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Collaborative Arrangements and Licensing Agreements [Abstract]

Fair Value Measurements

4. Fair Value Measurements

We use a three-tier fair value hierarchy to prioritize the inputs used in our fair value measurements. These tiers include: Level 1, defined as observable inputs such as quoted prices in active markets for identical assets, which includes our money market funds and treasury securities classified as available-for-sale securities and our investment in equity securities in publicly-held biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify the majority of our securities as Level 2. We obtain the fair value of our Level 2 investments from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value to the fair value based on observable market prices. During the nine months ended September 30, 2018, there were no transfers between our Level 1 and Level 2 investments. When we recognize transfers between levels of the fair value hierarchy, we recognize the transfer on the date the event or change in circumstances that caused the transfer occurs.

The following tables present the major security types we held at September 30, 2018 and December 31, 2017 that are regularly measured and carried at fair value. At September 30, 2018 and December 31, 2017, we did not have any financial instruments that we valued using Level 3 inputs. The tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities’ fair value (in thousands):

	At September 30, 2018		Quoted Prices in Active Markets (Level 1)		Significant Other Observable Inputs (Level 2)
Cash equivalents (1)	$	395,649	$	395,649	$	—
Corporate debt securities (2)		1,078,960		—		1,078,960
Debt securities issued by U.S. government agencies (3)		175,167		—		175,167
Debt securities issued by the U.S. Treasury (3)		164,053		164,053		—
Debt securities issued by states of the U.S. and political subdivisions of the states (3)		80,658		—		80,658
Total	$	1,894,487	$	559,702	$	1,334,785

	At December 31, 2017		Quoted Prices in Active Markets (Level 1)		Significant Other Observable Inputs (Level 2)
Cash equivalents (1)	$	86,262	$	86,262	$	—
Corporate debt securities (3)		647,461		—		647,461
Debt securities issued by U.S. government agencies (3)		136,325		—		136,325
Debt securities issued by the U.S. Treasury (3)		30,818		30,818		—
Debt securities issued by states of the U.S. and political subdivisions of the states (4)		93,932		—		93,932
Total	$	994,798	$	117,080	$	877,718

(1)

Included in cash and cash equivalents on our condensed consolidated balance sheet.

(2)

At September 30, 2018, $19.7 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.

(3)

Included in short-term investments on our condensed consolidated balance sheet.

(4)

At December 31, 2017, $3.5 million was included in cash and cash equivalents on our condensed consolidated balance sheet, with the difference included in short-term investments on our condensed consolidated balance sheet.

Other Fair Value Disclosures

Novartis Future Stock Purchase

In January 2017, we and Akcea entered into a SPA with Novartis. As part of the SPA, Novartis was required to purchase $50 million of Akcea’s common stock at the IPO price or our common stock at a premium if an IPO did not occur by April 2018. Therefore, at the inception of the SPA, we recorded a $5.0 million asset representing the fair value of the potential future premium we could have received if Novartis purchased our common stock. We determined the fair value of the future premium by calculating the value based on the stated premium in the SPA and estimating the probability of an Akcea IPO. We also included a lack of marketability discount when we determined the fair value of the premium because we would have issued unregistered shares to Novartis if they had purchased our common stock. We measured this asset using Level 3 inputs and recorded it in other assets on our consolidated balance sheet. Because Akcea completed its IPO before April 2018, Novartis did not purchase additional shares of Ionis stock. Therefore, we wrote-off the remaining balance to other expenses in the third quarter of 2017 because this asset no longer had any value.

The following is a reconciliation of the potential premium we would have received if Akcea had not completed its IPO, measured at fair value on a recurring basis using significant unobservable inputs (Level 3) for the nine months ended September 30, 2017 (in thousands):


Beginning balance of Level 3 instruments at January 1, 2017	$	—
Value of the potential premium we would have received from Novartis at inception of the SPA (January 2017)		5,035
Recurring fair value adjustment during the nine months ended September 30, 2017		(5,035	)
Ending balance of Level 3 instruments at September 30, 2017	$	—

Convertible Notes

Our 1 percent notes had a fair value of $725.7 million at September 30, 2018. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.

- Definition

The entire disclosure for the fair value of financial instruments (as defined), including financial assets and financial liabilities (collectively, as defined), and the measurements of those instruments as well as disclosures related to the fair value of non-financial assets and liabilities. Such disclosures about the financial instruments, assets, and liabilities would include: (1) the fair value of the required items together with their carrying amounts (as appropriate); (2) for items for which it is not practicable to estimate fair value, disclosure would include: (a) information pertinent to estimating fair value (including, carrying amount, effective interest rate, and maturity, and (b) the reasons why it is not practicable to estimate fair value; (3) significant concentrations of credit risk including: (a) information about the activity, region, or economic characteristics identifying a concentration, (b) the maximum amount of loss the entity is exposed to based on the gross fair value of the related item, (c) policy for requiring collateral or other security and information as to accessing such collateral or security, and (d) the nature and brief description of such collateral or security; (4) quantitative information about market risks and how such risks are managed; (5) for items measured on both a recurring and nonrecurring basis information regarding the inputs used to develop the fair value measurement; and (6) for items presented in the financial statement for which fair value measurement is elected: (a) information necessary to understand the reasons for the election, (b) discussion of the effect of fair value changes on earnings, (c) a description of [similar groups] items for which the election is made and the relation thereof to the balance sheet, the aggregate carrying value of items included in the balance sheet that are not eligible for the election; (7) all other required (as defined) and desired information.

+ References + Details

Other Obligations

9 Months Ended

Sep. 30, 2018

Other Obligations [Abstract]

Other Obligations

5. Other Obligations

Line of Credit Arrangement

In June 2015, we entered into a five-year revolving line of credit agreement with Morgan Stanley Private Bank, National Association, or Morgan Stanley. We amended the credit agreement in February 2016 to increase the amount available for us to borrow. Under the amended credit agreement, we can borrow up to a maximum of $30 million of revolving credit for general working capital purposes. Under the credit agreement interest is payable monthly in arrears on the outstanding principal at a borrowing rate based on our option of:

(i)	a floating rate equal to the one-month London Interbank Offered Rate, or LIBOR, in effect plus 1.25 percent per annum;

(ii)	a fixed rate equal to LIBOR plus 1.25 percent for a period of one, two, three, four, six, or twelve months as elected by us; or

(iii)

a fixed rate equal to the LIBOR swap rate during the period of the loan.

Additionally, we pay 0.25 percent per annum, payable quarterly in arrears, for any amount unused under the credit facility. As of September 30, 2018 we had $12.5 million in outstanding borrowings under the credit facility with a 2.31 percent fixed interest rate and a maturity date of September 2019, which we used to fund our capital equipment needs consistent with our historical practice to finance these costs.

The credit agreement includes customary affirmative and negative covenants and restrictions. We are in compliance with all covenants of the credit agreement.

Research and Development and Manufacturing Facilities

In July 2017, we purchased the building that houses our primary R&D facility and the building that houses our manufacturing facility for $79.4 million and $14.0 million, respectively. We financed the purchase of our primary R&D facility and our manufacturing facility, with mortgage debt of $51.3 million and $9.1 million, respectively. Our primary R&D facility mortgage has an interest rate of 3.88 percent. Our manufacturing facility has an interest rate of 4.20 percent. During the first five years of both mortgages, we are only required to make interest payments. Both mortgages mature in August 2027.

Collaborative Arrangements and Licensing Agreements

9 Months Ended

Sep. 30, 2018

Collaborative Arrangements and Licensing Agreements

6. Collaborative Arrangements and Licensing Agreements

Below, we have included all of our significant collaborations because we adopted Topic 606 on January 1, 2018. We have included new disclosures for each of our collaborations as required under Topic 606.

Strategic Partnership

Biogen

We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders. These collaborations combine our expertise in creating antisense drugs with Biogen's expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved drug to treat people with spinal muscular atrophy, or SMA. In December 2017, we entered into a collaboration with Biogen to identify new antisense drugs for the treatment of SMA. Additionally, we and Biogen are currently developing six other drugs to treat neurodegenerative diseases under these collaborations, including IONIS-SOD1_Rx for ALS, IONIS-MAPT_Rxfor Alzheimer’s disease_, IONIS-C9_Rxfor ALS, and IONIS-BIIB6_Rx, IONIS-BIIB7_Rx and IONIS-BIIB8_Rx to treat undisclosed neurodegenerative diseases. In addition to these drugs, we and Biogen are evaluating numerous additional targets to develop drugs to treat neurological diseases. Most recently, in April 2018, we entered into a new strategic collaboration for the treatment of neurological diseases with Biogen. From inception through September 2018, we have received over $1.9 billion from our Biogen collaborations, including $1 billion we received from Biogen in the second quarter of 2018 when we entered into the 2018 strategic neurology collaboration.

SPINRAZA

In January 2012, we entered into a collaboration agreement with Biogen to develop and commercialize SPINRAZA, an RNA-targeted therapy for the treatment of SMA. In December 2016, the FDA approved SPINRAZA for the treatment of SMA in pediatric and adult patients.

From inception through September 2018, we earned $717 million in total revenue under our SPINRAZA collaboration, including $281 million in revenue from SPINRAZA royalties and $436 million in R&D revenue. We are receiving tiered royalties ranging from 11 percent to 15 percent on any sales of SPINRAZA. We have exclusively in-licensed patents related to SPINRAZA from Cold Spring Harbor Laboratory and the University of Massachusetts. We pay Cold Spring Harbor Laboratory and the University of Massachusetts a low single digit royalty on sales of SPINRAZA. Biogen is responsible for all further global development, regulatory and commercialization activities and costs for SPINRAZA.

Over the course of our SPINRAZA collaboration, we identified two performance obligations, which were to perform R&D services and to deliver the SPINRAZA license to Biogen. As we achieved milestone payments for our R&D services, we included these amounts in our transaction price for our R&D services performance obligation. We recognized revenue for our R&D services performance obligation over our period of performance through December 2016. We recognized the $75 million license fee for SPINRAZA as revenue when we delivered the license to Biogen in July 2016 because Biogen had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Biogen.

We also earned additional milestone payments subsequent to delivering the license to Biogen that we recognized in full in the period each milestone payment became probable because we did not have a performance obligation related to each milestone payment. For example, we received $90 million of milestone payments for the approval of SPINRAZA in the EU and Japan in 2017 and recognized the full amounts into revenue in the period Biogen achieved the milestone events.

Neurology

In December 2012, we and Biogen entered into a collaboration agreement to develop and commercialize novel antisense drugs to up to three targets to treat neurodegenerative diseases. We are responsible for the development of each of the drugs through the completion of the initial Phase 2 clinical study for such drug. Biogen has the option to license a drug from each of the three programs through the completion of the first Phase 2 study for each program. We are currently advancing IONIS-MAPT_Rx for Alzheimer’s disease under this collaboration. If Biogen exercises its option for a drug, it will assume all further global development, regulatory and commercialization responsibilities and costs for that drug.

Under the terms of the agreement, we received an upfront payment of $30 million. Over the term of the collaboration, we are eligible to receive up to $210 million in a license fee and milestone payments per program, plus a mark-up on the cost estimate of the Phase 1 and 2 studies. The $210 million per program consists of up to $10 million in development milestone payments, plus a mark-up on the cost estimate of the Phase 1 and 2 studies and up to $130 million in milestone payments if Biogen achieves pre-specified regulatory milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on sales of any drugs resulting from each of the three programs. From inception through September 2018, we have received $58 million in milestone payments and upfront fees under this collaboration. We will achieve the next payment of $7.5 million if we continue to advance IONIS-MAPT_Rx.

At the commencement of this collaboration, we identified one performance obligation, which was to perform R&D services for Biogen. At inception, we determined the transaction price to be the $30 million upfront payment we received and allocated it to our single performance obligation. As we achieve milestone payments for our R&D services, we include these amounts in our transaction price for our R&D services performance obligation. We are recognizing revenue for our R&D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our performance obligation in December 2020. From inception through September 2018, we have included $40 million in total payments in the transaction price for our R&D services performance obligation.

2013 Strategic Neurology

In September 2013, we and Biogen entered into a long-term strategic relationship focused on applying antisense technology to advance the treatment of neurodegenerative diseases. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for neurological diseases and has the option to license drugs resulting from this collaboration. The exclusivity for neurological diseases will last through September 2019, and may be extended for any drug development programs Biogen is pursuing under the collaboration. We will usually be responsible for drug discovery and early development of antisense drugs and Biogen will have the option to license antisense drugs after Phase 2 proof of concept. In October 2016, we expanded our collaboration to include additional research activities we will perform. If Biogen exercises its option for a drug, it will assume all further global development, regulatory and commercialization responsibilities and costs for that drug. We are currently advancing five drugs, IONIS-SOD1_Rx, IONIS-C9_Rx, IONIS-BIIB6_Rx, IONIS-BIIB7_Rx and IONIS-BIIB8_Rx under this collaboration. Biogen will be responsible for all of the drug discovery and development activities for drugs using other modalities.

