PTCT 10-K & 10-Q changes, risk factors and insider trading

In response to changes in the regulatory environment or requests from regulators, we may elect, or be obliged, to postpone a regulatory submission to include additional analyses, which could cause delays in getting our products to market and substantially increase our costs. Changes in the regulatory environment or new requests from regulators may also result in our applications for marketing approval being rejected by the applicable regulatory authorities. Securing marketing authorization also requires the submission of information about the product manufacturing process to, and inspection (remotely or conductin of remote regulatory assessmentsperson) of manufacturing facilities by, the regulatory authorities. Changes to manufacturers, product candidate formulation, manufacturing processes and other product candidate attributes, such as the method of delivery, during product candidate development may also require additional studies to demonstrate the comparability of the product candidate using prior processes, formulation, or manufacturers, or with the prior attributes, to the product candidate using new the processes, formulation, or manufacturers, or with the new attributes.

Additionally, the CHMP’s negative opinion for Translarna and potential loss of the Translarna marketing authorization in the EEA may influence regulatory entities in other jurisdictions in which Translarna has been approved to reassess such approvals. For example, certain countries referencereferenced or dependdepended on the determination by the EMA when considering the grant of a marketing authorization. There is substantial risk that we wouldwill be unable to maintain our marketing authorizations in these countries in the event the EC decides not to renew or otherwise varies, suspends or withdraws our marketing authorization in the EEA.countries. Even in countries where our marketing authorization is maintained, there may be an impact on pricing and reimbursement of Translarna within those countries. Any potential reassessments or scheduled renewals of our marketing authorizations or impacts to pricing and reimbursement may lead to additional regulatory costs, requirements to complete additional clinical trials, restrictions on or removal of our marketing authorizations or loss of a significant portion of our revenue for Translarna in other jurisdictions, which could have a materialan adverse effect on our business, results of operations and financial condition.

In the United States, we may pursue the accelerated approval pathway for certain of our product candidates. However, the FDA may find that our product candidates do not qualify for accelerated approval. Moreover, even if we do ultimately receive accelerated approval, we would need to meet certain post approval requirements, such as completing a post-approval study confirming our product candidates’ clinical benefit that may require substantial time, effort, and funds. The FDA must specify the conditions for the required post approval studies, including enrollment targets, the study protocol, milestones, and target completion dates, by the time of approval and the FDA maymay, and frequently does, require that the post-approval studies be commenced before the date of approval. If this study does not confirm the product’s clinical benefit or if the study is not conducted in accordance with the FDA’s requirements, it would be subject to the risk of expedited FDA withdrawal. Additional regulatory requirements also include the pre-submission of promotional materials to the FDAFDA, periodic reporting, and potential restrictions, such as distribution restrictions, to assure the product’s safe use. In recent years, the accelerated approval pathway has come under significant governmental and public scrutiny. Accordingly, depending on the results of our studies, the FDA may be more conservative in granting accelerated approvalapproval, may require a different study design or statistical analysis, or, if granted, may be more apt to withdrawal approval if clinical benefit is not confirmed. Due to these and other uncertainties, we are unable to estimate the timing or potential for product candidates for which we may use the accelerated approval pathway or the cost or effort required to receive FDA approval. Further, even if we receive accelerated approval, there is no guarantee that we would be able to maintain such approval. For instance, our confirmatory studies may not confirm a product’s clinical benefit, in which case, the FDA could withdraw the product from the market, we may choose to voluntarily withdraw the product from the market, or we may need to conduct further studies to determine whether the product has a clinical benefit.

These risks may be increased for product candidates intended for the treatment of diseases for which there is little clinical experience, where we are using new endpoints or methodologies, or where the product candidates are new or novel. For example, there are no marketed therapies approved to treat the underlying cause of nmDMDHD and there is limited clinical trial experience with respect to drugs to treat nmDMDHD and other diseases that we are studying or have studied. As a result, the design and conduct of clinical trials for these diseases, particularly for drugs to address the underlying nonsense mutations causing these diseases in some subsets of patients, is subject to increased risk. Furthermore, because gene therapy products are a relatively new development, less is known about such products and product candidates and, accordingly there is an increased risk that such products may not perform as expected. Regulatory review agencies and the requirements and guidelines they promulgate may lengthen the regulatory review process, require us to perform additional or larger studies, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of our product candidates or lead to significant post-approval studies, limitations or restrictions.

In the event that a study’s primary endpoint is not met, companies may undertake certain analyses to further understand the data and potential reasons for the study results, including retrospective, post-hoc, and subgroup analyses. Because these analyses are not pre-planned and studies may not be adequately designed for these analyses, they may not be reliable and typically will not form the basis for regulatory approval. An unfavorable view of our data and analyses by regulatory authorities has and could continue to negatively impact our ability to obtain or maintain marketing authorizations, which would have a material adverse effect on our revenue and would materially harm our business, financial results and results of operations.

The manufacture of drugs, and especially biologic and gene therapy products is technically complex, requires extreme precision to meet specification requirements and necessitates substantial expertise and capital investment. Production difficulties caused by unforeseen events, even if seemingly minimal, may delay the availability of material for clinical studies and commercial product. For example, given the nature of biologics manufacturing, there is a risk of contamination. Any contamination could materially adversely affect our ability to produce our gene therapy product candidates on schedule and could, therefore, harm our results of operations and cause reputational damage.

In the United States, third-party payers, including government payers such as the Medicare and Medicaid programs, play an important role in determining the extent to which new drugs and biologics will be covered and reimbursed. Expensive specialty drugs in particular are often subject to restriction. The Medicare and Medicaid programs increasingly are used as models for how private payers and government payers develop their coverage and reimbursement policies. We cannot be assured that Medicare or Medicaid will cover our product candidates that may be approved or provide reimbursement without restriction and at adequate levels to realize a sufficient return on our investment. Our rebate payments may increase or our prices be adjusted under value-based purchasing arrangements based on evidence-based measures or outcomes-based measures for a patient or beneficiary based on use of our drug. Additionally, policymakers and federal agencies, including the Centers for Medicare & Medicaid Innovation, have signaled interest in testing or advancing new drug pricing models—such as so-called “most favored nation” or international reference pricing approaches—that would tie United States reimbursement levels to prices in foreign markets. Any such initiatives, if implemented, could reduce reimbursement for certain products, exert downward pricing pressure, and materially affect our business and financial results. Moreover, reimbursement agencies in the EU may be more conservative than CMS. It is difficult to predict what third-party payers will decide with respect to the coverage and reimbursement for our products for which we obtain marketing approval. Additionally, within Europe, each country has its own reimbursement regime employing various health technology assessmentassessment, or HTA, approaches to assess the cost-effectiveness of the product (for example, in the United Kingdom a HTA assessment is conducted by NICE) which may significantly affect the effective access to the market. While there is increased harmonization of this process as a result of Regulation 2021/2282 on HTAs, variation remains.

A substantialsignificant portion of our commercial sales currently occurs in territories outside of the United States which subjects us to additional business risks that could adversely affect our revenue and results of operations.

We commercialize Sephience, Translarna, Upstaza, Tegsedi and Waylivra outside of the United States. We have operations in multiple European countries, Latin AmericaAmerica, Japan and other territories. We expect that we will continue to expand our international operations in the future, including in emerging growth markets, pending successful completion of the applicable regulatory processes. International operations inherently subject us to a number of risks and uncertainties, including:

Furthermore, in some countries, including Brazil and Russia, orders for named patient sales may be for multiple months of therapy, which can lead to an unevenness in orders which could result in significant fluctuations in quarterly net product sales. Other factors may also contribute to fluctuations in quarterly net product sales including a product’s availability in any particular territory, government actions, economic pressures, political unrest and other factors. Net product sales are impacted by factors such as the timing of decisions by regulatory authorities and our ability to successfully negotiate favorable pricing and reimbursement processes on a timely basis in the countries in which we have or may obtain regulatory approval, including the United States, EEA and other territories.

Many countries, including the United States, restrict the export or import of products to or from certain countries through, for example, bans, sanction programs, and boycotts.embargoes. Such restrictions may preclude us from supplying products or generating revenue in certain countries or may require an export license prior to the export of the controlled item. Various laws, regulations and executive orders also restrict the use and dissemination outside of the United States, or the sharing with certain non-U.S. nationals, of information classified for national security purposes, as well as certain products and technical data relating to those products. Furthermore, if we, or third parties acting on our behalf, do not comply with these restrictions, we may be subject to substantial civil and criminal penalties and suspension or debarment from government contracting.

ThereOther than geographies where Translarna is approved or otherwise commercialized, there is currently no marketed therapy specifically for nmDMD, other than Translarna in the EEA.nmDMD. Santhera Pharmaceuticals has received approval of Agramee (vamorolone) in the United States for DMD patients ages 2 and up and in the EU and United Kingdom for patients ages 4 years and older. Sarepta Therapeutics has received approval of Elevidys for DMD patients 4 to 5 years of age with a confirmed mutation in the “DMD gene” in the United States and United Arab Emirates and Qatar. Sarepta Therapeutics has also received approval in the United States for two treatments (Exondys 51 (eteplirsen) and Vyondys 53 (golodirsen)) addressing the underlying cause of disease for different mutations in the DMD gene. Additionally, the FDA granted accelerated approval to Viltepso (viltolarsen) from NS Pharma for the treatment of DMD in patients with exon 53 skipping and Sarepta (Casimersen (SRP 4045) for the treatment of DMD in patients with exon 45 skipping. Viltepso (viltolarsen) from NS Pharma is also approved in Japan. Other biopharmaceutical companies are developing treatments addressing the underlying cause of disease for different mutations in the DMD gene, including, Dyne Therapeutics (DYNE-251), Wave Life Sciences (WVE-N53), Daiichi Sankyo (DS 5141)), and Nippon Shinyaku (Viltolarsen (NS 065/NCNP 01) and NS 089/NCNP 02)), and Astellas (AT 702). Additionally, other pharmaceutical companies are developing micro dystrophin gene therapies for patients with DMD regardless of genotype, including Pfizer (PF 06939926) and Solid Biosciences (SGT 001003) and REGENXBIO Inc. (RGX-202).

