IONS 10-K & 10-Q changes, risk factors and insider trading
Ionis Pharmaceuticals Inc. · Nasdaq · Pharmaceutical Preparations · CIK 874015 · All filings on SEC.gov
At a glance
What changed in the latest 10-K
Risk Factors
New heading “We use artificial intelligence in certain aspects of our business, and challenges with properly managing its use could adversely affect our business.”
Largest changes
“● subject us to financial or other penalties, regulatory investigations or actions, including mandatory and costly corrective actions, and otherwise subject us to litigation or other liabilities; and”see in full comparison
“We use artificial intelligence in certain aspects of our business, and challenges with properly managing its use could adversely affect our business.”see in full comparison
“Further, we believe that future coverage, reimbursement and pricing will likely be subject to increased restrictions both in the U.S. and in international markets. In the U.S., recent health reform measures have resulted in reductions in Medicare and other healthcare funding, and there have been several recent U.S. …”see in full comparison
Social media is increasingly being used to communicate about our medicines and the diseases our therapies are designed to treat. Social media practices in the biopharmaceutical industry continue to evolve and regulations relating to such use are not always clear and create uncertainty and risk of noncompliance with regulations applicable to our business.see in full comparisonThereDespite our efforts to provide guidelines and training to our employees regarding social media use and monitor social media communications, there isalso arisk that the unauthorized use ofinappropriatesocial media by our employees to communicate about our products or business, or any inadvertent disclosure ofsensitivematerial, nonpublic informationorthrough these means, may result in violations of applicable laws and regulations, which may result in significant legal and financial exposure and reputational damages that could have a material adverse impact on our business. Furthermore, negativeor inaccurateposts or comments about usonorsocialourmedia. We may also encounter criticismmedicines on social mediaregardingcould seriously damage ourcompany,reputation,management,brandorimagemedicines.andOur reputation could be damaged by negative publicity or if adverse information concerning us is posted on social media platforms or similar mediums, which we may not be able to reverse.goodwill. If any of these events were to occur or we otherwise fail to comply with applicable regulations, we could incur liability, face restrictive regulatory actions or incur other harm to our business.
“There are also significant risks involved in developing and deploying AI, and there can be no assurance that the usage of AI will enhance our medicines or the discovery or development of our product candidates or be beneficial to our business, including our efficiency or profitability. It is also uncertain how various laws will apply to content generated by AI. Various governmental authorities have proposed or enacted laws governing the development and use of AI technologies. …”see in full comparison
“Certain of our partners are pursuing other technologies or developing other medicines either on their own or in collaboration with others, including our competitors, to treat some of the same diseases our own collaborative programs target. Competition may negatively impact a partner’s focus on and commitment to our medicines and, as a result, could delay or otherwise negatively affect the commercialization of our medicines, including our commercial medicines and our medicines in development.”see in full comparison
Full comparison: every changed paragraph (144)
We have limited experience as a company in commercializing medicines and we will have to continue to invest significant resources to
develop our capabilities. If we are unable to effectively establish andor maintain marketing,an sales,effective marketcommercialization access, distribution, and related functions,infrastructure, or enter into agreements with third parties to commercialize our medicines, we may not be able to
successfully commercialize our medicines.
We have historically relied on third parties to commercialize
our marketed medicines and have limited experience as a company in commercializing medicines. TRYNGOLZAWe iscurrently ourhave firsttwo independently launched medicinemedicines, TRYNGOLZA and DAWNZERA, and we expect to independently launch additional medicines in the near future. Any failure to effectively
commercialize our medicines, including our failure to allocate resources to our commercial launches efficiently or timely, could adversely impact the revenue we generate from our medicines. If the commercialization of TRYNGOLZAour independently launched medicines and future sales of such are less successful than anticipated by us or our investors or securities analysts, our stock price could decline and our business may be harmed.
We will have to continue to invest significant financial and management resources to build and maintain the infrastructure required to
successfully commercialize our medicines. We will need to establish and maintain effective sales teams for each of our independently launched medicines and there are significant risks involved in managing a sales organization, including our ability to
hire, retain and incentivize qualified individuals, generate sufficient sales leads, provide adequate training to sales and marketing personnel, and effectively manage a geographically dispersed sales and marketing team. We must also continue to
scale-up existing internal support functions to aid our commercialization efforts.efforts, Further, these existing support functionswhich will need to work effectively in coordination with new commercial functional areas. Any failure to establish or maintain an
effective commercialization infrastructure, including our sales, marketing, market access, distribution, and related capabilities, scale-up our existing support functions, or effectively integrate new functional areas, could adversely affect our
ability to successfully commercialize our medicines.
The proximity of our current and planned upcoming independent launches could increase the likelihood that suchthe risks set forth above will occur.
The degree of market acceptance for our medicines, including our commercial medicines and our medicines in development, depends upon a
number ofseveral factors, including the:
● receipt and scope of marketing authorizations;
● establishment and demonstration in the medical and patient community of the efficacy and safety of our medicines, public perception regarding our medicines and their potential advantages over competing products;
● cost and effectiveness of our medicines compared to other available therapies;
● patient convenience of the dosing regimen for our medicines; and
● reimbursement policies of government and third-party payers.
Based on the profile of our medicines, physicians, patients, patient advocates, payers or the medical community in general may not accept or use any of the medicines that we or our partners may develop. For example, the product label for WAYLIVRA in the EU requires regular blood monitoring, which has negatively affected our ability to attract and retain patients for this medicine.
For example, the product label for WAYLIVRA in the EU requires regular blood monitoring, which has negatively affected our ability to
attract and retain patients for this medicine.
If government or other third-party payers fail to provide adequate coverage and payment rates for our medicines, including our commercial medicines and our medicines in development, or if healthcare reform measures increase our costs, decrease our sales, or negatively impact reimbursement for our products, our revenue will be limited.
Third-party payers, whether foreign or domestic, or governmental or commercial, are developing increasingly sophisticated methods of
controlling healthcare costs. In addition, in the U.S., no uniform policy of coverage and reimbursement for medicines exists among third-party payers. Therefore, coverage and reimbursement for medicines can differ significantly from payer to payer. For
example, the Affordable Care Act, or ACA, was passed in March 2010, and substantially changed the way healthcare is financed by both governmental and private insurers and continues to significantly impact the U.S. pharmaceutical industry. There have
been judicial and Congressional challenges to certain aspects of the ACA, as well as efforts to repeal or replace certain aspects of the ACA. It is unclear how future litigation and healthcare reform measures will impact the ACA and our business.
Further, we believe that future coverage, reimbursement and pricing will likely be subject to increased restrictions both in the U.S. and in international markets. In the U.S., recent health reform measures have resulted in reductions in Medicare and other healthcare funding, and there have been several recent U.S. Congressional inquiries, legislation and executive orders designed to, among other things, reduce drug prices, increase competition (including by enhancing support for generic and biosimilar drugs), lower out-of-pocket drug costs for patients, curtail spread pricing practices by pharmacy benefit managers, and foster scientific innovation to promote better health care and improved health. For example, the Affordable Care Act substantially changed the way healthcare is financed by both governmental and private insurers and continues to significantly impact the U.S. pharmaceutical industry. Since its enactment, there have been amendments and judicial, Congressional and executive branch challenges to certain aspects of the Affordable Care Act, as well as efforts to repeal or replace certain aspects of the Affordable Care Act. We expect that additional U.S. federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that the U.S. federal government will pay for healthcare products and services, which could result in reduced demand or revenue for our commercial medicines and our medicines in development.
In addition, the Inflation Reduction Act of 2022, or the IRA, includes key actions aimed at reducing the costs of prescription drugs and allows HHS to negotiate the price of certain single-source drugs covered under Medicare and establish a price cap on such drugs. The IRA, among other things, (1) directed HHS to negotiate the price of certain single-source drugs and biologics that have been on the market for at least seven years covered under Medicare, or the Medicare Drug Price Negotiation Program, and (2) imposed rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation. Each year, up to 20 products will be selected by HHS for the Medicare Drug Price Negotiation Program. Products subject to the Medicare Drug Price Negotiation Program are expected to experience a significant reduction in reimbursement from the Medicare program on a per unit basis.
The current U.S. Presidential administration is pursuing policies to reduce regulations and expenditures across government agencies, including at HHS, the FDA, CMS, and other related agencies, with a particular focus on most favored nation pricing equal to or lower than those paid in other developed nations. These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose additional policy changes that create uncertainty for our business. For example, in furtherance of the administration’s drug pricing initiatives, in December 2025, CMS issued proposed rules that, if finalized, would implement new mandatory and voluntary payment models to implement a most favored nation rebate model. These models are referred to as the GLOBE Model, GUARD Model and GENEROUS Model. At this time, it remains unclear whether the proposed models will be finalized and, if so, whether any changes will be made prior to their implementation. These and other recent actions and policies may significantly reduce U.S. drug prices, potentially impacting manufacturers’ global pricing strategies and profitability, while increasing their operational costs and compliance risks.
Further, we believe that future coverage, reimbursement and pricing will likely be subject to increased restrictions both in the U.S. and
in international markets. In the U.S., recent health reform measures have resulted in reductions in Medicare and other healthcare funding, and there have been several recent U.S. Congressional inquiries, legislation and executive orders designed to,
among other things, reduce drug prices, increase competition (including by enhancing support for generic and biosimilar drugs), lower out-of-pocket drug costs for patients, curtail spread pricing practices by pharmacy benefit managers, and foster
scientific innovation to promote better health care and improved health. In addition, the Inflation Reduction Act of 2022, or the IRA, includes key actions aimed at reducing the costs of prescription drugs and allows HHS to negotiate the price of
certain single-source drugs covered under Medicare and establish a price cap on such drugs. The IRA, among other things, (1) directs HHS to negotiate the price of certain single-source drugs and biologics that have been on the market for at least seven
years covered under Medicare, or the Medicare Drug Price Negotiation Program, and (2) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation. These provisions began to take effect progressively
starting in fiscal year 2023, although the Medicare Drug Price Negotiation Program is currently subject to legal challenges. Under this program, HHS has already announced the agreed-upon prices of the first drugs that were subject to price negotiations
and will announce the agreed-upon prices of additional drugs in the coming years. In response to an October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the CMS Innovation Center that will
be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care. It is unclear whether the models will be utilized in any health reform measures in the future. Further, on December 7, 2023, the Biden
administration announced an initiative to control the price of prescription drugs using march-in rights under the Bayh-Dole Act. On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance
Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights. While march-in rights have not previously been exercised, it
is uncertain if that will continue under the new framework. It is unclear whether or how these selected models or similar policy initiatives will impact prescription drug pricing in the future, particularly in light of the recent U.S. presidential and
congressional elections.
At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and
biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from
other countries and bulk purchasing. For example, on January 5, 2024, the FDA approved Florida’s Section 804 Importation Program, or SIP, proposal to import certain drugs from Canada for specific state healthcare programs. It is unclear how this
program will be implemented, including which drugs will be chosen, and whether it will be subject to legal challenges in the United States or Canada. Other states have also submitted SIP proposals that are pending review by the FDA. Any such approved
importation plans, when implemented, may result in lower drug prices for products covered by those programs. Third-party coverage and reimbursement for medicines may not be available or adequate in either the U.S. or international markets, which would
negatively affect the potential commercial success of our products, our revenue and our profits.