Under the terms of the agreement, we received an upfront payment of $100 million and are eligible to receive milestone payments, license fees and royalty payments for all drugs developed through this collaboration, with the specific amounts dependent upon the modality of the molecule advanced by Biogen. For each antisense molecule that is chosen for drug discovery and development under this collaboration, we are eligible to receive up to approximately $260 million in a license fee and milestone payments per program. The $260 million per program consists of approximately $60 million in development milestones, including amounts related to the cost of clinical trials, and up to $130 million in milestone payments if Biogen achieves pre-specified regulatory milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on sales from any antisense drugs developed under this collaboration. If Biogen chooses to advance drugs using other modalities, such as small molecules or monoclonal antibodies, we are eligible to receive up to $90 million in milestone payments per program. The $90 million per program consists of up to $35 million in development milestone payments and up to $55 million in milestone payments if Biogen achieves pre-specified regulatory milestones. In addition, we are eligible to receive tiered single-digit royalties on sales from any drugs using non-antisense modalities developed under this collaboration. From inception through September 2018, we have received over $170 million in upfront fees, milestone payments and other payments under this collaboration, not including a $10 million milestone payment we earned in the third quarter of 2018 for Biogen’s initiation of a Phase 1 study for IONIS-C9_Rxwhich we received in the fourth quarter of 2018. We will achieve the next payment of up to $10 million if we advance a program under this collaboration.

At the commencement of our strategic neurology collaboration, we identified one performance obligation, which was to perform R&D services for Biogen. At inception, we determined the transaction price to be the $100 million upfront payment we received and allocated it to our single performance obligation. As we achieve milestone payments for our R&D services, we include these amounts in our transaction price for our R&D services performance obligation. We are recognizing revenue for our R&D services performance obligation based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our performance obligation in September 2019. From inception through September 2018, we have included $145 million in total payments in the transaction price for our R&D services performance obligation. In the third quarter of 2018, we earned a $10 million milestone payment when Biogen initiated a Phase 1 study of IONIS-C9_Rx. We recognized this milestone payment in full in the third quarter because we do not have any performance obligations related to this milestone payment. Additionally, we concluded that the payment is not related to our R&D services performance obligation.

New antisense drugs for the treatment of SMA

In December 2017, we entered into a collaboration agreement with Biogen to identify new antisense drugs for the treatment of SMA. Biogen will have the option to license therapies arising out of this collaboration following the completion of preclinical studies. Upon licensing, Biogen will be responsible for all further global development, regulatory and commercialization activities and costs for such therapies. Under the collaboration agreement, we received a $25 million upfront payment in December 2017. We will receive development and regulatory milestone payments from Biogen if new drugs advance towards marketing approval. In total over the term of our collaboration, we are eligible to receive up to $1.2 billion in license fees, milestone payments and other payments, including up to $80 million for the achievement of development milestones, up to $180 million for the achievement of commercialization milestones and up to $800 million for the achievement of sales milestones. In addition, we are eligible to receive tiered royalties from the mid-teens to mid-20 percent range on net sales. We will achieve the next payment of up to $60 millionfor the license of a drug under this collaboration.

At the commencement of this collaboration, we identified one performance obligation, which was to perform R&D services for Biogen. We determined the transaction price to be the $25 million upfront payment we received when we entered into the collaboration. We allocated the transaction price to our single performance obligation. We are recognizing revenue for our R&D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our performance obligation in December 2020.

2018 Strategic Neurology Collaboration

In April 2018, we and Biogen entered into a new strategic collaboration to develop novel antisense drugs for a broad range of neurological diseases and entered into a SPA. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for these diseases for 10 years. We are responsible for the identification of antisense drug candidates based on selected targets, while Biogen will have the option to license therapies arising out of this collaboration and will be responsible for and pay for non-clinical studies, clinical development, manufacturing, and commercialization.

In the second quarter of 2018, we received $1 billion from Biogen, comprised of $625 million to purchase our stock at a 25 percent cash premium and $375 million in an upfront payment. We are eligible to receive up to $270 million for each drug that achieves marketing approval. In addition, we are eligible to receive tiered royalties up to the 20 percent range on net sales. We will achieve the next payment of $7.5 million if Biogen designates a target under this collaboration.

At the commencement of this collaboration, we identified one performance obligation, which was to perform R&D services for Biogen. We determined our transaction price to be $552 million, comprised of $375 million from the upfront payment and $177 million for the premium paid by Biogen for its purchase of our common stock. We determined the fair value of the premium we received by using the stated premium in the SPA and applying a lack of marketability discount. We included a lack of marketability discount in our valuation of the premium because Biogen received restricted shares. We allocated the transaction price to our single performance obligation. We are recognizing revenue for our R&D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our performance obligation in June 2028.

During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):

	Three Months Ended September 30,						Nine Months Ended September 30,
	2018			2017			2018			2017
SPINRAZA royalties (commercial revenue)	$	70.0		$	32.9		$	167.7		$	60.5
R&D revenue		34.8			54.9			66.9			137.1
Total revenue from our relationship with Biogen		104.8			87.8			234.6			197.6
Percentage of total revenue		72	%		74	%		58	%		57	%

Our condensed consolidated balance sheet at September 30, 2018 and December 31, 2017 included deferred revenue of $593.6 million and $93.6 million, respectively, related to our relationship with Biogen.

Research, Development and Commercialization Partners

AstraZeneca

Cardiac, Renal and Metabolic Diseases Collaboration

In July 2015, we and AstraZeneca formed a collaboration to discover and develop antisense therapies for treating cardiac, renal and metabolic diseases. Under our collaboration AstraZeneca has licensed three drugs from us. As part of the agreement, we granted AstraZeneca an exclusive license to IONIS-AZ4-2.5-L_Rx, a drug we designed to treat cardiovascular disease and our first drug that combines our Generation 2.5 and LIgand-Conjugated Antisense, or LICA, technology. We also granted AstraZeneca the option to license a drug for each additional target advanced under this research collaboration. In February 2018, AstraZeneca licensed a second drug under our collaboration, IONIS-AZ5-2.5_Rx, a drug we designed to treat a genetically associated form of kidney disease. In March 2018, AstraZeneca licensed a third drug under our collaboration, IONIS-AZ6-2.5-L_Rx, a drug we designed to inhibit an undisclosed target to treat patients with nonalcoholic steatohepatitis, or NASH. AstraZeneca is responsible for all further global development, regulatory and commercialization activities and costs for IONIS-AZ4-2.5-L_Rx, IONIS-AZ5-2.5_Rx andIONIS-AZ6-2.5-L_Rx and any other future drugs AstraZeneca licenses.

Under the terms of the agreement, we received a $65 million upfront payment. We are eligible to receive license fees and milestone payments of up to more than $4 billion as drugs under this collaboration advance, including up to $1.1 billion for the achievement of development milestones and up to $2.9 billion for regulatory milestones. In addition, we are eligible to receive tiered royalties up to the low teens on sales from any product that AstraZeneca successfully commercializes under this collaboration agreement. From inception through September 2018, we have received over $165 million in upfront fees, license fees, milestone payments, and other payments under this collaboration, including a $10 million milestone payment we earned in the third quarter of 2018 when AstraZeneca initiated a Phase 1 trial for IONIS-AZ4-2.5-L_Rx. We will achieve the next payment of $10 million under this collaboration if we advance a drug under this collaboration.

At the commencement of this collaboration, we identified one performance obligation, which was to perform R&D services for AstraZeneca. We determined the transaction price to be the $65 million upfront payment we received and we allocated it to our single performance obligation. We are recognizing revenue for our R&D services performance obligation as we perform services based on our effort to satisfy this performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy this performance obligation in August 2021. As we achieve milestone payments for our R&D services, we include these amounts in our transaction price for our R&D services performance obligation. From inception through September 2018, we have included $90 million in payments in the transaction price for our R&D services performance obligation.

We identified separate performance obligations upon AstraZeneca’s license of IONIS-AZ5-2.5_Rx and IONIS-AZ6-2.5-L_Rx in the first quarter of 2018 because the licenses are distinct from our other performance obligation and each other. We recognized each $30 million license fee in the first quarter of 2018 because AstraZeneca had full use of the licenses without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the licenses after we delivered them to AstraZeneca.

In the third quarter of 2018, we earned a $10 million milestone payment when AstraZeneca initiated a Phase 1 study of IONIS-AZ4-2.5-L_Rx. We recognized this milestone payment in full in the third quarter because we do not have any performance obligations related to this milestone payment. Additionally, we concluded that the payment is not related to our R&D services performance obligation.

Oncology Collaboration

In December 2012, we entered into a collaboration agreement with AstraZeneca to discover and develop antisense drugs to treat cancer. As part of the agreement, we granted AstraZeneca an exclusive license to develop and commercialize danvatirsen (formerly IONIS-STAT3-2.5_Rx) for the treatment of cancer. AstraZeneca is now responsible for all global development, regulatory and commercialization activities for danvatirsen. We and AstraZeneca have evaluated danvatirsen in people with head and neck cancer, advanced lymphoma and advanced metastatic hepatocellular carcinoma. AstraZeneca is evaluating danvatirsen in combination with Imfinzi (durvalumab), AstraZeneca’s programmed death ligand, or PD-L1, blocking drug, in people with head and neck cancer, metastatic bladder cancer and metastatic non-small cell lung cancer. In addition, we and AstraZeneca established an oncology research program. AstraZeneca has the option to license drugs resulting from the program, and if AstraZeneca exercises its option for a drug, it will be responsible for all further global development, regulatory and commercialization activities and costs for such drug.

Under the terms of this agreement, we received $31 million in upfront payments. We are eligible to receive milestone payments and license fees from AstraZeneca as programs advance in development. If AstraZeneca successfully develops danvatirsen and another drug under the research program, we could receive license fees and milestone payments of up to more than $450 million, including up to $152 million for the achievement of development milestones and up to $275 million for the achievement of regulatory milestones. In addition, we are eligible to receive tiered royalties up to the low to mid-teens on sales from any drugs resulting from these programs. From inception through September 2018, we have received $97.8 million in upfront fees, milestone payments, and other payments under this oncology collaboration, not including nearly $30 million in milestone payments we achieved when AstraZeneca advanced two programs in the fourth quarter of 2018. We will achieve the next payment of up to $25.0 million if we advance a drug under our cancer research program with AstraZeneca.

At the commencement of this collaboration, we identified four performance obligations. We determined the transaction price to be the $31 million in upfront payments we received. We allocated the transaction price based on the estimated stand-alone selling price of each of our performance obligations and recognized the associated revenue over the period of our performance. We recognized revenue for three of our obligations over our period of performance, concluding in March 2014. Our remaining performance obligation was to perform R&D services. We allocated $7.6 million to this performance obligation and recognized the associated revenue over the period of our performance, which ended in February 2018. As we achieved milestone payments for our R&D services, we included these amounts in our transaction price for our R&D services performance obligation.

During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with AstraZeneca (in millions, except percentage amounts):

	Three Months Ended September 30,								Nine Months Ended September 30,
	2018				2017				2018				2017
R&D revenue		$	14.2			$	4.8			$	86.5			$	14.8
Percentage of total revenue			10	%			4	%			21	%			4	%

Our condensed consolidated balance sheet at September 30, 2018 and December 31, 2017 included deferred revenue of $44.9 million and $57.7 million, respectively, related to our relationship with AstraZeneca.

Bayer

In May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI_Rx for the prevention of thrombosis. We were responsible for completing a Phase 2 study of IONIS-FXI_Rx in people with end-stage renal disease on hemodialysis. Under the terms of the agreement, we received a $100 million upfront payment in the second quarter of 2015. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI_Rx and to initiate development of IONIS-FXI-L_Rx, which Bayer licensed. In conjunction with the decision to advance these programs, we received a $75 million payment from Bayer. We are conducting a Phase 2b study evaluating IONIS-FXI_Rx in people with end-stage renal disease on hemodialysis to finalize dose selection. Additionally, we plan to develop IONIS-FXI-L_Rx through Phase 1. Following these studies and Bayer's decision to further advance these programs, Bayer will be responsible for all global development, regulatory and commercialization activities and costs for both drugs.

We are eligible to receive additional milestone payments as each drug advances toward the market. In total over the term of this collaboration, we are eligible to receive up to $385 million in license fees, milestone payments and other payments, including up to $125 million for the achievement of development milestones and up to $110 million for the achievement of commercialization milestones. In addition, we are eligible to receive tiered royalties in the low to high 20 percent range on gross margins of both drugs combined. From inception through September 2018, we have received over $175 million from our Bayer collaboration. We will achieve the next payment of $10 million if a program advances under this collaboration.

At the commencement of this collaboration, we identified three performance obligations. We determined the transaction price to be the $100 million in upfront payment we received. We allocated the transaction price based on the relative stand-alone selling prices of each of our performance obligations and recognized the associated revenue as follows:

●

We recognized $91.2 million for the exclusive license of IONIS-FXI_Rxin May 2015 because Bayer had full use of the license without any continuing involvement from us.

●

We recognized $4.3 million for the R&D services for IONIS-FXI_Rx over the period of our performance, which ended in November 2016.

●

We allocated $4.5 million for API, which we are recognizing into revenue as we deliver the API.