With the expiration of Emflaza’s orphan exclusivity for treatment of DMD in patients five years and older in February 2024, weWe face competition from generic versions of Emflaza for this indication.DMD. Although the FDA has not approved a corticosteroid specifically for DMD in the United States other than Emflaza, we face competition in the United States in the DMD market from prednisone/prednisolone, which, while not approved for DMD in the United States, is generically available and has been prescribed off label for DMD patients. Santhera has received approval of Agramee (vamorolone), in the United States for DMD patients ages 2 and up and in the European Union and United Kingdom for patients ages 4 years and older.

There are several pharmaceutical and biotechnology companies engaged in the development or commercialization of products against targets that are also targets of Tegsedi and Waylivra. For example, Ionis is developing Olezarsen for the treatment of FCS. Additionally, Waylivra faces competition from Myalept (metreleptin) produced by Chesi Farmaceutica, Inc., which is currently approved in Brazil for use in generalized lipodystrophy patients. Tegsedi faces competition from drugs like Onpattro (patisiran) which was launched by Alnylam Pharmaceuticals in the United States in 2018 and received approval in Brazil for the treatment of hATTR amyloidosis in 2020 as was well as AMVUTTRA (vutrisiran) which Alnylam Pharmaceuticals received approval for in the United States and Brazil in 2022 for the treatment of the polyneuropathy of hATTR amyloidosis in adults. Vyndaqel (tafamids meglumine) and Vyndamax (tafamidis) are commercialized in the United States, EU and some countries in Latin America by Pfizer. Other companies are also pursuing product candidates for the treatment of ATTR Amyloidosis with polyneuropathy including BridgeBio Pharma (AG 10), Intellia Therapeutics (NTLA2001), Proclara Biosciences (NPT 189) and SOM Biotech (tolcapone). For Waylivra, Ionis is developing Olezarsen for the treatment of FCS. Waylivra also faces competition from Myalept, (metreleptin) produced by Cheisi Farmaceutica, Inc., currently approved in Brazil for use in generalized lipodystrophy patients.

Sephience and Emflaza isare also eligible for reimbursement under the Medicare Part D program. Under Part D, Medicare beneficiaries may enroll in prescription drug plans offered by private entities, which will provide coverage of outpatient prescription drugs. Part D prescription drug formularies are required to include drugs within each therapeutic category and class of covered Part D drugs, though not necessarily all the drugs in each category or class. Any negotiated prices for our products covered by a Part D prescription drug plan likely will be lower than the prices we might otherwise obtain, and payment of Medicare Coverage Gap discounts may further reduce realization on Part D drugs. Further,In 2020, CMS isalso proposing to relaxrelaxed Part D coverage requirements to give plans more leverage in negotiating their formularies.

With respect to drugs eligible for reimbursement under Medicare Part B, on November 27, 2020, CMS issued an interim final rule implementing a Most Favored Nations payment model under which reimbursement for certain Medicare Part B drugs and biologicals will be based on a price that reflects the lowest per capita Gross Domestic Product-adjusted (GDP-adjusted) price of any non-U.S. member country of the Organisation for Economic Co-operation and Development (OECD) with a GDP per capita that is at least sixty percent of the U.S. GDP per capita. This rule now has been rescinded but other measures, including the Inflation Reduction Act of 2022, or IRA, have been enacted to address the costs of pharmaceuticals. The Inflation Reduction Act of 2022 requires manufacturers of selected drugs to negotiate discounted prices with the Secretary of the Department of Health and Human Services (HHS). Failure to reach an agreement can subject manufacturers to an excise tax or withdraw of all drug products from coverage under Medicare and Medicaid. Drug price negotiations and other program implementation measures could potentially be affected by the Executive Order, Initial Rescissions of Harmful Executive Orders and Actions, issued on January 20, 2025 and/or the anticipated change in leadership at Health and Human Services and the Centers for Medicare and Medicaid Services (CMS) under the new administration. Such rules and any additional healthcare reform measures could further constrain our business or limit the amounts that federal and state governments will pay for healthcare products and services, which could result in additional pricing pressures.

In addition, U.S. private health insurers often rely upon Medicare coverage policies and payment limitations in setting their own coverage and reimbursement policies. Any such coverage or payment limitations may result in a similar reduction in payments from non-governmental payors. Payment by private payors is also subject to payor-determined coverage and reimbursement policies that vary considerably and are subject to change without notice. We expect that coverage and reimbursement of Sephience and Emflaza in the United States will vary from commercial payor to commercial payor. Many commercial payors, such as managed care plans, manage access to prescription drugs partly to control costs to their plans, and may use drug formularies and medical policies to limit their exposure. Exclusion from policies can directly reduce product usage in the payor’s patient population and may negatively impact utilization in other payor plans, as well.

There has been recent negative publicity and increasing legislative and public scrutiny around pharmaceutical drug pricing in the U.S., in particular with respect to orphan drugs and specifically with respect to Emflaza. Moreover, U.S. government authorities and third-party payors are increasingly attempting to limit or regulate drug prices and reimbursement, often with particular focus on orphan drugs. For example, certain drugs with an orphan designation may become subject to price negotiations under the IRA. These dynamics may give rise to heightened attention and potential negative reactions to pricing decisions for Sephience and Emflaza and products for which we may receive regulatory approval in the future, possibly limiting our ability to generate revenue and attain profitability.

Moreover, in 2017, the U.S. Congress modified and amended certain provisions of the 2010 U.S. healthcare reform legislation (the Patient Protection and Affordable Care Act of 2010, as amended by the Health Care and Education Reconciliation Act of 2010, known collectively as the Affordable Care Act), which could have an impact onimpacts coverage and reimbursement for healthcare items and services covered by the federal and state healthcare programs as well as plans in the private health insurance market. The so-called “individual mandate” was repealed as part of tax reform legislation adopted in December 2017. Legal challenges to the Affordable Care Act continue to arise and there may be future efforts to modify, repeal, or otherwise invalidate all, or certain provisions of the Affordable Care Act. We cannot assure that the Affordable Care Act, as currently enacted or as amended in the future, will not adversely affect our business and financial results and we cannot predict how future federal or state legislative or administrative changes relating to healthcare reform will affect our business.

Additionally, the Budget Control Act of 2011, among other things, created measures for spending reductions by Congress. Failure of the Joint Select Committee on Deficit Reduction to reach required deficit reduction goals triggered the legislation’s automatic reduction to several government programs. This legislation resulted in aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, which went into effect in April 2013 and will remain in effect through 2031. However, pursuant to the CARES Act and subsequent legislation, these Medicare sequester reductions were suspended through the end of March 2022 and from April 2022 through June 2022, a 1% cut was in effect, with the full 2% cut remaining thereafter. The American Taxpayer Relief Act of 2012, among other things, reduced Medicare payments to several providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. These new laws may result in additional reductions in Medicare and other healthcare funding and otherwise affect the prices we may obtain for any of our product candidates for which we may obtain regulatory approval or the frequency with which any such product candidates isare prescribed or used.

In the EU, reference pricing systems and other measures may lead to cost containment and reduced prices with respect to Sephience for the treatment of PKU, Translarna for the treatment of nmDMD, Upstaza for the treatment of AADC deficiency and other product candidates that might receive marketing authorization in the future. Our inability to promptly obtain coverage and profitable payment rates from both government-funded and private payors for our product or any of our product candidates that may receive marketing authorization, or a reduction in coverage for payment rates for our product or any such product candidates, could have a material adverse effect on our business, results of operations and financial condition. In addition, in the EU, an authorized trader, such as a wholesaler, can purchase a medicine in one EU member state and obtain a license to import the product into another EU member state. This process is called “parallel distribution”. As a result, a purchaser in one EU member state may seek to import TranslarnaSephience from another EU member state where TranslarnaSephience is sold at a lower price. This could have a negative impact on our business, financial condition, results of operations and growth.

Similarly, sales of Sephience, Emflaza or our other products in the United States could also be reduced if they, or products similar to them, are imported into the United States from lower-priced markets, whether legally or illegally. For example, in the United States, prices for pharmaceuticals are generally higher than in the bordering nations of Mexico and Canada. In October 2020, the Department of Health and Human Services, or HHS, and the FDA published a final rule allowing states and other entities to develop a Section 804 Importation Program, or SIP, to import certain prescription drugs from Canada into the United States. Certain states have passed laws allowing for the importation of drugs from Canada with the intent of developing SIPs for review and approval by the FDA. Florida received approval for its SIP from the FDA. Further, on November 20,30, 2020, HHS finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through pharmacy benefit managers, unless the price reduction is required by law. The rule also creates a safe harbor for price reductions reflected at the point-of-sale, as well as a new safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers. The effective date of the new safe harbors and the revision to the discount safe harbor was delayed by court order until January 1, 2023. Recent legislation further delayed implementation of the new safe harbors and the revision to the discount safe harbor until January 1, 2032.

There may be future and have been changes in legal and regulatory requirements that may materially impact our results of operation.

Future changesChanges in legal and regulatory requirements may introduce new risks into our operations and future prospects, which we are not able to currently anticipate. By example, changes taking place in the United States associated with athe newcurrent federal administration, as well as changes in legal standards, including the reduced level of judicial deference due to administrative agencies following a 2024 Supreme Court decision, may introduce uncertainties with respect to our current and future operations and our future likelihood of success. It is possible that newNew federal or state laws or regulations may bebe, and have been, passed, or laws and regulations may bebe, and have been, enforced differently than they were before, which may expose us to additional legal and regulatory risk or uncertainty and require the expenditure of additional resources to ensure that we are able to comply. Such actions could also adversely restrict our business and operations. There could also be changes in the FDA’s approval standards that could impact our ability to obtain product approval and market our product candidates within the currently anticipated timeframes or otherwise impact the competitive market for our product candidates. Such changes may necessitate the conduct of additional development work, including preclinical and clinical trials, and manufacturing development. By example, for products intended for rare and serious diseases with unmet medical needs, the FDA is authorized to exercise regulatory flexibility when making a medical risk-benefit judgment. It is possible that whether and how the FDA exercises any regulatory flexibility,flexibility in any particular case, including with respect to specialized pathways, such as accelerated approval, may change, which could impact our ability to obtain product approval. Further, legal and regulatory changes may impact how we may market and sell our products in the future, if they are approved, as well as how they are reimbursed. Moreover, there could be changes in the federal workforceworkforce, including reductions in force that took place in 2025, and agency policies that may result in regulatory delays, including with respect to the FDA’s review of marketing applications and other submissions, and that may impact the ability to communicate with and obtain guidance from the agencies. AtWe this time, it is too early tocannot predict the exact nature of any changes that may take place or whether and how they may impact our business and results of operation.

