Consolidated Balance Sheets as of March 31, 2024 (unaudited) and December 31, 2023	3
	Condensed Consolidated Statements of Operations for the three months ended March 31, 2024 and 2023 (unaudited)	4
	Condensed Consolidated Statements of Comprehensive Loss for the three months ended March 31, 2024 and 2023 (unaudited)	5
	Condensed Consolidated Statements of Stockholders’ Equity for the three months ended March 31, 2024 and 2023 (unaudited)	6
	Condensed Consolidated Statements of Cash Flows for the three months ended March 31, 2024 and 2023 (unaudited)	7
	Notes to Condensed Consolidated Financial Statements (unaudited)	8
ITEM 2:	Management’s Discussion and Analysis of Financial Condition and Results of Operations:
	Overview	19
	Critical Accounting Estimates	21
	Results of Operations	21
	Liquidity and Capital Resources	27
ITEM 3:	Quantitative and Qualitative Disclosures about Market Risk	29
ITEM 4:	Controls and Procedures	29
PART II	OTHER INFORMATION	29
ITEM 1:	Legal Proceedings	29
ITEM 1A:	Risk Factors	29
ITEM 2:	Unregistered Sales of Equity Securities and Use of Proceeds	45
ITEM 3:	Default upon Senior Securities	45
ITEM 4:	Mine Safety Disclosures	45
ITEM 5:	Other Information	46
ITEM 6:	Exhibits	47
SIGNATURES		48

ITEM 1.

FINANCIAL STATEMENTS

		March 31, 2024				December 31, 2023
		(unaudited)
ASSETS
Current assets:
Cash and cash equivalents		$	348,889			$	399,266
Short-term investments			1,857,327				1,931,935
Contracts receivable			5,140				97,778
Inventories			30,259				28,425
Other current assets			174,060				184,449
Total current assets			2,415,675				2,641,853
Property, plant and equipment, net			72,795				71,043
Right-of-use assets			169,431				171,896
Deposits and other assets			106,027				105,280
Total assets		$	2,763,928			$	2,990,072
LIABILITIES AND STOCKHOLDERS’ EQUITY
Current liabilities:
Accounts payable		$	13,082			$	26,027
Accrued compensation			21,537				67,727
Accrued liabilities			106,048				147,894
Income taxes payable			2,210				2,151
0.125 percent convertible senior notes, net			44,377				44,332
Current portion of deferred contract revenue			130,406				151,128
Other current liabilities			9,988				8,831
Total current liabilities			327,648				448,090
Long-term deferred contract revenue			215,088				241,184
1.75 percent convertible senior notes, net			562,964				562,285
0 percent convertible senior notes, net			626,167				625,380
Liability related to sale of future royalties, net			525,072				513,736
Long-term lease liabilities			168,674				170,875
Long-term obligations			41,800				41,836
Total liabilities			2,467,413				2,603,386
Stockholders’ equity:
Common stock, $0.001 par value; 300,000,000 shares authorized, 145,844,719 and 144,340,526 shares issued and outstanding at March 31, 2024 (unaudited) and December 31, 2023, respectively			146				144
Additional paid-in capital			2,270,047				2,215,098
Accumulated other comprehensive loss			(34,964	)			(32,645	)
Accumulated deficit			(1,938,714	)			(1,795,911	)
Total stockholders’ equity			296,515				386,686
Total liabilities and stockholders’ equity		$	2,763,928			$	2,990,072

		Three Months Ended March 31,
		2024				2023
Revenue:
Commercial revenue:
SPINRAZA royalties		$	38,455			$	50,247
WAINUA royalties			1,125				—
Other commercial revenue			20,013				17,521
Total commercial revenue			59,593				67,768
Research and development revenue:
Collaborative agreement revenue			49,345				38,334
WAINUA joint development revenue			10,559				24,422
Total research and development revenue			59,904				62,756
Total revenue			119,497				130,524
Expenses:
Cost of sales			2,151				1,343
Research, development and patent			214,215				197,813
Selling, general and administrative			52,644				45,516
Total operating expenses			269,010				244,672
Loss from operations			(149,513	)			(114,148	)
Other income (expense):
Investment income			26,285				18,627
Interest expense			(4,151	)			(1,608	)
Interest expense related to sale of future royalties			(17,959	)			(15,515	)
Gain (loss) on investments			2,333				(529	)
Other income			277				230
Loss before income tax expense			(142,728	)			(112,943	)
Income tax expense			(75	)			(11,380	)
Net loss		$	(142,803	)		$	(124,323	)
Basic and diluted net loss per share		$	(0.98	)		$	(0.87	)
Shares used in computing basic and diluted net loss per share			145,538				142,735

		Three Months Ended March 31,
		2024				2023
Net loss		$	(142,803	)		$	(124,323	)
Unrealized losses on debt securities, net of tax			(2,205	)			8,393
Currency translation adjustment			(114	)			104
Comprehensive loss		$	(145,122	)		$	(115,826	)

		Common Stock								Additional				Accumulated Other				Accumulated				Total Stockholders’
Description		Shares				Amount				Paid in Capital				Comprehensive Loss				Deficit				Equity
Balance at December 31, 2022			142,058			$	142			$	2,059,850			$	(57,480	)		$	(1,429,625	)		$	572,887
Net loss			—				—				—				—				(124,323	)			(124,323	)
Change in unrealized losses, net of tax			—				—				—				8,393				—				8,393
Foreign currency translation			—				—				—				104				—				104
Issuance of common stock in connection with employee stock plans			965				1				2,560				—				—				2,561
Stock-based compensation expense			—				—				26,948				—				—				26,948
Balance at March 31, 2023			143,023			$	143			$	2,089,358			$	(48,983	)		$	(1,553,948	)		$	486,570
Balance at December 31, 2023			144,341			$	144			$	2,215,098			$	(32,645	)		$	(1,795,911	)		$	386,686
Net loss			—				—				—				—				(142,803	)			(142,803	)
Change in unrealized losses, net of tax			—				—				—				(2,205	)			—				(2,205	)
Foreign currency translation			—				—				—				(114	)			—				(114	)
Issuance of common stock in connection with employee stock plans			1,504				2				23,609				—				—				23,611
Stock-based compensation expense			—				—				31,340				—				—				31,340
Balance at March 31, 2024			145,845			$	146			$	2,270,047			$	(34,964	)		$	(1,938,714	)		$	296,515

		Three Months Ended March 31,
		2024				2023
Operating activities:
Net loss		$	(142,803	)		$	(124,323	)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation			2,547				2,604
Amortization of right-of-use operating lease assets			2,465				2,395
Amortization of other assets			639				607
Amortization of discount on investments, net			(9,257	)			(5,042	)
Amortization of debt issuance costs			1,667				1,486
Non-cash royalty revenue related to sale of royalties			(6,623	)			—
Non-cash interest related to sale of future royalties			17,806				15,363
Stock-based compensation expense			31,340				26,948
Loss (gain) on investments			(2,332	)			529
Non-cash losses related to other assets			133				445
Changes in operating assets and liabilities:
Contracts receivable			92,638				11,624
Inventories			(1,834	)			(167	)
Other current and long-term assets			13,381				5,312
Income taxes			59				11,037
Accounts payable			(13,869	)			(10,295	)
Accrued compensation			(46,190	)			(31,018	)
Accrued liabilities and other current liabilities			(42,887	)			(28,460	)
Deferred contract revenue			(46,818	)			(13,037	)
Net cash used in operating activities			(149,938	)			(133,992	)
Investing activities:
Purchases of short-term investments			(519,001	)			(688,278	)
Proceeds from sale of short-term investments			600,836				374,363
Purchases of property, plant and equipment			(4,493	)			(10,472	)
Acquisition of licenses and other assets, net			(1,237	)			(1,253	)
Net cash provided by (used in) investing activities			76,105				(325,640	)
Financing activities:
Proceeds from equity, net			23,609				2,560
Proceeds from sale of future royalties			—				500,000
Payments of transaction costs related to sale of future royalties			—				(10,434	)
Principal payments on mortgage debt			(39	)			(39	)
Net cash provided by financing activities			23,570				492,087
Effects of exchange rates on cash			(114	)			104
Net increase (decrease) in cash and cash equivalents			(50,377	)			32,559
Cash and cash equivalents at beginning of period			399,266				276,472
Cash and cash equivalents at end of period		$	348,889			$	309,031
Supplemental disclosures of cash flow information:
Interest paid		$	95			$	89
Income taxes paid		$	13			$	293
Supplemental disclosures of non-cash investing and financing activities:
Amounts accrued for capital and patent expenditures		$	924			$	3,058

ITEM 2.

MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

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Assessing the propriety of revenue recognition and associated deferred revenue;

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Determining the appropriate cost estimates for unbilled preclinical studies and clinical development activities; and

●

Assessing the appropriate estimate of anticipated future royalty payments under our royalty purchase agreement

		Three Months Ended March 31
		2024				2023
Total revenue		$	119.5			$	130.5
Total operating expenses		$	269.0			$	244.7
Loss from operations		$	(149.5	)		$	(114.1	)
Net loss		$	(142.8	)		$	(124.3	)

		Three Months Ended March 31,
		2024				2023
Revenue:
Commercial revenue:
SPINRAZA royalties		$	38.5			$	50.2
WAINUA royalties			1.1				—
Other commercial revenue:
TEGSEDI and WAYLIVRA revenue, net			8.6				6.5
Licensing and other royalty revenue			11.4				11.0
Total other commercial revenue			20.0				17.5
Total commercial revenue			59.6				67.7
Research and development revenue:
Amortization from upfront payments			41.5				15.6
Milestone payments			7.0				22.5
Other services			0.8				0.3
Collaborative agreement revenue			49.3				38.4
WAINUA joint development revenue			10.6				24.4
Total research and development revenue			59.9				62.8
Total revenue		$	119.5			$	130.5

		Three Months Ended March 31,
		2024				2023
WAINUA joint development revenue		$	10.6			$	24.4
Research and development expenses related to Phase 3 development of WAINUA			22.7				47.1
Medical affairs expenses for WAINUA			1.3				0.7
Commercialization expenses for WAINUA			6.0				1.3

		Three Months Ended March 31,
		2024				2023
Operating expenses, excluding non-cash compensation expense related to equity awards		$	237.7			$	217.7
Non-cash compensation expense related to equity awards			31.3				27.0
Total operating expenses		$	269.0			$	244.7

		Three Months Ended March 31,
		2024				2023
Cost of sales, excluding non-cash compensation expense related to equity awards		$	2.0			$	1.2
Non-cash compensation expense related to equity awards			0.2				0.1
Total cost of sales		$	2.2			$	1.3

		Three Months Ended March 31,
		2024				2023
Research, development and patent expenses, excluding non-cash compensation expense related to equity awards		$	192.0			$	178.2
Non-cash compensation expense related to equity awards			22.2				19.6
Total research, development and patent expenses		$	214.2			$	197.8

		Three Months Ended March 31,
		2024				2023
Drug discovery expenses, excluding non-cash compensation expense related to equity awards		$	28.2			$	24.6
Non-cash compensation expense related to equity awards			4.3				3.9
Total drug discovery expenses		$	32.5			$	28.5

		Three Months Ended March 31,
		2024				2023
WAINUA		$	21.7			$	37.0
Olezarsen			39.5				26.8
Donidalorsen			4.8				5.3
Zilganersen			2.1				1.7
Ulefnersen			3.5				2.3
Other development projects			25.1				17.4
Development overhead expenses			29.1				25.1
Total drug development expenses, excluding non-cash compensation expense related to equity awards			125.8				115.6
Non-cash compensation expense related to equity awards			10.4				8.8
Total drug development expenses		$	136.2			$	124.4

		Three Months Ended March 31,
		2024				2023
Medical affairs expenses, excluding non-cash compensation expense related to equity awards		$	4.7			$	4.3
Non-cash compensation expense related to equity awards			0.9				1.0
Total medical affairs expenses		$	5.6			$	5.3

		Three Months Ended March 31,
		2024				2023
Manufacturing and development chemistry expenses, excluding non-cash compensation expense related to equity awards		$	11.4			$	14.7
Non-cash compensation expense related to equity awards			2.3				2.1
Total manufacturing and development chemistry expenses		$	13.7			$	16.8

		Three Months Ended March 31,
		2024				2023
Personnel costs		$	7.8			$	6.5
Occupancy			7.1				7.3
Computer software and licenses			1.6				0.6
Insurance			0.9				0.9
Patent expenses			0.7				1.1
Consulting expenses			0.6				0.3
Other			3.2				2.3
Total R&D support expenses, excluding non-cash compensation expense related to equity awards			21.9				19.0
Non-cash compensation expense related to equity awards			4.3				3.8
Total R&D support expenses		$	26.2			$	22.8

		Three Months Ended March 31,
		2024				2023
Selling, general and administrative expenses, excluding non-cash compensation expense related to equity awards		$	43.7			$	38.2
Non-cash compensation expense related to equity awards			8.9				7.3
Total selling, general and administrative expenses		$	52.6			$	45.5

		Three Months Ended March 31,
		2024				2023
Convertible notes:
Non-cash amortization of debt issuance costs		$	1.6			$	1.3
Interest expense payable in cash			2.5				0.2
Interest on mortgage for manufacturing facility			0.1				0.1
Total interest expense		$	4.2			$	1.6

Contractual Obligations		Payments Due by Period (in millions)
(selected balances described below)		Total				Less than 1 year				More than 1 year
1.75% Notes (principal and interest payable)		$	620.3			$	10.1			$	610.2
0% Notes (principal payable)			632.5				—				632.5
0.125% Notes (principal and interest payable)			44.6				44.6				—
Operating leases			274.9				20.6				254.3
Building mortgage payments (principal and interest payable)			10.1				0.5				9.6
Other obligations (principal and interest payable)			0.7				0.1				0.6
Total		$	1,583.1			$	75.9			$	1,507.2

ITEM 4.

CONTROLS AND PROCEDURES

ITEM 1.

LEGAL PROCEEDINGS

ITEM 1A.

RISK FACTORS

●

Our ability to generate substantial revenue from the sale of our medicines;

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Τhe availability of adequate coverage and payment rates for our medicines;

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Our and our partners’ ability to compete effectively;

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Our ability to successfully manufacture our medicines;

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Our ability to successfully develop and obtain marketing approvals for our medicines;

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Our ability to secure and maintain effective corporate partnerships;

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Our ability to sustain cash flows and achieve consistent profitability;

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Our ability to protect our intellectual property;

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Our ability to maintain the effectiveness of our personnel;

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The impacts of health epidemics, climate change, war and other global events; and

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The other factors set forth below.

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receipt and scope of marketing authorizations;

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establishment and demonstration in the medical and patient community of the efficacy and safety of our medicines and their potential advantages over competing products;

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cost and effectiveness of our medicines compared to other available therapies;

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patient convenience of the dosing regimen for our medicines; and

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reimbursement policies of government and third-party payers.

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priced lower than our medicines;

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reimbursed more favorably by government and other third-party payers than our medicines;

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safer than our medicines;

●

more effective than our medicines; or

●

more convenient to use than our medicines.

●

Onasemnogene abeparvovec and risdiplam compete with SPINRAZA;

●

Taldefgrobep alfa, Evrysdi + GYM329 and NMD670 could compete with SPINRAZA;

●

Patisiran, tafamidis, tafamidis meglumine and vutrisiran compete with TEGSEDI and WAINUA;

●

Acoramidis, NTLA-2001 and NNC6019-0001 could compete with TEGSEDI and WAINUA;

●

ARO-APOC3 and pegozafermin could compete with WAYLIVRA and olezarsen;

●

Lanadelumab-flyo, C1 esterase inhibitor, berotralstat, C1 esterase inhibitor subcutaneous, garadacimab, deucrictibant,  NTLA-2002 and STAR-0215 could compete with donidalorsen;

●

Olpasiran, zerlasiran, lepodisiran and muvalaplin could compete with pelacarsen;

●

NI-005/AP-101 could compete with QALSODY;

●

VIR-2218 + PEG-IFN-α, VIR-3434 ± VIR-2218 ± PEG-IFN-α, VIR-2218 + BRII-179, NI-204VIR-2218 + GS-9688 + nivolumab, AB-729, imdusiran + Peg-IFNa-2α + NA, xalnesiran + RG6084 + NA, xalnesiran + NA, xalnesiran + pegIFN + NA, xalnesiran + RO7049389 + NA, xalnesiran + ruzotolimod + NA, RO7049389 + ruzotolimod + NA could complete with bepirovirsen; and

●

Budesonide, sparsentan, atrasentan, iptacopan, zigakibart, sibeprenlimab, atacicept, ravulizumab, vemircopan, felzartamab, povetacicept, avacincaptad pegol, pegcetacoplan, tinlarebant, danicopan, GT005, AVD-104 and ANX007 could compete with IONIS-FB-LRx.

●

in the U.S., TEGSEDI’s label contains a boxed warning for thrombocytopenia and glomerulonephritis;

●

TEGSEDI requires periodic blood and urine monitoring; and

●

in the U.S., TEGSEDI is available only through a REMS program.

●

fund our development activities for SPINRAZA and QALSODY;

●

seek and obtain regulatory approvals for SPINRAZA and QALSODY; and

●

successfully commercialize SPINRAZA and QALSODY.

●

such authorities may disagree with the design or implementation of our clinical studies;

●

we or our partners may be unable to demonstrate to the satisfaction of the FDA or other regulatory authorities that a medicine is safe and effective for any indication;

●

such authorities may not accept clinical data from studies conducted at clinical facilities that have deficient clinical practices or that are in countries where the standard of care is potentially different from the U.S.;

●

we or our partners may be unable to demonstrate that our medicine’s clinical and other benefits outweigh its safety risks to support approval;

●

such authorities may disagree with the interpretation of data from preclinical or clinical studies;

●

such authorities may find deficiencies in the manufacturing processes or facilities of third-party manufacturers who manufacture clinical and commercial supplies for our medicines; and

●

the approval policies or regulations of such authorities or their prior guidance to us or our partners during clinical development may significantly change in a manner rendering our clinical data insufficient for approval.

●

the clinical study may produce negative or inconclusive results;

●

regulators may require that we hold, suspend or terminate clinical research for noncompliance with regulatory requirements;

●

we, our partners, the FDA or foreign regulatory authorities could suspend or terminate a clinical study due to adverse side effects of a medicine on subjects or lack of efficacy in the trial;

●

we or our partners may decide, or regulators may require us, to conduct additional preclinical testing or clinical studies;

●

enrollment in our clinical studies may be slower than we anticipate;

●

we or our partners, including our independent clinical investigators, contract research organizations and other third-party service providers on which we rely, may not identify, recruit or train suitable clinical investigators at a sufficient number of study sites or timely enroll a sufficient number of study subjects in the clinical study;

●

the institutional review board for a prospective site might withhold or delay its approval for the study;

●

people who enroll in the clinical study may later drop out due to adverse events, a perception they are not benefiting from participating in the study, fatigue with the clinical study process or personal issues;

●

a clinical study site may deviate from the protocol for the study;

●

the cost of our clinical studies may be greater than we anticipate;

●

our partners may decide not to exercise any existing options to license and conduct additional clinical studies for our medicines; and

●

the supply or quality of our medicines or other materials necessary to conduct our clinical studies may be insufficient, inadequate or delayed.

●

AstraZeneca for the joint development and funding of WAINUA;

●

Novartis for development and funding of pelacarsen;

●

GSK for development and funding of bepirovirsen; and

●

Roche for development and funding of IONIS-FB-LRx.

