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Item 1A. Risk Factors

2026-02-25 compared with 2025-02-21 · 162 added, 94 removed, 472 unchanged (35% of the section changed)

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Risks Related to Clinical Development

We are a biopharmaceutical company with no approved products and no historical commercial revenue, which makes it difficult to assess our future prospects and financial results.

We are a biopharmaceutical company with a somewhat limited operating history as a publicly traded company.

Biopharmaceutical product development is a highly speculative undertaking and involves a substantial degree of uncertainty.

Our operations to date have been limited to developing our technology, undertaking pre-clinical studies and clinical trials of our pipeline candidates and conducting research to identify additional product candidates.

We have not yet successfully developed an approved product or generated revenue from product sales or successfully conducted a pivotal registration trial for one of our product candidates.

Consequently, the ability to accurately assess our future operating results or business prospects is significantly more limited than if we had a longer operating history or approved products on the market.

We expect that our financial condition and operating results will fluctuate significantly from period to period due to a variety of factors, many of which are beyond our control, including the success of our programs, decisions by regulatory bodies, actions taken by competitors or current or future licensees or collaborative partners, market and macroeconomic conditions and other factors identified in these risk factors.

Accordingly, the likelihood of our success must be evaluated in light of many potential challenges and variables associated with a clinical-stage biopharmaceutical company, many of which are outside of our control, and past results, including operating or financial results, should not be relied on as an indication of future results.

We are heavily dependent on the success of our product candidates in clinical development, and if any of these products fail to receive regulatory approval or are not successfully commercialized, our business would be adversely affected.

Our future success is substantially dependent on our ability and the ability of our collaborators to timely complete clinical trials and obtain marketing approval for, and then successfully commercialize, our clinical-stage product candidates, such as Icotyde and rusfertide.

We currently have no product candidates that are approved for commercial sale, and we may never develop a marketable product.

We expect that a substantial portion of our efforts and expenditures over the next few years will be devoted to our current product candidates and the development of other product candidates.

We cannot be certain that our product candidates will receive regulatory approval or, if approved, be successfully commercialized.

We expect that a substantial portion of our efforts and expenditures over the next few years will be devoted to our current product candidates and the development of other product candidates, including any product candidates resulting from our discovery and development program.

We cannot be certain that our product candidates will receive regulatory approval or, if approved, be successfully commercialized by us or our collaborators.

The research, testing, manufacturing, labeling, approval, sale, marketing and distribution of our product candidates will be subject to extensive regulation by the FDA and other regulatory authorities in the United States and other countries.

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We will need to successfully conduct and complete large, extensive clinical trials in the target patient populations to support a potential application for regulatory approval by the FDA or corresponding regulatory authorities.

Those trials, such as our ongoing VERIFY Phase 3 trial evaluating rusfertide for the treatment of PV or subsequent late-stage product candidates, may not demonstrate the safety and efficacy of our product candidates to support a marketing approval in the United States or other jurisdictions.

Those trials, such as our ongoing trials of Icotyde and rusfertide or subsequent late-stage product candidates, may not demonstrate the safety and efficacy of our product candidates for certain indications to support a marketing approval in the United States or other jurisdictions.

We do not have complete control over many of the factors upon which the successful development and commercialization of our product candidates will be dependent, including certain aspects of clinical development and the regulatory submission process, potential threats to our intellectual property rights and the manufacturing, marketing, distribution and sales efforts of our collaborators.

For product candidates that are licensed to third parties, including Icotyde and rusfertide, we generally will not have discretion over marketing decisions.

If we or our collaborators do not receive marketing approvals for our product candidates, we may not be able to continue our operations.

Our product candidates require additional clinical development, regulatory approval and secure sources of commercial manufacturing supply prior to commercialization.

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Moreover, any delay or setback in the development of any product candidate would be expected to adversely affect our business and cause our stock price to fall.

For example, our stock price dropped significantly in September 2021 following the announcement of a full clinical hold imposed by the FDA on our rusfertide clinical studies.

Our stock price also dropped significantly in April 2022 following the announcement of our voluntary withdrawal of Breakthrough Therapy Designation for rusfertide and the announcement of topline data from our Phase 2 clinical trial evaluating PN-943 in UC.

We are a biopharmaceutical company with no approved products and no historical commercial revenue, which makes it difficult to assess our future prospects and financial results.

Biopharmaceutical product development is a highly speculative undertaking and involves a substantial degree of uncertainty.

Our operations to date have been limited to developing our technology, undertaking pre-clinical studies and clinical trials of our pipeline candidates, conducting research to identify additional product candidates and entering into partnerships with collaborators for certain of our product candidates.

We have not yet successfully developed an approved product or generated revenue from product sales or successfully completed a pivotal registration trial for one of our product candidates.

We expect that our financial condition and operating results will fluctuate significantly from period to period due to a variety of factors, many of which are beyond our control, including the success of our programs, decisions by regulatory bodies, actions taken by competitors or current or future licensees or collaborators, market and macroeconomic conditions and other factors identified in these risk factors.

Accordingly, the likelihood of our success must be evaluated in light of many potential challenges and variables associated with a clinical-stage biopharmaceutical

company, many of which are outside of our control, and past results, including operating or financial results, should not be relied on as an indication of future results.

Clinical development is a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results.

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Further, given the patient populations for which we are developing therapeutics, we expect to have to evaluate long-term exposure to establish the safety of our therapeutics in a chronic-dose setting.

We have not yet completed a Phase 3 clinical trial or submitted an NDA.

As a result, we have no corporate history or track record of successfully completing these phases of the development cycle.

Product candidates in later stages of clinical trials may fail to show the desired safety and efficacy traits despite having progressed through pre-clinical studies and initial clinical trials.

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Based upon negative or inconclusive results, we may decide, or regulators may require us, to conduct additional clinical trials or pre-clinical studies.

In addition, success in clinical trials in a particular indication does not ensure that a product candidate will be successful in other indications.

Similarly, approval of a product candidate in a particular indication does not ensure that the product candidate will be successful in other indications currently being studied.

JNJ filed an NDA with the FDA in July 2025 and sought regulatory approval with additional global regulatory authorities thereafter for Icotyde in moderate-to-severe plaque psoriasis, and Takeda submitted an NDA for rusfertide for the treatment of PV in December 2025.