The biotechnology and pharmaceutical industries are highly competitive and subject to significant and rapid technological change. Our competitors engage in drug discovery throughout the world, are numerous, and include, among others, major pharmaceutical companies and
specialized biopharmaceutical firms. In addition, other companies are engaged in developing RNA-targeted technology. Our competitors maymay, succeedamong other things, relative to our medicines or medicines in developing medicines that aredevelopment:
● develop safer or more effective products;
● develop less costly products;
● receive more favorable reimbursement coverage;
● implement more effective approaches to sale and marketing;
● develop products that are more convenient to use than our medicines;
● have access to increased manufacturing capacity;
● obtain regulatory approval for products more quickly; or
● establish superior intellectual property positions.
These competitive developmentsadvantages could make our medicines, including our commercial medicines and our medicines in development, obsolete or
non-competitive.
Certain of our partners are pursuing other technologies or developing other medicines either on their own or in collaboration with others,
including our competitors, to treat some of the same diseases our own collaborative programs target. Competition may negatively impact a partner’s focus on and commitment to our medicines and, as a result, could delay or otherwise negatively affect the
commercialization of our medicines, including our commercial medicines and our medicines in development.
Many of our competitors have substantially greater financial, technical and human resources than we do. In addition, many of these
competitors have significantly greater experience than we do in conducting preclinical testing and human clinical studies of new pharmaceutical products, in obtaining FDA and other regulatory authorizations of such products and in commercializing such
products. Accordingly, our competitors may succeed in obtaining regulatory authorization for products earlier than we do or more successfully commercialize their products.
● TRYNGOLZA faces competition in FCS from a commercial competitor and, if approved for sHTG, could face competition from commercial competitors in the future;
● DAWNZERA faces competition from several commercial competitors, including an oral product, and could face competition from additional commercial competitors in the future;
● WAINUA faces competition in ATTRv-PN from numerous competitors, including an oral product, and, if approved for ATTR-CM, would face competition from several commercial competitors, including an oral product, and could face competition from additional commercial competitors in the future;
SPINRAZA injection for intrathecal use is an antisense medicine indicated for the treatment of SMA patients of all ages approved in over
50 countries. Specifically,● SPINRAZA faces competition from onasemnogene abeparvovec,both a gene therapy product that was approved in the U.S. in May 2019 and in the EU in May 2020 for the treatment of SMA, as well as risdiplam, an oral product for the
treatment of SMA that was approved in the U.S. in August 2020 and in the EU in March 2021.SMA. Biogen has in the past disclosed that SPINRAZA revenue decreased due to a reduction in demand as a result of increased competition and that future sales of
SPINRAZA may be adversely affected by competing products.products;
● QALSODY could face competition from a commercial competitor in the future; and
● Obudanersen, if approved, could face competition from commercial competitors in the future, including oral products.
For details regarding medicines that compete or may compete directly with our marketed medicines and late-stage medicines, refer to the section titled, Competition, in Part I, Item 1, Business.
Certain of our partners are pursuing other technologies or developing other medicines either on their own or in collaboration with others, including our competitors, to treat some of the same diseases that our own programs target. Competition may negatively impact a partner’s focus on and commitment to our medicines and, as a result, could delay or otherwise negatively affect the commercialization of our partnered medicines. Additionally, companies that are developing medicines that target the same patient populations as our medicines in development may compete with us to enroll participants in the clinical trials for such medicines, which could make it more difficult for us to complete enrollment for these clinical trials.
Following approval of a medicine, we and our partners must comply with comprehensive government regulations regarding the manufacture,
marketing and distribution of medicines. PromotionalThe communicationsFDA regardingand prescriptionforeign medicinesregulatory mustbodies be consistent withhave the informationauthority into impose significant restrictions on an approved medicine through the product’sproduct approved labeling.label. We or our partners may not obtain the labeling claims necessary or
desirable to successfully commercialize our medicines, including our commercial medicines and our medicines in development.
The FDA and foreign regulatory bodies have the authority to impose significant restrictions on an approved medicine through the product
label and on advertising, promotional and distribution activities.
PrescriptionPromotional communications regarding prescription medicines must be consistent with the information in the product’s approved labeling. Additionally, prescription medicines may be promoted only for the approved indication(s) in accordance with the approved label. The FDA and other
regulatory authorities actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability.
In addition, when approved, the FDA or a foreign regulatory authority may condition approval on the performance of post-approval clinical studies or patient monitoring, which could be time consuming and expensive. For example, in connection with the conditional marketing approval for WAYLIVRA in the EU, we are required to conduct a post-authorization safety study to evaluate the safety of WAYLIVRA on thrombocytopenia and bleeding in FCS patients taking WAYLIVRA. If the results of such post-marketing studies are not satisfactory, the FDA, EC or other foreign regulatory authorities may withdraw the marketing authorization or may condition continued marketing on commitments from us or our partners that may be expensive and time consuming to fulfill.
● fund our development activities for SPINRAZA and QALSODY;
● seek and obtain regulatory approvals for SPINRAZA and QALSODY; and
● successfully commercialize SPINRAZA and QALSODY.
We are relying on Biogen to obtain additional regulatory approvals for SPINRAZA and QALSODY, generate additional clinical data for
SPINRAZA and QALSODY, manufacture SPINRAZA and QALSODY, and successfully commercialize SPINRAZA and QALSODY. In general, we cannot control the amount and timing of resources that Biogen devotes to our collaborations. If Biogen fails to further develop
SPINRAZA or QALSODY, obtain additional regulatory approvals for SPINRAZA or QALSODY, manufacture SPINRAZA or QALSODY, or successfully commercialize SPINRAZA or QALSODY, or if Biogen’s efforts in any of these respects are ineffective, revenues for
SPINRAZA or QALSODY would be negatively affected.
We have entered into a collaborative arrangement with AstraZeneca to develop and commercialize WAINUA. Under the terms of the
collaboration agreement, we and AstraZeneca willare co-developco-developing and co-commercializeco-commercializing WAINUA in the U.S. and AstraZeneca will havehas the sole right to commercialize WAINUA in all other countries. As a company we do not have experience with
co-commercialization arrangements. We also do not have control over (1) the amount and timing of resources that AstraZeneca devotes to our collaboration, particularly outside of the U.S; (2) the pricing and reimbursement strategies for WAINUA; and (3)
whether AstraZeneca elects to terminate the collaborative arrangement. If the co-commercialization arrangement for WAINUA is not successful for any reason, WAINUA may not meet our commercial objectives and our revenues for WAINUA may be limited.
To successfully commercialize any of our medicines, we need
to optimize and manage large-scale commercial manufacturing capabilities either on a standalone basis or through a third-party manufacturer. As our drug development and commercial pipeline increases and matures, we will have a greater need for
clinical trial and commercial manufacturing capacity. We will also need tomust ensure that we have the manufacturing capabilities in place to support advances in our drug development activities, such as new chemistries. While we believe our current capabilities and those we obtain through third-party manufacturers support our manufacturing needs now, it will be important to expand our manufacturing infrastructure
in the future, which will likely require substantial expenditures. If we are not successful in executing this expansion, or if the demand for any of our commercial medicines exceeds our expectations, it could limit our ability to meet our manufacturing requirements and commercial objectives in the future.
We rely on third-party manufacturers to supply the drug substance and drug product for TRYNGOLZATRYNGOLZA, DAWNZERA and WAINUA and drug product for WAYLIVRA.
The operations of our suppliers, many of which are located outside of the United States, are subject to additional risks that are beyond our control. For example, theretariffs have been Congressional legislative proposals, such ason the recentraw billmaterials, titledcomponents, the
BIOSECUREor Act,equipment we use to discouragemanufacture contractingour with Chinese companies for the developmentproducts, or on our drug substance or finished products, will increase our manufacturing of pharmaceutical products.costs. In addition, merger and acquisition activity within the commercial manufacturing space could reduce the availability of
resources from our third-party manufacturers. Delays or disruption to our own or third-party commercial manufacturing capabilities for any reason could limit the commercial success of our medicines.
We and our partners may not obtain necessary regulatory approvals on a timely basis, if at all, for our medicines. It is possible that
regulatory authorities will not approve our medicines for marketing or our commercial medicines in additional markets or for additional indications. If the FDA or another regulatory authority believes that we or our partners have not sufficiently
demonstrated the safety or efficacy of any of our medicines, including our commercial medicines or our medicines in development, the authority will not approve the specificsuch medicine or will require additional studies, which could be time consuming and
expensive and delay or harm commercialization of the medicine. For example, in August 2018 we received a complete response letter from the FDA regarding the new drug application for WAYLIVRA in which the FDA determined that the safety concerns
identified with WAYLIVRA in our clinical development program outweighed the expected benefits of triglyceride lowering in patients with FCS. We also received a Notice of Non-Compliance Withdrawal Letter, or Non-W, from Health Canada for WAYLIVRA in
November 2018.
● such authorities may disagree with the design or implementation of our clinical studies;
● we or our partners may be unable to satisfactorily demonstrate that a medicine is safe and effective for any indication;
● such authorities may not accept clinical data from studies conducted at clinical facilities that have deficient clinical practices or that are in countries where the standard of care is potentially different from the U.S.;
● we or our partners may be unable to demonstrate that our medicine’s clinical and other benefits outweigh its safety risks to support approval;
● such authorities may disagree with the interpretation of data from preclinical or clinical studies;
● such authorities may find deficiencies in the manufacturing processes or facilities of third-party manufacturers who manufacture clinical and commercial supplies for our medicines; and
● the approval policies or regulations of such authorities or their prior guidance to us or our partners during clinical development may significantly change in a manner rendering our clinical data insufficient for approval.
For example, while we continue to activate sites in the U.S., Canada, U.K., Australia and Japan, we revised and resubmitted the study protocol for the REVEAL study of obudanersen to address changes requested by EU regulators and plan to initiate EU sites for this study in 2026. Importantly, we believe we are on track to complete enrollment for this study in 2026.
● the clinical study may produce negative or inconclusive results;
Management's Discussion & Analysis (MD&A)
Largest changes
“The remainder of our revenue came from programs under our R&D collaborations, including a $280 million upfront payment for the global license of sapablursen to Ono in the second quarter of 2025, reflecting the value that our pipeline and technology continues to generate.”see in full comparison
SG&A expenses includesee in full comparisonpersonnelpersonnel, information technology systems and outside costs associated with thepre-commercializationcommercialization andcommercializationpre-commercialization activities for our medicines and costs to support our company, our employees and our stockholders including, legal, human resources, investor relations and finance. Additionally, we include in SG&A expenses such costs as rent, repair and maintenance of buildings and equipment, depreciation and utilities costs that we need to support the corporate functions listed above. We also include fees we owe under our in-licensing agreements related to SPINRAZA andQALSODY.QALSODY and cost sharing payments associated with the co-commercialization activities under our WAINUA collaboration with AstraZeneca.
Insee in full comparison2023,2025, we completed a$575.0$770.0 million offering of our1.75%0% Notes due 2030 and used$488.2$267.6 million of the net proceeds to repurchase$504.4$200.0 million in principal of our0.125%0%Notes.Notes due 2026 at a premium. As a result ofthesetherepurchases,repurchase, we recognized induced conversion expense of $16.3 million, which we recordedaas$13.4othermillionexpensegaininonourearlyconsolidatedretirementstatement ofdebtoperationsinfor2023,thewhichyearreflectsended December 31, 2025. The induced conversion expense is the difference between theamounts weamount paid to repurchaseportionstheof our 0.125%0% Notes due 2026 and thenetif-convertedcarrying balancevalue of theliabilitynotes at the time thatwe repurchasedthedebt.debt repurchase terms were finalized. Refer to Part IV, Item 15, Note 7, Long-Term Obligations and Commitments, in the Notes to the Consolidated Financial Statements for further details regarding our convertible debt.
