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Item 1A. Risk Factors

2026-02-24 compared with 2025-02-27 · 270 added, 256 removed, 1397 unchanged (27% of the section changed)

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If these third parties fail to perform as expected or to comply with legal and regulatory requirements, our ability to commercialize our current or future products will be significantly impacted and we may be subject to regulatory sanctions;

● We may be unable to successfully or sufficiently expand our manufacturing capacity to meet demand for our products;

● We may be unable to successfully or sufficiently expand our manufacturing capacity to meet demand for our products and product candidates;

● We depend on the success of our product candidates and cannot guarantee that these product candidates will successfully complete development, receive regulatory approval, or be successfully commercialized;

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● We are required to pay substantial royalties and lump sum benchmark payments under our license or acquisition agreements with the NIH, Novartis, Clinigen, and Cellectis, and we must meet certain milestones to maintain our license rights;

● We rely on and collaborate with governmental, academic, and corporate partners or agencies to approve, improve, and develop TIL cell therapies for new indications for use in combination with other therapies and to evaluate new TIL manufacturing methods, the results of which, because the manufacturing processes are not within our control, and may be incorrect or unreliable;

● We have global operations, which expose us to additional risks, and any adverse event could have a material adverse effect on our results of operations and financial condition;

● We are currently operating in a period of economic uncertainty and capital markets disruption, which has been significantly impacted by geopolitical instability, ongoing military conflicts between Russia and Ukraine and between Israel and Hamas, Hezbollah, and the Houthis, and inflation.

Our business, financial condition and results of operations could be materially adversely affected by any negative impact on the global economy and capital markets resulting from the conflict in Ukraine and the Middle East, geopolitical tensions, or inflation.

Our business, financial condition and results of operations could be materially adversely affected by any negative impact on the global economy and capital markets resulting from the conflicts in Ukraine, the Middle East and other global conflicts, geopolitical tensions, or inflation.

Risks Related to Government Regulation:

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● Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not mean that we will be successful in obtaining or maintaining regulatory approval of our product candidates in other jurisdictions;

● Coverage and reimbursement may be limited or unavailable in certain market segments for our product candidates, which could make it difficult for us to sell our product candidates profitably.

● Coverage and reimbursement may be limited or unavailable in certain market segments for our products or product candidates, which could make it difficult for us to sell our product candidates profitably.

The summary risk factors described above should be read together with the text of the full risk factors below in this section entitled “Risk Factors” and the other information set forth in this Annual Report on Form 10-K, including our consolidated financial statements and the related notes, as well as in other documents that we file with the SEC.

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we expect to continue to incur losses, and we may never be profitable.

We are a commercial-stage biopharmaceutical company pioneering a transformational approach to treating cancer by harnessing the human immune system’s ability to recognize and destroy diverse cancer cells using therapies personalized for each patient.

Until recently, we did not have products approved for commercial sale and have not generated significant revenue from operations.

With the recent approval of the BLA, we began to generate revenue from the sale of our product Amtagvi ® in the second quarter of 2024.

Furthermore, following the acquisition of the worldwide rights to Proleukin ® in May 2023, or the Acquisition, we began to generate revenue from the sales of Proleukin ® .

Until the closing of the Proleukin ® acquisition, or the Acquisition, in May 2023, we did not have products approved for commercial sale and have not generated significant revenue from operations.

We began to generate revenue from the sale of Proleukin ® after the Acquisition, and from the sale of Amtagvi ® in the second quarter of 2024.

However, Proleukin ® revenues are dependent upon continued use in manufacturing and clinical settings by us and other cell therapy companies.

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However, our operations may not be profitable even if any of our products under development are successfully developed and produced and thereafter commercialized.

Furthermore, our profitability and gross margins are subject to fluctuations based on factors outside of our control, such as potential additional tariffs, discussed below, as well as any changes to corporate tax rates.

We may need additional financing to fund our operations and complete the development of our various product candidates and commercialization of our products, and if we are unable to obtain such financing, we may be unable to complete the development of our product candidates and commercialization of our products.

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In addition, our research and development and our operating costs have also been substantial and are expected to increase.

For example, in October 2018, we closed an underwritten public offering of our common stock.

The net proceeds from the offering, after deducting the underwriting discounts and commissions and other offering expenses payable by us, were $236.7 million.

In June 2020, we closed another underwritten offering of our common stock.

The net proceeds from the offering, after deducting the underwriting discounts and commissions and other offering expenses payable by us, were $567.0 million.

In July 2023, we closed another underwritten offering of our common stock.

The net proceeds from the offering, after deducting the underwriting discounts and commissions and other offering expenses payable by us, were $161.5 million.

In February 2021, we entered into an open market sale agreement, or the 2021 Sale Agreement, with Jefferies LLC, or Jefferies, which provided for the sale of up to $350.0 million of our common stock from time to time, which was subsequently increased to $500.0 million in November 2022 upon the execution of an updated open market sale agreement, or the 2022 Sale Agreement, with Jefferies.

In June 2023, we entered into a new open market sale agreement, or the 2023 Sale Agreement, with Jefferies, which superseded the 2022 Sale Agreement and provided for the sale of up to $450.0 million of our common stock from time to time.

In February 2024, we closed another underwritten offering of our common stock.

The net proceeds from the offering, after deducting the underwriting discounts and commissions and other offering expenses payable by us, were $197.4 million.

As of December 31, 2024, we had $330.1 million in cash, cash equivalents, investments, and restricted cash ($115.7 million of cash and cash equivalents, $208.1 million in short-term investments, and restricted cash of $6.4 million).

As of December 31, 2025, we had $303.0 million in cash, cash equivalents, short-term investments, and restricted cash ($163.1 million of cash and cash equivalents, $133.9 million in short-term investments, and $6.0 million in restricted cash).

With the approval of the BLA, we began to generate revenue from the sale of our product Amtagvi ® in the second quarter of 2024.

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● our ability to successfully commercialize our product candidates, if approved;

● our ability to have clinical and commercial product successfully manufactured consistent with FDA and foreign regulations, including those applicable in the EU;

● our ability to have clinical and commercial product successfully manufactured consistent with the FDA and foreign regulations, including those applicable in the EU;

● amount of sales and other revenues from product candidates that we may commercialize, if any, including the selling prices for such potential products and the availability of adequate third-party coverage and reimbursement for patients;

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Unless and until we can generate a sufficient amount of revenue, we may finance future cash needs through public or private equity offerings, license agreements, debt financings, collaborations, strategic alliances and marketing or distribution arrangements.

For example, in August 2025, we entered into an Amended and Restated Open Market Sale Agreement, or the 2025 Sale Agreement, with Jefferies, which provides for the sale of up to $350.0 million of our common stock from time to time.

Additional funds may not be available when we need them on terms that are acceptable to us, or at all.

We have no committed source of additional capital and if we are unable to raise additional capital in sufficient amounts or on terms acceptable to us, we may be required to delay or reduce the scope of or eliminate one or more of our research or development programs or our commercialization efforts.

We have no committed source of additional capital and if we are unable to raise additional capital in sufficient amounts or on terms acceptable to us, we may be required to undergo further reductions in our workforce or other corporate restructuring activities, or delay or reduce the scope of or eliminate one or more of our research or development programs or our commercialization efforts.

Our current license and collaboration agreements may also be terminated if we are unable to meet the payment obligations under those agreements.

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If we raise additional funds through strategic partnerships and alliances and licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies or product candidates, or grant licenses on terms unfavorable to us.

Subject to various spending levels approved by our Board of Directors, our management will have broad discretion in the use of the net proceeds from our capital raises, including our February 2024, July 2023, June 2020, October 2018 and January 2018 public offerings and the proceeds from sales pursuant to our “at-the-market” sale agreement with Jefferies LLC, and may not use them effectively.

Our management will have discretion in the application of the net proceeds from our capital raises, including our February 2024, July 2023, June 2020, October 2018, and January 2018 public offerings, and the proceeds from sales pursuant to the 2023 Sale Agreement with Jefferies, which provides for the sale of up to $450.0 million of our common stock from time to time, and our stockholders will not have the opportunity as part of their investment decision to assess whether the net proceeds from our capital raises are being used appropriately.

We may be unable to realize the expected benefits from restructuring activities, including workforce reductions, and our business might be adversely affected.

In August 2025, we announced a strategic restructuring plan with an associated reduction in workforce as a result of a review of current strategic priorities, resource allocation, and cost reduction intended to reduce operating costs, streamline operations, and extend our cash runway.

The workforce reduction of approximately 19 percent was substantially complete by end of September 30, 2025.

These types of restructuring and cost reduction activities are complex and may result in unintended consequences and costs, such as unforeseen delays in the implementation of our strategic initiatives, business and operational disruptions, decreased employee

morale and retention, loss of institutional knowledge and expertise, and potential impacts on financial reporting.

The reduction in our workforce could also make it difficult for us to pursue, or prevent us from pursuing, new opportunities, and initiatives due to insufficient personnel, or require us to incur additional and unanticipated costs to hire new personnel to pursue such opportunities or initiatives.

If we do not successfully manage the impact of the restructuring plan or any other similar activities that we may undertake in the future, we may not achieve the expected cost savings and other expected benefits in the expected timeframe or at all, and our business, financial condition, and results of operations may be materially adversely affected.

Subject to various spending levels approved by our Board of Directors, our management will have broad discretion in the use of the net proceeds from our capital raises, including proceeds from sales pursuant to our “at-the-market” sale agreement with Jefferies LLC, and may not use them effectively.

Our management will have discretion in the application of the net proceeds from our capital raises, including proceeds from sales pursuant to the 2025 Sale Agreement with Jefferies, which provides for the sale of up to $350.0 million of our common stock from time to time, and our stockholders will not have the opportunity as part of their investment decision to assess whether the net proceeds from our capital raises are being used appropriately.

You may not agree with our decisions, and our use of the proceeds from our capital raises may not yield any return to stockholders.

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The tax regimes to which we are subject or under which we operate are unsettled and may be subject to significant change.

Any such changes to existing federal and state tax laws could adversely impact our business, results of operations, and financial position as the impact of recent tax legislation is uncertain.

The tax rate applied is based on the estimated statutory rates in the UK as this is where our intangible assets, including our intellectual property, are domiciled, and as a result, we receive certain tax benefits.

Any such changes to existing federal and state tax laws or international and U.S.

corporate tax rates could adversely impact our business, results of operations, and financial position as the impact of recent tax legislation is uncertain.

In recent years, various tax legislations were signed into law.

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Certain provisions of the CARES Act amend or suspend certain provisions of the Tax Act.

For example, the tax relief measures under the CARES Act for businesses include a five-year net operating loss carryback, suspension of annual deduction limitation of 80% of taxable income from net operating losses generated in a tax year beginning after December 31, 2017, changes in the deductibility of interest, acceleration of alternative minimum tax credit refunds, payroll tax relief, and a technical correction to allow accelerated deductions for qualified improvement property.

alternative minimum tax credit refunds, payroll tax relief, and a technical correction to allow accelerated deductions for qualified improvement property.

On June 15, 2020, Assembly Bill 85 was passed in California, which suspended the use of net operating losses and limited the use of credits for certain corporations.

Following the change in U.S.

administration, there is uncertainty regarding future legislative and regulatory changes and policies related to matters such as taxation and importation, including tariffs, and any such proposed or enacted regulations, taxes, or tariffs by the current or a future U.S.

On July 4, 2025, the One Big Beautiful Bill Act, or the OBBBA, was enacted in the U.S.

The OBBBA includes significant provisions, such as the permanent extension of certain expiring provisions of the Tax Act, modifications to the international tax framework and the restoration of favorable tax treatment for certain business provisions.

The OBBBA has multiple effective dates, with certain provisions effective in 2025 and others implemented through 2027.

The OBBBA has enacted, among others, changes to eligibility requirements for premium tax credits, which is expected to result in less coverage in the ACA’s health insurance marketplace, or Marketplace, over the next few years.

The ACA premium tax credits expired at the end of 2025, which is expected to result in an additional loss of coverage for approximately an estimated 24 million people currently that were previously enrolled in insurance plans obtained through the Marketplace.

In addition, the OBBBA has made other changes to the enrollment and eligibility requirements for Medicaid, which is expected to result in the loss of coverage for certain individuals currently enrolled in Medicaid programs.

We are currently assessing the impact of the OBBBA on our consolidated financial statements.

There is uncertainty regarding future legislative and regulatory changes and policies related to matters such as taxation and importation, including tariffs, and any such proposed or enacted regulations, taxes, or tariffs by the current or a future U.S.

administration, Congress, or taxing and importation authorities in other jurisdictions could adversely impact the global economy and materially affect our tax obligations, tariff obligations, and operating results.

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The complexities of manufacturing cell therapy products require extensive collaboration with treatment centers including the provision of patient tumor tissue for manufacture.

Manufacturing is dependent on many factors including quality of the patient tumor tissue, treatment center training, and unique factors specific to autologous cell therapy manufacturing that can jeopardize the product approval, launch, scale, and capacity.

Manufacturing is dependent on many factors including quality of the patient tumor tissue, treatment center training, and unique factors specific to autologous cell

therapy manufacturing that can jeopardize the product approval, launch, scale, and capacity.