●

conduct clinical studies;

●

seek and obtain marketing authorizations; and

●

manufacture and commercialize our medicines.

●

pursue alternative technologies or develop alternative products that may be competitive with the medicine that is part of the collaboration with us;

●

pursue higher-priority programs or change the focus of its own development programs; or

●

choose to devote fewer resources to our medicines than it does to its own medicines.

●

successful commercialization of our commercial medicines;

●

the profile and launch timing of our medicines in development;

●

changes in existing collaborative relationships and our ability to establish and maintain additional collaborative arrangements;

●

continued scientific progress in our research, drug discovery and development programs;

●

the size of our programs and progress with preclinical and clinical studies;

●

the time and costs involved in obtaining marketing authorizations;

●

competing technological and market developments, including the introduction by others of new therapies that address our markets; and

●

our manufacturing requirements and capacity to fulfill such requirements.

●

compliance with differing or unexpected regulatory requirements for our medicines and foreign employees;

●

complexities associated with managing multiple payer reimbursement regimes, government payers or patient self-pay systems;

●

difficulties in staffing and managing foreign operations;

●

in certain circumstances, increased dependence on the commercialization efforts and regulatory compliance of third-party distributors or strategic partners;

●

foreign government taxes, regulations and permit requirements;

●

U.S. and foreign government tariffs, trade and export restrictions, price and exchange controls and other regulatory requirements;

●

anti-corruption laws, including the Foreign Corrupt Practices Act, or the FCPA, and its equivalent in foreign jurisdictions;

●

economic weakness, including inflation, natural disasters, war, acts of terrorism, political instability or public health issues or health epidemics, in particular foreign countries or globally;

●

fluctuations in currency exchange rates, which could result in increased operating expenses and reduced revenue, and other obligations related to doing business in another country;

●

compliance with tax, employment, privacy, immigration and labor laws, regulations and restrictions for employees living or traveling abroad;

●

workforce uncertainty in countries where labor unrest is more common than in the U.S.; and

●

changes in diplomatic and trade relationships.

●

interruption of our research, development and manufacturing efforts;

●

injury to our employees and others;

●

environmental damage resulting in costly clean up; and

●

liabilities under federal, state and local laws and regulations governing health and human safety, as well as the use, storage, handling and disposal of these materials and resultant waste products.

ITEM 2.

UNREGISTERED SALES OF EQUITY SECURITIES AND USE OF PROCEEDS

ITEM 3.

DEFAULT UPON SENIOR SECURITIES

ITEM 4.

MINE SAFETY DISCLOSURES

ITEM 5.

OTHER INFORMATION

a.

Exhibits

Exhibit Number		Description of Document
10.1		Advisory Services Agreement by and between the Registrant and Onaiza Cadoret-Manier dated March 15, 2024.
31.1		Certification by Chief Executive Officer pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as amended.
31.2		Certification by Chief Financial Officer pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as amended.
32.1*		Certification Pursuant to 18 U.S.C. Section 1350 as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.
101		The following financial statements from the Ionis Pharmaceuticals, Inc. Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, formatted in Inline Extensible Business Reporting Language (iXBRL): (i) condensed consolidated balance sheets, (ii) condensed consolidated statements of operations, (iii) condensed consolidated statements of comprehensive income (loss), (iv) condensed consolidated statements of stockholders’ equity, (v) condensed consolidated statements of cash flows and (vi) notes to condensed consolidated financial statements (detail tagged).
104		Cover Page Interactive Data File (formatted in iXBRL and included in exhibit 101).

*

This certification is deemed not filed for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liability of that section, nor shall it be deemed incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended.

Signatures		Title		Date
/s/ BRETT P. MONIA		Director and Chief Executive Officer
Brett P. Monia, Ph.D.		(Principal executive officer)		May 7, 2024
/s/ ELIZABETH L. HOUGEN		Executive Vice President, Finance and Chief Financial Officer
Elizabeth L. Hougen		(Principal financial and accounting officer)		May 7, 2024

v3.24.1.u1

Document and Entity Information - shares	3 Months Ended
	Mar. 31, 2024	May 01, 2024
Cover [Abstract]
Document Type	10-Q
Amendment Flag	false
Document Quarterly Report	true
Document Period End Date	Mar. 31, 2024
Current Fiscal Year End Date	--12-31
Document Fiscal Year Focus	2024
Document Fiscal Period Focus	Q1
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		145,965,374

v3.24.1.u1

CONDENSED CONSOLIDATED BALANCE SHEETS - USD ($) $ in Thousands	Mar. 31, 2024	Dec. 31, 2023
Current assets:
Cash and cash equivalents	$ 348,889	$ 399,266
Short-term investments	1,857,327	1,931,935
Contracts receivable	5,140	97,778
Inventories	30,259	28,425
Other current assets	174,060	184,449
Total current assets	2,415,675	2,641,853
Property, plant and equipment, net	72,795	71,043
Right-of-use assets	169,431	171,896
Deposits and other assets	106,027	105,280
Total assets	2,763,928	2,990,072
Current liabilities:
Accounts payable	13,082	26,027
Accrued compensation	21,537	67,727
Accrued liabilities	106,048	147,894
Income taxes payable	2,210	2,151
0.125 percent convertible senior notes, net	44,377	44,332
Current portion of deferred contract revenue	130,406	151,128
Other current liabilities	9,988	8,831
Total current liabilities	327,648	448,090
Long-term deferred contract revenue	215,088	241,184
Liability related to sale of future royalties, net	525,072	513,736
Long-term lease liabilities	168,674	170,875
Long-term obligations	41,800	41,836
Total liabilities	2,467,413	2,603,386
Stockholders' equity:
Common stock, $0.001 par value; 300,000,000 shares authorized, 145,844,719 and 144,340,526 shares issued and outstanding at March 31, 2024 (unaudited) and December 31, 2023, respectively	146	144
Additional paid-in capital	2,270,047	2,215,098
Accumulated other comprehensive loss	(34,964)	(32,645)
Accumulated deficit	(1,938,714)	(1,795,911)
Total stockholders' equity	296,515	386,686
Total liabilities and stockholders' equity	2,763,928	2,990,072
1.75 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	562,964	562,285
0 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	$ 626,167	$ 625,380

v3.24.1.u1

CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares	Mar. 31, 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)	145,844,719	144,340,526
Common stock, shares outstanding (in shares)	145,844,719	144,340,526
1.75 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	1.75%
0 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	0.00%	0.00%
0.125 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	0.125%	0.125%

v3.24.1.u1

CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS - USD ($) shares in Thousands, $ in Thousands	3 Months Ended
	Mar. 31, 2024	Mar. 31, 2023
Revenue:
Revenue	$ 119,497	$ 130,524
Expenses:
Cost of sales	2,151	1,343
Research, development and patent	214,215	197,813
Selling, general and administrative	52,644	45,516
Total operating expenses	269,010	244,672
Loss from operations	(149,513)	(114,148)
Other income (expense):
Investment income	26,285	18,627
Interest expense	(4,151)	(1,608)
Interest expense related to sale of future royalties	(17,959)	(15,515)
Gain (loss) on investments	2,333	(529)
Other income	277	230
Loss before income tax expense	(142,728)	(112,943)
Income tax expense	(75)	(11,380)
Net loss	$ (142,803)	$ (124,323)
Basic net loss per share (in dollars per share)	$ (0.98)	$ (0.87)
Diluted net loss per share (in dollars per share)	$ (0.98)	$ (0.87)
Shares used in computing basic net loss per share (in shares)	145,538	142,735
Shares used in computing diluted net loss per share (in shares)	145,538	142,735
Commercial Revenue [Member]
Revenue:
Revenue	$ 59,593	$ 67,768
SPINRAZA Royalties [Member]
Revenue:
Revenue	38,455	50,247
WAINUA Royalties [Member]
Revenue:
Revenue	1,125	0
Other Commercial Revenue [Member]
Revenue:
Revenue	20,013	17,521
Research and Development Revenue [Member]
Revenue:
Revenue	59,904	62,756
Collaborative Agreement Revenue [Member]
Revenue:
Revenue	49,345	38,334
WAINUA Joint Development Revenue [Member]
Revenue:
Revenue	$ 10,559	$ 24,422

v3.24.1.u1

CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($) $ in Thousands	3 Months Ended
	Mar. 31, 2024	Mar. 31, 2023
CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS [Abstract]
Net loss	$ (142,803)	$ (124,323)
Unrealized losses on debt securities, net of tax	(2,205)	8,393
Currency translation adjustment	(114)	104
Comprehensive loss	$ (145,122)	$ (115,826)

v3.24.1.u1

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	(124,323)	(124,323)
Change in unrealized losses, net of tax	0	0	8,393	0	8,393
Foreign currency translation	0	0	104	0	104
Issuance of common stock in connection with employee stock plans	$ 1	2,560	0	0	2,561
Issuance of common stock in connection with employee stock plans (in shares)	965
Stock-based compensation expense	$ 0	26,948	0	0	26,948
Balance at Mar. 31, 2023	$ 143	2,089,358	(48,983)	(1,553,948)	486,570
Balance (in shares) at Mar. 31, 2023	143,023
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	(142,803)	(142,803)
Change in unrealized losses, net of tax	0	0	(2,205)	0	(2,205)
Foreign currency translation	0	0	(114)	0	(114)
Issuance of common stock in connection with employee stock plans	$ 2	23,609	0	0	23,611
Issuance of common stock in connection with employee stock plans (in shares)	1,504
Stock-based compensation expense	$ 0	31,340	0	0	31,340
Balance at Mar. 31, 2024	$ 146	$ 2,270,047	$ (34,964)	$ (1,938,714)	$ 296,515
Balance (in shares) at Mar. 31, 2024	145,845