There can be no guarantee that the FDA or other regulatory authorities will ultimately approve these products.

For instance, the FDA could, where applicable, refuse to file our or our collaborators applications, require additional clinical or non-clinical data, request further analyses, conduct an advisory committee review, identify deficiencies following facility inspections, or issue a Complete Response Letter.

Moreover, results acceptable to support approval in one jurisdiction may be deemed inadequate by another regulatory authority to support regulatory approval in another jurisdiction.

To the extent that the results of the trials are not satisfactory to the FDA or comparable foreign regulatory authorities for support of a marketing application, we may be required to expend significant resources, which may not be available to us, to conduct additional trials in support of potential approval of our product candidates.

Even if regulatory approval is secured for a product candidate, the terms of such approval may limit the scope and use of the specific product candidate, which may also limit its commercial potential.

We may experience delays in ongoing clinical trials, and we do not know whether planned clinical trials will begin on time, need to be redesigned, enroll patients on time or be completed on schedule, if at all.

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Such authorities may impose a modification, suspension or termination due to a number of factors.

For example, our rusfertide clinical studies were subject to a three-week clinical hold by the FDA beginning in September 2021.

The clinical hold was triggered by a non-clinical finding in a 26-week rasH2 transgenic mouse model indicating benign and malignant subcutaneous skin tumors.

Also, in April 2022, the FDA indicated that it intended to rescind Breakthrough Therapy Designation for rusfertide in PV, and we voluntarily withdrew our request.

For additional information, see the risk factor entitled “Our product candidates may cause undesirable side effects or have other properties adversely impacting safety that delay or prevent their regulatory approval, restrict their approved labeling, or otherwise limit their commercial opportunity” below.

In addition, there are a significant number of global clinical trials in hematologic disorders that are currently ongoing, especially in Phases 2 and 3, making it highly competitive and challenging to recruit subjects.

Other companies targeting the same patient populations as our clinical trials for such medicines may make it more difficult for us to

complete enrollment in our clinical trials.

For example, our rusfertide clinical studies were subject to a three-week clinical hold by the FDA in September 2021.

In addition, there are a significant number of global clinical trials in inflammatory and immunology disorders, hematologic disorders and metabolic disorders that are currently ongoing, especially in Phases 2 and 3, making it highly competitive and challenging to recruit subjects.

Other companies targeting the same patient populations as our clinical

trials for such medicines may make it more difficult for us to complete enrollment in our clinical trials.

Furthermore, any negative results we may report in clinical trials of our product candidate may make it difficult or impossible to recruit and retain patients in other ongoing or subsequent clinical trials of that same product candidate.

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Our research programs may initially show promise in identifying potential product candidates yet fail to yield product candidates for clinical development for many reasons.

Our proprietary peptide platform may not result in any products of commercial value.

We have developed a proprietary peptide technology platform to enable the identification, testing, design and development of new product candidates.

Our proprietary technology platform may not result in any products of commercial value.

We have developed a proprietary technology platform to enable the identification, testing, design and development of new product candidates.

Our peptide platform may not yield additional product candidates that enter clinical development and, ultimately, become commercially valuable.

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We have focused our limited resources to pursue particular product candidates and indications, and consequently, we may fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success.

Because we have limited financial and managerial resources, we have historically focused on research programs and product candidates mainly on the development of rusfertide and the product candidates subject to our JNJ collaboration.

We have an ongoing commitment to optimize and focus resources toward our rusfertide program in PV.

addition, in keeping with our organizational prioritization of rusfertide in PV, plans to initiate trials of rusfertide in additional disease indications have been paused.

Because we have limited financial and managerial resources, we have historically focused on research programs and product candidates mainly for the development of rusfertide and the product candidates subject to our JNJ collaboration.

We have an ongoing commitment to optimize and focus resources on our drug discovery and development

programs addressing biologically and commercially validated targets.

In addition, in keeping with our organizational prioritization of rusfertide in PV, plans to initiate trials of rusfertide in additional disease indications have been paused.

As a result, we may forego or delay the pursuit of opportunities with other product candidates or for other indications that later prove to have greater commercial potential.

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Risks Related to our Financial Position and Capital Requirements

We have incurred a cumulative net loss since our inception and anticipate that we may incur significant losses in the future.

We have never generated any revenue from product sales and may never be profitable.

We have incurred a cumulative net loss since our inception and we may incur significant losses in the future.

We have never generated any revenue from product sales.

We have incurred a cumulative net operating loss since inception and may continue to incur operating losses in the future.

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We expect to continue to incur significant research, development and other expenses related to our ongoing operations and product development.

As a result, we expect to continue to incur losses in the future as we continue our development of, and seek regulatory approvals for, our product candidates.

We do not anticipate generating revenue from sales of products for a number of years, if ever, and we have not yet successfully completed registrational or pivotal clinical trials for our product candidates.

If any of our product candidates fail in clinical trials or do not gain regulatory approval or fail to achieve market acceptance, we may never become profitable.

Revenue we generate from our collaborations with JNJ, Takeda, and any future collaboration arrangements may not be sufficient to sustain our operations.

As a result, we may continue to incur losses in the future as we continue our development of, and seek regulatory approvals for, our product candidates.

To achieve profitability, we must, either directly or through collaboration relationships, meet certain milestones, successfully develop and obtain regulatory approval for one or more product candidates and effectively manufacture, market and sell any drugs we successfully develop.

Even if we or our collaborators successfully commercialize product candidates that receive regulatory approval, we may not be able to realize revenues at a level that would allow us to achieve or sustain profitability.

Accordingly, we may never generate significant revenue and, even if we do generate significant revenue, we may never achieve consistent profitability.

In addition, if any of our product candidates fail in clinical trials or do not gain regulatory approval or fail to achieve market acceptance, we may never become profitable.

Revenue we generate from our collaborations with JNJ, Takeda, and any future collaboration arrangements, if any, may not be sufficient to sustain our operations.

Failure to become and remain profitable may adversely affect the market price of our common stock and our ability to raise capital and continue operations.

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Further, in the event that the JNJ License and Collaboration Agreement or the Takeda Collaboration Agreement is terminated, we may not receive any additional fees or milestone payments under these agreements.

Absent the funding support obtained under these agreements, our further development of the collaboration product candidates would require significant additional capital from us, or the establishment of alternative collaborations with third parties, which may not be possible.