As a result of the complexities, the cost to manufacture biologics is generally higher than traditional small molecule chemical compounds, and the manufacturing process is less reliable and is more difficult to reproduce.

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Gen 2 is the FDA-approved, commercial manufacturing process for Amtagvi ® and has been selected for all ongoing and future company-sponsored clinical trials.

overruns, potential problems with process scale-up, process reproducibility, stability issues, lot consistency, and timely availability of raw materials.

Although we believe Gen 2 is a commercially viable process, there are risks associated with scaling to the level required for advanced clinical trials or commercialization, including, among others, cost overruns, potential problems with process scale-up, process reproducibility, stability issues, lot consistency, and timely availability of raw materials.

As a result of these challenges, we may experience delays in our clinical development and/or commercialization plans.

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Our current manufacturing strategy involves the use of CMOs in conjunction with our internal manufacturing capacity at the i CTC.

Currently our products and product candidates are manufactured internally at the i CTC and externally by WuXi Advanced Therapies, Inc., or Wuxi, and previously by Moffitt.

Currently our products and product candidates are manufactured internally at the i CTC and previously externally by Minaris Advanced Therapies, Inc., or Minaris, and the H.

Lee Moffitt Cancer Center, or Moffitt.

Additionally, we partner with American Red Cross, or ARC, to operate our facility to produce feeder cells for TIL manufacturing.

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There are only a limited number of these types of facilities and sources for the materials needed by TIL cell therapy manufacturers.

The i CTC and our CMO are aseptic manufacturing facilities that operate clean rooms for the production of TIL cell therapies, which are subject to contamination, labor, occupational safety, regulatory, climate, and environmental risks that could interfere with production.

The i CTC is an aseptic manufacturing facility that operates clean rooms for the production of TIL cell therapies, which are subject to contamination, labor, occupational safety, regulatory, climate, and environmental risks that could interfere with production.

Any problems or delays we or our CMOs experience in preparing for commercial scale manufacturing of a product, product candidate, or component thereof may result, in the case of product candidates, a delay in the approval thereof or, in the case of products, may impair our ability to manufacture commercial quantities or such quantities at an acceptable cost, which could result in the delay, prevention, or impairment of clinical development of our product candidates and commercialization of our products and could adversely affect our business.

Furthermore, if we or our commercial manufacturers fail to deliver the required commercial quantities of our product candidates on a timely basis and at reasonable costs, we would likely be unable to meet demand for our products and we would lose potential revenues.

Moreover, while we are expanding our capabilities to enable more internal manufacturing, should we continue to use CMOs, we may not succeed in maintaining our relationships with our current CMO or establishing relationships with additional or alternative CMOs.

Moreover, while we are expanding our capabilities to enable more internal manufacturing, should we continue to use CMOs, we may not succeed in maintaining our relationships with CMOs or establishing relationships with additional or alternative CMOs.

Our products and product candidates may compete with other products and product candidates for access to manufacturing facilities.

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● our ability to synchronize operations and standards to ensure that all aspects of manufacturing are consistent without deviations across facilities.

In addition, the manufacturing process and facilities for any products and product candidates that we may develop at the i CTC and or our CMOs is subject to FDA and foreign regulatory authority approval processes, and we or our CMOs will need to meet all applicable FDA and foreign regulatory authority requirements, including cGMP, on an ongoing basis.

In addition, the manufacturing process and facilities for any products and product candidates that we may develop at the i CTC or at our CMOs is subject to FDA and foreign regulatory authority approval processes, and we or our CMOs will need to meet all applicable FDA and foreign regulatory authority requirements, including cGMP, on an ongoing basis.

The cGMP requirements include quality control, quality assurance, and the maintenance of records and documentation.

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Further, we, in cooperation with our CMOs, must supply all necessary chemistry, manufacturing, and control documentation for a pre-approval inspection in support of a BLA on a timely basis.

Although both the internal and external facilities were approved by the FDA for commercial manufacturing of Amtagvi ® , there is no guarantee that we or our CMOs will be able to successfully pass all aspects of surveillance or pre-approval inspections by the FDA or other foreign regulatory authorities for Amtagvi ® or future product candidates.

Although both the internal and external facilities were approved by the FDA for commercial manufacturing of Amtagvi ® , there is no guarantee that we or our CMOs will be

able to successfully pass all aspects of surveillance or pre-approval inspections by the FDA or other foreign regulatory authorities for Amtagvi ® or future product candidates.

Our internal manufacturing facilities or our CMOs’ manufacturing facilities may be unable to comply with our specifications, cGMP, and with other FDA, state, and foreign regulatory requirements.

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For each of these biological raw materials (including live cells), chemicals and agents used for manufacturing, reagents, equipment, and materials, we rely and may in the future rely on treatment sites, limited manufacturers, sole source vendors, or a limited number of vendors.

An inability to continue to source product from any of these suppliers, which could be due to a number of issues, including regulatory actions or requirements affecting the supplier, adverse financial or other strategic developments experienced by a supplier, labor disputes or shortages, unexpected demands, or quality issues, could adversely affect our ability to satisfy demand for our product candidates, which could adversely and materially affect our product sales and operating results or our ability to conduct clinical trials, either of which could significantly harm our business.

An inability to continue to source product from any of these suppliers, which could be due to a number of issues, including regulatory actions or requirements affecting the supplier, adverse financial or other strategic developments experienced by a supplier, labor disputes or shortages, unexpected demands, quality issues, or recently imposed tariffs which could adversely affect our ability to satisfy demand for our products or product candidates and impact our cost of goods for our products or product candidates, which in turn could adversely and materially affect our product sales and operating results or our ability to conduct clinical trials, either of which could significantly harm our business.

As we continue to develop and scale our manufacturing process, we expect that we will need to obtain rights to and supplies of certain materials and equipment to be used as part of that process.

We may not be able to obtain rights to such materials on commercially reasonable terms, or at all, and if we are unable to alter our process in a commercially viable manner to avoid the use of such materials or find a suitable substitute, it would have a material adverse effect on our business.

We may not be able to obtain rights to such materials on commercially reasonable terms, or at all, and if we are unable to alter our process in a commercially viable manner to avoid the use of

such materials or find a suitable substitute, it would have a material adverse effect on our business.

Even if we are able to alter our process so as to use other materials or equipment, such a change may lead to a delay in our clinical development and/or commercialization plans.

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Payors may deny coverage or offer inadequate levels of reimbursement for these therapies if they determine that the product has not received appropriate clearances from the FDA or other government regulators or if they deem the therapies to be investigational or experimental, not medically necessary, or otherwise inappropriate.

Although we may apply for special government programs and prepare the market for product approval, there is no way to ensure that healthcare providers, insurance companies, or other third parties will reimburse our product at an expeditious rate.

Although we may apply for special government programs and prepare the market for product approval, there is no way to ensure that HCPs, insurance companies, or other third parties will reimburse our product at an expeditious rate.

Even if we obtain insurance coverage for our product from payors, there is no guarantee that third party payors will provide adequate coverage or reimbursement.

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If coverage and reimbursement are not available or are inadequate, ATCs and clinics may decide not to recommend our product, and there may be a slow uptake or variable or limited access, if at all, to our therapies.

Likewise, in the absence of a long-term agreement with an insurance company, there is no guarantee that an insurance company will enter into a single-case agreement with us or otherwise provide prior authorization for a particular case, in which case there may be no or inadequate coverage and reimbursement for our products.

inadequate coverage and reimbursement for our products.

Seeking prior authorization and negotiating the single-case agreement may take anywhere from days to months to obtain, if at all, and may cause ATCs, clinics and patients to decline to use our products.

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Our goal is to reduce the cost of manufacturing and providing our therapies.

However, unless we can reduce those costs to an acceptable amount, we may never be able to develop a commercially viable product.

However, unless we can reduce those costs to an acceptable amount, we may never be able to develop and commercialize our product candidates.

If we do not successfully develop and commercialize products based upon our approach or find suitable and economical sources for materials used in the production of our products, we will not become profitable, which would materially and adversely affect the value of our common stock.

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We have limited experience in manufacturing our adoptive cell therapy product candidate on a commercial scale, as do our partners.

As a result, we cannot give any assurance that the Gen 2 process or any future process that we select will be a manufacturing process that can produce our products in compliance with the applicable regulatory requirements, at a cost or in quantities necessary to make them commercially viable.

As a result, we cannot give any assurance that the Gen 2 process or any future process that we select will be a manufacturing process that can produce our product candidates in compliance with the applicable regulatory requirements, at a cost or in quantities necessary to make them commercially viable.

Moreover, we and our third-party manufacturers will have to continually adhere to current cGMP regulations enforced by the FDA and foreign regulatory authorities through facilities inspection programs.

If our facilities or any of the facilities of these manufacturers cannot demonstrate adequate assurance of compliance with applicable standards during a pre-approval inspection,

the approval of our products will not be granted.

If our facilities or any of the facilities of these manufacturers cannot demonstrate adequate assurance of compliance with applicable standards during a pre-approval inspection, the approval of our products will not be granted.

In complying with cGMP and foreign regulatory requirements, we and any of our third-party manufacturers will be obligated to expend time, money and effort in production, record-keeping, and quality control to assure that our products meet applicable specifications and other requirements.

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In particular, we expect to compete with other new therapies for our lead indications developed by companies such as BioNtech, Bristol-Myers Squibb, Daiichi Sankyo, Eisai, Genmab, Immunocore, IO Biotech, Merck, Moderna, Pfizer, Regeneron Pharmaceuticals, and Replimune.

We also may compete with other T cell therapies in development, including therapies based on genetically engineered T cell receptors rendered reactive against tumor-associated antigens prior to their administration, other genetically engineered TIL products, and TIL products designed to be reactive to specific neoantigens, by companies such as AbelZeta Pharma, Achilles Therapeutics, Adaptimmune Therapeutics, Alaunos Therapeutics, Biosyngen, GRIT Biotechnology, Immatics, Immunocore, Intima Bioscience, KSQ Therapeutics, Lyell Immunopharma, Marker Therapeutics, Obsidian Therapeutics, TILT Biotherapeutics, and others.

products designed to be reactive to specific neoantigens, by companies such as AbelZeta Pharma, Alaunos Therapeutics, Biosyngen, GRIT Biotechnology, Immatics, Immunocore, Intima Bioscience, KSQ Therapeutics, Marker Therapeutics, Obsidian Therapeutics, and others.

To date, these technologies have been primarily applicable to hematologic malignancies, but their application in solid tumor indications may create competition with us.

We may also face competition from immunotherapy treatments offered by companies such as Amgen, AstraZeneca, BioNTech, Bristol-Myers Squibb, Merck, Pfizer, Regeneron Pharmaceuticals, Roche, and others.

We may also face competition from novel IL-2 treatments in development by Alkermes, ILToo Pharma, Merck, Nektar Therapeutics, Sanofi, Werewolf Therapeutics, and others.

We may also face competition from companies offering immunotherapy treatments or from companies developing novel IL-2 treatments.

Many of these companies and our other current and potential competitors have substantially greater research and development capabilities and financial, scientific, regulatory, manufacturing, marketing, sales, human resources, and experience than we do.

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Universities and public and private research institutions around the world are also potential competitors.

For example, a Phase 3 M14TIL clinical trial comparing TIL to standard ipilimumab in patients with metastatic melanoma is currently being conducted in Europe by the Netherlands Cancer Institute, the Copenhagen County Herlev University Hospital, and the University of Manchester.

Results from the M14TIL clinical trial were presented at the European Society for Medical Oncology Congress in September 2022.

While these universities and public and private research institutions primarily have educational objectives, they may develop proprietary technologies that lead to other approved therapies by the FDA, European Commission, or other regulatory agencies, or that secure patent protection that we may need for the development of our technologies and products.

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We currently have a commercial team focused on our commercial strategy, but we do not have a large commercial infrastructure for the marketing, sale, and distribution of biopharmaceutical products.

In order to commercialize our products, we must continue to build our marketing, sales, and distribution capabilities or make arrangements with third parties to perform these services, which will take time and require significant financial expenditures, and we may not be successful in doing so.

In order to commercialize our products, we must continue to build our marketing, sales, and distribution capabilities or make arrangements with third parties to perform these services,

which will take time and require significant financial expenditures, and we may not be successful in doing so.

In addition, we rely on one or more third-party distributors for the commercial sale of our products.

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We, or our collaborators, will have to compete with other pharmaceutical and biotechnology companies to recruit, hire, train, manage, and retain marketing, sales, and commercial support personnel.

Although we have developed a commercial infrastructure, in the event we are

unable to continue to develop a successful commercial infrastructure, we may not be able to commercialize our current or future product candidates, which would limit our ability to generate product revenues.

Although we have developed a commercial infrastructure, in the event we are unable to continue to develop a successful commercial infrastructure, we may not be able to commercialize our current or future product candidates, which would limit our ability to generate product revenues.

Factors that may inhibit our efforts to commercialize our current or future products and product candidates and generate significant product revenues include:

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● the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines;

● unforeseen costs and expenses associated with creating an independent sales and marketing organization or engaging a contract sales organization.

● unforeseen costs and expenses associated with an independent sales and marketing organization or engaging a contract sales organization.

If our products or product candidates do not achieve broad market acceptance, the revenues that we generate from their sales will be limited.