v3.24.1.u1

CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	3 Months Ended		12 Months Ended
	Mar. 31, 2024	Mar. 31, 2023	Dec. 31, 2023
Operating activities:
Net loss	$ (142,803)	$ (124,323)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation	2,547	2,604
Amortization of right-of-use operating lease assets	2,465	2,395
Amortization of other assets	639	607
Amortization of discount on investments, net	(9,257)	(5,042)
Amortization of debt issuance costs	1,667	1,486
Non-cash royalty revenue related to sale of royalties	(6,623)	0
Non-cash interest related to sale of future royalties	17,806	15,363
Stock-based compensation expense	31,340	26,948
Loss (gain) on investments	(2,332)	529
Non-cash losses related to other assets	133	445
Changes in operating assets and liabilities:
Contracts receivable	92,638	11,624
Inventories	(1,834)	(167)
Other current and long-term assets	13,381	5,312
Income taxes payable	59	11,037
Accounts payable	(13,869)	(10,295)
Accrued compensation	(46,190)	(31,018)
Accrued liabilities and other current liabilities	(42,887)	(28,460)
Deferred contract revenue	(46,818)	(13,037)
Net cash used in operating activities	(149,938)	(133,992)
Investing activities:
Purchases of short-term investments	(519,001)	(688,278)
Proceeds from sale of short-term investments	600,836	374,363
Purchases of property, plant and equipment	(4,493)	(10,472)
Acquisition of licenses and other assets, net	(1,237)	(1,253)
Net cash provided by (used in) investing activities	76,105	(325,640)
Financing activities:
Proceeds from equity, net	23,609	2,560
Proceeds from sale of future royalties	0	500,000
Payments of transaction costs related to sale of future royalties	0	(10,434)
Principal payments on mortgage debt	(39)	(39)
Net cash provided by financing activities	23,570	492,087
Effects of exchange rates on cash	(114)	104
Net increase (decrease) in cash and cash equivalents	(50,377)	32,559
Cash and cash equivalents at beginning of period	399,266	276,472	$ 276,472
Cash and cash equivalents at end of period	348,889	309,031	$ 399,266
Supplemental disclosures of cash flow information:
Interest paid	95	89
Income taxes paid	13	293
Supplemental disclosures of non-cash investing and financing activities:
Amounts accrued for capital and patent expenditures	$ 924	$ 3,058

v3.24.1.u1

Organization and Basis of Presentation	3 Months Ended
	Mar. 31, 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 months ended March 31, 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 segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment. Use of Estimates We prepare our condensed consolidated financial statements in conformity with accounting principles generally accepted in the United States, or U.S., that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying notes. Actual results could differ from our estimates.

v3.24.1.u1

Significant Accounting Policies	3 Months Ended
	Mar. 31, 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 Adopted Accounting Standards We do not expect any recently issued accounting standards to have a material impact to our financial results.

v3.24.1.u1

Supplemental Financial Data	3 Months Ended
	Mar. 31, 2024
Supplemental Financial Data [Abstract]
Supplemental Financial Data	3. Supplemental Financial Data Inventories Our inventory consisted of the following (in thousands):   March 31, 2024     December 31, 2023   Raw materials:             Raw materials - clinical   $ 23,317     $ 20,985   Raw materials - commercial     705       1,809   Total raw materials     24,022       22,794   Work in process     6,037       5,477   Finished goods     200       154   Total inventories   $ 30,259     $ 28,425   Accrued Liabilities Our accrued liabilities consisted of the following (in thousands):   March 31, 2024     December 31, 2023   Clinical development expenses   $ 75,929     $ 105,967   In-licensing expenses     6,436       7,454   Commercial expenses     4,739       4,875   Other miscellaneous expenses     18,944       29,598   Total accrued liabilities   $ 106,048     $ 147,894

v3.24.1.u1

Revenues	3 Months Ended
	Mar. 31, 2024
Revenues [Abstract]
Revenues	4. Revenues During the three months ended March 31, 2024 and 2023, our revenues were comprised of the following (in thousands):   Three Months Ended March 31,       2024     2023   Revenue:             Commercial revenue:             SPINRAZA royalties   $ 38,455     $ 50,247   WAINUA royalties     1,125       —   Other commercial revenue:                 TEGSEDI and WAYLIVRA revenue, net     8,628       6,478   Licensing and other royalty revenue     11,385       11,043   Total other commercial revenue     20,013       17,521   Total commercial revenue     59,593       67,768   Research and development revenue:                 Collaborative agreement revenue     49,345       38,334   WAINUA joint development revenue     10,559       24,422   Total research and development revenue     59,904       62,756   Total revenue   $ 119,497     $ 130,524   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 from WAINUA sales. 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: When we enter into a collaboration agreement and receive an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation is for R&D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&D services. If part or all of the upfront payment is a license fee, we recognize as revenue the portion related to the license when we deliver the license to our partner because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. Milestone payments: We include variable consideration in the transaction price when it is probable. We typically include milestone payments for R&D services in the transaction price when they are achieved. We include these milestone payments when they are achieved because typically there is considerable uncertainty in the R&D processes that trigger these payments. Similarly, we include approval milestone payments in the transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting rules. We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, when we achieve a milestone payment from a partner for advancing a clinical study under a collaboration agreement, we add the milestone payment to the transaction price if the milestone relates to an ongoing R&D services performance obligation and recognize revenue related to the milestone payment over our estimated period of performance. If we have partially completed our performance obligation, then we record a cumulative-effect adjustment in the period we add the milestone payment to the transaction price. Conversely, we recognize in full those milestone payments that we earn based on our partners’ activities when our partner achieves the milestone event and we do not have a performance obligation. License fees: We recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery. 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 preparing to commercialize WAINUA with AstraZeneca in the U.S. We initially granted AstraZeneca exclusive rights to commercialize WAINUA outside the U.S., except for certain Latin American countries. In 2023, we expanded those rights to include Latin America. Under the terms of the agreement, we received a $200 million upfront payment in 2021. We evaluated our WAINUA collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing. We determined that we had a vendor-customer relationship within the scope of Accounting Standards Codification, or ASC, Topic 606, Revenue from Contracts with Customers, or ASC 606, for the license we granted to AstraZeneca and as a result we had one performance obligation. For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations after we delivered the license to AstraZeneca. We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within the scope of ASC Topic 808, Collaborative Arrangements, or ASC 808, because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is currently responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we made an accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca, net of our share of AstraZeneca’s development expenses, in the same period we incur the related development expenses. As AstraZeneca is responsible for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing WAINUA to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca related to commercial and medical affairs activities as reductions of our selling, general and administrative, or SG&A, expense and R&D expense, respectively.

v3.24.1.u1

Collaborative Arrangements and Licensing Agreements	3 Months Ended
	Mar. 31, 2024
Collaborative Arrangements and Licensing Agreements [Abstract]
Collaborative Arrangements and Licensing Agreements	5.  Collaborative Arrangements and Licensing Agreements Below, we have included our AstraZeneca and Biogen 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 two collaborations with AstraZeneca, one focused on the joint development and commercialization of WAINUA for the treatment of transthyretin amyloidosis, or ATTR, and one focused on the treatment of cardiovascular, renal and metabolic diseases. From inception through March 31, 2024, we have received nearly $910 million from these collaborations. In January 2024, we and AstraZeneca launched WAINUA in the U.S. for the treatment of adults with polyneuropathy caused by hereditary transthyretin amyloidosis, or 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. We will achieve the next payment of up to $30 million upon regulatory approval of WAINUA for ATTRv-PN in the European Union, or EU, under this collaboration. During the three months ended March 31, 2024 and 2023, we earned the following revenue from our relationship with AstraZeneca (in thousands, except percentage amounts):   Three Months Ended March 31,       2024     2023   Revenue from our relationship with AstraZeneca   $ 11,685     $ 24,425   Percentage of total revenue     10 %     19 % Our condensed consolidated balance sheet at March 31, 2024 included deferred contract revenue of $1.9 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 in the U.S. in April 2023. In addition, we and Biogen are currently developing numerous other investigational medicines to treat neurodegenerative diseases, including medicines in development to treat people with amyotrophic lateral sclerosis, or ALS, SMA, Angelman Syndrome, or AS, Alzheimer’s disease, or AD, and Parkinson’s disease, or PD. In addition to these medicines, our collaborations with Biogen include a substantial research pipeline that addresses a broad range of neurological diseases. From inception through March 31, 2024, we have received more than $3.8 billion in payments from our Biogen collaborations, including payments to purchase our stock. During the three months ended March 31, 2024 and 2023, we earned the following revenue from our relationship with Biogen (in thousands, except percentage amounts):   Three Months Ended March 31,       2024     2023   Revenue from our relationship with Biogen   $ 59,236     $ 70,501   Percentage of total revenue     50 %     54 % Our condensed consolidated balance sheets at March 31, 2024 and December 31, 2023 included deferred contract revenue of $287.2 million and $307.4 million, respectively, from our relationship with Biogen.

v3.24.1.u1

Basic and Diluted Net Loss Per Share	3 Months Ended
	Mar. 31, 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 months ended March 31, 2024 and 2023 by dividing our net loss by our weighted-average number of common shares outstanding during the period. Diluted net loss per share For the three months ended March 31, 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: ● 0 percent convertible senior notes, or 0% Notes; ● Note hedges related to the 0% Notes; ● 0.125 percent convertible senior notes, or 0.125% Notes; ● Note hedges related to the 0.125% Notes; ● Dilutive stock options; ● Unvested restricted stock units, or RSUs; ● Unvested performance restricted stock units, or PRSUs; and ● Employee Stock Purchase Plan, or ESPP. For the three months ended March 31, 2024, common stock underlying the 1.75 percent convertible senior notes, or 1.75% Notes, would also have had an anti-dilutive effect on net loss per share. Additionally as of March 31, 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.