Since inception, we have incurred significant operating losses. As of December 31, 2024,2025, we had an accumulated deficit of $3,646.9$2,964.2 million. We have financed our operations to date primarily through the private offerings of convertible senior notes, public and “at the market offerings” of common stock, proceeds from royalty purchase agreements, net proceeds from our borrowing under our credit agreement with Blackstone, private placements of our convertible preferred stock and common stock, collaborations, bank and institutional lender debt, other convertible debt, grant funding and clinical trial support from governmental and philanthropic organizations and patient advocacy groups in the disease areaareas addressed by our product candidates. We have historically relied on revenue generated from net sales of Translarna for the treatment of nmDMD in territories outside of the United States since 2014, Emflaza for the treatment of DMD in the United States since 2017, and Upstaza/Kebilidi for the treatment of AADC deficiency in the EEA and U.S. since May2022 2022.and 2025, respectively, and Sephience for the treatment of PKU since 2025. We have also relied on revenue associated with milestone and royalty payments from Roche pursuant to the SMA License Agreement under our SMA program and revenue generated from net sales of Tegsedi and Waylivra in Latin America and the Caribbean.Caribbean, and license revenues related to performance obligations already completed pursuant to the Novartis Agreement. Based on our current commercial, research and development plans, we expect to continue to incur significant operating expenses for the foreseeable future, which we anticipate will be partially offset by revenues generated from the sale of our products and our collaboration and royalty revenues. We expect tomay continue to generate operating losses through 20252026 and, while we anticipate that operating losses generated in future periods should decline versus prior periods, we may never generate profits from operations or maintain profitability. The net losses we incur may fluctuate significantly from period to period. There is a substantial risk that as a result of the EC’s adoption of the CHMP’s negative opinion we will lose a significant portion of our ability to generate revenue from sales of Translarna in the EEA.

We anticipate that we will continue to incur significant expenses in connection with our commercialization efforts in the United States, the EEA, Latin AmericaAmerica, Japan and other territories, including expenses related to our commercial infrastructure and corresponding sales and marketing, legal and regulatory, and distribution and manufacturing undertakings as well as administrative and employee-based expenses. In addition to the foregoing, we expect to continue to incur significant costs in connection with ongoing, planned and potential future clinical trials and studies for sepiapterin and our splicing and inflammation and ferroptosis programs as well as studies in our products for maintaining authorizations, label extensions and additional indications. We continue to seek marketing authorization for Translarna for the treatment of nmDMD in territories that we do not currently have marketing authorization in and we are exploring other potential mechanisms by which we may provide Translarna to nmDMD patients in the EEA if the EC adopts the CHMP’s negative opinion for Translarna. We also submitted an MAA to the EMA for sepiapterin for the treatment of PKU in March 2024, an NDA to the FDA for sepiapterin for the treatment of PKU in the third quarter of 2024, and an NDA to the FDA for vatiquinone for the treatment of FA in the fourth quarter of 2024. These efforts may significantly impact the timing and extent of our commercialization and manufacturing expenses.

With respect to our outstanding 1.50% convertible senior notes due September 15, 2026, or the 2026 Convertible Notes, cash interest payments are payable on a semi-annual basis in arrears, which will require total funding of $4.3 million annually. Additionally, the notes are currently convertible and will mature and become due and payable on September 15, 2026 unless earlier redeemed or converted.

Regulatory guidance under the 2017 Tax Act,IRA, the IRA,OBBBA, and suchother additionaltax-related legislation is and continues to be forthcoming, and such guidance could ultimately increase or lessen the impact of these laws on our business and financial condition. In addition, it is uncertain if and to what extent various states will conform to thechanges 2017to Tax Act, the IRA, and additionalfederal tax legislation.

Regulatory authorities in some jurisdictions, including the EUUnited States and the United States,EU, may designate drugs for relatively small patient populations as orphan drugs. We have obtained orphan drug designations from the EMAFDA and fromthe EMA for Sephience for the FDAtreatment forof patients with hyperphenylalaninemia, including hyperphenylalaninemia caused by PKU, Translarna for the treatment of nmDMD, Upstaza/Kebilidi for the treatment of AADC, Evrysdi for the treatment of SMA, sepiapterin for the treatment of patients with hyperphenylalaninemia, including hyperphenylalaninemia caused by PKU and vatiquinone for the treatment of FA. The FDA has also granted an orphan drug designation to Emflaza for the treatment of DMD. We may also seek orphan drug designation and exclusivity for other product candidates, if we believe that the product candidate may qualify. We, however, may not be able to obtain orphan drug designation in the future for any of our other product candidates and, even if we obtain designation, we may ultimately not be able to obtain orphan drug exclusivity. Obtaining orphan drug exclusivity, both in the EUUnited States and in the United States,EU, may be important to a product candidate’s future success.

In the United States, under FDA’s current policy, if a product with an orphan drug designation subsequently receives the first marketing authorization for the indication for which it has such designation, the product is entitled to seven years of market exclusivity which precludes the FDA from approving another marketing application for the “same drug” for the same orphan designated approved indication for that time period. When determining whether a drug is the “same drug” as an orphan designated product, the FDA looks to the products’ molecular features and use. The specific sameness criteria, however, varies based on whether the product is composed of small or large molecules and if the product is a gene therapy. Moreover, for gene therapies, the sameness criteria are currently evolving. For example, the FDA issued a final guidance document specific to sameness determinations. Depending on product characteristics, sameness may be determined by the FDA on a case-by-case basis, making it difficult to predict when FDA may approve a product and whether periods of exclusivity will effectively block competitors seeking to market products that are the same or similar to ours for the same intended use. Moreover, following the Catalyst Pharms., Inc. v. Becerra and FDA’s subsequent statement that it intends to continue to apply its regulations tying the scope of orphan-drug exclusivity to the uses or indications for which a drug is approved, as further described in this filing, the exact scope of orphan drug exclusivity may be an evolving space. Accordingly, whether any of our products or product candidates will be deemed to be the same as another product or product candidate is uncertain and the scope of any potential or received orphan drug exclusivity period, as well as any of our competitors that may block approval of one of our product candidates, may be subject to revision.

For certain of our products, periods of orphan drug exclusivity are important. For instance, for Emflaza, we have previously relied on non-patent market exclusivity periods under the Orphan Drug Act to commercialize Emflaza in the United States. Emflaza’s seven-year period of orphan drug exclusivity related to the treatment of DMD in patients five years and older expired in February 2024. We expectWith the expiration of this orphan drug exclusivityexclusivity, towe have significantseen negativean impactincrease on Emflaza net product revenue, as we facein competition from generic versions of Emflaza for this indication, which are generally priced less than Emflaza. Emflaza’s orphan drug exclusivity related to the treatment of DMD in patients two years of age to less than five expires in June 2026. Healthcare providers may also substitute the generic version(s) of Emflaza for patients two years of age to five, despite the fact that the generic version(s) will not be approved for such indication until after June 2026.

The respective orphan designation and exclusivity frameworks in the United States and in the EU are subject to change, and any such changes may affect our ability to obtain, or the impact of obtaining, EUUnited States or United StatesEU orphan designations in the future.

We, our products and product candidates, our operations, our facilities, our suppliers and our contract manufacturers, distributors, contract research organizations, clinical trial sites and contract testing laboratories are subject to extensive regulation by governmental authorities in the EEA,United States, the United States,EEA, and other territories, with regulations differing from country to country.

We are not permitted to market our product candidates in the EEA,United States, the United States,EEA, or other territories until we have received requisite regulatory approvals. In order to receive and maintain such approvals, and to be compliant with regulatory authority requirements, we and our third-party service providers must comply on a continuous basis with a broad array of regulations and requirements. Depending on the stage of product development and whether a product is approved these requirements may relate to establishment registration and product listing, the payment of user fees, manufacturing processes, risk management measures, quality and pharmacovigilance systems (including reporting of manufacturing deviations and adverse events), pre- and post-approval clinical and pre-clinical data and study conduct, labeling, packaging, advertising, marketing and promotional activities (including product sampling), record keeping, distribution, storage, and import and export of pharmaceutical products. Any regulatory approval of any of our products or product candidates, once obtained, may be withdrawn. For example, our marketing authorization for Translarna for the treatment of nmDMD in the EEA iswas subject to annual review and renewal by the EC following reassessment by the EMA of the benefit-risk balance of the authorization, as well as the specific obligation to conduct and report the results of Study 041. In JanuaryMarch 2024,2025, the EC adopted the opinion of the CHMP issued a negative opinion for the renewal of the conditional marketing authorization following a re-examination procedure. In May 2024, the EC decidedto not to adoptrenew the CHMP’s negative opinion for the renewal of the conditional marketing authorization of Translarna and returned such opinion to the CHMP for re-evaluation. In June 2024, following the EC’s request for re-review, the CHMP issued a negative opinion on the renewal of the conditional marketing authorization of Translarna for the treatment of nmDMD.nmDMD, Onresulting October 18, 2024, the CHMP maintained its negative opinion for the renewal of the conditional marketing authorization following the requested reexamination procedure. In accordance with EMA regulations, the EC has 67 days from the date of issuance to adopt the opinion. At this time, the EC has not yet adopted the negative opinion. If the EC adopts the negative opinion,in Translarna would no longer havehaving marketing authorization in the memberEEA. statesWe now must rely on individual countries to leverage Articles 117(3) and 5(1) of the EEA.EU Directive 2001/83 to allow continued commercial use of Translarna.

After approving a drug, the FDA may withdraw product approval if compliance with regulatory standards is not maintained or if safety problems occur after the product reaches the market. Requirements for additional clinical trials and studies to confirm safety and effectiveness may be imposed as a condition of marketing approval. In addition, the FDA requires surveillance programs to monitor approved products that have been commercialized, as well as REMS, and the agency has the power to require changes in labeling or to prevent further marketing and distribution of a product. For example, we were obligated to perform certain FDA post-marketing requirements in connection with our marketing authorization for Emflaza in the United States, including clinical safety studies. Additionally, ourin certain geographies, marketing authorizations for Translarna, Tegsedi and Waylivra in Brazil and our marketingproducts authorizationmay for Translarna in Russia arebe subject to renewal every five years.renewal. There is no guarantee that we will be able to complete our post-marketing obligations in accordance with the established timetables. Failure to complete the required studies in accordance with the established timetables or failure to provide the requisite periodic reports on the status of post-marketing studies in the absence of good cause could result in an enforcement action. Accordingly, we and others with whom we work must continue to expend time, money, and effort in all areas of regulatory compliance, including manufacturing and distribution.