In February 2017, when we amended our collaboration with Bayer, we identified two new performance obligations, one for the license of IONIS-FXI-L_Rx and one for R&D services. We determined the transaction price to be the $75 million payment. We allocated $64.9 million to the license of IONIS-FXI-L_Rx based on its estimated stand-alone selling price and recognized the associated revenue upon our delivery of the license in the first quarter of 2017. We allocated $10.1 million to our R&D services performance obligation based on an estimated stand-alone selling price. We are recognizing revenue for our R&D services performance obligation as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our R&D services performance obligation in May 2019.

During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Bayer (in millions, except percentage amounts):

	Three Months Ended September 30,								Nine Months Ended September 30,
	2018				2017				2018				2017
R&D revenue		$	1.9			$	0.4			$	3.3			$	66.0
Percentage of total revenue			1	%			0	%			1	%			19	%

Our condensed consolidated balance sheet at September 30, 2018 and December 31, 2017 included deferred revenue of $6.0 million and $9.3 million, respectively, related to our relationship with Bayer.

Janssen Biotech, Inc.

In December 2014, we entered into a collaboration agreement with Janssen Biotech, Inc. to discover and develop antisense drugs that can be locally administered, including oral delivery, to treat autoimmune disorders of the gastrointestinal tract. Janssen has the option to license drugs from us through the designation of a development candidate for up to three programs. Prior to option exercise we are responsible for the discovery activities to identify a development candidate. If Janssen exercises an option for one of the programs, it will be responsible for the global development, regulatory and commercial activities under that program. Under the terms of the agreement, we received $35 million in upfront payments. We are eligible to receive up to more than $800 million in license fees and milestone payments for these programs, including up to $175 million for the achievement of development milestones, up to $440 million for the achievement of regulatory milestones and up to $180 million for the achievement of commercialization milestones. From inception through September 2018, we have received $75 million, including $15 million in license fees when Janssen licensed IONIS-JBI1-2.5_Rx and IONIS-JBI2-2.5_Rx from us in 2016 and 2017, respectively. We also received $5 million in January 2018 for the initiation of a Phase 1 study of IONIS-JBI1-2.5_Rxin late 2017. In addition, we are eligible to receive tiered royalties up to the near teens on sales from any drugs resulting from this collaboration. We will achieve the next payment of $5 million if Janssen continues to advance a target under this collaboration.

At the commencement of this collaboration, we identified one performance obligation, which was to perform R&D services for Janssen. We determined the transaction price to be the $35 million upfront payments we received. We allocated the $35 million to our single performance obligation. As we achieved milestone payments for our R&D services, we included these amounts in our transaction price for our R&D services performance obligation. We recognized revenue for our R&D services performance obligation over our period of performance, through November 2017.

We identified separate performance obligations each time Janssen licensed one of our drugs under our collaboration because the licenses we granted to Janssen were distinct from our other performance obligations. We recognized the $10 million license fee for IONIS-JBI1-2.5_Rx in July 2016 and $5 million for the license of IONIS-JBI2-2.5_Rx in November 2017, because Janssen had full use of the licenses without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the licenses after we delivered them to Janssen.

During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Janssen (in millions, except percentage amounts):

	Three Months Ended September 30,								Nine Months Ended September 30,
	2018				2017				2018				2017
R&D revenue		$	0.9			$	3.4			$	6.6			$	18.1
Percentage of total revenue			1	%			3	%			2	%			5	%

We did not have any deferred revenue from our relationship with Janssen at September 30, 2018 or December 31, 2017.

Roche

Huntington's Disease

In April 2013, we formed an alliance with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, to develop treatments for Huntington's disease, or HD, based on our antisense technology. Roche had the option to license the drugs from us through the completion of the first Phase 1 trial. Under the agreement, we are responsible for the discovery and development of an antisense drug targeting huntingtin, or HTT, protein. We evaluated a drug targeting HTT, IONIS-HTT_Rx, in a Phase 1/2a clinical study in people with early stage HD.

In December 2017, upon completion of the Phase 1/2a study, Roche exercised its option to license IONIS-HTT_Rxand is now responsible for the global development, regulatory and commercialization activities for IONIS-HTT_Rx. Under the terms of the agreement, we received an upfront payment of $30 million in April 2013. In December 2016, we updated development activities for IONIS-HTT_Rx and as a result we were eligible for an additional $3 million payment, which we achieved in 2017. We are eligible to receive up to $365 million in a license fee and milestone payments including up to $70 million for the achievement of development milestones, up to $170 million for the achievement of regulatory milestones and up to $80 million for the achievement of commercialization milestones. In addition, we are eligible to receive up to $136.5 million in milestone payments for each additional drug successfully developed. We are also eligible to receive tiered royalties up to the mid-teens on any sales of any product resulting from this alliance. From inception through September 2018, we have received over $110 million in upfront fees, milestone payments and license fees for advancing IONIS-HTT_Rx, including the $45 million license fee we received in January 2018 for IONIS-HTT_Rx. We will achieve the next payment of $35 million if Roche initiates a pivotal study for IONIS-HTT_Rx.

At the commencement of this collaboration, we identified one performance obligation, which was to perform R&D services for Roche. We determined the transaction price to be the $30 million upfront payment we received and allocated it to our single performance obligation. As we achieved milestone payments for our R&D services, we included these amounts in our transaction price for our R&D services performance obligation. We recognized revenue for our R&D services performance obligation over our period of performance, through September 2017.

We identified a second performance obligation upon Roche’s license of IONIS-HTT_Rx in the fourth quarter of 2017 because the license we granted to Roche is distinct from our other performance obligation. We recognized the $45 million license fee for IONIS-HTT_Rx as revenue at that time because Roche had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Roche.

We do not have any remaining performance obligations related to IONIS-HTT_Rx under this collaboration with Roche, however we can still earn additional payments and royalties as Roche advances IONIS-HTT_Rx.

IONIS-FB-L_Rx for Complement-Mediated Diseases

In October 2018, we entered into a collaboration agreement with Roche to develop IONIS-FB-L_Rx for the treatment of complement-mediated diseases. The first indication we plan to pursue is the treatment of patients with Geographic Atrophy, or GA, the advanced stage of dry age-related macular degeneration, or AMD. We are responsible for conducting a Phase 2 study in patients with dry AMD. In addition, we are exploring the drug in a severe and rare renal indication. Roche has the option to license IONIS-FB-L_Rx at the completion of these studies. Upon licensing, Roche will be responsible for all further global development, regulatory and commercialization activities and costs.

Under this new collaboration agreement, we received a $75 million upfront payment in October 2018. We are eligible to receive up to $684 million in development, regulatory and sales milestone payments and license fees. In addition, we are also eligible to receive tiered royalties from the high teens to twenty percent on net sales. We will achieve the next payment of $20 million when we advance the Phase 2 study in patients with dry AMD.

During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):

	Three Months Ended September 30,								Nine Months Ended September 30,
	2018				2017				2018				2017
R&D revenue		$	1.8			$	4.5			$	5.4			$	5.9
Percentage of total revenue			1	%			4	%			1	%			2	%

We did not have any deferred revenue from our relationship with Roche at September 30, 2018 or December 31, 2017.

GSK

In March 2010, we entered into an alliance with GSK using our antisense drug discovery platform to discover and develop new drugs against targets for rare and serious diseases, including infectious diseases and some conditions causing blindness. Under the terms of the agreement, we received upfront payments of $35 million.

GSK is advancing two drugs targeting hepatitis B virus, or HBV, under our collaboration: IONIS-HBV_Rx and IONIS-HBV-L_Rx. GSK is currently conducting Phase 2 studies for both of these drugs, which we designed to reduce the production of viral proteins associated with HBV infection. In March 2016, we and GSK amended the development plan for IONIS-HBV_Rx to allow GSK to conduct all further development activities for this program. GSK has the exclusive option to license the drugs resulting from this alliance at Phase 2 proof-of-concept for a license fee.

Under our agreement, if GSK successfully develops these drugs and achieves pre-agreed sales targets, we could receive license fees and milestone payments of $262 million, including up to $47.5 million for the achievement of development milestones, up to $120 million for the achievement of regulatory milestones and up to $70 million for the achievement of commercialization milestones. In addition, we are eligible to receive tiered royalties up to the mid-teens on sales from any product that GSK successfully commercializes under this alliance. From inception through September 2018, we have received more than $162 million in payments under this alliance with GSK. We will achieve the next payment of up to $25 million if GSK licenses a drug under this program.

At the commencement of this collaboration, we identified one performance obligation, which was to perform R&D services for GSK. We determined the transaction price to be the $35 million upfront payment we received and allocated it to our single performance obligation. As we achieved milestone payments for our R&D services, we included these amounts in our transaction price for our R&D services performance obligation. We recognized revenue for our R&D services performance obligation over our period of performance, through March 2015. We do not have any remaining performance obligations under our collaboration with GSK, however we can still earn additional payments and royalties as GSK advances these drugs.

During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):

	Three Months Ended September 30,								Nine Months Ended September 30,
	2018				2017				2018				2017
R&D revenue		$	0.1			$	4.6			$	1.5			$	14.4
Percentage of total revenue			0	%			4	%			0	%			4	%

Our revenue for the nine months ended September 30, 2017, was from our work on the programs under our collaboration with GSK. We did not have any deferred revenue from our relationship with GSK at September 30, 2018 or December 31, 2017.

Akcea Collaborations

The following collaboration agreements relate to Akcea, our majority owned affiliate. Our consolidated results include all the revenue earned and cash received under these collaboration agreements. We reflect the noncontrolling interest attributable to other owners of Akcea’s common stock in a separate line on the statement of operations and a separate line within stockholders’ equity in our condensed consolidated balance sheet.

Novartis

In January 2017, we and Akcea initiated a collaboration with Novartis to develop and commercialize AKCEA-APO(a)-L_Rx and AKCEA-APOCIII-L_Rx.Under the collaboration agreement, Novartis has an exclusive option to further develop and commercialize AKCEA-APO(a)-L_Rx and AKCEA-APOCIII-L_Rx. Akcea is responsible for completing a Phase 2 program, conducting an end-of-Phase 2 meeting with the FDA and providing initial quantities of API for each drug. If Novartis exercises an option for one of these drugs, Novartis will be responsible for all further global development, regulatory and co-commercialization activities and costs for such drug.

Akcea received a $75 million upfront payment in the first quarter of 2017, of which it retained $60 million and paid us $15 million as a sublicense fee. If Novartis exercises its option for a drug, Novartis will pay Akcea a license fee equal to $150 million for each drug it licenses. In addition, for AKCEA-APO(a)-L_Rx, Akcea is eligible to receive up to $600 million in milestone payments, including $25 million for the achievement of a development milestone, up to $290 million for the achievement of regulatory milestones and up to $285 million for the achievement of commercialization milestones. In addition, for AKCEA-APOCIII-L_Rx, Akcea is eligible to receive up to $530 million in milestone payments, including $25 million for the achievement of a development milestone, up to $240 million for the achievement of regulatory milestones and up to $265 million for the achievement of commercialization milestones. Akcea is also eligible to receive tiered royalties in the mid-teens to low 20 percent range on net sales of AKCEA-APO(a)-L_Rx and AKCEA-APOCIII-L_Rx. Novartis will reduce these royalties upon the expiration of certain patents or if a generic competitor negatively impacts the product in a specific country. Akcea will pay 50 percent of these license fees, milestone payments and royalties to us as a sublicense fee. Akcea plans to co-commercialize any licensed drug commercialized by Novartis in selected markets under terms and conditions that we plan to negotiate with Novartis in the future, through its specialized sales force.

In conjunction with this collaboration, we and Akcea entered into a SPA with Novartis. As part of the SPA, Novartis purchased 1.6 million shares of our common stock for $100 million in the first quarter of 2017. As part of the SPA, Novartis was required to purchase $50 million of Akcea’s common stock at the IPO price or our common stock at a premium if an IPO did not occur by April 2018. Under the SPA, in July 2017, Novartis purchased $50 million of Akcea’s common stock in a separate private placement concurrent with the completion of its IPO at a price per share equal to the IPO price.

At the commencement of this collaboration, we identified four separate performance obligations:

●

R&D services for AKCEA-APO(a)-L_Rx;

●

R&D services for AKCEA-APOCIII-L_Rx;

●

API for AKCEA-APO(a)-L_Rx; and

●

API for AKCEA-APOCIII-L_Rx.

We determined that the R&D services for each drug and the API for each drug were distinct from our other performance obligations.

We determined our transaction price to be $108.4 million, comprised of the following:

●

$75 million from the upfront payment;

●

$28.4 million for the premium paid by Novartis for its purchase of our common stock at a premium in the first quarter of 2017; and

●

$5.0 million for the potential premium Novartis would have paid if they purchased our common stock in the future.

We allocated the transaction price based on the estimated stand-alone selling price of each performance obligation as follows:

●

$64.0 million for the R&D services for AKCEA-APO(a)-L_Rx;

●

$40.1 million for the R&D services for AKCEA-APOCIII-L_Rx;

●

$1.5 million for the delivery of AKCEA-APO(a)-L_Rx API; and

●

$2.8 million for the delivery of AKCEA-APOCIII-L_Rx API.