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Even after our products and product candidates are approved by the appropriate regulatory authorities for marketing and sale, they may not gain acceptance among physicians, patients, third-party payors, and others in the medical community.

If any product or product candidate for which we obtain regulatory approval does not gain an adequate level of market acceptance, we may not generate significant product revenues or become profitable.

product or product candidate for which we obtain regulatory approval does not gain an adequate level of market acceptance, we may not generate significant product revenues or become profitable.

Market acceptance of our products and product candidates by the medical community, patients, and third-party payors will depend on a number of factors, some of which are beyond our control.

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If the FDA or a foreign regulatory authority objects to any of our proposed proprietary product names, we may be required to adopt alternative names for our products and/or product candidates.

If we adopt alternative names, we would lose the benefit of any existing trademark applications for such product and/or product candidate and may be required to expend significant additional resources in an effort to identify a suitable product name that would qualify under applicable trademark laws, not infringe the existing rights of third parties, and be acceptable to

the FDA and foreign regulatory authorities.

We may be unable to build a successful brand identity for a new trademark in a timely manner or at all, which would limit our ability to commercialize our products and product candidates.

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For example, we continue to recruit a new Chief Executive Officer.

However, competition for qualified employees among companies in the biotechnology and biopharmaceutical industry is intense, and no assurance can be given that we will be able attract, hire, retain, and motivate the highly skilled employees that we need.

However, competition for qualified employees among companies in the biotechnology and biopharmaceutical industry is intense, and no assurance can be given that we will be able attract,

hire, retain, and motivate the highly skilled employees that we need.

Future growth will impose significant added responsibilities on members of management, including:

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Our future financial performance and our ability to commercialize our product candidates will depend, in part, on our ability to effectively manage any future growth, and our management may also have to divert a disproportionate amount of its attention away from day-to-day activities in order to devote a substantial amount of time to managing these growth activities.

Moreover, in August 2025, management approved a strategic restructuring plan with an associated reduction in workforce of approximately 19 percent as a result of a review of current strategic priorities, resource allocation, and cost reduction intended to reduce operating costs, streamline operations and extend our cash runway.

This reduction in our workforce may also make retention of our current personnel both more important and more challenging.

The workforce reduction resulted in the loss of longer-term employees, the loss of institutional knowledge and expertise, and the reallocation and combination of certain roles and responsibilities across the organization, all of which could adversely affect our operations.

Given the complexity of our business, we must continue to implement and improve our managerial, operational, and financial systems, manage our facilities and continue to recruit and retain qualified personnel.

We currently rely, and for the foreseeable future will continue to rely, in substantial part on certain independent organizations, advisors and consultants to provide certain services.

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If a third party fails to timely report or adjust prices as required or errs in calculating government pricing information from transactional data in our financial records, it could impact our discount and rebate liability, and potentially subject us to regulatory sanctions or False Claims Act lawsuits.

We may be unable to successfully or sufficiently expand our manufacturing capacity to meet demand for our products.

As noted above, we have limited experience in internal manufacturing our adoptive cell therapy product candidates on a commercial scale, as do our partners.

We anticipate expanding internal manufacturing capacity at our i CTC facility and potentially at our contract manufacturer, WuXi.

We may be unable to successfully or sufficiently expand our manufacturing capacity to meet demand for our products and product candidates.

As noted above, we have limited experience in internal manufacturing of our adoptive cell therapy products and product candidates on a commercial scale, as do our partners.

Currently our products and product candidates are manufactured internally at our i CTC facility and other third-party manufacturers.

In January 2026, we ended manufacturing activities at Minaris and centralized manufacturing of Amtagvi ® and our investigational TIL cell therapies at our i CTC facility.

There can be no assurance that our efforts to centralize manufacturing at the i CTC facility will succeed.

Scale-up of manufacturing may require additional validation studies, including capacity demonstration and/or comparability studies, each of which are subject to regulatory review, potential inspection, and approval.

Moreover, while we continue to expand our internal manufacturing capacity, the current geopolitical tensions with China may impact our ability to expand manufacturing capacity at our contract manufacturer, WuXi.

Recently, the Biden administration has signed multiple executive orders regarding China.

One particular executive order titled Advancing Biotechnology and Biomanufacturing Innovation for a Sustainable, Safe, and Secure American Bioeconomy, signed on September 12, 2022, will likely impact the pharmaceutical industry to encourage U.S.

domestic manufacturing of pharmaceutical products.

Additionally, in February 2024, the chair and ranking member of the House Select Committee on the Chinese Communist Party, Representatives Mike Gallagher and Raja Krishnamoorthi, respectively, along with Senators Gary Peters and Bill Hagerty, sent a letter to the Biden administration requesting that both WuXi AppTec Co., Ltd., WuXi’s parent company, and the affiliated WuXi Biologics be added to the Department of Defense’s Chinese Military Companies List (1260H list), the Department of Commerce’s Bureau of Industry and Security Entity List, and the Department of Treasury’s Non-SDN Chinese Military-Industrial Complex Companies List.

While the Biden administration did not take action on this letter, adding either or both previously mentioned WuXi entities on any or all of the aforementioned lists could materially impact our MSA with WuXi, and the current Trump administration could take action with regard to such letter.

The new administration may also enact regulations or policies that affect trade with China or otherwise impact the biopharmaceutical industry by enacting laws to restrict U.S.

biopharmaceutical companies from contracting with Chinese companies on the development, research or manufacturing of biopharmaceutical products.

Any additional executive orders, legislative action or potential sanctions on China could materially impact our current manufacturing partners.

Finally, there have been Congressional legislative proposals, such as a bill titled the BIOSECURE Act, to discourage contracting with certain Chinese companies, including two WuXi affiliates, on the development or manufacturing of pharmaceutical products.

The BIOSECURE Act passed the U.S.

House of Representatives on September 9, 2024.

The version of the BIOSECURE Act that passed the U.S.

House of Representatives included a grandfather clause that would allow contracts entered into with the Chinese companies named therein prior to the effective date of such legislation to survive until January 1, 2032.

The BIOSECURE Act did not pass the U.S.

Senate before expiring, thus not becoming law, but support for the legislation remains, and the current Trump administration has promised to take a hard line on Chinese entities.

While WuXi has recently entered into an agreement to be acquired by Altaris LLC, or Altaris, there is no guarantee that they will complete the transaction or that, after the transaction is completed, we will be able to continue to utilize their contract manufacturing services, as Altaris and its subsidiary Minaris Regenerative Medicine LLC, or Minaris, have limited resources and lack experience in supplying high volume commercial cell therapies for oncology

As a result, we may need to discontinue use of the WuXi manufacturing capacity and instead use the i CTC facility or other manufacturers to supply our therapies.

Regardless, any expansion of our internal and external manufacturing capability will also require us to invest substantial additional funds to hire and retain the technical personnel who have the necessary manufacturing experience.

As a result, we may not be able to successfully or sufficiently increase the manufacturing capacity for our product candidates or modify our manufacturing processes.

If we are unable to successfully increase the manufacturing capacity for a product candidate (as a result of lack of approval from, or capacity limitations imposed by, the FDA, or otherwise), the resulting capacity limitations could have a material adverse effect on our results of operations and financial condition.

In addition, if the i CTC facility is unable to meet production requirements, we may need to identify and qualify new contract manufacturers, which could result in additional costs and delays in meeting demand for Amtagvi ® and our product candidates.

Any significant delay in our ability to meet demand could have a material adverse effect on our business, financial condition and results of operations.

Any expansion of our internal and external manufacturing capability will also require us to invest substantial additional funds to hire and retain the technical personnel who have the necessary manufacturing experience.

As a result, we may not be able to successfully or sufficiently increase the manufacturing capacity for our products and product candidates or modify our manufacturing processes.

If we are unable to successfully increase the manufacturing capacity for a product or product candidate (as a result of lack of approval from, or capacity limitations imposed by, the FDA, or otherwise), the resulting capacity limitations could have a material adverse effect on our results of operations and financial condition.

In addition, if we are unable to successfully or sufficiently increase the manufacturing capacity at the i CTC facility to meet demand in a timely or economic manner, or at all, we may be dependent upon the performance and capacity of third-party manufacturers.

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We currently have two products approved for commercial sale.

We have invested a significant portion of our efforts and financial resources in the development of our current product and/or product candidates, including Amtagvi ® , lifileucel, and modified product candidates, IOV-4001, IOV-2001, IOV-3001, and IOV-5001, and expect that we will continue to invest heavily in our current product candidates, as well as in any future product candidates we may develop.

We have invested a significant portion of our efforts and financial resources in the development of our current product and/or product candidates and expect that we will continue to invest heavily in our current product candidates, as well as in any future product candidates we may develop.

Our business depends on the successful development and commercialization of our product candidates.

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Our product candidates will require additional clinical and non-clinical development, regulatory approval, commercial manufacturing arrangements, establishment of a commercial organization, significant marketing efforts, and further investment before we generate any revenue from product sales.

We cannot assure you that we will meet our timelines for our current or future clinical trials, which may be delayed or not completed for a number of reasons, including the continuing negative impact of the COVID-19 pandemic and any future pandemic or epidemic.

Additionally, the costs associated with development of cell therapy products may be significant due to the length of treatment and the supportive therapies provided to the patient during the treatment process.

We cannot assure you that we will meet our timelines for our current or future clinical trials, which may be delayed or not completed for a number of reasons, including any future pandemic or epidemic.

Additionally, the costs associated with development of cell therapy products may be significant due to the length of treatment and the supportive

therapies provided to the patient during the treatment process.

Supportive therapies may impact costs and patient viability and may potentially limit availability.

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Our treatment centers may not be able to obtain necessary supplies, such as lymphodepleting chemotherapy agents, because of shortages.

Our commercial products and investigational therapies will rely heavily on our ability to train centers and the centers’ ability to choose suitable patients and deliver a

complex regimen.

Our commercial products and investigational therapies will rely heavily on our ability to train centers and the centers’ ability to choose suitable patients and deliver a complex regimen.

We may be reliant on physicians with limited experience with TIL products and the associated regimens.

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ODD, however, may be lost if the indication for which we develop our designated product candidates does not meet the orphan criteria.

Moreover, following product approval, orphan exclusivity may be lost if the FDA determines, among other reasons, that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the product to meet the needs of patients with the rare disease or condition.

of patients with the rare disease or condition.

Even if we obtain orphan exclusivity, that exclusivity may not effectively protect the product from competition because different products can be approved for the same condition and the same product can be approved for different conditions.

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Failure can occur at any time during the clinical trial process.

As a result of the continuing impact of the COVID-19 pandemic, institutions and research sites that currently conduct clinical trials may not be able to return to normal clinical trial operations for some time or may no longer choose to participate in studies in the future.

Furthermore, clinical trials may be delayed or otherwise may be more difficult to execute in the future.

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Relying on third-party clinical investigators, CROs, or CMOs may force us to encounter delays and challenges that are outside of our control.

In addition to manufacturing TIL at the i CTC, we rely on a CMO in the U.S.

and Europe to manufacture TIL for use in our clinical trials and commercial use upon approval.

We may not be able to demonstrate sufficient comparability between products manufactured at different facilities to allow for inclusion of the clinical results from patients treated with products from these different facilities, or with our own manufacturing facility, in our product registrations, or to allow for use of the i CTC at the time of launch.

Further, our CMOs may not be able to manufacture TIL or otherwise fulfill their obligations to us because of interruptions to their business, including the loss of their key staff or interruptions to their raw material supply.

We rely on third party CROs and clinical trial sites to conduct, supervise, and monitor our clinical trials for our product candidates.

For example, we rely on third party CROs and clinical trial sites to conduct, supervise, and monitor our clinical trials for our product candidates.

We expect to continue to rely on third parties, such as CROs, clinical data management organizations, medical institutions, independent review organizations, and clinical investigators, to conduct our clinical trials.

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For example, we will remain responsible for ensuring that each of our clinical trials is conducted in accordance with the general investigational plan and protocols for the clinical trial and for ensuring that our preclinical studies are conducted in accordance with Good Laboratory Practices, or GLPs, as appropriate.

Moreover, the FDA and comparable foreign regulatory authorities require us to comply with Good Clinical Practices, or GCPs, for conducting, recording, and reporting the results of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity, and confidentiality of clinical trial participants are protected.

participants are protected.

Regulatory authorities enforce these requirements through periodic inspections (including pre-approval inspections upon completion of a BLA filing with the FDA) of clinical trial sponsors, clinical investigators, clinical trial sites and certain third parties including CMOs.

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We plan to initiate clinical trials in new indications and new cohorts in existing clinical trials.

For example, we

plan to commence a registrational trial in previously treated advanced undifferentiated pleomorphic sarcoma, or UPS, and dedifferentiated liposarcoma, or DDLPS, in the second quarter of 2026.

Even as these clinical trials progress, issues may arise that could require us to suspend or terminate such clinical trials or could cause the results of one cohort to differ from a prior cohort.

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On March 4, 2024, the FDA lifted the partial clinical hold on the IOV-LUN-202 trial, permitting us to resume patient enrollment.

A failure of one or more clinical trials can occur at any stage of testing, and our future

clinical studies may not be successful.