In addition, if either JNJ or Takeda fail to successfully commercialize Icotyde or rusfertide, respectively, if approved, we would not receive any royalty payments under these agreements.

Absent the funding support obtained under these agreements, our further development of the collaboration product candidates and our drug discovery and development programs would require significant additional capital from us, or the establishment of alternative collaborations with third parties, which may not be possible.

As of December 31, 2025, we had cash, cash equivalents and marketable securities of $646.0 million.

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However, we may need to have access to additional funds in the future in order to complete clinical development or commercialize our product candidates to a point where our operations generate net cash inflows.

Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our product candidates or technologies.

We have in the past and may in the future seek additional funding through a combination of equity offerings, including the use of the 2022 ATM Facility, debt financings, collaborations and/or licensing arrangements.

If we require additional capital, there may be dilution to our existing stockholders, our operations may be restricted, or we may be required to relinquish rights to our product candidates or technologies.

We have in the past and may in the future seek additional funding through a combination of equity offerings, debt financings, collaborations and/or licensing arrangements.

Additional funding may not be available to us on acceptable terms, or at all.

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and high interest rates.

The incurrence of indebtedness and/or the issuance of certain equity securities could result in fixed

payment obligations and could also result in certain additional restrictive covenants, such as limitations on our ability to incur debt and/or issue additional equity, limitations on our ability to acquire or license intellectual property rights and other operating restrictions that could adversely impact our ability to conduct our business.

The incurrence of indebtedness and/or the issuance of certain equity securities could result in fixed payment obligations and could also result in certain additional restrictive covenants, such as limitations on our ability to incur debt and/or issue additional equity, limitations on our ability to acquire or license intellectual property rights and other operating restrictions that could adversely impact our ability to conduct our business.

In addition, the issuance of additional equity securities by us, or the possibility of such issuance, may cause the market price of our common stock to decline.

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Risks Related to our Reliance on Third Parties

If JNJ does not elect to continue the development of icotrokinra, or if Takeda does not elect to develop and commercialize rusfertide, our business and business prospects would be adversely affected.

Icotrokinra, the product candidate in development pursuant to our JNJ collaboration, and rusfertide, the product candidate in development pursuant to the Takeda Collaboration Agreement, may prove to have undesirable or unintended side effects or other characteristics adversely affecting its safety, efficacy or cost effectiveness that could prevent or limit its approval for marketing and successful commercial use, or that could delay or prevent the commencement and/or completion of clinical trials.

If JNJ does not elect to continue the development of or successfully commercialize Icotyde, or if Takeda does not elect to commercialize rusfertide, our business and business prospects would be adversely affected.

Icotyde, the product candidate in development pursuant to the JNJ License and Collaboration Agreement, and rusfertide, the product candidate in development pursuant to the Takeda Collaboration Agreement, may prove to have undesirable or unintended side effects or other characteristics adversely affecting their safety, efficacy or cost effectiveness that could prevent or limit their approval for marketing and successful commercial use, or that could delay or prevent the commencement and/or completion of clinical trials.

Under the terms of the JNJ License and Collaboration Agreement, JNJ may terminate the agreement for convenience and without cause on written notice of a certain period.

In addition, prior to any termination of the agreement, JNJ will generally have control over the further clinical development of icotrokinra and any other licensed compounds.

JNJ’s decisions with respect to such development will affect the timing and availability of potential future payments under the agreement, if any.

For example, during the fourth quarter of 2021, a decision was made by JNJ to stop further development of both PTG-200 and PN-232 in favor of icotrokinra.

Under the terms of the Takeda Collaboration Agreement, Takeda may terminate the agreement for convenience in its entirety or as to a major region by providing advance written notice following the earliest of (i) the receipt of Phase 3 data with respect to the VERIFY clinical trial, (ii) the third anniversary of the effective date of the agreement or (iii) the occurrence of certain specified adverse events related to the clinical development of rusfertide.

If the JNJ License and Collaboration Agreement or the Takeda Collaboration Agreement is terminated early, or if JNJ’s or Takeda’s development activities are terminated early or suspended for an extended period of time, or are otherwise unsuccessful, our business and business prospects would be materially and adversely affected.

In addition, prior to any termination of the agreement, JNJ will generally have control over the further clinical development of Icotyde and any other licensed compounds and commercialization, if Icotyde is approved.

JNJ’s decisions with respect to such development and commercialization will affect the timing and availability of potential future payments under the agreement, if any.

Under the terms of the Takeda Collaboration Agreement, Takeda may terminate the agreement for convenience in its entirety or as to a major region by providing advance written notice to us.

If the JNJ License and Collaboration Agreement or the Takeda Collaboration Agreement are terminated early, if JNJ’s or Takeda’s development activities are terminated early or suspended for an extended period of time, or are otherwise unsuccessful, or if JNJ’s or Takeda’s commercialization efforts are deprioritized or unsuccessful, our business, financial condition and prospects would be materially and adversely affected.

We may have disagreements with JNJ during the term of the JNJ License and Collaboration Agreement or Takeda under the Takeda Collaboration Agreement, and if they are not settled amicably or in the favor of Protagonist, the result may harm our business.

We are subject to the risk of possible disagreements with JNJ regarding the development of icotrokinra or other matters under the JNJ License and Collaboration Agreement and Takeda regarding the development of rusfertide or other matters under the Takeda Collaboration Agreement, such as the interpretation of such agreement or ownership of proprietary rights.

Also, because the period of collaborative development under the agreement has ended, JNJ has sole decision-making authority for product candidates resulting from the collaboration, which could lead to disputes with JNJ.

We are subject to the risk of possible disagreements with JNJ regarding the development or commercialization of Icotyde, if approved, or other matters under the JNJ License and Collaboration Agreement and with Takeda regarding the development or commercialization of rusfertide, if approved, or other matters under the Takeda Collaboration Agreement, such as the interpretation of such agreements, milestones or royalty payments or ownership of proprietary rights.

Also, because the period of collaborative development under the agreement has ended, JNJ has sole decision-

making authority for product candidates resulting from the collaboration, which could lead to disputes with JNJ.

Disagreements with JNJ or Takeda could lead to litigation or arbitration, which would be expensive and would be time-consuming for our management and employees.

If agreements are not settled amicably or in our favor, our business, financial condition and prospects would be materially and adversely affected.