“Interest expense for 2024 was $17.0 million compared to $12.7 million for 2023. In June 2023, we completed a $575.0 million offering of our 1.75% Notes and repurchased $504.4 million in principal of our 0.125% Notes. As a result, beginning in the second quarter of 2023, our interest expense related to our convertible notes included interest expense incurred for our 1.75% Notes. Interest expense in 2024 included a full year of interest expense related to our 1.75% Notes.”see in full comparison
Investment income forsee in full comparison20242025 was$107.0$97.8 million compared to$89.0$107.0 million for2023.2024. Theincreasedecrease in investment income was primarily due toanaincreasedecrease in interest rates associated with our investments duringamajority of 20242025 compared to2023. In addition, our cash available for investing increased due to the $489.1 million net proceeds we received from our public common stock offering in September2024.Refer to Part IV, Item 15, Note 8, Stockholders’ Equity, in the Notes to the Consolidated Financial Statements for further details on the public offering.
We have financed our operations primarily from research and development collaborative agreements. We also financed our operations from commercial revenue fromsee in full comparisonSPINRAZASPINRAZA, WAINUA and QALSODY royalties and TEGSEDI and WAYLIVRA commercial revenue. In addition, we beganreceivingearning commercial revenue fromWAINUATRYNGOLZAroyaltiesproduct sales in2024.late December 2024 and DAWNZERA product sales in late August 2025. From our inception through December 31,2024,2025, we have earned approximately$7.9$8.9 billion in revenue. We have also financed our operations through the sale of our equity securities, the issuance of long-termdebt, the sale leaseback of facilitiesdebt and the sale of future royalties. From the time we were founded through December 31,2024,2025, we have raised net proceeds of approximately$2.6$2.8 billion from the sale of our equitysecurities, which includes our sale of 11.5 million shares of common stock for net proceeds of $489 million in September 2024.securities. Additionally, from our inception through December 31,2024,2025, we have borrowed approximately$2.7$3.5 billion under long-term debt arrangements and received proceeds of approximately $0.5 billion from the sale of future royalties to finance a portion of our operations.
Full comparison: every changed paragraph (41)
As noted in our Business Overview in Part I, Item 1, Business, for three decades, we have invented medicines that we believe bring better futures to people with serious diseases. Today, as a
pioneer in RNA-targeted medicines, we continue to drive innovation in RNA therapies. We currently have sixseven marketed medicines: TRYNGOLZA, DAWNZERA, WAINUA, SPINRAZA, QALSODY, TEGSEDI and WAYLIVRA. We also have a rich innovative late- and mid-stage pipeline in neurology, cardiologycardiometabolic diseases and rareselect diseases.areas of high patient needs. We currently have nine medicines in Phase 3 development and additional medicines in early and mid-stage development.
Refer to Part I, Item 1, Business, for further details on our business and key developments in our medicines.
The following table provides selected summary information from our consolidated statements of operations for 2025 and 2024 (in millions):
Below we have included our results of operations for 2024 compared to 2023. Refer to Part II, Item 7, Management’s Discussion and Analysis of Financial Condition and Results of Operations, of our 2023
Form 10-K for our results of operations for 2023 compared to 2022. The following table provides selected summary information from our consolidated statements of operations for 2024
and 2023 (in millions):
Commercial revenue in 2025 increased 49 percent compared to 2024. This increase was primarily driven by TRYNGOLZA product sales and higher royalty revenue.
The remainder of our revenue came from programs under our R&D collaborations, including a $280 million upfront payment for the global license of sapablursen to Ono in the second quarter of 2025, reflecting the value that our pipeline and technology continues to generate.
Commercial revenue in 2024 included new sources of commercial revenue with the launch of WAINUA in the U.S. in late January 2024 and the
launch of TRYNGOLZA in the U.S. in late December 2024. SPINRAZA royalties in 2024 compared to 2023 were impacted from an annual order from a single country that did not recur in 2024.
R&D revenue decreased in 2024 compared to 2023 primarily due to the decrease in WAINUA joint development revenue as development
activities relating to ATTRv-PN wound down with the commercial launch of WAINUA. In addition, R&D revenue decreased due to the timing of significant partner payments.
Our financial results for the years ended December 31, 20242025 and 20232024 reflected the cost-sharing provisions related to our collaboration with AstraZeneca to develop and
commercialize WAINUA for the treatment of ATTR. Under the terms of the collaboration agreement, AstraZeneca iswas currentlyresponsible payingfor 55 percent of the costs associated with the ongoing global Phase 3 development program.program through December 31, 2025. After December 31, 2025, AstraZeneca is responsible for 75 percent and 87.5 percent of development costs in the U.S. and the rest of the world, respectively. Because we are leading and
conducting the Phase 3 development program, we are recognizing as R&D revenue the 55 percentpercentage of cost-share funding AstraZeneca is responsible for, net of our share of AstraZeneca’s development expenses, in the same period we incur the related
development expenses.
Our WAINUA joint development revenue in 2024 and 2023 includesincluded a $30 million milestone payment from AstraZeneca that we earned when the
MHRA Medicines and Healthcare products Regulatory Agency, or MHRA, approved WAINUA for ATTRv-PN in the UK as WAINZUAWAINZUA. Research and adevelopment $50expenses millionrelated milestone payment from AstraZeneca that we earned whento the FDAPhase approved3 development of WAINUA fordecreased in 2025 compared to 2024 as development activities related to ATTRv-PN incontinued to wind down with the U.S.,commercial respectively.launch of WAINUA.
Operating expenses, excluding non-cash compensation expense related to equity awards, increased slightly in 20242025 compared to 2023.
2024. SG&A expenses increased year over year primarily due to the launches of WAINUATRYNGOLZA, DAWNZERA and TRYNGOLZA, including establishing the TRYNGOLZA field team in the second quarter of 2024, and advancing launch preparation activities for donidalorsen. R&D
expenses were essentially flat year over year as several late-stage studies ended.WAINUA.
Non-cash compensation expense related to equity awards increasedwere inessentially 2024flat comparedyear toover 2023year due to increased headcount andoffset by a higherlower stock
price on the grant date of annual equity awards in 20242025 compared to 2023.2024. We believe non-cash compensation expense related to equity awards is not indicative of our operating results or cash flows from our operations.
Our cost of sales is comprised of costs related to our commercial revenue, which consisted of manufacturing costs, including certain fixed
costs, transportation and freight, indirect overhead costs primarily associated with the manufacturing and distribution of TRYNGOLZA, DAWNZERA, TEGSEDI and WAYLIVRA and certain associated period costs.
Costs of sales for recently launched products, such as TRYNGOLZA and DAWNZERA, does not include the full cost of manufacturing until we manufacture and sell additional inventory after exhausting pre-launch inventory, which we previously recorded as R&D expense.
Drug discovery expenses, excluding non-cash compensation expense related to equity awards, decreasedincreased in 20242025 compared to 2023.2024 In 2023,as we
recognized $15continued millionto inadvance R&Dour expensetechnologies fordiscussed licensing Vect-Horus’ platform technology.above.
Our development expenses, excluding non-cash compensation expense related to equity awards, were essentially flatdecreased in 20242025 compared to
2023. 2024 as several late-stage studies ended. We expect our development expenses will continue to be stablestabilize as several late-stage studies end and we reallocate resources toward earlier stage programs.
Manufacturing and development chemistry expenses, excluding
non-cash compensation expense related to equity awards, decreasedincreased in 20242025 compared to 20232024 due to the timing of manufacturing performed by our contract manufacturing organizations for drug product and active pharmaceutical ingredients related to several late-stage programs. Refer to the
section titled, Manufacturing, in Part I, Item 1, Business, for further details on the activities and types of costs we incur
in our manufacturing process.
R&D support expenses, excluding non-cash compensation expense related to equity awards, were essentially flatincreased in 20242025 compared to
2023. 2024 primarily due to increased costs relating to computer software and licenses.
SG&A expenses include personnelpersonnel, information technology systems and outside costs associated with the pre-commercializationcommercialization and commercializationpre-commercialization activities for our
medicines and costs to support our company, our employees and our stockholders including, legal, human resources, investor relations and finance. Additionally, we include in SG&A expenses such costs as rent, repair and maintenance of buildings and
equipment, depreciation and utilities costs that we need to support the corporate functions listed above. We also include fees we owe under our in-licensing agreements related to SPINRAZA and QALSODY.QALSODY and cost sharing payments associated with the co-commercialization activities under our WAINUA collaboration with AstraZeneca.
SG&A expenses, excluding non-cash compensation expense related to equity awards, increased in 20242025 compared to 20232024 primarily due to the
launches of WAINUATRYNGOLZA, DAWNZERA and TRYNGOLZA,WAINUA. including establishing the TRYNGOLZA field team in the second quarter of 2024, and advancing launch preparation activities for donidalorsen.
We expect SG&A expenses to increase as we continue to invest in our independent commercial launches.
Investment income for 2024
2025 was $107.0$97.8 million compared to $89.0
$107.0 million for 2023.2024. The increasedecrease in investment income was primarily due to ana increasedecrease in interest rates associated with our investments during
a majority of 20242025 compared to 2023. In addition, our cash available for investing increased due to the $489.1 million net proceeds we received from our public common stock offering in September 2024. Refer to Part IV, Item 15, Note 8, Stockholders’ Equity, in the Notes to the Consolidated Financial Statements for further details on the public offering.
Interest expense for 2024 was $17.0 million compared to $12.7 million for 2023. In June 2023, we completed a $575.0 million offering of our 1.75% Notes and repurchased $504.4 million in principal of our 0.125% Notes.
As a result, beginning in the second quarter of 2023, our interest expense related to our convertible notes included interest expense incurred for our 1.75% Notes. Interest expense in 2024 included a full year of interest expense related to our 1.75%
Notes.
Gain (Loss) on Investments
We recorded a $2.9$10.2 million gain on investments and
$1.9 a $2.9 million loss on investments for 20242025 and 2023,2024, respectively. The period-over-period fluctuation in our gain (loss) on investments was primarily
driven by changes in the fair value of our investments in privately held and publicly traded biotechnology companies.
In 2023,2025, we completed a $575.0$770.0 million offering of our 1.75%
0% Notes due 2030 and used $488.2$267.6 million of the net proceeds to repurchase $504.4$200.0 million in principal of our 0.125%0% Notes.Notes due 2026 at a premium. As a result of thesethe repurchases,repurchase, we recognized induced conversion expense of $16.3 million, which we recorded aas $13.4other millionexpense gainin onour earlyconsolidated retirementstatement of debtoperations infor 2023,the whichyear reflectsended December 31, 2025. The induced conversion expense is the difference
between the amounts weamount paid to repurchase portionsthe of our 0.125%0% Notes due 2026 and the netif-converted carrying balancevalue of the liabilitynotes at the time that we repurchased the debt.debt repurchase terms were finalized. Refer to Part IV, Item 15, Note 7, Long-Term Obligations and Commitments, in the Notes to the Consolidated Financial Statements for further
details regarding our convertible debt.
We recorded an income tax expense of $1.8 million for 2025 compared to an income tax benefit of $6.2 million for 2024.
We recorded an income tax benefit of $6.2 million for 2024 compared to an income tax expense of $32.3 million for 2023.
The income tax expense for 2025 primarily relates to state income taxes, partially offset by a federal tax benefit related to a capital loss carryback. The income tax benefit duringfor 2024 primarily related to adjustments to prior year tax return positions for the royalty purchase agreement
with Royalty Pharma and deductions related to foreign SPINRAZA royalties.