A failure of one or more clinical trials can occur at any stage of testing, and our future clinical studies may not be successful.

Events that may prevent successful or timely initiation or completion of clinical development, or product approval include:

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● clinical trials of our product candidates producing negative or inconclusive results may fail to provide sufficient data and information to support product approval, or our studies may fail to reach the necessary level of statistical or clinical significance, which may result in our deciding, or regulators requiring us, to conduct additional clinical trials studies, or preclinical studies, or abandon product development programs;

our clinical trials are tested, and overall response rate and duration of response may be negatively affected by the inclusion of unconfirmed responses in preliminary results that we report if such responses are not later confirmed;

● early results from our clinical trials of our product candidates may be negatively affected by changes in efficacy measures such as overall response rate and duration of response as more patients are enrolled in our clinical trials or as new cohorts of our clinical trials are tested, and overall response rate and duration of response may be negatively affected by the inclusion of unconfirmed responses in preliminary results that we report if such responses are not later confirmed;

● we may not be able to demonstrate that a product candidate provides an advantage over current standards of care or current or future competitive therapies in development;

● there may be changes to the therapeutics or their regulatory status which we are administering in combination with our product candidates;

● delays in patient enrollment due to potential health epidemics, such as the COVID-19 pandemic;

● delays in patient enrollment due to potential health epidemics and pandemics;

● the FDA or comparable foreign regulatory authorities may fail to approve or subsequently find fault with the manufacturing processes or our manufacturing facilities for clinical and future commercial supplies;

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In addition, if we make manufacturing changes to our product candidates, we may be required to, or we may elect to, conduct additional studies to bridge our modified product candidates to earlier versions.

These changes may require regulatory approval or notification, may not have their desired effect, or the FDA or foreign regulatory authorities may not accept data from prior versions of the product to support an application, delaying our clinical trials or programs or necessitating additional clinical trials or preclinical studies.

These changes may require

regulatory approval or notification, may not have their desired effect, or the FDA or foreign regulatory authorities may not accept data from prior versions of the product to support an application, delaying our clinical trials or programs or necessitating additional clinical trials or preclinical studies.

For example, while our first BLA submission includes our Gen 2 manufacturing process, in the future we may seek to commercialize other manufacturing processes, such as our Gen 3 manufacturing process or our PD-1 selected TIL manufacturing process.

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We may not commence or complete clinical trials involving any of our products as projected or may not conduct them successfully.

We are currently conducting eight company-sponsored clinical trials to assess the overall safety and efficacy of Iovance TIL monotherapy and TIL combinations in patients with melanoma, cervical, endometrial, head and neck, and lung cancers across late-line and early treatment settings, as well as our genetically modified TIL cell therapy IOV-4001 and our peripheral blood lymphocyte, or PBL, technology for hematological malignancies.

We are currently conducting multiple company-sponsored clinical trials to assess the overall safety and efficacy of Iovance TIL monotherapy and TIL combinations in patients with solid tumor cancers.

However, we may experience difficulties in patient enrollment in our clinical trials for a variety of reasons.

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Many companies in the biotechnology, pharmaceutical, and medical device industries have suffered significant setbacks in late-stage clinical trials after achieving positive results in earlier development, and we cannot be certain that we will not face such setbacks.

Furthermore, the timely completion of clinical trials in accordance with their protocols depends, among other things, on our ability to enroll a sufficient number of patients who remain in the clinical trial until its conclusion, including the ability of us or our collaborators to conduct clinical trials under the constraints of the COVID-19 pandemic.

In addition, our clinical trials will compete with other clinical trials for product candidates that are in the same therapeutic areas as our product candidates, and this competition will reduce the number and types of patients available to us, because some patients who might have opted to enroll in our clinical trials may instead opt to enroll in a clinical trial being conducted by one of our competitors.

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We expect to rely on medical institutions, academic institutions, or CROs to conduct, supervise or monitor some or all aspects of clinical trials involving our products.

We will have less control over the timing and other aspects of these clinical trials than if we

conducted them entirely on our own.

We will have less control over the timing and other aspects of these clinical trials than if we conducted them entirely on our own.

If we fail to commence or complete, or experience delays in, any of our planned clinical trials, our stock price and our ability to conduct our business as currently planned could be harmed.

We currently anticipate that we will have to rely on our CMO to supplement the manufacturing capacity at the i CTC in manufacturing our adoptive cell therapy and biologic products for clinical trials.

If they fail to commence or complete, or experiences delays in, manufacturing our adoptive cell therapy and other biologic products, our planned clinical trials will be delayed, which will adversely affect our stock price and our ability to conduct our business as currently planned.

Iovance TIL cell therapies are manufactured for commercial use and clinical trials internally at the i CTC.

If we fail to commence or complete, or experiences delays in, manufacturing our products and product candidates, our planned clinical trials will be delayed, which will adversely affect our stock price and our ability to conduct our business as currently planned.

Clinical trials are expensive, time-consuming and difficult to design and implement, and our clinical trial costs may be higher than for more conventional therapeutic technologies or drug products.

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The results of studies in one set of patients or line of treatment may not be predictive of those obtained in another and the results in various human clinical trials reported in scientific and medical literature may not be indicative of results we obtain in our clinical trials.

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

Product candidates in later stages of clinical trials

may fail to show the desired safety and efficacy traits despite having progressed through preclinical studies and initial clinical trials.

Preclinical studies may also reveal unfavorable product candidate characteristics, including safety concerns.

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● clinical investigators enrolling patients who do not meet the enrollment criteria, requiring the inclusion of additional patients in the clinical trial;

● health epidemics, such as the COVID-19 pandemic, limiting our access to patients who would otherwise be eligible for enrollment, including treatment-naïve patients who may be more likely to seek standard of care therapies available at local treatment centers rather than enroll in a clinical trial at a larger hospital;

● health epidemics limiting our access to patients who would otherwise be eligible for enrollment, including treatment-naïve patients who may be more likely to seek standard of care therapies available at local treatment centers rather than enroll in a clinical trial at a larger hospital;

● approval of new indications for existing therapies or approval of new therapies in general;

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Such toxicities, which may arise from TIL cell therapy in general, including co-therapies, may include, for example, thrombocytopenia, chills, anemia, pyrexia, febrile neutropenia, diarrhea, neutropenia, vomiting, hypotension, and dyspnea.

For example, the update in October 2018 from the C-144-01 clinical trial included two grade 5 treatment emergent adverse events.

In addition, failure to manage toxicities, adverse events or side effects and to take recommended or other precautions may result in deaths or harm to patients.

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Under our license or acquisition agreements with the NIH, Novartis, Clinigen, and Cellectis for our adoptive cell therapy and immunotherapy technologies, we are currently required to pay both substantial benchmark payments and royalties to each entity based on our revenues from sales of our products utilizing the licensed or acquired technologies.

These payments could adversely affect the overall profitability for us of any products that we may seek to commercialize under these license agreements.

These payments could adversely affect the

overall profitability for us of any products that we may seek to commercialize under these license agreements.

In order to maintain our license rights under the NIH, Novartis, and Cellectis license agreements, we will need to meet certain specified milestones, subject to certain cure provisions, in the development of our product candidates, and a milestone payment is required to Clinigen upon the approval of lifileucel in melanoma.

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We are dependent on third parties to support our research, development, and supplement our internal manufacturing activities and, therefore, are subject to the efforts of these parties and our ability to successfully collaborate with these third parties.

As a result of our current strategy to supplement our internal manufacturing by outsourcing, we rely very heavily on third parties to perform for us the manufacturing of our products and/or product candidates.

We also license a portion of our technology from others.

We intend to rely upon both our internal facility, the i CTC, as well as our CMOs to produce large quantities of materials needed for clinical trials and product commercialization.

The i CTC currently supplies the majority of commercial Amtagvi ® and clinical lifileucel with additional capacity previously supplemented by a CMO, and certain clinical trials for our next-generation investigational TIL cell therapies are supported by CMOs.

Third party manufacturers may not be able to meet our needs with respect to timing, quantity, or quality.

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Any such delay may lower our revenues and potential profitability.

In addition, in order to supplement our own efforts to improve TIL manufacturing and develop TIL cell therapies in new indications in clinical trials, we currently work and collaborate with government and academic research institutions, medical institutions, and corporate partners such as the NCI, Moffitt, Memorial Sloan Kettering Cancer Center, Cellectis, and Novartis.

For example, in February 2026, we announced positive initial data from a pilot clinical trial led by MSKCC and supported by us of lifileucel in patients with advanced UPS or DDLPS who were refractory to at least one prior line of systemic therapy.

We also intend to continue to enter into additional third-party collaborative agreements in the future.

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● a collaborator with marketing and distribution rights to one or more of our product candidates that achieve regulatory approval may not commit sufficient resources to the marketing and distribution of such product candidate or product;

and/or product candidates, might lead to additional responsibilities for us with respect to products and/or product candidates, or might result in litigation or arbitration, any of which would be time consuming and expensive;

● disagreements with collaborators, including disagreements over proprietary rights, contract interpretation, or the preferred course of development, might cause delays or termination of the research, development, or commercialization of products and/or product candidates, might lead to additional responsibilities for us with respect to products and/or product candidates, or might result in litigation or arbitration, any of which would be time consuming and expensive;

● collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation;

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In addition to our own research and process development efforts, we seek to collaborate with government, academic research institutions and corporate partners to improve TIL manufacturing and to develop TIL cell therapies for new indications.

In 2017-2020, we announced our continued collaborations with Moffitt, MDACC, and others to evaluate new solid tumor and hematologic indications for TIL cell therapy in clinical trials and preclinical studies, as well as, in some cases, new TIL manufacturing approaches.

We continue to collaborate with the NCI, NIH, Moffitt, MDACC, and others to evaluate new solid tumor, including soft tissue sarcomas, and hematologic indications for TIL cell therapy in clinical trials and preclinical studies, as well as, in some cases, new TIL manufacturing approaches.

The results of these collaborations may be used to support our filing with the FDA of INDs to conduct more advanced clinical trials of our product candidates, or to otherwise analyze or make predictions or decisions with respect to our current or future product candidates.

However, because the majority of our collaborations are conducted at outside laboratories and we do not have complete control over how the studies are conducted or reported or over the manufacturing methods used to manufacture TIL product, the results of such studies, which we may use as the basis for our conclusions, projections or decisions with respect to our current or future products and product candidates, may be incorrect or unreliable, or may have a negative impact on us if the results of such studies are imputed to our products or proposed indications, even if such imputation is improper.

studies are imputed to our products or proposed indications, even if such imputation is improper.

For example, we have entered into collaborations with academic partners to perform clinical trials using TIL products that differ from our products, but the results of these clinical trials, if negative, may adversely impact our stock price and our development plans for our products.

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Cyberattacks could include the deployment of harmful malware, denial-of-service, ransomware, social engineering and other means to affect service reliability and threaten data confidentiality, privacy, integrity and availability.

Our business and technology partners face similar risks, and any security breach of their systems could adversely affect our security posture.

Our business and technology partners face similar risks, and any security breach of

their systems could adversely affect our security posture.

While we have invested, and continue to invest, in the protection of our data and information technology infrastructure, there can be no assurance that our efforts, or the efforts of our partners and vendors, will prevent service interruptions, or identify breaches in our systems, that could adversely affect our business and operations and/or result in the loss of critical or sensitive information, which could result in financial, legal, business or reputational harm to us.

In addition, our liability insurance may not be sufficient in type or amount to cover us against claims related to security breaches, cyberattacks and other cybersecurity related breaches.

Our business could be adversely affected by the effects of health epidemics, including the COVID-19 pandemic, in regions where we or third parties on which we rely have significant manufacturing facilities, concentrations of clinical trial sites or other business operations.

The COVID-19 pandemic could materially affect our operations, including at our headquarters in San Carlos, California, at our manufacturing facility in Philadelphia, Pennsylvania, which have previously been subject to state executive orders and shelter-in-place orders, and at our clinical trial sites, as well as the business or operations of our other manufacturers, CROs, or other third parties with whom we conduct business.

We, directly or through our third-party service providers, may adopt, use or incorporate artificial intelligence, or AI, technology and capabilities into the information technology systems or software that we use in our business and operations.

Defects in such AI technology or related security breaches, loss of data and other disruptions as well as changes in implementation standards and enforcement practices under a rapidly evolving regulatory framework for AI technology may adversely affect our business and operations and potentially expose us to increasing liability.

We, directly or through our third-party service providers, may adopt, use or incorporate AI technology and capabilities into information technology systems or software to help us operate our business more efficiently than existing industry tools.

The regulatory framework for AI technologies is rapidly evolving as many federal, state and foreign government bodies and agencies have introduced or are currently considering additional laws and regulations.

In addition, existing laws and regulations may be interpreted in ways that would affect the use of AI in our business.

As a result, implementation standards and enforcement practices are likely to remain uncertain for the foreseeable future, and we cannot yet determine the impact future laws, regulations, standards, or market perception of such requirements may have on our business and may not always be able to anticipate how to respond to these laws or regulations.

While there is currently no comprehensive federal legislation in the U.S.

that regulates the development or use of AI, several governmental agencies in the U.S.

jurisdictions have proposed or enacted laws regulating AI technologies by setting out principles intended to guide AI design and deployment for the public and private sectors and signaling the increase in government involvement and regulation over AI technologies.