Our current and future development and commercialization collaborations may not be successful.

Other than our collaboration with JNJ License and Collaboration Agreement and our collaboration with Takeda under the Takeda Collaboration Agreement, we have no active collaborations for any of our product candidates.

Our collaborations with JNJ and Takeda and any future collaboration arrangements may not ultimately be successful, which could have a negative impact on our business, results of operations, financial condition and growth prospects.

Other than our collaboration with JNJ under the JNJ License and Collaboration Agreement and our collaboration with Takeda under the Takeda Collaboration Agreement, we have no active collaborations for any of our product candidates.

Our collaborations with JNJ and Takeda and any future collaboration arrangements may not ultimately be successful, which could have a material and adverse effect on our business, financial condition and prospects.

We do not maintain significant rights or control of future development and commercialization activities under our collaboration with JNJ, or in ex-U.S.

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We rely on contract manufacturers to manufacture and provide product for us that meets applicable regulatory requirements.

We do not currently have, nor do we plan to develop, the infrastructure or capability internally to manufacture our drug supplies and we expect to continue to depend on contract manufacturers for the foreseeable future.

We do not currently have, nor do we plan to develop, the infrastructure or capability internally to

manufacture our drug supplies and we expect to continue to depend on contract manufacturers for the foreseeable future.

As we proceed with the development and potential commercialization of our product candidates, we will need to increase the scale at which the drug is manufactured, which will require the development of new manufacturing processes to potentially reduce the cost of goods.

We will rely on our internal process research and development efforts and those of contract manufacturers to develop the required manufacturing processes for cost-effective, large-scale

We will rely on our internal process research and development efforts and those of contract manufacturers to develop the required manufacturing processes for cost-effective, large-scale production.

If we and our contract manufacturers are not successful in converting to commercial-scale manufacturing, then our product costs may not be competitive and the development and/or commercialization of our product candidates would be materially and adversely affected.

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Moreover, we currently do not have any agreements for the commercial production of these raw materials.

Additionally, the United States and other countries have imposed and may continue to impose new trade restrictions and export regulations, including the potential for tariffs applicable to pharmaceutical products and their inputs, which may make access to materials necessary to produce our product candidates more costly or difficult to acquire.

Although we generally do not begin a clinical trial unless we believe we have a sufficient supply of a product candidate to complete the clinical trial, any significant delay in the supply of a product candidate, or the raw material components thereof, for an ongoing clinical trial due to the need to replace a contract manufacturer or other third-party manufacturer could considerably delay completion of our clinical trials, product testing and potential regulatory approval of our product candidates.

Potential business combinations or other strategic transactions may disrupt our business or divert management’s attention.

From time to time in the ordinary course of business, we explore potential business combination transactions or other strategic transactions or collaborations with third parties.

The consummation and performance of any such future transactions or collaborations will involve risks, such as diversion of managerial resources from day-to-day operations, exposure to litigation from the counterparties to any such transaction, other third parties or our stockholders, misjudgment with respect to the value, higher than expected transaction costs or an inability to successfully consummate any such transaction or collaboration.

As a result of these risks, we may not be able to achieve the expected benefits of any such transaction or collaboration or deliver the value thereof to our stockholders.

If we are unsuccessful in consummating any such transaction or collaboration, we may be required to reevaluate our business only after we have incurred substantial expenses and devoted significant management time and resources.

Risks Related to Regulatory Process and Other Legal Compliance Matters

The regulatory approval processes of the FDA and comparable foreign authorities are lengthy and time consuming, and if we are ultimately unable to obtain regulatory approval for our product candidates, our business will be substantially harmed.

The regulatory approval processes of the FDA and comparable foreign authorities are lengthy and time consuming, and if we or our collaborators are ultimately unable to obtain regulatory approval for our product candidates, our business will be substantially harmed.

Our business is substantially dependent on our ability to successfully develop, obtain regulatory approval for and then successfully commercialize our product candidates.

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Approval policies, regulations and the types and amount of clinical and manufacturing data necessary to gain approval may change during the course of clinical development and may vary among jurisdictions.

We have not obtained regulatory approval for any product candidate and it is possible that none of our existing product candidates or any product candidates we have in development or may seek to develop in the future will ever obtain regulatory approval.

We have not obtained regulatory approval for any product candidate

and it is possible that none of our existing product candidates or any product candidates we have in development or may seek to develop in the future will ever obtain regulatory approval.

Our product candidates could fail to receive regulatory approval for many reasons, including the following:

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Any of the foregoing possibilities could materially harm the prospects for our product candidates and business and operations.

Disruptions at the FDA and other government agencies could negatively affect the review of our regulatory submissions, which could negatively impact our business.

The ability of the FDA to review and approve regulatory submissions can be affected by a variety of factors, including statutory, regulatory and policy changes, inadequate government budget funding levels or a reduction in the FDA’s workforce and its ability to hire and retain key personnel, disruptions caused by government shutdowns, public health crises, the FDA’s ability to accept the payment of user fees, and other events that may otherwise affect the FDA’s ability to perform routine functions.

There have been mass layoffs of federal employees since the start of the current presidential administration in January 2025, the full impact of which is unclear at this time.

Such disruptions could significantly impact the ability of the FDA or other regulatory authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business.

For example, during the U.S.

government shut down in October 2025, the FDA was not able to accept applications for new drugs, generics, biologics, biosimilars or medical devices that require payment of a user fee.

In addition, the presidential administration has made and is expected to continue to make changes in the leadership of various U.S.

federal regulatory agencies and changes to U.S.

federal government policy that have led to, in some cases, legal challenges and uncertainty around the funding, functioning and policy priorities of the U.S.

federal regulatory agencies, including the FDA.

We are unable to predict the extent to which the presidential administration may impose or seek to impose leadership or policy changes at the FDA or changes to rules and policies impacting our business and operations.

It is unclear how these executive actions or other potential actions by the federal government will impact the FDA or other regulatory authorities that oversee our business.

Government proposals to reduce or eliminate budgetary deficits may include reduced allocations to the FDA and other related government agencies.

These budgetary pressures may reduce the FDA’s ability to perform its responsibilities, which could result in delays in our clinical trial timelines.