Regulatory authorities conduct ongoing reviews and inspections (remotely or remotein regulatory assessmentsperson) of marketed products, as well as sponsors and manufacturing facilities. Regulatory authorities also conduct inspections of manufacturing facilities and clinical trial sites before approving a product, which can delay approval. If compliance issues are found, it could also result in refusal to approve marketing applications, disruption of production or distribution of a product or product candidate, disruption, cancellation, or suspension of a study, or require substantial resources to correct.

Even if marketing authorization of a product candidate is granted, the approval may be subject to limitations on the indicated uses for which the product may be marketed, the product may have labeling that includes significant restrictions, warnings, including black box warnings, and contraindications, the regulatory authorities may not approve label claims necessary for successful product marketing, or the approval may be subject to significant conditions of approval, including the requirement of a REMS. A regulatory authority also may impose requirements for costly post-marketing studies or clinical trials and surveillance to monitor the safety or efficacy of the product. In addition, the competent authorities of each EU member state and the FDA closely regulate the post-approval marketing and promotion of drugs to ensure drugs are marketed only for the approved indications and in accordance with the provisions of the approved labeling and regulatory requirements. Such regulatory authorities can and do impose stringent restrictions on our communications regarding off-label use and if we do not comply with the laws governing promotion of approved drugs, we may be subject to enforcement action for off-label promotion. For example, violations of the FDCA relating to the promotion of prescription drugs may lead to civil and criminal penalties, investigations alleging violations of federal and state healthcare fraud and abuse laws, as well as state consumer protection laws. In 2025, FDA also increased its enforcement with respect to promotion and advertising.

Our approved products may face competition from products approved via abbreviated pathways as well as products approved pursuant to full applications. For example, our biologic products may face competition from biosimilar or interchangeable products. In 2025, FDA also potentially made it easier for sponsors of biosimilar or interchangeable products to obtain approval, easing requirements for biosimilar comparative efficacy clinical studies and interchangeable product switching studies. Sponsors seeking approval of biosimilar or interchangeable products to ours would reference our product in their applications. The applicable laws, however, establish certain protections for reference biologic products. For example, there is a complex and involved framework for sponsors to bring patent infringement actions and actions for declaratory judgment. Accordingly, we may need to pursue costly and time-consuming patent infringement actions, which may include certain statutorily specified regulatory steps before an infringement action may be brought. We may also need to spend time and money defending an action for declaratory judgement that is brought by the biosimilar product sponsor.

Another protection established for biologic products is a period of 12 years of exclusivity for reference products that begins on the date that the reference product was first licensed by the FDA. During this time, the FDA may not make the licensure of a biosimilar product effective. Biosimilar applications can, however, be submitted for FDA review beginning four years after the date of the reference product’s first licensure. This exclusivity period, however, is subject to certain limitations. For example, certain changes and supplements to an approved BLA, and certain subsequent applications filed by the same sponsor, manufacturer, licensor, predecessor in interest, or other related entity do not qualify for the 12-year exclusivity period. Moreover, there have been legislative efforts to decrease this period of exclusivity to a shorter timeframe. Future proposed budgets, international trade agreements and other arrangements or proposals may affect periods of exclusivity. Further, there is a risk that the FDA will not consider our biologic products to be reference products for competing products, potentially creating the opportunity for biosimilar competition sooner than anticipated. Additionally, this period of regulatory exclusivity does not apply to companies pursuing regulatory approval via their own traditional BLA, rather than via the abbreviated pathway. Moreover,Once the extent to whichapproved, a biosimilar,biosimilar oncemay approved,be willable to be substituted for any one of our reference products in a way that is similar to traditional generic substitution for non-biological products is not yet fully clear, and will depend on a number of marketplace and regulatory factors that are still developing.products. It is also possible that payers will give reimbursement preference to biosimilars, even over reference biologics, absent a determination of interchangeability. Similarly, in the EU, another company could gain approval for a competing product based on an MAAmarketing authorization application with a completely independent data package that includes pharmaceutical tests, preclinical tests and clinical trials.trials subject to any orphan exclusivity that may be in place.

Commercialization of Sephience, Translarna and Upstaza has been in, and is expected to continue to take place in, countries that tend to impose strict price controls, which may adversely affect our revenues. Failure to obtain and maintain acceptable pricing and reimbursement terms for Sephience for PKU, Translarna for the treatment of nmDMDnmDMD, or Upstaza for the treatment of AADC deficiency in the EEA and other countries where Translarnathese isproducts are available would delay or prevent us from marketing our product in such regions, which would adversely affect our business, results of operations, and financial condition. In addition, the decision of the EC to withdraw Translarna’s marketing authorization materially limits our ability to make Translarna available in the EEA on a reimbursed basis and may impact our revenues in the EEA and regions that relied on the EEA marketing authorization. In addition, some countries in the EEA may require us to make payments based on the withdrawal of the Translarna marketing authorization and related actions by regulatory authorities overseeing market access systems in those countries.

We are a global biopharmaceutical company thatdedicated discovers,to developsthe discovery, development and commercializescommercialization of clinically differentiated medicines that provide benefits tofor children and adults living with rare disorders. OurWe abilityare to innovate to identify new therapies and to globally commercialize products is the foundation that drives investment inadvancing a robust and diversified pipeline of transformative medicines.medicines Ouras part of our mission is to provide access to best-in-class treatments for patients whowith haveunmet littlemedical to no treatment options.needs. Our strategy is to leverage our strong scientific and clinical expertise and global commercial infrastructure to bringoptimize therapiesvalue tofor patients.our patients and other stakeholders. We believe that this allows us to maximize value for all of our stakeholders. We have a diversified therapeutic portfolio that includes several commercial products and product candidates in various stages of development, including clinical, pre-clinical and research and discovery stages, focused on the development of new treatments for multiple therapeutic areas for rare diseases relating to neurology and metabolism.

We have two products, TranslarnaTMTranslarna™ (ataluren) and Emflaza® (deflazacort), for the treatment of Duchenne muscular dystrophy, or DMD, a rare, life threatening disorder. While Translarna currentlypreviously hashad conditional approval in the EEA, in March 2025, the European Commission, or EC, adopted the negative opinion of the Committee of Medicinal Products for Human Use, or CHMP, of the European Medicines Agency, or EMA, to not renew the conditional marketing authorization inof the European Economic Area, or EEA,Translarna for the treatment of nonsensenmDMD. mutationHowever, Duchennethe muscularEC dystrophy,indicated that individual countries within the European Union, or nmDMD,EU, incan ambulatoryleverage patientsArticles aged two years117(3) and older.5(1) of the EU Directive 2001/83 to allow continued commercial use of Translarna. Translarna also has marketing authorization in Russiaadditional forgeographies outside of the treatmentEEA, though the EC adoption of nmDMDthe CHMP negative opinion and the withdrawal of the Translarna NDA in patients aged two years and older, and in Brazil for the treatmentUnited ofStates nmDMDmay inaffect ambulatoryfuture patients two years and older and for continued treatment of patients that become non-ambulatory, as well as in various other countries.reauthorizations. During the year ended December 31, 2024,2025, we recognized $339.9$235.3 million in salesnet ofproduct Translarna. We hold worldwide commercialization rights to Translarnarevenues for all indications in all territories.Translarna. Emflaza is approved in the United States for the treatment of DMD in patients two years and older. During the year ended December 31, 2024,2025, Emflazawe achievedrecognized $146.4 million in net salesproduct ofrevenues $207.2for million.Emflaza.

Each country, including each member state of the EEA, has its own pricing and reimbursement regulations. In order to commence commercial sale of product pursuant to our TranslarnaSephience marketing authorization in any particular country in the EEA, we must finalize pricing and reimbursement negotiations with the applicable government body in such country. As a result, our commercial launch will continue to be on a country-by-country basis. We also have made, and expect to continue to make, product available under early access programs, or EAP programs, or similar styled programs both in countries in the EEA and other territories. Our ability to negotiate, secure and maintain reimbursement for product under commercial and EAP programs can be subject to challenge in any particular country and can also be affected by political, economic and regulatory developments in such country.

Translarna is an investigational new drug in the United States. During the first quarter of 2017, we filed aan New Drug Application, or NDA,NDA for Translarna for the treatment of nmDMD over protest with the United States Food and Drug Administration, or FDA. In October 2017, the Office of Drug Evaluation I of the FDA issued a Completecomplete Responseresponse Letter, or CRL,letter for the NDA, stating that it was unable to approve the application in its current form. In response, we filed a formal dispute resolution request with the Office of New Drugs of the FDA. In February 2018, the Office of New Drugs of the FDA denied our appeal of the CRL.complete response letter. In its response, the Office of New Drugs recommended a possible path forward for theour ataluren NDA submission based on the accelerated approval pathway. This would involve a re-submission of an NDA containing the current data on effectiveness of ataluren with new data to be generated on dystrophin production in nmDMD patients’ muscles. We followed the FDA’s recommendation and collected, using newer technologies via procedures and methods that we designed, such dystrophin datadesigned in a new study, Study 045, and announced the results of Study 045 in February 2021. Study 045 did not meet its pre-specified primary endpoint. In June 2022, we announced top-line results from the placebo-controlled trial of Study 041.041, which was our 18 months, placebo-controlled trial, followed by an 18 months open label extension, of Translarna in the treatment of ambulatory patients with nmDMD aged five years or older. Following this announcement, we submitted a meeting request to the FDA to gain clarity on the regulatory pathway for a potential re-submission of an NDA for Translarna. The FDA provided initial written feedback that Study 041 does not provide substantial evidence of effectiveness to support NDA re-submission. We held a Type C meeting with the FDA in the fourth quarter of 2023 to discuss the totality of Translarna data. Based on feedback from the FDA, we re-submitted the NDA in July 2024, based on the results from Study 041 and from our international drug registry study for nmDMD patients receiving Translarna. In October 2024, the FDA accepted for review the resubmission of the NDA for Translarna for the treatment of nmDMD. AsFollowing thisfeedback wasfrom anFDA at the end of January 2026, we decided to withdraw the NDA resubmission followingfor aTranslarna. completeFurther responsedevelopment letterof toTranslarna for the NDAtreatment whichof was filed over protestnmDMD in 2016, the FDAUnited States is not obligated to follow the review timelines under PDUFA guidelines and an action date has not been provided.planned.

