Ionis Pharmaceuticals (IONS) risk factors, 2025 10-K

Risks Related to the Commercialization of our Medicines

1. 01If the market does not accept our medicines, including our commercial medicines and our medicines in development, we are not likely to generate substantial revenues or become consistently profitable
2. 02reimbursement policies of government and third-party payers
3. 03If 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, our revenue will be limited
4. 04If we or our partners fail to compete effectively, our medicines, including our commercial medicines and our medicines in development, will not generate significant revenues
5. 05These competitive developments could make our medicines, including our commercial medicines and our medicines in development, obsolete or non-competitive
6. 06GTX-102, alogabat and NNZ-2591 could compete with ION582
7. 07Our medicines could be subject to regulatory limitations following approval
8. 08The 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
9. 09We depend on our collaborations with Biogen for the development and commercialization of SPINRAZA and QALSODY
10. 10successfully commercialize SPINRAZA and QALSODY
11. 11We depend on our collaboration with AstraZeneca for the joint development and commercialization of WAINUA
12. 12If we are not successful in expanding our manufacturing capabilities or cannot manufacture our medicines or contract with a third party to manufacture our medicines at costs that allow us to charge competitive prices to buyers, we cannot market our products profitably

Risks Related to the Development and Regulatory Approval of our Medicines

1. 13If we or our partners fail to obtain regulatory approval for our medicines and additional approvals for our commercial medicines, we or our partners cannot sell them in the applicable markets
2. 14the 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
3. 15If the results of clinical testing indicate that any of our medicines are not suitable for commercial use, we may need to abandon one or more of our drug development programs
4. 16Even 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
5. 17the supply or quality of our medicines or other materials necessary to conduct our clinical studies may be insufficient, inadequate or delayed
6. 18We depend on third parties to conduct clinical studies for our medicines and any failure of those parties to fulfill their obligations could adversely affect our development and commercialization plans
7. 19Since corporate partnering is part of our strategy to fund the advancement and commercialization 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 our drug development programs
8. 20Roche for development and funding of sefaxersen
9. 21Even with funding from corporate partners, if our partners do not effectively perform their obligations under our agreements with them, it would delay or stop the progress of our drug development and commercial programs
10. 22manufacture and commercialize our medicines
11. 23choose to devote fewer resources to our medicines than it does to its own medicines
12. 24We 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

Risks related to our financial condition

1. 25If we fail to obtain timely funding, we may need to curtail or abandon some of our programs
2. 26our manufacturing requirements and capacity to fulfill such requirements
3. 27We have incurred losses, and our business will suffer if we fail to consistently achieve profitability in the future
4. 28We may not be entitled to obtain additional milestone payments under our royalty monetization agreement with Royalty Pharma

Risks related to our intellectual property

1. 29If we cannot protect our patent rights or our other proprietary rights, others may compete more effectively against us
2. 30Intellectual property litigation could be expensive and prevent us from pursuing our programs

Risks related to product liability

1. 31We are exposed to potential product liability claims, and insurance against these claims may not be available to us at a reasonable rate in the future or at all

Risks related to our personnel

1. 32The loss of key personnel, or the inability to attract and retain highly skilled personnel, could make it more difficult to run our business and reduce our likelihood of success

Risks related to health epidemics, climate change and other events

1. 33Our business may be adversely affected by health epidemics, climate change, extreme weather events, fires, earthquakes, war, civil or political unrest, terrorism or other catastrophic events

Risks related to personal information, cybersecurity, social media and artificial intelligence

1. 34We are dependent on data as well as information technology systems and infrastructure, which exposes us to data protection risks
2. 35require us to verify the correctness of database contents and otherwise subject us to litigation or other liabilities
3. 36The increasing use of social media platforms and artificial intelligence based software presents new risks and challenges

Risks related to our securities and the global credit markets

1. 37If we do not progress in our programs as anticipated, the price of our securities could decrease
2. 38If the price of our securities continues to be highly volatile, this could make it harder to liquidate your investment and could increase your risk of suffering a loss
3. 39Negative conditions in the global credit markets and financial services and other industries may adversely affect our business, financial condition or stock price
4. 40changes in diplomatic and trade relationships
5. 41Provisions in our certificate of incorporation, bylaws, convertible notes documents, call spread hedge transaction documents and Delaware law may prevent stockholders from receiving a premium for their shares
6. 42Future sales of our common stock in the public market could adversely affect the trading price of our securities

Risks related to compliance with laws

1. 43Our operations are subject to extensive legal and regulatory requirements affecting the health care industry
2. 44Because we use biological materials, hazardous materials, chemicals and radioactive compounds, if we do not comply with laws regulating the protection of the environment and health and human safety, our business could be adversely affected
3. 45liabilities under federal, state and local laws and regulations governing health and human safety, as well as the use, storage, handling and disposal of these materials and resultant waste products
4. 46Our business is subject to changing regulations for corporate governance and public disclosure that has increased both our costs and the risk of noncompliance

Risks related to taxes

1. 47Our ability to use our net operating loss carryovers and certain other tax attributes may be limited
2. 48We could be subject to additional tax liabilities