If a significant reduction in the FDA’s workforce occurs or the FDA’s budget is significantly reduced, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions or take other actions critical to the development or approval of our product candidates, and any delay in the acceptance, review or approval of our investigational new drug applications, clinical trial applications, marketing applications, facility inspections or lot-release/testing activities, could delay or increase the cost of our clinical trials and product launches, if any, which could have a material adverse effect on our business.

We may fail to obtain additional orphan drug designations from the FDA and/or the EMA for our product candidates, as applicable, and even if we obtain such designations, we may be unable to maintain the benefits associated with orphan drug designation, including the potential for market exclusivity.

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In the case of the JNJ License and Collaboration Agreement or the Takeda Collaboration Agreement, we may elect to exercise our right to co-detail products, which would require us to establish a U.S.

If we are not successful in

commercializing our product candidates, either on our own or through collaborations with one or more third parties, our future revenue will be materially and adversely impacted.

If we are not successful in commercializing our product candidates, either on our own or through collaborations with one or more third parties, our future revenue will be materially and adversely impacted.

Recently enacted and future legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product candidates and affect the prices we may obtain.

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and public funding for cost effectiveness research, which may be used by government and private third-party payors to make coverage and payment decisions.

Political, economic and regulatory

developments may further complicate developments in healthcare systems and pharmaceutical drug pricing.

In addition, in May 2025, the currrent administration issued an executive order entitled “Delivering Most-Favored-Nation Prescription Drug Pricing to American Patients,” which, among other things, directs the HHS and other agencies to communicate most-favored-nation price targets to pharmaceutical manufacturers to bring prices for U.S.

patients in line with comparably developed

nations and to facilitate direct-to-consumer purchasing programs.

The HHS subsequently issued guidance indicating the MFN target price is the lowest price paid in an Organization for Economic Co-operation and Development country with a GDP per capita of at least 60% of the U.S.

GDP per capita.

It is currently unclear whether and to what extent these measures will be implemented and what impact any such implementation would have on our business.

Further, there can be no assurance that the current administration or future administrations will not pursue different or additional measures that could impact drug pricing in the United States.

Political, economic and regulatory developments may further complicate developments in healthcare systems and pharmaceutical drug pricing.

These developments could, for example, impact our potential licensing agreements as commercial and collaborative partners may also consider the impact of these pressures on their licensing strategies.

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We currently conduct, and intend to continue to conduct, a substantial portion of the clinical trials for our product candidates outside of the United States.

If approved, we may commercialize our product candidates abroad.

If approved, we or our collaborators may commercialize our product candidates abroad.

We will thus be subject to the risks of doing business outside of the United States.

We currently conduct, and intend to continue to conduct, a substantial portion of our clinical trials outside of the United States and, if approved, we intend to also market our product candidates outside of the United States.

We are thus subject to risks associated with doing business outside of the United States.

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If we are unable to anticipate and address these risks properly, our business and financial results will be harmed.

We may fail or elect not to commercialize our product candidates, even if approved.

We cannot be sure that, if our clinical trials for any of our product candidates are successfully completed, we will be able to submit an NDA to the FDA or that any NDA we submit will be approved by the FDA in a timely manner, if at all.

We or our collaborators may fail or elect not to commercialize our product candidates, even if approved.

We cannot be sure that, if our clinical trials for any of our product candidates are successfully completed, we or our collaborators will be able to submit an NDA to the FDA or that any NDA we or our collaborators submit will be approved by the FDA in a timely manner, if at all.

In July 2025, Johnson & Johnson filed an NDA with the FDA for the approval of Icotyde for the treatment of adults and pediatric patients 12 years of age and older with moderate-to-severe plaque psoriasis and in January 2026, we and Takeda filed an NDA with the FDA for the approval of rusfertide for the treatment of adults with PV.

After completing clinical trials for a product candidate in humans, a drug dossier is prepared and submitted to the FDA as an NDA, and includes all pre-clinical studies and clinical trial data relevant to the safety and effectiveness of the product at the suggested dose and duration of use for the proposed indication as well as manufacturing information, in order to allow the FDA to review such drug dossier and to consider a product candidate for approval for commercialization in the United States.

If we are unable to submit an NDA with respect to any of our current product candidates, if any NDA we submit is not approved by the FDA, or we elect not to file an NDA, or if we are unable to obtain any required state and local distribution licenses or similar authorizations, we will be unable to commercialize that product.

If we or our collaborators are unable to submit an NDA with respect to any of our current product candidates, if any NDA we or our collaborators submit is not approved by the FDA, or we or our collaborators elect not to file an NDA, or if we or our collaborators are unable to obtain any required state and local distribution licenses or similar authorizations, we will be unable to commercialize that product.

The FDA can and does reject NDAs and require additional clinical trials, even when product candidates achieve favorable results in Phase 3 clinical trials.

Also, we may be subject to pricing pressures from competitive products that could make it difficult or impossible for us to commercialize the product candidate successfully.

If we fail to commercialize any of our product candidates, our business, financial condition, results of operations and prospects may be materially and adversely affected.

If we or our collaborators fail to commercialize any of our product candidates, our business, financial condition, results of operations and prospects may be materially and adversely affected.

The commercial success of any current or future product candidate will depend upon the degree of market acceptance by physicians, patients, third-party payors and others in the medical community.

We or our collaboration partners in any potential commercial launch of our product candidates may not be successful in achieving widespread patient or physician awareness or acceptance of such product candidate.

Even though we expect that our product candidate will be priced responsibly, if approved, there is no guarantee that it or any other product that we bring to the market directly or through a strategic partner will gain market acceptance by physicians, patients, third-party payors and others in the medical community.

We or our collaborators in any potential commercial launch of our product candidates may not be successful in achieving widespread patient or physician awareness or acceptance of such product candidate.

Even though we expect that our product candidates will be priced responsibly, if approved, there is no guarantee that it or any other product that we bring to the market directly or through a collaborator will gain market acceptance by physicians, patients, third-party payors and others in the medical community.

The degree of market acceptance of any of our product candidates, if approved for commercial sale, will depend on a number of factors, including but not limited to:

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Our efforts, or those of any strategic licensing or collaboration partner, to educate the medical community and third-party payors on the benefits of our product candidates may require significant resources, may be under-resourced compared to large well-funded pharmaceutical entities and may never be successful.

If ay product candidates we may develop in the future are approved but fail to achieve an adequate level of acceptance by physicians, patients, third-party payors and others in the medical community, we will not be able to generate sufficient revenue to become or remain profitable.