The significant increase in companies that have incorporated the use of AI in their businesses has also increased the SEC’s focus on AI-washing as a key enforcement priority.

In May 2024, the European Union legislators approved the EU Artificial Intelligence Act, or the EU AI Act, which establishes a comprehensive, risk-based governance framework for AI in the EU market.

The majority of the substantive requirements of the EU AI Act are not enforceable yet and are expected to apply from August 2, 2026.

In July 2025, the EU published a voluntary AI Code of Practice, which is intended to guide developers of AI systems in complying with the EU AI Act and avoid potential penalties.

The EU AI Act, and developing interpretation and application of the GDPR in respect of automated decision making, together with developing guidance and/or decisions in the impact of AI technology on data privacy, may affect our use of AI technologies and our ability to provide, improve or commercialize our business, require additional compliance measures and changes to our operations and processes, and result in increased compliance costs and potential increases in civil claims against us, and could adversely affect our business, operations and financial condition.

Further, interpretation and implementation of intellectual property protection in the field of AI are rapidly evolving and there is uncertainty and ongoing litigation in different jurisdictions as to the degree and extent of protection warranted for AI and relevant system inputs and outputs.

If we fail to obtain protection for intellectual property rights for any of our intellectual property that may incorporate or be developed using AI technologies, or later have our intellectual property rights invalidated or otherwise diminished, our competitors may be able to take advantage of our research and development efforts to develop competing products that could adversely affect our business, reputation and financial condition.

Further, other parties may have, or in the future may obtain, patents or other proprietary rights that would prevent, limit or interfere with our ability to use any AI technologies that we may develop or us in our business.

It is possible that further new laws and regulations will be adopted in the United States and in other non-U.S.

jurisdictions, or that existing laws and regulations, including competition and antitrust laws, may be interpreted in ways that would limit our ability to use AI technologies for our business, or require us to change the way we use AI technologies in a manner that negatively affects the performance of our system and business and the way in which we use AI technologies.

We may need to expend resources to adjust our system in certain jurisdictions if the laws, regulations, or decisions are not consistent across jurisdictions.

Further, the cost to comply with such laws, regulations or decisions and/or guidance interpreting existing laws, could be significant and would increase our operating expenses.

Such an increase in operating expenses, as well as any actual or perceived failure to comply with such laws and regulations, could materially and adversely affect our business, financial condition, results of operations, and prospects.

Our business could be adversely affected by the effects of health epidemics and pandemics, in regions where we or third parties on which we rely have significant manufacturing facilities, concentrations of clinical trial sites or other business operations.

Our business could be adversely affected by health epidemics in regions where we have offices, manufacturing facilities, concentrations of clinical trial sites or other business operations, and could cause significant disruption in the operations of clinical trial sites, third party manufacturers and CROs upon whom we rely.

For example, starting in December 2019, a novel strain of coronavirus, or COVID-19, was reported to have surfaced in Wuhan, China and spread to multiple countries, including the U.S.

and several European countries.

In March 2020, the World Health Organization declared COVID-19 a global pandemic and the U.S.

declared the COVID-19 pandemic a national emergency.

Similarly, during that time, the State of California declared a state of emergency related to the spread of the COVID-19 pandemic and the health officers of six San Francisco Bay Area counties, including San Mateo County where our headquarters in San Carlos is located, issued shelter-in-place orders.

In addition, on March 19, 2020, the Governor of California and the State Public Health Officer and Director of the California Department of Public Health ordered all individuals living in the State of California to stay at their place of residence for an indefinite period of time (subject to certain exceptions to facilitate authorized necessary activities) to mitigate the impact of the COVID-19 pandemic.

Throughout 2020 and 2021, similar executive orders were issued by state and local governments, and states of emergency had been declared at the state and local level in most jurisdictions throughout the U.S.

As recently as April 2022, ports and airports in Shanghai, China closed due to another outbreak of COVID-19, resulting in a lockdown of the city and disruption to export and import activities.

In the U.S., many of these executive orders have been rescinded, however, we remain vigilant and continue to monitor any ongoing effects of the COVID-19 pandemic closely to determine if additional actions are required.

Quarantines, shelter-in-place, and similar government orders, or the perception that such orders, shutdowns or other restrictions on the conduct of business operations could occur, related to the COVID-19 pandemic or other infectious diseases could impact personnel at third-party manufacturing facilities in the U.S.

Quarantines, shelter-in-place, and similar government orders, or the perception that such orders, shutdowns or other restrictions on the conduct of business operations could occur, related to pandemics or the spread of other infectious diseases could impact personnel at third-party manufacturing facilities in the U.S.

and other countries, or the availability or cost of materials, which would disrupt our supply chain.

In addition, our clinical trials may be affected by health epidemics, such as the COVID-19 pandemic.

Clinical site initiation, patient enrollment and patient monitoring may be delayed due to prioritization of hospital resources toward health epidemics, such as the COVID-19 pandemic.

In addition, our clinical trials may be affected by health epidemics and pandemics.

Clinical site initiation, patient enrollment and patient monitoring may be delayed due to prioritization of hospital resources toward health epidemics and pandemics.

Some sites may no longer be available to see patients for clinical trials.

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Patients may also miss follow-up visits after receiving our therapies during our clinical trials, which may or may not be rectified by future patient visits and which may result in the exclusion of data from such patients from the clinical trial data.

Similarly, our ability to recruit and retain patients and principal investigators and site staff who, as healthcare providers, may have heightened exposure to viruses that cause pandemic and epidemics, such as the virus that causes the COVID-19 pandemic, and such exposure may adversely impact our clinical trial operations.

Health epidemics, such as the COVID-19 pandemic, may also affect our ability to recruit treatment-naïve patients into our clinical trials, because those patients may be more likely to seek standard of care therapies available at local treatment centers rather than enroll in a clinical trial at a larger hospital.

We continue to monitor the impact, if any, of health epidemics, including the COVID-19 pandemic, on our current and future operations, including our regulatory filing timelines and strategy, as well as our preparation for commercial launch.

Similarly, our ability to recruit and retain patients and principal investigators and site staff who, as HCPs, may have heightened exposure to viruses that cause pandemics and epidemics, and such exposure may adversely impact our clinical trial operations.

Health epidemics, may also affect our ability to recruit treatment-naïve patients into our clinical trials, because those patients may be more likely to seek standard of care therapies available at local treatment centers rather than enroll in a clinical trial at a larger hospital.

We continue to monitor the impact, if any, of health epidemics and pandemics, on our current and future operations, including our regulatory filing timelines and strategy, as well as our preparation for commercial launch.

As with the COVID-19 pandemic, any restrictions regarding travel and face to face interactions or constraints on resources, either by us or our contractors, including our CMOs, may negatively impact our regulatory strategy or commercial launch preparations.

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Moreover, the collection and use of personal health data in the EU, which was formerly governed by the provisions of the EU Data Protection Directive, was replaced with the EU General Data Protection Regulation, or the GDPR, in May 2018.

confidentiality of the personal data, data breach notification and the use of third-party processors in connection with the processing of personal data.

The GDPR, which is wide-ranging in scope, imposes several requirements relating to the consent of the individuals to whom the personal data relates, the information provided to the individuals, the security and confidentiality of the personal data, data breach notification and the use of third-party processors in connection with the processing of personal data.

The GDPR also imposes strict rules on the transfer of personal data out of the EU to the U.S., provides an enforcement authority and imposes large penalties for noncompliance, including the potential for fines of up to €20 million or 4% of the annual global revenues of the noncompliant company, whichever is greater.

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The implementation of the GDPR has increased our responsibility and liability in relation to personal data that we process, including in clinical trials, and we may in the future be required to put in place additional mechanisms to ensure compliance with the GDPR, which could divert management’s attention and increase our cost of doing business.

In addition, new regulation or legislative actions regarding data privacy and security (together with applicable industry standards) may increase our costs of doing business.

In addition, new regulations or legislative actions regarding data privacy and security (together with applicable industry standards) may increase our costs of doing business.

If we fail to comply with the data protection laws in any EU member country or other jurisdiction, the data protection authority of such country or other jurisdiction may, in addition to fines, impose sanctions on us, which may include a prohibition that prevents us from transferring and/or processing personal data of data subjects from such country or other jurisdiction for a duration determined by the sanctioning authority.

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Our inability to conduct clinical trials in the EU member country or other jurisdiction for the duration of the sanction may delay and increase the cost of development of our products, with a material adverse effect on our business.

In this regard, we expect that there will continue to be new proposed laws, regulations, and industry standards relating to privacy and data protection in the U.S., the EU, and other jurisdictions, and we cannot determine the impact such future laws, regulations and standards may have on our business.

In this regard, we expect that there will continue to be new proposed laws, regulations, and industry standards

relating to privacy and data protection in the U.S., the EU, and other jurisdictions, and we cannot determine the impact such future laws, regulations and standards may have on our business.

Our failure to comply with state and/or national data protection laws and regulations could lead to government enforcement actions and significant penalties against us, and adversely impact our operating results.

There are numerous other laws and legislative and regulatory initiatives at the federal and state levels addressing privacy and security concerns, and some state privacy laws apply more broadly than the Health Insurance Portability and Accountability Act (as amended by the Health Information Technology for Economic and Clinical Health Act Act), or HIPAA, and associated regulations.

For example, California recently enacted legislation, the California Consumer Privacy Act, or CCPA, which went into effect January 1, 2020, and was recently amended and expanded by the California Privacy Rights Act, or CPRA, which will take effect on January 1, 2023.

The CCPA and CPRA, among other things, create new data privacy obligations for covered companies and provides new privacy rights to California residents, including the right to opt out of certain disclosures of their information.

The CCPA also created a private right of action with statutory damages for certain data breaches, thereby potentially increasing risks associated with a data breach.

Although the law includes limited exceptions, including for certain information collected as part of clinical trials as specified in the law, it may regulate or impact our processing of personal information depending on the context.

It remains unclear what, if any, additional modifications will be made to the CPRA by the California legislature or how it will be interpreted.

Therefore, the effects of the CCPA and CPRA are significant and will likely require us to modify our data processing practices and may cause us to incur substantial costs and expenses to comply.

There are numerous other laws and legislative and regulatory initiatives at the federal and state levels addressing privacy and security concerns, and some state privacy laws apply more broadly than the HIPPA (as amended by the HITECH Act), or HIPAA, and associated regulations.

For example, the California Consumer Privacy Act, or CCPA, which went into effect January 1, 2020, and as amended and expanded by the California Privacy Rights Act, or CPRA, which went into effect on January 1, 2023, among other things, create new data privacy obligations for covered companies and provides new privacy rights to California residents, including the right to opt out of certain disclosures of their information.

They also created a private right of action with statutory damages for certain data breaches, thereby potentially increasing risks associated with a data breach.

Although the California law includes limited exceptions, including for certain information collected as part of clinical trials as specified in the law, it may regulate or impact our processing of personal information depending on the context.

Additional modifications may continue to be made to the CPRA by the California legislature and their interpretation by regulators may continue to evolve.

Other states have begun to pass similar data protection laws, which may be amended from time to time.

Therefore, the effects of these state data protection laws are significant and will likely require us to modify our data processing practices and may cause us to incur substantial costs and expenses to comply.

If we engage in future acquisitions or strategic partnerships, this may increase our capital requirements, dilute our stockholders, cause us to incur debt or assume contingent liabilities, and subject us to other risks.

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Acquiring and thereafter operating larger new businesses will also increase our management, operating and reporting costs and burdens.

In addition, if we undertake acquisitions, we may issue dilutive securities, assume or incur debt obligations, incur large one-time expenses and acquire intangible assets that could result in significant future amortization expense.

Moreover, we may not be able to locate suitable acquisition opportunities and this inability could impair our ability to grow or obtain access to technology or products that may be important to the development of our business.

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and natural or man-made disasters, including famine, flood, fire, earthquake, storm, or disease.

Events like these, such as the ongoing war between Russia and Ukraine and rising conflict in the Middle East, could result in material adverse effects on macroeconomic conditions, currency exchange rates and financial markets, and may adversely affect our business, results of operations, and financial condition.

Events like these, such as the ongoing war between Russia and Ukraine, rising conflict in the Middle East and other global conflicts, could result in material adverse effects on macroeconomic conditions, currency exchange rates and financial markets, and may adversely affect our business, results of operations, and financial condition.

Furthermore, changes in regulations and policies by the new U.S.

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may also impact our operations as well as the financial markets and the global economy.

We are currently operating in a period of economic uncertainty and capital markets disruption, which has been significantly impacted by geopolitical instability, ongoing military conflicts between Russia and Ukraine and between Israel and Hamas, Hezbollah, and the Houthis, and inflation .

Our business, financial condition and results of operations could be materially adversely affected by any negative impact on the global economy and capital markets resulting from the conflicts in Ukraine and the Middle East, geopolitical tensions, or inflation.

and global markets are experiencing volatility and disruption following the escalation of geopolitical tensions and the continuation of the military conflict between Russia and Ukraine.

On February 24, 2022, a full-scale military invasion of Ukraine by Russian troops was reported.