In July 2025, H.R.1 - 119th Congress was signed into law, introducing significant changes to U.S. federal tax law. The new law restores current expensing of domestic R&D costs and allows us to accelerate the deduction for a significant amount of such costs we capitalized since 2022. These tax law changes did not have a material effect on our tax expense for the year ended December 31, 2025.
The decrease in income tax expense for 2024 compared to 2023 primarily related to the impact of the Royalty Pharma transaction in 2023. We
reflected the Royalty Pharma transaction as a taxable sale, which required us to include the proceeds from the sale, net of currently deductible issuance costs, as taxable income in 2023.
We generated a net loss of $453.9
$381.4 million for 20242025 compared to $366.3
$453.9 million for 2023.2024. Our net loss increaseddecreased for 2024
2025 compared to 20232024 primarily due to factors discussed in the sections above. Basic and diluted net loss per share for 20242025 were $3.04$2.38 compared to $2.56$3.04 for 2023.2024. Our net loss per share increaseddecreased for 20242025 compared to 20232024 primarily due to factors discussed in the sections above.
We have financed our operations primarily from research and
development collaborative agreements. We also financed our operations from commercial revenue from SPINRAZASPINRAZA, WAINUA and QALSODY royalties and TEGSEDI and WAYLIVRA commercial revenue. In addition, we began receivingearning commercial revenue from WAINUATRYNGOLZA royaltiesproduct sales in
2024. late December 2024 and DAWNZERA product sales in late August 2025. From our inception through December 31, 2024,2025, we
have earned approximately $7.9$8.9 billion in revenue. We have also
financed our operations through the sale of our equity securities, the issuance of long-term debt, the sale leaseback of facilitiesdebt and the sale of future royalties. From the time we were founded through December 31, 2024,2025, we have raised net proceeds of approximately $2.6$2.8 billion from the sale of our equity securities, which includes our sale
of 11.5 million shares of common stock for net proceeds of $489 million in September 2024.securities. Additionally, from our inception through December 31, 2024,2025, we have borrowed approximately $2.7$3.5 billion under long-term debt arrangements and received proceeds of approximately $0.5 billion from the sale of future royalties to finance a portion of our operations.
Our working capital decreased from 2024 to 2025 as we reclassified our 0% Notes due 2026 from non-current liabilities to current liabilities in the second quarter of 2025 because the notes are due in April 2026. During the same period, our long-term obligations increased due to the issuance of our 0% Notes due 2030, which was partially offset by the partial repurchase of our 0% Notes due 2026, in the fourth quarter of 2025.
Our working capital increased from 2023 to 2024 primarily due to a decrease in current liabilities as a result of lower deferred contract
revenue as of December 31, 2024 compared to December 31, 2023. During the same period, our long-term obligations did not change significantly.
Our contractual obligations consist primarily of our convertible debt. In addition, we also have a facility mortgage, facility leases, equipment financing arrangements and other obligations. In the third quarter of 2025, our build-to-suit lease in Carlsbad, California commenced, resulting in an increase to our contractual obligations related to operating leases. We believe our cash, cash equivalents and short-term investments, as well as plans for cash in the future, will be sufficient to fund our planned operations and these obligations. We have not entered into, nor do we currently have, any off-balance sheet arrangements (as defined under SEC rules).
● Assessing the propriety of revenue recognition and associated deferred revenue;
● Determining the appropriate cost estimates for unbilled preclinical studies and clinical development activities; and
● Assessing the appropriate estimate of anticipated future royalty payments under our royalty purchase agreement.
Identifying the performance obligations contained in the agreement Our assessment of what constitutes a separate performance obligation requires us to apply judgement. Specifically, we have to identify which goods and services we are required to provide under the contract are distinct.
Determining the transaction price, including any variable consideration To determine the transaction price, we review the amount of consideration we are eligible to earn under the agreement. We do not typically include any payments we may receive in the future in our initial transaction price since the payments are typically not probable because they are contingent upon certain future events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price that have become probable.
Allocating the transaction price to each of our performance obligations When we allocate the transaction price to more than one performance obligation, we make estimates of the relative stand-alone selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. The estimate of the relative stand-alone selling price requires us in some cases to make significant judgements. For example, when we deliver a license at the start of an agreement, we use valuation methodologies, such as the relief from royalty method, to value the license. Under this method we are required to make estimates including future sales, royalties on future product sales, contractual milestones, expenses, income taxes and discount rates. Additionally, when we estimate the selling price for R&D services, we make estimates, including: the number of internal hours we will spend on the services, the cost of work we and third parties will perform and the cost of clinical trial material we will use.
Whether a milestone payment is probable (discussed in detail above under “Determining the transaction price, including any variable consideration”); and If we are performing services, we recognize revenue over our estimated period of performance in a similar manner to the amortization of upfront payments (discussed above under “R&D Services with Upfront Payments”).
What changed in the latest 10-Q
Risk Factors
Largest changes
Our success depends to a significant degree upon whether we can continue to develop, secure and maintain intellectual property rights to proprietary products and services. However, we may not receive issued patents on any of our pending patent applications in the U.S. or in other countries and we may not be able to obtain, maintain or enforce our patents and other intellectual property rights, any of which could impact our ability to compete effectively. In addition, the scope of any of our issued patents may not be sufficiently broad to provide us with a competitive advantage. Furthermore, other parties may successfully challenge, invalidate or circumvent our issued patents or patents licensed to us so that our patent rights do not create an effective competitive barrier or revenue source. For example, on June 22, 2026, Biogen, Cold Spring Harbor Laboratory, and Ionis filed a patent infringement lawsuit in the District Court of Delaware following notice that Somerset Therapeutics, LLC had filed an Abbreviated New Drug Application, or ANDA, seeking approval to commercialize a generic version of SPINRAZA and alleging that certain patents covering SPINRAZA and its use are invalid or would not be infringed. If Somerset Therapeutics obtains a favorable ruling in such lawsuit, our revenues from SPINRAZA could be materially adversely affected.see in full comparison
“In December 2021, we entered into a collaborative agreement with AstraZeneca under which we granted AstraZeneca exclusive worldwide rights to develop and commercialize WAINUA, with the parties sharing responsibility and costs for development and U.S. commercialization activities, and AstraZeneca assuming sole responsibility for commercialization outside the U.S. We exercised our opt-out right under the agreement and the opt-out process set forth in the agreement is underway. In general, we cannot control the amount and timing of resources that AstraZeneca devotes to our collaboration. …”see in full comparison
“We have entered into a collaborative arrangement with AstraZeneca to develop and commercialize WAINUA. Under the terms of the collaboration agreement, we and AstraZeneca are co-developing and co-commercializing WAINUA in the U.S. and AstraZeneca has the sole right to commercialize WAINUA in all other countries. As a company we do not have experience with co-commercialization arrangements. …”see in full comparison
From time to time, we have to defend our intellectual property rights. If we are involved in an intellectual property dispute, we may need to litigate to defend our rights or assert them against others. Disputes can involve arbitration, litigation or proceedings declared by the U.S. PTO or the International Trade Commission or foreign patent authorities. Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses and could distract our technical and management personnel from their normal responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock. For example, in September 2025, we filed a claim against Arrowhead Pharmaceuticals, Inc., or Arrowhead, for patent infringement oversee in full comparisonArrowhead'sArrowhead’s commercialization of plozasiran, and Arrowhead filed a counterclaim against us seeking to invalidate that same patent. We are also a party to ongoing litigation involving a third party seeking regulatory approval to commercialize a generic version of SPINRAZA in the U.S. as described above. For details regardingthistheseproceeding,proceedings, refer to Part II, Item 1, Legal Proceedings.
“● WAINUA faces competition in ATTRv-PN from numerous competitors, including an oral product, and, if approved for ATTR-CM, would face competition from several commercial competitors, including an oral product, and could face competition from additional commercial competitors in the future;”see in full comparison
“● WAINUA faces competition from numerous competitors, including an oral product in markets outside the U.S.;”see in full comparison
Full comparison: every changed paragraph (37)
In addition, the Inflation Reduction Act of 2022, or the IRA, includes key actions aimed at reducing the costs of prescription drugs and allows HHSthe U.S. Department of Health and Human Services, or HHS, to negotiate the price of certain single-source drugs covered under Medicare and establish a price cap on such drugs. The IRA, among other things, (1) directed HHS to negotiate the price of certain single-source drugs and biologics that have been on the market for at least seven years covered under Medicare, or the Medicare Drug Price Negotiation Program, and (2) imposed rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation. Each year, up to 20 products will be selected by HHS for the Medicare Drug Price Negotiation Program. Products subject to the Medicare Drug Price Negotiation Program are expected to experience a significant reduction in reimbursement from the Medicare program on a per unit basis.
The current U.S. Presidential administration is pursuing policies to reduce regulations and expenditures across government agencies, including at HHS, the FDA, HHS, Centers for Medicare & Medicaid Services, or CMS, and other related agencies, with a particular focus on most favored nation pricing equal to or lower than those paid in other developed nations. These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose additional policy changes that create uncertainty for our business. For example, in furtherance of the administration’s drug pricing initiatives, in late 2025, CMS issued proposed rules that, if finalized, would implement new mandatory and voluntary payment models to implement a most favored nation rebate model. These models are referred to as the GLOBE Model, GUARD Model and GENEROUS Model. At this time, it remains unclear whether the proposed models will be finalized and, if so, whether any changes will be made prior to their implementation. These and other recent actions and policies may significantly reduce U.S. drug prices, potentially impacting manufacturers’ global pricing strategies and profitability, while increasing their operational costs and compliance risks.
If we or our partners fail to compete effectively, our medicines, including our commercial medicines and our medicines in development, will not generate significant revenues.*
● TRYNGOLZA faces competition in FCS from a commercial competitor and, if approved forin sHTG, could face competition from commercial competitors in the future;
● WAINUA faces competition from numerous competitors, including an oral product in markets outside the U.S.;
● WAINUA faces competition in ATTRv-PN from numerous competitors, including an oral product, and, if approved for ATTR-CM, would face competition from several commercial competitors, including an oral product, and could face competition from additional commercial competitors in the future;
In addition, when approved, the FDA or a foreign regulatory authority may condition approval on the performance of post-approval clinical studies or patient monitoring, which could be time consumingtime-consuming and expensive. For example, in connection with the conditional marketing approval for WAYLIVRA in the EU, we are required to conduct a post-authorization safety study to evaluate the safety of WAYLIVRA on thrombocytopenia and bleeding in FCS patients taking WAYLIVRA. If the results of such post-marketing studies are not satisfactory, the FDA, EC or other foreign regulatory authorities may withdraw the marketing authorization or may condition continued marketing on commitments from us or our partners that may be expensive and time consumingtime-consuming to fulfill.
If we or others identify side effects after any of our medicines are on the market, or if manufacturing problems occur subsequent to regulatory approval, or if we, our CMOscontract manufacturing organizations, or our partners fail to comply with regulatory requirements, we or our partners may, among other things, lose regulatory approval and be forced to withdraw products from the market, need to conduct additional clinical studies, incur restrictions on the marketing, distribution or manufacturing of the product, and/or change the labeling of our medicines.
We depend on our collaboration with AstraZeneca for the joint development and commercialization of WAINUA.*
In December 2021, we entered into a collaborative agreement with AstraZeneca under which we granted AstraZeneca exclusive worldwide rights to develop and commercialize WAINUA, with the parties sharing responsibility and costs for development and U.S. commercialization activities, and AstraZeneca assuming sole responsibility for commercialization outside the U.S. We exercised our opt-out right under the agreement and the opt-out process set forth in the agreement is underway. In general, we cannot control the amount and timing of resources that AstraZeneca devotes to our collaboration. In addition, we do not have control over whether AstraZeneca elects to terminate the collaborative arrangement. If AstraZeneca fails to further develop or successfully commercialize WAINUA for any reason, our revenues for WAINUA would be negatively affected.