If any product candidates we may develop in the future are approved but fail to achieve an adequate level of acceptance by physicians, patients, third-party payors and others in the medical community, we will not be able to generate sufficient revenue, either directly or through milestone and royalty payments from our collaborators, to become or remain profitable.

If the market opportunities for our approved product candidates, if any, are smaller than we expect, it could

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The potentially addressable patient population for our products may be limited or may not be amenable to treatment with our products, and new patients may become increasingly difficult to identify or access, which would adversely affect our results of operations and our business.

If the FDA or comparable foreign regulatory authorities approve generic versions of our approved product candidates , if any, or such authorities do not grant our approved product candidates appropriate periods of data or market exclusivity before approving a generic version, sales of our approved drug candidates could be adversely affected.

Once an NDA is approved, the drug covered thereby becomes a “reference-listed drug” in the FDA’s publication, “Approved Drug Products with Therapeutic Equivalence Evaluations.” Manufacturers may seek marketing approval of generic versions of reference-listed drugs through submission of Abbreviated New Drug Applications (“ANDAs”) in the United States.

Generic drugs may be significantly less costly to bring to market than the reference-listed drug and companies that produce generic drugs are generally able to offer them at lower prices.

Thus, following the introduction of a generic drug, a significant percentage of the sales of any branded product or reference-listed drug is typically lost to the generic drug.

The FDA may not approve an ANDA or a 505(b)(2) NDA for a generic drug until any applicable period of non-patent exclusivity for the reference-listed drug has expired.

The FDCA provides a period of five years of non-patent exclusivity for a new drug containing a new chemical entity.

During the exclusivity period, the FDA may not accept for review an ANDA or a 505(b)(2) NDA submitted by another company for another version of such product candidate where the applicant does not own or have a legal right of reference to all the data required for approval.

However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement.

The FDCA also provides three years of marketing exclusivity for an NDA, 505(b)(2) NDA or supplement to an approved NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example, for new indications, dosages or strengths of an existing product candidate.

This three-year exclusivity covers only the conditions associated with the new clinical investigations and does not prohibit the FDA from approving ANDAs for product candidates containing the original active agent for other conditions of use.

Five-year and three-year exclusivity will not delay the submission or approval of a full NDA.

However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the nonclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

Manufacturers may seek to launch generic drugs following the expiration of the marketing exclusivity period, even if we still have patent protection for such drugs.

Competition that our product candidates, such as Icotyde and rusfertide, if approved, may face from generic drugs could materially and adversely impact our future revenue, profitability and cash flows and substantially limit our ability to obtain a return on the investments we have made in those products.

Our future revenues, profitability and cash flows could also be materially and adversely affected and our ability to obtain a return on the investments we have made in our approved product candidates, if any, may be substantially limited if those drug candidates are not afforded the appropriate periods of non-patent exclusivity.

Risks Related to our Business and Industry

We face significant competition from other biotechnology and pharmaceutical companies, and our operating results will suffer if we or our collaboration partners fail to compete effectively.

We face significant competition from other biotechnology and pharmaceutical companies, and our operating results will suffer if we or our collaborators fail to compete effectively.

The biotechnology and pharmaceutical industries are intensely competitive and subject to rapid and significant technological change.

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If approved, our product candidates are expected to face competition from commercially available drugs as well as drugs that are in the development pipelines of our competitors.

Moreover, we also face increased competition from other companies that are using artificial intelligence, some of whom may be able to more quickly and effectively identify and develop novel product candidates compared to us and our business partners, which could impair our ability to compete effectively and have a material adverse effect on our business, results of operations or financial condition.

Pharmaceutical companies may invest heavily to accelerate discovery and development of novel compounds or to in-license novel compounds that could make our product candidates less competitive.

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A continued and prolonged public health crisis could have a material negative impact on our business, financial condition, and operating results.

Unstable market and macroeconomic conditions, including elevated and sustained inflation, may have serious adverse consequences on our business, financial condition and stock price.

geopolitical instability, including ongoing military conflicts between Russia and Ukraine and in the Middle East, rising tensions between China and Taiwan, and high interest rates.

In particular, the conflict in Ukraine has exacerbated market disruptions, including significant volatility in commodity prices, as well as supply chain interruptions, and has contributed to record inflation globally.

Unstable market and macroeconomic conditions, including tariffs or trade policy, may have serious adverse consequences on our business, financial condition and stock price.

As has been widely reported, we are currently operating in a period of macroeconomic uncertainty and capital markets disruption, which has been significantly impacted by domestic and global monetary and fiscal policy, trade regulations, including changes in trade policies, tariffs or other trade restrictions or the threat of such actions, geopolitical instability, including ongoing military conflicts between Russia and Ukraine and in the Middle East, rising tensions between China and Taiwan, and high interest rates.

Federal Reserve and other central banks may be unable to contain inflation through more restrictive monetary policy and inflation may increase or continue for a prolonged period of time.

Inflationary factors, such as increases in the cost of clinical supplies, interest rates, overhead costs and transportation costs may adversely affect our operating results.

We continue to monitor these events and the potential impact on our business.

Although we do not believe that inflation has had a material impact on our financial position or results of operations to date, our financial position or results of operations may be adversely affected in the future due to the macroeconomic factors discussed above, and such factors may lead to increases in the cost of manufacturing our product candidates and delays in initiating trials.

In addition, global credit and financial markets have experienced extreme volatility and disruptions in the past several years and the foregoing factors have led to and may continue to cause diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, uncertainty about economic stability and increased inflation.

Inflationary factors, such as increases in the cost of clinical supplies, interest rates, overhead costs and transportation

costs may adversely affect our operating results.

In addition, in September 2025, the United States announced the imposition of up to 100% tariffs on imported branded or patented pharmaceuticals, subject to certain exceptions.

There remains substantial uncertainty as to whether and when such tariffs may go into effect and whether such tariffs would apply to the importation of active pharmaceutical ingredients or bulk drug products that are intended for use in clinical trials and, more generally, about the duration of existing tariffs, tariff levels, implementation of announced tariffs, litigation challenging tariffs and whether additional tariffs or retaliatory actions may be imposed, modified or suspended.