v3.24.1.u1

Investments	3 Months Ended
	Mar. 31, 2024
Investments [Abstract]
Investments	7.  Investments The following table summarizes the contract maturity of the available-for-sale securities we held as of March 31, 2024: One year or less     69 % After one year but within two years     26 % After two years but within three and a half years     5 % Total     100 % As illustrated above, at March 31, 2024, 95 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 with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Standard & Poor’s, Moody’s or Fitch, respectively. At March 31, 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   March 31, 2024   Cost     Gains     Losses     Fair Value   Available-for-sale debt securities:                         Corporate debt securities (1)   $ 529,593     $ 87     $ (1,990 )   $ 527,690   Debt securities issued by U.S. government agencies     179,632       24       (409 )     179,247   Debt securities issued by the U.S. Treasury (1)     582,782       38       (1,372 )     581,448   Debt securities issued by states of the U.S. and political subdivisions of the states     15,017       29       (77 )     14,969   Total debt securities with a maturity of one year or less     1,307,024       178       (3,848 )     1,303,354   Corporate debt securities     248,548       405       (890 )     248,063   Debt securities issued by U.S. government agencies     115,152       134       (187 )     115,099   Debt securities issued by the U.S. Treasury     204,535       133       (1,086 )     203,582   Debt securities issued by states of the U.S. and political subdivisions of the states     1,420       —       (3 )     1,417   Total debt securities with a maturity of more than one year     569,655       672       (2,166 )     568,161   Total available-for-sale debt securities   $ 1,876,679     $ 850     $ (6,014 )   $ 1,871,515   Equity securities:                                 Publicly traded equity securities included in other current assets (2)   $ 11,897     $ 319     $ (3,756 )   $ 8,460   Privately held equity securities included in deposits and other assets (3)     23,115       25,001       (5,125 )     42,991   Total equity securities     35,012       25,320       (8,881 )     51,451   Total available-for-sale debt and equity securities   $ 1,911,691     $ 26,170     $ (14,895 )   $ 1,922,966     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 three months ended March 31, 2024, we recorded a $2.2 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 cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer, which are Level 3 inputs. In the three months ended March 31, 2024, there were no changes in the fair value of our investments in privately held companies. The following is a summary of our investments we consider to be temporarily impaired at March 31, 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     392     $ 487,939     $ (1,361 )   $ 96,219     $ (1,519 )   $ 584,158     $ (2,880 ) Debt securities issued by U.S. government agencies     80       176,956       (360 )     12,375       (236 )     189,331       (596 ) Debt securities issued by the U.S. Treasury     64       588,958       (1,773 )     86,772       (685 )     675,730       (2,458 ) Debt securities issued by states of the U.S. and political subdivisions of the states     53       7,978       (22 )     5,703       (58 )     13,681       (80 ) Total temporarily impaired securities     589     $ 1,261,831     $ (3,516 )   $ 201,069     $ (2,498 )   $ 1,462,900     $ (6,014 ) 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.

v3.24.1.u1

Fair Value Measurements	3 Months Ended
	Mar. 31, 2024
Fair Value Measurements [Abstract]
Fair Value Measurements	8.  Fair Value Measurements The following tables present the major security types we held at March 31, 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 March 31, 2024     Quoted Prices in Active Markets (Level 1)     Significant Other Observable Inputs (Level 2)   Cash equivalents (1)   $ 263,639     $ 263,639     $ —   Corporate debt securities (2)     775,753       —       775,753   Debt securities issued by U.S. government agencies (3)     294,346       —       294,346   Debt securities issued by the U.S. Treasury (3)     785,030       785,030       —   Debt securities issued by states of the U.S. and political subdivisions of the states (3)     16,386       —       16,386   Publicly traded equity securities included in other current assets (4)     8,460       8,460       —   Total   $ 2,143,614     $ 1,057,129     $ 1,086,485     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 (5)     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 (4)     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) $14.2 million was included in cash and cash equivalents, with the difference included in short-term investments. (3) Included in short-term investments. (4) Included in other current assets. (5) $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 $601.1 million, $627.8 million and $42.4 million at March 31, 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.

v3.24.1.u1

Stock-based Compensation Expense	3 Months Ended
	Mar. 31, 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 months ended March 31, 2024 and 2023 (in thousands):   Three Months Ended March 31,       2024     2023   Cost of sales   $ 204     $ 119   Research, development and patent expense     22,225       19,567   Selling, general and administrative expense     8,911       7,262   Total   $ 31,340     $ 26,948   As of March 31, 2024, total unrecognized estimated stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $71.1 million, $112.8 million and $16.8 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 1.4 years, 1.8 years and 2.2 years, respectively. Refer to Part IV, Item 15, Note 1, Organization and Significant Accounting Policies, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2023 for further details on how we determine the fair value of stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP. For the three months ended March 31, 2024 and 2023, we used the following weighted-average assumptions in our Black-Scholes calculations: Employee Stock Options:   Three Months Ended March 31,       2024     2023   Risk-free interest rate     4.0 %     3.6 % Dividend yield     0.0 %     0.0 % Volatility     44.0 %     47.5 % Expected life   6.3 years     6.3 years   ESPP:   Three Months Ended March 31,       2024     2023   Risk-free interest rate     5.3 %     5.2 % Dividend yield     0.0 %     0.0 % Volatility     38.4 %     36.7 % Expected life   6 months     6 months   RSUs: The weighted-average grant date fair value of RSUs granted to employees for the three months ended March 31, 2024 and 2023 was $53.54 and $39.85 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 granted to our executive officers for the three months ended March 31, 2024 and 2023 was $78.41 and $58.99 per share, respectively.

v3.24.1.u1

Income Taxes	3 Months Ended
	Mar. 31, 2024
Income Taxes [Abstract]
Income Taxes	10.  Income Taxes We recorded income tax expense of $0.1 million for the three months ended March 31, 2024 compared to $11.4 million for the same period in 2023. The decrease in income tax expense relates primarily to the impact of the royalty purchase agreement with Royalty Pharma on income tax expense for the three months ended March 31, 2023. 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. We continue to maintain a full valuation allowance on all of our net deferred tax assets.

v3.24.1.u1

Liability Related to Sale of Future Royalties	3 Months Ended
	Mar. 31, 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, our medicine in development to treat patients with elevated lipoprotein(a)-driven cardiovascular disease. 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 March 31, 2024, 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     (6,623 ) Interest expense related to sale of future royalties     17,806   Amortization of issuance costs related to sale of future royalties     153   Net liability related to sale of future royalties as of March 31, 2024   $ 525,072   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.

v3.24.1.u1

Convertible Debt	3 Months Ended
	Mar. 31, 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 convertible senior notes and used $488.2 million of the net proceeds from the issuance of the 1.75% Notes to repurchase $504.4 million in principal of our 0.125% Notes. We expect to use the remaining net proceeds to settle the 0.125% Notes that remain outstanding. At March 31, 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   $ 12.0   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 At March 31, 2024, we had the following 0% Notes outstanding (in millions except interest rate and price per share data):   0% Notes   Outstanding principal balance   $ 632.5   Unamortized debt issuance costs   $ 6.3   Maturity date   April 2026   Interest rate     0 % Effective interest rate     0.5 % Conversion price per share   $ 57.84   Effective conversion price per share with call spread   $ 76.39   Total shares of common stock subject to conversion     10.9   In conjunction with the 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our 0% Notes by increasing the effective conversion price on our 0% Notes. We increased our effective conversion price to $76.39 with the same number of underlying shares as our 0% Notes. The call spread cost us $46.9 million, of which $136.7 million was for the note hedge purchase, offset by $89.8 million we received for selling the warrants. Similar to our 0% Notes, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the 0% Notes. The note hedges will expire upon maturity of the 0% Notes, or April 2026. The note hedges and warrants are separate transactions and are not part of the terms of our 0% Notes. The holders of the 0% Notes do not have any rights with respect to the note hedges and warrants. We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our condensed consolidated balance sheets. Refer to Part IV, Item 15, Note 1, Organization and Significant Accounting Policies, of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2023 for our Call Spread accounting policy. We reassess our ability to continue to classify the note hedges and warrants in shareholders’ equity at each reporting period. 0.125 Percent Convertible Senior Notes and Call Spread As discussed above, in 2023, we repurchased $504.4 million of our 0.125% Notes. At March 31, 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% Notes that we have repurchased and are currently holding in treasury     0.5   In conjunction with the issuance of our 0.125% 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 0.125% Notes by increasing the effective conversion price on our 0.125% Notes. We increased our effective conversion price to $123.38 with the same number of underlying shares as our 0.125% Notes. The call spread cost us $52.6 million, of which $108.7 million was for the note hedge purchase, offset by $56.1 million we received for selling the warrants. Similar to our 0.125% Notes, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the 0.125% Notes. The note hedges will expire upon maturity of the 0.125% Notes, or December 2024. The note hedges and warrants are separate transactions and are not part of the terms of our 0.125% Notes. The holders of the 0.125% Notes do not have any rights with respect to the note hedges and warrants. As of March 31, 2024, 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 1.75%, 0% and 0.125% Notes are convertible under certain conditions, at the option of the note holders. We can settle conversions of the notes, at our election, in cash, shares of our common stock or a combination of both. We may not redeem the notes prior to maturity, and we do not have to provide a sinking fund for them. Holders of the notes may require us to purchase some or all of their notes upon the occurrence of certain fundamental changes, as set forth in the indentures governing the notes, at a purchase price equal to 100 percent of the principal amount of the notes to be purchased, plus any accrued and unpaid interest.

v3.24.1.u1

Legal Proceedings	3 Months Ended
	Mar. 31, 2024
Legal Proceedings [Abstract]
Legal Proceedings	13. 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.