We are recognizing revenue related to the R&D services for the AKCEA-APO(a)-L_Rx and AKCEA-APOCIII-L_Rx performance obligations as we perform services based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy the significant portion of our performance obligation for AKCEA-APO(a)-L_Rx by December 2018 with the remainder by the end of March 2019. We currently estimate we will satisfy the significant portion of our performance obligation for AKCEA-APOCIII-L_Rx by June 2019 with the remainder by the end of December 2019. We recognized the amount attributed to the API supply for AKCEA-APO(a)-L_Rx when we delivered it to Novartis in 2017. We recognized the amount attributed to the API supply for AKCEA-APOCIII-L_Rx when we delivered it to Novartis in May 2018.

Akcea is responsible for the development activities under this collaboration. As such, Akcea is recognizing the associated revenue in its statement of operations, and we reflect all of Akcea’s revenue in our consolidated results. Akcea pays us sublicense fees for payments that it receives under the collaboration and we recognize those fees as revenue in our Ionis Core operating segment results and Akcea recognizes the fees as R&D expense. In our consolidated results, we eliminate this sublicense revenue and expense. Any cash Akcea receives is included in our consolidated balance sheet.

During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):

	Three Months Ended September 30,								Nine Months Ended September 30,
	2018				2017				2018				2017
R&D revenue		$	7.2			$	9.9			$	42.7			$	21.7
Percentage of total revenue			5	%			8	%			10	%			6	%

Our condensed consolidated balance sheet at September 30, 2018 and December 31, 2017 included deferred revenue of $34.8 million and $70.7 million, respectively, related to our relationship with Novartis.

PTC Therapeutics

In August 2018, Akcea entered into an exclusive license agreement with PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin America. Under the license agreement, Akcea will receive up to $26 million of payments, including $12 million which it received in the third quarter of 2018, $6 million upon the earlier of FDA or EMA approval of WAYLIVRA and up to $8 million of regulatory milestone payments. Akcea will receive royalties from PTC in the mid-20 percent range on net sales in Latin America for each drug. PTC's obligation to pay Akcea royalties begins on the earlier of 12 months after the first commercial sale of a product in Brazil or the date that PTC recognizes revenue of at least $10 million in Latin America. These royalties may be reduced upon expiration of certain patents or if a generic competitor negatively impacts PTC’s market share. Consistent with the agreements between Ionis and Akcea, the companies will share all payments, including royalties.

At the commencement of this collaboration, we identified two performance obligations, which were the licenses Akcea granted to PTC to commercialize TEGSEDI and WAYLIVRA in Latin America in the third quarter of 2018. Akcea recognized $12 million in license fee revenue at that time because PTC had full use of both licenses without any continuing involvement from Akcea. Akcea does not have any remaining performance obligations under its collaboration with PTC. Akcea can still earn additional payments and royalties as PTC commercializes the drugs.

Akcea is responsible for the activities under this collaboration. As such, Akcea is recognizing the associated revenue in its statement of operations, and we reflect all of Akcea’s revenue in our consolidated results. Akcea pays us sublicense fees for payments that it receives under the collaboration and we recognize those fees as revenue in our Ionis Core operating segment results and Akcea recognizes the fees as SG&A expense. For example, during the third quarter of 2018, we recognized $7.2 million of sublicense revenue in our Ionis Core operating segment results related to our portion of the PTC license fee Akcea paid us. In our consolidated results, we eliminate this sublicense revenue and expense. Any cash Akcea receives is included in our consolidated balance sheet.

During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with PTC (in millions, except percentage amounts):

	Three Months Ended September 30,							Nine Months Ended September 30,
	2018				2017			2018				2017
R&D revenue		$	12.0			$	0.0		$	12.0			$	0.0
Percentage of total revenue			8	%			—			3	%			—

Our condensed consolidated balance sheet at September 30, 2018 and December 31, 2017 did not include any deferred revenue related to our relationship with PTC.

Segment Information and Concentration of Business Risk

9 Months Ended

Sep. 30, 2018

Segment Information and Concentration of Business Risk [Abstract]

Segment Information and Concentration of Business Risk

7. Segment Information and Concentration of Business Risk

We have two reportable segments Ionis Core and Akcea Therapeutics. At September 30, 2018 we owned approximately 75 percent of Akcea. In October 2018, we received an additional 1.7 million shares of Akcea’s stock when TEGSEDI was approved by the FDA, increasing our ownership percentage to 76 percent. Segment income (loss) from operations includes revenue less operating expenses attributable to each segment.

In our Ionis Core segment we are exploiting our antisense technology to generate a broad pipeline of first-in-class and/or best-in-class drugs for us and our partners. Our Ionis Core segment generates revenue from a multifaceted partnering strategy.

Akcea is a biopharmaceutical company focused on developing and commercializing drugs to treat patients with rare and serious diseases.

The following tables show our segment revenue and income (loss) from operations for the three and nine months ended September 30, 2018 and 2017 (in thousands), respectively.

Three Months Ended September 30, 2018	Ionis Core		Akcea Therapeutics			Elimination of Intercompany Activity			Total
Revenue:
Commercial revenue:
SPINRAZA royalties	$	70,010	$	—		$	—		$	70,010
Licensing and other royalty revenue		7,946		12,000			(7,200	)		12,746
Total commercial revenue		77,956		12,000			(7,200	)		82,756
R&D revenue under collaborative agreements		100,105		7,241			(44,707	)		62,639
Total segment revenue	$	178,061	$	19,241		$	(51,907	)	$	145,395
Total operating expenses	$	87,664	$	84,249		$	(7,946	)	$	163,967
Income (loss) from operations	$	90,397	$	(65,008	)	$	(43,961	)	$	(18,572	)

Three Months Ended September 30, 2017 (as revised)	Ionis Core		Akcea Therapeutics			Elimination of Intercompany Activity			Total
Revenue:
Commercial revenue:
SPINRAZA royalties	$	32,890	$	—		$	—		$	32,890
Licensing and other royalty revenue		1,727		—			—			1,727
Total commercial revenue		34,617		—			—			34,617
R&D revenue under collaborative agreements		73,791		9,906			—			83,697
Total segment revenue	$	108,408	$	9,906		$	—		$	118,314
Total operating expenses	$	81,019	$	26,013		$	(30	)	$	107,002
Income (loss) from operations	$	27,389	$	(16,107	)	$	30		$	11,312

Nine Months Ended September 30, 2018	Ionis Core		Akcea Therapeutics			Elimination of Intercompany Activity			Total
Revenue:
Commercial revenue:
SPINRAZA royalties	$	167,743	$	—		$	—		$	167,743
Licensing and other royalty revenue		9,432		12,000			(7,200	)		14,232
Total commercial revenue		177,175		12,000			(7,200	)		181,975
R&D revenue under collaborative agreements		232,850		42,670			(49,936	)		225,584
Total segment revenue	$	410,025	$	54,670		$	(57,136	)	$	407,559
Total operating expenses	$	279,084	$	213,428		$	(12,796	)	$	479,716
Income (loss) from operations	$	130,941	$	(158,758	)	$	(44,340	)	$	(72,157	)

Nine Months Ended September 30, 2017 (as revised)	Ionis Core		Akcea Therapeutics			Elimination of Intercompany Activity			Total
Revenue:
Commercial revenue:
SPINRAZA royalties	$	60,467	$	—		$	—		$	60,467
Licensing and other royalty revenue		5,639		—			—			5,639
Total commercial revenue		66,106		—			—			66,106
R&D revenue under collaborative agreements		312,976		21,712			(54,407	)		280,281
Total segment revenue	$	379,082	$	21,712		$	(54,407	)	$	346,387
Total operating expenses	$	242,753	$	120,884		$	(54,497	)	$	309,140
Income (loss) from operations	$	136,329	$	(99,172	)	$	90		$	37,247

The following table shows our total assets by segment at September 30, 2018 and December 31, 2017 (in thousands), respectively.

Total Assets	Ionis Core		Akcea Therapeutics		Elimination of Intercompany Activity			Total
September 30, 2018	$	2,446,425	$	379,128	$	(577,641	)	$	2,247,913
December 31, 2017 (as revised)	$	1,342,578	$	268,804	$	(288,608	)	$	1,322,774

We have historically funded our operations from collaborations with corporate partners and a relatively small number of partners have accounted for a significant percentage of our revenue. Revenue from significant partners, which is defined as ten percent or more of our total revenue, was as follows:

	Three Months Ended September 30,				Nine Months Ended September 30,
	2018		2017		2018		2017
				(as revised)				(as revised)
Partner A		72%		74%		58%		57%
Partner B		10%		4%		21%		4%
Partner C		5%		8%		10%		6%
Partner D		8%		0%		3%		0%
Partner E		1%		0%		1%		19%

Contracts receivables from two significant partners comprised approximately 84 percent of our contracts receivables at September 30, 2018 and December 31, 2017.

Basis of Presentation (Policies)	9 Months Ended
Basis of Presentation (Policies)	Sep. 30, 2018
Basis of Presentation [Abstract]
Basis of Presentation	We prepared the unaudited interim condensed consolidated financial statements for the three and nine months ended September 30, 2018 and 2017 on the same basis as the audited financial statements for the year ended December 31, 2017. 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. Results for the interim periods are not necessarily indicative of the results 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, 2017 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.
Consolidation	In the condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our majority owned affiliate, Akcea Therapeutics, Inc. and its wholly owned subsidiaries, which we formed in December 2014. Prior to Akcea’s initial public offering, or IPO, in July 2017, we owned 100 percent of Akcea. From the closing of Akcea’s IPO in July 2017 through mid-April 2018, we owned approximately 68 percent of Akcea. In the second and third quarters of 2018, we received additional shares of Akcea’s stock related to our license of TEGSEDI and AKCEA-TTR-L_Rx to Akcea, increasing our ownership percentage to approximately 75 percent. We reflected the increase in our ownership in these financial statements. In October 2018, we received an additional 1.7 million shares of Akcea’s stock when TEGSEDI received marketing authorization in the U.S., increasing our ownership to approximately 76 percent. Refer to the section titled “Noncontrolling Interest in Akcea” in Note 2, Significant Accounting Policies, for further information related to our accounting for our investment in Akcea.

Significant Accounting Policies (Policies)

9 Months Ended

Sep. 30, 2018

Significant Accounting Policies [Abstract]

Revenue Recognition

Adoption of New Revenue Recognition Accounting Standard (Topic 606)

The following tables summarize the adjustments we were required to make to amounts we originally reported in 2017 to adopt Topic 606 (in thousands, except per share amounts):

Condensed Consolidated Balance Sheet

	At December 31, 2017
	As Previously Reported under Topic 605			Topic 606 Adjustment			As Revised
Current portion of deferred revenue	$	106,465		$	18,871		$	125,336
Long-term portion of deferred revenue	$	72,708		$	35,318		$	108,026
Accumulated deficit	$	(1,187,398	)	$	(53,636	)	$	(1,241,034	)
Noncontrolling interest in Akcea Therapeutics, Inc.	$	87,847		$	(3,580	)	$	84,267
Total stockholders’ equity	$	418,719		$	(53,439	)	$	365,280

Condensed Consolidated Statement of Operations

	Three Months Ended September 30, 2017
	As Previously Reported under Topic 605			Topic 606 Adjustment			As Revised
Revenue:
Commercial revenue:
SPINRAZA royalties	$	32,890		$	—		$	32,890
Licensing and other royalty revenue		879			848			1,727
Total commercial revenue		33,769			848			34,617
Research and development revenue under collaborative agreements		87,142			(3,445	)		83,697
Total revenue	$	120,911		$	(2,597	)	$	118,314
Income (loss) from operations	$	13,909		$	(2,597	)	$	11,312
Net income (loss)	$	(4,896	)	$	(2,597	)	$	(7,493	)
Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders	$	(976	)	$	(1,635	)	$	(2,611	)
Net income (loss) per share, basic and diluted	$	0.00		$	(0.02	)	$	(0.02	)

	Nine Months Ended September 30, 2017
	As Previously Reported under Topic 605			Topic 606 Adjustment		As Revised
Revenue:
Commercial revenue:
SPINRAZA royalties	$	60,467		$	—	$	60,467
Licensing and other royalty revenue		4,983			656		5,639
Total commercial revenue		65,450			656		66,106
Research and development revenue under collaborative agreements		269,917			10,364		280,281
Total revenue	$	335,367		$	11,020	$	346,387
Income from operations	$	26,227		$	11,020	$	37,247
Net income (loss)	$	(12,636	)	$	11,020	$	(1,616	)
Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders	$	(8,716	)	$	11,982	$	3,266
Net income (loss) per share, basic	$	0.02		$	0.11	$	0.13
Net income (loss) per share, diluted	$	0.02		$	0.11	$	0.13

Condensed Consolidated Statement of Cash Flows

	Nine Months Ended September 30, 2017
	As Previously Reported under Topic 605			Topic 606 Adjustment			As Revised
Net income (loss)	$	(12,636	)	$	11,020		$	(1,616	)
Adjustments to reconcile net income (loss) to net cash provided by operating activities:
Deferred contract revenue	$	42,091		$	(11,020	)	$	31,071
Cash and cash equivalents at beginning of period	$	84,685		$	—		$	84,685
Cash and cash equivalents at end of period	$	159,184		$	—		$	159,184

●

Our updated revenue recognition policy reflecting Topic 606 is as follows:

Our Revenue Sources

Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue

Research and development revenue under collaborative agreements

Steps to Recognize Revenue

We use a five step process to determine the amount of revenue we should recognize and when we should recognize it. The five step process is as follows:

Identify the contract

Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the following criteria:

●

We and our partner approved the contract and we are both committed to perform our obligations;

●

We have identified our rights, our partner’s rights and the payment terms;

●

We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the contract; and

●

We believe collectability is probable.