Although we do not believe that the macroeconomic factors discussed above have had a material impact on our financial position or results of operations to date, our financial position or results of operations may be adversely affected in the future due to these factors, and such factors may lead to increases in the cost of manufacturing our product candidates and delays in initiating trials.

In addition, global credit and financial markets have experienced extreme volatility and disruption in the past several years and the foregoing factors have led to and may continue to cause diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, uncertainty about economic stability and continued inflation.

There can be no assurance that further deterioration in credit and financial markets and confidence in economic conditions will not occur.

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If our operations are found to be in violation of any of these laws or any other governmental laws and regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, disgorgement, imprisonment, integrity oversight and reporting obligations, exclusion from government funded healthcare programs, such as Medicare and Medicaid, disgorgement, contractual damages, reputational harm, diminished profits and the curtailment or restructuring of our operations.

If, and to the extent that, we or our collaboration partners are unable to comply with these regulations, our ability to earn potential royalties from sales of product candidates under our collaboration agreements would be materially and adversely impacted.

If, and to the extent that, we or our collaborators are unable to comply with these regulations, our ability to earn potential royalties from sales of product candidates under our collaboration agreements would be materially and adversely impacted.

If any of the physicians or other healthcare providers or entities with whom we expect to do business is found to be not in compliance with applicable laws, they may be subject to significant criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.

The imposition of any of these penalties or other commercial limitations could negatively impact our collaboration arrangements or cause our collaboration partners to terminate the related license and collaboration agreement, either of which would materially and adversely affect our business, financial condition and results of operations.

The imposition of any of these penalties or other commercial limitations could negatively impact our collaboration arrangements or cause our collaborators to terminate the related license and collaboration agreement, either of which would materially and adversely affect our business, financial condition and results of operations.

Our future success depends on our ability to retain our executive officers and to attract, retain and motivate qualified personnel.

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Our business is increasingly dependent on critical, complex and interdependent information technology systems, including internet-based systems, to support business processes as well as internal and external communications.

The size and complexity of our internal computer systems and those of our CROs, contract manufacturers, collaboration partners, and other third parties on which we rely may make them potentially vulnerable to breakdown, telecommunications and electrical failures, and malicious intrusion such as ransomware and computer viruses that may result in the impairment of key business processes.

The size and complexity of our internal computer systems and those of our CROs, contract manufacturers, collaborators, and other third parties on which we rely may make them potentially vulnerable to breakdown, telecommunications and electrical failures, and malicious intrusion such as ransomware and computer viruses that may result in the impairment of key business processes.

Our systems are potentially vulnerable to cybersecurity breaches, by employees or others, which may expose sensitive data to unauthorized persons.

The increasing use of artificial intelligence technologies by hackers may materially increase the sophistication, frequency and impact of cybersecurity attacks against us.

Such cybersecurity breaches or other cybersecurity incidents may allow hackers access to our pre-clinical compounds, strategies, discoveries, trade secrets and/or other confidential information.

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Any disruption or cybersecurity incident, to the extent it was to result in the loss, destruction, unavailability, alteration or dissemination of, or damage to, our data or applications, or for it to be believed or reported that any of these occurred, could harm our reputation, compel us to comply with federal and/or state breach notification laws, subject us to mandatory corrective action, require us to verify the correctness of database contents and otherwise subject us to liability under laws and regulations that protect personal data, resulting in increased costs or loss of revenue.

The risk of a cybersecurity incident or other informational technology disruption, particularly through cyber-attacks, has generally increased as the number, intensity and sophistication of attempted attacks and intrusions from

around the world has increased.

The risk of a cybersecurity incident or other informational technology disruption, particularly through cyberattacks, has generally increased as the number, intensity and sophistication of attempted attacks and intrusions from around the world has increased.

In addition, the use of artificial intelligence by cybercriminals may increase the frequency and severity of cybersecurity attacks, including against us or the third parties on which we rely.

Cybersecurity attacks and breaches may be difficult to detect and any delay in identifying them may increase the harm caused, and it may take considerable time for us to investigate and evaluate the full impact of cyberattacks, particularly for sophisticated attacks, which may inhibit our ability to provide prompt, full, and reliable information about cybersecurity incidents to our customers, regulators, and the public.

If we are unable to prevent such cybersecurity incidents or privacy violations or implement satisfactory remedial measures, our operations could be disrupted, and we may suffer loss of reputation, financial loss and other regulatory penalties.

Although we maintain liability insurance for cybersecurity incidents, such insurance may not be sufficient in type or amount to cover us against all claims related to cybersecurity incidents, breaches, and other related incidents.

If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could have a material adverse effect on the success of our business.

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We currently carry clinical trial liability insurance for our clinical trials.

Although we maintain such insurance, any claim that may be brought against us could result in a court judgment or settlement in an amount that is not covered, in whole or in part, by our insurance or that is in excess of the limits of our insurance coverage.

Although we maintain such insurance, any claim that may be brought against us could result in a court judgment or settlement in an amount that is

not covered, in whole or in part, by our insurance or that is in excess of the limits of our insurance coverage.

Our insurance policies also have various exclusions, and we may be subject to a product liability claim for which we have no coverage.

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The patent applications that we own or license may fail to result in issued patents in the United States or in other foreign countries, or they may fail to result in issued patents with claims that cover our product candidates or technologies in the United States or in other foreign countries.

Any failure to

identify relevant prior art relating to a patent or patent applications can invalidate a patent or prevent a patent from issuing.

Any failure to identify relevant prior art relating to a patent or patent applications can invalidate a patent or prevent a patent from issuing.

Even if patents have been issued, third parties may challenge the validity, enforceability or scope thereof, which may result in such patents being narrowed, invalidated or held unenforceable.

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For example, we primarily rely on trade secrets and confidentiality agreements to protect our peptide therapeutics technology platform.

Any disclosure to or misappropriation by third parties of our confidential proprietary information could enable competitors to quickly duplicate or surpass our technological achievements, thus eroding our competitive position in our market.

If we are unable to protect the confidentiality of our trade secrets and proprietary know-how or if competitors independently develop viable competing products, our business and competitive position may be harmed.

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Any issued patents covering our product candidates, including any patent that may issue as a result of our pending or future patent applications, could be found invalid or unenforceable if challenged in court in the United States or abroad.