We have entered into a collaborative arrangement with AstraZeneca to develop and commercialize WAINUA. Under the terms of the collaboration agreement, we and AstraZeneca are co-developing and co-commercializing WAINUA in the U.S. and AstraZeneca has the sole right to commercialize WAINUA in all other countries. As a company we do not have experience with co-commercialization arrangements. We also do not have control over (1) the amount and timing of resources that AstraZeneca devotes to our collaboration, particularly outside of the U.S; (2) the pricing and reimbursement strategies for WAINUA; and (3) whether AstraZeneca elects to terminate the collaborative arrangement. If the co-commercialization arrangement for WAINUA is not successful for any reason, WAINUA may not meet our commercial objectives and our revenues for WAINUA may be limited.
In addition, a Joint Steering Committee, or JSC, having equal membership from us and AstraZeneca, and various subcommittees oversee and coordinate the development, manufacturing, commercialization and other exploitation activities for WAINUA in the U.S. by mutual agreement. If any subcommittee cannot reach unanimous agreement on any matter within its respective scope of authority, such matter may be referred to the JSC for resolution. If the JSC cannot come to a mutual agreement on any particular matter, this could delay our ability to develop or commercialize WAINUA.
We rely on third-party manufacturers to supply the drug substance and drug product for TRYNGOLZA, DAWNZERA and WAINUA and drug product for WAYLIVRA. The operations of our suppliers, many of which are located outside of the United States, are subject to additional risks that are beyond our control. For example, tariffs on the raw materials, components, or equipment used to manufacture our products, or on our drug substance or finished products, will increase our manufacturing costs. On April 2, 2026, President Trump issued a proclamation that imposes tariffs of up to 100% on imported patented pharmaceutical products and active pharmaceutical ingredients, with specified exceptions. We are evaluating the potential impacts on our business related to the imposition of such tariffs.tariffs but believe any impacts will be limited and manageable. In addition, merger and acquisition activity within the commercial manufacturing space could reduce the availability of resources from our third-party manufacturers. Delays or disruption to our own or third-party commercial manufacturing capabilities for any reason could limit the commercial success of our medicines.
We and our partners may not obtain necessary regulatory approvals on a timely basis, if at all, for our medicines. It is possible that regulatory authorities will not approve our medicines for marketing or our commercial medicines in additional markets or for additional indications. If the FDA or another regulatory authority believes that we or our partners have not sufficiently demonstrated the safety or efficacy of any of our medicines, including our commercial medicines or our medicines in development, the authority will not approve such medicine or will require additional studies, which could be time consumingtime-consuming and expensive and delay or harm commercialization of the medicine. For example, in August 2018 we received a complete response letter from the FDA regarding the new drug application for WAYLIVRA in which the FDA determined that the safety concerns identified with WAYLIVRA in our clinical development program outweighed the expected benefits of triglyceride lowering in patients with FCS. We also received a Notice of Non-Compliance Withdrawal Letter, or Non-W, from Health Canada for WAYLIVRA in November 2018.
● such authorities may not accept clinical data from studies conducted at clinical facilities that have deficient clinical practices or that are in countries where the standard of care is potentially different from that in the U.S.;
Even if our medicines are successful in preclinical and human clinical studies, the medicines may not be successful in late-stage clinical studies. Similarly, topline, preliminary or interim data we release for any of our clinical studies may not be indicative of full or final results from such study.*
In the past, we have invested in clinical studies of medicines that have not met the primary clinical endpoints in their Phase 3 studies or have been discontinued for other reasons. For example, in July 2026, we and AstraZeneca announced that the CARDIO-TTRansform Phase 3 trial for eplontersen in patients with ATTR-CM did not meet the primary efficacy endpoint of the composite outcome of cardiovascular, or CV, mortality and recurrent CV clinical events up to Week 140 compared with placebo. In October 2021, Biogen reported that QALSODY did not meet the primary clinical endpoint in the Phase 3 VALOR study; however, trends favoring QALSODY were seen across multiple secondary and exploratory measures of disease activity and clinical function. In addition, in March 2021, Roche decided to discontinue dosing in the Phase 3 GENERATION HD1 study of tominersen in patients with manifest Huntington’s disease based on the results of a pre-planned review of data from the Phase 3 study conducted by an unblinded Independent Data Monitoring Committee. Similar results could occur in clinical studies for our other medicines.
We depend on independent clinical investigators, contract research organizations and other third-party service providers to conduct our clinical studies for our medicines and expect to continue to do so in the future. For example, we use clinical research organizations, such as Icon Clinical Research Limited, Medpace, Inc., Parexel International Corporation, Syneos Health, Inc. and Thermo Fisher Scientific Inc. for the clinical studies for our medicines, including WAINUA for the treatment of ATTR-CM, DAWNZERA, obudanersen, olezarsen, ulefnersen and zilganersen. We rely heavily on these parties for successful execution of our clinical studies, but do not control many aspects of their activities. For example, the investigators are not our employees, but we are responsible for ensuring that such investigators conduct each of our clinical studies in accordance with the general investigational plan and approved protocols for the study. Third parties may not complete activities on schedule or may not conduct our clinical studies in accordance with regulatory requirements or our stated protocols. For example, some of our key vendors have in the past experienced labor shortages, which impacted their ability to perform services for us for certain of our clinical trials. Subsequent failures of these third parties to carry out their obligations, or a termination of our relationship with such third parties, could delay or prevent the development, marketing authorization and commercialization of our medicines.
Since corporate partnering is part of our strategy to fund the advancement and commercialization of some of our development programs, if any of our collaborative partners fail to fund our collaborative programs, or if we cannot obtain additional partners, we may have to delay or stop progress on those drug development programs.*
● AstraZeneca for the joint development and funding of WAINUA;
We may not be able to benefit from designations for our medicines from regulatory authorities that are intended to confer benefits such as financial incentives or an accelerated regulatory pathway.*
In the U.S., under the Orphan Drug Act, the FDA may designate a medicine as an Orphan Drug if it is intended to treat a rare disease or condition affecting fewer than 200,000 individuals in the U.S. Orphan Drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process, but it can provide financial incentives, such as tax advantages and user-fee waivers, as well as longer regulatory exclusivity periods. The FDA has granted Orphan Drug designation to TRYNGOLZA for the treatment of patients with FCS, to WAINUA for the treatment of patients with ATTR, to ulefnersen for the treatment of patients with FUS-ALS, to obudanersen for the treatment of patients with Angelman syndrome, to salanersen for the treatment of patients with SMA, to sapablursen for the treatment of patients with PV, to ulefnersen for the treatment of patients with FUS-ALS, and to some of our earlier stage medicines. The FDA and EMA have granted Orphan Drug designation to DAWNZERA for the treatment of patients with HAE, to WAYLIVRA for the treatment of patients with FCS, to tominersen for the treatment of patients with HD, and to some of our earlier stage medicines. In addition, the EMA has granted Orphan Drug designation to WAYLIVRA for the treatment of patients with FPL. Even if approval is obtained for a medicine that has been designated as an Orphan Drug, we may lose Orphan Drug exclusivity if the FDA or EMA determines that the request for designation was materially defective or if we cannot assure sufficient quantity of the applicable medicine to meet the needs of patients with the rare disease or condition, or if a competitor is able to gain approval for the same or a substantially similar medicine in a safer or more effective form or that makes a major contribution to patient care. If we lose Orphan Drug exclusivity on any of our medicines, we may face increased competition and lose market share for such medicine.
We may also seek rare pediatric disease designation for some of our medicines. The FDA defines “rare pediatric disease” as a serious or life-threatening disease in which the serious or life-threatening manifestations primarily affect individuals aged from birth to 18 years or is a rare disease or condition within the meaning of the Orphan Drug Act. Designation of a medicine as a medicine for a rare pediatric disease does not guarantee that a marketing application for such medicine will meet the eligibility criteria for a rare pediatric disease priority review voucher, or PRV, at the time the application is approved. Under the FDCA,Federal Food, Drug and Cosmetic Act, we will need to request a rare pediatric disease PRV in our original marketing application for any potential medicine for which we have received rare pediatric disease designation. The FDA may determine that a marketing application for any such medicine, if approved, does not meet the eligibility criteria for a PRV. Under the current statutory sunset provisions, the PRV program will sunset after September 30, 2029, and the FDA may not award PRVs under this program after such date.
Many of our medicines are undergoing clinical studies or are in the early stages of research and development. Most of our programs will require significant additional research, development, manufacturing, preclinical and clinical testing, marketing authorizations, preclinical activities and commitment of significant additional resources prior to their successful commercialization. In addition, as we commercialize more medicines on our own, we will need to invest significant financial resources to continue developing the infrastructure required to successfully commercialize our medicines, including building and maintaining new support functions, scaling up existing internal support functions and expanding our manufacturing capabilities. All of these activities will require significant cash. As of MarchJune 31,30, 2026, we had cash, cash equivalents and short-term investments equal to $1.9$2.1 billion. If we or our partners do not meet our goals to successfully commercialize our medicines, including our commercial medicines, or to license certain medicines and proprietary technologies, we will need additional funding in the future. Our future capital requirements will depend on many factors such as:
Because drug discovery and development require substantial lead-time and money prior to commercialization, our expenses have generally exceeded our revenue since we were founded in January 1989. As of MarchJune 31,30, 2026, we had an accumulated deficit of approximately $2.7$2.8 billion and stockholders’ equity of approximately $0.5$0.4 billion. Most of our income has historically come from collaborative arrangements, including commercial revenue from royalties and R&D revenue, with additional income from research grants and the sale or licensing of our patents, as well as interest income. We will now and continuing into the foreseeable future need to investcontinue investing significant financial resources to commercialize medicines on our ownown, and we expect that our income in the future willrevenue to be driven primarily by commercial sales. If we do not earn substantial revenue from commercial sales, we may incur additional operating losses in the future, which could restrict our ability to successfully develop additional medicines or sustain future profitability.
If we cannot protect our patent rights or our other proprietary rights, others may compete more effectively against us.*
Our success depends to a significant degree upon whether we can continue to develop, secure and maintain intellectual property rights to proprietary products and services. However, we may not receive issued patents on any of our pending patent applications in the U.S. or in other countries and we may not be able to obtain, maintain or enforce our patents and other intellectual property rights, any of which could impact our ability to compete effectively. In addition, the scope of any of our issued patents may not be sufficiently broad to provide us with a competitive advantage. Furthermore, other parties may successfully challenge, invalidate or circumvent our issued patents or patents licensed to us so that our patent rights do not create an effective competitive barrier or revenue source. For example, on June 22, 2026, Biogen, Cold Spring Harbor Laboratory, and Ionis filed a patent infringement lawsuit in the District Court of Delaware following notice that Somerset Therapeutics, LLC had filed an Abbreviated New Drug Application, or ANDA, seeking approval to commercialize a generic version of SPINRAZA and alleging that certain patents covering SPINRAZA and its use are invalid or would not be infringed. If Somerset Therapeutics obtains a favorable ruling in such lawsuit, our revenues from SPINRAZA could be materially adversely affected.