WeWith respect to Emflaza, we have previously relied on Emflaza’s seven-year marketing exclusivity period in the United States for its approved indications under the provisions of the Orphan Drug Act of 1983, or the Orphan Drug Act, when commercializing Emflaza.Emflaza Emflaza’s seven-year period of orphan drug exclusivity related tofor the treatment of DMD in patients five years and olderolder, which expired in February 2024. We expectWith the expiration of this orphan drug exclusivityexclusivity, we have seen an increase in competition from generics, which has, and we expect will continue to havehave, a significant negative impact on Emflaza net product revenue. Emflaza’s orphan drug exclusivity related to the treatment of DMD in patients two years of age to less than five expires in June 2026. See “Item 1. Business-Government Regulation” for further discussion with respect to marketing protection we rely on.

Upstaza/Kebilidi is a gene therapy for the treatment of Aromatic L Amino Decarboxylase, or AADC, deficiency, a rare central nervous system, or CNS, disorder arising from reductions in the enzyme AADC that results from mutations in the dopa decarboxylase gene. In July 2022, the EC approved Upstaza for the treatment of AADC deficiency for patients 18 months and older within the EEA. In November 2022, the Medicines and Healthcare Products Regulatory Agency approved Upstaza for the treatment of AADC deficiency for patients 18 months and older within the United Kingdom. In November 2024, the FDA granted accelerated approval of our gene therapy for the treatment of children and adults with AADC deficiency, which is marketed with the brand name Kebilidi in the United States. We are obligated to complete certain post-marketing requirements in connection with the FDA's approval, including clinical safety studies.

We hold the rights for the commercialization of Tegsedi and Waylivra for the treatment of rare diseases in countries in Latin America and the Caribbean pursuant to a Collaboration and License Agreement, or the Tegsedi-Waylivra Agreement, dated August 1, 2018, by and between us and Akcea Therapeutics, Inc., or Akcea, a subsidiary of Ionis Pharmaceuticals, Inc. Tegsedi has received marketing authorization in the United States, European Union, or EU, and Brazil for the treatment of stage 1 or stage 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis, or hATTR amyloidosis. In August 2021, ANVISA, the Brazilian health regulatory authority, approved Waylivra as the first treatment for familial chylomicronemia syndrome, or FCS, in Brazil. In December 2022, ANVISA approved Waylivra for the treatment of familial partial lipodystrophy, or FPL. Waylivra has also received marketing authorization in the EU for the treatment of FCS.

Our inflammation and ferroptosis platform consists of small molecule compounds that target oxidoreductase enzymes that regulate oxidative stress and inflammatory pathways central to the pathology of a number of CNS and non-CNS diseases. The most advanced molecule in our inflammation and ferroptosis platform is vatiquinone. We announced topline results from a registration-directed Phase 3 trial of vatiquinone in children and young adults with Friedreich’s ataxia, or FA, called MOVE-FA, in May 2023. While the studytrial did not meet its primary endpoint of statistically significant change in modified Friedreich Ataxia Rating Scale, or mFARS, score at 72 weeks in the primary analysis population,endpoint, vatiquinone treatment did demonstrate significant benefit on key disease subscales and secondary endpoints. In addition, in the population of subjects that completed the study protocol, significance was reached in the mFARS endpoint and several secondary endpoints,subscales, including the upright stability subscale.subscale, Furthermore, vatiquinone wasas well tolerated.as on other disease relevant endpoints. In October 2024, we announced that the pre-specified endpoint for two different FA long-term extension studies was met, with statistically significant evidence of durable treatment benefit on disease progression. In December 2024, we submitted an NDA to the FDA for vatiquinone for the treatment of children and adults living with FA. In FebruaryAugust 2025, the FDA acceptedissued fora filingcomplete response letter related to the NDA stating that substantial evidence of efficacy was not demonstrated for vatiquinone and grantedthat priorityan reviewadditional adequate and well-controlled study would be needed to support NDA resubmission. We met with the FDA in the fourth quarter of 2025 to discuss the vatiquinone development program. FDA suggested an additional study be conducted to support NDA resubmission. FDA stated in the meeting minutes that this study could be an open label study with a targetnatural regulatoryhistory actioncontrol dategroup. We plan to meet with FDA in the second quarter of August2026 19,to 2025.discuss the design of this new study.

The success of our products and any other product candidates we may develop depends largely on obtaining and maintaining reimbursement from governments and third-party insurers. During 2024,2025, our revenues were primarily generated from sales of Sephience for the treatment of PKU in the U.S. and EEA, Translarna for the treatment of nmDMD in countries where we were able to obtain acceptable commercial pricing and reimbursement terms and in select countries where we are permitted to distribute Translarna under our EAP programs or through similar styled programs, and from sales of Emflaza for the treatment of DMD in the United States. There is a substantial risk that as a result of the EC’s adoption of the CHMP’s negative opinion we will lose a significant portion of our ability to generate revenue from sales of Translarna in the EEA. We also generated revenue from sales of Upstaza/Kebilidi for the treatment of AADC deficiency in the EEA and in the U.S., and have recognized revenue associated with milestone and royalty payments from Roche pursuant to a License and Collaboration Agreement, or the SMA License Agreement, by and among us, Roche and, for the limited purposes set forth therein, the SMA Foundation, under our SMA program.program and we have recognized license revenues related to performance obligations completed pursuant to the Novartis Agreement.

In October 2022, we entered into the Credit Agreement, dated October 27, 2022, by and among us and certain of our subsidiaries from time to time party thereto, as guarantors, or, collectively with us, the Loan Parties, funds and other affiliated entities advised or managed by Blackstone Life Sciences and Blackstone Credit, or collectively, Blackstone, as lenders, together with their permitted assignees, the Lenders, and Wilmington Trust, National Association, as the administrative agent for the Lenders, or the Blackstone Credit Agreement.Agreement, The Blackstone Credit Agreement provided for fundings of up to $950.0 million consisting of a committed loan facility consisting of a senior secured term loan facility funded on October 27, 2022, or the Closing Date, in the aggregate principal amount of $300.0 million, and a delayed draw term loan facility of up to $150.0 million to be funded at our request within 18 months of the Closing Date subject to specified conditions, and further contemplating the potential for up to $500.0 million of additional financing, to the extent that we requested such additional financing and subject to the Lenders’ agreement to provide such additional financing and to mutual agreement on terms. In October 2023,which we terminated thein BlackstoneOctober Credit Agreement.2023. In connection with the termination of the Blackstone Credit Agreement, we repaid outstanding principal of $300.0 million, accrued interest of $2.1 million, an additional $82.0 million in prepayment premiums, exit fees, and creditor expenses, and $0.2 million in legal fees. We recorded a loss on the extinguishment of debt of $92.7 million which is included on the statement of operations for the period ended December 31, 2023. The loss on extinguishment of debt consisted of $82.0 million in prepayment premiums, exit fees, and creditor expenses and debt issuance costs of $10.7 million. All liens and security interests securing the loans made pursuant to the Blackstone Credit Agreement were released upon termination.

In November 2024, we entered into the Novartis Agreement relating to our PTC518votoplam HD program which includes related molecules. Pursuant to the Novartis Agreement, we will continue to conduct the ongoing Phase 2A Clinical Trial and the ongoing OLE Clinical Trial pursuant to its existing development plan, with the goal of transitioning the ongoing OLE Clinical Trial to Novartis within 12 months after the effective date. Novartis will beis responsible for all other development of licensed compounds and licensed products and the manufacture and commercialization of licensed compounds and licensed products worldwide. While Novartis has taken over responsibility for the further development of the votoplam program, we continue to collaborate with Novartis on next steps. Under the Novartis Agreement, and upon the closing of the transaction contemplated by the Novartis Agreement in January 2025, we received an upfront payment of $1.0 billion on the effective date and can receive up to $1.9 billion in development, regulatory and sales milestones, a 40% share of U.S. profits and losses, and tiered double-digit royalties on ex-U.S. salessales. See “Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations—Liquidity and capital resources—Sources of Liquidity” for additional information.

We have financed our operations to date primarily through the private offerings of convertible senior notes, public and “at the market offerings” of common stock, proceeds from royalty purchase agreements, net proceeds from our borrowings under our credit agreement with Blackstone, private placements of our convertible preferred stock and common stock, collaborations, bank and institutional lender debt, other convertible debt, grant funding and clinical trial support from governmental and philanthropic organizations and patient advocacy groups in the disease areaareas addressed by our product candidates. We have relied on revenue generated from net sales of Translarnaour for the treatment of nmDMD in territories outside of the United States since 2014, Emflaza for the treatment of DMD in the United States since 2017 and Upstaza for the treatment of AADC deficiency in the EEA since 2022.products. We have also relied on revenue associated with milestone and royalty payments from Roche pursuant to the SMA License Agreement under our SMA program and revenuelicense generatedrevenues fromrelated netto salesperformance ofobligations Tegsedicompleted andpursuant Waylivra in Latin America andto the Caribbean.Novartis Agreement.

As of December 31, 2024,2025, we had an accumulated deficit of $3,646.9$2,964.2 million. We had a net income of $682.6 million for the year ended December 31, 2025, and a net loss of $363.3 million, $626.6 million,million and $559.0a net loss of $626.6 million for the fiscal years ended December 31, 2024, 20232024 and 2022,2023, respectively.