Identify the performance obligations

Determine the transaction price

Allocate the transaction price

●

Estimated future product sales;

●

Estimated royalties on future product sales;

●

Contractual milestone payments;

●

Expenses we expect to incur;

●

Income taxes; and

●

A discount rate.

●

The number of internal hours we estimate we will spend performing these services;

●

The estimated cost of work we will perform;

●

The estimated cost of work that we will contract with third parties to perform; and

●

The estimated cost of API we will use.

We do not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.

Recognize revenue

The following are examples of when we typically recognize revenue based on the types of payments we receive.

Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue

Research and development revenue under collaboration agreements:

Upfront Payments

Milestone Payments

License Fees

Amendments to Agreements

From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the accounting for the amendment:

If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and

If the goods and/or services are at a stand-alone selling price.

Multiple Agreements

●

Whether the agreements were negotiated together with a single objective;

●

Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or

●

Whether the goods and/or services promised under the agreements are a single performance obligation.

Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting guidance requires us to account for them as a combined arrangement.

Contracts Receivable

Unbilled SPINRAZA Royalties

Deferred Revenue

The following table summarizes the adjustments we were required to make to our deferred revenue amounts to adopt Topic 606 (in thousands):

	At December 31, 2017
	As Previously Reported under Topic 605			Topic 606 Adjustment			As Revised
Current portion of deferred revenue		$	106,465		$	18,871		$	125,336
Long-term portion of deferred revenue			72,708			35,318			108,026
Total deferred revenue		$	179,173		$	54,189		$	233,362

●

$24.2 million from Biogen;

●

$15.9 million from AstraZeneca;

●

$11.8 from Novartis; and

●

$2.3 million from other partners.

Noncontrolling Interest in Akcea Therapeutics, Inc.

Cash, Cash Equivalents and Investments

Cash, cash equivalents and investments

Inventory Valuation

Inventory valuation

Research and Development Expenses

Research, development and patent expenses

Patent Expenses

Long-Lived Assets

Long-lived assets

Use of Estimates

Use of estimates

Basic and Diluted Net Income (Loss) per Share

Basic and diluted net income (loss) per share

Basic net income (loss) per share

Our basic net loss per share for the three months ended September 30, 2018, was calculated as follows (in thousands, except per share amounts):

Three months ended September 30, 2018	Weighted Average Shares Owned in Akcea		Akcea’s Net Income (Loss) Per Share			Ionis’ Portion of Akcea’s Net Loss

Common shares		65,538	$	(0.73	)	$	(47,843	)
Akcea’s net loss attributable to our ownership						$	(47,843	)
Ionis’ stand-alone net income							43,226
Net loss available to Ionis common stockholders						$	(4,616	)
Weighted average shares outstanding							143,314
Basic net loss per share						$	(0.03	)

Our basic net loss per share for the nine months ended September 30, 2018, was calculated as follows (in thousands, except per share amounts):

Nine months ended September 30, 2018	Weighted Average Shares Owned in Akcea		Akcea’s Net Loss Per Share			Ionis’ Portion of Akcea’s Net Loss

Common shares		57,347	$	(1.93	)	$	(110,680	)
Akcea’s net loss attributable to our ownership						$	(110,680	)
Ionis’ stand-alone net income							67,517
Net income available to Ionis common stockholders						$	(43,162	)
Weighted average shares outstanding							132,518
Basic net loss per share						$	(0.33	)

Our basic net income per share for the three months ended September 30, 2017, was calculated as follows (in thousands, except per share amounts):

Three months ended September 30, 2017	Weighted Average Shares Owned in Akcea		Akcea’s Net Loss Per Share			Ionis’ Portion of Akcea’s Net Loss

Common shares		36,556	$	(0.33	)	$	(12,063	)
Preferred shares		5,651		(0.01	)		(57	)
Akcea’s net loss attributable to our ownership						$	(12,120	)
Ionis’ stand-alone net income							10,144
Net loss available to Ionis common stockholders						$	(1,976	)
Weighted average shares outstanding							124,370
Basic net income per share						$	(0.02	)

Our basic net income per share for the nine months ended September 30, 2017, was calculated as follows (in thousands, except per share amounts):

Nine months ended September 30, 2017	Weighted Average Shares Owned in Akcea		Akcea’s Net Loss Per Share			Ionis’ Portion of Akcea’s Net Loss

Common shares		12,319	$	(3.12	)	$	(38,435	)
Preferred shares		21,055		(2.16	)		(45,479	)
Akcea’s net loss attributable to our ownership						$	(83,914	)
Ionis’ stand-alone net income							100,235
Net income available to Ionis common stockholders						$	16,321
Weighted average shares outstanding							123,746
Basic net income per share						$	0.13

Dilutive net income (loss per share)

●

1 percent convertible senior notes;

●

2¾ percent convertible senior notes;

●

Dilutive stock options;

●

Unvested restricted stock units; and

●

Employee Stock Purchase Plan, or ESPP.

Nine months ended September 30, 2017	Income (Numerator)		Shares (Denominator)		Per-Share Amount

Net income available to Ionis common stockholders	$	16,321		123,746	$	0.13
Effect of dilutive securities:
Shares issuable upon exercise of stock options		—		1,658
Shares issuable upon restricted stock award issuance		—		430
Shares issuable related to our ESPP		—		24
Income available to Ionis common stockholders, plus assumed conversions	$	16,321		125,858	$	0.13

For the nine months ended September 30, 2017, the calculation excluded the 1 percent and 2¾ percent notes because the effect on diluted earnings per share was anti-dilutive.

Accumulated Other Comprehensive Loss

Accumulated other comprehensive loss

	Three Months Ended September 30,						Nine Months Ended September 30,
	2018			2017			2018			2017
Beginning balance accumulated other comprehensive loss	$	(32,637	)	$	(30,372	)	$	(31,759	)	$	(30,358	)
Unrealized gains (losses) on securities (1)		133			215			(834	)		610
Amounts reclassified from accumulated other comprehensive loss		—			—			—			(374	)
Currency translation adjustment		(28	)		(42	)		61			(77	)
Net current period other comprehensive income (loss)		105			173			(773	)		159
Ending balance accumulated other comprehensive loss	$	(32,532	)	$	(30,199	)	$	(32,532	)	$	(30,199	)

(1)

There was no income tax expense or benefit related to elements of other comprehensive income (loss) for the three and nine months ended September 30, 2018 and 2017.

Convertible Debt

Convertible debt

Segment Information

Segment information

Stock-Based Compensation Expense

Stock-based compensation expense

Employee Stock Options:

	Nine Months Ended September 30,
	2018		2017
Risk-free interest rate		2.3%		1.8%
Dividend yield		0.0%		0.0%
Volatility		63.1%		66.1%
Expected life		4.6 years		4.5 years

Board of Director Stock Options:

	Nine Months Ended September 30,
	2018		2017
Risk-free interest rate		2.8 %		2.2 %
Dividend yield		0.0 %		0.0 %
Volatility		61.5 %		61.2 %
Expected life		6.6 years		6.6 years

ESPP:

	Nine Months Ended September 30,
	2018		2017
Risk-free interest rate		1.8%		0.8%
Dividend yield		0.0%		0.0%
Volatility		47.3%		59.9%
Expected life		6 months		6 months

	Three Months Ended September 30,						Nine Months Ended September 30,
	2018			2017			2018			2017
Research, development and patent		$	18,780		$	16,181		$	57,698		$	48,443
Selling, general and administrative			16,103			5,291			39,512			15,199
Total non-cash stock-based compensation expense		$	34,883		$	21,472		$	97,210		$	63,642

Impact of Recently Issued Accounting Standards

Impact of recently issued accounting standards

Significant Accounting Policies (Tables)

9 Months Ended

Sep. 30, 2018

Significant Accounting Policies [Abstract]

Adjustments Made to Adopt New Revenue Accounting Guidance

The following tables summarize the adjustments we were required to make to amounts we originally reported in 2017 to adopt Topic 606 (in thousands, except per share amounts):

Condensed Consolidated Balance Sheet

	At December 31, 2017
	As Previously Reported under Topic 605			Topic 606 Adjustment			As Revised
Current portion of deferred revenue	$	106,465		$	18,871		$	125,336
Long-term portion of deferred revenue	$	72,708		$	35,318		$	108,026
Accumulated deficit	$	(1,187,398	)	$	(53,636	)	$	(1,241,034	)
Noncontrolling interest in Akcea Therapeutics, Inc.	$	87,847		$	(3,580	)	$	84,267
Total stockholders’ equity	$	418,719		$	(53,439	)	$	365,280

Condensed Consolidated Statement of Operations

	Three Months Ended September 30, 2017
	As Previously Reported under Topic 605			Topic 606 Adjustment			As Revised
Revenue:
Commercial revenue:
SPINRAZA royalties	$	32,890		$	—		$	32,890
Licensing and other royalty revenue		879			848			1,727
Total commercial revenue		33,769			848			34,617
Research and development revenue under collaborative agreements		87,142			(3,445	)		83,697
Total revenue	$	120,911		$	(2,597	)	$	118,314
Income (loss) from operations	$	13,909		$	(2,597	)	$	11,312
Net income (loss)	$	(4,896	)	$	(2,597	)	$	(7,493	)
Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders	$	(976	)	$	(1,635	)	$	(2,611	)
Net income (loss) per share, basic and diluted	$	0.00		$	(0.02	)	$	(0.02	)

	Nine Months Ended September 30, 2017
	As Previously Reported under Topic 605			Topic 606 Adjustment		As Revised
Revenue:
Commercial revenue:
SPINRAZA royalties	$	60,467		$	—	$	60,467
Licensing and other royalty revenue		4,983			656		5,639
Total commercial revenue		65,450			656		66,106
Research and development revenue under collaborative agreements		269,917			10,364		280,281
Total revenue	$	335,367		$	11,020	$	346,387
Income from operations	$	26,227		$	11,020	$	37,247
Net income (loss)	$	(12,636	)	$	11,020	$	(1,616	)
Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders	$	(8,716	)	$	11,982	$	3,266
Net income (loss) per share, basic	$	0.02		$	0.11	$	0.13
Net income (loss) per share, diluted	$	0.02		$	0.11	$	0.13

Condensed Consolidated Statement of Cash Flows

	Nine Months Ended September 30, 2017
	As Previously Reported under Topic 605			Topic 606 Adjustment			As Revised
Net income (loss)	$	(12,636	)	$	11,020		$	(1,616	)
Adjustments to reconcile net income (loss) to net cash provided by operating activities:
Deferred contract revenue	$	42,091		$	(11,020	)	$	31,071
Cash and cash equivalents at beginning of period	$	84,685		$	—		$	84,685
Cash and cash equivalents at end of period	$	159,184		$	—		$	159,184

The following table summarizes the adjustments we were required to make to our deferred revenue amounts to adopt Topic 606 (in thousands):

	At December 31, 2017
	As Previously Reported under Topic 605			Topic 606 Adjustment			As Revised
Current portion of deferred revenue		$	106,465		$	18,871		$	125,336
Long-term portion of deferred revenue			72,708			35,318			108,026
Total deferred revenue		$	179,173		$	54,189		$	233,362

Basic Net Loss per Share

Our basic net loss per share for the three months ended September 30, 2018, was calculated as follows (in thousands, except per share amounts):

Three months ended September 30, 2018	Weighted Average Shares Owned in Akcea		Akcea’s Net Income (Loss) Per Share			Ionis’ Portion of Akcea’s Net Loss

Common shares		65,538	$	(0.73	)	$	(47,843	)
Akcea’s net loss attributable to our ownership						$	(47,843	)
Ionis’ stand-alone net income							43,226
Net loss available to Ionis common stockholders						$	(4,616	)
Weighted average shares outstanding							143,314
Basic net loss per share						$	(0.03	)

Basic and Diluted Net Income Per Share

Nine months ended September 30, 2017	Income (Numerator)		Shares (Denominator)		Per-Share Amount

Net income available to Ionis common stockholders	$	16,321		123,746	$	0.13
Effect of dilutive securities:
Shares issuable upon exercise of stock options		—		1,658
Shares issuable upon restricted stock award issuance		—		430
Shares issuable related to our ESPP		—		24
Income available to Ionis common stockholders, plus assumed conversions	$	16,321		125,858	$	0.13

For the nine months ended September 30, 2017, the calculation excluded the 1 percent and 2¾ percent notes because the effect on diluted earnings per share was anti-dilutive.

Changes in Accumulated Other Comprehensive Income (Loss)

	Three Months Ended September 30,						Nine Months Ended September 30,
	2018			2017			2018			2017
Beginning balance accumulated other comprehensive loss	$	(32,637	)	$	(30,372	)	$	(31,759	)	$	(30,358	)
Unrealized gains (losses) on securities (1)		133			215			(834	)		610
Amounts reclassified from accumulated other comprehensive loss		—			—			—			(374	)
Currency translation adjustment		(28	)		(42	)		61			(77	)
Net current period other comprehensive income (loss)		105			173			(773	)		159
Ending balance accumulated other comprehensive loss	$	(32,532	)	$	(30,199	)	$	(32,532	)	$	(30,199	)

(1)

There was no income tax expense or benefit related to elements of other comprehensive income (loss) for the three and nine months ended September 30, 2018 and 2017.