v3.24.1.u1

Insider Trading Arrangements	3 Months Ended
	Mar. 31, 2024 shares
Trading Arrangements, by Individual
Material Terms of Trading Arrangement	During the quarter ended March 31, 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** B. Lynne Parshall Board Member   Termination   January 3, 2024   X       122,638   Upon the execution of all instructions provided in the plan Joseph Klein, III Board Member   Adoption   January 3, 2024   X       82,000   The earlier to occur of (i) December 31, 2025, and (ii) Upon the execution of all instructions provided in the plan Joseph Baroldi EVP, Chief Business Officer   Adoption   January 5, 2024   X       40,000   The earlier to occur of (i) March 31, 2025, and (ii) Upon the execution of all instructions provided in the plan Eugene Schneider EVP, Chief Clinical Development and Operations Officer   Adoption   January 12, 2024   X       40,633   The earlier to occur of (i) July 29, 2025, and (ii) Upon the execution of all instructions provided in the plan Elizabeth Hougen EVP, Finance & Chief Financial Officer   Adoption   January 12, 2024   X       178,200   The earlier to occur of (i) October 11, 2025, and (ii) Upon the execution of all instructions provided in the plan Patrick O'Neil Chief Legal Officer & General Counsel   Termination   February 14, 2024   X       170,830   Upon the execution of all instructions provided in the plan B. Lynne Parshall Board Member   Adoption   February 21, 2024   X       145,568   The earlier to occur of (i) June 30, 2025, and (ii) Upon the execution of all instructions provided in the plan Patrick O'Neil Chief Legal Officer & General Counsel     Adoption   February 21, 2024   X       252,747   The earlier to occur of (i) May 31, 2025, and (ii) Upon the execution of all instructions provided in the plan
B. Lynne Parshall [Member]
Trading Arrangements, by Individual
Name	B. Lynne Parshall
Title	Board Member
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	February 21, 2024
Rule 10b5-1 Arrangement Terminated	true
Non-Rule 10b5-1 Arrangement Terminated	false
Termination Date	January 3, 2024
Joseph Klein, III [Member]
Trading Arrangements, by Individual
Name	Joseph Klein, III
Title	Board Member
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	January 3, 2024
Arrangement Duration	729 days
Aggregate Available	82,000
Joseph Baroldi [Member]
Trading Arrangements, by Individual
Name	Joseph Baroldi
Title	EVP, Chief Business Officer
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	January 5, 2024
Arrangement Duration	452 days
Aggregate Available	40,000
Eugene Schneider [Member]
Trading Arrangements, by Individual
Name	Eugene Schneider
Title	EVP, Chief Clinical Development and Operations Officer
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	January 12, 2024
Arrangement Duration	565 days
Aggregate Available	40,633
Elizabeth Hougen [Member]
Trading Arrangements, by Individual
Name	Elizabeth Hougen
Title	EVP, Finance & Chief Financial Officer
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	January 12, 2024
Arrangement Duration	639 days
Aggregate Available	178,200
Patrick O'Neil [Member]
Trading Arrangements, by Individual
Name	Patrick O'Neil
Title	Chief Legal Officer & General Counsel
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	February 21, 2024
Rule 10b5-1 Arrangement Terminated	true
Non-Rule 10b5-1 Arrangement Terminated	false
Termination Date	February 14, 2024
Termination [Member] | B. Lynne Parshall [Member]
Trading Arrangements, by Individual
Arrangement Duration
Aggregate Available	122,638
Termination [Member] | Patrick O'Neil [Member]
Trading Arrangements, by Individual
Arrangement Duration
Aggregate Available	170,830
Adoption [Member] | B. Lynne Parshall [Member]
Trading Arrangements, by Individual
Arrangement Duration	496 days
Aggregate Available	145,568
Adoption [Member] | Patrick O'Neil [Member]
Trading Arrangements, by Individual
Arrangement Duration	466 days
Aggregate Available	252,747

v3.24.1.u1

Organization and Basis of Presentation (Policies)	3 Months Ended
	Mar. 31, 2024
Organization and Basis of Presentation [Abstract]
Basis of Presentation	We prepared the unaudited interim condensed consolidated financial statements for the three months ended March 31, 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 segment, Ionis operations, because our chief decision maker reviews operating results on an aggregate basis and manages our operations as a single operating segment.
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 U.S., that require us to make estimates and assumptions that affect the amounts reported in our condensed consolidated financial statements and accompanying notes. Actual results could differ from our estimates.

v3.24.1.u1

Significant Accounting Policies (Policies)	3 Months Ended
	Mar. 31, 2024
Significant Accounting Policies [Abstract]
Recently Adopted Accounting Standards	Recently Adopted Accounting Standards We do not expect any recently issued accounting standards to have a material impact to our financial results.

v3.24.1.u1

Basic and Diluted Net Loss Per Share (Policies)	3 Months Ended
	Mar. 31, 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 months ended March 31, 2024 and 2023 by dividing our net loss by our weighted-average number of common shares outstanding during the period. Diluted net loss per share For the three months ended March 31, 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: ● 0 percent convertible senior notes, or 0% Notes; ● Note hedges related to the 0% Notes; ● 0.125 percent convertible senior notes, or 0.125% Notes; ● Note hedges related to the 0.125% Notes; ● Dilutive stock options; ● Unvested restricted stock units, or RSUs; ● Unvested performance restricted stock units, or PRSUs; and ● Employee Stock Purchase Plan, or ESPP. For the three months ended March 31, 2024, common stock underlying the 1.75 percent convertible senior notes, or 1.75% Notes, would also have had an anti-dilutive effect on net loss per share. Additionally as of March 31, 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.

v3.24.1.u1

Supplemental Financial Data (Tables)	3 Months Ended
	Mar. 31, 2024
Supplemental Financial Data [Abstract]
Inventories	Inventories Our inventory consisted of the following (in thousands):   March 31, 2024     December 31, 2023   Raw materials:             Raw materials - clinical   $ 23,317     $ 20,985   Raw materials - commercial     705       1,809   Total raw materials     24,022       22,794   Work in process     6,037       5,477   Finished goods     200       154   Total inventories   $ 30,259     $ 28,425
Accrued Liabilities	Accrued Liabilities Our accrued liabilities consisted of the following (in thousands):   March 31, 2024     December 31, 2023   Clinical development expenses   $ 75,929     $ 105,967   In-licensing expenses     6,436       7,454   Commercial expenses     4,739       4,875   Other miscellaneous expenses     18,944       29,598   Total accrued liabilities   $ 106,048     $ 147,894

v3.24.1.u1

Revenues (Tables)	3 Months Ended
	Mar. 31, 2024
Revenues [Abstract]
Revenues	During the three months ended March 31, 2024 and 2023, our revenues were comprised of the following (in thousands):   Three Months Ended March 31,       2024     2023   Revenue:             Commercial revenue:             SPINRAZA royalties   $ 38,455     $ 50,247   WAINUA royalties     1,125       —   Other commercial revenue:                 TEGSEDI and WAYLIVRA revenue, net     8,628       6,478   Licensing and other royalty revenue     11,385       11,043   Total other commercial revenue     20,013       17,521   Total commercial revenue     59,593       67,768   Research and development revenue:                 Collaborative agreement revenue     49,345       38,334   WAINUA joint development revenue     10,559       24,422   Total research and development revenue     59,904       62,756   Total revenue   $ 119,497     $ 130,524

v3.24.1.u1

Collaborative Arrangements and Licensing Agreements (Tables)	3 Months Ended
	Mar. 31, 2024
AstraZeneca [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the three months ended March 31, 2024 and 2023, we earned the following revenue from our relationship with AstraZeneca (in thousands, except percentage amounts):   Three Months Ended March 31,       2024     2023   Revenue from our relationship with AstraZeneca   $ 11,685     $ 24,425   Percentage of total revenue     10 %     19 %
Biogen [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the three months ended March 31, 2024 and 2023, we earned the following revenue from our relationship with Biogen (in thousands, except percentage amounts):   Three Months Ended March 31,       2024     2023   Revenue from our relationship with Biogen   $ 59,236     $ 70,501   Percentage of total revenue     50 %     54 %

v3.24.1.u1

Investments (Tables)	3 Months Ended
	Mar. 31, 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 March 31, 2024: One year or less     69 % After one year but within two years     26 % After two years but within three and a half years     5 % Total     100 %
Summary of Investments	The following is a summary of our investments (in thousands):   Amortized     Gross Unrealized     Estimated   March 31, 2024   Cost     Gains     Losses     Fair Value   Available-for-sale debt securities:                         Corporate debt securities (1)   $ 529,593     $ 87     $ (1,990 )   $ 527,690   Debt securities issued by U.S. government agencies     179,632       24       (409 )     179,247   Debt securities issued by the U.S. Treasury (1)     582,782       38       (1,372 )     581,448   Debt securities issued by states of the U.S. and political subdivisions of the states     15,017       29       (77 )     14,969   Total debt securities with a maturity of one year or less     1,307,024       178       (3,848 )     1,303,354   Corporate debt securities     248,548       405       (890 )     248,063   Debt securities issued by U.S. government agencies     115,152       134       (187 )     115,099   Debt securities issued by the U.S. Treasury     204,535       133       (1,086 )     203,582   Debt securities issued by states of the U.S. and political subdivisions of the states     1,420       —       (3 )     1,417   Total debt securities with a maturity of more than one year     569,655       672       (2,166 )     568,161   Total available-for-sale debt securities   $ 1,876,679     $ 850     $ (6,014 )   $ 1,871,515   Equity securities:                                 Publicly traded equity securities included in other current assets (2)   $ 11,897     $ 319     $ (3,756 )   $ 8,460   Privately held equity securities included in deposits and other assets (3)     23,115       25,001       (5,125 )     42,991   Total equity securities     35,012       25,320       (8,881 )     51,451   Total available-for-sale debt and equity securities   $ 1,911,691     $ 26,170     $ (14,895 )   $ 1,922,966     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 three months ended March 31, 2024, we recorded a $2.2 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 cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer, which are Level 3 inputs. In the three months ended March 31, 2024, there were no changes in the fair value of our investments in privately held companies.
Temporarily Impaired Investments	The following is a summary of our investments we consider to be temporarily impaired at March 31, 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     392     $ 487,939     $ (1,361 )   $ 96,219     $ (1,519 )   $ 584,158     $ (2,880 ) Debt securities issued by U.S. government agencies     80       176,956       (360 )     12,375       (236 )     189,331       (596 ) Debt securities issued by the U.S. Treasury     64       588,958       (1,773 )     86,772       (685 )     675,730       (2,458 ) Debt securities issued by states of the U.S. and political subdivisions of the states     53       7,978       (22 )     5,703       (58 )     13,681       (80 ) Total temporarily impaired securities     589     $ 1,261,831     $ (3,516 )   $ 201,069     $ (2,498 )   $ 1,462,900     $ (6,014 )