We anticipate that we will continue to incur significant expenses in connection with our commercialization efforts in the United States, the EEA, Latin AmericaAmerica, Japan and other territories, including expenses related to our commercial infrastructure and corresponding sales and marketing, legal and regulatory, and distribution and manufacturing undertakings as well as administrative and employee-based expenses. In addition to the foregoing, we expect to continue to incur significant costs in connection with ongoing, planned and potential future clinical trials and studies for sepiapterin and our splicing and inflammation and ferroptosis programs as well as studies in our products for maintaining authorizations, label extensions and additional indications. WeIn continueAugust to seek marketing authorization for Translarna for2025, the treatmentFDA of nmDMD in territories that we do not currently have marketing authorization in and we are exploring other potential mechanisms by which we may provide Translarna to nmDMD patients in the EEA if the EC adopts the CHMP’s negative opinion for Translarna followingissued a re-examinationcomplete procedure.response Weletter also submitted an MAArelated to the EMANDA stating that substantial evidence of efficacy was not demonstrated for sepiapterinvatiquinone forand the treatment of PKU in March 2024,that an additional adequate and well-controlled study would be needed to support NDA toresubmission. We met with the FDA for sepiapterin for the treatment of PKU in the third quarter of 2024, and an NDA to the FDA for vatiquinione for the treatment of FA in the fourth quarter of 2024.2025 Theseto efforts may significantly impactdiscuss the timingvatiquinone anddevelopment extentprogram. FDA suggested an additional study be conducted to support NDA resubmission. FDA stated in the meeting minutes that this study could be an open label study with a natural history control group. We plan to meet with FDA in the second quarter of our2026 commercializationto anddiscuss manufacturingthe expenses.design of this new study.

With respect to our outstanding 2026 Convertible Notes, cash interest payments are payable on a semi-annual basis in arrears, which will require total funding of $4.3 million annually. BorrowingsThese undernotes theare Blackstonecurrently Credit Agreement, which was terminated in October 2023, bore interest at a variable rate equal to, at our option, either an adjusted Term SOFR rate plus sevenconvertible and awill quartermature percentand (7.25%)become due and payable on September 15, 2026 unless earlier redeemed or the Base Rate plus six and a quarter percent (6.25%), subject to a floor of one percent (1%) and two percent (2%) with respect to Term SOFR rate and Base Rate (each as defined in the Blackstone Credit Agreement), respectively.converted.

In MayJune 2024,2025, weSephience announcedwas thegranted validationmarketing and acceptance for review of an MMA for sepiapterinauthorization by the EMAEC for the treatment of PKU.children Inand connectionadults living with thisPKU. event and pursuantPursuant to the Censa Merger Agreement, wethe paidapproval triggered a $15.0$25.0 million regulatorymilestone milestonepayable to the former Censa securityholders. In July 2024,2025, weSephience announcedwas the submission of an NDA to thegranted FDA for sepiapterinapproval for the treatment of pediatricchildren and adultadults patientsliving with PKU, including the full spectrum of ages and disease subtypes.PKU. Pursuant to the Censa Merger Agreement, the decision to submit the NDAapproval triggered a $25.0$32.5 million regulatory milestone payment to the former Censa securityholders. InAs Septemberof 2024,December 31, 2025, we announced the FDA acceptance for filing of the NDA. In connection with this event and pursuant to the Censa Merger Agreement, wehave paid a $25.0 million regulatory milestone to the former Censa securityholders.securityholders all potential regulatory milestones relating to Sephience.

We have never been profitable and we will need to generate significant revenues to achieve and sustain profitability, and we may never do so. Accordingly, we may need to obtain substantial additional funding in connection with our continuing operations. Adequate additional financing may not be available to us on acceptable terms, or at all. If we are unable to raise capital when needed or on attractive terms, we could be forced to delay, reduce or eliminate our research and development programs or our commercialization efforts.

To date, our net product revenues have consisted primarily of sales of Translarna for the treatment of nmDMD in territories outside of the United States, and sales of Emflaza for the treatment of DMD in the United States. Beginning in the second half of 2025, our net product revenues also includes Sephience for the treatment of PKU. There is a substantial risk that as a result of the EC’s adoption of the CHMP’s negative opinion we will lose a significant portion of our ability to generate revenue from sales of Translarna in the EEA. Our process for recognizing revenue is described below under “Critical accounting policies and significant judgments and estimates—Revenue recognition”.

Roche and the SMA Foundation Collaboration. In November 2011, we entered into the SMA License Agreement pursuant to which we are collaborating with Roche and the SMA Foundation to further develop and commercialize compounds identified under our SMA program with the SMA Foundation. The research component of this agreement terminated effective December 31, 2014. We are eligible to receive additional payments from Roche if specified events are achieved with respect to each licensed product, including up to $135.0 million in research and development event milestones, up to $325.0 million in sales milestones upon achievement of specified sales events, and up to double digit royalties on worldwide annual net sales of a commercial product. As of December 31, 2024,2025, we had recognized a total of $310.0 million in milestone payments and $545.6$789.8 million in royalties on net sales pursuant to the SMA License Agreement. As of December 31, 2024,2025, there are no remaining research and development event milestones that we can receive. The remaining potential sales milestones as of December 31, 20242025 are $150.0 million upon achievement of certain sales events.

Novartis Collaboration. On November 27, 2024, we and Novartis entered into the Novartis Agreement relating to our PTC518votoplam HD program which includes related molecules. Under the Novartis Agreement, and upon the closing of the transaction contemplated by the Novartis Agreement in January 2025, we received an upfront payment of $1.0 billion on the effective date and can receive up to $1.9 billion in development, regulatory and sales milestones, a 40% share of U.S. profits and losses, and tiered double-digit royalties on ex-U.S. sales. See “Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations—Liquidity and capital resources—Sources of Liquidityliquidity” for additional information.

We expect our research and development expenses to fluctuate in connection with our ongoing activities, particularly in connection with our activities for sepiapterin and our splicing and inflammation and ferroptosis programs and performance of any post-marketing requirements imposed by regulatory agencies with respect to our products. The timing and amount of these expenses will depend upon the outcome of our ongoing clinical trials and the costs associated with our planned clinical trials. The timing and amount of these expenses will also depend on the costs associated with potential future clinical trials of our products or product candidates and the related expansion of our research and development organization, regulatory requirements, advancement of our preclinical programs, and product and product candidate manufacturing costs. In 2023, as part of our strategic pipeline prioritizations, we decided to discontinue our preclinical and early research programs for our gene therapy and oncology platforms, reducing research and development expenses in these areas.

For the year ended December 31, 2024,2025, compared to the years ended December 31, 20232024 and 2022,2023, the decreasechanges inreflect developmentprogressing expensesthrough primarilydifferent reflectedphases theof decrease in program spend related to our strategic pipeline prioritization in 2023studies as we continuedcontinue to focus our resources on our differentiated, high potential research and development programs. The decrease is primarily due to a decrease relating to Global DMD, Gene Therapy, and Splicing platform, offset by an increase in Sephience related development.

For the year ended December 31, 2024,2025, compared to the years ended December 31, 20232024 and 2022,2023, the decrease in research expenses was primarily related to our strategic pipeline prioritization in 2023 where we discontinued several preclinical and early research programs. The decrease also reflects our continued focus of our resources on product candidates approaching approval during the current year periods.

For the year ended December 31, 2024,2025, compared to the years ended December 31, 20232024 and 2022,2023, the increasechanges in milestone expenses primarily related to no milestones expensed in year the ended December 31, 2025, as compared to the achievement of a $15.0 million success-based regulatory milestone for the validation and acceptance of an MMA for sepiapterinSephience for PKU in May 2024, the achievement of a $25.0 million regulatory milestone for the decision to submit an NDA to the FDA for sepiapterinSephience for PKU in July 2024, and the achievement of a $25.0 million regulatory milestone for the acceptance of an NDA toby the FDA for sepiapterinSephience for PKU in September 2024, as compared to the achievement of a $30.0 million success-based development milestone for the completion of enrollment of a Phase 3 clinical trial for sepiapterinSephience for PKU in February 2023, and no milestones achieved in the year ended December 31, 2022.2023.

Payroll, benefits, and share-based stock compensation. Consists of costs incurred for salaries and wages, bonus, payroll taxes, benefits and stock-basedshare-based stock compensation associated with employees involved in research and development activities. Stock-basedShare-based stock compensation may fluctuate from period to period based on factors that are not within our control, such as our stock price on the dates stock-basedshare-based grants are issued.

For the year ended December 31, 2024,2025, compared to the years ended December 31, 20232024 and 2022,2023, the change in facilities and other expenses primarily related to decreases in facility-based expenses at our facility in Hopewell Township, New Jersey as a result of an amendment and restatement of our lease for such facility.facility and at our facility in Warren, New Jersey as a result of an amendment to our lease for such facility in the year ended December 31, 2024.

Interest expense, net consists of interest expense from the liability for the sale of future royalties related to the Original Royalty Purchase Agreement, the A&R Royalty Purchase Agreement, the 2026 Convertible Notes outstanding,outstanding and the Blackstone Credit Agreement that we repaid and terminated in October 2023, the 3.00% convertible senior notes due 2022, or the 2022 Convertible Notes, that we repaid in August 2022, offset by interest income earned on investments.

Net product revenues. Our net product revenue primarily consists of sales of Translarna in territories outside of the U.S. and sales of Emflaza in the U.S., both for the treatment of DMD. Beginning in the second half of 2025, our net product revenues also includes sales of Sephience for the treatment of PKU. We recognize revenue when performance obligations with customers have been satisfied. Our performance obligations are to provide products based on customer orders from distributors, hospitals, specialty pharmacies or retail pharmacies. The performance obligations are satisfied at a point in time when our customer obtains control of the product, which is typically upon delivery. We invoice customers after the products have been delivered and invoice payments are generally due within 30 to 90 days of invoice date. We determine the transaction price based on fixed consideration in its contractual agreements. Contract liabilities arise in certain circumstances when consideration is due for goods not yet provided. As we have identified only one distinct performance obligation, the transaction price is allocated entirely to the product sale. In determining the transaction price, a significant financing component does not exist since the timing from when we deliver product to when the customers pay for the product is typically less than one year. Customers in certain countries pay in advance of product delivery. In those instances, payment and delivery typically occur in the same month.

Sephience (sepiapterin) is a product for the treatment of phenylketonuria, or PKU, a rare inherited metabolic disease characterized by the body’s inability to break down an essential amino acid called phenylalanine, and which can result in neurological and other symptoms. In June 2025, Sephience was granted marketing authorization by the European Commission, or EC, for the treatment of children and adults living with PKU within the European Economic Area, or EEA. In July 2025, Sephience was approved by the U.S. Food and Drug Administration, or FDA, for the treatment of pediatric and adult patients living with PKU in the United States age one month and above. In December 2025, Sephience was approved by the Japanese Ministry of Health, Labor and Welfare, or MHLW, for the treatment of children and adults living with PKU in Japan, where the label includes individuals of all ages and the full spectrum of disease severity. In February 2026, Sephience was approved by ANVISA, the Brazilian health regulatory authority, for the treatment of children and adults living with PKU in Brazil. Sephience is also approved in additional geographies. During the three months ended MarchJune 31,30, 2026, we recognized $124.6$151.3 million in net sales of Sephience.