Weighted-Average Assumptions for Stock Options

Employee Stock Options:

	Nine Months Ended September 30,
	2018		2017
Risk-free interest rate		2.3%		1.8%
Dividend yield		0.0%		0.0%
Volatility		63.1%		66.1%
Expected life		4.6 years		4.5 years

Board of Director Stock Options:

	Nine Months Ended September 30,
	2018		2017
Risk-free interest rate		2.8 %		2.2 %
Dividend yield		0.0 %		0.0 %
Volatility		61.5 %		61.2 %
Expected life		6.6 years		6.6 years

Weighted-Average Assumptions for ESPP

ESPP:

	Nine Months Ended September 30,
	2018		2017
Risk-free interest rate		1.8%		0.8%
Dividend yield		0.0%		0.0%
Volatility		47.3%		59.9%
Expected life		6 months		6 months

Stock-Based Compensation Expense

	Three Months Ended September 30,						Nine Months Ended September 30,
	2018			2017			2018			2017
Research, development and patent		$	18,780		$	16,181		$	57,698		$	48,443
Selling, general and administrative			16,103			5,291			39,512			15,199
Total non-cash stock-based compensation expense		$	34,883		$	21,472		$	97,210		$	63,642

Investments (Tables)

9 Months Ended

Sep. 30, 2018

Investments [Abstract]

Contract Maturity of Available-for-Sale Securities

The following table summarizes the contract maturity of the available-for-sale securities we held as of September 30, 2018:

One year or less	80%
After one year but within two years	15%
After two years but within three years	5%
Total	100%

Summary of Investments

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

			Gross Unrealized
September 30, 2018	Cost (1)		Gains		Losses			Estimated Fair Value
Available-for-sale securities:
Corporate debt securities (2)	$	841,397	$	23	$	(1,264	)	$	840,156
Debt securities issued by U.S. government agencies		143,008		2		(169	)		142,841
Debt securities issued by the U.S. Treasury (2)		154,280		—		(89	)		154,191
Debt securities issued by states of the U.S. and political subdivisions of the states (2)		49,873		—		(330	)		49,543
Total securities with a maturity of one year or less		1,188,558		25		(1,852	)		1,186,731
Corporate debt securities		240,208		16		(1,420	)		238,804
Debt securities issued by U.S. government agencies		32,435		—		(109	)		32,326
Debt securities issued by the U.S. Treasury		9,872		—		(10	)		9,862
Debt securities issued by states of the U.S. and political subdivisions of the states		31,666		—		(551	)		31,115
Total securities with a maturity of more than one year		314,181		16		(2,090	)		312,107
Total available-for-sale securities	$	1,502,739	$	41	$	(3,942	)	$	1,498,838

			Gross Unrealized
December 31, 2017	Cost (1)		Gains		Losses			Estimated Fair Value
Available-for-sale securities:
Corporate debt securities	$	500,599	$	2	$	(752	)	$	499,849
Debt securities issued by U.S. government agencies		83,926		—		(212	)		83,714
Debt securities issued by the U.S. Treasury		29,428		—		(17	)		29,411
Debt securities issued by states of the U.S. and political subdivisions of the states (2)		29,240		4		(122	)		29,122
Total securities with a maturity of one year or less		643,193		6		(1,103	)		642,096
Corporate debt securities		148,663		8		(1,059	)		147,612
Debt securities issued by U.S. government agencies		52,779		—		(168	)		52,611
Debt securities issued by the U.S. Treasury		1,409		—		(2	)		1,407
Debt securities issued by states of the U.S. and political subdivisions of the states		65,550		—		(740	)		64,810
Total securities with a maturity of more than one year		268,401		8		(1,969	)		266,440
Total available-for-sale securities	$	911,594	$	14	$	(3,072	)	$	908,536

(1)

Our available-for-sale securities are held at amortized cost.

(2)

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

Temporarily Impaired Investments

			Less than 12 Months of Temporary Impairment					More than 12 Months of Temporary Impairment					Total Temporary Impairment
(In thousands)	Number of Investments		Estimated Fair Value		Unrealized Losses			Estimated Fair Value		Unrealized Losses			Estimated Fair Value		Unrealized Losses
Corporate debt securities		495	$	889,172	$	(1,687	)	$	83,706	$	(997	)	$	972,878	$	(2,684	)
Debt securities issued by U.S. government agencies		51		132,231		(139	)		26,862		(139	)		159,093		(278	)
Debt securities issued by the U.S. Treasury		32		164,053		(99	)		—		—			164,053		(99	)
Debt securities issued by states of the U.S. and political subdivisions of the states		48		25,687		(191	)		51,747		(690	)		77,434		(881	)
Total temporarily impaired securities		626	$	1,211,143	$	(2,116	)	$	162,315	$	(1,826	)	$	1,373,458	$	(3,942	)

Fair Value Measurements (Tables)

9 Months Ended

Sep. 30, 2018

Assets Measured at Fair Value on a Recurring Basis

	At September 30, 2018		Quoted Prices in Active Markets (Level 1)		Significant Other Observable Inputs (Level 2)
Cash equivalents (1)	$	395,649	$	395,649	$	—
Corporate debt securities (2)		1,078,960		—		1,078,960
Debt securities issued by U.S. government agencies (3)		175,167		—		175,167
Debt securities issued by the U.S. Treasury (3)		164,053		164,053		—
Debt securities issued by states of the U.S. and political subdivisions of the states (3)		80,658		—		80,658
Total	$	1,894,487	$	559,702	$	1,334,785

	At December 31, 2017		Quoted Prices in Active Markets (Level 1)		Significant Other Observable Inputs (Level 2)
Cash equivalents (1)	$	86,262	$	86,262	$	—
Corporate debt securities (3)		647,461		—		647,461
Debt securities issued by U.S. government agencies (3)		136,325		—		136,325
Debt securities issued by the U.S. Treasury (3)		30,818		30,818		—
Debt securities issued by states of the U.S. and political subdivisions of the states (4)		93,932		—		93,932
Total	$	994,798	$	117,080	$	877,718

(1)

Included in cash and cash equivalents on our condensed consolidated balance sheet.

(2)

(3)

Included in short-term investments on our condensed consolidated balance sheet.

(4)

Reconciliation of Assets Measured at Fair Value on a Recurring Basis Using Significant Unobservable Inputs (Level 3)


Beginning balance of Level 3 instruments at January 1, 2017	$	—
Value of the potential premium we would have received from Novartis at inception of the SPA (January 2017)		5,035
Recurring fair value adjustment during the nine months ended September 30, 2017		(5,035	)
Ending balance of Level 3 instruments at September 30, 2017	$	—

Collaborative Arrangements and Licensing Agreements (Tables)

9 Months Ended

Sep. 30, 2018

AstraZeneca [Member]

Collaborative Arrangements and Licensing Agreements [Abstract]

Collaborative Arrangements and Licensing Agreements [Abstract]

During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with AstraZeneca (in millions, except percentage amounts):

	Three Months Ended September 30,								Nine Months Ended September 30,
	2018				2017				2018				2017
R&D revenue		$	14.2			$	4.8			$	86.5			$	14.8
Percentage of total revenue			10	%			4	%			21	%			4	%

Biogen [Member]

Collaborative Arrangements and Licensing Agreements [Abstract]

During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):

	Three Months Ended September 30,						Nine Months Ended September 30,
	2018			2017			2018			2017
SPINRAZA royalties (commercial revenue)	$	70.0		$	32.9		$	167.7		$	60.5
R&D revenue		34.8			54.9			66.9			137.1
Total revenue from our relationship with Biogen		104.8			87.8			234.6			197.6
Percentage of total revenue		72	%		74	%		58	%		57	%

Bayer [Member]

Janssen Biotech, Inc. [Member]

During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Bayer (in millions, except percentage amounts):

	Three Months Ended September 30,								Nine Months Ended September 30,
	2018				2017				2018				2017
R&D revenue		$	1.9			$	0.4			$	3.3			$	66.0
Percentage of total revenue			1	%			0	%			1	%			19	%

Collaborative Arrangements and Licensing Agreements [Abstract]

Collaborative Arrangements and Licensing Agreements [Abstract]

During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Janssen (in millions, except percentage amounts):

	Three Months Ended September 30,								Nine Months Ended September 30,
	2018				2017				2018				2017
R&D revenue		$	0.9			$	3.4			$	6.6			$	18.1
Percentage of total revenue			1	%			3	%			2	%			5	%

Novartis [Member]

Collaborative Arrangements and Licensing Agreements [Abstract]

During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):

	Three Months Ended September 30,								Nine Months Ended September 30,
	2018				2017				2018				2017
R&D revenue		$	7.2			$	9.9			$	42.7			$	21.7
Percentage of total revenue			5	%			8	%			10	%			6	%

Roche [Member]

Collaborative Arrangements and Licensing Agreements [Abstract]

During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):

	Three Months Ended September 30,								Nine Months Ended September 30,
	2018				2017				2018				2017
R&D revenue		$	1.8			$	4.5			$	5.4			$	5.9
Percentage of total revenue			1	%			4	%			1	%			2	%

GSK [Member]

PTC Therapeutics [Member]

During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):

	Three Months Ended September 30,								Nine Months Ended September 30,
	2018				2017				2018				2017
R&D revenue		$	0.1			$	4.6			$	1.5			$	14.4
Percentage of total revenue			0	%			4	%			0	%			4	%

Collaborative Arrangements and Licensing Agreements [Abstract]

Segment Information and Concentration of Business Risk [Abstract]

During the three and nine months ended September 30, 2018 and 2017, we earned the following revenue from our relationship with PTC (in millions, except percentage amounts):

	Three Months Ended September 30,							Nine Months Ended September 30,
	2018				2017			2018				2017
R&D revenue		$	12.0			$	0.0		$	12.0			$	0.0
Percentage of total revenue			8	%			—			3	%			—

Segment Information and Concentration of Business Risk (Tables)

9 Months Ended

Sep. 30, 2018

Segment Information

The following tables show our segment revenue and income (loss) from operations for the three and nine months ended September 30, 2018 and 2017 (in thousands), respectively.

Three Months Ended September 30, 2018	Ionis Core		Akcea Therapeutics			Elimination of Intercompany Activity			Total
Revenue:
Commercial revenue:
SPINRAZA royalties	$	70,010	$	—		$	—		$	70,010
Licensing and other royalty revenue		7,946		12,000			(7,200	)		12,746
Total commercial revenue		77,956		12,000			(7,200	)		82,756
R&D revenue under collaborative agreements		100,105		7,241			(44,707	)		62,639
Total segment revenue	$	178,061	$	19,241		$	(51,907	)	$	145,395
Total operating expenses	$	87,664	$	84,249		$	(7,946	)	$	163,967
Income (loss) from operations	$	90,397	$	(65,008	)	$	(43,961	)	$	(18,572	)

Three Months Ended September 30, 2017 (as revised)	Ionis Core		Akcea Therapeutics			Elimination of Intercompany Activity			Total
Revenue:
Commercial revenue:
SPINRAZA royalties	$	32,890	$	—		$	—		$	32,890
Licensing and other royalty revenue		1,727		—			—			1,727
Total commercial revenue		34,617		—			—			34,617
R&D revenue under collaborative agreements		73,791		9,906			—			83,697
Total segment revenue	$	108,408	$	9,906		$	—		$	118,314
Total operating expenses	$	81,019	$	26,013		$	(30	)	$	107,002
Income (loss) from operations	$	27,389	$	(16,107	)	$	30		$	11,312

Nine Months Ended September 30, 2018	Ionis Core		Akcea Therapeutics			Elimination of Intercompany Activity			Total
Revenue:
Commercial revenue:
SPINRAZA royalties	$	167,743	$	—		$	—		$	167,743
Licensing and other royalty revenue		9,432		12,000			(7,200	)		14,232
Total commercial revenue		177,175		12,000			(7,200	)		181,975
R&D revenue under collaborative agreements		232,850		42,670			(49,936	)		225,584
Total segment revenue	$	410,025	$	54,670		$	(57,136	)	$	407,559
Total operating expenses	$	279,084	$	213,428		$	(12,796	)	$	479,716
Income (loss) from operations	$	130,941	$	(158,758	)	$	(44,340	)	$	(72,157	)

Nine Months Ended September 30, 2017 (as revised)	Ionis Core		Akcea Therapeutics			Elimination of Intercompany Activity			Total
Revenue:
Commercial revenue:
SPINRAZA royalties	$	60,467	$	—		$	—		$	60,467
Licensing and other royalty revenue		5,639		—			—			5,639
Total commercial revenue		66,106		—			—			66,106
R&D revenue under collaborative agreements		312,976		21,712			(54,407	)		280,281
Total segment revenue	$	379,082	$	21,712		$	(54,407	)	$	346,387
Total operating expenses	$	242,753	$	120,884		$	(54,497	)	$	309,140
Income (loss) from operations	$	136,329	$	(99,172	)	$	90		$	37,247

The following table shows our total assets by segment at September 30, 2018 and December 31, 2017 (in thousands), respectively.