v3.24.1.u1

Fair Value Measurements (Tables)	3 Months Ended
	Mar. 31, 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 March 31, 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 March 31, 2024     Quoted Prices in Active Markets (Level 1)     Significant Other Observable Inputs (Level 2)   Cash equivalents (1)   $ 263,639     $ 263,639     $ —   Corporate debt securities (2)     775,753       —       775,753   Debt securities issued by U.S. government agencies (3)     294,346       —       294,346   Debt securities issued by the U.S. Treasury (3)     785,030       785,030       —   Debt securities issued by states of the U.S. and political subdivisions of the states (3)     16,386       —       16,386   Publicly traded equity securities included in other current assets (4)     8,460       8,460       —   Total   $ 2,143,614     $ 1,057,129     $ 1,086,485     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 (5)     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 (4)     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) $14.2 million was included in cash and cash equivalents, with the difference included in short-term investments. (3) Included in short-term investments. (4) Included in other current assets. (5) $33.0 million was included in cash and cash equivalents, with the difference included in short-term investments.

v3.24.1.u1

Stock-based Compensation Expense (Tables)	3 Months Ended
	Mar. 31, 2024
Stock-based Compensation Expense [Abstract]
Stock-Based Compensation Expense	The following table summarizes stock-based compensation expense for the three months ended March 31, 2024 and 2023 (in thousands):   Three Months Ended March 31,       2024     2023   Cost of sales   $ 204     $ 119   Research, development and patent expense     22,225       19,567   Selling, general and administrative expense     8,911       7,262   Total   $ 31,340     $ 26,948
Weighted-Average Assumptions for Stock Options	Employee Stock Options:   Three Months Ended March 31,       2024     2023   Risk-free interest rate     4.0 %     3.6 % Dividend yield     0.0 %     0.0 % Volatility     44.0 %     47.5 % Expected life   6.3 years     6.3 years
Weighted-Average Assumptions for ESPP	ESPP:   Three Months Ended March 31,       2024     2023   Risk-free interest rate     5.3 %     5.2 % Dividend yield     0.0 %     0.0 % Volatility     38.4 %     36.7 % Expected life   6 months     6 months

v3.24.1.u1

Liability Related to Sale of Future Royalties (Tables)	3 Months Ended
	Mar. 31, 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     (6,623 ) Interest expense related to sale of future royalties     17,806   Amortization of issuance costs related to sale of future royalties     153   Net liability related to sale of future royalties as of March 31, 2024   $ 525,072

v3.24.1.u1

Convertible Debt (Tables)	3 Months Ended
	Mar. 31, 2024
1.75% Notes [Member]
Convertible Debt [Abstract]
Convertible Senior Notes	At March 31, 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   $ 12.0   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 March 31, 2024, we had the following 0% Notes outstanding (in millions except interest rate and price per share data):   0% Notes   Outstanding principal balance   $ 632.5   Unamortized debt issuance costs   $ 6.3   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 March 31, 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% Notes that we have repurchased and are currently holding in treasury     0.5

v3.24.1.u1

Organization and Basis of Presentation (Details)	3 Months Ended
	Mar. 31, 2024 Segment
Organization and Basis of Presentation [Abstract]
Number of operating segments	1

v3.24.1.u1

Supplemental Financial Data, Inventories (Details) - USD ($) $ in Thousands	Mar. 31, 2024	Dec. 31, 2023
Inventory [Abstract]
Raw materials	$ 24,022	$ 22,794
Work in process	6,037	5,477
Finished goods	200	154
Total inventories	30,259	28,425
Clinical [Member]
Inventory [Abstract]
Raw materials	23,317	20,985
Commercial [Member]
Inventory [Abstract]
Raw materials	$ 705	$ 1,809

v3.24.1.u1

Supplemental Financial Data, Accrued Liabilities (Details) - USD ($) $ in Thousands	Mar. 31, 2024	Dec. 31, 2023
Accrued Liabilities [Abstract]
Clinical development expenses	$ 75,929	$ 105,967
In-licensing expenses	6,436	7,454
Commercial expenses	4,739	4,875
Other miscellaneous expenses	18,944	29,598
Total accrued liabilities	$ 106,048	$ 147,894

v3.24.1.u1

Revenues (Details) $ in Thousands	3 Months Ended		12 Months Ended
	Mar. 31, 2024 USD ($)	Mar. 31, 2023 USD ($)	Dec. 31, 2021 USD ($) PerformanceObligation Component
Revenues [Abstract]
Revenue	$ 119,497	$ 130,524
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	55.00%
Commercial Revenue [Member]
Revenues [Abstract]
Revenue	$ 59,593	67,768
SPINRAZA Royalties [Member]
Revenues [Abstract]
Revenue	38,455	50,247
WAINUA Royalties [Member]
Revenues [Abstract]
Revenue	1,125	0
Other Commercial Revenue [Member]
Revenues [Abstract]
Revenue	20,013	17,521
TEGSEDI and WAYLIVRA Revenue, Net [Member]
Revenues [Abstract]
Revenue	8,628	6,478
Licensing and Other Royalty Revenue [Member]
Revenues [Abstract]
Revenue	11,385	11,043
Research and Development Revenue [Member]
Revenues [Abstract]
Revenue	59,904	62,756
Collaborative Agreement Revenue [Member]
Revenues [Abstract]
Revenue	49,345	38,334
WAINUA Joint Development Revenue [Member]
Revenues [Abstract]
Revenue	$ 10,559	$ 24,422

v3.24.1.u1

Collaborative Arrangements and Licensing Agreements, AstraZeneca (Details) $ in Thousands	3 Months Ended
	Mar. 31, 2024 USD ($) Agreement	Mar. 31, 2023 USD ($)	Dec. 31, 2023 USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 119,497	$ 130,524
AstraZeneca [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement	2
Revenue	$ 11,685	$ 24,425
Deferred contract revenue	$ 1,900		$ 0
AstraZeneca [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage	10.00%	19.00%
AstraZeneca [Member] | Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	$ 910,000
WAINUA [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement	1
WAINUA [Member] | Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next payment to be achieved	$ 30,000
Cardiovascular, Renal and Metabolic Diseases [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement	1

v3.24.1.u1

Collaborative Arrangements and Licensing Agreements, Biogen (Details) - USD ($) $ in Thousands	3 Months Ended
	Mar. 31, 2024	Mar. 31, 2023	Dec. 31, 2023
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 119,497	$ 130,524
Biogen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	59,236	$ 70,501
Deferred contract revenue	$ 287,200		$ 307,400
Biogen [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage	50.00%	54.00%
Biogen [Member] | Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	$ 3,800,000

v3.24.1.u1

Basic and Diluted Net Loss Per Share (Details)	Mar. 31, 2024	Dec. 31, 2023	Mar. 31, 2023
0% Notes [Member]
Diluted Net Loss per Share [Abstract]
Interest rate on convertible senior notes	0.00%	0.00%	0.00%
0.125% Notes [Member]
Diluted Net Loss per Share [Abstract]
Interest rate on convertible senior notes	0.125%	0.125%	0.125%
1.75% Notes [Member]
Diluted Net Loss per Share [Abstract]
Interest rate on convertible senior notes	1.75%

v3.24.1.u1

Investments, Contract Maturity of Available-for-Sale Securities (Details)	3 Months Ended
	Mar. 31, 2024
Contract Maturity of Available-for-Sale Securities [Abstract]
One year or less	69.00%
After one year but within two years	26.00%
After two years but within three and a half years	5.00%
Total	100.00%
Maximum contract maturity period, range 1	1 year
Maximum contract maturity period, range 2	2 years
Maximum contract maturity period, range 3	3 years 6 months
Percentage of available-for-sale securities with a maturity of less than two years	95.00%