Translarna is an investigational new drug in the United States. In 2017, we filed ana new drug application, or NDA, for Translarna for the treatment of nmDMD over protest with the FDA and in October 2017, the Office of Drug Evaluation I of the FDA issued a complete response letter for the NDA, stating that it was unable to approve the application in its current form. We re-submitted the NDA in July 2024 and in October 2024, the FDA accepted for review the resubmission of the NDA for Translarna for the treatment of nmDMD. Following feedback from the FDA, we decided to withdraw the NDA resubmission for Translarna in February 2026. Further development of Translarna for the treatment of nmDMD in the United States is not planned.

Translarna has marketing authorization in additional geographies outside of the EEA, though the EC adoption of the CHMP negative opinion and the withdrawal of the Translarna NDA in the United States may affect future reauthorizations. During the three months ended MarchJune 31,30, 2026, we recognized $59.0$42.2 million in net sales for Translarna. Emflaza is approved in the United States for the treatment of DMD in patients two years and older. During the three months ended MarchJune 31,30, 2026, we recognized $21.5$24.6 million in net sales for Emflaza.

We have previously relied on Emflaza’s seven-year marketing exclusivity period in the United States for its approved indications under the provisions of the Orphan Drug Act of 1983, or the Orphan Drug Act, when commercializing Emflaza for the treatment of DMD in patients five years and older, which expired in February 2024. With the expiration of this orphan drug exclusivity, we have seen an increase in competition from generics, which has, and we expect will continue to have, a negative impact on Emflaza net product revenue. Emflaza’s orphan drug exclusivity related to the treatment of DMD in patients two years of age to less than five expiresexpired in June 2026.

We hold the rights for the commercialization of Tegsedi and Waylivra for the treatment of rare diseases in countries in Latin America and the Caribbean pursuant to a Collaboration and License Agreement, or the Tegsedi-Waylivra Agreement, dated August 1, 2018, by and between us and Akcea Therapeutics, Inc., or Akcea, a subsidiary of Ionis Pharmaceuticals, Inc. Tegsedi has received marketing authorization in the United States, EU, and Brazil for the treatment of stage 1 or stage 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis, or hATTR amyloidosis. In August 2021, ANVISA, the Brazilian health regulatory authority, approved Waylivra as the first treatment for familial chylomicronemia syndrome, or FCS, in Brazil. Waylivra has also received marketing authorization in the EU for the treatment of FCS. In December 2022, ANVISA approved Waylivra for the treatment of familial partial lipodystrophy, or FPL.lipodystrophy.

In November 2024, we entered into a License and Collaboration Agreement with Novartis Pharmaceuticals Corporation, or Novartis, relating to our votoplam program, or the Novartis Agreement, which included related molecules. While Novartis has taken over responsibility for the further development of the votoplam program, we continue to collaborate with Novartis on next steps. In May 2025, we announced that the Phase 2 study of votoplam met its primary endpoints of blood HTT lowering and safety. The results on the full study population are consistent with the previously reported evidence of dose-dependent HTT lowering, favorable safety profile and early signals of dose-dependent clinical effect at 12 months in Stage 2 patients. In addition, at 24 months of treatment, there were continued trends of dose-dependent favorable clinical effect relative to a propensity-matched natural history cohort as well as dose-dependent NfL lowering. In the fourth quarter of 2025, an End-of-Phase 2 meeting was held with the FDA, and we reached alignment on design of a global Phase 3 clinical trial. In April 2026, Novartis announced that it had commenced the global Phase 3 study.clinical trial, which is expected to enroll approximately 770 individuals with early symptomatic disease, randomized 3:2 to receive votoplam 10 milligrams or placebo, and includes an interim analysis. Also in April 2026, we reported positive topline results from the 24-month interim analysis of the PIVOT-HD long-term extension study, with favorable dose-dependent effects on disease progression for Stage 2 HD patients following 24 months of votoplam treatment compared to an external natural history cohort, with 52% slowing of disease progression on the Composite Unified Huntington’s Disease Rating Scale at the 10 milligram dose level. WeWhile andthe Phase 3 clinical trial remains the base case for votoplam approval, we are working with Novartis willto continuefinalize a plan to reviewengage with FDA to discuss the data24-month andresults discussin potentialthe regulatorysecond interactions.half of 2026.

Our inflammation and ferroptosis platform consists of small molecule compounds that target oxidoreductase enzymes that regulate oxidative stress and inflammatory pathways central to the pathology of a number of CNS and non-CNS diseases. The most advanced molecule in our inflammation and ferroptosis platform is vatiquinone. We announced topline results from a registration-directed Phase 3 trial of vatiquinone in children and young adults with Friedreich’s ataxia, or FA, called MOVE-FA, in May 2023. While the trial did not meet its primary endpoint, vatiquinone treatment did demonstrate significant benefit on key disease subscales, including the upright stability subscale, as well as on other disease relevant endpoints. In October 2024, we announced that the pre-specified endpoint for two different FA long-term extension studies was met, with statistically significant evidence of durable treatment benefit on disease progression. In December 2024, we submitted an NDA to the FDA for vatiquinone for the treatment of children and adults living with FA. In August 2025, the FDA issued a complete response letter related to the NDA stating that substantial evidence of efficacy was not demonstrated for vatiquinone and that an additional adequate and well-controlled study would be needed to support NDA resubmission. We met with the FDA in the fourth quarter of 2025 to discuss the vatiquinone development program, at which time the FDA suggested an additional study be conducted to support NDA resubmission. In April 2026, we again met with FDA to discuss the design of a new trial to provide additional data to support NDA resubmission. Based on the meeting discussion and written feedback, we plan to initiate anthe PROVE-FA open label study using matched natural history control in the third quarter of 2026. This study is expected to enroll approximately 120 patients ages 7 to 21 and the study primary endpoint is the change in mFARS from baseline to month 24.

In November 2024, we entered into the Novartis Agreement relating to our votoplam HD program which includes related molecules. Novartis is responsible for all other development of licensed compounds and licensed products and the manufacture and commercialization of licensed compounds and licensed products worldwide. While Novartis has taken over responsibility for the further development of the votoplam program, we continue to collaborate with Novartis on next steps. Under the Novartis Agreement, and upon the closing of the transaction contemplated by the Novartis Agreement in January 2025, we received an upfront payment of $1.0 billion on the effective date and we are eligible to receive up to $1.9 billion in development, regulatory and sales milestones, a 40% share of U.S. profits and losses, and tiered double-digit royalties on ex-U.S. sales. We have also recognized revenue associated with milestone payments from Novartis pursuant to the Novartis Agreement. In April 2026, Novartis notified us that it had initiated the first Phase 3 clinical trial for a Licensed Product (as defined in the Novartis Agreement), which pursuant to the Novartis Agreement, triggered a $50.0 million milestone payment to us. The $50.0 million development milestone is recorded as collaboration and license revenue for the three and six months ended June 30, 2026.

In August 2019, we entered into an At the Market Offering Sales Agreement, or the Sales Agreement, with Cantor Fitzgerald and RBC Capital Markets, LLC, or together, the Sales Agents, pursuant to which, we may offer and sell shares of our common stock, having an aggregate offering price of up to $125.0 million from time to time through the Sales Agents by any method that is deemed to be an “at the market offering” as defined in Rule 415(a)(4) promulgated under the Securities Act of 1933, as amended, or the Securities Act. During the three and six months ended MarchJune 31,30, 2026, we did not issue or sell any shares of common stock pursuant to the Sales Agreement. The remaining shares of our common stock available to be issued and sold, under the Sales Agreement, have an aggregate offering price of up to $93.0 million as of MarchJune 31,30, 2026.

As of MarchJune 31,30, 2026, we had an accumulated deficit of $2,967.0$2,883.5 million. We had a net loss of $2.8 million and net income of $866.6$80.7 million and $801.7 million for the threesix months ended MarchJune 31,30, 2026 and 2025, respectively.

We also have certain significant contractual obligations and commercial commitments that require funding and we have disclosed these items under the heading “Management’s Discussion and Analysis of Financial Condition and Results of Operations-Funding Obligations” in our 2025 Annual Report. There were no material changes to these obligations and commitments during the period ended MarchJune 31,30, 2026. Furthermore, since we are a public company, we have incurred and expect to continue to incur additional costs associated with operating as such including significant legal, accounting, investor relations and other expenses.

During the three and six months ended MarchJune 31,30, 2026 and 2025, net product revenues consisted of the following:

Disaggregated net product revenues by country for the three and six months ended MarchJune 31,30, 2026 and 2025, are as follows:

For thethree threeand six months ended MarchJune 31,30, 2026, three of our distributors each accounted for over 10% of our net product sales. For thethree threeand six months ended MarchJune 31,30, 2025, three and two of our distributorsdistributors, respectively, each accounted for over 10% of our net product sales.

Roche and the SMA Foundation Collaboration. In November 2011, we entered into the SMA License Agreement pursuant to which we are collaborating with Roche and the SMA Foundation to further develop and commercialize compounds identified under our SMA program with the SMA Foundation. The research component of this agreement terminated effective December 31, 2014. We are eligible to receive additional payments from Roche if specified events are achieved with respect to each licensed product, including up to $135.0 million in research and development event milestones, up to $325.0 million in sales milestones upon achievement of specified sales events, and up to double digit royalties on worldwide annual net sales of a commercial product. As of MarchJune 31,30, 2026, we had recognized a total of $310.0 million in milestone payments and $836.6$907.7 million in royalties on net sales pursuant to the SMA License Agreement. As of MarchJune 31,30, 2026, there are no remaining research and development event milestones that we can receive. The remaining potential sales milestones as of MarchJune 31,30, 2026 are $150.0 million upon achievement of certain sales events.

For the three and six months ended MarchJune 31,30, 2026 and 2025, we did not recognize collaboration revenue related to the SMA License Agreement with Roche.

For the three and six months ended MarchJune 31,30, 2026 and 2025,2026, we recognized $46.8$71.1 million and $36.4$117.9 million of royalty revenue, respectively, related to Evrysdi. For the three and six months ended June 30, 2025, we recognized $57.6 million and $94.0 million of royalty revenue, respectively, related to Evrysdi.