Although the length and impact of the ongoing military conflict is highly unpredictable, the conflict in Ukraine could lead to market disruptions, including significant volatility in commodity prices, credit and capital markets, as well as supply chain interruptions, and changes in inflation.

We are continuing to monitor inflation, the situation in Ukraine, and global capital markets, and assessing the potential impacts on our business.

The global economy has been, and may continue to be, negatively impacted by Russia’s invasion of Ukraine.

As a result of Russia’s invasion of Ukraine, the U.S., the EU, the UK, and other G7 countries, among other countries, have imposed substantial financial and economic sanctions on certain industry sectors and parties in Russia.

Broad restrictions on exports to Russia have also been imposed.

These measures include:

(i) comprehensive financial sanctions against major Russian banks;

(ii) additional designations of Russian individuals with significant business interests and government connections;

(iii) designations of individuals and entities involved in Russian military activities;

and (iv) enhanced export controls and trade sanctions limiting Russia’s ability to import various

Russian military actions and the resulting sanctions could continue to adversely affect the global economy and financial markets and lead to instability and lack of liquidity in capital markets, potentially making it more difficult for us to obtain additional funds.

In addition, on October 7, 2023, Hamas militants and members of other terrorist organizations infiltrated Israel’s southern border from the Gaza Strip and conducted a series of terror attacks on civilian and military targets.

Thereafter, Hamas launched extensive rocket attacks on Israeli population and industrial centers located along the Israeli border with the Gaza Strip.

Shortly following the attack, Israel’s security cabinet declared war against Hamas and launched an aerial bombardment of various targets within the Gaza Strip.

The Israeli government subsequently called for the evacuation of over one million residents of the northern part of the Gaza Strip and began a ground invasion of the Gaza Strip that remains ongoing.

Other terrorist and/or regional organizations have joined the hostilities as well, including Hezbollah in Lebanon, and the Houthis in Yemen, and it is possible that Palestinian military organizations in the West Bank will also join, resulting in a further widening of the conflict.

The intensity and duration of Israel’s current wars are difficult to predict as are such wars’ economic implications on the global economy.

There are also current geopolitical tensions with China.

Recently, the Biden administration has signed multiple executive orders regarding China.

domestic manufacturing of pharmaceutical products.

Additionally, on February 28, 2024, President Biden signed Executive Order 14117 (“Preventing Access to Americans’ Bulk Sensitive Personal Data and United States Government-Related Data by Countries of Concern”) which implements a new framework to protect the privacy of personal data shared between the U.S.

and Europe, which may, in effect, impact privacy laws with “countries of concern” such as China or Russia.

Moreover, there have been Congressional legislative proposals, such as the bill titled the BIOSECURE Act, to discourage contracting with Chinese companies, including two WuXi affiliates, on the development or manufacturing of pharmaceutical products.

The BIOSECURE Act did not pass in 2024, but support for the policies contained therein remains broad in Congress, and the bill could be reintroduced in 2025.

Any additional executive action, legislative action, or potential sanctions with respect to China could materially impact our current manufacturing partners and our agreements with them, including our MSA with WuXi.

For example, in February 2024, the chair and ranking member of the House Select Committee on the Chinese Communist Party, Representatives Mike Gallagher and Raja Krishnamoorthi, respectively, along with Senators Gary Peters and Bill Hagerty sent a letter to the Biden administration requesting that both WuXi AppTec Co., Ltd., WuXi’s parent company, and the affiliated WuXi Biologics be added to the Department of Defense’s Chinese Military Companies List (1260H list), the Department of Commerce’s Bureau of Industry and Security Entity List, and the Department of Treasury’s Non-SDN Chinese Military-Industrial Complex Companies List.

The new administration may also enact new regulations or policies that affect trade with China or otherwise impact the biopharmaceutical industry by enacting laws to restrict U.S.

biopharmaceutical companies from contracting with Chinese companies on the development, research or manufacturing of biopharmaceutical products.

Any additional executive orders, legislative action or potential sanctions on China could materially impact our current manufacturing partners.

Although our business has not been materially impacted by the ongoing military conflicts between Russia and Ukraine or Israel and Hamas, Hezbollah, and the Houthis, geopolitical tensions, tariffs, or inflation to date, it is impossible to predict the extent to which our operations, or those of our suppliers and manufacturers, will be impacted in the short and long term, or the ways in which the conflict may impact our business.

The extent and duration of the conflicts in Ukraine and the Middle East, geopolitical tensions, inflation, sanctions and resulting market disruptions are impossible to predict, but could be substantial.

Our business, financial condition and results of operations could be materially adversely affected by any negative impact on the global economy and capital markets resulting from the conflicts in Ukraine, the Middle East and other global conflicts, geopolitical tensions, or inflation.

Our results of operations could be adversely affected by general conditions in the global economy, the global financial markets and global political conditions.

The financial markets and the global economy may also be adversely affected by the current or anticipated impact of military conflict, including the ongoing conflicts in Ukraine, the Middle East and other global conflicts, terrorism or other geopolitical events, political tensions between the U.S.

and China, or inflation.

For example, the BIOSECURE Act was signed into law in December 2025 as part of the Fiscal Year 2026 National Defense Authorization Act.

The BIOSECURE Act restricts U.S.

government agencies from purchasing or obtaining certain biotechnology equipment or services from “biotechnology companies of concern,” or BCCs;

entering, extending or renewing a contract with any entity using biotechnology equipment or services provided by a BCC to perform a government contract;

or granting government funds or loans for such biotechnology equipment or services provided by the BCC.

The BIOSECURE Act may have significant implications for U.S.

companies with government contracts that obtain biotechnology equipment or services from a BCC, including contracts with the Department of Veterans Affairs, and any related impact on reimbursement under Medicaid or Medicare Part B.

Sanctions imposed by the U.S.

and other countries in response to such conflicts and political tensions may also adversely impact our business, the financial markets and the global economy, and any economic countermeasures by the affected countries or others could exacerbate market and economic instability, and lead to instability and lack of liquidity in capital markets, potentially making it more difficult for us to obtain additional funds.

Although our business has not been materially impacted by the ongoing military conflicts in Ukraine or the Middle East, geopolitical tensions, tariffs, or inflation to date, it is impossible to predict the extent to which our operations, or those of our suppliers and manufacturers, will be impacted in the short and long term, or the ways in which the conflict may impact our business.

The extent and duration of the conflicts in Ukraine, the Middle East and other global conflicts, geopolitical tensions, inflation, sanctions and resulting market disruptions are impossible to predict, but could be substantial.

Any such disruptions may also magnify the impact of other risks described herein.

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Furthermore, we are required to make certain future payments under the Proleukin ® acquisition agreement that are denominated in non-U.S.

dollars, including future deferred consideration and earnout payments based on Proleukin ® sales.

dollars, including future deferred consideration and earnout payments based

on Proleukin ® sales.

As such, we face exposure to adverse movements in foreign currency exchange rates, including movements in foreign currency for the future milestone payment.

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The process of obtaining FDA and other required regulatory approvals, including foreign approvals, is expensive and often takes many years and can vary substantially based upon the type, complexity and novelty of the products involved.

In addition, regulatory agencies may lack experience with our technologies and products, which may lengthen the regulatory review process, increase our development costs and delay or prevent their commercialization.

In addition, regulatory agencies may lack experience with our technologies and products, or may experience changes in review personnel which may alter the FDA’s advice with respect to our strategy and submissions, which in turn, may lengthen the regulatory review process, increase our development costs and delay or prevent their commercialization.

Prior to Amtagvi ® , no adoptive cell therapy using a TIL product had been approved for marketing by the FDA.

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The FDA and foreign regulatory approval process is lengthy and time-consuming, and we may experience significant delays in the clinical development and regulatory approval of our product candidates.

We completed our first submission of a rolling BLA to the FDA for lifileucel in March 2023.

The FDA accepted our BLA for Amtagvi ® for patients with advanced melanoma in May 2023 and granted lifileucel Priority Review.

The FDA originally assigned November 25, 2023 as the target action date for a decision under PDUFA, however, the FDA then reassigned February 24, 2024 as the revised target action date before approving the BLA on February 16, 2024.

A BLA must include extensive preclinical and clinical data and supporting information to establish the product candidate’s safety and effectiveness for each desired indication.

Our BLA submissions and expected timelines for our product candidates are based on our interpretation of communications received from the FDA to date regarding each product candidate and are subject to revision if additional communications are received from the FDA.

As such, we may experience delays with FDA approval of additional BLAs.

We are conducting registrational trials for advanced NSCLC and frontline advanced melanoma cancer with our lifileucel product candidate.

These trials, which we refer to as IOV-LUN-202 Cohorts 1 and 2 in the case of advanced NSCLC and TILVANCE-301 in the case of advanced melanoma, are currently underway and have been the subject of formal FDA meetings and communications.

For instance, on December 22, 2023, the FDA placed a clinical hold on the IOV-LUN-202 trial in response to a reported Grade 5 (fatal) serious adverse event potentially related to the non-myeloablative lymphodepletion pre-conditioning regimen, and we paused enrollment and the lifileucel treatment regimen for new patients in IOV-LUN-202 during the clinical hold.

On March 4, 2024, the FDA lifted the partial clinical hold on the IOV-LUN-202 trial, permitting us to resume patient enrollment.

As such, we may experience delays with FDA approval of BLAs for our product candidates.

We are conducting registrational trials for advanced NSCLC and frontline advanced melanoma cancer with our lifileucel product candidate, and we plan to commence a registrational trial in previously treated advanced UPS and DDLPS in the second quarter of 2026.

The ongoing trials, which we refer to as IOV-LUN-202 Cohorts 1 and 2 in the case of advanced NSCLC and TILVANCE-301 in the case of advanced melanoma, are currently underway and have been the subject of formal FDA meetings and communications.

For instance, on December 22, 2023, the FDA placed a clinical hold on the IOV-LUN-202 trial in response to a reported Grade 5 (fatal) serious adverse event potentially related to the non-myeloablative lymphodepletion, or NMA-LD, pre-conditioning regimen, and we paused enrollment and the lifileucel treatment regimen for new patients in IOV-LUN-202 during the clinical hold.

On March 4, 2024, the FDA lifted the partial clinical hold on the IOV-LUN-202 trial, permitting us to resume patient

enrollment using a reduced NMA-LD regimen.

Our current beliefs regarding the registration pathway for lifileucel in these indications are based on our interpretation of communications with the FDA to date and our efforts to address such communications, which may be incorrect.

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Protocol revisions may have an adverse effect on the results reported to date.

Changes to implement an

independent review committee and assay validation and implementation, and the data within these clinical trials may not ultimately be supportive of product approval, all of which could result in significant delays to our currently anticipated timeline for development and approval of the lifileucel product candidate or prevent their approval.

Changes to implement an independent review committee and assay validation and implementation, and the data within these clinical trials may not ultimately be supportive of product approval, all of which could result in significant delays to our currently anticipated timeline for development and approval of the lifileucel product candidate or prevent their approval.

A BLA must also include significant information regarding the chemistry, manufacturing and controls for the product.

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For example, the FDA has limited experience with commercial development of cell therapies for cancer.

We may also not be able to successfully utilize the BTD designation we have received for metastatic cervical cancer to successfully complete the development and commercialization of Amtagvi ® for this indication.

We may not be able to reach agreement with the FDA on an interpretation of outcomes from our meetings, including meetings we have held with the FDA in relation to our C-145-04 clinical trial and future meetings.

In addition, as previously disclosed, Iovance began a confirmatory Phase 3 clinical trial, TILVANCE-301, of lifileucel in combination with pembrolizumab in frontline metastatic melanoma in late 2022.

As previously disclosed, Iovance began a confirmatory Phase 3 clinical trial, TILVANCE-301, of lifileucel in combination with pembrolizumab in frontline metastatic melanoma in late 2022.

The FDA previously granted Fast Track Designation for lifileucel in combination with pembrolizumab for the treatment of immune checkpoint inhibitor-naïve metastatic melanoma.

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In addition, any delays in completing our clinical trials will increase our costs, slow down our product development and approval process and jeopardize our ability to commence product sales and generate revenue.

The FDA’s review of our regulatory submissions may be delayed in the future due to reasons beyond our control (such as the reductions of staffing or other resources at the FDA.

FDA operations are affected by various factors, such as shifting government priorities, budgets and funding levels, authorization and payment of user fees, the ability to hire and retain key personnel, as well as other statutory, regulatory, and policy changes impacting HHS, the FDA, or other HHS agencies.

Specifically, in 2025, FDA faced a reduction in size, a prolonged federal government shutdown, as well as frequent administrative turnover and agency restructuring following the institution of the new administration, which have directly or indirectly impacted FDA’s ability to support research and development activities.

If legislation, administrative action, or changes in policy prevent the FDA or other regulatory authorities from conducting routine inspections, reviews, or other regulatory activities, it could significantly impact the ability of the FDA to provide feedback on our clinical programs, meet with or engage in other informal interactions with us, and review and process our regulatory

submissions (including our pending regulatory submissions) in a timely manner.

These developments may also reduce the FDA’s capacity to engage in pre-approval or other meetings.

In addition, any future government shutdown or a widespread freeze on federal funding could significantly impact the ability of the FDA to timely review and process our regulatory submissions or cause other agencies that support the FDA to slow their work.