Intellectual property litigation could be expensive and prevent us from pursuing our programs.*
From time to time, we have to defend our intellectual property rights. If we are involved in an intellectual property dispute, we may need to litigate to defend our rights or assert them against others. Disputes can involve arbitration, litigation or proceedings declared by the U.S. PTO or the International Trade Commission or foreign patent authorities. Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses and could distract our technical and management personnel from their normal responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock. For example, in September 2025, we filed a claim against Arrowhead Pharmaceuticals, Inc., or Arrowhead, for patent infringement over Arrowhead'sArrowhead’s commercialization of plozasiran, and Arrowhead filed a counterclaim against us seeking to invalidate that same patent. We are also a party to ongoing litigation involving a third party seeking regulatory approval to commercialize a generic version of SPINRAZA in the U.S. as described above. For details regarding thisthese proceeding,proceedings, refer to Part II, Item 1, Legal Proceedings.
In recent years, extreme weather events and changing weather patterns have become more common. As a result, we are potentially exposed to varying natural disaster or extreme weather risks such as fires, hurricanes, tornadoes, droughts, floods, or other events that may result from the impact of climate change on the environment, any of which could impact our business and manufacturing operations. The potential impacts of climate change may also include increased operating costs associated with additional regulatory requirements and investments in reducing energy, water use and greenhouse gas emissions. In addition, we currently manufacture most of our research and clinical supplies in a manufacturing facility located in Carlsbad, California, and various regions within California have experienced numerous catastrophic wildfires. We manufacture the finished drug product for TRYNGOLZA, DAWNZERA, WAYLIVRADAWNZERA and eplontersen for ongoing clinical trialsWAYLIVRA at third-party contract manufacturers. Biogen manufactures the finished drug product for SPINRAZA and QALSODY and AstraZeneca is responsible for WAINUA’s commercial drug supply. The facilities and the equipment we, our partners and our contract manufacturers use to research, develop and manufacture our medicines would be costly to replace and could require substantial lead time to repair or replace.
There are also significant risks involved in developing and deploying AI, and there can be no assurance that the usage of AI will enhance our medicines or the discovery or development of our product candidates or be beneficial to our business, including our efficiency or profitability. It is also uncertain how various laws will apply to content generated by AI. Various governmentalgovernment authorities have proposed or enacted laws governing the development and use of AI technologies. We are subject to the risks of new or enhanced governmental or regulatory scrutiny, litigation, or other legal liability, ethical concerns, negative consumer perceptions as to automation and AI, or other complications that could adversely affect our business, reputation, or financial results.
The market price of our common stock, like that of the securities of many other biopharmaceutical companies, has been and is likely to continue to be highly volatile. These fluctuations in our common stock price may significantly affect the trading price of our securities. During the 12 months preceding MarchJune 31,30, 2026, the closing market price of our common stock ranged from $86.50 to $25.51$39.94 per share. Many factors can affect the market price of our securities, including, for example, fluctuations in our operating results, financing transactions, announcements ofrelated to collaborations, clinical study results, technological innovations or new products being developed by us or our competitors, the commercial success of our approved medicines, governmental regulation, marketing authorizations, changes in payers’ reimbursement policies, developments in patent or other proprietary rights and public concern regarding the safety of our medicines.
The provisions of our convertible senior notes could make it more difficult or more expensive for a third party to acquire us. Upon the occurrence of certain transactions constituting a fundamental change, holders of the notes will have the right, at their option, to require us to repurchase all of their notes or a portion of their notes, which may discourage certain types of transactions in which our stockholders might otherwise receive a premium for their shares over the then-current market prices. As of MarchJune 31,30, 2026, we had threetwo outstanding convertible senior notes, our 0% Notes due 2030, which mature in December 2030, and our 1.75% Notes due 2028, which mature in June 2028, and our 0% Notes due 2026, which matured in April 2026.2028.
Additionally, in connection with the issuance of our 0% Notes due 2026, we entered into certain call spread transactions consisting of convertible note hedges, which were exercised in April 2026, and warrant transactions, which becomebecame exercisable commencing on July 1, 2026. The terms of the warrant transactions are subject to adjustment in connection with certain events, including upon the announcement of certain mergers or other business transactions involving us. In addition, the warrants may be required to be settled or unwound in connection with a merger or other business transaction involving us, which could make an acquisition of our company significantly more expensive to the purchaser.
Future sales of substantial amounts of our common stock in the public market, or the perception that such sales could occur, could adversely affect trading prices of our securities. For example, we may issue approximately 18.6 million shares of our common stock upon conversion of our 0% Notes due 2030 and 1.75% Notes due 2028. In connection with the issuance of the 0% Notes due 2026, we entered into certain call spread transactions consisting of convertible note hedges and warrant transactions covering 10.9 million shares. The convertible note hedges offset the dilution to holders of common stock that arose from the conversion of those notes. However, the anti-dilutive effect of the convertible note hedges is offset by the related warrant transactions, which becomebecame exercisable commencing on July 1, 2026. The addition of any of these shares into the public market may have an adverse effect on the price of our securities.
In addition, in connection with the warrant transactions, the counterparties may modify their hedge positions from time to timetime, including during the exercise period, by purchasing and selling shares of our common stock, other of our securities, or other instruments, including over-the-counter derivative instruments, that they may wish to use in connection with such hedging, which may have an adverse impact on the trading price of our common stock.
Our operations are subject to extensive legal and regulatory requirements affecting the health care industry, including federal, state, and foreign fraud and abuse (including anti-kickback laws and false claims laws), transparency laws, such as the federal Sunshine Act, and health information privacy and security laws, which are subject to change at any time. It is possible that governmentalgovernment authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. Penalties for violations of applicable healthcare laws and regulations may include significant civil, criminal and administrative penalties, damages, disgorgement, fines, imprisonment, exclusion of products from government funded healthcare programs, such as Medicare and Medicaid, and additional reporting requirements and oversight if we enter into a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws. In addition, violations may also result in reputational harm, diminished profits and future earnings.
Management's Discussion & Analysis (MD&A)
New heading “Net Income (Loss) and Net Income (Loss) per Share”
Removed heading “Net Loss and Net Loss per Share”
Largest changes
“WAINUA (WAINZUA in Europe) is a once monthly, self-administered subcutaneous LICA medicine that is approved in numerous countries, including the U.S., EU, UK, Canada and China, for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis, or ATTRv-PN, a debilitating, progressive, and fatal disease. In January 2024, we and AstraZeneca launched WAINUA in the U.S. for the treatment of adults with ATTRv-PN. …”see in full comparison
“Olezarsen is our investigational medicine currently under regulatory review for sHTG, a second potential indication with a broad patient population. The FDA has granted Priority Review of olezarsen, with a Prescription Drug User Fee Act, or PDUFA, action date of June 30, 2026. In March 2026, the European Medicines Agency, or EMA, accepted an indication extension application for olezarsen for the treatment of adult patients with sHTG. The regulatory submissions were based on positive results from the pivotal Phase 3 CORE and CORE2 studies in sHTG, as well as data from the Phase 3 Essence study. …”see in full comparison
“WAINUA (WAINZUA in Europe) is a once monthly, self-administered subcutaneous LICA medicine that is approved in numerous countries, including the U.S., EU, UK, Canada and China, for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis, or ATTRv-PN, a debilitating, progressive, and fatal disease. In January 2024, we and AstraZeneca launched WAINUA in the U.S. for the treatment of adults with ATTRv-PN. …”see in full comparison
“The remainder of our revenue came from programs under our research and development, or R&D, collaborations, reflecting the value that our pipeline and technology continues to generate. Our R&D revenue during the three months ended March 31, 2026 included a $50 million milestone payment we earned when Roche initiated a Phase 1 trial for an investigational medicine for HD and $30 million in milestone payments we earned from GSK when regulatory filings for bepirovirsen were accepted for review in Japan and the European Union, or EU.”see in full comparison
Full comparison: every changed paragraph (42)
With twomultiple independent commercial launches now underway, we have transitioned into a fully integrated commercial-stage biotechnology company. We currently have seven marketed medicines to treat serious diseases: TRYNGOLZA (olezarsen), DAWNZERA (donidalorsen), WAINUA (eplontersen), SPINRAZA (nusinersen), QALSODY (tofersen), TEGSEDI (inotersen) and WAYLIVRA (volanesorsen). InFollowing addition,approval by the U.S. Food and Drug Administration, or FDA, in June 2026, we are positioned to independently launchlaunched two medicines, olezarsenTRYNGOLZA for the treatment of severe hypertriglyceridemia, or sHTG,sHTG. andIn addition, we are on track to independently launch zilganersen for Alexander disease, or AxD, in 2026, assuming regulatory approval. We also have a rich innovative pipeline across our focus areas of neurology, cardiometabolic diseases and select areas of high patient needs. We currently have threetwo wholly owned medicines and sixeight partnered medicines in Phase 3 development, including obudanersen for Angelman syndrome, or AS, which wehas advancedcompleted intoenrollment aof the Phase 3 study in the second quarter of 2025.study. We also have additional medicines in early and mid-stage development.
Our multiple sources of revenue and strongsolid financial foundation enable our continued investments to support ongoing and planned launches and to advance our wholly owned medicines in development. Our key recent achievements, combined with our independent and partnered product launches anticipated by the end of 2027, position us well to help millions of patients with serious diseases and deliver increasing product and royalty revenue.
TRYNGOLZA is a once monthly, self-administered LIgand-Conjugated Antisense, or LICA, medicine approved in the United States, or U.S., as an adjunct to diet to reduce triglycerides and the risk of acute pancreatitis in adults with sHTG and as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome, or FCS. TRYNGOLZA is also approved in the European Union, or EU, Canada and the United Kingdom, or UK, as an adjunct to diet in adult patients for the treatment of genetically confirmed FCS. TRYNGOLZA is the first and only treatment approved by the U.S. Food and Drug Administration, or FDA,FDA that significantly and substantially reduces triglyceride levels in adults with FCSsHTG and provides a clinically meaningful reduction in acute pancreatitis, or AP, events. TRYNGOLZA is the first medicine we are commercializing independently in the U.S. Sobi has exclusive rights to commercialize TRYNGOLZA in countries outside of the U.S., Canada and China.
DAWNZERA is an RNA-targeted medicine approved in the U.S. for prophylaxis to prevent attacks of hereditary angioedema, or HAE, in adult and pediatric patients 12 years of age and older. DAWNZERA is also approved in the EU and UK for the routine prevention of recurrent attacks of HAE in the same age group. DAWNZERA 80mg is self-administered via subcutaneous autoinjector once every four or eight weeks. DAWNZERA is the first and only FDA-approved RNA-targeted prophylactic therapy for HAE. DAWNZERA has the potential to offer durable efficacy, a favorable safety and tolerability profile, and the longest available dosing interval. DAWNZERA is the second medicine we are commercializing independently in the U.S. We licensed commercialization rights for DAWNZERA in Europe and the Asia-Pacific region to Otsuka Pharmaceutical Co., Ltd., or Otsuka.
WAINUA (WAINZUA in Europe) is a once monthly, self-administered subcutaneous LICA medicine that is approved in numerous countries, including the U.S., EU, UK, Canada and China, for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis, or ATTRv-PN, a debilitating, progressive, and fatal disease. In January 2024, we and AstraZeneca launched WAINUA in the U.S. for the treatment of adults with ATTRv-PN. The launch of WAINUA is underway in numerous countries, including the countries in the EU, following the approval by the European Commission, or EC, in March 2025. We and AstraZeneca are co-commercializing WAINUA in the U.S. AstraZeneca has exclusive rights to commercialize WAINUA outside of the U.S. From inception through March 31, 2026, we have earned more than $640 million in revenues from our WAINUA collaboration, including approximately $80 million in royalties on sales of WAINUA.