Novartis Collaboration for votoplam HD. In November 2024, we entered into the Novartis Agreement with Novartis related to our votoplam HD program. Upon the closing of the transaction contemplated by the Novartis Agreement in January 2025, we received an upfront payment of $1.0 billion on the effective date and are eligible to receive up to $1.9 billion in development, regulatory and sales milestones, a 40% share of U.S. profits and losses, and tiered double-digit royalties on ex-U.S. sales. During the three and six months ended MarchJune 31,30, 2026, we recognized $0.1$50.6 million and $50.7 million in license revenues, respectively, primarily related to worka performeddevelopment milestone pursuant to our Novartis Agreement for Novartis.Novartis’s initiation of the first Phase 3 clinical trial for a Licensed Product (as defined in the Novartis Agreement), which triggered a $50.0 million milestone payment to us. During the three and six months ended MarchJune 31,30, 2025, we recognized $989.8$2.9 million and $992.7 million in license revenuesrevenues, respectively, related to performance obligations completed pursuant to the Novartis Agreement. Collaboration and license revenue during the three months ended MarchJune 31,30, 2025, was partially offset by $3.6$3.5 million related to a refund for a prior collaboration arrangement in relation to votoplam.

The following table provides research and development expense for our most advanced principal product development programs, for the three and six months ended MarchJune 31,30, 2026 and 2025.

For the three and six months ended MarchJune 31,30, 2026, compared to the three and six months ended MarchJune 31,30, 2025, the changes reflect progressing through different phases of studies as we continue to focus our resources on our differentiated, high potential research and development programs. The decrease is primarily due to a decrease in costs relating to Global DMD, Gene Therapy, Splicing platform, Inflammation & Ferroptosis platform, and Sephience related development.

For the three and six months ended MarchJune 31,30, 2026, compared to the three and six months ended MarchJune 31,30, 2025, the decreaseincrease in research expenses primarily reflectedrelated ourto continuedincreased focusinvestment in research programs and advancement of our resources on product candidates approaching approval during the currentclinical year periods.pipeline.

For the three and six months ended MarchJune 31,30, 2026, compared to the three and six months ended MarchJune 31,30, 2025, the increase in payroll, benefits, and share-based stock compensation expenses primarily related to an increase in share-based stock compensationcompensation, and increases in salaries due to annual merit increases for the three and six months ended MarchJune 31,30, 2026 compared to the three and six months ended MarchJune 31,30, 2025.

Facilities and other.other indirect costs. Consists of indirect costs incurred for the benefit of multiple programs, including information technology, and other facility-based expenses, such as rent expense.

For the three months ended MarchJune 31,30, 2026, compared to the three months ended MarchJune 31,30, 2025, the change in facilities and other expensesindirect costs was relatively flat. For the six months ended June 30, 2026, compared to the six months ended June 30, 2025, the change in facilities and other indirect costs was related to new leases that commenced in the second half of 2025.

Interest expense, net consists of interest expense from the liability for the sale of future royalties related to the A&R Royalty Purchase AgreementAgreement, the 2026 Convertible Notes outstanding, and the 20262031 Convertible Notes outstanding, partially offset by interest income earned on investments.

During the three and six months ended MarchJune 31,30, 2026, there were no material changes to our critical accounting policies as reported in our 2025 Annual Report.

Three months ended MarchJune 31,30, 2026 compared to the three months ended MarchJune 31,30, 2025

The following table summarizes revenues and selected expense and other income data for the three months ended MarchJune 31,30, 2026 and 2025.

Net product revenue. Net product revenue was $225.6$238.8 million for the three months ended MarchJune 31,30, 2026, an increase of $72.1$120.5 million, or 47%,over 100%, from $153.4$118.3 million for the three months ended MarchJune 31,30, 2025. The increase in net product revenue was primarily due to an increase in net product sales of $151.3 million for Sephience, which is in the first year of its launch, partially offset by a decrease in net product sales of $11.7 million for Emflaza and $17.3 million for Translarna. The decrease in Emflaza sales is primarily driven by additional generic competition. The decrease in Translarna sales is primarily due to the EC’s adoption of the CHMP’s negative opinion.

Collaboration and license revenue. Collaboration and license revenue was $0.1$50.6 million for the three months ended MarchJune 31,30, 2026, aan decreaseincrease of $986.1$47.7 million, or over 100%, from $986.2$2.9 million for the three months ended MarchJune 31,30, 2025. For the three months ended MarchJune 31,30, 2026, we recognized $0.1$50.6 millionmillion, primarily related to worka performeddevelopment milestone. In April 2026, Novartis notified the Company that it had initiated the first Phase 3 clinical trial for Novartis.a Licensed Product (as defined in the Novartis Agreement). Pursuant to the Novartis Agreement, this triggered a $50.0 million milestone payment to us. For the three months ended MarchJune 31,30, 2025, we recognized $989.8$2.9 million related to license revenue from the Novartis Agreement which was partially offset by $3.6 million related to a refund for aperformance priorobligations collaborationcompleted arrangementduring inthe relation to votoplam.period.

Royalty revenue. Royalty revenue was $46.8$71.1 million for the three months ended MarchJune 31,30, 2026, an increase of $10.4$13.5 million, or 29%,23%, from $36.4$57.6 million for the three months ended MarchJune 31,30, 2025. The increase in royalty revenue was due to higher Evrysdi sales in the three months ended MarchJune 31,30, 2026 as compared to the three months ended MarchJune 31,30, 2025. In accordance with the SMA License Agreement, we are entitled to recognize royalties on worldwide annual net sales of the product, which royalties have been sold.product. See “Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations—Overview—Corporate Updates—Funding.”

Cost of product, collaboration and license sales, excluding amortization of acquired intangible assets. Cost of product, collaboration and license sales, excluding amortization of acquired intangible assets was $28.0$19.9 million for the three months ended MarchJune 31,30, 2026, an increase of $15.2$8.5 million, or over 100%,74%, from $12.9$11.4 million for the three months ended MarchJune 31,30, 2025. Cost of product, collaboration and license sales, excluding amortization of acquired intangible assets during the periods consistedconsists primarily of the costs associated with the Novartis agreement, as well as production costs, royalty payments,payments associated with Sephience and Upstaza/Kebilidi net product sales, costs associated with sales of Emflaza,Sephience, Translarna, Sephience,Upstaza/Kebilidi, and Upstaza/Kebilidi.Emflaza product sold during the period, as well as the production costs associated with these products. The increase was primarily duedriven to costs associated withby the Novartisincrease agreement,in Upstaza/Kebilidinet product sales, which impacted the cost for products sold and royalty payments,expense andfor coststhe associated with new product launches and sales.period.

Amortization of acquired intangible assets. Amortization of acquired intangible assets was $11.6$11.8 million for the three months ended MarchJune 31,30, 2026, an increase of $7.8 million, or over 100%, from $3.8$4.1 million for the three months ended MarchJune 31,30, 2025. The increase to the intangible assets balance was primarily related to Upstaza/ Kebildi and Sephience intangible assets recorded as a result of the regulatory approvals and net sales milestones as well as the Censa Rights Satisfaction Agreement, which increased the corresponding amortization for those assets.

Research and development expense. Research and development expense was $100.9$99.2 million for the three months ended MarchJune 31,30, 2026, a decrease of $8.1$13.8 million, or 7%,12%, from $109.0$113.0 million for the three months ended MarchJune 31,30, 2025. The decrease in research and development expenses primarily related to decreases in development program spend as we continued to focus our resources on our differentiated, high potential research and development programs.

Selling, general and administrative expense. Selling, general and administrative expense was $86.2$80.6 million for the three months ended MarchJune 31,30, 2026, ana increasedecrease of $5.2$4.6 million, or 6%,5%, from $81.0$85.3 million for the three months ended MarchJune 31,30, 2025. The increasedecrease reflectedis ourprimarily continued investmentdue to supporta ourdecrease commercialin activities,selling includingexpenses ourrelated expandingto commercialprelaunch portfolio.activities for Sephience.

Tangible asset impairment and losses on transactions, net. Tangible asset impairment and losses on transactions, net wasdecreased $0.9 million for the three months ended March 31, 2026, an increase of $0.8$0.1 million, or over 100%, from $0.1 million for the three months ended MarchJune 31,30, 2025. The increasedecrease in tangible asset impairment and losses on transactions primarily related to no impairments and gains or losses during the three months ended June 30, 2026 as compared to $0.1 million loss on lease terminations and a $0.8 million loss related to inventoryfixed asset impairments in the three months ended MarchJune 31, 2026 as compared to $0.1 million loss on sales of fixed assets in the three months ended March 31,30, 2025.

Interest expense, net. Interest expense, net was $49.0$48.5 million for the three months ended MarchJune 31,30, 2026, an increase of $14.9$18.1 million, or 44%,60%, from $34.1$30.4 million for the three months ended MarchJune 31,30, 2025. The increase in interest expense, net was primarily due to an increase in interest expense related to the liability for the sale of future royalties related to the A&R Royalty Purchase Agreement.

Other income (expense),expense, net. Other income,expense, net was $1.6$3.0 million for the three months ended MarchJune 31,30, 2026, a changedecrease of $7.9$2.8 million, or over 100%,49%, from other expense, net of $6.3$5.7 million for the three months ended MarchJune 31,30, 2025. The changedecrease in other incomeexpense, (expense), netnet, primarily relatedrelates to net realized and unrealized gains onfrom foreign currency of $1.4$0.4 million for the three months ended MarchJune 31,30, 2026, a change of $7.8 million, compared to net realized and unrealized losslosses onfrom foreign currency of $6.4$8.7 million for the three months ended MarchJune 31,30, 2025. This decrease was partially offset by an inducement expense of $3.4 million related to the repurchase of a portion of the 2026 Convertible Notes and other items of $2.8 million.

Income tax expense.(expense) benefit. Income tax expense was $0.3$14.0 million for the three months ended MarchJune 31,30, 2026, a decreasechange of $62.9$20.3 million, or 99%,over 100%, compared to income tax expensebenefit of $63.3$6.2 million for the three months ended MarchJune 31,30, 2025. The decreasechange in income tax (expense) benefit was driven by the projected utilization of additional tax attributes in 2026 as a result of the provisions within the One Big Beautiful Bill Act, as well as recognition of revenue associated with the A&R Royalty Purchase Agreement.