Any such factors could have a material adverse effect on our business.

Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not mean that we will be successful in obtaining or maintaining regulatory approval of our product candidates in other jurisdictions.

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For example, even if the FDA grants marketing approval of a product candidate, comparable regulatory authorities in foreign jurisdictions must also approve the manufacturing, marketing and promotion of the product candidate in those countries.

Approval procedures vary among jurisdictions and can involve requirements and administrative review periods different from, and greater than, those in the U.S., including additional preclinical studies or clinical trials as clinical studies conducted in one jurisdiction may not be accepted by regulatory authorities in

other jurisdictions.

In many jurisdictions outside the U.S., a product candidate must be approved for reimbursement before it can be approved for sale in that jurisdiction.

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In addition, we, our contractors, and our collaborators are and will remain responsible for FDA compliance, including requirements related to product design, testing, clinical trials and preclinical studies approval, manufacturing processes and quality, labeling, packaging, distribution, adverse event and deviation reporting, storage, advertising, marketing, promotion, sale, import, export, submissions of safety and other post-marketing information and reports such as deviation reports, establishment registration, product listing, annual user fees, and recordkeeping for our product candidates.

Initiatives established by the current presidential administration have led to greater regulatory scrutiny around prescription drug promotion, in particular direct-to-consumer (DTC) advertising, coinciding with a presidential memorandum that directed FDA to intensify oversight and enforcement under existing authorities and to initiate rulemaking to eliminate the “adequate provision” loophole that allows safety information to be placed in separate formats or locations.

While FDA continues to regulate advertising and promotion under the FDCA and implementing standards, there has been a significant increase in warning letters and untitled letters

issued by the agency’s Office of Prescription Drug Promotion.

Failure to comply with current or forthcoming FDA requirements may trigger enforcement by FDA, DOJ, or HHS Office of Inspector General (as well as state authorities), which may result in warning letters, civil and criminal penalties, agreements restricting promotional practices, and significant reputational harm.

We and any of our collaborators, including our contract manufacturers, could be subject to periodic unannounced inspections by the FDA to monitor and ensure compliance with regulatory requirements.

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If we fail to comply with applicable healthcare and promotional laws, including fraud and abuse and information privacy and security laws, we could face substantial penalties and our business, financial condition, results of operations, and prospects could be adversely affected.

As a biopharmaceutical company, we are subject to many federal and state healthcare laws, including the federal Anti-Kickback Statute, or the AKS, the federal civil and criminal False Claims Act, or the FCA, the civil monetary penalties statute, or the CMP Law, the Medicaid Drug Rebate statute and other price reporting requirements, the Veterans Health Care Act of 1992, or the VHCA, HIPAA, the Foreign Corrupt Practices Act of 1977, or FCPA, the Patient Protection and Affordable Care Act of 2010, or the ACA, and similar state laws.

Even though we do not and will not control referrals of healthcare services or bill directly to Medicare, Medicaid, or other third-party payors, certain federal and state healthcare laws and regulations pertaining to fraud and abuse, disclosures, and patients’ rights are and will be applicable to our business.

As a biopharmaceutical company, we are subject to many federal and state healthcare laws, such laws may include the federal Anti-Kickback Statute, or the AKS, the federal civil and criminal False Claims Act, or the FCA, the civil monetary penalties statute, or the CMP Law, the Medicaid Drug Rebate statute and other price reporting requirements, the Veterans Health Care Act of 1992, or the VHCA, HIPAA, the Foreign Corrupt Practices Act of 1977, or FCPA, the ACA, and similar state laws.

If we do not comply with all applicable laws, we may be subject to enforcement by both the federal government and the states in which we conduct our business as well as by other third parties, such as patients.

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Laws and regulations require calculation and reporting of complex pricing information for prescription drugs, and compliance will require us to invest in significant resources and develop a price reporting infrastructure or depend on third parties to compute and report our drug pricing.

Pricing reported to the Centers for Medicare & Medicaid Services, or CMS, must be certified.

Pricing reported to CMS must be certified.

Non-compliant activities expose us to FCA risk if they result in overcharging agencies, underpaying rebates to agencies, or causing agencies to overpay providers.

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federal or state health care programs, corporate integrity agreements, and the curtailment or restructuring of our operations, any of which could materially adversely affect our ability to operate our business and our financial results.

If any of the physicians or other healthcare providers or entities with whom we expect to do business, including our collaborators, is found not to be in compliance with applicable laws, they may be subject to criminal, civil, or administrative sanctions, including but not limited to, exclusions from participation in government healthcare programs, which could also materially affect our business.

If any of the physicians or other HCPs or entities with whom we expect to do business, including our collaborators, is found not to be in compliance with applicable laws, they may be subject to criminal, civil, or administrative sanctions, including but not limited to, exclusions from participation in government healthcare programs, which could also materially affect our business.

In order to obtain additional clarification on the AKS or the CMP Law, a written interpretative advisory opinion can be requested from the Department of Health and Human Services’ Office of Inspector General, or OIG, regarding existing or contemplated arrangements.

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Thus, we and any of our collaborators will not be able to promote any products we develop for indications or uses for which they are not approved.

In the U.S., engaging in the impermissible promotion of our products, following approval, for off-label uses can also subject us to false claims and other litigation under federal and state statutes, including fraud and abuse and consumer protection laws, which can lead to civil and criminal penalties and fines, agreements with governmental authorities that materially restrict the manner in which we promote or distribute therapeutic products and do business through, for example, corporate integrity agreements, suspension or exclusion from participation in federal and state healthcare programs, and debarment from government contracts and refusal of future orders under existing contracts.

In the U.S., engaging in the impermissible promotion of our products, following approval, for off-label uses can also subject us to false claims and other litigation under federal and state statutes, including fraud and abuse and consumer protection laws, which can lead to civil and criminal penalties, damages, fines, and actions, agreements with governmental authorities that materially restrict the manner in which we promote or distribute therapeutic products and do business through, for example, corporate integrity agreements, suspension or exclusion from participation in federal and state healthcare programs, and debarment from government contracts and refusal of future orders under existing contracts.

These false claims statutes include the federal civil FCA, which allows any individual to bring a lawsuit against a biopharmaceutical company on behalf of the federal government alleging submission of false or fraudulent claims or causing others to present such false or fraudulent claims, for payment by a federal program such as Medicare or Medicaid.

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This growth in litigation has increased the risk that a biopharmaceutical company will have to defend a false claim action, pay settlement fines or restitution, as well as criminal and civil penalties, agree to comply with burdensome reporting and compliance obligations, and be excluded from Medicare, Medicaid, or other federal and state healthcare programs.

If we or our future collaborators do not lawfully promote our approved products, if any, we may become subject to such

litigation and, if we do not successfully defend against such actions, those actions may have a material adverse effect on our business, financial condition, results of operations and prospects.

If we or our future collaborators do not lawfully promote our approved products, if any, we may become subject to such litigation and, if we do not successfully defend against such actions, those actions may have a material adverse effect on our business, financial condition, results of operations and prospects.

Although an effective compliance program can mitigate the risk of investigation and prosecution for violations of these laws, the risks cannot be entirely eliminated.

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Moreover, specific rules may apply in each EU member state as regards the interactions between MSLs and HCPs.

Coverage and reimbursement may be limited or unavailable in certain market segments for our product candidates, which could make it difficult for us to sell our product candidates profitably.

Coverage and reimbursement may be limited or unavailable in certain market segments for our products or product candidates, which could make it difficult for us to sell our product candidates profitably.

In both domestic and foreign markets, sales of our product candidates, if approved, depend on the availability of coverage and adequate reimbursement from third-party payors.

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Third-party payors, including government health care programs, decide which drugs and treatments they will cover and the amount of reimbursement.

Coverage decisions may depend upon clinical and economic standards that disfavor new drug products when more established or lower cost therapeutic alternatives are already available or subsequently become available.

Coverage decisions may depend upon clinical and economic standards that disfavor new drug products

when more established or lower cost therapeutic alternatives are already available or subsequently become available.

If reimbursement is not available, or is available only to limited levels, our product candidates may be competitively disadvantaged, and we, or our collaborators, may not be able to successfully commercialize our product candidates.

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In addition, third-party payors are requiring higher levels of evidence of the benefits and clinical outcomes of new technologies and are challenging the prices charged.

We, and our collaborators, cannot be sure that coverage will be

available for any product candidate that we, or they, commercialize and, if available, that the reimbursement rates will be adequate.

We, and our collaborators, cannot be sure that coverage will be available for any product candidate that we, or they, commercialize and, if available, that the reimbursement rates will be adequate.

Further, the net reimbursement for drug products may be subject to additional reductions if there are changes to laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the U.S.

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● the availability of capital.

Further, executive orders were signed to implement Most Favored Nation drug pricing policies designed to align certain prescription drug prices in the U.S.

to lower prices available in other countries.

Investigations are being conducted to examine price differentials and consider policy approaches for implementation, including through administrative action, and letters have been sent to pharmaceutical companies demanding further reduced prices more in line with Most Favored Nation pricing.

If such Most Favored Nation policies are implemented, changes to drug pricing are expected to affect the profitability of pharmaceutical and biotech companies in the U.S.

as well as in other countries, as a price referencing policy to the U.S.

market could make it commercially unviable to commercialize a drug product in a price constrained market.

The details of the proposed policies are unclear, and the final terms and impact remain uncertain and may pose long-term risks to our business and our future commercialization plans of our products and product candidates.

In addition, the Fair Prescription Drug Prices for Americans Act was re-introduced in May 2025 and proposes to cap the retail list price of prescription drugs and biological products in the United States at the average retail list price for such product among certain countries.

Although it is uncertain if these pricing proposals will take effect, reducing drug prices remains

a bipartisan effort and, if made effective, could significantly impact coverage, pricing, and reimbursement for any approved product.

These and other similar developments could significantly limit the degree of market acceptance of our products or any of our other product candidates that receive marketing authorization.

We expect that healthcare reform measures that may be adopted in the future may result in increased manufactured financial liability and additional downward pressure on the price that we may receive for any of our product candidates, if approved.

Any reduction in reimbursement from Medicare or other government health care programs may result in a similar reduction in payments from private payors.

Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors, which may adversely affect our future profitability.

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Moreover, on April 10, 2024, the European Parliament adopted its position on the European Commission proposal to reform EU pharmaceutical legislation, consisting of a new directive replacing Directive 2001/83/EC and a new regulation replacing Regulation (EC) 726/2004.

If approved, this will represent the most significant review of EU pharmaceutical legislation since 2004.

The Council of the EU and European parliament reached a provisional agreement in December 2025, which if approved by the council and parliament through the EU ordinary legislative procedure, will represent the most significant review of EU pharmaceutical legislation since 2004.

The changes proposed are far reaching, including a change in the period of standard regulatory exclusivity, a package of incentives aimed at addressing unmet medical needs, and an extension of the so-called Bolar exemption.

Moreover, it is unclear how regulations and sub-regulatory policy, which fluctuate continually, may affect interpretation and further implementation of the existing law and its practical effects on our business.

Moreover, it is unclear how regulations and sub-regulatory policy, which fluctuate continually, may affect the interpretation and further implementation of the existing law and its practical effects on our business.

We are unable to predict the future course of federal or state healthcare legislation in the U.S.

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799 (2024), will impact the FDA’s enforcement and decision-making authority.

Loper Bright explicitly overturned Chevron deference, which previously gave

judicial deference to administrative action by agencies in the executive branch.

Loper Bright explicitly overturned Chevron deference, which previously gave judicial deference to administrative action by agencies in the executive branch.

Furthermore, the Supreme Court’s decision in Corner Post may result in challenges to FDA decisions by new litigants long into the future.

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There is also an increasing focus on the price of drugs, both at the state and federal levels, and it is likely that additional pricing controls will be enacted and could harm our business, financial condition and results of operations.

For instance, states such as California have begun enacting transparency laws aimed at curbing drug price increases and with the change in administration it is possible that President Trump may issue executive orders with the potential to change a number of prior executive branch actions on drug pricing.

We continue to monitor the potential impact of proposals and recently enacted legislation to lower prescription drug costs at the federal and state level.

As an example, of changes enacted by a new administration, the Inflation Reduction Act, or the IRA, was signed into law in August 2022 by President Biden, which makes significant changes to how drugs are covered and paid for under the Medicare program, including the creation of financial penalties for drugs whose prices rise faster than the rate of inflation, redesign of the Medicare Part D program to require manufacturers to bear more of the liability for certain drug benefits, and government price-setting for certain Medicare Part D drugs, starting in 2026, and Medicare Part B drugs starting in 2028.

As an example, of changes enacted by a new administration, the IRA, or the IRA, was signed into law in August 2022 by President Biden,

which makes significant changes to how drugs are covered and paid for under the Medicare program, including the creation of financial penalties for drugs whose prices rise faster than the rate of inflation, redesign of the Medicare Part D program to require manufacturers to bear more of the liability for certain drug benefits, and government price-setting for certain Medicare Part D drugs, which started in 2026, and Medicare Part B drugs starting in 2028.

We continue to evaluate what effect, if any, the IRA may have on our business.

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The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability or commercialize our products.

Further, CMS recently proposed two mandatory payment model pilots, the Guarding U.S.