SPINRAZA is an antisense medicine for the treatment of patients with spinal muscular atrophy, or SMA, a progressive, debilitating and often fatal genetic disease. Higher dose SPINRAZA was approved and launched in the U.S. and EU for the treatment of SMA. Higher dose SPINRAZA is also approved in Japan. Our partner, Biogen, is responsible for commercializing SPINRAZA worldwide. From inception through March 31, 2026, we have earned more than $2.5 billion in revenues from our SPINRAZA collaboration, including more than $2.1 billion in royalties on sales of SPINRAZA.
WAINUA (WAINZUA in Europe) is a once monthly, self-administered subcutaneous LICA medicine that is approved in numerous countries, including the U.S., EU, UK, Canada and China, for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis, or ATTRv-PN, a debilitating, progressive, and fatal disease. In January 2024, we and AstraZeneca launched WAINUA in the U.S. for the treatment of adults with ATTRv-PN. The launch of WAINUA is underway in numerous countries, including the countries in the EU, following the approval by the European Commission, or EC, in March 2025. AstraZeneca is our commercialization partner for WAINUA.
Olezarsen is our investigational medicine currently under regulatory review for sHTG, a second potential indication with a broad patient population. The FDA has granted Priority Review of olezarsen, with a Prescription Drug User Fee Act, or PDUFA, action date of June 30, 2026. In March 2026, the European Medicines Agency, or EMA, accepted an indication extension application for olezarsen for the treatment of adult patients with sHTG. The regulatory submissions were based on positive results from the pivotal Phase 3 CORE and CORE2 studies in sHTG, as well as data from the Phase 3 Essence study. In 2025, the positive results from these studies were presented and published in The New England Journal of Medicine. Additionally, the FDA granted Breakthrough Therapy designation to olezarsen as an adjunct to diet to reduce triglyceride levels in adults with sHTG. We licensed commercialization rights for olezarsen in most countries outside of the U.S., Canada and China to Sobi.
Zilganersen is our investigational medicine for AxD. The FDA has granted Priority Review of zilganersen, with a PDUFAPrescription Drug User Fee Act, or PDUFA, action date of September 22, 2026. The regulatory submission was based on the positive results from the Phase 3 portion of the pivotal study in children and adults with AxD. These results were presented at the Child Neurology Society Annual Meeting in October 2025 and the American Academy of Neurology Annual Meeting in April 2026. We established an expanded access program in the U.S. for eligible patients aged two and older living with AxD. Zilganersen has received Fast Track and Rare Pediatric Disease designations from the FDA and received Orphan Drug designation from both the FDA and the EMA. We licensed commercialization rights for zilganersen in countries outside of the U.S. to Recordati.
Obudanersen is our medicine in development for AS. In JuneJuly 2025,2026, we initiatedcompleted enrollment of the Phase 3 study, REVEAL, which we designed to evaluate the efficacy and safety of obudanersen. In addition, we are continuing to conduct the open label Phase 1/2 study, HALOS, of obudanersen in patients with AS designed to assess the safety, tolerability and activity of multiple ascending doses of obudanersen administered intrathecally. In 2025, we presented positive 12- and 18-month long-term extension data from the HALOS study which supports continued development. The FDA and EMA granted Orphan Drug designation to obudanersen. Additionally, the FDA granted Breakthrough Therapy, Fast Track and Rare Pediatric designations to obudanersen.
Bepirovirsen is our medicine in development for chronic hepatitis B, or CHB. GSK is developing bepirovirsen. In January 2026, we and GSK announced positive topline results from the B-Well 1 and B-Well 2 pivotal Phase 3 studies of bepirovirsen in patients with CHB. Bepirovirsen has been accepted for regulatory review in three markets – the EU, China and Japan. Additional submissions are planned. The FDA has granted Priority Review of bepirovirsen, with a PDUFA action date of October 26, 2026. In May 2026, GSK presented positive Phase 3 data for bepirovirsen at the 2026 European Association for the Study of the Liver, or EASL, Congress. Bepirovirsen is also under regulatory review in the EU, China and Japan, with additional submissions planned. The FDA, Center for Drug Evaluation, or CDE, of National Medical Products Administration, or NMPA, of China and Japanese Ministry of Health, Labour and Welfare, or MHLW, granted bepirovirsen Fast Track designation, Breakthrough Therapy designation and SENKU (formerly known as SAKIGAKE) designation, respectively, for the treatment of patients with CHB.
Eplontersen is our medicine in development to treat patients with transthyretin amyloidosis cardiomyopathy, or ATTR-CM. In July 2026, we and AstraZeneca announced that the CARDIO-TTRansform trial for eplontersen in patients with ATTR-CM missed the primary efficacy endpoint of the composite outcome of cardiovascular, or CV, mortality and recurrent CV clinical events up to Week 140 compared with placebo. In this contemporary patient population treated with standard of care, including a majority on a stabilizer, adding eplontersen did not provide a statistically significant benefit. We and AstraZeneca are continuing to analyze the full data set, and results will be shared with the scientific community at the European Society of Cardiology, or ESC, Congress in August 2026.
Eplontersen is our medicine in development to treat patients with transthyretin amyloidosis cardiomyopathy, or ATTR-CM. We completed enrollment in the Phase 3 CARDIO-TTRansform study in July 2023. The FDA granted Fast Track designation to eplontersen for the treatment of patients with ATTR-CM. Additionally, the FDA and EMA granted Orphan Drug designation to eplontersen for the treatment of ATTR.
Salanersen is our medicine in development for SMA. In the second quarter of 2026, Biogen advanced salanersen into Phase 3 development in patients with SMA and the FDA granted Breakthrough Therapy designation to salanersen based on positive interim Phase 1 results. Salanersen has also received Orphan Drug designation for the treatment of SMA.
Sapablursen is our medicine in development for polycythemia vera, or PV. In the second quarter of 2026, Ono advanced sapablursen into Phase 3 development in patients with PV. Sapablursen has received FDA Fast Track, Orphan Drug and Breakthrough Therapy designations for the treatment of PV.
Total revenue for the three and six months ended MarchJune 31,30, 2026 was $246.1$267.9 million and $514.0 million, respectively, compared to $131.6$452.0 million and $583.7 million for the same periodperiods in 20252025, respectively, and was comprised of the following (in millions):
Commercial revenue for the three months and six months ended MarchJune 31,30, 2026 increased 42%15% and 27%, respectively, compared to the same periodperiods in 2025. This increase was primarily driven by TRYNGOLZA and DAWNZERA product sales.
Research and development, or R&D, revenue for the three and six months ended June 30, 2026 decreased compared to the same periods in 2025 due to the $280 million upfront payment we earned for the global license of sapablursen to Ono Pharmaceutical Co., Ltd. in the second quarter of 2025, which was partially offset by partner payments we achieved in the first half of 2026. We recognized approximately $100 million and $180 million of R&D revenue in the three and six months ended June 30, 2026, respectively, from license fees and milestone payments from multiple partnerships.
The remainder of our revenue came from programs under our research and development, or R&D, collaborations, reflecting the value that our pipeline and technology continues to generate. Our R&D revenue during the three months ended March 31, 2026 included a $50 million milestone payment we earned when Roche initiated a Phase 1 trial for an investigational medicine for HD and $30 million in milestone payments we earned from GSK when regulatory filings for bepirovirsen were accepted for review in Japan and the European Union, or EU.
Our financial results for the three and six months ended MarchJune 31,30, 2026 and 2025 reflected the cost-sharing provisions related to our collaboration with AstraZeneca to develop and commercialize WAINUA for the treatment of ATTR. From inception through December 31, 2025, AstraZeneca was responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. AfterDuring Decemberthe 31,six 2025,months ended June 30, 2026, AstraZeneca iswas responsible for 75 percent of costs for development activities intended solely to support U.S. regulatory approvals and 87.5 percent of costs for development activities intended to support global regulatory approvals. Because we are leading and conducting the Phase 3 development program, we are recognizing as R&D revenue the percentage of cost-share funding AstraZeneca is responsible for, net of our share of AstraZeneca's development expenses, in the same period we incur the related development expenses.
As AstraZeneca iswas responsible for the majority of the medical affairs and commercial costs in the U.S. and all costs associated with bringing WAINUA to market outside the U.S.,U.S. during the three and six months ended June 30, 2026 and 2025, we are recognizingrecognized cost-share funding we receivereceived from AstraZeneca related to these activities as a reduction of our medical affairs and commercialization expenses, which we classify as R&D and selling, general and administrative, or SG&A expenses, respectively. We expect our medical affairs and commercialization expenses to increase as WAINUA advances toward the market for ATTR-CM under our collaboration with AstraZeneca.
Operating expenses, excluding non-cash compensation expense related to equity awards, for the three months and six months ended MarchJune 31,30, 2026 increased compared to the same periodperiods in 2025. SG&A expenses increased as anticipated year over year primarily due to investments related to the commercialization efforts for TRYNGOLZA and DAWNZERA as well asand launch preparation activitiespreparations for olezarsen in sHTG and zilganersen in AxD. We expect our operating expenses, excluding non-cash compensation expense related to equity awards, to continue to increase during the remainder of 2026 as we advance our commercialization activities.
Non-cash compensation expense related to equity awards for the three and six months ended MarchJune 31,30, 2026 increased compared to the same periodperiods in 2025 due to a higher stock price on the grant date of annual equity awards in 2026 compared to 2025 and increased headcount. We employed 1,480 people as of June 30, 2026 compared to 1,166 people as of June 30, 2025. We believe non-cash compensation expense related to equity awards is not indicative of our operating results or cash flows from our operations.
Drug discovery expenses, excluding non-cash compensation expense related to equity awards, increasedwere essentially flat in the three and six months ended MarchJune 31,30, 2026 compared to the same periodperiods in 2025 as we continued to advance our technologies discussed above.2025.
Our development expenses, excluding non-cash compensation expense related to equity awards, decreased for the three and six months ended MarchJune 31,30, 2026 compared to the same periodperiods in 2025 as several late-stage studies ended. We expect our development expenses will continue to stabilize as several late-stage studies end and we reallocate resources toward earlier stage programs.
Medical affairs expenses, excluding non-cash compensation expense related to equity awards, increased in the three and six months ended MarchJune 31,30, 2026 compared to the same periodperiods in 2025 as we continued advancing our late-stage pipeline.
ManufacturingThe period over period fluctuations in manufacturing and development chemistry expenses, excluding non-cash compensation expense related to equity awards, increased in the three months ended March 31, 2026 compared to the same period in 2025were due to the timing of manufacturing performed by our contract manufacturing organizations for drug product and active pharmaceutical ingredients related to several late-stage programs.
R&D support expenses, excluding non-cash compensation expense related to equity awards, increased in the three and six months ended MarchJune 31,30, 2026 compared to the same periodperiods in 2025 primarily due to increased occupancy and personnel costs.
SG&A expenses, excluding non-cash compensation expense related to equity awards, increased in the three and six months ended MarchJune 31,30, 2026 compared to the same periodperiods in 2025 primarily due to investments related to commercialization efforts for TRYNGOLZA and DAWNZERA as well as launch preparation activities for olezarsen in sHTG and zilganersen in AxD. We expect SG&A expenses to increase as we continue to invest in our independent commercial launches.
Investment income for the three and six months ended June 30, 2026 decreased compared to the same periods in 2025 due to a decrease in our cash balance during the three months ended June 30, 2026 compared to the same period in 2025. Our cash balance decreased due to the repayment upon maturity of our 0% Notes due 2026 in April 2026.