v3.24.1.u1

Investments, Summary of Investments (Details) $ in Thousands		3 Months Ended
		Mar. 31, 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		$ 1,307,024	$ 1,316,219
Gross unrealized gains		178	415
Gross unrealized losses		(3,848)	(5,238)
Estimated fair value		1,303,354	1,311,396
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		569,655	651,628
Gross unrealized gains		672	3,063
Gross unrealized losses		(2,166)	(1,197)
Estimated fair value		568,161	653,494
Available-for-sale Debt Securities [Abstract]
Amortized cost		1,876,679	1,967,847
Gross unrealized gains		850	3,478
Gross unrealized losses		(6,014)	(6,435)
Estimated fair value		1,871,515	1,964,890
Equity Securities [Abstract]
Amortized cost		35,012	35,012
Gross unrealized gains		25,320	25,237
Gross unrealized losses		(8,881)	(10,957)
Estimated fair value		51,451	49,292
Available-for-sale Debt and Equity Securities [Abstract]
Amortized cost		1,911,691	2,002,859
Gross unrealized gains		26,170	28,715
Gross unrealized losses		(14,895)	(17,392)
Estimated fair value		1,922,966	2,014,182
Corporate Debt Securities [Member]
Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]
Amortized cost	[1]	529,593	559,967
Gross unrealized gains		87	157
Gross unrealized losses		(1,990)	(2,625)
Estimated fair value		527,690	557,499
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		248,548	243,151
Gross unrealized gains		405	1,270
Gross unrealized losses		(890)	(692)
Estimated fair value		248,063	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		179,632	224,711
Gross unrealized gains		24	64
Gross unrealized losses		(409)	(611)
Estimated fair value		179,247	224,164
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		115,152	110,138
Gross unrealized gains		134	547
Gross unrealized losses		(187)	(21)
Estimated fair value		115,099	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]	582,782	513,784
Gross unrealized gains		38	152
Gross unrealized losses		(1,372)	(1,889)
Estimated fair value		581,448	512,047
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		204,535	294,873
Gross unrealized gains		133	1,239
Gross unrealized losses		(1,086)	(480)
Estimated fair value		203,582	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		15,017	17,757
Gross unrealized gains		29	42
Gross unrealized losses		(77)	(113)
Estimated fair value		14,969	17,686
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		1,420	3,466
Gross unrealized gains		0	7
Gross unrealized losses		(3)	(4)
Estimated fair value		1,417	3,469
Publicly Traded Equity Securities [Member]
Equity Securities [Abstract]
Amortized cost	[2]	11,897	11,897
Gross unrealized gains		319	236
Gross unrealized losses		(3,756)	(5,832)
Estimated fair value		8,460	6,301
Available-for-sale Debt and Equity Securities [Abstract]
Unrealized gain on equity securities		2,200
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		(5,125)	(5,125)
Estimated fair value		42,991	$ 42,991
Available-for-sale Debt and Equity Securities [Abstract]
Unrealized gain on equity securities		$ 0
[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 three months ended March 31, 2024, we recorded a $2.2 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 cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer, which are Level 3 inputs. In the three months ended March 31, 2024, there were no changes in the fair value of our investments in privately held companies.

v3.24.1.u1

Investments, Investments Temporarily Impaired (Details) $ in Thousands	Mar. 31, 2024 USD ($) Investment
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	589
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 1,261,831
More than 12 months of temporary impairment	201,069
Total temporary impairment	1,462,900
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(3,516)
More than 12 months of temporary impairment	(2,498)
Total temporary impairment	$ (6,014)
Corporate Debt Securities [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	392
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 487,939
More than 12 months of temporary impairment	96,219
Total temporary impairment	584,158
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(1,361)
More than 12 months of temporary impairment	(1,519)
Total temporary impairment	$ (2,880)
Debt Securities Issued by U.S. Government Agencies [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	80
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 176,956
More than 12 months of temporary impairment	12,375
Total temporary impairment	189,331
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(360)
More than 12 months of temporary impairment	(236)
Total temporary impairment	$ (596)
Debt Securities Issued by the U.S. Treasury [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	64
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 588,958
More than 12 months of temporary impairment	86,772
Total temporary impairment	675,730
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(1,773)
More than 12 months of temporary impairment	(685)
Total temporary impairment	$ (2,458)
Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	53
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 7,978
More than 12 months of temporary impairment	5,703
Total temporary impairment	13,681
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(22)
More than 12 months of temporary impairment	(58)
Total temporary impairment	$ (80)

v3.24.1.u1

Fair Value Measurements (Details) - USD ($) $ in Thousands		Mar. 31, 2024		Dec. 31, 2023		Mar. 31, 2023
Fair Value Measurements [Abstract]
Available-for-sale securities		$ 1,871,515		$ 1,964,890
Equity securities		$ 51,451		$ 49,292
1.75% Notes [Member]
Fair Value Measurements [Abstract]
Interest rate on convertible senior notes		1.75%
0% Notes [Member]
Fair Value Measurements [Abstract]
Interest rate on convertible senior notes		0.00%		0.00%		0.00%
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		$ 8,460		$ 6,301
Recurring Basis [Member]
Fair Value Measurements [Abstract]
Cash equivalents	[1]	263,639		185,424
Total		2,143,614		2,156,615
Recurring Basis [Member] | Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		775,753	[2]	801,228	[3]
Recurring Basis [Member] | Corporate Debt Securities [Member] | Cash and Cash Equivalents [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		14,200		33,000
Recurring Basis [Member] | Debt Securities Issued by U.S. Government Agencies [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities	[4]	294,346		334,828
Recurring Basis [Member] | Debt Securities Issued by the U.S. Treasury [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities	[4]	785,030		807,679
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]	16,386		21,155
Recurring Basis [Member] | Publicly Traded Equity Securities [Member] | Other Current Assets [Member]
Fair Value Measurements [Abstract]
Equity securities	[5]	8,460		6,301
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member]
Fair Value Measurements [Abstract]
Cash equivalents		263,639		185,424
Total		1,057,129		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		785,030		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		8,460		6,301
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member]
Fair Value Measurements [Abstract]
Cash equivalents		0		0
Total		1,086,485		1,157,211
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 1.75% Notes [Member]
Fair Value Measurements [Abstract]
Convertible notes		601,100		661,100
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 0% Notes [Member]
Fair Value Measurements [Abstract]
Convertible notes		627,800		667,800
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 0.125% Notes [Member]
Fair Value Measurements [Abstract]
Convertible notes		42,400		42,400
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		775,753		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		294,346		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		16,386		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] $14.2 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] Included in other current assets.

v3.24.1.u1

Stock-based Compensation Expense (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended
	Mar. 31, 2024	Mar. 31, 2023
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense	$ 31,340	$ 26,948
Cost of Sales [Member]
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense	204	119
Research, Development and Patent Expense [Member]
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense	22,225	19,567
Selling, General and Administrative Expense [Member]
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense	8,911	$ 7,262
Stock Options [Member]
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation expense related to non-vested stock options	$ 71,100
Weighted average period for recognition	1 year 4 months 24 days
Stock Options [Member] | Employees [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate	4.00%	3.60%
Dividend yield	0.00%	0.00%
Volatility	44.00%	47.50%
Expected life	6 years 3 months 18 days	6 years 3 months 18 days
ESPP [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate	5.30%	5.20%
Dividend yield	0.00%	0.00%
Volatility	38.40%	36.70%
Expected life	6 months	6 months
RSUs [Member]
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation cost related to non-vested units	$ 112,800
Weighted average period for recognition	1 year 9 months 18 days
RSUs [Member] | Employees [Member]
RSUs and PRSUs [Abstract]
Weighted-average grant date fair value (in dollars per share)	$ 53.54	$ 39.85
PRSUs [Member]
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation cost related to non-vested units	$ 16,800
Weighted average period for recognition	2 years 2 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	100.00%
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	0.00%
PRSUs [Member] | Granted in 2024 [Member] | Maximum [Member]
RSUs and PRSUs [Abstract]
Percentage of units guaranteed to vest	200.00%
PRSUs [Member] | Granted in 2023 [Member] | Executive Officers [Member]
RSUs and PRSUs [Abstract]
Vesting percentage	100.00%
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	0.00%
PRSUs [Member] | Granted in 2023 [Member] | Executive Officers [Member] | Maximum [Member]
RSUs and PRSUs [Abstract]
Percentage of units guaranteed to vest	200.00%

v3.24.1.u1

Income Taxes (Details) - USD ($) $ in Thousands	3 Months Ended
	Mar. 31, 2024	Mar. 31, 2023
Income Taxes [Abstract]
Income tax expense	$ 75	$ 11,380

v3.24.1.u1

Liability Related to Sale of Future Royalties (Details) - USD ($) $ in Thousands	1 Months Ended	3 Months Ended		12 Months Ended
	Jan. 31, 2023	Mar. 31, 2024	Mar. 31, 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		(6,623)	0
Interest expense related to sale of future royalties		17,806	$ 15,363
Net liability related to sale of future royalties		525,072		$ 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%
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		$ (6,623)		(44,628)
Interest expense related to sale of future royalties		17,806		68,238
Amortization of issuance costs related to sale of future royalties		153		560
Net liability related to sale of future royalties		525,072		$ 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		25.00%
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		45.00%
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		25.00%

v3.24.1.u1

Convertible Debt (Details) - USD ($) $ / shares in Units, shares in Millions, $ in Millions	3 Months Ended	12 Months Ended
	Mar. 31, 2024	Dec. 31, 2023	Dec. 31, 2021	Dec. 31, 2019	Mar. 31, 2023
1.75% Notes [Member]
Convertible Debt [Abstract]
Face amount of offering		$ 575.0
Repurchase of convertible senior notes		$ 488.2
Outstanding principal balance	$ 575.0
Unamortized debt issuance costs	$ 12.0
Maturity date	Jun. 30, 2028
Interest rate	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	100.00%
0% Notes [Member]
Convertible Debt [Abstract]
Outstanding principal balance	$ 632.5
Unamortized debt issuance costs	$ 6.3
Maturity date	Apr. 30, 2026
Interest rate	0.00%	0.00%			0.00%
Effective interest rate	0.50%
Conversion price per share (in dollars per share)	$ 57.84
Effective conversion price per share with call spread (in dollars per share)	$ 76.39
Total shares of common stock subject to conversion (in shares)	10.9
Cost of call spread			$ 46.9
Purchase of note hedges			136.7
Proceeds from issuance of warrants			$ 89.8
Percentage of principal amount used as purchase price upon occurrence of fundamental change	100.00%
0.125% Notes [Member]
Convertible Debt [Abstract]
Repurchase of convertible senior notes		$ 504.4
Outstanding principal balance	$ 44.5
Unamortized debt issuance costs	$ 0.1
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				$ 52.6
Purchase of note hedges				108.7
Proceeds from issuance of warrants				$ 56.1
Percentage of principal amount used as purchase price upon occurrence of fundamental change	100.00%

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