Medicare Against Rising Drug Costs, or GUARD, Model, focused on Part D drugs, and Global Benchmark for Efficient Drug Pricing, or GLOBE, focused on Part B drugs, which will require pharmaceutical companies to pay additional rebates on certain medicines, including central nervous system agents for the treatment of multiple sclerosis, whose U.S.

net-of-discount prices exceed those in certain other countries.

Legislative and regulatory proposals may also be made to expand post-approval requirements and restrict sales and promotional activities for drugs.

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We continue to monitor the potential impact of these and other proposals to lower prescription drug costs at the federal and state level.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing within state healthcare programs and payers, including price or patient reimbursement constraints, rebates and other price concessions, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and other purchasing approaches.

We are unable to predict the future course of federal or state healthcare legislation in the U.S.

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General political uncertainty may have an adverse impact on our operating performance and results of operations.

Changing regulatory policies resulting from the changing political environment could impact our regulatory and compliance costs and future revenues, all of which could materially and adversely affect our business, financial condition, and operating results.

Changing regulatory policies resulting from the political environment could impact our regulatory and compliance costs and future revenues, all of which could materially and adversely affect our business, financial condition, and operating results.

Failure to adapt to or comply with evolving regulatory requirements or investor or stakeholder expectations and standards could negatively impact our reputation, ability to do business with certain partners, access to capital, and our stock price.

In particular, the U.S.

continues to experience significant political events that cast uncertainty on global financial and economic markets, especially following the recent election.

administration and recent congressional seat turnover may result in increased regulatory and economic uncertainty.

Changes in federal policy by the executive branch and regulatory agencies may occur over time through the new presidential

administration’s and/or Congress’s policy and personnel changes, which could lead to changes involving the level of oversight and focus on the biopharmaceutical industry.

However, the nature, timing, and economic and political effects of such potential changes remain highly uncertain.

It is presently unclear exactly what actions the new presidential administration in the U.S.

will implement, and if implemented, how these actions may impact the biopharmaceutical industry in the U.S.

Any actions taken by the new presidential administration may have a negative impact on the U.S.

economy and on our business, financial condition, and results of operations.

Changes in U.S.

federal policy by the executive branch and regulatory agencies may continue to occur, which could lead to changes involving the level of oversight, reimbursement to and focus on the biopharmaceutical industry operations globally.

However, the nature, timing, and effects of such potential changes remain highly uncertain.

It is presently unclear exactly what additional actions the administration in the U.S.

will implement, and if implemented, how these actions may impact the biopharmaceutical industry, and our company specifically, in the U.S.

and worldwide.

There is currently significant uncertainty about the future of trade relationships around the world, including potential changes to trade laws and regulations, trade policies, and tariffs.

The administration has used emergency authority to impose tariffs on imported branded pharmaceuticals and subsequently reported to have negotiated agreements with certain countries including the United Kingdom and Japan.

For example, on April 2, 2025, the Administration announced more tariffs imposed pursuant to the International Emergency Economic Powers Act, designated “reciprocal tariffs” purportedly in response to the trade deficit national emergency

announced on virtually all imported products from all countries.

The reciprocal tariffs imposed a 10% tariff on most countries, which were to increase to a higher, country-specific tariff rate on countries identified in Annex 1 of the executive order.

The country-specific tariffs were later paused for 90 days.

In addition, the Administration, through the Department of Commerce, has an ongoing investigation into the pharmaceutical industry pursuant to Section 232 of the Trade Expansion Act of 1962, whereby the President may impose additional tariffs on imports within the pharmaceutical industry if deemed necessary based on national security grounds.

In addition, the Administration announced a 100% tariff, effective October 1, 2025, on any branded or patented pharmaceuticals imported into the U.S., unless the relevant drug manufacturer has or is in the process of building a manufacturing facility in the U.S., which has been paused as negotiations with large drug manufacturers continue.

Further, the President signed an executive order to reduce prescription drug pricing, including to implement Most Favored Nation drug pricing policies designed to align certain prescription drug prices in the U.S.

to lower prices available in other countries.

Agreements with major pharmaceutical companies were announced to lower prices or offer medicines on the TrumpRx platform.

The details of each of these proposals are unclear, and the final terms remain uncertain.

As a result of these dynamics, we cannot predict the impact to our relationships with third-party manufacturers or our business of any future changes to the U.S.’ or other countries’ trading relationships or the impact of new laws or regulations adopted by the U.S.

or other countries.

Evolving international trade relations, new legislation and tariffs may adversely impact our operations and/or financial condition by limiting or preventing the activities of third parties that we engage, increasing import costs or increasing the cost of our operations.

New or increased tariffs, export controls or other trade barriers could result in higher prices for the materials we use and the products and product candidates we are developing and could materially impact our supply chain and manufacturing costs.

We are subject to a variety of U.S.

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and similar foreign fraudulent misconduct laws, or report financial information or data accurately or to disclose unauthorized activities to us.

If we obtain FDA approval of any of our product candidates and begin commercializing those products in the U.S., our potential exposure under such laws will increase significantly, and our costs associated with compliance with such laws are also likely to increase.

If we obtain FDA approval of any of our product candidates and begin commercializing those products in the U.S., our potential exposure under such laws will increase significantly, and our costs

associated with compliance with such laws are also likely to increase.

These laws may impact, among other things, our current activities with principal investigators and research patients, as well as proposed and future sales, marketing, and education programs.

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Efforts to ensure that our business arrangements will comply with applicable healthcare laws may involve substantial costs.

It is possible that governmental and enforcement authorities will conclude that our, or our employees’, consultants’, collaborators’, contractors’, or vendors’ business practices may not comply with current or future statutes, regulations or case law interpreting applicable

fraud and abuse or other healthcare laws and regulations.

If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business, including the imposition of civil, criminal and administrative penalties, damages, disgorgement, monetary fines, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, compliance agreements, withdrawal of product approvals, and curtailment of our operations, among other things, any of which could adversely affect our ability to operate our business and our results of operations.

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If there is litigation against us, we may not be able to continue our operations.

Should third parties file patent applications or be issued patents claiming technology also used or claimed by us, we may be required to participate in interference proceedings in the USPTO to determine priority of invention.

We may be required to participate in interference proceedings involving our issued patents and pending applications.

We may be required to cease using the technology or to license rights from prevailing third parties as a result of an unfavorable outcome in an interference proceeding.

A prevailing party in that case may not offer us a license on commercially acceptable terms.

Issued patents covering our product candidates could be found invalid or unenforceable if challenged in court or the USPTO.

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No assurance can be given that the NIH has not previously licensed, or that the NIH hereafter will not license to other biotechnology companies some or all of the non-exclusive technologies available to us under the NIH License Agreement.

In addition, one pending U.S.

patent application in the NIH License Agreement is not owned solely by the NIH.

No assurance can be given that NIH’s co-owner of the certain pending U.S.

patent application in the NIH License Agreement has not previously licensed, or that the co-owner thereafter will not license, to other biotechnology companies some or all of the technologies available to us.

In addition, one U.S.

patent in the NIH License Agreement is not owned solely by the NIH.

No assurance can be given that NIH’s co-owner of the certain U.S.

patent in the NIH License Agreement has not previously licensed, or that the co-owner thereafter will not license, to other biotechnology companies some or all of the technologies available to us.

Co-ownership of these intellectual properties will create issues with respect to our ability to enforce the intellectual property rights in courts and will create issues with respect to the accountability of one entity with respect to the other.

Since the NCI and numerous other academic institutions already use TIL cell therapy for the treatment of metastatic melanoma and other indications, their methods and data are also available to third parties, who may want to enter into our line of business and compete against us.

Other than the Gen 2 manufacturing process, our licensed rights, and our method of use rights in certain indications,

we currently do not own any exclusive rights on our entire product portfolio that could be used to fully prevent third parties from duplicating our business plan or from otherwise directly competing against us.

Other than the Gen 2 manufacturing process, our licensed rights, and our method of use rights in certain indications, we currently do not own any exclusive rights on our entire product portfolio that could be used to fully prevent third parties from duplicating our business plan or from otherwise directly competing against us.

While additional technologies that may be developed under our CRADA may be licensed to us on an exclusive basis, no assurance can be given that our existing exclusive rights will be sufficient to prevent others from competing with us and developing substantially similar products.

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The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents, trade secrets and other intellectual property protection, particularly those relating to biopharmaceutical products, which could make it difficult for us to stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally.

Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our patent applications at

risk of not issuing and could provoke third parties to assert claims against us.

We may not prevail in any lawsuits that we initiate, and the damages or other remedies awarded, if any, may not be commercially meaningful.

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Litigation may be necessary to defend against or pursue these claims.

For example, we are currently engaged in litigation involving counterclaims that we have brought relating to theft of certain of our trade secrets, breach of confidentiality, and related counterclaims.

Even if we are successful in resolving these claims, litigation could result in substantial costs and be a distraction to our management and employees.

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The market price of our common stock is likely to be volatile and could fluctuate widely in response to many factors, including but not limited to:

● volatility and instability in the capital markets due to the COVID-19 pandemic;

● volatility and instability in the capital markets due to potential health epidemics and pandemics;

● announcements of the results of clinical trials by us, our collaborators, or our competitors, or negative developments with respect to similar products, including those being developed by our collaborators;

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To raise additional capital, we may in the future offer additional shares of our common stock or other securities convertible into or exchangeable for our common stock at prices that may be lower than the current price per share of our common stock.

In addition, investors purchasing shares or other securities in the future could have rights superior

to existing stockholders.

In addition, investors purchasing shares or other securities in the future could have rights superior to existing stockholders.

The price per share at which we sell additional shares of our common stock, or securities convertible or exchangeable into common stock, in future transactions may be higher or lower than the price per share paid by investors in prior offerings.

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In addition, in the future, we may issue additional shares of common stock or other equity or debt securities convertible into common stock in connection with a financing, acquisition, litigation settlement, employee arrangements or otherwise.

For example, in February 2024, we issued 23,014,000 shares of common stock in connection with an underwritten public offering, and we may offer additional shares under our automatic shelf registration statement in the future.

For example, in August 2025, we entered into a Sale Agreement with Jefferies with respect to an at the market offering program, under which we may, from time to time, issue and sell up to $350.0 million of our common stock, and we may offer additional shares under our automatic shelf registration statement in the future.

Future issuances may result in substantial dilution to our existing stockholders and could cause our stock price to decline.

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The Company continues to vigorously defend against the complaint.

The outcome of this and other future litigation is uncertain.

Also, on May 15, 2025, two putative securities class actions were filed against us and certain of our officers, alleging violations of federal securities laws for allegedly making materially false and misleading statements regarding our expected revenue for fiscal year 2025, which the plaintiffs claim artificially inflated the price of our common stock.

On June 5, 2025, two putative shareholder derivative lawsuits were filed, purportedly brought on behalf of Iovance against certain current and former officers and directors of the Company.

The lawsuits contain allegations based on or similar to those in the putative securities class actions and claim, among other things, that the defendants breached their fiduciary duties and violated Section 14(a) of the 1934 Act by issuing or causing the Company to issue false and misleading disclosures concerning the Company’s financial forecasts for fiscal year 2025.

The outcome of these and other future litigation is uncertain.

Our Board of Directors could issue one or more additional series of preferred stock without stockholder approval with the effect of diluting existing stockholders and impairing their voting and other rights.

Our certificate of incorporation, as amended, authorizes the issuance of up to 50,000,000 shares of “blank check” preferred stock (of which only 17,000 shares were issued as Series A Convertible Preferred Stock and 11,500,000 shares were issued as Series B Convertible Preferred Stock) with designations, rights, and preferences as may be determined from time to time by our Board of Directors.

Our certificate of incorporation, as amended, authorizes the issuance of up to 50,000,000 shares of “blank check” preferred stock (of which only 17,000 shares were authorized for issuance as Series A Convertible Preferred Stock and 11,500,000 shares were authorized for issuance as Series B Convertible Preferred Stock) with designations, rights, and preferences as may be determined from time to time by our Board of Directors.

Our Board of Directors is empowered, without stockholder approval, to issue one or more series of preferred stock with dividend, liquidation, conversion, voting, or other rights which could dilute the interest of, or impair the voting power of, our common stockholders.

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Our certificate of incorporation, as amended, provides that, subject to limited exceptions, the Court of Chancery of the State of Delaware shall, to the fullest extent permitted by law, be the sole and exclusive forum for (1) any derivative action or proceeding brought on our behalf, (2) any action asserting a claim of breach of a fiduciary duty owed by any of our directors, officers, employees or agents to us or our stockholders, creditors or other constituents, (3) any action asserting a claim against us arising pursuant to any provision of the Delaware General Corporation Law, our certificate of incorporation, as amended, or our amended and restated bylaws, or (4) any other action asserting a claim against us that is governed by the internal affairs doctrine.

Any person or entity purchasing or otherwise acquiring any interest in shares of our capital stock shall be deemed to have notice of and to have consented to the provisions of our

certificate of incorporation described above.

Any person or entity purchasing or otherwise acquiring any interest in shares of our capital stock shall be deemed to have notice of and to have consented to the provisions of our certificate of incorporation described above.

This choice of forum provision may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, officers, or other employees, which may discourage such lawsuits against us and our directors, officers, and employees.

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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