We recorded $17.3$17.5 million and $34.8 million of interest expense related to the sale of future royalties in the three and six months ended MarchJune 31,30, 20262026, respectively, compared to $18.8$18.6 million and $37.5 million in the same periodperiods in 2025.2025, respectively. These amounts are related to the Royalty Pharma Investments, or Royalty Pharma, transaction, in which we sold a minority interest in our future SPINRAZA and pelacarsen royalties to Royalty Pharma for a $500 million upfront payment and $625 million of potential future payments. Refer to Part I, Item 1, Note 10, Liability Related to Sale of Future Royalties, in the Notes to Condensed Consolidated Financial Statements for further details.
We recorded a net gain on investments of $22.6 million for the three months ended March 31, 2026 compared to a net loss on investments of $2.2 million for the same period in 2025 primarily due to changes in the fair value of investments in publicly traded biotechnology companies. Refer to Part I, Item 1, Note 7, Investments, in the Notes to Condensed Consolidated Financial Statements for further details.
Net Loss and Net Loss per Share
The following table sets forth information on netgain (loss) andon investments, net loss per share (in millions, except per share amountsmillions):
The period over period fluctuations in gain (loss) on investments were primarily due to changes in the fair value of investments in publicly traded biotechnology companies.
Net Income (Loss) and Net Income (Loss) per Share
The following table sets forth information on net income (loss) and net income (loss) per share (in millions, except per share amounts):
The period-over-period fluctuations in our net income (loss) were driven by factors discussed in the sections above.
We have financed our operations primarily from research and development collaborative agreements. We also financed our operations from commercial revenue from SPINRAZA, WAINUA and QALSODY royalties and TEGSEDI and WAYLIVRA commercial revenue. In addition, we began earning commercial revenue from TRYNGOLZA product sales in late December 2024 and DAWNZERA product sales in late August 2025. From our inception through MarchJune 31,30, 2026, we have earned approximately $9.1$9.4 billion in revenue. We have also financed our operations through the sale of our equity securities, the issuance of long-term debt and the sale of future royalties. From the time we were founded through MarchJune 31,30, 2026, we have raised net proceeds of approximately $2.9 billion from the sale of our equity securities. Additionally, from our inception through MarchJune 31,30, 2026, we have borrowed approximately $3.5 billion under long-term debt arrangements and received proceeds of $0.5 billion from the sale of future royalties to finance a portion of our operations.
From December 31, 2025 to MarchJune 31,30, 2026, our working capital and our long-term obligations did not change significantly. In April 2026, we paid the remaining principal balance of our 0% Notes due 2026 upon maturity. Refer to Part I, Item 1, Note 11, Convertible Debt, in the Notes to Condensed Consolidated Financial Statements for further details.
The following table summarizes our contractual obligations, excluding our liability related to the sale of future royalties, as of MarchJune 31,30, 2026. The table provides a breakdown of when obligations become due.
In addition to contractual obligations, we had outstanding purchase orders as of MarchJune 31,30, 2026 for the purchase of services, capital equipment and materials as part of our normal course of business.
IONS insider buying and selling (Form 4)
Since 2026-04-11, insiders reported open-market purchases in 1 Form 4 filing (1 insider, 2 trade dates, 20,000 shares, about $1.1M) and open-market sales in 20 filings (14 insiders, 15 trade dates, 360,372 shares, about $27.9M; 17 of these filings say the sales were made under a Rule 10b5-1 trading plan). Net open-market shares: -340,372 (purchases minus sales); net value about -$26.9M.Totals add up every open-market (code P and S) line in those filings, using the prices reported in the filings. Awards, option exercises, tax withholding and gifts are listed below but not counted.
| Trade date | Insider | Transaction | Shares | Price | Value |
|---|---|---|---|---|---|
| 2026-08-31 | Bennett C Frank |
Other | 110 | $51.31 | $5.6K |
| 2026-08-31 | O'neil Patrick R. |
Other | 63 | $51.31 | $3.2K |
| 2026-08-31 | Monia Brett P |
Other | 98 | $51.31 | $5.0K |
| 2026-08-31 | Birchler Brian |
Other | 58 | $51.31 | $3.0K |
| 2026-07-31 | Hayden Michael R |
Open-market purchase | 5,000 | $51.60 | $258.0K |
| 2026-07-30 | Hayden Michael R |
Open-market purchase | 15,000 | $53.38 | $800.7K |
| 2026-07-15 | Herman Joan E |
Option exercise | 5,220 | — | — |
| 2026-07-15 | Berthelsen Spencer R |
Option exercise | 5,220 | — | — |
| 2026-07-07 | Bennett C Frank |
Open-market sale |
15,000 | $85.46 | $1.3M |
| 2026-07-07 | Bennett C Frank |
Open-market sale |
5,536 | $83.58 | $462.7K |
| 2026-07-07 | Bennett C Frank |
Other |
15,000 | — | — |
| 2026-07-07 | Diaz Allene M. |
Open-market sale |
10,111 | $85.42 | $863.7K |
| 2026-07-07 | Diaz Allene M. |
Option exercise |
10,111 | $47.11 | $476.3K |
| 2026-07-07 | Kordasiewicz Holly B. |
Open-market sale |
362 | $84.30 | $30.5K |
| 2026-07-01 | Klein Joseph Iii |
Option exercise |
11,518 | $39.94 | $460.0K |
| 2026-07-01 | Klein Joseph Iii |
Open-market sale |
99 | $79.45 | $7.9K |
| 2026-07-01 | Klein Joseph Iii |
Open-market sale |
11,419 | $79.04 | $902.6K |
| 2026-06-26 | Baroldi Joseph |
Option exercise |
3,866 | $56.78 | $219.5K |
| 2026-06-26 | Baroldi Joseph |
Option exercise |
1,769 | $32.60 | $57.7K |
| 2026-06-26 | Baroldi Joseph |
Open-market sale |
5,635 | $80.16 | $451.7K |
| 2026-06-26 | O'neil Patrick R. |
Open-market sale |
3,069 | $80.00 | $245.5K |
| 2026-06-26 | Schneider Eugene |
Option exercise |
26,000 | $60.89 | $1.6M |
| 2026-06-26 | Schneider Eugene |
Open-market sale |
26,000 | $81.05 | $2.1M |
| 2026-06-26 | Monia Brett P |
Option exercise |
50,000 | $56.78 | $2.8M |
| 2026-06-26 | Monia Brett P |
Open-market sale |
50,000 | $80.59 | $4.0M |
| 2026-06-25 | Monia Brett P |
Option exercise |
21,072 | $32.60 | $686.9K |
| 2026-06-25 | Monia Brett P |
Open-market sale |
21,072 | $78.49 | $1.7M |
| 2026-06-25 | Swayze Eric |
Open-market sale |
10,602 | $79.18 | $839.5K |
| 2026-06-24 | Monia Brett P |
Open-market sale |
14,565 | $78.41 | $1.1M |
| 2026-06-24 | Monia Brett P |
Option exercise |
14,565 | $32.60 | $474.8K |
| 2026-06-15 | Berthelsen Spencer R |
Option exercise |
8,000 | $24.42 | $195.4K |
| 2026-06-15 | Berthelsen Spencer R |
Open-market sale |
8,000 | $73.49 | $587.9K |
| 2026-06-12 | Kordasiewicz Holly B. |
Option exercise |
19,895 | $56.78 | $1.1M |
| 2026-06-12 | Kordasiewicz Holly B. |
Open-market sale |
19,842 | $74.05 | $1.5M |
| 2026-06-12 | Kordasiewicz Holly B. |
Open-market sale |
41,004 | $73.09 | $3.0M |
| 2026-06-12 | Kordasiewicz Holly B. |
Option exercise |
7,951 | $60.89 | $484.1K |
| 2026-06-12 | Kordasiewicz Holly B. |
Option exercise |
21,000 | $60.89 | $1.3M |
| 2026-06-12 | Kordasiewicz Holly B. |
Option exercise |
12,000 | $32.60 | $391.2K |
| 2026-06-01 | Berthelsen Spencer R |
Option exercise |
8,000 | $24.42 | $195.4K |
| 2026-06-01 | Berthelsen Spencer R |
Open-market sale |
8,000 | $75.67 | $605.4K |
| 2026-05-14 | Monia Brett P |
Open-market sale |
3,220 | $78.68 | $253.3K |
| 2026-05-14 | Monia Brett P |
Option exercise |
3,220 | $32.60 | $105.0K |
| 2026-05-13 | Monia Brett P |
Option exercise |
1,316 | $32.60 | $42.9K |
| 2026-05-13 | Monia Brett P |
Open-market sale |
1,316 | $78.01 | $102.7K |
| 2026-05-04 | Loscalzo Joseph |
Option exercise |
10,968 | $38.06 | $417.4K |
| 2026-05-04 | Loscalzo Joseph |
Option exercise |
12,000 | $40.05 | $480.6K |
| 2026-05-04 | Loscalzo Joseph |
Option exercise |
10,321 | $41.08 | $424.0K |
| 2026-05-04 | Loscalzo Joseph |
Option exercise |
16,000 | $42.88 | $686.1K |
| 2026-05-04 | Loscalzo Joseph |
Option exercise |
12,000 | $60.20 | $722.4K |
| 2026-05-04 | Loscalzo Joseph |
Open-market sale |
17,781 | $75.58 | $1.3M |
| 2026-05-04 | Loscalzo Joseph |
Option exercise |
16,000 | $64.80 | $1.0M |
| 2026-05-04 | Loscalzo Joseph |
Open-market sale |
59,508 | $74.90 | $4.5M |
| 2026-05-01 | Klein Joseph Iii |
Open-market sale |
8,680 | $73.35 | $636.7K |
| 2026-05-01 | Klein Joseph Iii |
Option exercise |
10,111 | $47.11 | $476.3K |
| 2026-05-01 | Klein Joseph Iii |
Open-market sale |
1,431 | $74.45 | $106.5K |
| 2026-04-28 | Baroldi Joseph |
Open-market sale |
1,626 | $71.79 | $116.7K |
| 2026-04-16 | Jenne Kyle |
Open-market sale | 4,902 | $75.17 | $368.5K |
| 2026-04-16 | Birchler Brian |
Open-market sale | 973 | $75.04 | $73.0K |
| 2026-04-16 | Baroldi Joseph |
Open-market sale | 5,619 | $74.56 | $419.0K |
| 2026-04-15 | Parshall B Lynne |
Open-market sale |
534 | $76.97 | $41.1K |
Well-known investors holding IONS (13F)
| Investor | Quarter | Shares | Reported value | % of their 13F | Change vs prior quarter |
|---|---|---|---|---|---|
| Two Sigma Investments | 2026-06-30 | 6,252,342 | $495.7M | 0.37% | Added 7% |
| Tweedy, Browne | 2026-06-30 | 2,280,311 | $180.8M | 13.7% | No change |
| Citadel Advisors (Ken Griffin) | 2026-06-30 | 0 | $134.7M | 0.08% | No change |
| Renaissance Technologies | 2026-06-30 | 559,414 | $44.4M | 0.06% | Added 83% |
| ARK Investment Management (Cathie Wood) | 2026-06-30 | 300,770 | $23.8M | 0.15% | Added 4% |
| D. E. Shaw & Co. | 2026-06-30 | 297,041 | $23.6M | 0.01% | Reduced 31% |
| Millennium Management (Israel Englander) | 2026-06-30 | 288,872 | $22.9M | 0.02% | Reduced 73% |
| Citadel Advisors (Ken Griffin) | 2026-06-30 | 236,284 | $18.7M | 0.01% | Reduced 75% |
| Gotham Asset Management (Joel Greenblatt) | 2026-06-30 | 121,252 | $9.6M | 0.02% | Added 23% |
| AQR Capital Management (Cliff Asness) | 2026-06-30 | 22,059 | $1.7M | 0.0% | Reduced 23% |