Total Assets	Ionis Core		Akcea Therapeutics		Elimination of Intercompany Activity			Total
September 30, 2018	$	2,446,425	$	379,128	$	(577,641	)	$	2,247,913
December 31, 2017 (as revised)	$	1,342,578	$	268,804	$	(288,608	)	$	1,322,774

Revenue from Significant Partners

	Three Months Ended September 30,				Nine Months Ended September 30,
	2018		2017		2018		2017
				(as revised)				(as revised)
Partner A		72%		74%		58%		57%
Partner B		10%		4%		21%		4%
Partner C		5%		8%		10%		6%
Partner D		8%		0%		3%		0%
Partner E		1%		0%		1%		19%

Basis of Presentation (Details) - Akcea [Member] - shares shares in Millions	1 Months Ended	7 Months Ended
	Oct. 31, 2018	Jul. 31, 2017	Sep. 30, 2018	Apr. 30, 2018	Mar. 31, 2018
Basis of Presentation [Abstract]
Percentage ownership before IPO		100.00%
Percentage ownership		68.00%	75.00%	75.00%	68.00%
Subsequent Event [Member]
Basis of Presentation [Abstract]
Percentage ownership	76.00%
Additional shares of Akcea stock received when TEGSEDI received marketing authorization in the U.S. (in shares)	1.7

Significant Accounting Policies, Revenue Recognition - Adoption of Topic 606 (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended		9 Months Ended		12 Months Ended
	Sep. 30, 2018	Sep. 30, 2017	Sep. 30, 2018	Sep. 30, 2017	Dec. 31, 2017
Condensed Consolidated Balance Sheet [Abstract]
Current portion of deferred revenue	$ 157,145		$ 157,145		$ 125,336
Long-term portion of deferred revenue	523,384		523,384		108,026
Accumulated deficit	(1,287,369)		(1,287,369)		(1,241,034)
Noncontrolling interest in Akcea Therapeutics, Inc.	129,594		129,594		84,267
Total stockholders' equity	840,144		840,144		365,280
Condensed Consolidated Statement of Operations [Abstract]
Revenue	145,395	$ 118,314	407,559	$ 346,387
Income (loss) from operations	(18,572)	11,312	(72,157)	37,247
Net income (loss)	(20,365)	(7,493)	(87,747)	(1,616)
Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders	$ (4,559)	$ (2,611)	$ (46,335)	$ 3,266
Net income (loss) per share, basic (in dollars per share)	$ (0.03)	$ (0.02)	$ (0.33)	$ 0.13
Net income per share, diluted (in dollars per share)	$ (0.03)	$ (0.02)	$ (0.33)	$ 0.13
Condensed Consolidated Statement of Cash Flows [Abstract]
Net income (loss)	$ (20,365)	$ (7,493)	$ (87,747)	$ (1,616)
Adjustments to reconcile net income (loss) to net cash provided by operating activities [Abstract]
Deferred contract revenue			447,168	31,071
Cash and cash equivalents at beginning of period			129,630	84,685	84,685
Cash and cash equivalents at end of period	479,891	159,184	479,891	159,184	129,630
Increase in revenue from amortization of milestone payments achieved under new revenue guidance		500		27,900
Decrease in revenue from amortization of payments using input method under new revenue guidance		(4,000)		(17,500)
Commercial Revenue [Member]
Condensed Consolidated Statement of Operations [Abstract]
Revenue	82,756	34,617	181,975	66,106
SPINRAZA Royalties [Member]
Condensed Consolidated Statement of Operations [Abstract]
Revenue	70,010	32,890	167,743	60,467
Licensing and Other Royalty Revenue [Member]
Condensed Consolidated Statement of Operations [Abstract]
Revenue	12,746	1,727	14,232	5,639
Research and Development Revenue Under Collaborative Agreements [Member]
Condensed Consolidated Statement of Operations [Abstract]
Revenue	$ 62,639	83,697	$ 225,584	280,281
Topic 606 [Member]
Revenue Recognition [Abstract]
Cumulative effect of adoption on retained earnings					(53,600)
Topic 606 [Member] \| As Previously Reported Under Topic 605 [Member]
Condensed Consolidated Balance Sheet [Abstract]
Current portion of deferred revenue					106,465
Long-term portion of deferred revenue					72,708
Accumulated deficit					(1,187,398)
Noncontrolling interest in Akcea Therapeutics, Inc.					87,847
Total stockholders' equity					418,719
Condensed Consolidated Statement of Operations [Abstract]
Revenue		120,911		335,367
Income (loss) from operations		13,909		26,227
Net income (loss)		(4,896)		(12,636)
Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders		$ (976)		$ (8,716)
Net income (loss) per share, basic (in dollars per share)		$ 0		$ 0.02
Net income per share, diluted (in dollars per share)		$ 0		$ 0.02
Condensed Consolidated Statement of Cash Flows [Abstract]
Net income (loss)		$ (4,896)		$ (12,636)
Adjustments to reconcile net income (loss) to net cash provided by operating activities [Abstract]
Deferred contract revenue				42,091
Cash and cash equivalents at beginning of period				84,685	84,685
Cash and cash equivalents at end of period		159,184		159,184
Topic 606 [Member] \| As Previously Reported Under Topic 605 [Member] \| Commercial Revenue [Member]
Condensed Consolidated Statement of Operations [Abstract]
Revenue		33,769		65,450
Topic 606 [Member] \| As Previously Reported Under Topic 605 [Member] \| SPINRAZA Royalties [Member]
Condensed Consolidated Statement of Operations [Abstract]
Revenue		32,890		60,467
Topic 606 [Member] \| As Previously Reported Under Topic 605 [Member] \| Licensing and Other Royalty Revenue [Member]
Condensed Consolidated Statement of Operations [Abstract]
Revenue		879		4,983
Topic 606 [Member] \| As Previously Reported Under Topic 605 [Member] \| Research and Development Revenue Under Collaborative Agreements [Member]
Condensed Consolidated Statement of Operations [Abstract]
Revenue		87,142		269,917
Topic 606 [Member] \| Topic 606 Adjustment [Member]
Condensed Consolidated Balance Sheet [Abstract]
Current portion of deferred revenue					18,871
Long-term portion of deferred revenue					35,318
Accumulated deficit					(53,636)
Noncontrolling interest in Akcea Therapeutics, Inc.					(3,580)
Total stockholders' equity					(53,439)
Condensed Consolidated Statement of Operations [Abstract]
Revenue		(2,597)		11,020
Income (loss) from operations		(2,597)		11,020
Net income (loss)		(2,597)		11,020
Net income (loss) attributable to Ionis Pharmaceuticals, Inc. common stockholders		$ (1,635)		$ 11,982
Net income (loss) per share, basic (in dollars per share)		$ (0.02)		$ 0.11
Net income per share, diluted (in dollars per share)		$ (0.02)		$ 0.11
Condensed Consolidated Statement of Cash Flows [Abstract]
Net income (loss)		$ (2,597)		$ 11,020
Adjustments to reconcile net income (loss) to net cash provided by operating activities [Abstract]
Deferred contract revenue				(11,020)
Cash and cash equivalents at beginning of period				0	$ 0
Cash and cash equivalents at end of period		0		0
Topic 606 [Member] \| Topic 606 Adjustment [Member] \| Commercial Revenue [Member]
Condensed Consolidated Statement of Operations [Abstract]
Revenue		848		656
Topic 606 [Member] \| Topic 606 Adjustment [Member] \| SPINRAZA Royalties [Member]
Condensed Consolidated Statement of Operations [Abstract]
Revenue		0		0
Topic 606 [Member] \| Topic 606 Adjustment [Member] \| Licensing and Other Royalty Revenue [Member]
Condensed Consolidated Statement of Operations [Abstract]
Revenue		848		656
Topic 606 [Member] \| Topic 606 Adjustment [Member] \| Research and Development Revenue Under Collaborative Agreements [Member]
Condensed Consolidated Statement of Operations [Abstract]
Revenue		$ (3,445)		$ 10,364

Significant Accounting Policies, Revenue Recognition - Revenue Sources (Details) $ in Thousands	1 Months Ended				3 Months Ended				9 Months Ended
	Dec. 31, 2017 USD ($) PerformanceObligation	Feb. 28, 2017 USD ($) PerformanceObligation	May 31, 2015 USD ($) PerformanceObligation	Dec. 31, 2012 USD ($) PerformanceObligation	Sep. 30, 2018 USD ($)	Jun. 30, 2018 Agreement	Sep. 30, 2017 USD ($)	Jun. 30, 2015 USD ($)	Sep. 30, 2018 USD ($)	Sep. 30, 2017 USD ($)	Aug. 31, 2018 PerformanceObligation	Dec. 31, 2016 PerformanceObligation
Revenue Recognition [Abstract]
Revenue					$ 145,395		$ 118,314		$ 407,559	$ 346,387
Period of time after billing when payment is received									3 months
Deferred Revenue [Abstract]
Revenue recognized					37,200		31,600		$ 80,400	84,400
Current portion of deferred revenue	$ 125,336				157,145				157,145
Long-term portion of deferred revenue	108,026				523,384				523,384
Total deferred revenue	233,362
Biogen [Member]
Revenue Recognition [Abstract]
Number of agreements \| Agreement						2
Licensing and Other Royalty Revenue [Member]
Revenue Recognition [Abstract]
Revenue					12,746		1,727		14,232	5,639
SMA Collaboration with Biogen [Member]
Revenue Recognition [Abstract]
Upfront payment received	$ 25,000
Number of separate performance obligations \| PerformanceObligation	1
Neurology [Member]
Revenue Recognition [Abstract]
Upfront payment received				$ 30,000
Milestone payment earned and amortized over period of performance							10,000
Number of separate performance obligations \| PerformanceObligation				1
SPINRAZA [Member]
Revenue Recognition [Abstract]
Revenue					10,000
Number of separate performance obligations \| PerformanceObligation												2
Bayer [Member]
Revenue Recognition [Abstract]
Number of separate performance obligations \| PerformanceObligation		3
Deferred Revenue [Abstract]
Total deferred revenue	$ 9,300				6,000				6,000
Bayer [Member]
Revenue Recognition [Abstract]
Upfront payment received			$ 100,000					$ 100,000
Number of separate performance obligations \| PerformanceObligation			3
Bayer [Member]
Revenue Recognition [Abstract]
Upfront payment received		$ 75,000
Number of separate performance obligations \| PerformanceObligation		2
PTC Therapeutics [Member]
Revenue Recognition [Abstract]
Revenue					12,000		0		12,000	0
Number of separate performance obligations \| PerformanceObligation											2
Deferred Revenue [Abstract]
Total deferred revenue	0				0				$ 0
PTC Therapeutics [Member] \| TEGSEDI [Member]
Revenue Recognition [Abstract]
Revenue					$ 12,000
As Previously Reported Under Topic 605 [Member] \| Topic 606 [Member]
Revenue Recognition [Abstract]
Revenue							120,911			335,367
Deferred Revenue [Abstract]
Current portion of deferred revenue	106,465
Long-term portion of deferred revenue	72,708
Total deferred revenue	179,173
As Previously Reported Under Topic 605 [Member] \| Topic 606 [Member] \| Licensing and Other Royalty Revenue [Member]
Revenue Recognition [Abstract]
Revenue							879			4,983
Topic 606 Adjustment [Member] \| Topic 606 [Member]
Revenue Recognition [Abstract]
Revenue							(2,597)			11,020
Deferred Revenue [Abstract]
Current portion of deferred revenue	18,871
Long-term portion of deferred revenue	35,318
Total deferred revenue	54,189
Topic 606 Adjustment [Member] \| Topic 606 [Member] \| Biogen [Member]
Deferred Revenue [Abstract]
Total deferred revenue	24,200
Topic 606 Adjustment [Member] \| Topic 606 [Member] \| AstraZeneca [Member]
Deferred Revenue [Abstract]
Total deferred revenue	15,900
Topic 606 Adjustment [Member] \| Topic 606 [Member] \| Novartis [Member]
Deferred Revenue [Abstract]
Total deferred revenue	11,800
Topic 606 Adjustment [Member] \| Topic 606 [Member] \| Other Partners [Member]
Deferred Revenue [Abstract]
Total deferred revenue	$ 2,300
Topic 606 Adjustment [Member] \| Topic 606 [Member] \| Licensing and Other Royalty Revenue [Member]
Revenue Recognition [Abstract]
Revenue							$ 848			$ 656

Significant Accounting Policies, Noncontrolling Interest in Akcea (Details) - Akcea [Member] - shares shares in Millions	1 Months Ended	7 Months Ended
	Oct. 31, 2018	Jul. 31, 2017	Sep. 30, 2018	Apr. 30, 2018	Mar. 31, 2018
Noncontrolling Interest in Akcea Therapeutics, Inc. [Abstract]
Percentage ownership before IPO		100.00%
Percentage ownership		68.00%	75.00%	75.00%	68.00%
Subsequent Event [Member]
Noncontrolling Interest in Akcea Therapeutics, Inc. [Abstract]
Percentage ownership	76.00%
Additional shares of Akcea stock received when TEGSEDI received marketing authorization in the U.S. (in shares)	1.7

Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)	Sep. 30, 2018 Company
Cash, Cash Equivalents and Investments [Abstract]
Number of publicly-held companies in which there is an equity ownership interest of less than 20%	1
Number of privately-held companies in which there is an equity ownership interest of less than 20%	4

Significant Accounting Policies, Inventory Valuation (Details) - USD ($) $ in Thousands	9 Months Ended
	Sep. 30, 2018	Sep. 30, 2017
Inventory Valuation [Abstract]
Inventory write-off	$ 0	$ 0

Significant Accounting Policies, Basic and Diluted Net Income (Loss) per Share (Details) - USD ($) $ / shares in Units, shares in Thousands, $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2018	Sep. 30, 2017	Sep. 30, 2018	Sep. 30, 2017	Dec. 31, 2017
Basic Net Income (Loss) per Share [Abstract]
Dividend rate				6.00%
Conversion ratio			converted into common stock on a 1:1 basis
Basic net income (loss) per share (in dollars per share)	$ (0.03)	$ (0.02)	$ (0.33)	$ 0.13
Net income (loss)	$ (4,559)	$ (2,611)	$ (46,335)	$ 3,266
Net income (loss) available to Ionis common shareholders	$ (4,616)	$ (1,976)	$ (43,162)	$ 16,321
Shares used in computing basic net income (loss) per share (in shares)	143,314	124,370	132,518	123,746
Income available to Ionis common shareholders, plus assumed conversions				$ 16,321
Shares issuable related to our ESPP				24
Shares used in computing diluted net income per share (in shares)	143,314	124,370	132,518	125,858
Diluted net income per share (in dollars per share)	$ (0.03)	$ (0.02)	$ (0.33)	$ 0.13
1 Percent Convertible Senior Notes [Member]
Basic Net Income (Loss) per Share [Abstract]
Interest rate on convertible senior notes	1.00%	1.00%	1.00%	1.00%	1.00%
2 3/4 Percent Convertible Senior Notes [Member]
Basic Net Income (Loss) per Share [Abstract]
Interest rate on convertible senior notes	2.75%	2.75%	2.75%	2.75%
Stock Options [Member]
Basic Net Income (Loss) per Share [Abstract]
Shares issuable related to stock-based compensation (in shares)				1,658
Restricted Stock Awards [Member]
Basic Net Income (Loss) per Share [Abstract]
Shares issuable related to stock-based compensation (in shares)				430
Ionis [Member]
Basic Net Income (Loss) per Share [Abstract]
Net income (loss)	$ 43,226	$ 10,144	$ 67,517	$ 100,235
Akcea [Member]
Basic Net Income (Loss) per Share [Abstract]
Net income (loss)	$ (47,843)	$ (12,120)	$ (110,680)	$ (83,914)
Akcea [Member] \| Preferred Stock [Member]
Basic Net Income (Loss) per Share [Abstract]
Weighted average shares owned in Akcea (in shares)		5,651		21,055
Basic net income (loss) per share (in dollars per share)		$ (0.01)		$ (2.16)
Net income (loss)		$ (57)		$ (45,479)
Akcea [Member] \| Common Stock [Member]
Basic Net Income (Loss) per Share [Abstract]
Weighted average shares owned in Akcea (in shares)	65,538	36,556	57,347	12,319
Basic net income (loss) per share (in dollars per share)	$ (0.73)	$ (0.33)	$ (1.93)	$ (3.12)
Net income (loss)	$ (47,843)	$ (12,063)	$ (110,680)	$ (38,435)

Significant Accounting Policies, Accumulated Other Comprehensive Loss (Details) - USD ($)
$ in Thousands

3 Months Ended

9 Months Ended

Sep. 30, 2018

Sep. 30, 2017

Sep. 30, 2018

Sep. 30, 2017

Accumulated Other Comprehensive Income (Loss) [Roll Forward]

Beginning balance

$ 365,280

Net current period other comprehensive income (loss)

$ 105

$ 173

(773)

$ 159

Ending balance

840,144

Accumulated Other Comprehensive Loss [Member]

Accumulated Other Comprehensive Income (Loss) [Roll Forward]

Beginning balance

(32,637)

(30,372)

(31,759)

(30,358)

Ending balance

(32,532)

(30,199)

(32,532)

(30,199)

Unrealized Gains (Losses) on Securities [Member]

Accumulated Other Comprehensive Income (Loss) [Roll Forward]

Other comprehensive income (loss) before reclassifications

^[1]

133

215

(834)

610

Amounts reclassified from accumulated other comprehensive loss

(374)

Other comprehensive income (loss), tax

Currency Translation Adjustment [Member]

Accumulated Other Comprehensive Income (Loss) [Roll Forward]

Other comprehensive income (loss) before reclassifications

$ (28)

$ (42)

$ 61

$ (77)

[1]	There was no income tax expense or benefit related to elements of other comprehensive income (loss) for the three and nine months ended September 30, 2018 and 2017.

Significant Accounting Policies, Segment Information (Details)	9 Months Ended
	Sep. 30, 2018 Segment
Segment Information [Abstract]
Number of operating segments	2

Significant Accounting Policies, Stock-Based Compensation Expense (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2018	Sep. 30, 2017	Sep. 30, 2018	Sep. 30, 2017
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense	$ 34,883	$ 21,472	$ 97,210	$ 63,642
Research, Development and Patent [Member]
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense	18,780	16,181	57,698	48,443
Selling, General and Administrative [Member]
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense	16,103	5,291	$ 39,512	$ 15,199
Employee Stock Options [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate			2.30%	1.80%
Dividend yield			0.00%	0.00%
Volatility			63.10%	66.10%
Expected life			4 years 7 months 6 days	4 years 6 months
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation expense related to non-vested stock options	139,500		$ 139,500
Weighted average period for recognition			1 year 3 months 18 days
Board of Director Stock Options [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate			2.80%	2.20%
Dividend yield			0.00%	0.00%
Volatility			61.50%	61.20%
Expected life			6 years 7 months 6 days	6 years 7 months 6 days
ESPP [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate			1.80%	0.80%
Dividend yield			0.00%	0.00%
Volatility			47.30%	59.90%
Expected life			6 months	6 months
RSUs [Member]
Stock-based Compensation Expense [Abstract]
Vesting period			4 years
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation cost related to non-vested RSUs	32,600		$ 32,600
Weighted average period for recognition			1 year 7 months 6 days
RSUs [Member] \| Employees [Member]
Stock-based Compensation Expense [Abstract]
Weighted-average grant date fair value (in dollars per share)			$ 51.83
RSUs [Member] \| Board of Directors [Member]
Stock-based Compensation Expense [Abstract]
Weighted-average grant date fair value (in dollars per share)			$ 42.88
Akcea [Member]
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense	$ 12,700	$ 4,700	$ 31,200	$ 11,800

Investments, Contract Maturity of Available-for-Sale Securities (Details)	9 Months Ended
	Sep. 30, 2018 Company
Contract Maturity of Available-for-Sale Securities [Abstract]
One year or less	80.00%
After one year but within two years	15.00%
After two years but within three years	5.00%
Total	100.00%
Percentage of available-for-sale securities with a maturity of less than two years	95.00%
Maximum contract maturity period, range 1	1 year
Maximum contract maturity period, range 2	2 years
Maximum contract maturity period, range 3	3 years
Ownership Interests in Private and Public Companies [Abstract]
Number of privately-held companies in which there is an equity ownership interest of less than 20%	4
Number of publicly-held companies in which there is an equity ownership interest of less than 20%	1

Investments, Summary of Investments (Details) - USD ($)
$ in Thousands

Sep. 30, 2018

Dec. 31, 2017

Available-for-sale Securities [Member]

^[1]

$ 1,502,739

$ 911,594

(3,942)

(3,072)

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

1,498,838

908,536

^[1]

1,188,558

643,193

(1,852)

(1,103)

Available-for-sale Securities [Member] | Securities with Maturity of More than One Year [Member]

1,186,731

642,096

^[1]

314,181

268,401

(2,090)

(1,969)

Corporate Debt Securities [Member] | Securities with Maturity of One Year or Less [Member]

312,107

266,440

^[1]

841,397

^[2]

500,599

(1,264)

(752)

Corporate Debt Securities [Member] | Securities with Maturity of More than One Year [Member]

840,156

499,849

^[1]

240,208

148,663

(1,420)

(1,059)

Debt Securities issued by U.S. Government Agencies [Member] | Securities with Maturity of One Year or Less [Member]

238,804

147,612

^[1]

143,008

83,926

(169)

(212)

Debt Securities issued by U.S. Government Agencies [Member] | Securities with Maturity of More than One Year [Member]

142,841

83,714

^[1]

32,435

52,779

(109)

(168)

Debt Securities issued by the U.S. Treasury [Member] | Securities with Maturity of One Year or Less [Member]

32,326

52,611

^[1]

154,280

^[2]

29,428

(89)

(17)

Debt Securities issued by the U.S. Treasury [Member] | Securities with Maturity of More than One Year [Member]

154,191

29,411

9,872

^[1]

1,409

(10)

(2)

Debt Securities issued by States of the U.S. and Political Subdivisions of the States [Member] | Securities with Maturity of One Year or Less [Member]

9,862

1,407

^[1],[2]

49,873

29,240

(330)

(122)

Debt Securities issued by States of the U.S. and Political Subdivisions of the States [Member] | Securities with Maturity of More than One Year [Member]

49,543

29,122

^[1]

31,666

65,550

(551)

(740)

$ 31,115

$ 64,810

[1]	Our available-for-sale securities are held at amortized cost.
[2]	Includes investments classified as cash equivalents on our condensed consolidated balance sheet.

Investments, Investments Temporarily Impaired (Details) $ in Thousands	Sep. 30, 2018 USD ($) Investment
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	626
Estimated fair value, less than 12 months of temporary impairment	$ 1,211,143
Unrealized losses, less than 12 months of temporary impairment	(2,116)
Estimated fair value, more than 12 months of temporary impairment	162,315
Unrealized losses, more than 12 months of temporary impairment	(1,826)
Estimated fair value, total temporary impairment	1,373,458
Unrealized losses, total temporary impairment	$ (3,942)
Corporate Debt Securities [Member]
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	495
Estimated fair value, less than 12 months of temporary impairment	$ 889,172
Unrealized losses, less than 12 months of temporary impairment	(1,687)
Estimated fair value, more than 12 months of temporary impairment	83,706
Unrealized losses, more than 12 months of temporary impairment	(997)
Estimated fair value, total temporary impairment	972,878
Unrealized losses, total temporary impairment	$ (2,684)
Debt Securities issued by U.S. Government Agencies [Member]
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	51
Estimated fair value, less than 12 months of temporary impairment	$ 132,231
Unrealized losses, less than 12 months of temporary impairment	(139)
Estimated fair value, more than 12 months of temporary impairment	26,862
Unrealized losses, more than 12 months of temporary impairment	(139)
Estimated fair value, total temporary impairment	159,093
Unrealized losses, total temporary impairment	$ (278)
Debt Securities issued by the U.S. Treasury [Member]
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	32
Estimated fair value, less than 12 months of temporary impairment	$ 164,053
Unrealized losses, less than 12 months of temporary impairment	(99)
Estimated fair value, more than 12 months of temporary impairment	0
Unrealized losses, more than 12 months of temporary impairment	0
Estimated fair value, total temporary impairment	164,053
Unrealized losses, total temporary impairment	$ (99)
Debt Securities issued by States of the U.S. and Political Subdivisions of the States [Member]
Temporarily Impaired Investments [Abstract]
Number of investments \| Investment	48
Estimated fair value, less than 12 months of temporary impairment	$ 25,687
Unrealized losses, less than 12 months of temporary impairment	(191)
Estimated fair value, more than 12 months of temporary impairment	51,747
Unrealized losses, more than 12 months of temporary impairment	(690)
Estimated fair value, total temporary impairment	77,434
Unrealized losses, total temporary impairment	$ (881)

Fair Value Measurements, Fair Value Measurements on a Recurring Basis (Details) - USD ($)
$ in Thousands

Sep. 30, 2018

Dec. 31, 2017

Transfers from Level 1 to Level 2

$ 0

Transfers from Level 2 to Level 1

Recurring Basis [Member]

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

Cash equivalents

^[1]

395,649

$ 86,262

Total

1,894,487

994,798

Recurring Basis [Member] | Corporate Debt Securities [Member] | Cash and Cash Equivalents [Member]

1,078,960

^[2]

647,461

^[3]

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

19,700

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

^[3]

175,167

136,325

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

^[3]

164,053

30,818

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

80,658

^[3]

93,932

^[4]

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

3,500

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

Cash equivalents

395,649

86,262

Total

559,702

117,080

Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities issued by U.S. Government Agencies [Member]

Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities issued by the U.S. Treasury [Member]

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]

164,053

30,818

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

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

Cash equivalents

Total

1,334,785

877,718

Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities issued by U.S. Government Agencies [Member]

1,078,960

^[2]

647,461

Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities issued by the U.S. Treasury [Member]

175,167

136,325

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]