As more groups become engaged in scientific research and product development in fields related to our product candidates, such as hepcidin mimetics or IL-23R, the risk of our patents, or patents that we have in-licensed, being challenged through patent interferences, derivation proceedings, oppositions, re-examinations, litigation or other means will likely increase.

As more groups become engaged in scientific research and product development in fields related to our product candidates, such as hepcidin mimetics or IL-23R, the risk of our patents, or patents that we have in-licensed, being challenged through derivation proceedings, oppositions, re-examinations, litigation or other means will likely increase.

An adverse outcome in a patent dispute could have a material adverse effect on our business by:

● causing us to lose patent rights in the relevant jurisdiction(s);

● subjecting our collaboration partners or us to litigation, or otherwise preventing the commercialization of product candidates in the relevant jurisdiction(s);

● requiring our collaboration partners or us to obtain licenses to the disputed patents, cease using the disputed technology or develop or obtain alternative technologies.

An adverse outcome in a patent dispute could severely harm our collaborations or cause our collaboration partners to terminate their respective agreements.

● subjecting our collaborators or us to litigation, or otherwise preventing the commercialization of product candidates in the relevant jurisdiction(s);

● requiring our collaborators or us to obtain licenses to the disputed patents, cease using the disputed technology or develop or obtain alternative technologies.

An adverse outcome in a patent dispute could severely harm our collaborations or cause our collaborators to terminate their respective agreements.

Litigation or other legal proceedings relating to intellectual property claims, with or without merit, are unpredictable and generally expensive and time consuming and, even if resolved in our favor, are likely to divert significant resources from our core business, including distracting our technical and management personnel from their normal responsibilities.

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Despite the contractual provisions employed when working with third parties, the need to share trade secrets and other confidential information increases the risk that such trade secrets become known by our competitors, are inadvertently incorporated into the technology of others, or are disclosed or used in violation of these agreements.

Enforcing a claim that a party illegally obtained and is using our trade secrets is challenging and the outcome is unpredictable.

In addition, courts outside of the United States may be less willing to protect trade secrets.

Given that our proprietary position is based, in part, on our know-how and trade secrets, a competitor’s discovery of our trade secrets or other unauthorized use or disclosure would impair our competitive position and may have an adverse effect on our business and results of operations.

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The stock market in general and the market for biotechnology companies in particular have experienced extreme volatility that has often been unrelated to the operating performance of particular companies.

As a result of this volatility, investors may experience losses on their investment in our common stock, including due to the factors discussed in these “Risk Factors” and elsewhere in this Annual Report.

As a result of this volatility, payouts under, as well as the incentive value of, our stock-based compensation arrangements for employees can fluctuate and investors may experience losses on their investment in our common stock, including due to the factors discussed in these “Risk Factors” and elsewhere in this Annual Report.

Volatility in our share price could subject us to securities class action litigation.

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Any material weakness or other failure to maintain internal control over financial reporting could severely inhibit our ability to accurately report our financial condition or results of operations.

If we are not able to comply with the requirements of Section 404 or if we or our independent registered public accounting firm are unable to attest to the effectiveness of our internal control over

financial reporting, investors may lose confidence in the accuracy and completeness of our financial reports, the market price of our stock could decline and we could be subject to sanctions or investigations by Nasdaq, the SEC, or other regulatory authorities, which would require additional financial and management resources.

If we are not able to comply with the requirements of Section 404 or if we or our independent registered public accounting firm are unable to attest to the effectiveness of our internal control over financial reporting, investors may lose confidence in the accuracy and completeness of our financial reports, the market price of our stock could decline and we could be subject to sanctions or investigations by Nasdaq, the SEC, or other regulatory authorities, which would require additional financial and management resources.

Shareholder activism could cause material disruption to our business.

Publicly traded companies have increasingly become subject to campaigns by activist investors advocating corporate actions such as actions related to environment, social and governance matters, financial restructuring, increased borrowing, dividends, share repurchases or even sales of assets or the entire company.

Responding to proxy contests and other actions by such activist investors or others in the future could be costly and time consuming, disrupt our operations and divert the attention of our board of directors and senior management from the pursuit of our business strategies, which could adversely affect our results of operations and financial condition.

Our certificate of incorporation provides that the Court of Chancery of the State of Delaware is the exclusive forum for substantially all disputes between us and our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or employees.

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To the extent that we continue to generate taxable losses, unused losses will carry forward to offset future taxable income, if any, until such unused losses expire.

Under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, if a corporation undergoes an “ownership change,” generally defined as a greater than fifty percentage point change (by value) in its equity ownership by certain stockholders over a three-year period, the corporation’s ability to use its pre-change net operating loss carryforwards, or NOLs, and other pre-change tax attributes (such as research and development tax credits) to offset its post-change taxable income or tax liability may be limited.

Under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, if a corporation undergoes an “ownership change,” generally defined as a greater than fifty percentage point change (by value) in its equity ownership by certain stockholders over a three-year period, the corporation’s ability to use its pre-change NOLs, and other pre-change tax attributes (such as research and development tax credits) to offset its post-change taxable income or tax liability may be limited.

We have experienced ownership changes in the past, resulting in annual limitations in our ability to use our NOLs and credits.

In addition, we may experience subsequent ownership changes as a result of future equity offerings or other changes in the ownership of our stock, some of which

are beyond our control.

In addition, we may experience subsequent ownership changes as a result of future equity offerings or other changes in the ownership of our stock, some of which are beyond our control.

As a result, the amount of the NOLs and tax credit carryforwards presented in our financial statements could be limited and may expire unused.

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We cannot assure you, however, that our estimates, or the assumptions underlying them, will be correct.

We could be subject to additional tax liabilities.

We are subject to U.S.

federal, state, and local taxes in the United States and other countries.

Significant judgment is required in evaluating our tax positions.

During the ordinary course of business, there are many activities and transactions for which the ultimate tax determination is uncertain.

In addition, our tax obligations and effective tax rates could be adversely affected by changes in the relevant tax, accounting and other laws, regulations, principles and interpretations and the prudence and feasibility of possible tax planning strategies.

We continue to monitor new tax legislation, such as the One Big Beautiful Bil Act, enacted in 2025, which permits the expensing of certain research and development expenditures in the United States incurred in tax years beginning in 2025, or other developments since significant changes in tax legislation, or in the interpretation of existing legislation, could materially and adversely affect our financial condition and operating results.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1A. Risk Factors